Miracle-dz/UniFAR-FTUs huggingface dataset:
Emerging role of NRF2 in chemoresistance by regulating drug-metabolizing enzymes and efflux transporters

Abstract Chemoresistance is a disturbing barrier in cancer therapy, which always results in limited therapeutic options and unfavorable prognosis. Nuclear factor E2-related factor 2 (NRF2) controls the expression of genes encoding cytoprotective enzymes and transporters that protect against oxidative stress and electrophilic injury to maintain intrinsic redox homeostasis. However, recent studies have demonstrated that aberrant activation of NRF2 due to genetic and/or epigenetic mutations in tumor contributes to the high expression of phase I and phase II drug-metabolizing enzymes, phase III transporters, and other cytoprotective proteins, which leads to the decreased therapeutic efficacy of anticancer drugs through biotransformation or extrusion during chemotherapy. Therefore, a better understanding of the role of NRF2 in regulation of these enzymes and transporters in tumors is necessary to find new strategies that improve chemotherapeutic efficacy. In this review, we summarized the recent findings about the chemoresistance-promoting role of NRF2, NRF2-regulated phase I and phase II drug-metabolizing enzymes, phase III drug efflux transporters, and other cytoprotective genes. Most importantly, the potential of NRF2 was proposed to counteract drug resistance in cancer treatment.
Cost Optimization of Distributed Computing System with Dynamic Re-Allocation

Distributed Computing System (DCS) is a combination of application and system programs that exchanges data across a number of independent terminals connected by a communication network. Cost optimization in DCS can be achieve by optimize the performance of DCS. In task allocation two types of approaches are available and these are dynamic and static. Dynamic approach of task allocation is much better as compare to static, since it makes the best use of available computational resources in DCS. Task allocation problem can be describe as 'm' number tasks are required to execute on 'n' number of processors where number tasks (m) is always greater than number of processors (n) (m>n). This research offers a cost optimization algorithm with dynamic re- allocation of tasks to allocate the 'm' number of tasks on 'n' number of processors in DCS and their execution completes in k number of phases. Proposed algorithm is tested in MATLAB environment and it is noticed that obtained results are better as compared to past algorithms. Cost optimization dynamic model present in this research is helpful in performance optimization of DCS and also reduce the cost of task allocation in DCS.
Impact of growth mode, phase, and rate on the metabolic state of the extremely thermophilic archaeon Pyrococcus furiosus.

The archaeon Pyrococcus furiosus is emerging as a metabolic engineering platform for production of fuels and chemicals, such that more must be known about this organism's characteristics in bioprocessing contexts. Its ability to grow at temperatures from 70 to greater than 100°C and thereby avoid contamination, offers the opportunity for long duration, continuous bioprocesses as an alternative to batch systems. Toward that end, we analyzed the transcriptome of P. furiosus to reveal its metabolic state during different growth modes that are relevant to bioprocessing. As cells progressed from exponential to stationary phase in batch cultures, genes involved in biosynthetic pathways important to replacing diminishing supplies of key nutrients and genes responsible for the onset of stress responses were up-regulated. In contrast, during continuous culture, the progression to higher dilution rates down-regulated many biosynthetic processes as nutrient supplies were increased. Most interesting was the contrast between batch exponential phase and continuous culture at comparable growth rates (∼0.4 hr-1 ), where over 200 genes were differentially transcribed, indicating among other things, N-limitation in the chemostat and the onset of oxidative stress. The results here suggest that cellular processes involved in carbon and electron flux in P. furiosus were significantly impacted by growth mode, phase and rate, factors that need to be taken into account when developing successful metabolic engineering strategies.
Incorporation of Procedure-specific Risk Into the ACS-NSQIP Surgical Risk Calculator Improves the Prediction of Morbidity and Mortality After Pancreatoduodenectomy

Objective: This multicenter study sought to evaluate the accuracy of the American College of Surgeons National Surgical Quality Improvement Program's (ACS-NSQIP) surgical risk calculator for predicting outcomes after pancreatoduodenectomy (PD) and to determine whether incorporating other factors improves its predictive capacity. Background: The ACS-NSQIP surgical risk calculator has been proposed as a decision-support tool to predict complication risk after various operations. Although it considers 21 preoperative factors, it does not include procedure-specific variables, which have demonstrated a strong predictive capacity for the most common and morbid complication after PD – clinically relevant pancreatic fistula (CR-POPF). The validated Fistula Risk Score (FRS) intraoperatively predicts the occurrence of CR-POPF and serious complications after PD. Methods: This study of 1480 PDs involved 47 surgeons at 17 high-volume institutions. Patient complication risk was calculated using both the universal calculator and a procedure-specific model that incorporated the FRS and surgeon/institutional factors. The performance of each model was compared using the c-statistic and Brier score. Results: The FRS was significantly associated with 30-day mortality, 90-day mortality, serious complications, and reoperation (all P < 0.0001). The procedure-specific model outperformed the universal calculator for 30-day mortality (c-statistic: 0.79 vs 0.68; Brier score: 0.020 vs 0.021), 90-day mortality, serious complications, and reoperation. Neither surgeon experience nor institutional volume significantly predicted mortality; however, surgeons with a career PD volume >450 were less likely to have serious complications (P < 0.001) or perform reoperations (P < 0.001). Conclusions: Procedure-specific complication risk influences outcomes after pancreatoduodenectomy; therefore, risk adjustment for performance assessment and comparative research should consider these preoperative and intraoperative factors along with conventional ACS-NSQIP preoperative variables.
Global Expression of Simulated Microgravity-Responsive Genes in Xenopus Liver Cells

Abstract The random positioning machine (RPM) is a method used to generate a simulated-microgravity environment at approximately 0 g. Using an RPM, we analyzed the global gene expression of A8 cells derived from the liver of adult Xenopus laevis. A range of genes on a Xenopus 44K-scale microarray were up- or downregulated two-fold or more: 43 genes (up, 36 genes; down, 7 genes) on culture day 5 in RPM, 74 genes (up, 48 genes; down, 26 genes) on day 8, 105 genes (up, 71 genes; down, 34 genes) on day 10, and 132 genes (up, 98 genes; down, 34 genes) on day 15. Five genes were upregulated two-fold or more throughout culturing in RPM, while only one gene was downregulated over the entire time. We then compared the expression patterns of the RPM-dependent genes in the A8 cells with those in A6 cells established from the kidney of adult Xenopus laevis. Six upregulated genes and three downregulated genes showed the same expression patterns throughout the culturing of A6 and A8 cells in RPM. Such globally responsive genes may play a common role in the cell response to simulated microgravity. We were particularly interested in the downregulation of SPARC in both cell types in RPM, which supported previous observations from simulated-microgravity experiments on earth or microgravity in space. We conclude that SPARC is plays a key role in the response of a cell to microgravity.
Effect of Asperity-Scale Tensile Stresses on the Wear Behavior of Normally Oriented Fiber-Reinforced Polymer Composites©

Wear of unidirectional continuous fiber-reinforced polymer composites with fiber orientation normal to the contact plane, sliding over scribed stainless steel disks having a controlled surface topography, is investigated in relation to the tensile stresses developed near the contact region. The composite is modeled as a transversely isotropic half-space whose effective elastic moduli are estimated from composite micro-mechanical considerations. The scribed disk is treated as a rough surface whose controlled topographical features serve as model hemispherical indenters against the composite. With friction coefficients obtained from, the wear experiments, the tensile stress field at and below the composite surface is estimated. From this, an estimate of the theoretical depth of fiber-matrix separation (fiber debonding) is calculated based on the composite transverse tensile strength. A correlation between the wear rate and theoretical depth of debonding was shown for several composites. Presented at the 48t.
Climate, CO 2 , and demographic impacts on global wildfire emissions

Abstract. Wildfires are by far the largest contributor to global biomass burning and constitute a large global source of atmospheric traces gases and aerosols. Such emissions have a considerable impact on air quality and constitute a major health hazard. Biomass burning also influences the radiative balance of the atmosphere and is thus not only of societal, but also of significant scientific interest. There is a common perception that climate change will lead to an increase in emissions as hot and dry weather events that promote wildfire will become more common. However, even though a few studies have found that the inclusion of CO2 fertilisation of photosynthesis and changes in human population patterns will tend to somewhat lower predictions of future wildfire emissions, no such study has included full ensemble ranges of both climate predictions and population projections, including the effect of different degrees of urbanisation. Here, we present a series of 124 simulations with the LPJ–GUESS–SIMFIRE global dynamic vegetation–wildfire model, including a semi-empirical formulation for the prediction of burned area based on fire weather, fuel continuity and human population density. The simulations use Climate Model Intercomparison Project 5 (CMIP5) climate predictions from eight Earth system models. These were combined with two Representative Concentration Pathways (RCPs) and five scenarios of future human population density based on the series of Shared Socioeconomic Pathways (SSPs) to assess the sensitivity of emissions to the effect of climate, CO2 and humans. In addition, two alternative parameterisations of the semi-empirical burned-area model were applied. Contrary to previous work, we find no clear future trend of global wildfire emissions for the moderate emissions and climate change scenario based on the RCP 4.5. Only historical population change introduces a decline by around 15 % since 1900. Future emissions could either increase for low population growth and fast urbanisation, or continue to decline for high population growth and slow urbanisation. Only for high future climate change (RCP8.5), wildfire emissions start to rise again after ca. 2020 but are unlikely to reach the levels of 1900 by the end of the 21st century. We find that climate warming will generally increase the risk of fire, but that this is only one of several equally important factors driving future levels of wildfire emissions, which include population change, CO2 fertilisation causing woody thickening, increased productivity and fuel load and faster litter turnover in a warmer climate.
GLI1 Is a Direct Transcriptional Target of EWS-FLI1 Oncoprotein*

Ewing sarcoma family of tumors (ESFT) is an undifferentiated neoplasm of the bone and soft tissue. ESFT is characterized by a specific chromosomal translocation occurring between chromosome 22 and (in most cases) chromosome 11, which generates an aberrant transcription factor, EWS-FLI1. The function of EWS-FLI1 is essential for the maintenance of ESFT cell survival and tumorigenesis. The Hedgehog pathway is activated in several cancers. Oncogenic potential of the Hedgehog pathway is mediated by increasing the activity of the GLI family of transcription factors. Recent evidence suggests that EWS-FLI1 increases expression of GLI1 by an unknown mechanism. Our data from chromatin immunoprecipitation and promoter reporter studies indicated GLI1 as a direct transcriptional target of EWS-FLI1. Expression of EWS-FLI1 in non-ESFT cells increased GLI1 expression and GLI-dependent transcription. We also detected high levels of GLI1 protein in ESFT cell lines. Pharmacological inhibition of GLI1 protein function decreased proliferation and soft agar colony formation of ESFT cells. Our results establish GLI1 as a direct transcriptional target of EWS-FLI1 and suggest a potential role for GLI1 in ESFT tumorigenesis.
Carnivora Population Dynamics Are as Slow and as Fast as Those of Other Mammals: Implications for Their Conservation

Of the 285 species of Carnivora 71 are threatened, while many of these species fulfill important ecological roles in their ecosystems as top or meso-predators. Population transition matrices make it possible to study how age-specific survival and fecundity affect population growth, extinction risks, and responses to management strategies. Here we review 38 matrix models from 35 studies on 27 Carnivora taxa, covering 11% of the threatened Carnivora species. We show that the elasticity patterns (i.e. distribution over fecundity, juvenile survival and adult survival) in Carnivora cover the same range in triangular elasticity plots as those of other mammal species, despite the specific place of Carnivora in the food chain. Furthermore, reproductive loop elasticity analysis shows that the studied species spread out evenly over a slow-fast continuum, but also quantifies the large variation in the duration of important life cycles and their contributions to population growth rate. These general elasticity patterns among species, and their correlation with simple life history characteristics like body mass, age of first reproduction and life span, enables the extrapolation of population dynamical properties to unstudied species. With several examples we discuss how this slow-fast continuum, and related patterns of variation in reproductive loop elasticity, can be used in the formulation of tentative management plans for threatened species that cannot wait for the results of thorough demographic studies. We argue, however, that such management programs should explicitly include a plan for learning about the key demographic rates and how these are affected by environmental drivers and threats.
Tonometry to estimate intestinal perfusion in newborn piglets

AIM To determine the correlation between gastric intramucosal pH and superior mesenteric artery (SMA) flow in newborn piglets. METHODS Fourteen newborn piglets were randomly assigned to either a control or to an epinephrine group which received 0,1,2,4,0 μg/kg/min of epinephrine for 60 minutes, each dose. Gastric tonometry was performed, SMA flow was measured, and intramucosal pH and the ratio of tonometer pCO2 over arterial pCO2 (rCO2) were calculated. RESULTS Intramucosal pH decreased over time in both groups, but tended to be lower in the epinephrine group. With increasing dose of epinephrine, SMA flow decreased; this in turn increased rCO2 (p = 0.04) with a tendency to decrease intramucosal pH (p = 0.06). CONCLUSIONS Gastric tonometry may be useful in human neonates to evaluate gut ischaemia.
Preventing Radiobleaching of Cyanine Fluorophores Enhances Stability of Nuclear/NIRF Multimodality Imaging Agents

Despite the large interest in nuclear/optical multimodality imaging, the effect of radiation on the fluorescence of fluorophores remains largely unexplored. Herein, we report on the radiobleaching of cyanine fluorophores and describe conditions to provide robust radioprotection under practical (pre)clinical settings. We determined the radiosensitivity of several cyanine fluorescent compounds, including IRDye 800CW (800CW) and a dual modality imaging tetrapeptide containing DOTA as chelator and Dylight 800 as fluorophore, exposed to increasing activities of 111In, 68Ga, or 213Bi (γ, EC/β, and α emitter, respectively). An activity and type of radiation-dependent radiation-induced loss of fluorescence, radiobleaching, of 800CW was observed upon incubation with escalating activities of 111In, 68Ga, or 213Bi. 68Ga showed the largest radiolytic effect, followed by 111In and 213Bi. The addition of oxygen radical scavengers including ethanol, gentisic acid, and ascorbic acid (AA), provided a concentration dependent radioprotective effect. These results supported the hypothesis of a free radical-mediated radiobleaching mechanism. AA provided the most robust radioprotection over a wide range of concentrations and preserved fluorescence at much higher radioactivity levels. Overall, both near-infrared fluorescent compounds displayed similar sensitivity, except for 213Bi-irradiated solutions, where the dual modality construct exhibited enhanced radiolysis, presumably due to direct radiation damage from α particles. Concurrently, AA was not able to preserve fluorescence of the dual-modality molecule labeled with 213Bi. Our findings have important consequences for several research areas including ROS sensing, radiation-mediated drug release (uncaging), fluorescent dosimetry, and in the preparation of dual-modality radiopharmaceuticals.
One year later: mental illness prevalence and disparities among New Orleans residents displaced by Hurricane Katrina.

OBJECTIVES We examined whether there were high levels of mental illness among displaced New Orleans, LA, residents in the fall of 2006, 1 year after Hurricane Katrina. METHODS We used data from the Displaced New Orleans Residents Pilot Study, which measured the prevalence of probable mild or moderate and serious mental illness among a representative sample of people who resided in New Orleans at the time of the hurricane, including people who evacuated the city and did not return. We also analyzed disparities in mental illness by race, education, and income. RESULTS We found high rates of mental illness in our sample and major disparities in mental illness by race, education, and income. Severe damage to or destruction of an individual's home was a major covariate of mental illness. CONCLUSIONS The prevalence of mental illness remained high in the year following Hurricane Katrina, in contrast to the pattern found after other disasters. Economic losses and displacement may account for this finding as well as the disparity in mental illness between Blacks and Whites.
Interactive comment on “ Diurnal variations of stratospheric ozone measured by ground-based microwave remote sensing at the Mauna Loa NDACC site : measurement validation and GEOSCCM model comparison ”

The diurnal variation of ozone in the stratosphere and lower mesosphere is analyzed using data from a ground-based microwave radiometer operating at the Mauna Loa NDACC station since the 1990s. Presented are considerations concerning the internal quality of the measurements, a verification study of the quality of the observed diurnal variability in comparison with external data sets obtained from different satellite instruments, and model comparisons aiming at testing the modelled ozone diurnal variation in a chemistry-climate model.
Alcohol and drug use among sexual minority college students and their heterosexual counterparts: the effects of experiencing and witnessing incivility and hostility on campus

Purpose Research suggests that discrimination contributes to increased substance use among sexual minorities. Subtle discrimination and witnessing mistreatment, however, have received little attention. Using minority stress theory as a conceptual framework the authors examined the intersection of sexual orientation, experiencing and witnessing incivility and hostility, and students’ alcohol and drug use. The authors hypothesized that experiencing/witnessing incivility/hostility would mediate the relationship between sexual minority status and drinking and drug use, as well as problematic use of these substances. Methods Data were taken from a campus climate survey (n = 2497; age mean [M] = 23.19 years; 61% female; 17% sexual minorities). Controlling for demographics, logistic regressions depicted specifications for each path of the mediation analysis and bootstrapping was used to assess the significance of each sexual minority-mistreatment-drinking/drug use path. Results Experiencing incivility mediated the relationship between sexual minority status and problematic drinking. Sexual minority college students were more likely to personally experience incivility (adjusted odds ratio [AOR] = 1.87; 95% confidence interval [CI] = 1.51–2.33), which was associated with greater odds of problematic drinking (AOR = 1.64; 95% CI = 1.35–2.00). The mediation path was significant at P < 0.001. Further, witnessing hostility mediated the relationship between sexual minority status and problematic drinking. Sexual minority college students were more likely to witness hostility (AOR = 1.87, 95% CI = 1.48–2.36), which was associated with greater odds of problematic drinking (AOR = 1.53; 95% CI = 1.24–1.90). The mediation path was significant at P < 0.01. Conclusion The results provide further evidence for minority stress theory and suggest that clinical alcohol use interventions with sexual minorities need to assess personal incivilities and witnessing interpersonal mistreatment, especially hostility. Campus climate interventions that address subtle discrimination as well as harassment and violence may help reduce problematic drinking.
Association between COMT Val158Met and psychiatric disorders: A comprehensive meta‐analysis

Catechol‐O‐methyltransferase (COMT) Val158Met is widely regarded as potentially important for understanding the genetic etiology of many different psychiatric disorders. The present study appears to be the first comprehensive meta‐analysis of COMT genetic association studies to cover all psychiatric disorders for which there were available data, published in any language, and with an emphasis on investigating disorder subtypes (defined clinically or by demographic or other variables). Studies were included if they reported one or more datasets (i.e., some studies examined more than one clinical group) in which there were sufficient information to compute effect sizes. A total of 363 datasets were included, consisting of 56,998 cases and 74,668 healthy controls from case control studies, and 2,547 trios from family based studies. Fifteen disorders were included. Attention‐deficit hyperactivity disorder and panic disorder were associated with the Val allele for Caucasian samples. Substance‐use disorder, defined by DSM‐IV criteria, was associated with the Val allele for Asian samples. Bipolar disorder was associated with the Met allele in Asian samples. Obsessive‐compulsive disorder tended to be associated with the Met allele only for males. There was suggestive evidence that the Met allele is associated with an earlier age of onset of schizophrenia. Results suggest pleiotropy and underscore the importance of examining subgroups—defined by variables such as age of onset, sex, ethnicity, and diagnostic system—rather than examining disorders as monolithic constructs.