Guang-Chao Chen

Mature adipocytes and myocytes are derived from a common mesenchymal precursor. While IGF-1 promotes the differentiation of both cell types, the signaling pathways that specify the distinct cell fates are largely unknown. Here, we show that the Rho GTPase and its regulator, p190-B RhoGAP, are components of a critical switch in the adipogenesis-myogenesis "decision." Cells derived from embryos lacking p190-B RhoGAP exhibit excessive Rho activity, are defective for adipogenesis, but undergo myogenesis in response to IGF-1 exposure. In vitro, activation of Rho-kinase by Rho inhibits adipogenesis and is required for myogenesis. The activation state of Rho following IGF-1 signaling is determined by the tyrosine-phosphorylation status of p190-B RhoGAP and its resulting subcellular relocalization. Moreover, adjusting Rho activity is sufficient to alter the differentiation program of adipocyte and myocyte precursors. Together, these results identify the Rho GTPase as an essential modulator of IGF-1 signals that direct the adipogenesis-myogenesis cell fate decision.

Autophagy is a highly conserved catabolic process that degrades and recycles intracellular components through the lysosomes. Atg9 is the only integral membrane protein among autophagy-related (Atg) proteins thought to carry the membrane source for forming autophagosomes. Here we show that Drosophila Atg9 interacts with Drosophila tumor necrosis factor receptor-associated factor 2 (dTRAF2) to regulate the c-Jun N-terminal kinase (JNK) signaling pathway. Significantly, depletion of Atg9 and dTRAF2 compromised JNK-mediated intestinal stem cell proliferation and autophagy induction upon bacterial infection and oxidative stress stimulation. In mammalian cells, mAtg9 interacts with TRAF6, the homolog of dTRAF2, and plays an essential role in regulating oxidative stress-induced JNK activation. Moreover, we found that ROS-induced autophagy acts as a negative feedback regulator of JNK activity by dissociating Atg9/mAtg9 from dTRAF2/TRAF6 in Drosophila and mammalian cells, respectively. Our findings indicate a dual role for Atg9 in the regulation of JNK signaling and autophagy under oxidative stress conditions.

The ubiquitin-proteasome system (UPS) and autophagy are two major quality control processes whose impairment is linked to a wide variety of diseases. The coordination between UPS and autophagy remains incompletely understood. Here, we show that ubiquitin ligase UBE3C and deubiquitinating enzyme TRABID reciprocally regulate K29/K48-branched ubiquitination of VPS34. We find that this ubiquitination enhances the binding of VPS34 to proteasomes for degradation, thereby suppressing autophagosome formation and maturation. Under ER and proteotoxic stresses, UBE3C recruitment to phagophores is compromised with a concomitant increase of its association with proteasomes. This switch attenuates the action of UBE3C on VPS34, thereby elevating autophagy activity to facilitate proteostasis, ER quality control and cell survival. Specifically in the liver, we show that TRABID-mediated VPS34 stabilization is critical for lipid metabolism and is downregulated during the pathogenesis of steatosis. This study identifies a ubiquitination type on VPS34 and elucidates its cellular fate and physiological functions in proteostasis and liver metabolism.

Excessive generation and accumulation of highly reactive oxidizing molecules causes oxidative stress and oxidative damage to cellular components. Accumulating evidence indicates that autophagy diminishes oxidative damage in cells and maintains redox homeostasis by degrading and recycling intracellular damaged components. Here, we show that TRAF6 E3 ubiquitin ligase and A20 deubiquitinase coordinate to regulate ATG9A ubiquitination and autophagy activation in cells responding to oxidative stress. The ROS-dependent TRAF6-mediated non-proteolytic, K48/63-linked ubiquitination of ATG9A enhances its association with Beclin 1 and the assembly of VPS34-UVRAG complex, thereby stimulating autophagy. Notably, expression of the ATG9A ubiquitination mutants impairs ROS-induced VPS34 activation and autophagy. We further find that lipopolysaccharide (LPS)-induced ROS production also stimulates TRAF6-mediated ATG9A ubiquitination. Ablation of ATG9A causes aberrant TLR4 endosomal trafficking and decreases IRF-3 phosphorylation in LPS-stimulated macrophages. Our findings provide important insights into how K48/K63-linked ubiquitination of ATG9A contributes to the regulation of oxidative stress-induced autophagy.

Relative potency factors (RPFs) for per- and polyfluoroalkyl substances (PFAS) have previously been derived based on liver effects in rodents for the purpose of performing mixture risk assessment with primary input from biomonitoring studies. However, in 2020, EFSA established a tolerable weekly intake for four PFAS assuming equal toxic potency for immune suppressive effects in humans. In this study we explored the possibility of deriving RPFs for immune suppressive effects using available data in rodents and humans. Lymphoid organ weights, differential blood cell counts, and clinical chemistry from 28-day studies in male rats from the National Toxicology Program (NTP) were combined with modeled serum PFAS concentrations to derive internal RPFs by applying dose-response modelling. Identified functional studies used diverse protocols and were not suitable for derivation of RPFs but were used to support immunotoxicity of PFAS in a qualitative manner. Furthermore, a novel approach was used to estimate internal RPFs based on epidemiological data by dose-response curve fitting optimization, looking at serum antibody concentrations and key cell populations from the National Health and Nutrition Examination Survey (NHANES). Internal RPFs were successfully derived for PFAS based on rat thymus weight, spleen weight, and globulin concentration. The available dose-response information for blood cell counts did not show a significant trend. Immunotoxic potency in serum was determined in the order PFDA > PFNA > PFHxA > PFOS > PFBS > PFOA > PFHxS. The epidemiological data showed inverse associations for the sum of PFOA, PFNA, PFHxS, and PFOS with serum antibody concentrations to mumps and rubella, but the data did not allow for deduction of reliable internal RPF estimates. The internal RPFs for PFAS based on decreased rat lymphoid organ weights are similar to those previously established for increased rat liver weight, strengthening the confidence in the overall applicability of these RPFs.

Macroautophagy/autophagy is a complex degradation process with a dual role in cell death that is influenced by the cell types that are involved and the stressors they are exposed to. Ferroptosis is an iron-dependent oxidative form of cell death characterized by unrestricted lipid peroxidation in the context of heterogeneous and plastic mechanisms. Recent studies have shed light on the involvement of specific types of autophagy (e.g. ferritinophagy, lipophagy, and clockophagy) in initiating or executing ferroptotic cell death through the selective degradation of anti-injury proteins or organelles. Conversely, other forms of selective autophagy (e.g. reticulophagy and lysophagy) enhance the cellular defense against ferroptotic damage. Dysregulated autophagy-dependent ferroptosis has implications for a diverse range of pathological conditions. This review aims to present an updated definition of autophagy-dependent ferroptosis, discuss influential substrates and receptors, outline experimental methods, and propose guidelines for interpreting the results.

Abstract Quantitative risk assessments of chemicals are routinely performed using in vivo data from rodents; however, there is growing recognition that non‐animal approaches can be human‐relevant alternatives. There is an urgent need to build confidence in non‐animal alternatives given the international support to reduce the use of animals in toxicity testing where possible. In order for scientists and risk assessors to prepare for this paradigm shift in toxicity assessment, standardization and consensus on in vitro testing strategies and data interpretation will need to be established. To address this issue, an Expert Working Group (EWG) of the 8th International Workshop on Genotoxicity Testing (IWGT) evaluated the utility of quantitative in vitro genotoxicity concentration‐response data for risk assessment. The EWG first evaluated available in vitro methodologies and then examined the variability and maximal response of in vitro tests to estimate biologically relevant values for the critical effect sizes considered adverse or unacceptable. Next, the EWG reviewed the approaches and computational models employed to provide human‐relevant dose context to in vitro data. Lastly, the EWG evaluated risk assessment applications for which in vitro data are ready for use and applications where further work is required. The EWG concluded that in vitro genotoxicity concentration‐response data can be interpreted in a risk assessment context. However, prior to routine use in regulatory settings, further research will be required to address the remaining uncertainties and limitations.

A novel carbon allotrope, T-carbon, is attempted to obtain by using plasma enhanced chemical vapor deposition (PECVD) on the substrates of polycrystalline diamond and single crystalline diamond, respectively. Our measured x-ray diffraction, Raman and infrared spectra of the new form of carbon are in good agreement with the calculated results of T-carbon, and the lattice parameter meets with the results of calculation as well as the high resolution electron microscopy of T-carbon nanowires synthesized by the pulsed laser irradiating modification of carbon multiwall nanotubes, revealing that the phase of T-carbon can be identified in our samples. The experimental preparation of T-carbon by PECVD method indicates that the massive production of T-carbon may be feasible, and extensive investigations with high-throughput experiments on this novel phase are highly expected.

Data dissemination in Internet of Vehicles (IoVs) is attracting more and more attention. However, few efforts have been made on mixed data dissemination in urban scenario. The rigid Quality of Service (QoS) requirements of Emergency Messages (EMs), the varied QoS tolerant degrees of Service Messages (SMs), and the complex transmission environment in urban scenario pose great challenges. In this paper, a Cluster-based Vehicle-to-Vehicle (V2V) approach for Mixed Data Dissemination (CMDD) is proposed to tackle the aforementioned challenges in urban scenario of IoVs. The proposed approach consists of two main algorithms: the bus-based clustering and the mixed data scheduling. To deal with the complex and harsh transmission environment in urban scenario, we propose to use buses, which have fixed driving routes and schedules as well as sufficient resources, to act as cluster heads. Meanwhile, multiple characteristics are deeply analyzed and artfully utilized in the design of the clustering algorithm, to achieve efficient data dissemination from buses to ordinary vehicles. To meet the rigid and personalized QoS requirements of EMs/SMs under stringent resources, a new priority calculation method is proposed and mixed data are scheduled accordingly. Simulation results show that the proposed approach achieves remarkable performance advantage in terms of data download delay, emergency warning ratio and service response ratio.

Autophagy is essential for maintaining cellular homeostasis and survival under various stress conditions. Autophagy-related gene 9 (Atg9) encodes a multipass transmembrane protein thought to act as a membrane carrier for forming autophagosomes. However, the molecular regulation and physiological importance of Atg9 in animal development remain largely unclear. Here, we generated Atg9 null mutant flies and found that loss of Atg9 led to shortened lifespan, locomotor defects, and increased susceptibility to stress. Atg9 loss also resulted in aberrant adult midgut morphology with dramatically enlarged enterocytes. Interestingly, inhibiting the TOR signaling pathway rescued the midgut defects of the Atg9 mutants. In addition, Atg9 interacted with PALS1-associated tight junction protein (Patj), which associates with TSC2 to regulate TOR activity. Depletion of Atg9 caused a marked decrease in TSC2 levels. Our findings revealed an antagonistic relationship between Atg9 and TOR signaling in the regulation of cell growth and tissue homeostasis.

Paxillin is a prominent focal adhesion docking protein that regulates cell adhesion and migration. Although numerous paxillin-binding proteins have been identified and paxillin is required for normal embryogenesis, the precise mechanism by which paxillin functions in vivo has not yet been determined. We identified an ortholog of mammalian paxillin in Drosophila (Dpax) and have undertaken a genetic analysis of paxillin function during development. Overexpression of Dpax disrupted leg and wing development, suggesting a role for paxillin in imaginal disc morphogenesis. These defects may reflect a function for paxillin in regulation of Rho family GTPase signaling as paxillin interacts genetically with Rac and Rho in the developing eye. Moreover, a gain-of-function suppressor screen identified a genetic interaction between Dpax and cdi in wing development. cdi belongs to the cofilin kinase family, which includes the downstream Rho target, LIM kinase (LIMK). Significantly, strong genetic interactions were detected between Dpax and Dlimk, as well as downstream effectors of Dlimk. Supporting these genetic data, biochemical studies indicate that paxillin regulates Rac and Rho activity, positively regulating Rac and negatively regulating Rho. Taken together, these data indicate the importance of paxillin modulation of Rho family GTPases during development and identify the LIMK pathway as a critical target of paxillin-mediated Rho regulation.

<h2>Abstract</h2> FF domains are poorly understood protein motifs found in all eukaryotes but in a very small number of proteins. They typically occur in tandem arrays and appear predominantly in splicing and transcription factors. Curiously, they are also present in the p190 family of cytoplasmic Rho GTPase activating proteins (GAPs). We identified the serum-responsive transcriptional regulator TFII-I as a specific interactor with the p190 RhoGAP FF domains. p190 sequesters TFII-I in the cytoplasm via the FF domains, but upon PDGF receptor-mediated phosphorylation of an FF domain, TFII-I is released from p190 and translocates to the nucleus where it can activate transcription of serum-inducible genes including c-<i>fos</i>. These findings reveal a pathway by which mitogens promote gene transcription and indicate a role for FF domains in phosphorylation-mediated signal transduction.

Autophagy and molecular chaperones both regulate protein homeostasis and maintain important physiological functions. Atg7 (autophagy-related gene 7) and Hsp27 (heat shock protein 27) are involved in the regulation of neurodegeneration and aging. However, the genetic connection between Atg7 and Hsp27 is not known.The appearances of the fly eyes from the different genetic interactions with or without polyglutamine toxicity were examined by light microscopy and scanning electronic microscopy. Immunofluorescence was used to check the effect of Atg7 and Hsp27 knockdown on the formation of autophagosomes. The lifespan of altered expression of Hsp27 or Atg7 and that of the combination of the two different gene expression were measured.We used the Drosophila eye as a model system to examine the epistatic relationship between Hsp27 and Atg7. We found that both genes are involved in normal eye development, and that overexpression of Atg7 could eliminate the need for Hsp27 but Hsp27 could not rescue Atg7 deficient phenotypes. Using a polyglutamine toxicity assay (41Q) to model neurodegeneration, we showed that both Atg7 and Hsp27 can suppress weak, toxic effect by 41Q, and that overexpression of Atg7 improves the worsened mosaic eyes by the knockdown of Hsp27 under 41Q. We also showed that overexpression of Atg7 extends lifespan and the knockdown of Atg7 or Hsp27 by RNAi reduces lifespan. RNAi-knockdown of Atg7 expression can block the extended lifespan phenotype by Hsp27 overexpression, and overexpression of Atg7 can extend lifespan even under Hsp27 knockdown by RNAi.We propose that Atg7 acts downstream of Hsp27 in the regulation of eye morphology, polyglutamine toxicity, and lifespan in Drosophila.

As listed by the European Chemicals Agency, the three elements in evaluating the hazards of engineered nanomaterials (ENMs) include the integration and evaluation of toxicity data, categorization and labeling of ENMs, and derivation of hazard threshold levels for human health and the environment. Assessing the hazards of ENMs solely based on laboratory tests is time-consuming, resource intensive, and constrained by ethical considerations. The adoption of computational toxicology into this task has recently become a priority. Alternative approaches such as (quantitative) structure-activity relationships ((Q)SAR) and read-across are of significant help in predicting nanotoxicity and filling data gaps, and in classifying the hazards of ENMs to individual species. Thereupon, the species sensitivity distribution (SSD) approach is able to serve the establishment of ENM hazard thresholds sufficiently protecting the ecosystem. This article critically reviews the current knowledge on the development of in silico models in predicting and classifying the hazard of metallic ENMs, and the development of SSDs for metallic ENMs. Further discussion includes the significance of well-curated experimental datasets and the interpretation of toxicity mechanisms of metallic ENMs based on reported models. An outlook is also given on future directions of research in this frontier.

Attenuation of organic compounds in sewage treatment plants (STPs) is affected by a complex interplay between chemical (e.g. ionization, hydrolysis), physical (e.g. sorption, volatilization), and biological (e.g. biodegradation, microbial acclimation) processes. These effects should be accounted for individually, in order to develop predictive cheminformatics tools for STPs. Using measured data from 70 STPs in the Netherlands for 69 chemicals (pharmaceuticals, herbicides, etc.), we highlighted the influences of 1) chemical ionization, 2) sorption to sludge, and 3) acclimation of the microbial consortia on the primary removal of chemicals. We used semi-empirical corrections for each of these influences to deduce biodegradation rate constants upon which quantitative structure-biodegradation relationships (QSBRs) were developed. As shown by a global QSBR, biodegradation in STPs generally relates to structural complexity, size, energetics, and charge distribution. Statistics of the global QSBR were reasonable, being R2training = 0.69 (training set of 51 compounds) and R2validation = 0.50 (validation set of 18 compounds). Class-specific QSBRs utilized electronic properties potentially relating to rate-limiting enzymatic steps. For class-specific QSBRs, values of R2 of in between 0.7 and 0.8 were obtained. With caution, environmental risk assessment methodologies may apply these models to estimate biodegradation rates for ‘data-poor’ compounds. The approach also highlights ‘meta data’ on STP operational parameters needed to develop QSBRs of better predictability in the future.

Nowadays, traffics on the roads are getting more and more congested due to the fast-rising number of vehicles and the increasing need of citizens for mobility. Accidents happen frequently and result great loss of lives and properties. Internet of Vehicles (IoVs), as an important part of Internet of Things (IoTs), is placed high hope for enhancing traffic safety and controlling the damage caused by traffic accidents. According to statistics, most accidents can be avoided if drivers can be notified of a danger timely, so the key to minimize the damage introduced by road traffic accidents is the realization of fast and efficient data dissemination. However, great challenges exist due to the transmission characteristics of IoVs, such as high-speed movement of vehicles and dynamic changing network topologies. In this paper, we propose a vehicle-to-vehicle cooperative video alert dissemination mechanism for transmitting accident video in the highway scenario of IoVs. A two-way cooperative transmission strategy is designed. Vehicles in the same direction of accident vehicle are formed into clusters and communicate within clusters, while vehicles in the opposite direction select relay vehicles to help spreading video fast and reliably. The difficulties brought in by the characteristics of IoVs are solved through careful considerations of multiple factors such as vehicles' speeds, locations, distances, channel conditions and data receiving statuses in the design of the mechanism. Moreover, Scalable Video Coding (SVC) technology is used for encoding the original accident video, to take care of the performance degradation caused by the heterogeneity of vehicles in different locations. Instantly Decodable Network Coding (IDNC) technology is adopted during the cooperative transmission to further improve the transmission efficiency and reliability. Simulation results justify the proposed mechanism that it effectively shortens the accident video transmission delay, increases the success warning ratio, enhances the reconstructed video quality and improves the user satisfaction.

This review establishes an inventory of existing toxicity data on nanoparticles (NPs) with the purpose of developing (Quantitative) Structure-Activity Relationships for NPs (nano-[Q]SARs), and also of maximising the use of scientific sources for NP risk assessment. From a data search carried out on 27 February 2014, a total of 910 publications were retrieved from the Web of Science™ Core Collection, and a database comprising 886 records of toxicity endpoints, based on these publications, was built. The test organisms mainly comprised bacteria, algae, yeast, protozoa, nematoda, crustacea and fish. The NPs consisted mostly of metals, metal oxides, nanocomposites and quantum dots. The data were analysed further, in order to: a) categorise each toxicity endpoint and the biological effects triggered by the NPs; b) survey the characterisation of the NPs used; and c) assess whether the data were suitable for nano-(Q)SAR development. Despite the efforts of numerous scientific programmes on nanomaterial safety and design, our study concluded that lack of data consistency prevents the use of experimental data in developing and validating nano-(Q)SARs. Finally, an outlook on the future of nano-(Q)SAR development is provided.

Organic compounds are capable of generating hydroxyl radicals (˙OH) through their excited triplet states in natural water.

Singlet oxygen (1O2) is capable of degrading organic contaminants and inducing cell damage and inactivation of viruses. It is mainly generated through the interaction of dissolved oxygen with excited triplet states of dissolved organic matter (DOM) in natural waters. The present study aims at revealing the underlying mechanism of 1O2 generation and providing a potential tool for predicting the quantum yield of 1O2 (Φ1O2) generation from DOM by constructing a quantitative structure-activity relationship (QSAR) model. The determined Φ1O2 values for the selected DOM-analogs range from (0.54 ± 0.23) × 10-2 to (62.03 ± 2.97) × 10-2. A QSAR model was constructed and was proved to have satisfactory goodness-of-fit and robustness. The QSAR model was successfully used to predict the Φ1O2 of Suwannee River fulvic acid. Mechanistic interpretation of the descriptors in the model showed that hydrophobicity, molecular complexity and the presence of carbonyl groups in DOM play crucial roles in the generation of 1O2 from DOM. The presence of other heteroatoms besides O, such as N and S, also affects the generation of 1O2. The results of this study provide valuable insights into the generation of 1O2 from DOM in sunlit natural waters.

Ubiquitination and the reverse process deubiquitination regulate protein stability and function during animal development. The Drosophila USP5 homolog Leon functions as other family members of unconventional deubiquitinases, disassembling free, substrate-unconjugated polyubiquitin chains to replenish the pool of mono-ubiquitin, and maintaining cellular ubiquitin homeostasis. However, the significance of Leon/USP5 in animal development is still unexplored. In this study, we generated leon mutants to show that Leon is essential for animal viability and tissue integrity during development. Both free and substrate-conjugated polyubiquitin chains accumulate in leon mutants, suggesting that abnormal ubiquitin homeostasis caused tissue disorder and lethality in leon mutants. Further analysis of protein expression profiles in leon mutants shows that the levels of all proteasomal subunits were elevated. Also, proteasomal enzymatic activities were elevated in leon mutants. However, proteasomal degradation of ubiquitinated substrates was impaired. Thus, aberrant ubiquitin homeostasis in leon mutants disrupts normal proteasomal degradation, which is compensated by elevating the levels of proteasomal subunits and activities. Ultimately, the failure to fully compensate the dysfunctional proteasome in leon mutants leads to animal lethality and tissue disorder.

Epidermal growth factor receptor (EGFR) pathway substrate 15 (Eps15) is a newly identified substrate for protein tyrosine phosphatase N3 (PTPN3), which belongs to the FERM-containing PTP subfamily comprising five members including PTPN3, N4, N13, N14, and N21. We solved the crystal structures of the PTPN3-Eps15 phosphopeptide complex and found that His812 of PTPN3 and Pro850 of Eps15 are responsible for the specific interaction between them. We defined the critical role of the additional residue Tyr676 of PTPN3, which is replaced by Ile939 in PTPN14, in recognition of tyrosine phosphorylated Eps15. The WPD loop necessary for catalysis is present in all members but not PTPN21. We identified that Glu instead of Asp in the WPE loop contributes to the catalytic incapability of PTPN21 due to an extended distance beyond protonation targeting a phosphotyrosine substrate. Together with in vivo validations, our results provide novel insights into the substrate specificity and plasticity of FERM-containing PTPs.

Antibiotic resistance in environmental matrices becomes urgently significant for public health and has been considered as an emerging environmental contaminant. In this work, the ampicillin-resistant Escherichia coli (AR E. coli) and corresponding resistance genes (blaTEM-1) were effectively eliminated by the electrocatalytic process, and the dissemination risk of antibiotic resistance was also investigated. All the AR E. coli (∼8 log) was inactivated and 8.17 log blaTEM-1 was degraded by the carbon nanotubes/agarose/titanium (CNTs/AG/Ti) electrode within 30 min. AR E. coli was inactivated mainly attributing to the damage of cell membrane, which was attacked by reactive oxygen species and subsequent leakage of intracellular cytoplasm. The blaTEM-1 was degraded owing to the strand breaking in the process of electrocatalytic degradation. Furthermore, the dissemination risk of antibiotic resistance was effectively controlled after being electrocatalytic treatment. This study provided an effective electrocatalytic technology for the inactivation of antibiotic resistant bacteria and control of antibiotic resistance dissemination risk in the aqueous environment.

The mainstream polishing methods were reviewed in light of polycrystalline CVD diamond wafer with large area. The principles, equipment, and processes of the mainstream polishing methods were reviewed, and the processing characteristics of these methods were compared. The material removal rate (MRR), polishing rate (PR), and minimum surface roughness (Ra) obtained by each polishing method were summed up. The non-contact method has a relatively higher MRR than the contact method, while the contact method has a relatively smaller final roughness than the non-contact method. Two factors, K (K = ΔRa/Δm, ΔRa is the reduction of the surface roughness, Δm is the mass loss) and CI (CI = K/t, t is the total polishing time), were proposed to evaluate the influence of the polishing parameters on the polishing course in the contact polishing methods and to describe the feature of each polishing method, respectively. The variation of the K value indicated that the polishing load and the polishing plate speed did not always influence the polishing effect monotonically in every contact polishing method, and it should be optimized to obtain fine surface roughness with the tiny mass loss. The CI value showed that the non-contact polishing method possessed the feature of high roughness improvement with low mass loss in the unit polishing time. These results reveal how to move forward on the path to polishing large area polycrystalline CVD diamond wafer.

Aiming at the long-standing difficulties in polishing polycrystalline chemical vapor deposition (CVD) diamond wafers efficiently and safely, a thermo-chemical polishing (TCP) method of molten iron erosion polishing (MIEP) was proposed, thus achieving rapid improvement of the surface roughness (Ra) for polycrystalline diamond wafers. By designing the experimental equipment and parameters, the diamond wafers were immersed in molten iron to be polished. The experimental results of surface roughness measured by white light interferometer showed that the original surface roughness (Ra, ~30.850 μm) was reduced to ~5.204 μm in 10 s of MIEP. Followed by 10 min of mechanical polishing (MP) further polishing, the average Ra was reduced to ~14 nm. The material removal rate (MRR) of the MIEP reached 46,800 μm/h, and the average polishing rate (PR) reached 157.395 μm/min. The thorough analysis of Raman and X-ray photoelectron spectroscopy (XPS) results revealed the material removal mechanism as the dissolution and the diffusion of carbon atoms into molten iron, which caused the high MRR of this new polishing method.

The authors report the integration of ferroelectric Pb(Zr0.52,Ti0.48)O3 (PZT) thin film on single crystal diamond by using Al2O3 as a buffer layer and SrTiO3 as a seed layer. The PZT film exhibits a remanent in-plane polarization of 2Pr=31 μC/cm2 and a coercive field of 36 kV/cm. The electrical properties of the metal-ferroelectric-insulator-semiconductor (MFIS) capacitor using boron-doped single crystal diamond epilayer are investigated. The leakage current of the MFIS device is found to be greatly reduced as compared to that of the metal/diamond Schottky diode. Although the overall capacitance-voltage characteristic shows a trap dominated hysteresis behavior, the ferroelectric polarization induced voltage shift is demonstrated under positive gate voltage.

The steroid hormone 20-hydroxyecdysone (ecdysone) is the key regulator of postembryonic developmental transitions in insects and controls metamorphosis by triggering the morphogenesis of adult tissues from larvae. The Rho GTPase, which mediates cell shape change and migration, is also an essential regulator of tissue morphogenesis during development. Rho activity can modulate gene expression, in part, by activating LIM kinase (LIMK) and consequently affecting actin-induced SRF transcriptional activity. We have established a link between Rho-LIMK-SRF signaling and the ecdysone-induced transcriptional response during Drosophila development. Specifically, we determined that the Rho GTPase, via LIMK, regulates the expression of several ecdysone-responsive genes, including those encoding the ecdysone receptor itself, a downstream transcription factor (Br-C), and Stubble, a transmembrane protease required for proper leg formation. Stubble and Br-C mutants exhibit strong genetic interactions with several Rho pathway components in the formation of adult structures, but not with Rac or Cdc42. In cultured SL2 cells, inhibition of Rho, F-actin assembly, or SRF blocks the transcriptional response to ecdysone. Together, these findings indicate a link between Rho-LIMK signaling and steroid hormone-induced gene expression in the context of metamorphosis and thereby establish a novel role for the Rho GTPase in development.

Ultrananocrystalline diamond (UNCD) films were prepared by microwave plasma chemical vapor deposition using argon-rich CH4/H2/Ar plasmas with different H2 concentrations from 5 to 20%. The influence of the H2 concentration on the microstructure, morphology and phase composition of the UNCD films was investigated by SEM, XRD, surface profilometry and Raman spectroscopy. It is found that the grain size and surface roughness increase with the H2 concentration. The grain size of the UNCD is less than 6 nm when the H2 concentration is less than 10% and it is still less than 10 nm even when the concentration is 20%. The thickness of the UNCD films is 1.75, 1.80, 1.65 and 2.9 μm using H2 concentrations of 5, 10, 15 and 20%, respectively. All the films are dense and compact in the cross section, and smooth on the top surface.

Abstract Biodegradation is the principal environmental dissipation process of chemicals. As such, it is a dominant factor determining the persistence and fate of organic chemicals in the environment, and is therefore of critical importance to chemical management and regulation. In the present study, the authors developed in silico methods assessing biodegradability based on a large heterogeneous set of 825 organic compounds, using the techniques of the C4.5 decision tree, the functional inner regression tree, and logistic regression. External validation was subsequently carried out by 2 independent test sets of 777 and 27 chemicals. As a result, the functional inner regression tree exhibited the best predictability with predictive accuracies of 81.5% and 81.0%, respectively, on the training set (825 chemicals) and test set I (777 chemicals). Performance of the developed models on the 2 test sets was subsequently compared with that of the Estimation Program Interface (EPI) Suite Biowin 5 and Biowin 6 models, which also showed a better predictability of the functional inner regression tree model. The model built in the present study exhibits a reasonable predictability compared with existing models while possessing a transparent algorithm. Interpretation of the mechanisms of biodegradation was also carried out based on the models developed. Environ Toxicol Chem 2014;33:2688–2693 . © 2014 SETAC

This study aimed to investigate the biomechanical properties of anterior cruciate ligament (ACL); tibial, femoral articular cartilage; and meniscus in knee joints receiving computer-aided or conventional ACL reconstruction. Three-dimensional (3D) knee joint finite element models were established for healthy volunteers (normal group) and patients receiving computer-aided surgery (CAS) or conventional (traditional surgery [TS]) ACL reconstruction. The stress and stress distribution on the ACL, tibial, femoral articular cartilage, and meniscus were examined after force was applied on the 3D knee joint finite element models. No significant differences were observed in the stress on ACL among normal group, CAS group, and TS group when a femoral backward force was loaded. However, when a vertical force of 350 N was loaded on the knee joints, TS group had significant higher stress on the articular cartilage and meniscus than the other two groups at any flexion angle of 0, 30, 60, and 90 degrees. However, no significant differences were observed between CAS group and normal group. In conclusion, computer-aided ACL reconstruction has advantages over conventional surgery approach in restoring the biomechanical properties of knee joints, thus reducing the risk of damage to the knee joint cartilage and meniscus after ACL reconstruction.

Diamond films have been deposited by a tandem type of radio frequency inductive coupled plasma jet source with the maximum deposition time of 150 h. The morphology, impurity and crystal structure of the deposited films were characterized. By controlling the feed gas composition, nano- and micro-crystal diamond films were deposited on silicon substrates without any metal impurity detected, and the single crystal diamond film was deposited on a diamond substrate with regular crystal lattice structure. Plasma diagnosed by optical emission spectra revealed that this plasma jet source possessed of the high values of the electron temperature (averaged at 2.2eV) and the plasma density (averaged at 4.0 × 1016/cm3), as well as the stable plasma composition fitting for the diamond growth.

The Monte Carlo Risk Assessment (MCRA) platform is a web-based tool that can be used for the cumulative risk assessment of pesticides. As underlined by the Transparency Regulation, interoperability and open access to data and tools is essential to ensure transparency and sustainability of EU food chain risk assessments. The transparency of MCRA was achieved by open-source publication of the source code of the model implementations and defining a governance structure for the MCRA software. The aim of the governance structure is to ensure sustainability and quality of the MCRA software, allow for further development of the software with new models and functionality, and support implementation of cumulative risk assessment according to the requirements described in EU Regulation No. 396/2005. The governance described in Part 1 of this report indicates how decisions on the regulatory aspects within MCRA are taken. It also describes how future development needs of MCRA in the context of the DG SANTE – EFSA action plan or in the context of future regulatory implementation requirements for cumulative risk assessment set by the European Commission are identified. The MCRA software consists of two packages: the MCRA core library and the MCRA web platform. The MCRA core library contains the model implementations and is publicly available to increase transparency and stimulate interoperability with models developed by co-creators. The MCRA web platform ensures accessibility of a user-friendly interface for conducting cumulative risk assessments following harmonized regulatory requirements. Part 2 of this report provides guidance on how to use the MCRA core models and Part 3 supplies a framework for interoperability of the MCRA model.

Harmonized methodology for retrospective dietary cumulative risk assessment (CRA) of pesticides was established by the European Commission (EC) and the European Food Safety Authority (EFSA) in 2018, in close collaboration with the Dutch National Institute for Public Health and the Environment (RIVM). An update of this regulatory methodology (RM) was proposed and adopted by EFSA in 2022 in a CRA on craniofacial alterations. This updated RM was implemented in version 10 of the MCRA software and validated as part of the first action defined in the third framework partnership agreements between EFSA and RIVM. This report describes the implementation of this updated methodology in the MCRA software for risk assessment. This is done from a proposed framework of standard regulatory actions (SRAs). SRAs offer a user-friendly and simple to use option for regulators to perform retrospective and prospective CRAs in MCRA according to agreed-upon RMs. This report provides guidance on the use of an SRA for a retrospective dietary CRA for craniofacial alterations according to the updated RM in MCRA version 10.

The CDC6 gene product from Saccharomyces cerevisiae is required for transition from late G1 to S phase of the cell cycle. We have investigated the subcellular localization of the CDC6 protein in yeast to explore where Cdc6p exerts its gene function (s). Using affinity-purified sera we localized Cdc6p to the cytoplasm and the nuclear matrix by both subcellular fractionation and indirect immunofluorescence microscopy. The nuclear localization was confirmed to be in the nuclear scaffold by the low-salt extraction method. The Cdc6p cannot be detected in the mitochondrial or plasma membrane fractions. Using indirect immunofluorescence, we found that a subpopulation of Cdc6p migrated into the nucleus after G1/S transition and diminished after M phase, suggesting its temporal role in nuclear DNA replication. The predicted Cdc6p polypeptide contains a conserved nuclear localization, 27PLKRKKL33, similar to that of the SV40 large T antigen and other nuclear proteins. To test whether this peptide segment plays a role in mediating nuclear transport, we have carried out site-directed mutagenesis to alter the conserved 29Lys to Thr and Arg. The wild-type nuclear localization signal of Cdc6p was found to mediate the LacZ reporter gene fused to CDC6 efficiently to the nucleus, but not the mutated versions of the nuclear localization motif. The results suggested that 29Lys is important in mediating nuclear localization, the 29Thr and 29Arg mutant versions of the CDC6 gene were also unable to complement the cdc6 temperature-sensitive mutant. However, when these mutants were expressed from a multicopy plasmid, the mutated genes could complement the mutation. Similar results were obtained in the cdc6-disrupted cells. Taken together, we suggest that (i) Cdc6p is predominantly located in the cytoplasm, (ii) the nuclear entry of Cdc6p is cell cycle dependent, and (iii) nuclear entry of Cdc6p is mediated by its nuclear localization signal. The presence of Cdc6p in both the nucleus and the cytoplasm suggests a model that Cdc6p exerts its gene function in DNA replication and mitotic restraint in the cell cycle.

We identify Kette, a key regulator of actin polymerization, as a substrate for Drosophila protein tyrosine phosphatase PTP61F, as well as for dAbl tyrosine kinase. We further show that dAbl is a direct substrate for PTP61F. Therefore, Kette phosphotyrosine levels are regulated both directly and indirectly by PTP61F. Kette and PTP61F genetically interact in the regulation of F-actin organization in pupal eye discs, suggesting that tyrosine phosphorylation is essential for the proper regulation of Kette-mediated actin dynamics. This hypothesis was confirmed by demonstrating the loss of Kette-mediated F-actin organization and lamella formation in S2 cells in a Kette Y482F mutant in which the dAbl phosphorylation site was eliminated. Our results establish for the first time that PTP61F and dAbl ensure proper actin organization through the coordinated and reversible tyrosine phosphorylation of Kette.

Radio-frequency inductively coupled plasma jet is utilized to grow diamond films to combine the advantages of clean deposition environment and large deposition area. Before diamond growth, the simulation of deposition environment is studied to understand the flow field and the properties of the plasma. The optical emission spectra (OES) are also applied to diagnose the rf plasma. The plasma density ne and the electron temperature Te deduced from the data measured by OES are about 1.0 × 1014 l/cm3 and 1.4 eV, which are in good agreement with the data calculated in the simulation. Based on the data from both simulation and measurement, the optimized growth parameters are determined to grow diamond films. Nano-crystalline diamond with cauliflower-like morphology is obtained. The crystalline feature and impurity of as-grown films are also studied.

To date our understanding of Drosophila receptor protein tyrosine phosphatases (R-PTPs) in the regulation of signal transduction is limited. Of the seven R-PTPs identified in flies, six are involved in the axon guidance that occurs during embryogenesis. However, whether and how R-PTPs may control key steps of Drosophila development is not clear. In this study we investigated the potential role of Drosophila R-PTPs in developmental processes outside the neuronal system and beyond the embryogenesis stage. Through systematic data mining of available microarray databases, we found the mRNA level of PTP52F to be highly enriched in the midgut of flies at the larva-pupa transition. This finding was confirmed by gut tissue staining with a specific antibody. The unique spatiotemporal expression of PTP52F suggests that it is possibly involved in regulating metamorphosis during the transformation from larva to pupa. To test this hypothesis, we employed RNA interference to examine the defects of transgenic flies. We found that ablation of endogenous PTP52F led to high lethality characterized by the pharate adult phenotype, occurring due to post pupal eclosion failure. These results show that PTP52F plays an indispensable role during the larva-pupa transition. We also found that PTP52F could be reclassified as a member of the subtype R3 PTPs instead of as an unclassified R-PTP without a human ortholog, as suggested previously. Together, these findings suggest that Drosophila R-PTPs may control metamorphosis and other biological processes beyond our current knowledge.

During autophagy defense against invading microbes, certain lipid types are indispensable for generating specialized membrane-bound organelles. The lipid composition of autophagosomes remains obscure, as does the issue of how specific lipids and lipid-associated enzymes participate in autophagosome formation and maturation. Helicobacter pylori is auxotrophic for cholesterol and converts cholesterol to cholesteryl glucoside derivatives, including cholesteryl 6'-O-acyl-α-D-glucoside (CAG). We investigated how CAG and its biosynthetic acyltransferase assist H. pylori to escape host-cell autophagy.We applied a metabolite-tagging method to obtain fluorophore-containing cholesteryl glucosides that were utilized to understand their intracellular locations. H. pylori 26695 and a cholesteryl glucosyltransferase (CGT)-deletion mutant (ΔCGT) were used as the standard strain and the negative control that contains no cholesterol-derived metabolites, respectively. Bacterial internalization and several autophagy-related assays were conducted to unravel the possible mechanism that H. pylori develops to hijack the host-cell autophagy response. Subcellular fractions of H. pylori-infected AGS cells were obtained and measured for the acyltransferase activity.The imaging studies of fluorophore-labeled cholesteryl glucosides pinpointed their intracellular localization in AGS cells. The result indicated that CAG enhances the internalization of H. pylori in AGS cells. Particularly, CAG, instead of CG and CPG, is able to augment the autophagy response induced by H. pylori. How CAG participates in the autophagy process is multifaceted. CAG was found to intervene in the degradation of autophagosomes and reduce lysosomal biogenesis, supporting the idea that intracellular H. pylori is harbored by autophago-lysosomes in favor of the bacterial survival. Furthermore, we performed the enzyme activity assay of subcellular fractions of H. pylori-infected AGS cells. The analysis showed that the acyltransferase is mainly distributed in autophago-lysosomal compartments.Our results support the idea that the acyltransferase is mainly distributed in the subcellular compartment consisting of autophagosomes, late endosomes, and lysosomes, in which the acidic environment is beneficial for the maximal acyltransferase activity. The resulting elevated level of CAG can facilitate bacterial internalization, interfere with the autophagy flux, and causes reduced lysosomal biogenesis.

This paper used optical emission spectroscopy (OES) to study the gas phase in high power DC arc plasma jet chemical vapour deposition (CVD) during diamond films growth processes. The results show that all the deposition parameters (methane concentration, substrate temperature, gas flow rate and ratio of H2/Ar) could strongly influence the gas phase. C2 is found to be the most sensitive radical to deposition parameters among the radicals in gas phase. Spatially resolved OES implies that a relative high concentration of atomic H exists near the substrate surface, which is beneficial for diamond film growth. The relatively high concentrations of C2 and CH are correlated with high deposition rate of diamond. In our high deposition rate system, C2 is presumed to be the main growth radical and CH is also believed to contribute the diamond deposition.

Single crystal diamonds were deposited on high pressure high temperature (HPHT) substrate with high growth rate, up to 18.5 μm/h, by using dual radio-frequency inductive coupled plasma jet. The methane flux was found to influence the growth rate of single crystal diamond. The reason for this might be ascribed to the electron temperature increase, raising the flux of methane, based on the plasma diagnosis results by optical emission spectra (OES). The results of Raman spectroscopy and the X-ray rocking-curve indicated that as-deposited diamonds are of good quality.

Monodansylpentane (MDH) is a fluorophore that displays selective labeling of lipid droplets (LDs). The dye preferentially segregates into the neutral lipid cores of LDs and emits blue fluorescence, compatible with the simultaneous use of green and red fluorescent reporters in multi-color live-cell imaging. MDH can be used for visualizing LDs not only in cell cultures, but also in fixed tissues such as the fat body and ovaries from Drosophila. MDH is therefore a versatile marker for LDs in fluorescence microscopy.

Recently, NIH has funded a center for autophagy research named the Autophagy, Inflammation, and Metabolism (AIM) Center of Biomedical Research Excellence, located at the University of New Mexico Health Science Center (UNM HSC), with aspirations to promote autophagy research locally, nationally, and internationally. The center has 3 major missions: (i) to support junior faculty in their endeavors to develop investigations in this area and obtain independent funding; (ii) to develop and provide technological platforms to advance autophagy research with emphasis on cellular approaches for high quality reproducible research; and (iii) to foster international collaborations through the formation of an International Council of Affiliate Members and through hosting national and international workshops and symposia. Scientifically, the AIM center is focused on autophagy and its intersections with other processes, with emphasis on both fundamental discoveries and applied translational research.

Strontium titanate (STO) films were directly deposited on Ib (100) single crystal diamond by r.f. magnetron sputtering. The as-deposited STO film was in amorphous state. On the other hand, the crystalline STO film was obtained under the optimized condition of a deposition temperature of 250 °C and a post-annealing temperature of 650 °C. STO/diamond junctions were fabricated on boron-doped homoepitaxial layers grown on p+-type single crystal diamond substrates. Electrical properties of the STO/diamond junction were investigated by changing the surface terminations of diamond with hydrogen or oxygen and the crystallinity of the STO film. It was found that the amorphous STO acted like a semi-insulator on H-diamond surface and that the amorphous STO/O-diamond junction behaved like a Schottky diode. The crystalline STO/O-diamond showed a complex rectifying behavior. The crystalline STO film possessed a higher dielectric constant as compared to that of the amorphous one.

Abstract A two-dimensional axisymmetric numerical study has been carried out to analyze the Ar jet driven by the radio frequency of 13.56 MHz under the condition of the chamber pressure of 0.1 atm in the inductively coupled plasma (ICP). The flow field, the temperature field and the electromagnetic field are evaluated under the condition of different cooling methods, i.e. , sheath gas-cooling and water-cooling. Based on the calculated data, we have found that the temperature homogeneous zone is larger by using the water-cooling method than that of sheath gas-cooling case. The energy density in the former case is 1.6E7 W/m 3 , over one and a half times the sheath gas-cooling method, which means that the energy consumption efficiency is higher under the condition of water-cooling rather than that of the sheath gas-cooling.

Based on the observation and reanalysis data, the relationship between the Madden–Julian Oscillation (MJO) over the Maritime Continent (MC) and the tropical Pacific–Indian Ocean associated mode was analyzed. The results showed that the MJO over the MC region (95°–150° E, 10° S–10° N) (referred to as the MC–MJO) possesses prominent interannual and interdecadal variations and seasonally “phase-locked” features. MC–MJO is strongest in the boreal winter and weakest in the boreal summer. Winter MC–MJO kinetic energy variation has significant relationships with the El Niño–Southern Oscillation (ENSO) in winter and the Indian Ocean Dipole (IOD) in autumn, but it correlates better with the tropical Pacific–Indian Ocean associated mode (PIOAM). The correlation coefficient between the winter MC–MJO kinetic energy index and the autumn PIOAM index is as high as −0.5. This means that when the positive (negative) autumn PIOAM anomaly strengthens, the MJO kinetic energy over the winter MC region weakens (strengthens). However, the correlation between the MC–MJO convection and PIOAM in winter is significantly weaker. The propagation of MJO over the Maritime Continent differs significantly in the contrast phases of PIOAM. During the positive phase of the PIOAM, the eastward propagation of the winter MJO kinetic energy always fails to move across the MC region and cannot enter the western Pacific. However, during the negative phase of the PIOAM, the anomalies of MJO kinetic energy over the MC is not significantly weakened, and MJO can propagate farther eastward and enter the western Pacific. It should be noted that MJO convection is more likely to extend to the western Pacific in the positive phases of PIOAM than in the negative phases. This is significant different with the propagation of the MJO kinetic energy.

As an emerging brand new type of engineering material for a variety of important high technology applications,a deep understanding of the mechanical behavior of the freestanding diamond films has become an urgent task of vital importance.The purpose of this review article is to present state-of-the-art researches on the fracture strength and toughness,and the fracture mechanisms of this engineering material.Testing methods of the fracture strength and fracture toughness of the freestanding diamond film were introduced briefly.Typical data were presented.Suggestions in the improvement of mechanical properties and more safe and efficient use of this kind of new engineering material were discussed.

Quantitative risk assessments of chemicals are routinely performed in rodents; however, there is growing recognition that non-animal approaches can be human-relevant alternatives. There is an urgent need to build confidence in non-animal alternatives given the international support to reduce the use of animals in toxicity testing where possible. In order for scientists and risk assessors to prepare for this paradigm shift in toxicity assessment, standardization and consensus on in vitro testing strategies and data interpretation will need to be established. To address this issue, an Expert Working Group (EWG) of the 8th International Workshop on Genotoxicity Testing (IWGT) evaluated the utility of quantitative in vitro genotoxicity concentration-response data for risk assessment. The EWG first evaluated available in vitro methodologies and then examined the variability and maximal response of in vitro tests to estimate biologically relevant values for the critical effect sizes considered adverse or unacceptable. Next, the EWG reviewed the approaches and computational models employed to provide human-relevant dose context to in vitro data. Lastly, the EWG evaluated risk assessment applications for which in vitro data are ready for use and applications where further work is required. The EWG concluded that in vitro genotoxicity concentration-response data can be interpreted in a risk assessment context. However, prior to routine use in regulatory settings, further research will be required to address the remaining uncertainties and limitations.

Abstract In response to ionizing radiation (IR), stem cells undergo cell cycle arrest, senescence, premature differentiation, or cell death. The decision between survival and death is critical during tumorigenesis and effective killing of cancer cells. We used the larval Drosophila lymph gland, a hematopoietic organ, as a model to understand the mechanism for cell fate decisions during stem cell development. The hematopoietic progenitors survived or died via apoptosis when larvae were irradiated in early or late third instar larval (L3) stages, respectively. In late L3 progenitors, the basal level of polo ( Drosophila PLK1) was low, enabling IR-induced activation of lok ( Drosophila CHK2), which was necessary and sufficient for inducing autophagy and reactive oxygen species (ROS) production resulting in cell death. The high level of polo in early L3 progenitors negatively regulated lok resulting in significantly low or undetectable levels of ROS or autophagy, respectively. The surviving early L3 progenitors underwent cell cycle arrest followed by premature differentiation affected by tefu ( Drosophila ATM) and lok mutation. These results provide clues for designing effective therapeutic strategies for cancer. Summary statement We elucidated the mechanism underlying cell fate decisions during stem cell development in larval Drosophila , which will help develop effective cancer treatment modalities.

The structure determination of protein tyrosine phosphatase (PTP): phospho-protein complexes, which is essential to understand how specificity is achieved at the amino acid level, remains a significant challenge for protein crystallography and cryoEM due to the transient nature of binding interactions. Using rPTPεD1 and phospho-SrcKD as a model system, we have established an integrative workflow to address this problem, by means of which we generate a protein:phospho-protein complex model using predetermined protein structures, SAXS and pTyr-tailored MD simulations. Our model reveals transient protein-protein interactions between rPTPεD1 and phospho-SrcKD and is supported by three independent experimental validations. Measurements of the association rate between rPTPεD1 and phospho-SrcKD showed that mutations on the rPTPεD1: SrcKD complex interface disrupts these transient interactions, resulting in a reduction in protein-protein association rate and, eventually, phosphatase activity. This integrative approach is applicable to other PTP: phospho-protein complexes and the characterization of transient protein-protein interface interactions.

The boron-oxygen-nitrogen (BON) films have been grown on Si wafer by the low-frequency rf-plasma-enhanced metal-organic chemical vapour deposition method. The homogeneous film structure of completely amorphous BON is first fabricated on a low-temperature-made buffer at 500°C with N2 plasma and is observed with a high-resolution-electron microscope by the transmission-electron diffraction. The results show that the interfaces among substrate/buffer/film are clear and straight in the structured film. A heterogeneous film containing nano-sized crystalline particles is also grown by a routine growth procedure as a referential structure. The C-V characteristic is measured on both the amorphous and crystal-containing films by using the metal-oxide-semiconductor structure. The dielectric constants of the films are, therefore, deduced to be 5.9 and 10.5 for the amorphous and crystal-containing films, respectively. The C-V results also indicate that more trapped charges exist in the amorphous film. The binding energy of the B, O, and N atoms in the amorphous film is higher than that in the crystal-containing one, and the N-content in the latter is found to be higher than that in the former by x-ray photo-electron spectroscopy. The different electrical property of the films is thought to originate from the energy state of the covalent electrons.

In Figure 3A in this article, (Cell 113, 147–158), some of the “+” and “−” indicators in the lower portion of the panel were incorrectly assigned during the final formatting of the figure. The corrected version of this figure is shown below. The description of the results in the text and in the figure legend is accurate and these changes have no bearing on the experimental results or the conclusions. We apologize for any inconvenience that this error has caused.

Self-standing CVD diamond films with different dominant crystalline surfaces are polished by the thermal-iron plate polishing method. The influence of the dominant crystalline surfaces on polishing efficiency is investigated by measuring the removal rate and final roughness. The smallest rms roughness of 0.14 μm is measured with smallest removal rate in the films with the initial (220) dominant crystalline surface. Activation energy for the polishing is analysed by the Arrhenius relation. It is found that the values are 170 kJ/mol, 222 kJ/mol and 214 kJ/mol for the film with three different dominant crystalline surfaces. Based on these values, the polishing cause is regarded as the graphitization-controlling process. In the experiment, we find that transformation of the dominant crystalline surfaces from (111) to (220) always appears in the polishing process when we polish the (111) dominant surface.

Thermal stress in large area free-standing diamond films was remarkable during the post-deposition cooling of direct current (DC) arc plasma jet chemical vapor deposition (CVD) process. In this research, the stress release caused by delamination of Cr interlayer was of great importance to ensure the integrity of free-standing diamond film. The effects of Cr interlayer on Mo substrate, namely composite substrate, on thermal stress were investigated. Thermo-mechanical coupling analysis of the thermal stress was applied by finite element analysis (FEA) using ANSYS code. It was found that the interlayer could be destroyed first by the large thermal stress, and then the stress could be released and the probability of diamond film crack initiation would be reduced. The stress concentration at the bent edge of diamond film was also discussed. In addition, diamond films deposited on Mo substrates with and without Cr interlayer were prepared by DC arc plasma jet CVD system and experimental measurements were used to characterize these films. It was found that composite substrate could be an effective method of growing free-standing crack-free diamond films by DC arc plasma jet CVD system when there is no special requirement to the film strength.

CVD diamond was revealed as an important functional material in the 21^th Century because of its unique physical and chemical properties as well as its wafer or block appearance easily adopted by the industry application and society life. However, this kind of promising material was grown too hard to sustain the application in the industry. This paper reviewed the present station of CVD diamond growth theory and technique. Analysis of the growth procedure was also done. Based on these works, a novel study idea was proposed to raise the CVD diamond growth rate,<italic> i.e.</italic>, focused the mass transportation in the growth procedure instead of the seeking the key radical. Then, the attempt to raise the growth rate of CVD diamond might be instructed according to the suggestion of the theory of crystal growth. It was emphasized that the temperature gradient on the growth surface should be reasonably designed and utilized.

This volume constitutes a collection of research that brings to the fore one of the most important global challenges facing the world today: the energy transition. Addressing this challenge and achieving the sustainable development goals calls for international collaboration, and as the chapters in this report illustrate, bringing together scholars from different disciplines, backgrounds and geographies offers a holistic perspective for a sustainable transition. Moreover, the report simultaneously addresses the development, context, implementation and dissemination of energy transition solutions.

The dielectric properties of free-standing diamond films grown by the dc arc-jet plasma method are measured by an impedance analyser in the temperature range of 298-573 K and at frequencies between 1000 Hz and 1 MHz. In the temperature and frequency ranges, the loss tangent can be expressed as a function of temperature and frequency. The loss tangent increases slightly with increasing temperature and frequency. The dielectric properties of the diamond films decrease with the increasing deposited temperature. The structure and quality of diamond films have been analysed by scanning electron microscopy, x-ray diffraction and Raman spectroscopy.

We attempt to coat a multi-spectrum chemical-vapour-deposition ZnS substrate with smooth crystalline diamond films on the top of properly designed ceramic interlayer, which provides protection for ZnS against corrosion by the H2–CH4 microwave plasma and mitigates the thermal expansion coefficient mismatching between diamond and ZnS. However, difficulties in the homogeneous diamond nucleation on a ceramic interlayer were encountered. It was found that high rate nucleation of diamond could be induced by a metal or semiconductor mask placed on the top of ZnS.

Langmuir probes and Faraday cups have been used to characterize electron cyclotron resonance plasmas which have been used in the depositions of GaN films on the substrate of (0001)α-Al2O3.These plasmas were generated with microwave power(Pw) from 300W to 1100W at pressures(p) range from 0.8Pa to 0.05Pa using N2 as the plasma source.The relationship between the plasma parameter,such as ion density(Ni),electron temperature(Te),plasma potential(Vp) and ion current density(Ji),and system parameters,such as pW and p,is given.And the axial and radial distributions of Te,Ni,Vp and Ji are presented.The growth rate and the quality of the GaN film strongly depend on the growth condition.The higher the plasma density,the higher the N/Ga ratio of GaN film.When the microwave power was 850W and gas pressure was 0.22Pa,the plasma near the substrate was characterized by a Te near 1.4eV and plasma density near 2.0×1011 cm-3,and the growth rate of GaN was as high as 0.9μm/h.The full width at half maximum of double-crystal X-ray diffraction rocking curve is 16 arcmin.

A nano-crystlline diamond film is grown by the dc arcjet chemical vapor deposition method. The film is characterized by scanning electron microscopy, high-resolution transmission electron microscopy (HRTEM), x-ray diffraction (XRD) and Raman spectra, respectively. The nanocrystalline grains are averagely with 80 nm in the size measured by XRD, and further proven by Raman and HRTEM. The observed novel morphology of the growth surface, pineapple-like morphology, is constructed by cubo-octahedral growth zones with a smooth faceted top surface and coarse side surfaces. The as-grown film possesses (100) dominant surface containing a little amorphous sp2 component, which is far different from the nano-crystalline film with the usual cauliflower-like morphology.

Autophagy is a highly conserved lysosomal degradation pathway, which has been shown to play a pivotal role during normal physiological and pathological conditions. Many proteins and signaling pathways have been shown to regulate autophagy during different stages of the process. Modifying autophagy-related proteins (Atg) by posttranslational modification (PTM) is an important way to control proper autophagic activity. Ubiquitination is one of the PTM that has a crucial role in controlling protein stability and functions. Proteins can be conjugated with ubiquitin chains with different topologies that are associated with different outcomes. Many autophagy regulators are found to be substrates for ubiquitin E3 ligases or deubiquitinating enzymes (DUBs). Ubiquitination modifications of these autophagy regulators result in autophagy induction or termination. Moreover, ubiquitin is also involved in selective autophagy by acting as a degradation signal. Here, we are going to review how E3 ligases and DUBs function in autophagy regulation and discuss the recent findings about ubiquitination regulation in autophagy-related processes and diseases.

Large sized single crystalline diamond grain was first successfully grown by chemical vapor deposition(CVD) method in 2002.Since then,the hot tide of CVD diamond has been raised in the sphere of carbon material all over the world.In the meanwhile,the application of CVD single crystalline diamond into various spheres was also developed.These researches gradually delineated that CVD single crystalline diamond could be widely utilized in the new century,and deeply influence the society life,national defense and science development.This paper reviewed the development of CVD single crystalline diamond and application into the particle detector.

Ultrananocrystalline diamond (UNCD) films were prepared by microwave plasma chemical vapor deposition using argon-rich CH4/H2/Ar plasmas with different H2 concentrations from 5% to 20%. The influence of the H2 concentration on the microstructure, morphology and phase composition of the UNCD films was investigated by SEM, XRD, surface profilometry and Raman spectroscopy. It is found that the grain size and surface roughness increase with the H2 concentration. The grain size of the UNCD is less than 6 nm when the H2 concentration is less than 10% and it is still less than 10 nm even when the concentration is 20%. The thickness of the UNCD films is 1.75, 1.80, 1.65 and 2.9 μm using H2 concentrations of 5%, 10%, 15% and 20%, respectively. All the films are dense and compact in the cross section, and smooth on the top surface. [New Carbon Materials 2013, 28(2): 134–139]

An electron cyclotron resonance assisted plasma with N2 being the plasma source gas was employed to deposit hexagonal GaN on (0001) surface of α-Al2O3 substrate. By special gas distributor, trimethgallium was introduced into reactant zone. A 10 × 10 mm uniform GaN film was gained with relatively low deposition temperature, 560°C, and high growth rate of 1.4 μm/h. A good crystal microstructure was confirmed by its spectrum with full width at half maximum of 15 arcmin.

Optical emission spectroscopy (OES) was used to study the gas phase composition near the substrate surface during diamond deposition by high-power DC arc plasma jet chemical vapor deposition (CVD). C2 radical was determined as the main carbon radical in this plasma atmosphere. The deposition parameters, such as substrate temperature, anode-substrate distance, methane concentration, and gas flow rate, were inspected to find out the influence on the gas phase. A strong dependence of the concentrations and distribution of radicals on substrate temperature was confirmed by the design of experiments (DOE). An explanation for this dependence could be that radicals near the substrate surface may have additional ionization or dissociation and also have recombination, or are consumed on the substrate surface where chemical reactions occur.

Boron-doping is an effective way to improve resistivity of diamond films that can be used for electrochemical electrode.In our study,boron-doped diamond(BDD) films were grown by chemical vapor deposition(CVD) on single crystal silicon substrate,and were characterized by resistivity measurement by 4-point probe method,SEM,Raman spectroscopy and electrochemistry working station.The resistivity of diamond films was reduced as the volume percentage of boron in the source gas increasing and the value of 2.0×10-3Ω·cm can be found when abundant boron were doped.Meanwhile,the quality of the diamond films was deteriorated with the increasing of boron doped.The grain size decreased and the residual stress obtained from micro-Raman spectrum increased,non-diamond peak appeared clearly when the doping level was increased.Wide electrochemical potential window,high anode polarization,and low background current in acid solution can be found with the measurement of electrochemistry for diamond film electrode.

The NIH-funded center for autophagy research named Autophagy, Inflammation, and Metabolism (AIM) Center of Biomedical Research Excellence, located at the University of New Mexico Health Science Center is now completing its second year as a working center with a mission to promote autophagy research locally, nationally, and internationally. The center has thus far supported a cadre of 6 junior faculty (mentored PIs; mPIs) at a near-R01 level of funding. Two mPIs have graduated by obtaining their independent R01 funding and 3 of the remaining 4 have won significant funding from NIH in the form of R21 and R56 awards. The first year and a half of setting up the center has been punctuated by completion of renovations and acquisition and upgrades for equipment supporting autophagy, inflammation and metabolism studies. The scientific cores usage, and the growth of new studies is promoted through pilot grants and several types of enablement initiatives. The intent to cultivate AIM as a scholarly hub for autophagy and related studies is manifested in its Vibrant Campus Initiative, and the Tuesday AIM Seminar series, as well as by hosting a major scientific event, the 2019 AIM symposium, with nearly one third of the faculty from the International Council of Affiliate Members being present and leading sessions, giving talks, and conducting workshop activities. These and other events are often videostreamed for a worldwide scientific audience, and information about events at AIM and elsewhere are disseminated on Twitter and can be followed on the AIM web site. AIM intends to invigorate research on overlapping areas between autophagy, inflammation and metabolism with a number of new initiatives to promote metabolomic research. With the turnover of mPIs as they obtain their independent funding, new junior faculty are recruited and appointed as mPIs. All these activities are in keeping with AIM’s intention to enable the next generation of autophagy researchers and help anchor, disseminate, and convey the depth and excitement of the autophagy field.

Celecoxib is the most recent non steroidal anti-inflammatory analgesic, and has been gradually used in the treatment of acute pain, rheumatism and osteoarthritis. This paper analyzes the analgesic effect of celecoxib in the treatment of knee osteoarthritis and put forward a new mechanism of knee joint extensor reconstruction assisted by bone anchor. The experimental group was given celecoxib 200 mg/ time and 1 time /d. The results showed that VAS (Visual Analogue Scale) decreased gradually in both groups on the 1st, 3rd and 7th day of treatment and VAS in experimental group was lower than that in control group at the same time point (P<0.05). At the 1 year follow-up, experience group had a significant improvement on the Lysholm (69.33 ± 8.38 preoperatively and 88.65 ± 12.93 postoperatively) and Kujula (69.33 ± 8.38 preoperatively and 88.65 ±12.93 postoperatively) knee scores (P<0.05). The results showed that celecoxib had a good analgesic effect in patients with knee osteoarthritis and reducing the release of inflammatory factors may be its mechanism..

Objective To evaluate the accuracy of a 3D-printed template used to assist the preparation of tibial tunnel in reconstruction of anterior cruciate ligament (ACL). Methods Twenty healthy adult cadaveric knees were scanned by computed tomography(CT) and magnetic resonance imaging (MRI). The knees were from 11 males and 9 females who had died at an average age of 36 years (range, from 27 to 68 years) and from 8 left and 12 right sides. Individualized 3D reconstruction models of the knee joint were established based on their imaging data. According to the anatomic footprints of the virtual tibial tunnel, 20 individualized navigation templates were designed and printed by 3D printing. The templates were used to assisst preparation of tibial tunnels in the ACL reconstruction for the 20 cadaveric knees. After operation, CT scanning was conducted again to compare the corresponding postitions between the preoperative virtual tunnel and the postoperative actual tunnel. The positions of the tibial tunnel were described by the Tsukada method. Results The ratio of the distance between the tunnel outlet center and the medial edge of the tibia to the distance between the median and lateral edges of the tibial plateau was 49.7%±2.1% for the preoperative virtual tibial tunnel and 48.8%±2.8% for the postoperative actural tunnel, showing no significant difference between them (t=1.971, P=0.063). The ratio of the distance between the tunnel outlet center and the anterior edge of the tibia to the distance between the anerior and posterior edges of the tibial plateau was 41.3%±1.3% for the preoperative virtual tibial tunnel and 40.3%±3.7% for the postoperative actural tunnel, showing no significant difference between them(t=1.494, P=0.152). Conclusion 3D printing can be used to design and manufacture a navigation template which can accurately assist preparation of tibial bone tunnel in ACL reconstruction. Key words: Knee joint; Anterior cruciate ligament; 3D printing technology; Template; Tibial bone tunnel

This report highlights research from the Sino-Danish Center (SDC), the fruit of a consolidated and strong bilateral partnership for collaboration in science, technology and innovation between universities in China and Denmark.In 2020, SDC celebrates its ten-year anniversary, making it a perfect moment to present some of the academic outcomes of this partnership.This volume constitutes a collection of research that brings to the fore one of the most important global challenges facing the world today: the energy transition.Addressing this challenge and achieving the sustainable development goals calls for international collaboration, and as the chapters in this report illustrate, bringing together scholars from different disciplines, backgrounds and geographies offers a holistic perspective for a sustainable transition.Moreover, the report simultaneously addresses the development, context, implementation and dissemination of energy transition solutions.

Crack patterns in self-standing diamond film were observed as network-shape pattern, river-shape and circle-shape pattern, depending on growth temperature. Fracture mechanism was firstly studied by atomic force microscope (AFM) on the fractured section. Both intergranular fracture and transgranular fracture were found by this technique. Transgranular fracture was easy to observe in network-shape pattern, and intergranular fracture was found in circle-shape pattern. The river-shape pattern seemed to result from the combination of inter- and trans-granular fracture. X-ray diffraction (XRD) test was done on all of growth side, nucleation side and fractured section of the film body. Corresponding to XRD results, transgranular fracture took place in the film with (111)-crystalline surface being dominant in all of the three detected surfaces. Intergranular fracture occurred in the film with (220)-crystalline surface being dominant in all of the three detected surfaces. Raman test showed that the intrinsic stress was in the range of several tens MPa to several hundreds MPa. Micro-Raman test on fractured section indicated that there was the distribution of stress in the film body. Also by micro-Raman, testing along the crack path indicated that crystalline structure with few defects was benefit for blocking the propagation of crack. A mechanical model was set up to analyze the effect of dominant surface on fracture strength. Based on the experimental results and mechanical analysis, crack-free self-standing diamond films with 2mm in thickness and 120mm in diameter were successfully grown by controlling the crystalline structure of the films.

A surface engineering approach for a novel pre-treatment of hard metal tool substrate for optimum adhesion of diamond coatings is presented. Firsfly, an alkaline solution was used to etch the WC grains to generate a rough surface for better mechanical interlocking. Subsequently, surface Co was removed by etching in acid solution. Then the hard metal substrate was boronized to form a compound interlayer which acted as an efficient diffusion barrier to prevent the outward diffusion of Co. Novel nano-microcrystalline composite diamond film coatings with a very smooth surface was deposited on the surface engineering pre-treated hard metal surface. Promising results of measurement in adhesion strength as well as field cutting tests have been obtained.

Model predictive control (MPC) allows efficient use of energy systems and can provide considerable energy savings.However, finding a proper configuration of MPC in specific energy systems remains challenging.This doctoral project aims to develop methods of deriving the best combination of models and optimization schemes for a given energy system.The project goal will be achieved by testing different models and optimization techniques of MPC in a virtual testbed.An analysis of how to choose models and corresponding optimization techniques will be conducted based on test results.Three case studies will be carried out to evaluate the proposed methodology.It is expected to advance knowledge of setting up appropriate MPC configuration for energy systems and speed up MPC transition from academic research to wider industry implementation.

First Page