Qian Wang

The thermal properties of a suspended metallic single-wall carbon nanotube (SWNT) are extracted from its high-bias (I−V) electrical characteristics over the 300−800 K temperature range, achieved by Joule self-heating. The thermal conductance is approximately 2.4 nW/K, and the thermal conductivity is nearly 3500 Wm-1K-1 at room temperature for a SWNT of length 2.6 μm and diameter 1.7 nm. A subtle decrease in thermal conductivity steeper than 1/T is observed at the upper end of the temperature range, which is attributed to second-order three-phonon scattering between two acoustic modes and one optical mode. We discuss sources of uncertainty and propose a simple analytical model for the SWNT thermal conductivity including length and temperature dependence.

Obstructive sleep apnea is associated with an increased risk of cardiovascular events; whether treatment with continuous positive airway pressure (CPAP) prevents major cardiovascular events is uncertain.After a 1-week run-in period during which the participants used sham CPAP, we randomly assigned 2717 eligible adults between 45 and 75 years of age who had moderate-to-severe obstructive sleep apnea and coronary or cerebrovascular disease to receive CPAP treatment plus usual care (CPAP group) or usual care alone (usual-care group). The primary composite end point was death from cardiovascular causes, myocardial infarction, stroke, or hospitalization for unstable angina, heart failure, or transient ischemic attack. Secondary end points included other cardiovascular outcomes, health-related quality of life, snoring symptoms, daytime sleepiness, and mood.Most of the participants were men who had moderate-to-severe obstructive sleep apnea and minimal sleepiness. In the CPAP group, the mean duration of adherence to CPAP therapy was 3.3 hours per night, and the mean apnea-hypopnea index (the number of apnea or hypopnea events per hour of recording) decreased from 29.0 events per hour at baseline to 3.7 events per hour during follow-up. After a mean follow-up of 3.7 years, a primary end-point event had occurred in 229 participants in the CPAP group (17.0%) and in 207 participants in the usual-care group (15.4%) (hazard ratio with CPAP, 1.10; 95% confidence interval, 0.91 to 1.32; P=0.34). No significant effect on any individual or other composite cardiovascular end point was observed. CPAP significantly reduced snoring and daytime sleepiness and improved health-related quality of life and mood.Therapy with CPAP plus usual care, as compared with usual care alone, did not prevent cardiovascular events in patients with moderate-to-severe obstructive sleep apnea and established cardiovascular disease. (Funded by the National Health and Medical Research Council of Australia and others; SAVE ClinicalTrials.gov number, NCT00738179 ; Australian New Zealand Clinical Trials Registry number, ACTRN12608000409370 .).

This paper examines the role of affiliation with the ruling Communist Party in the operation of private enterprises in China. Using a nationwide survey of private firms, we find that the Party membership of private entrepreneurs has a positive effect on the performance of their firms when human capital and other relevant variables are controlled. We further find that Party membership helps private entrepreneurs to obtain loans from banks or other state institutions, and affords them more confidence in the legal system. Finally, we find Party membership to be more important to firm performance in regions with weaker market institutions and weaker legal protection.

The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) pandemic continues, with devasting consequences for human lives and the global economy1,2. The discovery and development of virus-neutralizing monoclonal antibodies could be one approach to treat or prevent infection by this coronavirus. Here we report the isolation of sixty-one SARS-CoV-2-neutralizing monoclonal antibodies from five patients infected with SARS-CoV-2 and admitted to hospital with severe coronavirus disease 2019 (COVID-19). Among these are nineteen antibodies that potently neutralized authentic SARS-CoV-2 in vitro, nine of which exhibited very high potency, with 50% virus-inhibitory concentrations of 0.7 to 9 ng ml−1. Epitope mapping showed that this collection of nineteen antibodies was about equally divided between those directed against the receptor-binding domain (RBD) and those directed against the N-terminal domain (NTD), indicating that both of these regions at the top of the viral spike are immunogenic. In addition, two other powerful neutralizing antibodies recognized quaternary epitopes that overlap with the domains at the top of the spike. Cryo-electron microscopy reconstructions of one antibody that targets the RBD, a second that targets the NTD, and a third that bridges two separate RBDs showed that the antibodies recognize the closed, 'all RBD-down' conformation of the spike. Several of these monoclonal antibodies are promising candidates for clinical development as potential therapeutic and/or prophylactic agents against SARS-CoV-2. A diverse collection of potent neutralizing antibodies against the SARS-CoV-2 spike protein have been isolated from five patients with severe COVID-19 and high serum neutralization titres.

Cloud Computing has been envisioned as the next-generation architecture of IT Enterprise. It moves the application software and databases to the centralized large data centers, where the management of the data and services may not be fully trustworthy. This unique paradigm brings about many new security challenges, which have not been well understood. This work studies the problem of ensuring the integrity of data storage in Cloud Computing. In particular, we consider the task of allowing a third party auditor (TPA), on behalf of the cloud client, to verify the integrity of the dynamic data stored in the cloud. The introduction of TPA eliminates the involvement of the client through the auditing of whether his data stored in the cloud are indeed intact, which can be important in achieving economies of scale for Cloud Computing. The support for data dynamics via the most general forms of data operation, such as block modification, insertion, and deletion, is also a significant step toward practicality, since services in Cloud Computing are not limited to archive or backup data only. While prior works on ensuring remote data integrity often lacks the support of either public auditability or dynamic data operations, this paper achieves both. We first identify the difficulties and potential security problems of direct extensions with fully dynamic data updates from prior works and then show how to construct an elegant verification scheme for the seamless integration of these two salient features in our protocol design. In particular, to achieve efficient data dynamics, we improve the existing proof of storage models by manipulating the classic Merkle Hash Tree construction for block tag authentication. To support efficient handling of multiple auditing tasks, we further explore the technique of bilinear aggregate signature to extend our main result into a multiuser setting, where TPA can perform multiple auditing tasks simultaneously. Extensive security and performance analysis show that the proposed schemes are highly efficient and provably secure.

Using cloud storage, users can remotely store their data and enjoy the on-demand high-quality applications and services from a shared pool of configurable computing resources, without the burden of local data storage and maintenance. However, the fact that users no longer have physical possession of the outsourced data makes the data integrity protection in cloud computing a formidable task, especially for users with constrained computing resources. Moreover, users should be able to just use the cloud storage as if it is local, without worrying about the need to verify its integrity. Thus, enabling public auditability for cloud storage is of critical importance so that users can resort to a third-party auditor (TPA) to check the integrity of outsourced data and be worry free. To securely introduce an effective TPA, the auditing process should bring in no new vulnerabilities toward user data privacy, and introduce no additional online burden to user. In this paper, we propose a secure cloud storage system supporting privacy-preserving public auditing. We further extend our result to enable the TPA to perform audits for multiple users simultaneously and efficiently. Extensive security and performance analysis show the proposed schemes are provably secure and highly efficient. Our preliminary experiment conducted on Amazon EC2 instance further demonstrates the fast performance of the design.

Cloud Computing is the long dreamed vision of computing as a utility, where users can remotely store their data into the cloud so as to enjoy the on-demand high quality applications and services from a shared pool of configurable computing resources. By data outsourcing, users can be relieved from the burden of local data storage and maintenance. However, the fact that users no longer have physical possession of the possibly large size of outsourced data makes the data integrity protection in Cloud Computing a very challenging and potentially formidable task, especially for users with constrained computing resources and capabilities. Thus, enabling public auditability for cloud data storage security is of critical importance so that users can resort to an external audit party to check the integrity of outsourced data when needed. To securely introduce an effective third party auditor (TPA), the following two fundamental requirements have to be met: 1) TPA should be able to efficiently audit the cloud data storage without demanding the local copy of data, and introduce no additional on-line burden to the cloud user; 2) The third party auditing process should bring in no new vulnerabilities towards user data privacy. In this paper, we utilize and uniquely combine the public key based homomorphic authenticator with random masking to achieve the privacy-preserving public cloud data auditing system, which meets all above requirements. To support efficient handling of multiple auditing tasks, we further explore the technique of bilinear aggregate signature to extend our main result into a multi-user setting, where TPA can perform multiple auditing tasks simultaneously. Extensive security and performance analysis shows the proposed schemes are provably secure and highly efficient.

The pandemic outbreak of coronavirus disease 2019 (COVID-19) is rapidly spreading all over the world. Reports from China showed that about 20% of patients developed severe disease, resulting in a fatality of 4%. In the past two months, we clinical immunologists participated in multi-rounds of MDT (multidiscipline team) discussion on the anti-inflammation management of critical COVID-19 patients, with our colleagues dispatched from Chinese leading PUMC Hospital to Wuhan to admit and treat the most severe patients. Here, from the perspective of clinical immunologists, we will discuss the clinical and immunological characteristics of severe patients, and summarize the current evidence and share our experience in anti-inflammation treatment, including glucocorticoids, IL-6 antagonist, JAK inhibitors and choloroquine/hydrocholoroquine, of patients with severe COVID-19 that may have an impaired immune system.

(This paper was submitted as an invited paper to IEEE Reviews in Biomedical Engineering on April 6, 2020.) The pandemic of coronavirus disease 2019 (COVID-19) is spreading all over the world. Medical imaging such as X-ray and computed tomography (CT) plays an essential role in the global fight against COVID-19, whereas the recently emerging artificial intelligence (AI) technologies further strengthen the power of the imaging tools and help medical specialists. We hereby review the rapid responses in the community of medical imaging (empowered by AI) toward COVID-19. For example, AI-empowered image acquisition can significantly help automate the scanning procedure and also reshape the workflow with minimal contact to patients, providing the best protection to the imaging technicians. Also, AI can improve work efficiency by accurate delination of infections in X-ray and CT images, facilitating subsequent quantification. Moreover, the computer-aided platforms help radiologists make clinical decisions, i.e., for disease diagnosis, tracking, and prognosis. In this review paper, we thus cover the entire pipeline of medical imaging and analysis techniques involved with COVID-19, including image acquisition, segmentation, diagnosis, and follow-up. We particularly focus on the integration of AI with X-ray and CT, both of which are widely used in the frontline hospitals, in order to depict the latest progress of medical imaging and radiology fighting against COVID-19.

Due to the increasing popularity of cloud computing, more and more data owners are motivated to outsource their data to cloud servers for great convenience and reduced cost in data management. However, sensitive data should be encrypted before outsourcing for privacy requirements, which obsoletes data utilization like keyword-based document retrieval. In this paper, we present a secure multi-keyword ranked search scheme over encrypted cloud data, which simultaneously supports dynamic update operations like deletion and insertion of documents. Specifically, the vector space model and the widely-used TF x IDF model are combined in the index construction and query generation. We construct a special tree-based index structure and propose a “Greedy Depth-first Search” algorithm to provide efficient multi-keyword ranked search. The secure kNN algorithm is utilized to encrypt the index and query vectors, and meanwhile ensure accurate relevance score calculation between encrypted index and query vectors. In order to resist statistical attacks, phantom terms are added to the index vector for blinding search results. Due to the use of our special tree-based index structure, the proposed scheme can achieve sub-linear search time and deal with the deletion and insertion of documents flexibly. Extensive experiments are conducted to demonstrate the efficiency of the proposed scheme.

Photonic components with adjustable parameters, such as variable-focal-length lenses or spectral filters, which can change functionality upon optical stimulation, could offer numerous useful applications. Tuning of such components is conventionally achieved by either micro- or nanomechanical actuation of their constituent parts, by stretching or by heating. Here, we report a novel approach for making reconfigurable optical components that are created with light in a non-volatile and reversible fashion. Such components are written, erased and rewritten as two-dimensional binary or greyscale patterns into a nanoscale film of phase-change material by inducing a refractive-index-changing phase transition with tailored trains of femtosecond pulses. We combine germanium–antimony–tellurium-based films with a diffraction-limited resolution optical writing process to demonstrate a variety of devices: visible-range reconfigurable bichromatic and multi-focus Fresnel zone plates, a super-oscillatory lens with subwavelength focus, a greyscale hologram, and a dielectric metamaterial with on-demand reflection and transmission resonances. A metasurface composed of pixels of optically switchable phase change material yields a photonic platform that can be configured on demand to perform a variety of optical tasks.

<h2>Summary</h2><h3>Background</h3> The ongoing COVID-19 pandemic warrants accelerated efforts to test vaccine candidates. We aimed to assess the safety and immunogenicity of an inactivated severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine candidate, BBIBP-CorV, in humans. <h3>Methods</h3> We did a randomised, double-blind, placebo-controlled, phase 1/2 trial at Shangqiu City Liangyuan District Center for Disease Control and Prevention in Henan Province, China. In phase 1, healthy people aged 18–80 years, who were negative for serum-specific IgM/IgG antibodies against SARS-CoV-2 at the time of screening, were separated into two age groups (18–59 years and ≥60 years) and randomly assigned to receive vaccine or placebo in a two-dose schedule of 2 μg, 4 μg, or 8 μg on days 0 and 28. In phase 2, healthy adults (aged 18–59 years) were randomly assigned (1:1:1:1) to receive vaccine or placebo on a single-dose schedule of 8 μg on day 0 or on a two-dose schedule of 4 μg on days 0 and 14, 0 and 21, or 0 and 28. Participants within each cohort were randomly assigned by stratified block randomisation (block size eight) and allocated (3:1) to receive vaccine or placebo. Group allocation was concealed from participants, investigators, and outcome assessors. The primary outcomes were safety and tolerability. The secondary outcome was immunogenicity, assessed as the neutralising antibody responses against infectious SARS-CoV-2. This study is registered with www.chictr.org.cn, ChiCTR2000032459. <h3>Findings</h3> In phase 1, 192 participants were enrolled (mean age 53·7 years [SD 15·6]) and were randomly assigned to receive vaccine (2 μg [n=24], 4 μg [n=24], or 8 μg [n=24] for both age groups [18–59 years and ≥60 years]) or placebo (n=24). At least one adverse reaction was reported within the first 7 days of inoculation in 42 (29%) of 144 vaccine recipients. The most common systematic adverse reaction was fever (18–59 years, one [4%] in the 2 μg group, one [4%] in the 4 μg group, and two [8%] in the 8 μg group; ≥60 years, one [4%] in the 8 μg group). All adverse reactions were mild or moderate in severity. No serious adverse event was reported within 28 days post vaccination. Neutralising antibody geometric mean titres were higher at day 42 in the group aged 18–59 years (87·7 [95% CI 64·9–118·6], 2 μg group; 211·2 [158·9–280·6], 4 μg group; and 228·7 [186·1–281·1], 8 μg group) and the group aged 60 years and older (80·7 [65·4–99·6], 2 μg group; 131·5 [108·2–159·7], 4 μg group; and 170·87 [133·0–219·5], 8 μg group) compared with the placebo group (2·0 [2·0–2·0]). In phase 2, 448 participants were enrolled (mean age 41·7 years [SD 9·9]) and were randomly assigned to receive the vaccine (8 μg on day 0 [n=84] or 4 μg on days 0 and 14 [n=84], days 0 and 21 [n=84], or days 0 and 28 [n=84]) or placebo on the same schedules (n=112). At least one adverse reaction within the first 7 days was reported in 76 (23%) of 336 vaccine recipients (33 [39%], 8 μg day 0; 18 [21%], 4 μg days 0 and 14; 15 [18%], 4 μg days 0 and 21; and ten [12%], 4 μg days 0 and 28). One placebo recipient in the 4 μg days 0 and 21 group reported grade 3 fever, but was self-limited and recovered. All other adverse reactions were mild or moderate in severity. The most common systematic adverse reaction was fever (one [1%], 8 μg day 0; one [1%], 4 μg days 0 and 14; three [4%], 4 μg days 0 and 21; two [2%], 4 μg days 0 and 28). The vaccine-elicited neutralising antibody titres on day 28 were significantly greater in the 4 μg days 0 and 14 (169·5, 95% CI 132·2–217·1), days 0 and 21 (282·7, 221·2–361·4), and days 0 and 28 (218·0, 181·8–261·3) schedules than the 8 μg day 0 schedule (14·7, 11·6–18·8; all p<0·001). <h3>Interpretation</h3> The inactivated SARS-CoV-2 vaccine, BBIBP-CorV, is safe and well tolerated at all tested doses in two age groups. Humoral responses against SARS-CoV-2 were induced in all vaccine recipients on day 42. Two-dose immunisation with 4 μg vaccine on days 0 and 21 or days 0 and 28 achieved higher neutralising antibody titres than the single 8 μg dose or 4 μg dose on days 0 and 14. <h3>Funding</h3> National Program on Key Research Project of China, National Mega projects of China for Major Infectious Diseases, National Mega Projects of China for New Drug Creation, and Beijing Science and Technology Plan.

Arrays of electrical devices with each comprising multiple single-walled carbon nanotubes (SWNT) bridging metal electrodes are obtained by chemical vapor deposition (CVD) of nanotubes across prefabricated electrode arrays. The ensemble of nanotubes in such a device collectively exhibits large electrical conductance changes under electrostatic gating, owing to the high percentage of semiconducting nanotubes. This leads to the fabrication of large arrays of low-noise electrical nanotube sensors with 100% yield for detecting gas molecules. Polymer functionalization is used to impart high sensitivity and selectivity to the sensors. Polyethyleneimine coating affords n-type nanotube devices capable of detecting NO2 at less than 1 ppb (parts-per-billion) concentrations while being insensitive to NH3. Coating Nafion (a polymeric perfluorinated sulfonic acid ionomer) on nanotubes blocks NO2 and allows for selective sensing of NH3. Multiplex functionalization of a nanotube sensor array is carried out by microspotting. Detection of molecules in a gas mixture is demonstrated with the multiplexed nanotube sensors.

Emerging evidence indicates that the inflammatory mechanisms involved in the pathophysiology of osteoarthritis (OA) differ from those in rheumatoid arthritis. This Review explores the mechanisms of chronic, low-grade inflammation in OA, discusses the evidence of their central role in its pathogenesis, and explores how they might be targeted to prevent or treat OA. Osteoarthritis (OA) has long been viewed as a degenerative disease of cartilage, but accumulating evidence indicates that inflammation has a critical role in its pathogenesis. Furthermore, we now appreciate that OA pathogenesis involves not only breakdown of cartilage, but also remodelling of the underlying bone, formation of ectopic bone, hypertrophy of the joint capsule, and inflammation of the synovial lining. That is, OA is a disorder of the joint as a whole, with inflammation driving many pathologic changes. The inflammation in OA is distinct from that in rheumatoid arthritis and other autoimmune diseases: it is chronic, comparatively low-grade, and mediated primarily by the innate immune system. Current treatments for OA only control the symptoms, and none has been FDA-approved for the prevention or slowing of disease progression. However, increasing insight into the inflammatory underpinnings of OA holds promise for the development of new, disease-modifying therapies. Indeed, several anti-inflammatory therapies have shown promise in animal models of OA. Further work is needed to identify effective inhibitors of the low-grade inflammation in OA, and to determine whether therapies that target this inflammation can prevent or slow the development and progression of the disease.

Hadrons are composite particles made of quark and gluons. Interestingly, some excited hadronic states resemble the deuteron viewed as a barely bound neutron-proton system. Such hadronic molecules are spatially extended systems lying very close to decay thresholds. This work reviews the current experimental evidence for hadronic molecules and related theoretical descriptions, including effective field theories and lattice quantum chromodynamics.

Secretion of the cytokine interleukin-1β (IL-1β) by macrophages, a major driver of pathogenesis in atherosclerosis, requires two steps: Priming signals promote transcription of immature IL-1β, and then endogenous "danger" signals activate innate immune signaling complexes called inflammasomes to process IL-1β for secretion. Although cholesterol crystals are known to act as danger signals in atherosclerosis, what primes IL-1β transcription remains elusive. Using a murine model of atherosclerosis, we found that cholesterol crystals acted both as priming and danger signals for IL-1β production. Cholesterol crystals triggered neutrophils to release neutrophil extracellular traps (NETs). NETs primed macrophages for cytokine release, activating T helper 17 (TH17) cells that amplify immune cell recruitment in atherosclerotic plaques. Therefore, danger signals may drive sterile inflammation, such as that seen in atherosclerosis, through their interactions with neutrophils.

Carbon nanotube field-effect transistors commonly comprise nanotubes lying on SiO2 surfaces exposed to the ambient environment. It is shown here that the transistors exhibit hysteresis in their electrical characteristics because of charge trapping by water molecules around the nanotubes, including SiO2 surface-bound water proximal to the nanotubes. Hysteresis persists for the transistors in vacuum since the SiO2-bound water does not completely desorb in vacuum at room temperature, a known phenomenon in SiO2 surface chemistry. Heating under dry conditions significantly removes water and reduces hysteresis in the transistors. Nearly hysteresis-free transistors are obtainable by passivating the devices with polymers that hydrogen bond with silanol groups on SiO2 (e.g., with poly(methyl methacrylate) (PMMA)). However, nanotube humidity sensors could be explored with suitable water-sensitive coatings. The results may have implications to field-effect transistors made from other chemically derived materials.

Neutrophils are critical for antifungal defense, but the mechanisms that clear hyphae and other pathogens that are too large to be phagocytosed remain unknown. We found that neutrophils sensed microbe size and selectively released neutrophil extracellular traps (NETs) in response to large pathogens, such as Candida albicans hyphae and extracellular aggregates of Mycobacterium bovis, but not in response to small yeast or single bacteria. NETs were fundamental in countering large pathogens in vivo. Phagocytosis via dectin-1 acted as a sensor of microbe size and prevented NET release by downregulating the translocation of neutrophil elastase (NE) to the nucleus. Dectin-1 deficiency led to aberrant NET release and NET-mediated tissue damage during infection. Size-tailored neutrophil responses cleared large microbes and minimized pathology when microbes were small enough to be phagocytosed.

Cloud Computing has been envisioned as the next-generation architecture of IT Enterprise. It moves the application software and databases to the centralized large data centers, where the management of the data and services may not be fully trustworthy. This unique paradigm brings about many new security challenges, which have not been well understood. This work studies the problem of ensuring the integrity of data storage in Cloud Computing. In particular, we consider the task of allowing a third party auditor (TPA), on behalf of the cloud client, to verify the integrity of the dynamic data stored in the cloud. The introduction of TPA eliminates the involvement of client through the auditing of whether his data stored in the cloud is indeed intact, which can be important in achieving economies of scale for Cloud Computing. The support for data dynamics via the most general forms of data operation, such as block modification, insertion and deletion, is also a significant step toward practicality, since services in Cloud Computing are not limited to archive or backup data only. While prior works on ensuring remote data integrity often lacks the support of either public verifiability or dynamic data operations, this paper achieves both. We first identify the difficulties and potential security problems of direct extensions with fully dynamic data updates from prior works and then show how to construct an elegant verification scheme for seamless integration of these two salient features in our protocol design. In particular, to achieve efficient data dynamics, we improve the Proof of Retrievability model [1] by manipulating the classic Merkle Hash Tree (MHT) construction for block tag authentication. Extensive security and performance analysis show that the proposed scheme is highly efficient and provably secure.

Power train electrification is promoted as a potential alternative to reduce carbon intensity of transportation. Lithium-ion batteries are found to be suitable for hybrid electric vehicles (HEVs) and pure electric vehicles (EVs), and temperature control on lithium batteries is vital for long-term performance and durability. Unfortunately, battery thermal management (BTM) has not been paid close attention partly due to poor understanding of battery thermal behaviour. Cell performance change dramatically with temperature, but it improves with temperature if a suitable operating temperature window is sustained. This paper provides a review on two aspects that are battery thermal model development and thermal management strategies. Thermal effects of lithium-ion batteries in terms of thermal runaway and response under cold temperatures will be studied, and heat generation methods are discussed with aim of performing accurate battery thermal analysis. In addition, current BTM strategies utilised by automotive suppliers will be reviewed to identify the imposing challenges and critical gaps between research and practice. Optimising existing BTMs and exploring new technologies to mitigate battery thermal impacts are required, and efforts in prioritising BTM should be made to improve the temperature uniformity across the battery pack, prolong battery lifespan, and enhance the safety of large packs.

As Cloud Computing becomes prevalent, more and more sensitive information are being centralized into the cloud. For the protection of data privacy, sensitive data usually have to be encrypted before outsourcing, which makes effective data utilization a very challenging task. Although traditional searchable encryption schemes allow a user to securely search over encrypted data through keywords and selectively retrieve files of interest, these techniques support only exact keyword search. That is, there is no tolerance of minor typos and format inconsistencies which, on the other hand, are typical user searching behavior and happen very frequently. This significant drawback makes existing techniques unsuitable in Cloud Computing as it greatly affects system usability, rendering user searching experiences very frustrating and system efficacy very low. In this paper, for the first time we formalize and solve the problem of effective fuzzy keyword search over encrypted cloud data while maintaining keyword privacy. Fuzzy keyword search greatly enhances system usability by returning the matching files when users' searching inputs exactly match the predefined keywords or the closest possible matching files based on keyword similarity semantics, when exact match fails. In our solution, we exploit edit distance to quantify keywords similarity and develop an advanced technique on constructing fuzzy keyword sets, which greatly reduces the storage and representation overheads. Through rigorous security analysis, we show that our proposed solution is secure and privacy-preserving, while correctly realizing the goal of fuzzy keyword search.

<h3>Importance</h3> A vaccine against coronavirus disease 2019 (COVID-19) is urgently needed. <h3>Objective</h3> To evaluate the safety and immunogenicity of an investigational inactivated whole-virus COVID-19 vaccine in China. <h3>Interventions</h3> In the phase 1 trial, 96 participants were assigned to 1 of the 3 dose groups (2.5, 5, and 10 μg/dose) and an aluminum hydroxide (alum) adjuvant–only group (n = 24 in each group), and received 3 intramuscular injections at days 0, 28, and 56. In the phase 2 trial, 224 adults were randomized to 5 μg/dose in 2 schedule groups (injections on days 0 and 14 [n = 84] vs alum only [n = 28], and days 0 and 21 [n = 84] vs alum only [n = 28]). <h3>Design, Setting, and Participants</h3> Interim analysis of ongoing randomized, double-blind, placebo-controlled, phase 1 and 2 clinical trials to assess an inactivated COVID-19 vaccine. The trials were conducted in Henan Province, China, among 96 (phase 1) and 224 (phase 2) healthy adults aged between 18 and 59 years. Study enrollment began on April 12, 2020. The interim analysis was conducted on June 16, 2020, and updated on July 27, 2020. <h3>Main Outcomes and Measures</h3> The primary safety outcome was the combined adverse reactions 7 days after each injection, and the primary immunogenicity outcome was neutralizing antibody response 14 days after the whole-course vaccination, which was measured by a 50% plaque reduction neutralization test against live severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). <h3>Results</h3> Among 320 patients who were randomized (mean age, 42.8 years; 200 women [62.5%]), all completed the trial up to 28 days after the whole-course vaccination. The 7-day adverse reactions occurred in 3 (12.5%), 5 (20.8%), 4 (16.7%), and 6 (25.0%) patients in the alum only, low-dose, medium-dose, and high-dose groups, respectively, in the phase 1 trial; and in 5 (6.0%) and 4 (14.3%) patients who received injections on days 0 and 14 for vaccine and alum only, and 16 (19.0%) and 5 (17.9%) patients who received injections on days 0 and 21 for vaccine and alum only, respectively, in the phase 2 trial. The most common adverse reaction was injection site pain, followed by fever, which were mild and self-limiting; no serious adverse reactions were noted. The geometric mean titers of neutralizing antibodies in the low-, medium-, and high-dose groups at day 14 after 3 injections were 316 (95% CI, 218-457), 206 (95% CI, 123-343), and 297 (95% CI, 208-424), respectively, in the phase 1 trial, and were 121 (95% CI, 95-154) and 247 (95% CI, 176-345) at day 14 after 2 injections in participants receiving vaccine on days 0 and 14 and on days 0 and 21, respectively, in the phase 2 trial. There were no detectable antibody responses in all alum-only groups. <h3>Conclusions and Relevance</h3> In this interim report of the phase 1 and phase 2 trials of an inactivated COVID-19 vaccine, patients had a low rate of adverse reactions and demonstrated immunogenicity; the study is ongoing. Efficacy and longer-term adverse event assessment will require phase 3 trials. <h3>Trial Registration</h3> Chinese Clinical Trial Registry Identifier:ChiCTR2000031809

<h3>Importance</h3> Although effective vaccines against COVID-19 have been developed, additional vaccines are still needed. <h3>Objective</h3> To evaluate the efficacy and adverse events of 2 inactivated COVID-19 vaccines. <h3>Design, Setting, and Participants</h3> Prespecified interim analysis of an ongoing randomized, double-blind, phase 3 trial in the United Arab Emirates and Bahrain among adults 18 years and older without known history of COVID-19. Study enrollment began on July 16, 2020. Data sets used for the interim analysis of efficacy and adverse events were locked on December 20, 2020, and December 31, 2020, respectively. <h3>Interventions</h3> Participants were randomized to receive 1 of 2 inactivated vaccines developed from SARS-CoV-2 WIV04 (5 µg/dose; n = 13 459) and HB02 (4 µg/dose; n = 13 465) strains or an aluminum hydroxide (alum)–only control (n = 13 458); they received 2 intramuscular injections 21 days apart. <h3>Main Outcomes and Measures</h3> The primary outcome was efficacy against laboratory-confirmed symptomatic COVID-19 14 days following a second vaccine dose among participants who had no virologic evidence of SARS-CoV-2 infection at randomization. The secondary outcome was efficacy against severe COVID-19. Incidence of adverse events and reactions was collected among participants who received at least 1 dose. <h3>Results</h3> Among 40 382 participants randomized to receive at least 1 dose of the 2 vaccines or alum-only control (mean age, 36.1 years; 32 261 [84.4%] men), 38 206 (94.6%) who received 2 doses, contributed at least 1 follow-up measure after day 14 following the second dose, and had negative reverse transcriptase–polymerase chain reaction test results at enrollment were included in the primary efficacy analysis. During a median (range) follow-up duration of 77 (1-121) days, symptomatic COVID-19 was identified in 26 participants in the WIV04 group (12.1 [95% CI, 8.3-17.8] per 1000 person-years), 21 in the HB02 group (9.8 [95% CI, 6.4-15.0] per 1000 person-years), and 95 in the alum-only group (44.7 [95% CI, 36.6-54.6] per 1000 person-years), resulting in a vaccine efficacy, compared with alum-only, of 72.8% (95% CI, 58.1%-82.4%) for WIV04 and 78.1% (95% CI, 64.8%-86.3%) for HB02 (<i>P</i> &lt; .001 for both). Two severe cases of COVID-19 occurred in the alum-only group and none occurred in the vaccine groups. Adverse reactions 7 days after each injection occurred in 41.7% to 46.5% of participants in the 3 groups; serious adverse events were rare and similar in the 3 groups (WIV04: 64 [0.5%]; HB02: 59 [0.4%]; alum-only: 78 [0.6%]). <h3>Conclusions and Relevance</h3> In this prespecified interim analysis of a randomized clinical trial, treatment of adults with either of 2 inactivated SARS-CoV-2 vaccines significantly reduced the risk of symptomatic COVID-19, and serious adverse events were rare. Data collection for final analysis is pending. <h3>Trial Registration</h3> ClinicalTrials.gov Identifier:NCT04510207; Chinese Clinical Trial Registry:ChiCTR2000034780

Cloud computing has been envisioned as the next-generation architecture of IT enterprise. In contrast to traditional solutions, where the IT services are under proper physical, logical and personnel controls, cloud computing moves the application software and databases to the large data centers, where the management of the data and services may not be fully trustworthy. This unique attribute, however, poses many new security challenges which have not been well understood. In this article, we focus on cloud data storage security, which has always been an important aspect of quality of service. To ensure the correctness of users' data in the cloud, we propose an effective and flexible distributed scheme with two salient features, opposing to its predecessors. By utilizing the homomorphic token with distributed verification of erasure-coded data, our scheme achieves the integration of storage correctness insurance and data error localization, i.e., the identification of misbehaving server (s). Unlike most prior works, the new scheme further supports secure and efficient dynamic operations on data blocks, including: data update, delete and append. Extensive security and performance analysis shows that the proposed scheme is highly efficient and resilient against Byzantine failure, malicious data modification attack, and even server colluding attacks.

Three-dimensional flower-like and hierarchical porous carbon material (FHPC) has been fabricated through a simple and efficient carbonization method followed by chemical activation with flower-like ZnO as template and pitch as carbon precursor. The hierarchical porous structure is composed of numerous micropores and well-defined mesopores in the interconnected macroporous walls. The FHPC electrode can achieve a relatively high capacitance of 294 F g−1 at a scan rate of 2 mV s−1 and excellent rate capability (71% retention at 500 mV s−1) with superior cycle stability (only 2% loss after 5000 cycles) in 6 mol L−1 KOH electrolyte. The symmetric supercapacitor fabricated with FHPC electrodes delivers a high energy density of 15.9 Wh kg−1 at a power density of 317.5 W kg−1 operated in the voltage range of 0–1.8 V in 1 mol L−1 Na2SO4 aqueous electrolyte.

Single walled carbon nanotubes with Pd Ohmic contacts and lengths ranging from several microns down to 10 nm are investigated by electron transport experiments and theory. The mean-free path (MFP) for acoustic phonon scattering is estimated to be ${l}_{\mathrm{ap}}\ensuremath{\sim}300\text{ }\text{ }\mathrm{nm}$, and that for optical phonon scattering is ${l}_{\mathrm{op}}\ensuremath{\sim}15\text{ }\text{ }\mathrm{nm}$. Transport through very short ($\ensuremath{\sim}10\text{ }\text{ }\mathrm{nm}$) nanotubes is free of significant acoustic and optical phonon scattering and thus ballistic and quasiballistic at the low- and high-bias voltage limits, respectively. High currents of up to $70\text{ }\ensuremath{\mu}\mathrm{A}$ can flow through a short nanotube. Possible mechanisms for the eventual electrical breakdown of short nanotubes at high fields are discussed. The results presented here have important implications to high performance nanotube transistors and interconnects.

Cloud storage enables users to remotely store their data and enjoy the on-demand high quality cloud applications without the burden of local hardware and software management. Though the benefits are clear, such a service is also relinquishing users' physical possession of their outsourced data, which inevitably poses new security risks toward the correctness of the data in cloud. In order to address this new problem and further achieve a secure and dependable cloud storage service, we propose in this paper a flexible distributed storage integrity auditing mechanism, utilizing the homomorphic token and distributed erasure-coded data. The proposed design allows users to audit the cloud storage with very lightweight communication and computation cost. The auditing result not only ensures strong cloud storage correctness guarantee, but also simultaneously achieves fast data error localization, i.e., the identification of misbehaving server. Considering the cloud data are dynamic in nature, the proposed design further supports secure and efficient dynamic operations on outsourced data, including block modification, deletion, and append. Analysis shows the proposed scheme is highly efficient and resilient against Byzantine failure, malicious data modification attack, and even server colluding attacks.

Abstract SARS-CoV-2 Omicron subvariants BA.2.12.1 and BA.4/5 have surged notably to become dominant in the United States and South Africa, respectively 1,2 . These new subvariants carrying further mutations in their spike proteins raise concerns that they may further evade neutralizing antibodies, thereby further compromising the efficacy of COVID-19 vaccines and therapeutic monoclonals. We now report findings from a systematic antigenic analysis of these surging Omicron subvariants. BA.2.12.1 is only modestly (1.8-fold) more resistant to sera from vaccinated and boosted individuals than BA.2. However, BA.4/5 is substantially (4.2-fold) more resistant and thus more likely to lead to vaccine breakthrough infections. Mutation at spike residue L452 found in both BA.2.12.1 and BA.4/5 facilitates escape from some antibodies directed to the so-called class 2 and 3 regions of the receptor-binding domain 3 . The F486V mutation found in BA.4/5 facilitates escape from certain class 1 and 2 antibodies but compromises the spike affinity for the viral receptor. The R493Q reversion mutation, however, restores receptor affinity and consequently the fitness of BA.4/5. Among therapeutic antibodies authorized for clinical use, only bebtelovimab retains full potency against both BA.2.12.1 and BA.4/5. The Omicron lineage of SARS-CoV-2 continues to evolve, successively yielding subvariants that are not only more transmissible but also more evasive to antibodies.

Electric-field-directed growth of single-walled carbon nanotubes by chemical-vapor deposition is demonstrated. The field-alignment effect originates from the high polarizability of single-walled nanotubes. Large induced dipole moments lead to large aligning torques and forces on the nanotube, and prevent randomization of nanotube orientation by thermal fluctuations and gas flows. The results shall open up possibilities in directed growth of ordered molecular-wire architectures and networks on surfaces.

Cracks are typical line structures that are of interest in many computer-vision applications. In practice, many cracks, e.g., pavement cracks, show poor continuity and low contrast, which brings great challenges to image-based crack detection by using low-level features. In this paper, we propose DeepCrack - an end-to-end trainable deep convolutional neural network for automatic crack detection by learning high-level features for crack representation. In this method, multi-scale deep convolutional features learned at hierarchical convolutional stages are fused together to capture the line structures. More detailed representations are made in larger-scale feature maps and more holistic representations are made in smaller-scale feature maps. We build DeepCrack net on the encoder-decoder architecture of SegNet, and pairwisely fuse the convolutional features generated in the encoder network and in the decoder network at the same scale. We train DeepCrack net on one crack dataset and evaluate it on three others. The experimental results demonstrate that DeepCrack achieves F-Measure over 0.87 on the three challenging datasets in average and outperforms the current state-of-the-art methods.

High performance enhancement mode semiconducting carbon nanotube field-effect transistors (CNTFETs) are obtained by combining ohmic metal-tube contacts, high dielectric constant HfO2 films as gate insulators, and electrostatically doped nanotube segments as source/drain electrodes. The combination of these elements affords high ON currents, subthreshold swings of ~ 70-80 mV/decade, and allows for low OFF currents and suppressed ambipolar conduction. The doped source and drain approach resembles that of MOSFETs and can impart excellent OFF states to nanotube FETs under aggressive vertical scaling. This presents an important advantage over devices with metal source/drain, or devices commonly referred to as Schottky barrier FETs.

Recently, self-healing hydrogel bioelectronic devices have raised enormous interest for their tissue-like mechanical compliance, desirable biocompatibility, and tunable adhesiveness on bioartificial organs. However, the practical applications of these hydrogel-based sensors are generally limited by their poor fulfillment of stretchability and sensitivity, brittleness under subzero temperature, and single sensory function. Inspired by the fiber-reinforced microstructures and mechano-transduction systems of human muscles, a self-healing (90.8%), long-lasting thermal tolerant and dual-sensory hydrogel-based sensor is proposed, with high gauge factor (18.28) within broad strain range (268.9%), low limit of detection (5% strain), satisfactory thermosensation (−0.016 °C–1), and highly discernible temperature resolution (2.7 °C). Especially by introducing a glycerol/water binary solvent system, desirable subzero-temperature self-healing performance, high water-retaining, and durable adhesion feature can be achieved, resulting from the ice crystallization inhibition and highly dynamic bonding. On account of the advantageous mechanoreception and thermosensitive capacities, a flexible touch keyboard for signature identification and a “fever indicator” for human forehead’s temperature detection can be realized by this hydrogel bioelectronic device.

The BQ and XBB subvariants of SARS-CoV-2 Omicron are now rapidly expanding, possibly due to altered antibody evasion properties deriving from their additional spike mutations. Here, we report that neutralization of BQ.1, BQ.1.1, XBB, and XBB.1 by sera from vaccinees and infected persons was markedly impaired, including sera from individuals boosted with a WA1/BA.5 bivalent mRNA vaccine. Titers against BQ and XBB subvariants were lower by 13- to 81-fold and 66- to 155-fold, respectively, far beyond what had been observed to date. Monoclonal antibodies capable of neutralizing the original Omicron variant were largely inactive against these new subvariants, and the responsible individual spike mutations were identified. These subvariants were found to have similar ACE2-binding affinities as their predecessors. Together, our findings indicate that BQ and XBB subvariants present serious threats to current COVID-19 vaccines, render inactive all authorized antibodies, and may have gained dominance in the population because of their advantage in evading antibodies.

Single-walled carbon nanotubes (SWNT) are grown by a plasma enhanced chemical vapor deposition (PECVD) method at 600 °C. The nanotubes are of high quality as characterized by microscopy, Raman spectroscopy, and electrical transport measurements. High performance field effect transistors are obtained with the PECVD nanotubes. Interestingly, electrical characterization reveals that nearly 90% of the nanotubes are semiconductors and thus highly preferential growth of semiconducting over metallic tubes in the PECVD process. Control experiments with other nanotube materials find that HiPco nanotubes consist of ∼61% semiconductors, while laser ablation preferentially grows metallic SWNTs (∼70%). The characterization method used here should also be applicable to assessing the degree of chemical separation of metallic and semiconducting nanotubes.

It has been reported that protein adsorption on single-walled carbon nanotube field effect transistors (FETs) leads to appreciable changes in the electrical conductance of the devices, a phenomenon that can be exploited for label-free detection of biomolecules with a high potential for miniaturization. This work presents an elucidation of the electronic biosensing mechanisms with a newly developed microarray of nanotube "micromat" sensors. Chemical functionalization schemes are devised to block selected components of the devices from protein adsorption, self-assembled monolayers (SAMs) of methoxy(poly(ethylene glycol))thiol (mPEG-SH) on the metal electrodes (Au, Pd) and PEG-containing surfactants on the nanotubes. Extensive characterization reveals that electronic effects occurring at the metal-nanotube contacts due to protein adsorption constitute a more significant contribution to the electronic biosensing signal than adsorption solely along the exposed lengths of the nanotubes.

Federated learning, i.e., a mobile edge computing framework for deep learning, is a recent advance in privacy-preserving machine learning, where the model is trained in a decentralized manner by the clients, i.e., data curators, preventing the server from directly accessing those private data from the clients. This learning mechanism significantly challenges the attack from the server side. Although the state-of-the-art attacking techniques that incorporated the advance of Generative adversarial networks (GANs) could construct class representatives of the global data distribution among all clients, it is still challenging to distinguishably attack a specific client (i.e., user-level privacy leakage), which is a stronger privacy threat to precisely recover the private data from a specific client. This paper gives the first attempt to explore user-level privacy leakage against the federated learning by the attack from a malicious server. We propose a framework incorporating GAN with a multi-task discriminator, which simultaneously discriminates category, reality, and client identity of input samples. The novel discrimination on client identity enables the generator to recover user specified private data. Unlike existing works that tend to interfere the training process of the federated learning, the proposed method works “invisibly” on the server side. The experimental results demonstrate the effectiveness of the proposed attacking approach and the superior to the state-of-the-art.

Carbon nanotube field-effect transistors with structures and properties near the scaling limit with short (down to 50 nm) channels, self aligned geometries, palladium electrodes with low contact resistance and high-k dielectric gate insulators are realized. Electrical transport in these miniature transistors is near ballistic up to high biases at both room and low temperatures. Atomic layer deposited (ALD) high-k films interact with nanotube sidewalls via van der Waals interactions without causing weak localization at 4 K. New fundamental understanding of ballistic transport, optical phonon scattering and potential interfacial scattering mechanisms in nanotubes are obtained.

Abstract Sorafenib is a multikinase inhibitor capable of facilitating apoptosis, mitigating angiogenesis and suppressing tumor cell proliferation. In late-stage hepatocellular carcinoma (HCC), sorafenib is currently an effective first-line therapy. Unfortunately, the development of drug resistance to sorafenib is becoming increasingly common. This study aims to identify factors contributing to resistance and ways to mitigate resistance. Recent studies have shown that epigenetics, transport processes, regulated cell death, and the tumor microenvironment are involved in the development of sorafenib resistance in HCC and subsequent HCC progression. This study summarizes discoveries achieved recently in terms of the principles of sorafenib resistance and outlines approaches suitable for improving therapeutic outcomes for HCC patients.

Osteoarthritis, the breakdown of cartilage in synovial joints, has long been viewed as the result of 'wear and tear', but this report shows that dysregulation of the complement system has an active role in the pathogenesis of this disease. Osteoarthritis, characterized by the breakdown of articular cartilage in synovial joints, has long been viewed as the result of 'wear and tear'1. Although low-grade inflammation is detected in osteoarthritis, its role is unclear2,3,4. Here we identify a central role for the inflammatory complement system in the pathogenesis of osteoarthritis. Through proteomic and transcriptomic analyses of synovial fluids and membranes from individuals with osteoarthritis, we find that expression and activation of complement is abnormally high in human osteoarthritic joints. Using mice genetically deficient in complement component 5 (C5), C6 or the complement regulatory protein CD59a, we show that complement, specifically, the membrane attack complex (MAC)-mediated arm of complement, is crucial to the development of arthritis in three different mouse models of osteoarthritis. Pharmacological modulation of complement in wild-type mice confirmed the results obtained with genetically deficient mice. Expression of inflammatory and degradative molecules was lower in chondrocytes from destabilized joints from C5-deficient mice than C5-sufficient mice, and MAC induced production of these molecules in cultured chondrocytes. Further, MAC colocalized with matrix metalloprotease 13 (MMP13) and with activated extracellular signal-regulated kinase (ERK) around chondrocytes in human osteoarthritic cartilage. Our findings indicate that dysregulation of complement in synovial joints has a key role in the pathogenesis of osteoarthritis.

We report the fabrication of single-walled carbon nanotube (SWNT) DNA sensors and the sensing mechanism. The simple and generic protocol for label-free detection of DNA hybridization is demonstrated with random sequence 15mer and 30mer oligonucleotides. DNA hybridization on gold electrodes, instead of on SWNT sidewalls, is mainly responsible for the acute electrical conductance change due to the modulation of energy level alignment between SWNT and gold contact. This work provides concrete experimental evidence on the effect of SWNT−DNA binding on DNA functionality, which will help to pave the way for future designing of SWNT biocomplexes for applications in biotechnology in general and also DNA-assisted nanotube manipulation techniques.

An electromechanical system is constructed to explore the electrical properties of various types of suspended single-walled carbon nanotubes under the influence of tensile stretching. Small band-gap semiconducting (or quasimetallic) nanotubes exhibit the largest resistance changes and piezoresistive gauge factors ( approximately 600 to 1000) under axial strains. Metallic nanotubes exhibit much weaker but nonzero sensitivity. Comparison between experiments and theoretical predictions and potential applications of nanotube electromechanical systems for physical sensors (e.g., strain gauges, pressure sensors, etc.) are discussed.

The emerging COVID-19 caused by SARS-CoV-2 infection poses severe challenges to global public health. Serum antibody testing is becoming one of the critical methods for the diagnosis of COVID-19 patients. We investigated IgM and IgG responses against SARS-CoV-2 nucleocapsid (N) and spike (S) protein after symptom onset in the intensive care unit (ICU) and non-ICU patients. 130 blood samples from 38 COVID-19 patients were collected. The levels of IgM and IgG specific to N and S protein were detected by ELISA. A series of blood samples were collected along the disease course from the same patient, including 11 ICU patients and 27 non-ICU patients for longitudinal analysis. N and S specific IgM and IgG (N-IgM, N-IgG, S-IgM, S-IgG) in non-ICU patients increased after symptom onset. N-IgM and S-IgM in some non-ICU patients reached a peak in the second week, while N-IgG and S-IgG continued to increase in the third week. The combined detection of N and S specific IgM and IgG could identify up to 75% of SARS-CoV-2 infected patients in the first week. S-IgG was significantly higher in non-ICU patients than in ICU patients in the third week. In contrast, N-IgG was significantly higher in ICU patients than in non-ICU patients. The increase of S-IgG positively correlated with the decrease of C-reactive protein (CRP) in non-ICU patients. N and S specific IgM and IgG increased gradually after symptom onset and can be used for detection of SARS-CoV-2 infection. Analysis of the dynamics of S-IgG may help to predict prognosis.

Medical imaging plays a critical role in various clinical applications. However, due to multiple considerations such as cost and radiation dose, the acquisition of certain image modalities may be limited. Thus, medical image synthesis can be of great benefit by estimating a desired imaging modality without incurring an actual scan. In this paper, we propose a generative adversarial approach to address this challenging problem. Specifically, we train a fully convolutional network (FCN) to generate a target image given a source image. To better model a nonlinear mapping from source to target and to produce more realistic target images, we propose to use the adversarial learning strategy to better model the FCN. Moreover, the FCN is designed to incorporate an image-gradient-difference-based loss function to avoid generating blurry target images. Long-term residual unit is also explored to help the training of the network. We further apply Auto-Context Model to implement a context-aware deep convolutional adversarial network. Experimental results show that our method is accurate and robust for synthesizing target images from the corresponding source images. In particular, we evaluate our method on three datasets, to address the tasks of generating CT from MRI and generating 7T MRI from 3T MRI images. Our method outperforms the state-of-the-art methods under comparison in all datasets and tasks.

Single-crystal Ge nanowires are synthesized by a low-temperature (275 °C) chemical vapor deposition (CVD) method. Boron doped p-type GeNW field-effect transistors (FETs) with back-gates and thin SiO2 (10 nm) gate insulators are constructed. Hole mobility higher than 600 cm2/V s is observed in these devices, suggesting high quality and excellent electrical properties of as-grown Ge wires. In addition, integration of high-κ HfO2 (12 nm) gate dielectric into nanowire FETs with top-gates is accomplished with promising device characteristics obtained. The nanowire synthesis and device fabrication steps are all performed below 400 °C, opening a possibility of building three-dimensional electronics with CVD-derived Ge nanowires.

Acid in ionic liquid was demonstrated as an efficient system for hydrolysis of lignocellulosic materials with improved total reducing sugars (TRS) yield under mild conditions. TRS yields were up to 66%, 74%, 81% and 68% for hydrolysis of corn stalk, rice straw, pine wood and bagasse, respectively, in C4mimCl in the presence of 7 wt% hydrogen chloride at 100 °C under atmospheric pressure within 60 min. Different combinations between ionic liquids, such as C6mimCl, C4mimBr, AmimCl, C4mimHSO4, and SbmimHSO4, and acids, including sulfuric acid, nitric acid, phosphoric acid, as well as maleic acid, afforded similar results albeit longer reaction time was generally required comparing with the combination of C4mimCl and hydrochloric acid. FT-IR spectra and elemental analysis of the recovered residues indicated that modification of lignin occurred during sulfuric acid catalyzed hydrolysis. In addition, kinetic modeling based on experimental data suggested that the hydrolysis likely followed a consecutive first-order reaction sequence, where k1 and k2, the rate constants for TRS formation and TRS degradation, were determined as 0.068 min−1 and 0.007 min−1, respectively. This novel system may be valuable to facilitate cost-efficient conversion of biomass into biofuels and biobased products.

An oxygen assisted hydrocarbon chemical vapor deposition (CVD) method is developed to afford large-scale highly reproducible ultra high-yield growth of vertical single-walled carbon nanotubes (SWNT). It is revealed that reactive hydrogen (H)-species, inevitable in hydrocarbon-based growth, are damaging to the formation of sp2-like SWNTs. The addition of oxygen scavenges H-species and provides a powerful control over the C/H ratio to favor SWNT growth. The revelation of the roles played by hydrogen and oxygen leads to a unified and universal optimum growth condition for SWNTs. Further, a versatile method is developed to form vertical SWNT films on any substrate, lifting a major substrate-type limitation for aligned SWNTs.

Plutus is a cryptographic storage system that enables secure file sharing without placing much trust on the file servers. In particular, it makes novel use of cryptographic primitives to protect and share files. Plutus features highly scalable key management while allowing individual users to retain direct control over who gets access to their files. We explain the mechanisms in Plutus to reduce the number of cryptographic keys exchanged between users by using filegroups, distinguish file read and write access, handle user revocation efficiently, and allow an untrusted server to authorize file writes. We have built a prototype of Plutus on OpenAFS. Measurements of this prototype show that Plutus achieves strong security with overhead comparable to systems that encrypt all network traffic.

Abstract Potassium‐ion batteries (KIBs) are very promising alternatives to lithium‐ion batteries (LIBs) for large‐scale energy storage. However, traditional carbon anode materials usually show poor performance in KIBs due to the large size of K ions. Herein, a carbonization‐etching strategy is reported for making a class of sulfur (S) and oxygen (O) codoped porous hard carbon microspheres (PCMs) material as a novel anode for KIBs through pyrolysis of the polymer microspheres (PMs) composed of a liquid crystal/epoxy monomer/thiol hardener system. The as‐made PCMs possess a porous architecture with a large Brunauer–Emmett–Teller surface area (983.2 m 2 g −1 ), an enlarged interlayer distance (0.393 nm), structural defects induced by the S/O codoping and also amorphous carbon nature. These new features are important for boosting potassium ion storage, allowing the PCMs to deliver a high potassiation capacity of 226.6 mA h g −1 at 50 mA g −1 over 100 cycles and be displaying high stability by showing a potassiation capacity of 108.4 mA h g −1 over 2000 cycles at 1000 mA g −1 . The density functional theory calculations demonstrate that S/O codoping not only favors the adsorption of K to the PCMs electrode but also reduces its structural deformation during the potassiation/depotassiation. The present work highlights the important role of hierarchical porosity and S/O codoping in potassium storage.

EK1 is a broad-spectrum human coronavirus fusion inhibitor for combating infection of current and emerging coronaviruses.

Contacting metallic single-walled carbon nanotubes by palladium (Pd) affords highly reproducible ohmic contacts and allows for detailed elucidation of ballistic transport in metallic nanotubes. The Pd ohmic contacts are more reliable than titanium (Ti) previously used for ballistic nanotube devices. In contrast, Pt contacts appear to give non-ohmic contacts to metallic nanotubes. For both ohmic and non-ohmic contacts, the length of the nanotube under the metal contact area is electrically turned off. Transport occurs from metal to nanotube at the edges of the contacts. Measurements with large numbers of Pd contacted nanotube samples reveal that the mean free path for defect scattering in SWNTs grown by chemical vapor deposition can be up to 4 microns. The mean free paths for acoustic phonon scattering are on the order of 500 nm at room temperature and >> 4 microns at low temperatures.

Freely suspended metallic single-walled carbon nanotubes (SWNTs) exhibit reduced current carrying ability compared to those lying on substrates, and striking negative differential conductance at low electric fields. Theoretical analysis reveals significant self-heating effects including electron scattering by hot nonequilibrium optical phonons. Electron transport characteristics under strong self-heating are exploited for the first time to probe the thermal conductivity of individual SWNTs (approximately 3600 W m-1 K-1 at T=300 K) up to approximately 700 K, and reveal a 1/T dependence expected for umklapp phonon scattering at high temperatures.

As the black cesium lead iodide (CsPbI3) tends to transit into a yellow δ-phase at ambient, it is imperative to develop a stabilized black phase for photovoltaic applications. Herein, we report a distorted black CsPbI3 film by exploiting the synergistic effect of hydroiodic acid (HI) and phenylethylammonium iodide (PEAI) additives. It is found that the HI induces formation of hydrogen lead iodide (HPbI3+x), an intermediate to the distorted black phase with appropriate band gap of 1.69 eV; while PEAI provides nucleation for optimized crystallization. More importantly, it stabilizes the distorted black phase by hindering phase transition via its steric effects. Upon optimization, we have attained solar cell efficiency as high as 15.07%. Specifically, the bare cell without any encapsulation shows negligible efficiency loss after 300 h of light soaking. The device keeps 92% of its initial cell efficiency after being stored for 2 months under ambient conditions.

The growing cost of tuning and managing computer systems is leading to out-sourcing of commercial services to hosting centers. These centers provision thousands of dense servers within a relatively small real-estate in order to host the applications/services of different customers who may have been assured by a service-level agreement (SLA). Power consumption of these servers is becoming a serious concern in the design and operation of the hosting centers. The effects of high power consumption manifest not only in the costs spent in designing effective cooling systems to ward off the generated heat, but in the cost of electricity consumption itself. It is crucial to deploy power management strategies in these hosting centers to lower these costs towards enhancing profitability. At the same time, techniques for power management that include shutting down these servers and/or modulating their operational speed, can impact the ability of the hosting center to meet SLAs. In addition, repeated on-off cycles can increase the wear-and-tear of server components, incurring costs for their procurement and replacement. This paper presents a formalism to this problem, and proposes three new online solution strategies based on steady state queuing analysis, feedback control theory, and a hybrid mechanism borrowing ideas from these two. Using real web server traces, we show that these solutions are more adaptive to workload behavior when performing server provisioning and speed control than earlier heuristics towards minimizing operational costs while meeting the SLAs.

A new photothermal coupling agent for photothermal ablation (PTA) therapy of tumors is developed based on ultrathin PEGylated W18O49 nanowires. After being injected with the nanowire solution, the in vivo tumors exhibit a rapid temperature rise to 50.0 ± 0.5 °C upon irradiation with NIR laser light at a safe, low intensity (0.72 W cm−2) for 2 min (left-hand mouse in the figure),), resulting in the efficient PTA of cancer cells in vivo in 10 min. As a service to our authors and readers, this journal provides supporting information supplied by the authors. Such materials are peer reviewed and may be re-organized for online delivery, but are not copy-edited or typeset. Technical support issues arising from supporting information (other than missing files) should be addressed to the authors. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.

Abstract Motivation: RNA-seq has been widely used in transcriptome analysis to effectively measure gene expression levels. Although sequencing costs are rapidly decreasing, almost 70% of all the human RNA-seq samples in the gene expression omnibus do not have biological replicates and more unreplicated RNA-seq data were published than replicated RNA-seq data in 2011. Despite the large amount of single replicate studies, there is currently no satisfactory method for detecting differentially expressed genes when only a single biological replicate is available. Results: We present the GFOLD (generalized fold change) algorithm to produce biologically meaningful rankings of differentially expressed genes from RNA-seq data. GFOLD assigns reliable statistics for expression changes based on the posterior distribution of log fold change. In this way, GFOLD overcomes the shortcomings of P-value and fold change calculated by existing RNA-seq analysis methods and gives more stable and biological meaningful gene rankings when only a single biological replicate is available. Availability: The open source C/C++ program is available at http://www.tongji.edu.cn/∼zhanglab/GFOLD/index.html Contact: xsliu@jimmy.harvard.edu or yzhang@tongji.edu.cn Supplementary information: Supplementary data are available at Bioinformatics online.

It is imperative to develop a large-aspect-ratio grain-based thin film with low trap density for high-performance inorganic perovskite CsPbI2Br solar cells. Herein, by using Mn2+ ion doping to modulate film growth, we achieved CsPbI2Br grains with aspect ratios as high as 8. It is found that Mn2+ ions insert into the interstices of the CsPbI2Br lattice during the growth process, leading to suppressed nucleation and a decreased growth rate. The combination aids in the achievement of larger CsPbI2Br crystalline grains for increased JSC values as high as 14.37 mA/cm2 and FFs as large as 80.0%. Moreover, excess Mn2+ ions passivate the grain boundary and surface defects, resulting in effectively decreased recombination loss with improved hole extraction efficiency, which enhances the built-in electric field and hence increases VOC to 1.172 V. As a result, the champion device achieves stabilized efficiency as high as 13.47%, improved by 13% compared with only 11.88% for the reference device.

The cyclooxygenases COX-1 and COX-2 catalyze the first committed step of prostaglandin synthesis from arachidonic acid. Previous studies in rodent stroke models have shown that the inducible COX-2 isoform promotes neuronal injury, and the administration of COX-2 inhibitors reduces infarct volume. We investigated the function of PGE 2 , a principal prostaglandin product of COX-2 enzymatic activity, in neuronal survival in cerebral ischemia. PGE 2 exerts its downstream effects by signaling through a class of four distinct G-protein-coupled EP receptors (for E-prostanoid: EP1, EP2, EP3, and EP4) that have divergent effects on cAMP and phosphoinositol turnover and different anatomical distributions in brain. The EP2 receptor subtype is abundantly expressed in cerebral cortex, striatum, and hippocampus, and is positively coupled to cAMP production. In vitro studies of dispersed neurons and organotypic hippocampal cultures demonstrated that activation of the EP2 receptor was neuroprotective in paradigms of NMDA toxicity and oxygen glucose deprivation. Pharmacologic blockade of EP2 signaling by inhibition of protein kinase A activation reversed this protective effect, suggesting that EP2-mediated neuroprotection is dependent on cAMP signaling. In the middle cerebral artery occlusion-reperfusion model of transient forebrain ischemia, genetic deletion of the EP2 receptor significantly increased cerebral infarction in cerebral cortex and subcortical structures. These studies indicate that activation of the PGE 2 EP2 receptor can protect against excitotoxic and anoxic injury in a cAMP-dependent manner. Taken together, these data suggest a novel mechanism of neuroprotection mediated by a dominant PGE 2 receptor subtype in brain that may provide a target for therapeutic intervention.

Hydrogen is an attractive energy carrier due to its potentially high energy efficiency and low generation of pollutants, which can be used for transportation and stationary power generation. However, hydrogen is not readily available in sufficient quantities and the production cost is still high. Steam methane reforming (SMR) process is now the most widely used technology for H2 production, but this process is complex and cannot get thorough carbon capture. Hydrogen production using chemical looping technology has received a great deal of attention in recent years because it can produce hydrogen with higher process efficiency and can capture carbon dioxide. Many researchers have carried out intensive research work on the hydrogen production processes using chemical looping technology. Based on the previous studies stated in the literature, the authors try to give an overview on the recent advances of two categories, chemical looping reforming (CLR) and chemical looping hydrogen production (CLH) processes. Besides, the characteristics of the processes are pointed out based on the comparison with the conventional SMR process. The existing technical problems and the aspects of future research of each approach are also summarized.

A novel human coronavirus, Middle East respiratory syndrome coronavirus (MERS-CoV), has caused outbreaks of a SARS-like illness with high case fatality rate. The reports of its person-to-person transmission through close contacts have raised a global concern about its pandemic potential. Here we characterize the six-helix bundle fusion core structure of MERS-CoV spike protein S2 subunit by X-ray crystallography and biophysical analysis. We find that two peptides, HR1P and HR2P, spanning residues 998–1039 in HR1 and 1251–1286 in HR2 domains, respectively, can form a stable six-helix bundle fusion core structure, suggesting that MERS-CoV enters into the host cell mainly through membrane fusion mechanism. HR2P can effectively inhibit MERS-CoV replication and its spike protein-mediated cell–cell fusion. Introduction of hydrophilic residues into HR2P results in significant improvement of its stability, solubility and antiviral activity. Therefore, the HR2P analogues have good potential to be further developed into effective viral fusion inhibitors for treating MERS-CoV infection. MERS-CoV is a novel human coronavirus that has recently caused outbreaks of respiratory illness with high case fatality rate. Here the authors characterize the membrane fusion apparatus of MERS-CoV and develop a peptide that can inhibit virus fusion and replication in vitro.

Exosomes are cell-derived vesicles and are abundant in biological fluids; they contain RNA molecules which may serve as potential diagnostic biomarkers in ‘precision medicine’. To promote the clinical application of exosomal RNA (exoRNA), many isolation methods must be compared and validated. Exosomes in cell culture medium (CCM) and serum may be isolated using ultracentrifugation (UC), ExoQuick or Total Exosome Isolation Reagent (TEI), and exoRNA may be extracted using TRIzol-LS, SeraMir, Total Exosome RNA Isolation (TER), HiPure Liquid RNA/miRNA kit (HLR), miRNeasy or exoRNeasy. ExoRNA was assessed using NanoDrop, Bioanalyzer 2100, quantitative polymerase chain reaction and high-throughput sequencing. UC showed the lowest recovery of particles, but the highest protein purity for exosome isolation. For isolation of exoRNA, we found that combinations of the TEI and TER methods resulted in high extraction efficiency and purity of small RNA obtained using CCM. High yield and a narrow size distribution pattern of small RNA were shown in exoRNA isolated by exoRNeasy from serum. In RNA profile analysis, the small RNA constituent ratio, miRNA content and amount varied as a result of methodological differences. This study showed that different methods may introduce variations in the concentration, purity and size of exosomes and exoRNA. Herein we discuss the advantages and disadvantages of each method and their application to different materials, therefore providing a reference according to research design.

Circular RNAs (circRNAs) represent a new type of regulatory RNA which forms a covalently closed continuous loop from back-splicing events, a process in which the downstream 5' splice site and the 3' splice site are covalently linked. Emerging evidence indicates that circRNAs exert a new layer of transcriptional and post-transcriptional regulation of gene expression. However, there is no standard nomenclature of circRNA, although the study of circRNAs has exploded in the past few years. Here we present circbank ( www.circbank.cn ), a comprehensive database for human circRNAs, where a novel naming system of circRNAs based on the host genes of circRNAs was implemented. In addition to the new naming system, circbank collected other five features of circRNAs including the miRNA binding site, conservation of circRNAs, m6A modification of circRNAs, mutation of circRNAs and protein-coding potential of circRNAs. Circbank is publicly available and allows users to query, browse and download circRNAs with all six features we provided, based on different search criteria. The database may serve as a resource to facilitate the research of function and regulation of circRNAs.

This work demonstrates multistage complementary NOR, OR, NAND, and AND logic gates and ring oscillators (frequency ∼220 Hz) with arrays of p- and n-type nanotube field effect transistors (FETs). The demonstration is made possible by progress in three aspects of nanotube synthesis and integration. First, patterned growth leads to large numbers of nanotube FETs in an array, as up to 70% of individual nanotubes are semiconductors. Second, metal electrodes are successfully embedded underneath nanotubes and used as local gates. Third, complementary logic gates are made possible by converting p-type FETs in an array into n-type FETs by a local electrical manipulation and doping approach.

Alzheimer's disease (AD) affects half the US population over the age of 85 and is universally fatal following an average course of 10 years of progressive cognitive disability. Genetic and genome-wide association studies (GWAS) have identified about 33 risk factor genes for common, late-onset AD (LOAD), but these risk loci fail to account for the majority of affected cases and can neither provide clinically meaningful prediction of development of AD nor offer actionable mechanisms. This cohort study generated large-scale matched multi-Omics data in AD and control brains for exploring novel molecular underpinnings of AD. Specifically, we generated whole genome sequencing, whole exome sequencing, transcriptome sequencing and proteome profiling data from multiple regions of 364 postmortem control, mild cognitive impaired (MCI) and AD brains with rich clinical and pathophysiological data. All the data went through rigorous quality control. Both the raw and processed data are publicly available through the Synapse software platform.

Recent advances highlight a pivotal role for cellular metabolism in programming immune responses. Here, we demonstrate that cell-autonomous generation of nicotinamide adenine dinucleotide (NAD+) via the kynurenine pathway (KP) regulates macrophage immune function in aging and inflammation. Isotope tracer studies revealed that macrophage NAD+ derives substantially from KP metabolism of tryptophan. Genetic or pharmacological blockade of de novo NAD+ synthesis depleted NAD+, suppressed mitochondrial NAD+-dependent signaling and respiration, and impaired phagocytosis and resolution of inflammation. Innate immune challenge triggered upstream KP activation but paradoxically suppressed cell-autonomous NAD+ synthesis by limiting the conversion of downstream quinolinate to NAD+, a profile recapitulated in aging macrophages. Increasing de novo NAD+ generation in immune-challenged or aged macrophages restored oxidative phosphorylation and homeostatic immune responses. Thus, KP-derived NAD+ operates as a metabolic switch to specify macrophage effector responses. Breakdown of de novo NAD+ synthesis may underlie declining NAD+ levels and rising innate immune dysfunction in aging and age-associated diseases.

The coronavirus disease (COVID-19) is rapidly spreading all over the world, and has infected more than 1,436,000 people in more than 200 countries and territories as of April 9, 2020. Detecting COVID-19 at early stage is essential to deliver proper healthcare to the patients and also to protect the uninfected population. To this end, we develop a dual-sampling attention network to automatically diagnose COVID-19 from the community acquired pneumonia (CAP) in chest computed tomography (CT). In particular, we propose a novel online attention module with a 3D convolutional network (CNN) to focus on the infection regions in lungs when making decisions of diagnoses. Note that there exists imbalanced distribution of the sizes of the infection regions between COVID-19 and CAP, partially due to fast progress of COVID-19 after symptom onset. Therefore, we develop a dual-sampling strategy to mitigate the imbalanced learning. Our method is evaluated (to our best knowledge) upon the largest multi-center CT data for COVID-19 from 8 hospitals. In the training-validation stage, we collect 2186 CT scans from 1588 patients for a 5-fold cross-validation. In the testing stage, we employ another independent large-scale testing dataset including 2796 CT scans from 2057 patients. Results show that our algorithm can identify the COVID-19 images with the area under the receiver operating characteristic curve (AUC) value of 0.944, accuracy of 87.5%, sensitivity of 86.9%, specificity of 90.1%, and F1-score of 82.0%. With this performance, the proposed algorithm could potentially aid radiologists with COVID-19 diagnosis from CAP, especially in the early stage of the COVID-19 outbreak.

<h2>Summary</h2> All-inorganic perovskite shows great potential for photovoltaic applications due to its excellent solar cell performance and atmospheric stability. Here, a CsPbI_2+xBr_1−x perovskite solar cell with a graded bandgap is explored using CsPbBrI₂ and CsPbI₃ quantum dots as component cells. Four strategies were pursued to boost the device performance. First, CsPbI₂Br film was fabricated as the main absorber, with the component cell showing remarkable power conversion efficiency (PCE) as high as 13.45%. Second, by Mn²⁺ substitution, SCN⁻ capping, and [(NH₂)₂CH]⁺ treatment, stable and high-mobility CsPbI₃ quantum dot (QD) film was attained. Third, a halide-ion-profiled heterojunction was designed at the CsPbBrI₂/CsPbI₃ QD interface to achieve proper band-edge bending as graded bandgap for improved carrier collection. Finally, the CsPbI₃ QD layer was optimized in the graded bandgap structure to achieve maximum overall light harvesting. As a result, the device achieved a PCE of 14.45%. This is the highest efficiency ever reported for inorganic perovskite solar cells.

Abstract Each component layer in a perovskite solar cell plays an important role in the cell performance. Here, a few types of polymers including representative p‐type and n‐type semiconductors, and a classical insulator, are chosen to dope into a perovskite film. The long‐chain polymer helps to form a network among the perovskite crystalline grains, as witnessed by the improved film morphology and device stability. The dewetting process is greatly suppressed by the cross‐linking effect of the polymer chains, thereby resulting in uniform perovskite films with large grain sizes. Moreover, it is found that the polymer‐doped perovskite shows a reduced trap‐state density, likely due to the polymer effectively passivating the perovskite grain surface. Meanwhile the doped polymer formed a bridge between grains for efficient charge transport. Using this approach, the solar cell efficiency is improved from 17.43% to as high as 19.19%, with a much improved stability. As it is not required for the polymer to have a strict energy level matching with the perovskite, in principle, one may use a variety of polymers for this type of device design.

To investigate the status of Phosphatidylinositol 3-kinase (PI3K)/PTEN/AKT/mammalian target of rapamycin (mTOR) pathway and its correlation with clinicopathological features and matrix metalloproteinase-2, -9 (MMP-2, 9) in human hepatocellular carcinoma (HCC).PTEN, Phosphorylated AKT (p-AKT), Phosphorylated mTOR (p-mTOR), MMP-2, MMP-9 and Ki-67 expression levels were evaluated by immunohistochemistry on tissue microarrays containing 200 HCCs with paired adjacent non-cancerous liver tissues. PTEN, MMP-2 and MMP-9 mRNA levels were determined by real-time RT-PCR in 36 HCCs. The relationships between PI3K/PTEN/AKT/mTOR pathway and clinicopathological factors and MMP-2, 9 were analyzed in HCC.In HCC, PTEN loss and overexpression of p-AKT and p-mTOR were associated with tumor grade, intrahepatic metastasis, vascular invasion, TNM stage and high Ki-67 labeling index (P < 0.05). PTEN loss was correlated with p-AKT, p-mTOR and MMP-9 overexpression. Furthermore, PTEN and MMP-2, 9 mRNA levels were down-regulated and up-regulated in HCC compared with paired non-cancerous liver tissues, respectively (P < 0.01). PTEN, MMP-2 and MMP-9 mRNA levels were correlated with tumor stage and metastasis. There was an inverse correlation between PTEN and MMP-9 mRNA expression. However, PI3K/PTEN/AKT/mTOR pathway was not correlated with MMP-2.PI3K/PTEN/AKT/mTOR pathway, which is activated in HCC, is involved in invasion and metastasis through up-regulating MMP-9 in HCC.

Abstract All‐inorganic CsPbBrI 2 perovskite has great advantages in terms of ambient phase stability and suitable band gap (1.91 eV) for photovoltaic applications. However, the typically used structure causes reduced device performance, primarily due to the large recombination at the interface between the perovskite, and the hole‐extraction layer (HEL). In this paper, an efficient CsPbBrI 2 perovskite solar cell (PSC) with a dimensionally graded heterojunction is reported, in which the CsPbBrI 2 material is distributed within bulk–nanosheet–quantum dots or 3D–2D–0D dimension‐profiled interface structure so that the energy alignment is optimized in between the valence and conduction bands of both CsPbBrI 2 and the HEL layers. Specifically, the valence‐/conduction‐band edge is leveraged to bend with synergistic advantages: the graded combination enhances the hole extraction and conduction efficiency with effectively decreased recombination loss during the hole‐transfer process, leading to an enhanced built‐in electric field, hence a high V OC of as much as 1.19 V. The profiled structure induces continuously upshifted energy levels, resulting in a higher J SC of as much as 12.93 mA cm −2 and fill factor as high as 80.5%, and therefore record power conversion efficiency (PCE) of 12.39%. As far as it is known, this is the highest PCE for CsPbBrI 2 perovskite‐based PSC.

This paper presents an investigation on a single-mode-multimode-single-mode fiber structure. A one-way guided-mode propagation analysis for the circular symmetry waveguide is employed to model the light propagation and the approximated formulations are derived and evaluated concerning the accuracy. Phase conjunction of the multimode interference within the fiber structure is revealed. A simple way to predict and analyze the spectral response of the structure is presented through the space to wavelength mapping with the derived approximated formulations. The prediction of spectral response is verified numerically and experimentally.

Generalized nucleus segmentation techniques can contribute greatly to reducing the time to develop and validate visual biomarkers for new digital pathology datasets. We summarize the results of MoNuSeg 2018 Challenge whose objective was to develop generalizable nuclei segmentation techniques in digital pathology. The challenge was an official satellite event of the MICCAI 2018 conference in which 32 teams with more than 80 participants from geographically diverse institutes participated. Contestants were given a training set with 30 images from seven organs with annotations of 21,623 individual nuclei. A test dataset with 14 images taken from seven organs, including two organs that did not appear in the training set was released without annotations. Entries were evaluated based on average aggregated Jaccard index (AJI) on the test set to prioritize accurate instance segmentation as opposed to mere semantic segmentation. More than half the teams that completed the challenge outperformed a previous baseline. Among the trends observed that contributed to increased accuracy were the use of color normalization as well as heavy data augmentation. Additionally, fully convolutional networks inspired by variants of U-Net, FCN, and Mask-RCNN were popularly used, typically based on ResNet or VGG base architectures. Watershed segmentation on predicted semantic segmentation maps was a popular post-processing strategy. Several of the top techniques compared favorably to an individual human annotator and can be used with confidence for nuclear morphometrics.

Starches, a storage form of carbohydrates, are a major source of calories in the human diet and a primary feedstock for bioindustry. We report a chemical-biochemical hybrid pathway for starch synthesis from carbon dioxide (CO2) and hydrogen in a cell-free system. The artificial starch anabolic pathway (ASAP), consisting of 11 core reactions, was drafted by computational pathway design, established through modular assembly and substitution, and optimized by protein engineering of three bottleneck-associated enzymes. In a chemoenzymatic system with spatial and temporal segregation, ASAP, driven by hydrogen, converts CO2 to starch at a rate of 22 nanomoles of CO2 per minute per milligram of total catalyst, an ~8.5-fold higher rate than starch synthesis in maize. This approach opens the way toward future chemo-biohybrid starch synthesis from CO2.

While various monocyte chemokine systems are increased in expression in osteoarthritis (OA), the hierarchy of chemokines and chemokine receptors in mediating monocyte/macrophage recruitment to the OA joint remains poorly defined. Here, we investigated the relative contributions of the CCL2/CCR2 versus CCL5/CCR5 chemokine axes in OA pathogenesis.Ccl2-, Ccr2-, Ccl5- and Ccr5-deficient and control mice were subjected to destabilisation of medial meniscus surgery to induce OA. The pharmacological utility of blocking CCL2/CCR2 signalling in mouse OA was investigated using bindarit, a CCL2 synthesis inhibitor, and RS-504393, a CCR2 antagonist. Levels of monocyte chemoattractants in synovial tissues and fluids from patients with joint injuries without OA and those with established OA were investigated using a combination of microarray analyses, multiplexed cytokine assays and immunostains.Mice lacking CCL2 or CCR2, but not CCL5 or CCR5, were protected against OA with a concomitant reduction in local monocyte/macrophage numbers in their joints. In synovial fluids from patients with OA, levels of CCR2 ligands (CCL2, CCL7 and CCL8) but not CCR5 ligands (CCL3, CCL4 and CCL5) were elevated. We found that CCR2+ cells are abundant in human OA synovium and that CCR2+ macrophages line, invade and are associated with the erosion of OA cartilage. Further, blockade of CCL2/CCR2 signalling markedly attenuated macrophage accumulation, synovitis and cartilage damage in mouse OA.Our findings demonstrate that monocytes recruited via CCL2/CCR2, rather than by CCL5/CCR5, propagate inflammation and tissue damage in OA. Selective targeting of the CCL2/CCR2 system represents a promising therapeutic approach for OA.

The emergence of human infection with a novel H7N9 influenza virus in China raises a pandemic concern. Chicken H9N2 viruses provided all six of the novel reassortant's internal genes. However, it is not fully understood how the prevalence and evolution of these H9N2 chicken viruses facilitated the genesis of the novel H7N9 viruses. Here we show that over more than 10 y of cocirculation of multiple H9N2 genotypes, a genotype (G57) emerged that had changed antigenicity and improved adaptability in chickens. It became predominant in vaccinated farm chickens in China, caused widespread outbreaks in 2010-2013 before the H7N9 viruses emerged in humans, and finally provided all of their internal genes to the novel H7N9 viruses. The prevalence and variation of H9N2 influenza virus in farmed poultry could provide an important early warning of the emergence of novel reassortants with pandemic potential.

Fluorogenic Cu(I)-catalyzed alkyne-azide cycloaddition (CuAAC) reactions have emerged as a powerful tool for bioconjugation, materials science, organic synthesis and drug discovery. This review highlights the design of the recent development of fluorogenic CuAAC reactions as well as their applications.

Pores and pores: Metal–organic framework (MOF) nanospheres with long-range ordered mesopores, the walls of which are composed of microporous structure units, were synthesized in binary solvent systems of ionic liquid and supercritical CO2. The MOF nanostructure has many potential applications and its preparation could easily be applied to MOFs with other metal ions and ligands.

Ti3C2Tx, a 2D titanium carbide in the MXenes family, is obtained from Ti3AlC2 through selective etching of the Al layer. Due to its good conductivity and high volumetric capacitance, Ti3C2Tx is regarded as a promising candidate for supercapacitors. In this paper, the fabrication of Ti3C2Tx/RGO composites with different proportions of Ti3C2Tx and RGO is reported, in which RGO acts as a conductive “bridge” to connect different Ti3C2Tx blocks and a matrix to alleviate the volume change during charge/discharge process. In addition, RGO nanosheets can serve as a second nanoscale current collector and support as well for the electrode. The electrochemical performance of the as-fabricated Ti3C2Tx/RGO electrodes, characterized by CV, GCD, and EIS, are also reported. A highest specific capacitance (Cs) of 154.3 F/g at 2 A/g is obtained at the Ti3C2Tx: RGO weight ratio of 7:1 combined with an outstanding capacity retention (124.7 F/g) after 6000 cycles at 4 A/g.

The fear responses to environmental threats play a fundamental role in survival. Little is known about the neural circuits specifically processing threat-relevant sensory information in the mammalian brain. We identified parvalbumin-positive (PV(+)) excitatory projection neurons in mouse superior colliculus (SC) as a key neuronal subtype for detecting looming objects and triggering fear responses. These neurons, distributed predominantly in the superficial SC, divergently projected to different brain areas, including the parabigeminal nucleus (PBGN), an intermediate station leading to the amygdala. Activation of the PV(+) SC-PBGN pathway triggered fear responses, induced conditioned aversion, and caused depression-related behaviors. Approximately 20% of mice subjected to the fear-conditioning paradigm developed a generalized fear memory.

Dear Editor, The rapid spread of SARS-CoV-2 (also known as 2019-nCoV and HCoV-191), a novel lineage B betacoronavirus (βCoV), has caused a global pandemic of coronavirus disease (COVID-19). It has been speculated that RRAR, a unique furin-like cleavage site (FCS) in the spike protein (S), which is absent in other lineage B βCoVs, such as SARS-CoV, is responsible for its high infectivity and transmissibility.2

The public key infrastructure-based authentication protocol provides basic security services for the vehicular ad hoc networks (VANETs). However, trust and privacy are still open issues due to the unique characteristics of VANETs. It is crucial to prevent internal vehicles from broadcasting forged messages while simultaneously preserving the privacy of vehicles against the tracking attacks. In this paper, we propose a blockchain-based anonymous reputation system (BARS) to establish a privacy-preserving trust model for VANETs. The certificate and revocation transparency is implemented efficiently with the proofs of presence and absence based on the extended blockchain technology. The public keys are used as pseudonyms in communications without any information about real identities for conditional anonymity. In order to prevent the distribution of forged messages, a reputation evaluation algorithm is presented relying on both direct historical interactions and indirect opinions about vehicles. A set of experiments is conducted to evaluate BARS in terms of security, validity, and performance, and the results show that BARS is able to establish a trust model with transparency, conditional anonymity, efficiency, and robustness for VANETs.

Ageing is characterized by the development of persistent pro-inflammatory responses that contribute to atherosclerosis, metabolic syndrome, cancer and frailty1-3. The ageing brain is also vulnerable to inflammation, as demonstrated by the high prevalence of age-associated cognitive decline and Alzheimer's disease4-6. Systemically, circulating pro-inflammatory factors can promote cognitive decline7,8, and in the brain, microglia lose the ability to clear misfolded proteins that are associated with neurodegeneration9,10. However, the underlying mechanisms that initiate and sustain maladaptive inflammation with ageing are not well defined. Here we show that in ageing mice myeloid cell bioenergetics are suppressed in response to increased signalling by the lipid messenger prostaglandin E2 (PGE2), a major modulator of inflammation11. In ageing macrophages and microglia, PGE2 signalling through its EP2 receptor promotes the sequestration of glucose into glycogen, reducing glucose flux and mitochondrial respiration. This energy-deficient state, which drives maladaptive pro-inflammatory responses, is further augmented by a dependence of aged myeloid cells on glucose as a principal fuel source. In aged mice, inhibition of myeloid EP2 signalling rejuvenates cellular bioenergetics, systemic and brain inflammatory states, hippocampal synaptic plasticity and spatial memory. Moreover, blockade of peripheral myeloid EP2 signalling is sufficient to restore cognition in aged mice. Our study suggests that cognitive ageing is not a static or irrevocable condition but can be reversed by reprogramming myeloid glucose metabolism to restore youthful immune functions.

As next-generation artificial enzymes, nanozymes have shown great promise for tumor catalytic therapy. In particular, their peroxidase-like activity has been employed to catalyze hydrogen peroxide (H2O2) to produce highly toxic hydroxyl radicals (•OH) to kill tumor cells. However, limited by the low affinity between nanozymes with H2O2 and the low level of H2O2 in the tumor microenvironment, peroxidase nanozymes usually produced insufficient •OH to kill tumor cells for therapeutic purposes. Herein, we present a pyrite peroxidase nanozyme with ultrahigh H2O2 affinity, resulting in a 4144- and 3086-fold increase of catalytic activity compared with that of classical Fe3O4 nanozyme and natural horseradish peroxidase, respectively. We found that the pyrite nanozyme also possesses intrinsic glutathione oxidase-like activity, which catalyzes the oxidation of reduced glutathione accompanied by H2O2 generation. Thus, the dual-activity pyrite nanozyme constitutes a self-cascade platform to generate abundant •OH and deplete reduced glutathione, which induces apoptosis as well as ferroptosis of tumor cells. Consequently, it killed apoptosis-resistant tumor cells harboring KRAS mutation by inducing ferroptosis. The pyrite nanozyme also exhibited favorable tumor-specific cytotoxicity and biodegradability to ensure its biosafety. These results indicate that the high-performance pyrite nanozyme is an effective therapeutic reagent and may aid the development of nanozyme-based tumor catalytic therapy.

One of the key issues facing public healthcare is the global trend of an increasingly ageing society which continues to present policy makers and caregivers with formidable healthcare and socio-economic challenges. Ageing is the primary contributor to a broad spectrum of chronic disorders all associated with a lower quality of life in the elderly. In 2019, the Chinese population constituted 18 % of the world population, with 164.5 million Chinese citizens aged 65 and above (65+), and 26 million aged 80 or above (80+). China has become an ageing society, and as it continues to age it will continue to exacerbate the burden borne by current family and public healthcare systems. Major healthcare challenges involved with caring for the elderly in China include the management of chronic non-communicable diseases (CNCDs), physical frailty, neurodegenerative diseases, cardiovascular diseases, with emerging challenges such as providing sufficient dental care, combating the rising prevalence of sexually transmitted diseases among nursing home communities, providing support for increased incidences of immune diseases, and the growing necessity to provide palliative care for the elderly. At the governmental level, it is necessary to make long-term strategic plans to respond to the pressures of an ageing society, especially to establish a nationwide, affordable, annual health check system to facilitate early diagnosis and provide access to affordable treatments. China has begun work on several activities to address these issues including the recent completion of the of the Ten-year Health-Care Reform project, the implementation of the Healthy China 2030 Action Plan, and the opening of the National Clinical Research Center for Geriatric Disorders. There are also societal challenges, namely the shift from an extended family system in which the younger provide home care for their elderly family members, to the current trend in which young people are increasingly migrating towards major cities for work, increasing reliance on nursing homes to compensate, especially following the outcomes of the 'one child policy' and the 'empty-nest elderly' phenomenon. At the individual level, it is important to provide avenues for people to seek and improve their own knowledge of health and disease, to encourage them to seek medical check-ups to prevent/manage illness, and to find ways to promote modifiable health-related behaviors (social activity, exercise, healthy diets, reasonable diet supplements) to enable healthier, happier, longer, and more productive lives in the elderly. Finally, at the technological or treatment level, there is a focus on modern technologies to counteract the negative effects of ageing. Researchers are striving to produce drugs that can mimic the effects of 'exercising more, eating less', while other anti-ageing molecules from molecular gerontologists could help to improve 'healthspan' in the elderly. Machine learning, 'Big Data', and other novel technologies can also be used to monitor disease patterns at the population level and may be used to inform policy design in the future. Collectively, synergies across disciplines on policies, geriatric care, drug development, personal awareness, the use of big data, machine learning and personalized medicine will transform China into a country that enables the most for its elderly, maximizing and celebrating their longevity in the coming decades. This is the 2nd edition of the review paper (Fang EF et al., Ageing Re. Rev. 2015).

Motivated by the recent study of inspiring thermoelectric properties in bulk SnSe [Zhao et al., Nature, 2014, 508, 373] and the experimental synthesis of SnSe sheets [Chen et al., J. Am. Chem. Soc., 2013, 135, 1213], we have carried out systematic calculations for a single-layered SnSe sheet focusing on its stability, electronic structure and thermoelectric properties by using density functional theory combined with Boltzmann transport theory. We have found that the sheet is dynamically and thermally stable with a band gap of 1.28 eV, and the figure of merit (ZT) reaches 3.27 (2.76) along the armchair (zigzag) direction with optimal n-type carrier concentration, which is enhanced nearly 7 times compared to its bulk counterpart at 700 K due to quantum confinement effect. Furthermore, we designed four types of thermoelectric couples by assembling single-layered SnSe sheets with different transport directions and doping types, and found that their efficiencies are all above 13%, which are higher than those of thermoelectric couples made of commercial bulk Bi2Te3 (7%-8%), suggesting the great potential of single-layered SnSe sheets for heat-electricity conversion.

A significant requirement for a bone implant is to replicate the functional gradient across the bone to mimic the localization change in stiffness. In this work, continuous functionally graded porous scaffolds (FGPSs) based on the Schwartz diamond unit cell with a wide range of graded volume fraction were manufactured by selective laser melting (SLM). The micro-topology, strut dimension characterization and effect of graded volume fraction on the mechanical properties of SLM-processed FGPSs were systematically investigated. The micro-topology observations indicate that diamond FGPSs with a wide range of graded volume fraction from 7.97% to 19.99% were fabricated without any defects, showing a good geometric reproduction of the original designs. The dimensional characterization demonstrates the capability of SLM in manufacturing titanium diamond FGPSs with the strut size of 483-905µm. The elastic modulus and yield strength of the titanium diamond FGPSs can be tailored in the range of 0.28-0.59GPa and 3.79-17.75MPa respectively by adjusting the graded volume fraction, which are comparable to those of the cancellous bone. The mathematical relationship between the graded porosity and compression properties of a FGPS was revealed. Furthermore, two equations based on the Gibson and Ashby model have been established to predict the modulus and yield strength of SLM-processed diamond FGPSs. Compared to homogeneous diamond porous scaffolds, FGPSs provide a wide range of mutative pore size and porosity, which are potential to be tailored to optimize the pore space for bone tissue growth. The findings provide a basis of new methodologies to design and manufacture superior graded scaffolds for bone implant applications.

Despite the high economic and ecological importance of forests, our knowledge of the genomic evolution of trees under salt stress remains very limited. Here we report the genome sequence of the desert poplar, Populus euphratica, which exhibits high tolerance to salt stress. Its genome is very similar and collinear to that of the closely related mesophytic congener, P. trichocarpa. However, we find that several gene families likely to be involved in tolerance to salt stress contain significantly more gene copies within the P. euphratica lineage. Furthermore, genes showing evidence of positive selection are significantly enriched in functional categories related to salt stress. Some of these genes, and others within the same categories, are significantly upregulated under salt stress relative to their expression in another salt-sensitive poplar. Our results provide an important background for understanding tree adaptation to salt stress and facilitating the genetic improvement of cultivated poplars for saline soils.

Materials that exhibit X-ray-excited luminescence have great potential in radiation detection, security inspection, biomedical applications and X-ray astronomy1–5. However, high-performance materials are almost exclusively limited to ceramic scintillators, which are typically prepared under high temperatures6. Herein we report metal-free organic phosphors based on a molecular design that supports efficient triplet exciton harvesting to enhance radioluminescence. These organic scintillators exhibit a detection limit of 33 nGy s–1, which is 167 times lower than the standard dosage for X-ray medical examination and we demonstrate their potential application in X-ray radiography. These findings provide a fundamental design principle and new route for the creation of promising alternatives to incumbent inorganic scintillators. Furthermore, they offer new opportunities for development of flexible, stretchable X-ray detectors and imagers for non-destructive radiography testing and medical imaging. Organic, metal-free materials that act as efficient X-ray scintillators could bring new opportunities for X-ray imaging.

A dual-trans method to print the first functional liquid-metal circuit layout on poly(vinyl chloride) film, and then transfer it into a poly(dimethylsiloxane) substrate through freeze phase transition processing for the fabrication of a flexible electronic device. A programmable soft electronic band and a temperature-sensing module wirelessly communicate with a mobile phone, demonstrating the efficiency and capability of the method. As a service to our authors and readers, this journal provides supporting information supplied by the authors. Such materials are peer reviewed and may be re-organized for online delivery, but are not copy-edited or typeset. Technical support issues arising from supporting information (other than missing files) should be addressed to the authors. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.

Facility managers usually conduct reactive maintenance or preventive maintenance strategies in building maintenance management. However, there are some limitations that reactive maintenance cannot prevent failure, and preventive maintenance cannot predict the future condition of MEP components and repair in advance to extend the lifetime of facilities. Therefore, this study aims to apply a predictive maintenance strategy with advanced technologies to overcome these limitations. Building information modeling (BIM) and Internet of Things (IoT) have the potential to improve the efficiency of facility maintenance management (FMM). Despite the significant efforts that have been made to apply BIM and IoT to the architecture, engineering, construction, and facility management (AEC/FM) industry, BIM and IoT integration for FMM is still at an initial stage. In order to provide a better maintenance strategy for building facilities, a data-driven predictive maintenance planning framework based on BIM and IoT technologies for FMM was developed, consisting of an information layer and an application layer. Data collection and data integration among the BIM models, FM system, and IoT network are undertaken in the information layer, while the application layer contains four modules to achieve predictive maintenance, namely: (1) condition monitoring and fault alarming module, (2) condition assessment module, (3) condition prediction module, and (4) maintenance planning module. Machine learning algorithms, ANN and SVM, are used to predict the future condition of MEP components. Furthermore, the developed framework was applied in an illustrative example to validate the feasibility of the approach. The results show that the constantly updated data obtained from the information layer together with the machine learning algorithms in the application layer can efficiently predict the future condition of MEP components for maintenance planning.

The mechanical properties of epithelial to mesenchymal transition (EMT) and a pancreatic cancer subpopulation with stem cell properties have been increasingly recognized as potent modulators of the effective of therapy. In particular, pancreatic cancer stem cells (PCSCs) are functionally important during tumor relapse and therapy resistance. In this review we have surveyed recent advances in the role of EMT and PCSCs in tumor progression, metastasis and treatment resistance, and the mechanisms of integrated with biochemical signals and the underlying pathways involved in treatment resistance of pancreatic cancer. These findings highlight the importance of confirming stem-cells markers and complex molecular signaling pathways controlling EMT and cancer stem cells in pancreatic cancer during tumor formation, progression, and response to therapy.