Miracle-dz/UniFAR-FTUs huggingface dataset:
Phenotype, development, and biological function of myeloid-derived suppressor cells

CD11b+Gr-1+ myeloid-derived suppressor cells (MDSCs) are an important population of innate regulatory cells mainly comprising monocytic MDSCs (M-MDSCs) with a phenotype of CD11b+Ly6G−Ly6Chigh and granulocytic MDSCs (G-MDSCs) with a phenotype of CD11b+Ly6G+Ly6Clow in mice. They play crucial roles in the pathogenesis of cancers, chronic infections, autoimmune diseases, and transplantation. Various extracellular factors such as lipopolysaccharide (LPS), macrophage colony-stimulating factor (M-CSF), granulocyte macrophage colony-stimulating factor (GM-CSF), stem cell factor (SCF), interleukin (IL)-6, interferon gamma (IFNγ), IL-1β, vascular endothelial growth factor (VEGF), Hsp72, IL-13, C5a, and prostaglandin E2 (PGE2) can induce MDSC differentiation, whereas IL-4 and all-trans-retinoic acid can inhibit this process. For the intracellular signals, signal transducer and activator of transcription (STAT) family members, C/EBPβ and cyclooxigenase-2 (COX-2) promote MDSC function, whereas interferon regulatory factor-8 (IRF-8) and Smad3 downregulate MDSC activity. The immunosuppressive function of MDSCs is mediated through various effector molecules, primarily cellular metabolism-related molecules such as nitric oxide (NO), arginase, reactive oxygen species (ROS), transforming growth factor β (TGFβ), IL-10, indoleamine 2,3-dioxygenase (IDO), heme oxygenase-1 (HO-1), carbon monoxide (CO), and PGE2. In this article, we will summarize the molecules involved in the induction and function of MDSCs as well as the regulatory pathways of MDSCs.
Statistical analysis of the accelerated life testing for fighter-bomber wheel hubs

Accelerated life testing (ALT) is used to get information quickly on life distributions. This study describes an accelerated life testing for fighter-bomber wheel hubs that is representative of actual service conditions. The acceleration models are proposed based on the fatigue life tests of 2014 aluminum alloy, which is extensively used to make fighter-bomber wheel hubs. The BLUE (best linear unbiased estimation) and MLE (maximum likelihood estimation) are adopted in the estimation of the acceleration models, and the acceleration models under the conditions of different SCF (stress concentration factor) are compared by statistical method to determine the sensitivity of SCF to the acceleration factor of the fighter-bomber wheel hubs made by 2014Al.
Treatment for BK virus: incidence, risk factors and outcomes for kidney transplant recipients in the United States

There has been a notable rise of BK virus among kidney transplant recipients. Single‐center reports have identified risk factors for development of BK virus. However, there has not been an assessment of risk factors and incidence of this complication at a national level. This study utilized newly collected follow‐up information from the national SRTR database to investigate incidence, risk factors and outcomes for solitary kidney transplant recipients associated with treatment for BK virus (TBKV) from 2004 to 2006. Logistic and Cox models were utilized to assess risk factors and evaluate graft survival associated with TBKV. Incidence of TBKV was 1.6% at 6 months and 2.6% at 1 year following transplantation. Patients with and without TBKV at 6 months had 79% and 90% 3‐year overall graft survival respectively. Risk factors included advanced donor age, pediatric, African American and male recipients, human leukocyte antigen‐mismatching and tacrolimus and thymoglobulin induction as baseline immunosuppression. Acute rejection episodes were more frequent prior to and following TBKV. TBKV is a common and rising incidence, varies based on transplant characteristics and should be included as a safety endpoint in studies investigating immunosuppressive protocols. Careful monitoring and further understanding of disease etiology and treatment strategies are needed.
Risk-averse trees for learning from logged bandit feedback

Logged data is one of the most widespread form of recorded information, since it can be acquired by almost any system and stored at a little cost. Customarily, the interaction logs between the system and a user (or environment) present the structure of a sequential decision process: given a context, the system performs an action and the user provides a feedback about it. This structure is common to a wide range of real-world micro-economic applications, e.g., e-commerce websites and advertisement campaigns. The problem of learning a policy from such logged interactions to take more profitable decisions in the future is known as the Learning from Logged Bandit Feedback (LLBF) problem. In this paper, we propose RADT, an algorithm specifically shaped for the LLBF setting and based on a risk-averse learning method which exploits the joint use of regression trees and statistical confidence bounds. Differently from existing techniques developed for this setting, RADT generates policies aiming to maximize a lower bound on the expected reward and provides a clear characterization of those features in the context that influence the process the most. Finally, we provide a wide experimental campaign over both synthetic and real-world datasets showing empirical evidence that RADT outperforms both state-of-the-art machine learning classification and regression techniques and existing methods addressing the LLBF setting.
Correlation of primate red nucleus discharge with muscle activity during free‐form arm movements.

1. We recorded from 239 neurons located in the magnocellular division of the red nucleus of four alert macaque monkeys. At the same time, we recorded electromyographic (EMG) signals from as many as twenty electrodes chronically implanted on muscles of the shoulder, arm, forearm and hand. We recorded EMG signals for periods ranging from several months to a year. 2. The monkeys were trained to perform three free‐form food retrieval tasks, each of which activated all of the recorded muscles and most of the neurons. The ‘prehension’ task required simply that the monkey grasp a piece of food from a fixed point in space. The ‘barrier’ task required the monkey to reach around a small barrier to obtain the food, and the ‘Kluver’ task required that food be removed from small holes. During the prehension task, we found approximately equal numbers of neurons that were strongly active while the hand was being moved toward the target (70% of units), and while the food was being grasped (60%). Relatively few units were active as the hand was returned to the mouth (15%). 3. Data files of 1‐2 min duration were collected while the monkey performed a single behavioural task. Whenever possible, we recorded files for all three tasks from each neuron. For each file we calculated long time‐span analog cross‐correlations (+/‐ 1.28 s) between instantaneous neuronal firing rate and each of the full‐wave rectified, low‐pass filtered EMG signals. We used the peak correlation and the time of the peak as two summary measures of the functional relation between modulation of neuronal activity and EMG. 4. The magnitude of the strongest correlations was between 0.4 and 0.5 (normalized to a perfect correlation of +/‐ 1.0). Distal muscles were the most frequently correlated, and extensors were more frequently correlated than flexors. For all monkeys, the lags for well correlated muscles were distributed broadly about a uni‐modal value near 0 ms. Eighty five per cent of the correlations larger than or equal to 0.25 had peaks between ‐150 and 200 ms. 5. The activity of each neuron was represented in a muscle co‐ordinate system by an n‐dimensional ‘functional linkage vector’, each element of which was the peak correlation with one of n muscles. The vector for any given neuron points in a particular direction in muscle space, depending on the similarity between the activity of the neuron and the activity of each muscle. (ABSTRACT TRUNCATED AT 400 WORDS)
Soluble CD40 ligand impairs the anti-platelet function of peripheral blood angiogenic outgrowth cells via increased production of reactive oxygen species

Summary Adult peripheral blood angiogenic early outgrowth cells (EOCs), also known as early endothelial progenitor cells, interact with other blood and vascular cells and may regulate atherothrombosis. We have previously shown that endothelial progenitor cells inhibit platelet function and thrombus formation. The CD40L/CD40 axis is a thrombo-inflammatory mediator that affects platelet and endothelial functions. It has been shown that EOCs express CD40, whereas platelets represent the major source of its soluble ligand (sCD40L), which impairs EOC function. We aimed to test the hypothesis that the sCD40L/CD40 axis affects the anti-platelet function of EOCs. Human peripheral blood mononuclear cell-derived EOCs in culture inhibited platelet aggregation. Pre-treatment of EOCs with sCD40L reduced their in-hibitory effect on platelet aggregation in a CD40-dependent manner. EOCs viability and release of the anti-aggregating agents, prostacyclin and nitric oxide, were not affected by sCD40L. However, production of reactive oxygen species (ROS) was increased in sCD40L–treated EOCs. Blockade of ROS reversed the effects of sCD40L–treated EOCs on platelet aggregation. This study reveals that the sCD40L/CD40 axis impairs the anti-platelet properties of EOCs through increased production of ROS. These data may explain the link between elevated levels of sCD40L, impaired activity of EOCs and enhanced platelet reactivity, and consequently the occurrence of atherothrombotic disease.
A new approach to decision support for environmental conflict resolution

An environmental conflict that occurred in Elmira, a small town in southwestern Ontario, Canada is re-examined using a modified version of the Graph Model for Conflict Resolution (GMCR). A newly developed decision support system (DSS) is utilized to carry out the analysis using the new “Inverse GMCR” approach. The new DSS features automatic graph drawing and in-depth conflict analysis, and provide new insights.
Assessing the effects of age, sex and shared environment on the genetic aetiology of depression in childhood and adolescence.

BACKGROUND Depressive symptoms and disorder are experienced by a significant proportion of young people and have long-lasting deleterious effects. The aims of the current investigation were to examine the aetiology of depressive symptoms using a twin design. In particular to examine the effects of sex, age, maternal depression and anxiety symptoms and to examine the aetiology of high depression scores. METHODS Questionnaires were sent to the families of a population-based sample of twins aged between 8 and 17 years. Parents and children over the age of 11 were asked to complete the Mood and Feelings Questionnaire and Hospital Anxiety and Depression Scale (mothers only). Responses were obtained from 1463 families and data were analysed using genetic model fitting and DeFries and Fulker regression analysis. RESULTS Depressive symptoms, particularly when self-rated, were significantly genetically influenced. There was evidence of significant heterogeneity according to age, with shared environmental factors more important and genetic factors less important for children aged 8 to 10 than for adolescents aged 11 to 17 years. Some but not all of the shared environmental influences on parent-rated depressive symptoms were accounted for by maternal symptoms of depression and anxiety. There was a significant effect of gender for self-rated depressive symptoms. For boys, genetic factors were of greater importance and common environmental influences of less importance than for girls. Shared environmental effects had a substantial influence on high self-rated depression scores. Adolescents who scored highly on self-rated depression questionnaires experienced significantly more shared life events and their mothers had significantly higher internalising symptoms than adolescents who scoredwithin the normal range. CONCLUSIONS The results of this study add to the evidence that the aetiology of depressive symptoms differs by age, with genetic factors becoming more important from childhood to adolescence. Some but not all of the shared environmental effect observed for mother-rated depression scores is due to maternal depression and anxiety symptoms. For self-rated depressive symptoms, the importance of genetic and environmental factors may also differ by sex, with genetic influences more important for boys. The aetiology of high depression symptom scores, when self-rated, appears to differ from scores within the normal range in that shared environmental factors appear to be more important. Further research is needed to identify these shared environmental factors using longitudinal models that test genetic and environmental mediation.
Cloudy corneas as an initial presentation of multiple myeloma

Summary We report a case of previously unsuspected myeloma, presenting with cornea verticillata due to intracorneal paraprotein deposition. History An 85-year-old female presented via her optician with a 4-month history of cloudy vision. She had undergone an uneventful bilateral phacoemulsification surgery 7 years earlier. Extensive spiraling corneal epithelial opacification was noted on slit-lamp examination. On further investigation, she was found to have a previously unsuspected low-grade multiple myeloma. We established the nature of the corneal deposits with corneal epithelial biopsy histopathology and electron microscopy. It is very rare for multiple myeloma to present in this fashion. Ophthalmologists should be aware that such a presentation may rarely be due to systemic multiple myeloma.
Thickness-shear frequencies of an infinite quartz plate with material property variation along the thickness

Properties of the quartz crystal blank of a resonator is assumed homogeneous, uniform, and perfect in design, manufacturing, and applications. As end products, quartz crystal resonators are frequently exposed to gases and liquids which can cause surface damage and internal degradation of blanks under increasingly hostile conditions. The combination of service conditions and manufacturing process including chemical etching and polishing can inevitably modify the surface of quartz crystal blanks with changes of material properties, raising the question of what will happen to vibrations of quartz crystal resonators of thickness-shear type if such modifications to blanks are to be evaluated for sensitive applications. Such questions have been encountered in other materials and structures with property variations either on purpose or as the effect of environmental or natural processes commonly referred to as functionally graded materials, or FGMs. Analyses have been done in applications as part of studies on FGMs in structural as well as in acoustic wave device applications. A procedure based on series solutions has been developed in the evaluation of frequency changes and features in an infinite quartz crystal plate of AT-cut with the symmetric material variation pattern given in a cosine function with the findings that the vibration modes are now closely coupled. These results can be used in the evaluation of surface damage and corrosion of quartz crystal blanks of resonators in sensor applications or development of new structures of resonators.
Queueing network models for electric vehicle charging station with battery swapping

Electric Vehicle (EV) charging stations with battery swapping, as one promising energy supplement solution to cope with the increasing in EVs, demand a theoretical performance analysis framework. In this paper, we propose a queueing network model to serve as such a framework for battery swapping stations with a locally-charging mode. The model is a mixed queueing network with an open queue of EVs and a closed queue of batteries. Based on mild assumptions, we show the equilibrium equations for the queueing system, and the steady-state distribution is the solution of these finite equilibrium equations. In order to show the uniqueness of the solution, we prove the ergodicity of the system. Meanwhile, by leveraging the embedded Markov chain, we present an alternative yet much easier way to compute the steady-state distribution. Based on the steady-state distribution, various important performance indicators have been analytically determined. Simulation results demonstrate the validity of the queueing network model and reveal rich insights for the infrastructure planning of practical battery swapping stations.
Keeping track of time under ice and snow in a sub‐arctic lake: plasma melatonin rhythms in Arctic charr overwintering under natural conditions

Abstract: Although photoperiod is considered as a major environmental cue for timing of seasonal events in fish, little is known about the photic information perceived by fish in different aquatic environments. The strongly seasonal Arctic charr, Salvelinus alpinus, reside in lakes covered by thick ice and snow throughout the dark winter in the north. In the present study, we have measured diel changes in their plasma melatonin concentrations from September to June in Lake Storvatnet (70°N), northern Norway. In addition, we have measured the in vitro melatonin production of Arctic charr pineal glands held at experimental light conditions. From September to April a diel profile in plasma melatonin was seen in the charr in Lake Storvatn, with highest concentrations at night. This profile reflected the prevailing above‐surface photoperiod, even in February when there were minimal changes in sub‐surface irradiance between day and night. In June, plasma melatonin was low throughout the 24‐hr cycle, despite there being a marked sub‐surface difference in irradiance between night and day. At this time the irradiance in night probably remained above the threshold for suppression of melatonin production. The in vitro experiments revealed no endogenous rhythm in the pineal melatonin secretion, supporting the conclusion that the diel profile seen in the Arctic charr in their natural habitat was driven by ambient photoperiod. In conclusion, the Arctic charr appear to keep track of time even under the extreme conditions of high latitudes during winter, when lakes have thick ice and snow cover.
In Vivo and In Vitro Hepatoprotective Effects of Geranium koreanum Methanolic Extract via Downregulation of MAPK/Caspase-3 Pathway

Geranium koreanum (GK) is an indigenous Chinese herbal medicine widely used for the treatment of various inflammation and liver disorders. However, the exact mechanism of action of GK remains unknown. This study aimed to investigate the protective effect and related molecular mechanism of GK on NaAsO2-induced cytotoxicity in HepG2 cells and liver damage in mice. The cytoprotective role of GK was assessed on HepG2 cells using MTT assay. Oxidative stress and lactate dehydrogenase levels were measured with ROS and LDH assay. Histopathology and serum enzymes levels were estimated. The molecular mechanism was evaluated by qPCR and immunoblotting to ensure the hepatoprotective role of GK against NaAsO2 intoxication in mice. We found cotreatment with GK significantly attenuated NaAsO2-induced cell viability loss, intracellular ROS, and LDH release. Hepatic histopathology and serum biochemical parameters, ALT, and AST were notably improved by cotreatment with GK. Beside, GK markedly altered both mRNA and protein expression level of MAPK. The proapoptotic and antiapoptotic protein Bax/Bcl-2 ratio was significantly regulated by GK. Moreover, GK remarkably suppressed the postapoptotic transcription protein cleaved caspase-3 expression. The present study reveals that GK possesses hepatoprotective activity which is probably involved in the modulation of the MAPK/caspase-3 pathway.
Overall survival benefit with lapatinib in combination with trastuzumab for patients with human epidermal growth factor receptor 2-positive metastatic breast cancer: final results from the EGF104900 Study.

PURPOSE Phase III EGF104900 data demonstrated that lapatinib plus trastuzumab significantly improved progression-free survival (PFS) and clinical benefit rate versus lapatinib monotherapy, offering a chemotherapy-free option for patients with heavily pretreated human epidermal growth factor receptor 2 (HER2) -positive metastatic breast cancer (MBC). Final planned overall survival (OS) analysis from EGF104900 is reported here. PATIENTS AND METHODS Patients with HER2-positive MBC whose disease progressed during prior trastuzumab-based therapies were randomly assigned to receive lapatinib monotherapy or lapatinib in combination with trastuzumab. OS and updated PFS data are presented using Kaplan-Meier curves and log-rank tests stratified for hormone receptor and visceral disease status. Subgroup analyses were conducted to identify characteristics of patients deriving the greatest clinical benefit. RESULTS In this updated final analysis of all patients randomly assigned with strata (n = 291), lapatinib plus trastuzumab continued to show superiority to lapatinib monotherapy in PFS (hazard ratio [HR], 0.74; 95% CI, 0.58 to 0.94; P = .011) and offered significant OS benefit (HR, 0.74; 95% CI, 0.57 to 0.97; P = .026). Improvements in absolute OS rates were 10% at 6 months and 15% at 12 months in the combination arm compared with the monotherapy arm. Multiple baseline factors, including Eastern Cooperative Oncology Group performance status of 0, nonvisceral disease, < three metastatic sites, and less time from initial diagnosis until random assignment, were associated with improved OS. Incidence of adverse events was consistent with previously reported rates. CONCLUSION These data demonstrated a significant 4.5-month median OS advantage with the lapatinib and trastuzumab combination and support dual HER2 blockade in patients with heavily pretreated HER2-positive MBC.
‘Wrong bonds’ in sputtered amorphous Ge2Sb2Te5

The structure of sputtered amorphous Ge2Sb2Te5 was investigated by high energy x-ray diffraction, neutron diffraction and Ge-, Sb- and Te K-edge EXAFS measurements. The five datasets were modelled simultaneously in the framework of the reverse Monte Carlo simulation technique. It was found that apart from Te–Sb and Te–Ge bonds existing in the crystalline phases, Ge–Ge and Sb–Ge bonding is also significant in sputtered amorphous Ge2Sb2Te5. According to our results, all components obey the ‘8-N’ rule.
Quantification of deuterated bisphenol A in serum, tissues, and excreta from adult Sprague-Dawley rats using liquid chromatography with tandem mass spectrometry.

Bisphenol A (BPA) is an important industrial chemical used in the manufacture of polycarbonate plastic products, epoxy resin-based food can liners, and paper products. The presence of BPA in urine of >90% of Americans aged 6-60 suggests ubiquitous and frequent exposure and is problematic because of the potential for endocrine disruption. The ubiquity of environmental BPA in common laboratory supplies used for sample collection, storage, and analysis greatly increases the likelihood of false positive determinations, particularly at trace levels. The current study validated using liquid chromatography/tandem mass spectrometry (LC/MS/MS) in conjunction with deuterated BPA as the dosing material to circumvent contamination for high sensitivity quantifications in rat serum, tissues, urine, and feces. The methods described provided measurements of both estrogen receptor-active aglycone and metabolically deactivated conjugated forms of BPA, a distinction that is critical to assessing toxicological potential. The adequacy of the described methodology was substantiated by its utility in analyzing samples from rats treated orally with a 100 µg/kg body weight dose of d6-BPA. These results emphasize the challenges inherent in measuring BPA in biological samples and how employing stable isotope labeled dosing can facilitate pharmacokinetic studies needed to understand BPA metabolism and disposition. Such studies conducted in experimental animal models, in conjunction with properly validated human biomonitoring data, will be the basis for PBPK modeling of BPA in environmentally exposed humans.