Miracle-dz/UniFAR-FTUs huggingface dataset:
Atezolizumab (MPDL3280A) Monotherapy for Patients With Metastatic Urothelial Cancer: Long-term Outcomes From a Phase 1 Study

Importance Atezolizumab (anti–programmed death ligand 1) has demonstrated safety and activity in advanced and metastatic urothelial carcinoma, but its long-term clinical profile remains unknown. Objective To report long-term clinical outcomes with atezolizumab therapy for patients with metastatic urothelial carcinoma. Design, Setting, and Participants Patients were enrolled in an expansion cohort of an ongoing, open-label, phase 1 study. Median follow-up was 37.8 months (range, >0.7 to 44.4 months). Enrollment occurred between March 2013 and August 2015 at US and European academic medical centers. Eligible patients had measurable disease per Response Evaluation Criteria in Solid Tumors version 1.1, Eastern Cooperative Oncology Group performance status 0 to 1, and a representative tumor sample. Programmed death ligand 1 expression on immune cells was assessed (VENTANA SP142 assay). Interventions Atezolizumab was given intravenously every 3 weeks until unacceptable toxic effects, protocol nonadherence, or loss of clinical benefit. Main Outcomes and Measures Primary outcome was safety. Secondary outcomes included objective response rate, duration of response, and progression-free survival. Response and overall survival were assessed in key baseline subgroups. Results Ninety-five patients were evaluable (72 [76%] male; median age, 66 years [range, 36-89 years]). Forty-five (47%) received atezolizumab as third-line therapy or greater. Nine patients (9%) had a grade 3 to 4 treatment-related adverse event, mostly within the first treatment year; no serious related adverse events were observed thereafter. One patient (1%) discontinued treatment due to a related event. No treatment-related deaths occurred. Responses occurred in 26% (95% CI, 18%-36%) of patients. Median duration of response was 22.1 months (range, 2.8 to >41.0 months), and median progression-free survival was 2.7 months (95% CI, 1.4-4.3 months). Median overall survival was 10.1 months (95% CI, 7.3-17.0 months); 3-year OS rate was 27% (95% CI, 17%-36%). Response occurred in 40% (95% CI, 26%-55%; n = 40) and 11% (95% CI, 4%-25%; n = 44) of patients with programmed death ligand 1 expression of at least 5% tumor-infiltrating immune cells (IC2/3) or less than 5% (IC0/1), respectively. Median overall survival in patients with IC2/3 and IC0/1 was 14.6 months (95% CI, 9.0 months to not estimable) and 7.6 months (95% CI, 4.7 to 13.9 months), respectively. Conclusions and Relevance Atezolizumab remained well tolerated and provided durable clinical benefit to a heavily pretreated metastatic urothelial carcinoma population in this long-term study. Trial Registration clinicaltrials.gov Identifier: NCT01375842
Cross Validation Through Two-Dimensional Solution Surface for Cost-Sensitive SVM

Model selection plays an important role in cost-sensitive SVM (CS-SVM). It has been proven that the global minimum cross validation (CV) error can be efficiently computed based on the solution path for one parameter learning problems. However, it is a challenge to obtain the global minimum CV error for CS-SVM based on one-dimensional solution path and traditional grid search, because CS-SVM is with two regularization parameters. In this paper, we propose a solution and error surfaces based CV approach (CV-SES). More specifically, we first compute a two-dimensional solution surface for CS-SVM based on a bi-parameter space partition algorithm, which can fit solutions of CS-SVM for all values of both regularization parameters. Then, we compute a two-dimensional validation error surface for each CV fold, which can fit validation errors of CS-SVM for all values of both regularization parameters. Finally, we obtain the CV error surface by superposing $K$ validation error surfaces, which can find the global minimum CV error of CS-SVM. Experiments are conducted on seven datasets for cost sensitive learning and on four datasets for imbalanced learning. Experimental results not only show that our proposed CV-SES has a better generalization ability than CS-SVM with various hybrids between grid search and solution path methods, and than recent proposed cost-sensitive hinge loss SVM with three-dimensional grid search, but also show that CV-SES uses less running time.
Effect of media presentations on willingness to commit to organ donation

Significance We often encounter cases of organ donation in the press or on television. How might these stories affect readers? We found that reading coverage of cases that include identifying information about the receiver (saved by organ donations) increased participants’ willingness to commit to organ donation themselves, to donate the organs of a deceased relative, or to support a transition to an “opt-out” policy. Conversely, identifying the deceased donor induced thoughts of death rather than about saving lives, resulting in fewer participants willing to donate organs or to support policies that facilitate organ donation. We show that most of the stories that appear in the press include an identified donor rather than an identified receiver, possibly reducing organ donations. We examine how presentations of organ donation cases in the media may affect people's willingness to sign organ donation commitment cards, donate the organs of a deceased relative, support the transition to an “opt-out” policy, or donate a kidney while alive. We found that providing identifying information about the prospective recipient (whose life was saved by the donation) increased the participants’ willingness to commit to organ donation themselves, donate the organs of a deceased relative, or support a transition to an “opt-out” policy. Conversely, identifying the deceased donor tended to induce thoughts of death rather than about saving lives, resulting in fewer participants willing to donate organs or support measures that facilitated organ donation. A study of online news revealed that identification of the donor is significantly more common than identification of the recipient in the coverage of organ donation cases—with possibly adverse effects on the incidence of organ donations.
Classifying diabetes-burden: A factor analysis of the Problem Areas in Diabetes Scale

This study sought to identify salient factors associated with the Problem Areas in Diabetes Scale to facilitate improved assessment and treatment of diabetes-related burden. Exploratory factor analysis assessed the factor structure of the Problem Areas in Diabetes Scale among 224 Veterans with uncontrolled type 2 diabetes and depressive symptoms. A four-factor solution of emotional, diabetes management, treatment, and social support burden subscales was extracted. These factors represent clinically relevant components of diabetes burden that include but go beyond symptoms of depression. The Problem Areas in Diabetes subscales may expand assessments for depression and improve medical and behavioral health interventions for patients with diabetes.
Reduced Inhibition within Layer IV of Sert Knockout Rat Barrel Cortex is Associated with Faster Sensory Integration

Abstract Neural activity is essential for the maturation of sensory systems. In the rodent primary somatosensory cortex (S1), high extracellular serotonin (5‐HT) levels during development impair neural transmission between the thalamus and cortical input layer IV (LIV). Rodent models of impaired 5‐HT transporter (SERT) function show disruption in their topological organization of S1 and in the expression of activity‐regulated genes essential for inhibitory cortical network formation. It remains unclear how such alterations affect the sensory information processing within cortical LIV. Using serotonin transporter knockout (Sert−/−) rats, we demonstrate that high extracellular serotonin levels are associated with impaired feedforward inhibition (FFI), fewer perisomatic inhibitory synapses, a depolarized GABA reversal potential and reduced expression of KCC2 transporters in juvenile animals. At the neural population level, reduced FFI increases the excitatory drive originating from LIV, facilitating evoked representations in the supragranular layers II/III. The behavioral consequence of these changes in network excitability is faster integration of the sensory information during whisker‐based tactile navigation, as Sert−/− rats require fewer whisker contacts with tactile targets and perform object localization with faster reaction times. These results highlight the association of serotonergic homeostasis with formation and excitability of sensory cortical networks, and consequently with sensory perception.
The Determinants and Effects of Relational Governance on IOS Usage in the Manufacturer-Supplier Relationships

Managing electronic cooperation in the manufacturer-supplier relationship is a key to successful development of an interorganizational systems (IOS) usage, and identifying the determinants of relational governance is important. However, limited empirical researches have been made to validate the effects of relational governance on IOS usage between trading partners. From several perspectives, We build an integrated framework, and use 2 automobile and 4 airline companies in china, 124 usable responses to empirically evaluate the model. Results show that relational governance including joint planning and joint problems solving has strong association with IOS usage in terms of advantage and diversity. Furthermore, reciprocal investment in form of IT and trust between manufacturer and supplier are proved to effective to promote IOS usage, these two determinants of relational governance have a moderating effect on the two dimensions of IOS usage . However, interdependence and uncertainty are found to be not effective to promote IOS usage.
Studying tunability of some NIR semiconductor lasers by external cavity setup

In this paper, tunability of three near-infrared semiconductor lasers which typically lase at 808 nm, 892 nm and 980 nm is studied. Both Littrow (wavelength dependent beam direction setup) and Littman (wavelength independent beam direction setup) configurations have been used. The wavelength and the power of the output beam of the laser have been measured. In all three cases, Littrow configuration shows a little better tuning range. In both Littrow and Littman configurations the wavelengths near the main wavelength of the laser had more power. The highest achieved power of these lasers in the Littrow setup was more than that of the Littman setup.
Fused silica segments: a possible solution for x-ray telescopes with very high angular resolution like Lynx/XRS

In order to look beyond Chandra, the Lynx/XRS mission has been proposed in USA and is currently studied by NASA. The optic will have an effective area of 2.5 m2 and an angular resolution of 0.5 arcsec HEW at 1 keV. In order to fulfill these requirements different technologies are considered, with the approaches of both full and segmented shells (that, possibly, can be also combined together). Concerning the production of segmented mirrors, a variety of thin substrates (glass, metal, silicon) are envisaged, that can be produced using both direct polishing or replication methods. Innovative post-fabrication correction methods (such as piezoelectric or magneto-restrictive film actuators on the back surface, differential deposition, ion implantation) are being also considered in order to reach the final tolerances. In this paper we are presenting a technology development based on fused silica (SiO2) segmented substrates, owing the low coefficient of thermal expansion of Fused Silica and its high chemical stability compared to other glasses. Thin SiO2 segmented substrates (typically 2 mm thick) are figured by direct polishing combined with final profile ion figuring correction, while the roughness reduction is reached with pitch tools. For the profile and roughness correction, the segments are glued to a substrate. In this paper we present the current status of this technology.
ULV-Turbo Cache for an Instantaneous Performance Boost on Asymmetric Architectures

An asymmetric architecture is commonly used in modern embedded systems to reduce energy consumption. The systems tend to execute more applications in the energy-efficient core, which typically employs ultralow voltage (ULV) to save energy. However, caches become a reliability and performance barrier that limits the minimum operating voltage and blocks system performance in the ULV environment. The poor performance of an ultralow-voltage core causes most workload requirements to awaken and then execute on the host core, leading to high energy consumption. In this paper, we propose a ULV-Turbo cache based on a ULV-selective-ally 8T static random access memory (SRAM) that is able to perform reliable ultralow-voltage operation and provide the speedup function of SRAM rows ally. The system is able to speed up the ULV core instantaneously and execute more applications with the ULV-Turbo cache. In our system-wide evaluation based on a real attitude and heading reference system workload on an asymmetric wearable system, the ULV-Turbo cache reduces the energy consumption of the entire system by approximately 36%.
Investigation of the Effect of Using Different Material Models on Finiste Element Simulations of Machining | NIST

Choosing the appropriate constitutive model is important for finite element analyses (FEA) of different metal forming processes. Due to the presence of high values of strain, strain rate and temperature in machining, it is extremely important to evaluate the performance of the different material models. Typically these were developed at much lower strains, strain rates and temperature. To model orthogonal machining, we use coupled thermo-mechanical analysis of machining using a commercial finite element analysis system. The workpiece material, AISI 1045, is both well characterized in the form of different constitutive models and widely used in industry. We use three different constitutive models for AISI 1045 deforming under high strain rate and temperature, the Oxley model, Johnson-Cook model, and Maekawa history dependent model. To normalize the comparison of the performance of these models, the friction coefficient for each simulation is set to a value that results in the closest match between the predicted cutting force and measured cutting force. A detailed comparison of the other process outputs of interest, namely, thrust force, chip thickness, shape of the primary and secondary shear zones and temperature distributions, is carried out to compare the performance of different material models to each other and experimental results.
Experimentally Induced Selenosis in Yellow-Bellied Slider Turtles (Trachemys scripta scripta)

Selenosis, or selenium toxicosis, occurs in wildlife and livestock, usually because of excessive intake of selenium via selenium-containing plants. Although it is known that wild slider turtles can accumulate large amounts of selenium, little is known about how selenium exposure may affect these reptiles. In this study, the authors report histopathologic changes in yellow-bellied sliders (Trachemys scripta scripta) caused by experimental exposure to selenomethionine. Microscopic changes in kidney and claw tissue were most significant and resembled those reported in birds. Turtles in the selenium treatment groups had acute tubular degeneration and regeneration in the kidney, with hyaline droplets in the high-dose animals, and changes in the claws ranging from epidermal hyperplasia with disorganization and intercellular edema to ulceration, and accumulation of seroheterophilic exudate between the epidermis and cornified layer. Although selenium burdens in this study are comparable with values found in wild slider turtles, more data are needed to determine if similar histopathologic abnormalities arise in wild animals exposed to high levels of selenium.
Maternal Supplementation with Folic Acid and Other Vitamins and Risk of Leukemia in Offspring: A Childhood Leukemia International Consortium Study

Background: Maternal prenatal supplementation with folic acid and other vitamins has been inconsistently associated with a reduced risk of childhood acute lymphoblastic leukemia (ALL). Little is known regarding the association with acute myeloid leukemia (AML), a rarer subtype. Methods: We obtained original data on prenatal use of folic acid and vitamins from 12 case-control studies participating in the Childhood Leukemia International Consortium (enrollment period: 1980–2012), including 6,963 cases of ALL, 585 cases of AML, and 11,635 controls. Logistic regression was used to estimate pooled odds ratios (ORs) and 95% confidence intervals (CIs), adjusted for child’s age, sex, ethnicity, parental education, and study center. Results: Maternal supplements taken any time before conception or during pregnancy were associated with a reduced risk of childhood ALL; odds ratios were 0.85 (95% CI = 0.78–0.92) for vitamin use and 0.80 (0.71–0.89) for folic acid use. The reduced risk was more pronounced in children whose parents’ education was below the highest category. The analyses for AML led to somewhat unstable estimates; ORs were 0.92 (0.75–1.14) and 0.68 (0.48–0.96) for prenatal vitamins and folic acid, respectively. There was no strong evidence that risks of either types of leukemia varied by period of supplementation (preconception, pregnancy, or trimester). Conclusions: Our results, based on the largest number of childhood leukemia cases to date, suggest that maternal prenatal use of vitamins and folic acid reduces the risk of both ALL and AML and that the observed association with ALL varied by parental education, a surrogate for lifestyle and sociodemographic characteristics.
In Vitro Antiviral Activity and Resistance Profile of the Next-Generation Hepatitis C Virus NS5A Inhibitor Pibrentasvir

ABSTRACT Pibrentasvir (ABT-530) is a novel and pan-genotypic hepatitis C virus (HCV) NS5A inhibitor with 50% effective concentration (EC50) values ranging from 1.4 to 5.0 pM against HCV replicons containing NS5A from genotypes 1 to 6. Pibrentasvir demonstrated similar activity against a panel of chimeric replicons containing HCV NS5A of genotypes 1 to 6 from clinical samples. Resistance selection studies were conducted using HCV replicon cells with NS5A from genotype 1a, 1b, 2a, 2b, 3a, 4a, 5a, or 6a at a concentration of pibrentasvir that was 10- or 100-fold over its EC50 for the respective replicon. With pibrentasvir at 10-fold over the respective EC50, only a small number of colonies (0.00015 to 0.0065% of input cells) with resistance-associated amino acid substitutions were selected in replicons containing genotype 1a, 2a, or 3a NS5A, and no viable colonies were selected in replicons containing NS5A from other genotypes. With pibrentasvir at 100-fold over the respective EC50, very few colonies (0.0002% of input cells) were selected by pibrentasvir in genotype 1a replicon cells while no colonies were selected in other replicons. Pibrentasvir is active against common resistance-conferring substitutions in HCV genotypes 1 to 6 that were identified for other NS5A inhibitors, including those at key amino acid positions 28, 30, 31, or 93. The combination of pibrentasvir with HCV inhibitors of other classes produced synergistic inhibition of HCV replication. In summary, pibrentasvir is a next-generation HCV NS5A inhibitor with potent and pan-genotypic activity, and it maintains activity against common amino acid substitutions of HCV genotypes 1 to 6 that are known to confer resistance to currently approved NS5A inhibitors.
An Iterative Hierarchical Key Exchange Scheme for Secure Scheduling of Big Data Applications in Cloud Computing

As the new-generation distributed computing platform, cloud computing environments offer high efficiency and low cost for data-intensive computation in big data applications. Cloud resources and services are available in pay-as-you-go mode, which brings extraordinary flexibility and cost-effectiveness as well as zero investment in their own computing infrastructure. However, these advantages come at a price-people no longer have direct control over their own data. Based on this view, data security becomes a major concern in the adoption of cloud computing. Authenticated Key Exchange (AKE) is essential to a security system that is based on high efficiency symmetric-key encryption. With virtualization technology being applied, existing key exchange schemes such as Internet Key Exchange (IKE) becomes time-consuming when directly deployed into cloud computing environment. In this paper we propose a novel hierarchical key exchange scheme, namely Cloud Background Hierarchical Key Exchange (CBHKE). Based on our previous work, CBHKE aims at providing secure and efficient scheduling for cloud computing environment. In our new scheme, we design a two-phase layer-by-layer iterative key exchange strategy to achieve more efficient AKE without sacrificing the level of data security. Both theoretical analysis and experimental results demonstrate that when deployed in cloud computing environment, efficiency of the proposed scheme is dramatically superior to its predecessors CCBKE and IKE schemes.
Combinations of L-NG-monomethyl-arginine and oseltamivir against pandemic influenza A virus infections in mice

L-NG-monomethyl-arginine (L-NMMA) is an experimental compound that suppresses nitric oxide production in animals. The compound was combined with oseltamivir to treat lethal influenza A/California/04/2009 (H1N1) pandemic virus infections in mice. Treatments were given twice a day for five days starting 4 h (oseltamivir, by oral gavage) or three days (L-NMMA, by intraperitoneal route; corresponding to the time previously reported for nitric oxide induction in the animals) after infection. Low doses of oseltamivir were used in order to demonstrate synergy or antagonism. Oseltamivir monotherapy protected 70% of mice from death at 1 mg/kg/day. L-NMMA (40 and 80 mg/kg/day) was ineffective alone in preventing mortality. Compared to oseltamivir treatment alone, L-NMMA combined with oseltamivir was synergistically effective (as evaluated by three-dimensional MacSynergy analysis), resulting in survival increases from 20 to 70% when 40 or 80 mg/kg/day of L-NMMA was combined with 0.3 mg/kg/day of oseltamivir, and from 70 to 100% survival increases when these doses were combined with 1 mg/kg/day of oseltamivir. These data demonstrate that a nitric oxide inhibitor such as L-NMMA has the potential to be beneficial when combined with oseltamivir in treating influenza virus infections.
Quill: A Framework for Constructing Negotiated Texts - With a Case Study on the US Constitutional Convention of 1787

This paper describes a new approach to the presentation of records relating to formal negotiations and the texts that they create. It describes the architecture of a model, platform, and web-interface (https://www.quillproject.net) that can be used by domain-experts to convert the records typical of formal negotiations in to a model of decision-making (with minimal training). This model has implications for both research and teaching, by allowing for better qualitative and quantitative analysis of negotiations. The platform emphasizes the reconstruction as closely as possible of the context within which proposals and decisions are made. A generic platform, its usability, and benefits are illustrated by a presentation of the records relating to the 1787 Constitutional Convention that wrote the Constitution of the United States.