X. Wang

Poly(3,4-ethylenedioxythiophene)-poly(styrenesulfonate) (PEDOT:PSS) is an attractive conducting polymer, albeit its rheological properties are inappropriate for direct ink writing (DIW). Here it is hypothesized that a suspension of PEDOT:PSS with a non-conducting highly spinnable viscoelastic polymer, e.g., polyethylene oxide (PEO), will significantly facilitate printability and enhance the electrical conductivity (EC) of PEDOT:PSS-PEO. It is also hypothesized that high-humidity post-treatment will enhance the EC even further, and the application of the electric field can facilitate the DIW speed beyond the capabilities of current commercial 3D printers. The rheological behavior of PEDOT:PSS suspensions with several non-conducting polymers was explored in the experiments. The EC of the suspensions was measured, including the effect of high-humidity post-treatment. High-speed DIW of the optimal suspension was experimentally demonstrated with the applied electric field. The findings revealed that PEO serves as a secondary dopant, and the suspension of 4.33 wt% PEDOT:PSS-52 wt% PEO possesses the EC > 15 times higher than that of PEDOT:PSS. Many 2D, 2.5D and 3D functional traces were printed at high resolution at the DIW speed up to 8.64 m/s (>10 times faster than current commercial printers), facilitated by the applied electric field. Post-treatment at 80–90% relative humidity enhanced the EC more than twice.

Whereas the growth of the cranial base cartilage is thought to be regulated solely by genes, epiphyseal growth plates are known to respond to mechanical stresses. This disparity has led to our hypothesis that chondrocyte proliferation is accelerated by mechanical stimuli above natural growth. Two-Newton tensile forces with static and cyclic waveforms were delivered in vivo to the premaxillae of actively growing rabbits for 20 min/day over 12 consecutive days. The average number of BrdU-labeled chondrocytes in the proliferating zone treated with cyclic forces was significantly higher than both static forces of matching peak magnitude and sham controls representing natural chondral growth. Cyclic forces also evoked greater area of the proliferating zone than both static forces and sham controls. Thus, chondrocyte proliferation is enhanced by mechanical stresses in vivo, especially those with oscillatory waveform. Analysis of these data suggests that genetically coded chondral growth is up-regulated by mechanical signals.

•Few prognostic markers of human papillomavirus-driven oropharyngeal cancer (HPV-OPC) exist. •We conducted the first large HPV16 whole-genome sequencing study of 384 HPV16+OPCs •We found eight HPV16 SNPs to be strongly associated with HPV-OPC prognosis. •Median survival was 4 years for HPV-OPC patients with ≥1 high-risk HPV16 SNPs versus 19 years for patients without. •HPV16 SNPs improved predictive accuracy for HPV-OPC overall survival compared with age, stage, treatment and smoking alone. Purpose A significant barrier to adoption of de-escalated treatment protocols for human papillomavirus-driven oropharyngeal cancer (HPV-OPC) is that few predictors of poor prognosis exist. We conducted the first large whole-genome sequencing (WGS) study to characterize the genetic variation of the HPV type 16 (HPV16) genome and to evaluate its association with HPV-OPC patient survival. Patients and methods A total of 460 OPC tumor specimens from two large United States medical centers (1980-2017) underwent HPV16 whole-genome sequencing. Site-specific variable positions [single nucleotide polymorphisms (SNPs)] across the HPV16 genome were identified. Cox proportional hazards model estimated hazard ratios (HRs) and 95% confidence intervals (CIs) for overall survival by HPV16 SNPs. Harrell C-index and time-dependent positive predictive value (PPV) curves and areas under the PPV curves were used to evaluate the predictive accuracy of HPV16 SNPs for overall survival. Results A total of 384 OPC tumor specimens (83.48%) passed quality control filters with sufficient depth and coverage of HPV16 genome sequencing to be analyzed. Some 284 HPV16 SNPs with a minor allele frequency ≥1% were identified. Eight HPV16 SNPs were significantly associated with worse survival after false discovery rate correction (individual prevalence: 1.0%-5.5%; combined prevalence: 15.10%); E1 gene position 1053 [HR for overall survival (HRos): 3.75, 95% CI 1.77-7.95; Pfdr = 0.0099]; L2 gene positions 4410 (HRos: 5.32, 95% CI 1.91-14.81; Pfdr = 0.0120), 4539 (HRos: 6.54, 95% CI 2.03-21.08; Pfdr = 0.0117); 5050 (HRos: 6.53, 95% CI 2.34-18.24; Pfdr = 0.0030), and 5254 (HRos: 7.76, 95% CI 2.41–24.98; Pfdr = 0.0030); and L1 gene positions 5962 (HRos: 4.40, 95% CI 1.88-10.31; Pfdr = 0.0110) and 6025 (HRos: 5.71, 95% CI 2.43-13.41; Pfdr = 0.0008) and position 7173 within the upstream regulatory region (HRos: 9.90, 95% CI 3.05-32.12; Pfdr = 0.0007). Median survival time for patients with ≥1 high-risk HPV16 SNPs was 3.96 years compared with 18.67 years for patients without a high-risk SNP; log-rank test P < 0.001. HPV16 SNPs significantly improved the predictive accuracy for overall survival above traditional factors (age, smoking, stage, treatment); increase in C-index was 0.069 (95% CI 0.019-0.119, P < 0.001); increase in area under the PPV curve for predicting 5-year survival was 0.068 (95% CI 0.015-0.111, P = 0.008). Conclusions HPV16 genetic variation is associated with HPV-OPC prognosis and can improve prognostic accuracy. A significant barrier to adoption of de-escalated treatment protocols for human papillomavirus-driven oropharyngeal cancer (HPV-OPC) is that few predictors of poor prognosis exist. We conducted the first large whole-genome sequencing (WGS) study to characterize the genetic variation of the HPV type 16 (HPV16) genome and to evaluate its association with HPV-OPC patient survival. A total of 460 OPC tumor specimens from two large United States medical centers (1980-2017) underwent HPV16 whole-genome sequencing. Site-specific variable positions [single nucleotide polymorphisms (SNPs)] across the HPV16 genome were identified. Cox proportional hazards model estimated hazard ratios (HRs) and 95% confidence intervals (CIs) for overall survival by HPV16 SNPs. Harrell C-index and time-dependent positive predictive value (PPV) curves and areas under the PPV curves were used to evaluate the predictive accuracy of HPV16 SNPs for overall survival. A total of 384 OPC tumor specimens (83.48%) passed quality control filters with sufficient depth and coverage of HPV16 genome sequencing to be analyzed. Some 284 HPV16 SNPs with a minor allele frequency ≥1% were identified. Eight HPV16 SNPs were significantly associated with worse survival after false discovery rate correction (individual prevalence: 1.0%-5.5%; combined prevalence: 15.10%); E1 gene position 1053 [HR for overall survival (HRos): 3.75, 95% CI 1.77-7.95; Pfdr = 0.0099]; L2 gene positions 4410 (HRos: 5.32, 95% CI 1.91-14.81; Pfdr = 0.0120), 4539 (HRos: 6.54, 95% CI 2.03-21.08; Pfdr = 0.0117); 5050 (HRos: 6.53, 95% CI 2.34-18.24; Pfdr = 0.0030), and 5254 (HRos: 7.76, 95% CI 2.41–24.98; Pfdr = 0.0030); and L1 gene positions 5962 (HRos: 4.40, 95% CI 1.88-10.31; Pfdr = 0.0110) and 6025 (HRos: 5.71, 95% CI 2.43-13.41; Pfdr = 0.0008) and position 7173 within the upstream regulatory region (HRos: 9.90, 95% CI 3.05-32.12; Pfdr = 0.0007). Median survival time for patients with ≥1 high-risk HPV16 SNPs was 3.96 years compared with 18.67 years for patients without a high-risk SNP; log-rank test P < 0.001. HPV16 SNPs significantly improved the predictive accuracy for overall survival above traditional factors (age, smoking, stage, treatment); increase in C-index was 0.069 (95% CI 0.019-0.119, P < 0.001); increase in area under the PPV curve for predicting 5-year survival was 0.068 (95% CI 0.015-0.111, P = 0.008). HPV16 genetic variation is associated with HPV-OPC prognosis and can improve prognostic accuracy.

Cyclooxygenase-2 (COX-2) gene expression in the lung is induced in pathological conditions such as asthma and pneumonia; however, the exact impact of COX-2 gene expression in the airway in regulating inflammatory and immunological response in the lung is not understood. To define a physiological role of inducible COX-2 in airway epithelial cells, we developed a novel line of transgenic mice, referred to as CycloOxygenase-2 TransActivated (COTA) mice, that overexpress a COX-2 transgene in the distribution of the CC-10 promoter in response to doxycycline. In response to doxycycline treatment, COX-2 expression was increased in airway epithelium of COTA mice and whole lung tissue contained a three- to sevenfold increase in prostaglandin E(2) (PGE(2)), prostaglandin D(2) (PGD(2)) thromboxane B(2) (TXB(2)) and 6-Keto prostaglandin F(2alpha) (PGF(2alpha)) compared to wild-type and untreated COTA mice. Interestingly, primary mouse tracheal epithelial cells from COTA mice produced only PGE(2) by doxycycline-induced COX-2 activation, providing an indication of cellular specificity in terms of mediator production. In the ovalbumin model, in which doxycycline was given at the sensitization stage, there was an increase in interleukin (IL)-4 level in lung tissue from COTA mice compared to untreated COTA and wild-type mice. In addition, COTA mice that were treated with doxycycline had impaired clearance of Pseudomonas aeruginosa pneumonia compared to wild-type mice. COX-2 gene expression in airway epithelial cells has an important role in determining immunological response to infectious and allergic agents.

Here, the addition of an electrode to the printhead in direct-ink-writing (DIW) generates an electric field (E.F.) between the electrode and the printing nozzle. The extruded ink, as an ionic conductor, is then pulled by the Coulomb force in the direction of printing, resulting in much faster writing speeds and much thinner traces (lines) and smaller widths. Limitations in speed and resolution are practically removed here because the integration of an electrode into the printhead allowed successful prints at 13.2 m/s, ~13 times faster than in other published works, as to our knowledge, and almost ~30 times faster than in most commercial printers, which are limited to 0.5 m/s. A print speed of 13.2 m/s is reached in the present work, which unlocks the speed restrictions associated with DIW and holds great promise for new design opportunities. In addition, by means of E.F., an improved resolution up to 35 μm line width has been achieved here. It should be emphasized that the high printing speed and fine resolution demonstrated in this work are still not the physical limits of the method but rather only the restrictions imposed by the present experimental setup.

2) 水资源 "三生" 子系统承载力差异显著， 生产、 生活和生态子系统的承载力均呈现提升态势； 生产和生 态子系统的承载力在空间上表现出 "东高西低" 的分布特征， 生活子系统承载力则呈现 "中部强 于四周" 的交替式分布规律。 (3) 西藏水资源承载力子系统处于较高水平耦合状态， 水资源承载 力子系统耦合协调度呈现出 "藏东南高于藏西北， 林芝市显著优于其他地市" 的空间分布特征。 关键词：水资源承载力； "三生"

Abstract After years of peripheral water injection with no significant scaling issues, pattern water injection and water injection at the GOC (Inner Ring Water Injection, or IRWI) are planned to be implemented in various reservoirs of this giant field. In a few pilot pairs, seawater injection is already taking place at a smaller spacing than historically applied. This allows testing of the injection schemes and assessment of the effect of heterogeneities before deploying pattern water injection and IRWI in the longer term. In this context, the scaling risk at the producer has been evaluated. The scaling risk assessment carried out with a thermodynamic prediction model has shown both SrSO4 and CaSO4 risks due to the mixing of formation water with injected seawater. This modelling fails to take account of geochemical reactions occurring in the reservoir; consequently, the scaling risk is usually overestimated. In this work, a reactive transport reservoir modelling tool has been used to investigate the impact of injection water composition on the scaling risk at the producer. In this model, the following are incorporated: aqueous component transport, partitioning of CO2 between aqueous and hydrocarbon phases, aqueous speciation reactions, mineral precipitation/dissolution reactions and heat transport. The simulations have considered full and reduced sulfate seawater injection with and without the presence of a thief zone. When full seawater is injected, the producer faces a risk of CaSO4 and no risk of SrSO4. This is the consequence of various coupled in situ mineral reactions, including dissolution and precipitation of carbonates and sulfates, which depend on propagation of temperature and CO2 desaturation fronts, as well as the other aqueous components. With the presence of a thief zone, SrSO4 presents a small scaling risk soon after seawater breakthrough; CaSO4 deposition has an initial peak soon after SrSO4 scaling. When reduced sulfate seawater is injected with and without the presence of the thief zone, there is no scaling risk for either SrSO4 or CaSO4. The results obtained by the reactive transport modelling tool match the general trends of scale deposition observed in the pattern injection well pair pilot to date. In this pilot a thief zone was identified in the vicinity of the injector and has contributed to accelerated water breakthrough at the producer. A peak in SrSO4 scale was observed in the early phase of water production, in agreement with the modelling results. A geochemical transport reservoir model was able to provide a full picture of seawater breakthrough at the production well, considering the impact of the thief zone. The required level of sulfate in the injected seawater, to prevent sulfate scales at the producer, has been determined. These results will help determine the scale mitigation strategy for the future development of this field.

Recently, the development of foundation models has led to significant advances in the ability of artificial intelligence (AI) to generate multimodal content such as text and images. However, specialized industrial scenarios such as finance, which require high levels of security and compliance, pose challenges for the application of generative AI due to its uncontrollability. To address this issue, we propose FinGuard, a multimodal AI-generated content (AIGC) guardrail specifically designed for financial scenarios. We provide detailed definitions of the general quality, financial compliance, and security dimensions of AIGC, and implement the evaluation and inspection of multimodal AIGC including text and images. Our proposed FinGuard has been applied to a financial marketing application serving hundreds of millions of users.

Purpose/Objective(s) Human papillomavirus-associated (HPV+) head and neck squamous cell carcinoma (HNSCC) is the fastest rising cancer in North America, with generally favourable prognosis. There is significant interest in treatment de-escalation for these patients, but 15-30% of patients recur after primary treatment, reflecting a need for improved risk-stratification tools. We sought to develop a molecular test to predict survival of patients with newly diagnosed HPV+ HNSCC. Materials/Methods We created an RNA-based prognostic score which was successfully validated in six cohorts comprising a total of 906 patients, including blinded external validations in a large retrospective cohort (n = 269) and in a prospective cohort (BD2Decide, NCT02832102, n = 286). We assessed the feasibility of using IHC to calculate the UWO3 score using an immunohistochemistry-based tissue microarray cohort (n = 197). Transcriptomic data from two aggressive treatment de-escalation cohorts were used to assess ability of UWO3 to identify patients who recur. Multivariate Cox models were used to assess the associations between the UWO3 score and outcomes, adjusting for potential confounders. Results Analysis of HPV+ HNSCC tumours revealed three distinct tumor microenvironment subtypes: immune rich, immune desert, and mixed. A three gene immune score (UWO3) classified patients into the three immune groups and was strongly associated with disease-free survival in six datasets, including blinded validation in a retrospective and a prospective dataset. Pooled analysis (n = 906) demonstrated that the immune rich group had superior disease-free survival at 5 years. The association between UWO3 immune class and time to recurrence was independent of patient age, sex, smoking status, alcohol intake status, and AJCC 8th edition clinical stage. Finally, UWO3 was able to identify patients who respond to aggressive treatment de-escalation to 30 Gy radiation in two treatment de-escalation cohorts. Conclusion The UWO3 immune score could inform clinical decision making for patients with HPV+ HNSCC based on robust outcome prediction across six independent cohorts. The superior survival of immune rich patients supports de-intensification strategies for this cohort, while the inferior outcomes of the immune desert patients suggest potential for intensification and/or immunotherapy. Prospective de-escalation and intensification clinical trials are currently being planned. Human papillomavirus-associated (HPV+) head and neck squamous cell carcinoma (HNSCC) is the fastest rising cancer in North America, with generally favourable prognosis. There is significant interest in treatment de-escalation for these patients, but 15-30% of patients recur after primary treatment, reflecting a need for improved risk-stratification tools. We sought to develop a molecular test to predict survival of patients with newly diagnosed HPV+ HNSCC. We created an RNA-based prognostic score which was successfully validated in six cohorts comprising a total of 906 patients, including blinded external validations in a large retrospective cohort (n = 269) and in a prospective cohort (BD2Decide, NCT02832102, n = 286). We assessed the feasibility of using IHC to calculate the UWO3 score using an immunohistochemistry-based tissue microarray cohort (n = 197). Transcriptomic data from two aggressive treatment de-escalation cohorts were used to assess ability of UWO3 to identify patients who recur. Multivariate Cox models were used to assess the associations between the UWO3 score and outcomes, adjusting for potential confounders. Analysis of HPV+ HNSCC tumours revealed three distinct tumor microenvironment subtypes: immune rich, immune desert, and mixed. A three gene immune score (UWO3) classified patients into the three immune groups and was strongly associated with disease-free survival in six datasets, including blinded validation in a retrospective and a prospective dataset. Pooled analysis (n = 906) demonstrated that the immune rich group had superior disease-free survival at 5 years. The association between UWO3 immune class and time to recurrence was independent of patient age, sex, smoking status, alcohol intake status, and AJCC 8th edition clinical stage. Finally, UWO3 was able to identify patients who respond to aggressive treatment de-escalation to 30 Gy radiation in two treatment de-escalation cohorts. The UWO3 immune score could inform clinical decision making for patients with HPV+ HNSCC based on robust outcome prediction across six independent cohorts. The superior survival of immune rich patients supports de-intensification strategies for this cohort, while the inferior outcomes of the immune desert patients suggest potential for intensification and/or immunotherapy. Prospective de-escalation and intensification clinical trials are currently being planned.