Miracle-dz/UniFAR-FTUs huggingface dataset:
Insights into Deglutathionylation Reactions

Glutaredoxins are small proteins with a conserved active site (-CXX(C/S)-) and thioredoxin fold. These thiol disulfide oxidoreductases catalyze disulfide reductions, preferring GSH-mixed disulfides as substrates. We have developed a new real-time fluorescence-based method for measuring the deglutathionylation activity of glutaredoxins using a glutathionylated peptide as a substrate. Mass spectrometric analysis showed that the only intermediate in the reaction is the glutaredoxin-GSH mixed disulfide. This specificity was solely dependent on the unusual γ-linkage present in glutathione. The deglutathionylation activity of both wild-type Escherichia coli glutaredoxin and the C14S mutant was competitively inhibited by oxidized glutathione, with Ki values similar to the Km values for the glutathionylated peptide substrate, implying that glutaredoxin primarily recognizes the substrate via the glutathione moiety. In addition, wild-type glutaredoxin showed a sigmoidal dependence on GSH concentrations, the activity being significantly decreased at low GSH concentrations. Thus, under oxidative stress conditions, where the ratio of GSH/GSSG is decreased, the activity of glutaredoxin is dramatically reduced, and it will only have significant deglutathionylation activity once the oxidative stress has been removed. Different members of the protein disulfide isomerases (PDI) family showed lower activity levels when compared with glutaredoxins; however, their deglutathionylation activities were comparable with their oxidase activities. Furthermore, in contrast to the glutaredoxin-GSH mixed disulfide intermediate, the only intermediate in the PDI-catalyzed reaction was PDI peptide mixed disulfide.
Novel Techniques for Combating DC Offset in Diversity Combined ACO-OFDM

In this paper we present two novel techniques of diversity combined asymmetrically clipped optical orthogonal frequency division multiplexing (ACO-OFDM). The techniques are able to achieve better performance than conventional ACO OFDM while being unaffected by the variations in the zeroth subcarrier. Zeroth subcarrier variations are caused by DC offsets present in the biasing of the transmitter light emitting diode and receiver photo diode, and low frequency interference due to background noise sources such as fluorescent and incandescent lamps. Simulation results are presented which show that the new methods achieve better performance than ACO-OFDM.
Cytoreductive surgery plus hyperthermic intraperitoneal chemotherapy improves survival for peritoneal carcinomatosis from colorectal cancer: a systematic review and meta-analysis of current evidence

Objectives The therapeutic efficacy of cytoreductive surgery (CRS) plus hyperthermic intraperitoneal chemotherapy (HIPEC) for patients with peritoneal carcinomatosis (PC) from colorectal cancer (CRC) is still under debate. This meta-analysis and systematic review of published literature on this comprehensive strategy aims to evaluate its efficacy on CRC patients with PC. Methods A systemic review with meta-analysis of published literatures on treatment of CRS plus HIPEC for patients with PC from CRC was performed. In addition, a summary of study results of published literatures concerning CRS plus HIPEC treating patients with PC from CRC was also conducted. Results A total of 76 studies were selected, including 1 randomized controlled trial, 14 non-randomized controlled studies, and 61 non-controlled studies. The pooled hazard ratios (HRs) for overall survival (OS) in the 15 researches for meta-analysis was 2.67 (95% CI, 2.21-3.23, I2= 0%, P < 0.00001), and no significant evidence of publication bias was found. The difference of chemotherapy regimens of HIPEC was not associated with OS and DFS (disease-free survival) after CRS and HIPEC, with no significant difference of heterogeneity (P = 0.27, I2 = 24.1%). In both groups of mitomycin C based HIPEC group and oxaliplatin group, patients received HIPEC had significant better survival (P < 0.00001). The mean mortality and morbidity for HIPEC program were 2.8% and 33.0%, respectively. Conclusions This meta-analysis revealed that comprehensive therapeutic strategy of CRS plus HIPEC could bring survival benefit for selected patients with PC from CRC with acceptable safety.
In vitro susceptibility and virological outcome to darunavir and lopinavir are independent of HIV type-1 subtype in treatment-naive patients

Background The effect of HIV type-1 (HIV-1) subtype on in vitro susceptibility and virological response to darunavir (DRV) and lopinavir (LPV) was studied using a broad panel of primary isolates, and in recombinant clinical isolates from treatment-naive, HIV-1-infected patients in the Phase III trial, AntiRetroviral Therapy with TMC114 ExaMined In naive Subjects (ARTEMIS). Methods Patients received DRV/ritonavir (DRV/r) 800/100 mg once daily (n=343) or LPV/ritonavir (LPV/r) 800/200 mg total daily dose (n=346), plus a fixed daily dose of emtricitabine and tenofovir disoproxil fumarate. Results DRV demonstrated high antiviral activity against a broad panel of HIV-1 major group (M) and outlier group (O) primary isolates in peripheral blood mononuclear cells, with a median 50% effective concentration (EC50) of 0.52 nM. Most (61%) patients in ARTEMIS harboured HIV-1 subtype B; other prevalent subtypes were C (13%) and CRF01_AE (17%); 9% harboured other subtypes. Median EC50 values (interquartile range) for DRV were 1.79 nM (1.3–2.6) for subtype B, 1.12 nM (0.8–1.4) for C and 1.27 nM (1.0–1.7) for CRF01_AE. Virological response to DRV/r (HIV-1 RNA<50 copies/ml [intent-to-treat, time-to-loss of virological response algorithm]) was 81%, 87% and 85% for patients with subtype B, C and CRF01_AE infections, respectively. Similar results were observed in the LPV/r treatment group. Conclusions In vitro susceptibility to DRV was comparable across HIV-1 subtypes in a broad panel of primary isolates and in recombinant clinical isolates. Once daily DRV/r 800/100 mg and LPV/r 800/200 mg were highly effective in ARTEMIS irrespective of the HIV-1 subtype studied, confirming their broad anti-HIV-1 activity.
Advanced TSV-Based Crystal Resonator Devices Using 3-D Integration Scheme With Hermetic Sealing

An advanced crystal resonator device scheme using Cu through-silicon via (TSV), 3-D integration, and Si packaging technologies is successfully demonstrated. In addition to robust structural quality, the crystal resonator packaging has excellent electrical characteristics of low leakage current and reliability against harsh environment for MIL-STD-883 hermetic encapsulation. Using 3-D integration technologies and Si packaging, the proposed TSV-based crystal resonator device possesses the manufacturability potential while conventional ones using a metal lid or ceramic enclosure.
INTRODUCTION 1 On the consistency of the SIFT Method

This note is devoted to the mathematical arguments proving that Lowe’s Scale-Invariant Feature Transform (SIFT [23]), a very successful image matching method, is indeed similarity invariant. The mathematical proof is given under the assumption that the gaussian smoothing performed by SIFT gives aliasing free sampling. The validity of this main assumption is confirmed by a rigorous experimental procedure. These results explain why SIFT outperforms all other image feature extraction methods when it comes to scale invariance.
A simplified electrophoretic system for determining molecular weights of proteins.

Electrophoresis of 31 different proteins in commercially prepared polyacrylamide gradient gels, Gradipore, yields a linear relationship between a hypothetical limiting pore size (the reciprocal of a limiting gel concentration, GL) and the cube root of the mol.wt. , over the range 13 500-9000 000. A regression analysis of these data reveals that 98.6% of all variability in 1/GL is explained by the molecular weight, and this degree of accuracy compares favourably with existing methods for the determination of molecular weight by retardation of mobility in polyacrylamide. This new procedure has the additional advantages that molecular-weight standards can be obtained from readily available body fluids or tissue extracts by localizing enzymes and other proteins by standard histochemical methods, and that the same electrophoretic system can be used in determining molecular weights as is used in routine surveys of populations for individual and species variation in protein heterogeneity.
Optimal Government Policies in Models with Heterogeneous Agents

In this paper we develop a new methodology for finding optimal government policies in economies with heterogeneous agents. The methodology is solely based on three classes of equilibrium conditions from the government’s and individual agent’s optimization problems: 1) the first order conditions; 2) the stationarity condition on the distribution function; and, 3) the aggregate market clearing conditions. These conditions form a system of functional equations which we solve numerically. The solution takes into account simultaneously the effect of government policy on individual allocations and (from the government’s point of view) optimal distribution of agents in the steady state. This general methodology is applicable to a wide range of optimal government policies in models with heterogeneous agents. We illustrate it on a steady state Ramsey problem with heterogeneous agents, finding the optimal tax schedule. JEL Keywords: Optimal macroeconomic policy, optimal taxation, computational techniques, heterogeneous agents, distribution of wealth and income
The SDSS-DR5 Survey for Proximate Damped Lyα Systems

Using the Sloan Digital Sky Survey Data Release 5 (SDSS-DR5), we survey proximate damped Lyα systems (PDLAs): absorption-line systems with H I column density NHI ⩾ 2×1020 cm−2 at velocity separation δ v < 3000 km s−1 from their background quasar. Many of these absorbers may be physically associated with their background quasars, and their statistics allow us to study quasar environments out to z ∼ 5. However, the large ionizing flux emitted by a quasar can ionize the neutral gas in a nearby galaxy, possibly giving rise to a “proximity effect,” analogous to the similar effect observed in the Lyα forest. From a sample of 108 PDLAs, we measure the HI frequency distribution f(NHI, X), incidence, and gas mass density of the PDLAs near luminous quasars over the redshift interval z = 2.2–5. The incidence and mass density of PDLAs at z ∼ 3 is approximately twice that of intervening DLAs, while at z < 2.5 and >3.5 the f(NHI, X) distribution is enhanced but statistically consistent with the intervening population. We interpret the observed enhancement of PDLAs around quasars in terms of quasar-galaxy clustering and compare the strength of the clustering signal to the expectation from independent measures of the respective clustering strengths of DLAs and quasars, as well as a complementary analysis of the clustering of absorbers around quasars in the transverse direction. We find that there are a factor of 5-10 fewer PDLAs around quasars than expected and interpret this result as evidence for the hypothesis that the ionizing flux from the quasars photoevaporates H I in nearby DLA galaxies, thus reducing their cross section for DLA absorption. This constitutes the first detection of a “proximity effect” for DLAs.
Toward an Analytic Framework of Interdisciplinary Reasoning and Communication (IRC) Processes in Science

Students need to think and work across disciplinary boundaries in the twenty-first century. However, it is unclear what interdisciplinary thinking means and how to analyze interdisciplinary interactions in teamwork. In this paper, drawing on multiple theoretical perspectives and empirical analysis of discourse contents, we formulate a theoretical framework that helps analyze interdisciplinary reasoning and communication (IRC) processes in interdisciplinary collaboration. Specifically, we propose four interrelated IRC processes—integration, translation, transfer, and transformation, and develop a corresponding analytic framework. We apply the framework to analyze two meetings of a project that aims to develop interdisciplinary science assessment items. The results illustrate that the framework can help interpret the interdisciplinary meeting dynamics and patterns. Our coding process and results also suggest that these IRC processes can be further examined in terms of interconnected sub-processes. We also discuss the implications of using the framework in conceptualizing, practicing, and researching interdisciplinary learning and teaching in science education.
An Overview of Educational Programs

The goals for education of children with autism and related disorders are the same as for all other children: helping develop their potential for personal self-sufficiency and independence. For children with autism spectrum disorders (ASDs), there are additional challenges. These include social–communication challenges, behavioral and sensory issues, and problems with organization and transitions. Starting in the 1950s, parents and teachers began to try to deal with these problems and educate children with autism. Some of these early attempts, particularly the ones begun by parents, resulted in schools or programs that still are very active today. These programs were started because at that time public schools were not mandated to serve all children. Another strategy had been the attempt by some well meaning but misguided professionals to ‘‘correct’’ what they saw as poor parenting by providing intensive psychotherapeutic interventions to children with autism; this idea rested on the ‘‘refrigerator mother’’ idea of what caused autism (see chapter 2), and as this idea was shown to clearly be wrong, many of these programs either closed or turned their attention to other kinds of problems. Other factors did, however, increase interest in providing educational services to children with autism. These factors came both from research and public policy. On the research side, an awareness that behavioral interventions could improve the development of children with autism stimulated a tremendous interest in developing better methods for intervention. On the social policy side, passage of Public Law 94-142 in 1975 mandated schools to begin providing appropriate educational services to children with autism. Before this law was passed only a minority of children with autism received school based serviced. Since the passage of Public Law 94-142, more and more children on the autism spectrum have been enrolled in school programs and been able to make substantial progress. As a result of this and subsequent laws, the schools and educational intervention have assumed a central role in helping children make gains in social,
Sensoring the Future: Complex Geographies of Connectivity and Communication

Visions of an interconnected future are on the rise that foresee technologies moving toward ubiquitous “everywhere” computing and the rise of the “Internet of Things. ” This article examines emerging trends in informational connectivity that indicates shifts toward upcoming scenarios of re-imagined geographies and spatial landscapes that are sensored and networked. I examine how the relationships, processes, and flows between people, physical objects, and the environment will make implicit information explicit and engagement between the physical and the digital more commonplace. These are the scenarios presented by emerging applications of location-specific, informationally augmented objects: a real-time sensored future.
Progression of Alport Kidney Disease in Col4a3 Knock Out Mice Is Independent of Sex or Macrophage Depletion by Clodronate Treatment

Alport syndrome is a genetic disease of collagen IV (α3, 4, 5) resulting in renal failure. This study was designed to investigate sex-phenotype correlations and evaluate the contribution of macrophage infiltration to disease progression using Col4a3 knock out (Col4a3KO) mice, an established genetic model of autosomal recessive Alport syndrome. No sex differences in the evolution of body mass loss, renal pathology, biomarkers of tubular damage KIM-1 and NGAL, or deterioration of kidney function were observed during the life span of Col4a3KO mice. These findings confirm that, similar to human autosomal recessive Alport syndrome, female and male Col4a3KO mice develop renal failure at the same age and with similar severity. The specific contribution of macrophage infiltration to Alport disease, one of the prominent features of the disease in human and Col4a3KO mice, remains unknown. This study shows that depletion of kidney macrophages in Col4a3KO male mice by administration of clodronate liposomes, prior to clinical onset of disease and throughout the study period, does not protect the mice from renal failure and interstitial fibrosis, nor delay disease progression. These results suggest that therapy targeting macrophage recruitment to kidney is unlikely to be effective as treatment of Alport syndrome.
Efficient and sustained gene expression in primary T lymphocytes and primary and cultured tumor cells mediated by adeno-associated virus plasmid DNA complexed to cationic liposomes

We have used cationic liposomes to facilitate adeno-associated virus (AAV) plasmid transfections of primary and cultured cell types. AAV plasmid DNA complexed with liposomes showed levels of expression several fold higher than those of complexes with standard plasmids. In addition, long-term expression (> 30 days) of the gene, unlike the transient expression demonstrated by typical liposome-mediated transfection with standard plasmids, was observed. Southern analysis of chromosomal DNA further substantiated the hypothesis that the long-term expression was due to the presence of the transgene in the AAV plasmid-transfected group and not in the standard plasmid-transfected group. AAV plasmid-liposome complexes induced levels of transgene expression comparable to those obtained by recombinant AAV transduction. Primary breast, ovarian, and lung tumor cells were transfectable with the AAV plasmid DNA-liposome complexes. Transfected primary and cultured tumor cells were able to express transgene product even after lethal irradiation. High-level gene expression was also observed in freshly isolated CD3+, CD4+, and CD8+ T cells from normal human peripheral blood. Transfection efficiency ranged from 10 to 50% as assessed by intracellular interleukin-2 levels in interleukin-2-transfected cells. The ability to express transgenes in primary tumor and lymphoid cells may be applied toward tumor vaccine studies and protocols which may eventually permit highly specific modulation of the cellular immune response in cancer and AIDS.
DNA damage stabilizes interaction of CSB with the transcription elongation machinery

The Cockayne syndrome B (CSB) protein is essential for transcription-coupled DNA repair (TCR), which is dependent on RNA polymerase II elongation. TCR is required to quickly remove the cytotoxic transcription-blocking DNA lesions. Functional GFP-tagged CSB, expressed at physiological levels, was homogeneously dispersed throughout the nucleoplasm in addition to bright nuclear foci and nucleolar accumulation. Photobleaching studies showed that GFP-CSB, as part of a high molecular weight complex, transiently interacts with the transcription machinery. Upon (DNA damage-induced) transcription arrest CSB binding these interactions are prolonged, most likely reflecting actual engagement of CSB in TCR. These findings are consistent with a model in which CSB monitors progression of transcription by regularly probing elongation complexes and becomes more tightly associated to these complexes when TCR is active.
Common Ingroup Identity Model

The common ingroup identity model is a strategy for reducing prejudice. The model assumes that intergroup biases are rooted in the universal tendency to simplify a complex environment by classifying objects and people into groups or categories. This process of categorization often occurs spontaneously on the basis of physical similarity, proximity, or shared fate. The common ingroup identity model reveals how changing the ways people socially categorize others can reduce intergroup prejudice and bias. Keywords: intergroup cooperation; contact hypothesis; discrimination; prejudice; social categorization; attribution theory; decategorization; recategorization; dual-identity representation; personalization; mutual differentiation; problem-solving workshop
Detecting Aquaporin Function and Regulation

Water is the major component of cells and tissues throughout all forms of life. Fluxes of water and solutes through cell membranes and epithelia are essential for osmoregulation and energy homeostasis. Aquaporins are membrane channels expressed in almost every organism and involved in the bidirectional transfer of water and small solutes across cell membranes. Aquaporins have important biological roles and have been implicated in several pathophysiological conditions suggesting a great translational potential in aquaporin-based diagnostics and therapeutics. Detecting aquaporin function is critical for assessing regulation and screening for new activity modulators that can prompt the development of efficient medicines. Appropriate methods for functional analysis comprising suitable cell models and techniques to accurately evaluate water and solute membrane permeability are essential to validate aquaporin function and assess short-term regulation. The present review describes established assays commonly used to assess aquaporin function in cells and tissues, as well as the experimental biophysical strategies required to reveal functional regulation and identify modulators, the first step for aquaporin drug discovery.
Nucleolin, a Shuttle Protein Promoting Infection of Human Monocytes by Francisella tularensis

Background Francisella tularensis is a highly virulent facultative intracellular bacterium, disseminating in vivo mainly within host mononuclear phagocytes. After entry into macrophages, F. tularensis initially resides in a phagosomal compartment, whose maturation is then arrested. Bacteria escape rapidly into the cytoplasm, where they replicate freely. We recently demonstrated that nucleolin, an eukaryotic protein able to traffic from the nucleus to the cell surface, acted as a surface receptor for F. tularensis LVS on human monocyte-like THP-1 cells. Methodology/Principal Findings Here, we followed the fate of nucleolin once F. tularensis has been endocytosed. We first confirmed by siRNA silencing experiments that expression of nucleolin protein was essential for binding of LVS on human macrophage-type THP-1 cells. We then showed that nucleolin co-localized with intracellular bacteria in the phagosomal compartment. Strikingly, in that compartment, nucleolin also co-localized with LAMP-1, a late endosomal marker. Co-immunoprecipation assays further demonstrated an interaction of nucleolin with LAMP-1. Co-localization of nucleolin with LVS was no longer detectable at 24 h when bacteria were multiplying in the cytoplasm. In contrast, with an iglC mutant of LVS, which remains trapped into the phagosomal compartment, or with inert particles, nucleolin/bacteria co-localization remained almost constant. Conclusions/Significance We herein confirm the importance of nucleolin expression for LVS binding and its specificity as nucleolin is not involved in binding of another intracellular pathogen as L. monocytogenes or an inert particle. Association of nucleolin with F. tularensis during infection continues intracellularly after endocytosis of the bacteria. The present work therefore unravels for the first time the presence of nucleolin in the phagosomal compartment of macrophages.