Miracle-dz/UniFAR-FTUs huggingface dataset:
Kinetic evidence against partitioning of the ubiquinone pool and the catalytic relevance of respiratory-chain supercomplexes

Significance Mitochondria produce ATP by using respiration to drive ATP synthase. Respiration is catalyzed by several membrane-bound complexes that are structurally organized into supercomplex assemblies. Supercomplexes have been proposed to confer a catalytic advantage by channeling of substrates between enzymes in the assemblies. Here, we test three simple predictions of the behavior of the mammalian respiratory chain that depend on whether channeling in supercomplexes is kinetically important and show that it is not. We reinterpret previous data taken to support substrate channeling and reveal an alternative explanation for these data. Finally, we discuss alternative proposals for why the respiratory-chain complexes have evolved to form supercomplex structures. In mitochondria, four respiratory-chain complexes drive oxidative phosphorylation by sustaining a proton-motive force across the inner membrane that is used to synthesize ATP. The question of how the densely packed proteins of the inner membrane are organized to optimize structure and function has returned to prominence with the characterization of respiratory-chain supercomplexes. Supercomplexes are increasingly accepted structural entities, but their functional and catalytic advantages are disputed. Notably, substrate “channeling” between the enzymes in supercomplexes has been proposed to confer a kinetic advantage, relative to the rate provided by a freely accessible, common substrate pool. Here, we focus on the mitochondrial ubiquinone/ubiquinol pool. We formulate and test three conceptually simple predictions of the behavior of the mammalian respiratory chain that depend on whether channeling in supercomplexes is kinetically important, and on whether the ubiquinone pool is partitioned between pathways. Our spectroscopic and kinetic experiments demonstrate how the metabolic pathways for NADH and succinate oxidation communicate and catalyze via a single, universally accessible ubiquinone/ubiquinol pool that is not partitioned or channeled. We reevaluate the major piece of contrary evidence from flux control analysis and find that the conclusion of substrate channeling arises from the particular behavior of a single inhibitor; we explain why different inhibitors behave differently and show that a robust flux control analysis provides no evidence for channeling. Finally, we discuss how the formation of respiratory-chain supercomplexes may confer alternative advantages on energy-converting membranes.
Better quality of response to lenalidomide plus dexamethasone is associated with improved clinical outcomes in patients with relapsed or refractory multiple myeloma

Background This retrospective pooled analysis of two phase III trials (MM-009/MM-010) compared clinical outcomes of patients who achieved a complete response or very good partial response to treatment with lenalidomide plus dexamethasone with the outcomes of those who only achieved a partial response. Design and Methods Patients (n=353) received lenalidomide (25 mg/day for 21 days of each 28-day cycle) plus dexamethasone (40 mg on days 1–4, 9–12, and 17–20 for four cycles, and only on days 1–4 after the first four cycles). Time to response, duration of response, time-to-progression, overall survival, and adverse events were investigated for patients who had a complete or very good partial response and compared with those of patients who had a partial response. Results At the time of unblinding, 32% of patients had achieved a complete or very good partial response and 28% had a partial response. Half (50.5%) of the patients who had a partial response as their initial response achieved a complete or very good partial response with further treatment. The probability of achieving a complete or very good partial response with continued lenalidomide treatment decreased with delayed achievement of a partial response (by cycle 4 versus later); however, it remained clinically significant. With an extended follow-up of 48 months, the median response duration, time-to-progression, and overall survival were longer in patients with a complete or very good partial response than in those with a partial response (24.0 versus 8.3 months, P<0.001; 27.7 versus 12.0 months, P<0.001; not reached versus 44.2 months, P=0.021, respectively). The benefit of a complete or very good partial response was independent of when it was achieved. Conclusions Continuing treatment with lenalidomide plus dexamethasone to achieve best response, in the absence of disease progression and toxicity, provided deeper remissions and greater clinical benefit over time for patients in this study.
Implications of Visual Attention Phenomena for Models of Preferential Choice

We use computational modeling to examine the ability of evidence accumulation models to produce the reaction time (RT) distributions and attentional biases found in behavioral and eye-tracking research. We focus on simulating RTs and attention in binary choice with particular emphasis on whether different models can predict the late onset bias (LOB), commonly found in eye movements during choice (sometimes called the gaze cascade). The first finding is that this bias is predicted by models even when attention is entirely random and independent of the choice process. This shows that the LOB is not evidence of a feedback loop between evidence accumulation and attention. Second, we examine models with a relative evidence decision rule and an absolute evidence rule. In the relative models a decision is made once the difference in evidence accumulated for 2 items reaches a threshold. In the absolute models, a decision is made once 1 item accumulates a certain amount of evidence, independently of how much is accumulated for a competitor. Our core result is simple—the existence of the late onset gaze bias to the option ultimately chosen, together with a positively skewed RT distribution means that the stopping rule must be relative not absolute. A large scale grid search of parameter space shows that absolute threshold models struggle to predict these phenomena even when incorporating evidence decay and assumptions of either mutual inhibition or feedforward inhibition.
An empirical study of overriding in open source Java

Inheritance is a key feature of object-oriented programming. Overriding is one of the most important parts of inheritance, allowing a subclass to replace methods implemented in its superclass. Unfortunately, the way programmers use overriding in practise is not well understood. We present the first large-scale empirical study of overriding. We describe a suite of metrics that measure overriding and present a corpus analysis that uses those metrics to analyse 100 open-source applications, containing over 100,000 separate classes and interfaces. We found substantial overriding: most subclasses override at least one method and many classes that only declare overriding methods. We also found questionable uses of overriding, such as removing superclass method implementations by overriding them with empty method bodies.
Molecular dynamics simulation of effective thermal conductivity of vapor-filled nanogap and nanocavity

The effect of adsorption on momentum au and thermal aT accommodation coefficients and effective thermal conductivity ⟨kf⟩ of Ar vapor-filled Pt nanogap and nanocavity is examined using nonequilibrium molecular dynamics (MD) simulations. For the accommodation coefficients, the increase in solid-fluid or fluid-fluid interatomic interactions within adsorbed layer causes transitions in magnitudes of au and aT near Ar triple-point temperature. In the nanogap, ⟨kf⟩ MD results are in close agreement with the available closed-form solution for transition-flow regime, i.e., Knudsen number 0.1<KnL<10, using the MD results of aT. In the nanocavity, the adiabatic sidewalls do not significantly alter the gas mean free path and ⟨kf⟩, and the sparse adsorption coverage on the sidewalls results in a negligibly small fluid circulation by surface diffusion under a temperature gradient.
From images to traffic behavior - A UAV tracking and monitoring application

An implemented system for achieving high level situation awareness about traffic situations in an urban area is described. It takes as input sequences of color and thermal images which are used to construct and maintain qualitative object structures and to recognize the traffic behavior of the tracked vehicles in real time. The system is tested both in simulation and on data collected during test flights. To facilitate the signal to symbol transformation and the easy integration of the streams of data from the sensors with the GIS and the chronicle recognition system, DyKnow, a stream-based knowledge processing middleware, is used. It handles the processing of streams, including the temporal aspects of merging and synchronizing streams, and provides suitable abstractions to allow high level reasoning and narrow the sense reasoning gap.
Risk behavior of Internet shopping: comparison of college students' versus non-student adults'

This paper makes direct and empirical comparisons of college students and nonstudents as subjects in the understanding of e-Consumer risk behavior. Moreover, the research hypotheses are tested by investigating both search goods and experience goods. It is thus possible to evaluate the potential generalizability of the research results. Results show that most products in the study, when associated with the purchase on the Internet, are significantly riskier online than offline. But both student and nonstudent respondents perceive less channel risk and are also less channel risk-averse online than offline in flight tickets (search goods). The results indicate a consistency between nonstudent respondents' channel risk attitudes and their actual shopping behavior on the Internet. But neither student respondents' channel risk attitudes nor their channel risk perceptions are reflected on their actual shopping behavior on the Internet.
Dimension Reduction for Hyperspectral Image Classification via Support Vector based Feature Extraction

Usually feature extraction is applied for dimension reduction in hyperspectral data classification problems. Many studies show that nonparametric weighted feature extraction (NWFE) is a powerful tool for extracting hyperspectral image features. The detection of class boundaries is an important part in NWFE and the weighted mean was defined for this purpose. In this paper, a kernel-based feature extraction is proposed based on a new class boundary detection mechanism. The soft-margin support vector machine (SVM) binary classifier and the support vector domain description (SVDD) are applied to detect the boundaries between two classes and one class, respectively. The results of real data experiments show that the proposed method outperforms original NWFE.
The Role of Peroxisome Proliferator-Activated Receptor-γ and Estrogen Receptors in Genistein-Induced Regulation of Vascular Tone in Female Rat Aortas

Background: Genistein (GST) is a phytoestrogen that binds estrogen receptors (ER) to produce a protective cardiovascular effect. It also has been shown binding peroxisome proliferator-activated receptor-γ (PPAR-γ). Methods: In the present study, we assessed the role of PPAR-γ and ER in GST-mediated regulation of vascular tone in female rat aortas by in vitro tension measurement, immunohistochemistry, immunofluorescence, immunoprecipitation and Western blot analysis. Results: In aortas pretreated with GW9662 (inhibitor of PPAR-γ), ICI182780 (inhibitor of ER) and a combination of GW9662 and ICI182780, the magnitudes of GST-induced dilatation were attenuated. N(G)-nitro-L-arginine methyl ester had a similar effect. ER-β and PPAR-γ colocalized in all 3 layers of the aortas, while ER-α and PPAR-γ colocalized only in the vascular endothelium and adventitia. In GST-treated whole-cell protein samples, we demonstrated coimmunoprecipitation of ER-β (not ER-α) and PPAR-γ. The expression of ER-β and PPAR-γ in nuclear protein from GST-treated samples increased, which was partially reversed by either GW9662 or ICI182780 and more efficiently reversed using a combination of GW9662 and ICI182780. Conclusion: Our findings suggest that GST can relax phenylephrine-induced vascular contraction in female rat aortas, which is mediated by PPAR-γ and ER-β.
Postoperative Discomfort due to Peripheral Residual Nerve Blocks in Outpatients who had Carpal Tunnel Surgery

Introduction: The aim of our study was to assess the discomfort due to residual distal and proximal blocks in outpatients operated for carpal tunnel release. Methods: The study was conducted on a cohort of ambulatory patients having undergone open surgery for carpal tunnel release in peripheral blocks. Patients went home 2-3 hours after surgery. On the third postoperative day, They were called, and were asked to determine the discomfort caused by residual obstruction after discharge from the hospital on a verbal scale (absent, minor, slight, very important and very important) . According to the degrees of discomfort, we separated the patients into two groups and compared the two using the Fisher exact test and Student’s t-test Results: Between November 2006 and January 2008, 185 patients were contacted three days after their release and analyzed (105 distal PNBs and 80 proximal PNBs). Age, gender, body mass index, ASA score, postoperative pain scores were not different between groups. The musculocutaneous nerve was blocked in 23% of distal PNBs and in 81% of proximal ones (p<0.001). Overall, distal PNBs induced less discomfort than proximal PNBs (p=0.041). Nevertheless, 20% of patients with distal PNBs express mild to very important discomfort, versus 30% of patients with proximal PNBs (p=0.124). Discussion: Despite dramatic differences in anaesthetised and paralysed territories between the two groups, wrist PNBs induce only slightly less postoperative discomfort due to residual block than proximal PNBs. Therefore, the clinical impact of this discomfort seems limited since in both groups, 70 to 80% of patients reported no or minor discomfort.
Cytokine gene expression profile distinguishes CD4+/CD57+ T cells of the nodular lymphocyte predominance type of Hodgkin's lymphoma from their tonsillar counterparts

Little is known about the cytokine profile of nodular lymphocyte predominance Hodgkin's lymphoma (NLPHL) and the significance of the characteristic rosetting CD4+/CD57+ T cells. We analysed the T lymphocyte populations isolated from lymph node suspensions from five patients with NLPHL, two with follicular hyperplasia and progressive transformation of germinal centres (PTGC), three with classical Hodgkin's lymphoma (CHL) and five with hyperplasia of the tonsil. We sorted the T cells based on expression of CD3, CD4 and CD57 by flow cytometry and evaluated the cytokine mRNA profiles of the T cells with quantitative RT‐PCR. NLPHL cases were as rich in T cells as the CHL cases, but all NLPHL cases had a much higher frequency of CD4+/CD57+ T cells. In contrast to the CD4+/CD57+ T cells from tonsils, IL2 and IL4 mRNAs were consistently absent from the CD4+/CD57+ T cells of NLPHL. Even after stimulation, no IL4 transcripts could be detected in the CD4+/CD57+ T cells of NLPHL. On the other hand, IFNγ transcripts were elevated in NLPHL and PTGC T cell subsets as compared to tonsillar T cell subsets. IL13 mRNA was exclusively produced by the T cells of CHL cases, indicating that IL13 may be a key cytokine in CHL. In conclusion, elevated levels of CD4+/CD57+ T cells are characteristic of NLPHL and these T cells display a distinct cytokine mRNA profile. Copyright © 2005 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
A Comparative Perspective of Intercultural Sensitivity Between College Students and Multinational Employees in China

Using the Intercultural Sensitivity Scale formulated by G. M. Chen and Starosta, the intercultural sensitivity of English major students, non-English major students, and multinational employees in China were investigated. In this study, intercultural sensitivity was defined as consisting of interaction engagement, interaction confidence, respect for cultural differences, interaction enjoyment, and interaction attentiveness. The focus of this research was to explore how intercultural sensitivity was structured among subjects of different English learning and intercultural communication experience. A series of results generated by multiple regressions showed different weightings of the 5 elements of intercultural sensitivity of the 3 subsamples. For example, respect for cultural differences for English major students was affected by interaction engagement and enjoyment, whereas for multinational employees it was only affected by interaction enjoyment. The study also found that English major students felt interaction enjoyment more easily than non-English major students and multinational employees.
The Causal Relationship between Job Satisfaction and Organizational Commitment

Satisfaction (JS) and Organizational Commitment (OC) have been the subjects of a large amount of empirical research, but the nature of the causal relationship between JS and OC is still disputed. This paper provides a thorough assessment of the causal relationship between JS and OC by controlling the influence of personal traits and organizational attributes. Comparing the four models (JS OC, JS -> OC, OC -> JS, and no causal effect between JS and OC), our result shows that the reciprocal relation model best fits the data.
Effect of electrostatic charge, flow, delay and multiple actuations on the in vitro delivery of salbutamol from different small volume spacers for infants.

BACKGROUND: A study was undertaken to determine the influences of electrostatic charge, flow, delay, and multiple actuations on the in vitro delivery of salbutamol generated by a pressurised metered dose inhaler (pMDI) from small volume spacers used in infants. METHODS: Ten actuations from a salbutamol pMDI were drawn at different flow rates after either single or multiple actuations, with or without delay, through either static or reduced static spacers. An ionic detergent was used to reduce the charge of plastic spacers (Babyhaler, Babyspacer, Aerochamber, Nebuhaler). Electrostatic charge was measured using an electrometer. A multistage liquid impinger was used to determine the particle size distribution of the output of the pMDI through the spacers. RESULTS: Electrostatic charge on the surface of plastic spacers had the greatest influence on delivery, causing a decrease in drug delivery. Reducing charge by coating the surface with ionic detergent resulted in an increase of 46.5-71.1% (p < 0.001) in small (< 6.8 microns) particle delivery from small volume plastic spacers. Lower flow, delay, and multiple actuations resulted in decreased delivery from static spacers. Lower flow resulted in a decrease of 15% in small (< 9.6 microns) particle delivery. Delay and multiple actuations resulted in a decrease of 40.7% and 76.0%, respectively, in small (< 6.8 microns) particle delivery. The influences of lower flow, delay, and multiple actuations were greatly reduced or even eliminated by reducing charge. However, multiple actuations still resulted in a significant decreased delivery (p < 0.05). The reduced static Nebuhaler had a higher delivery than all small volume spacers. CONCLUSIONS: Electrostatic charge has a major influence on the delivery of salbutamol from small volume spacers. Using a metal spacer or ionic detergent coating of plastic spacers resulted in no or reduced charge and hence in improved delivery. Lower flow, delay, and multiple actuations played a major part only in static spacers.
Exocytosis in Sea Urchin Eggs a

Exocytotic release of stored secretory products also occurs elsewhere than in exocrine and endocrine cells and at the synapse. For example, eggs and oocytes secrete enzymes and the components of extracellular coats after fertilization. The secretory process a t fertilization is in all respects very similar to other forms of exocytotic secretion. It is under second-messenger control; calcium is the usual stimulatory messenger. It involves membrane fusion and dispersal of the contents of stored secretory granules. The sea urchin egg is a versatile cell. One of its roles is as a secretory cell. Ten thousand secretory granules are released over a 20-s period at fertilization in response to an increase in intracellular calcium ([Ca''],). In the unfertilized egg, the secretory granules form a closely packed monolayer just beneath the plasma membrane. After fertilization, none remain. The most useful feature of the sea urchin egg from the point of view of understanding exocytosis is that the secretory granules are all docked in the unfertilized egg. The docking is sufficiently tight to allow the isolation of the plasma membrane with all its secretory granules still attached. When calcium is added, the secretory granules undergo rapid and concerted exocytosis. It is also possible to use rougher treatments to detach the secretory granules from the plasma membrane. If these granules are then added back to naked plasma membrane, they reattach. They will all undergo exocytosis when calcium is added. This is still the only example of the reconstitution of an exocytotic mechanism in vitro that responds to calcium with anything like the efficiency of exocytosis in the living cell.
Role of Glutaredoxin in Metabolic Oxidative Stress

Epitope-tagged glutaredoxin (GRX) was utilized to determine the role of GRX in oxidative stress-induced signaling and cytotoxicity in glucose-deprived human cancer cells (MCF-7/ADR and DU-145). GRX-overexpressing cells demonstrated resistance to glucose deprivation-induced cytotoxicity and decreased activation of c-Jun N-terminal kinase (JNK1). Deletion mutants showed the C-terminal portion of apoptosis signal-regulating kinase 1 (ASK1) bound GRX, and glucose deprivation disrupted binding. Treatment withl-buthionine-(S,R)-sulfoximine reduced glutathione content by 99% and prevented glucose deprivation-induced dissociation of GRX from ASK1. A thiol antioxidant,N-acetyl-l-cysteine, or overexpression of an H2O2 scavenger, catalase, inhibited glucose deprivation-induced dissociation of GRX from ASK1. GRX active site cysteine residues (Cys22 and Cys25) were required for dissociation of GRX from ASK1 during glucose deprivation. Kinase assays revealed that SEK1 and JNK1 were regulated in an ASK1-dependent fashion during glucose deprivation. Overexpression of GRX or catalase inhibited activation of ASK1-SEK1-JNK1 signaling during glucose deprivation. These results demonstrate that GRX is a negative regulator of ASK1 and dissociation of GRX from ASK1 activates ASK1-SEK1-JNK1 signaling leading to cytotoxicity during glucose deprivation. These results support the hypothesis that the GRX-ASK1 interaction is redox sensitive and regulated in a glutathione-dependent fashion by H2O2.
Complete completion using types and weights

Developing modern software typically involves composing functionality from existing libraries. This task is difficult because libraries may expose many methods to the developer. To help developers in such scenarios, we present a technique that synthesizes and suggests valid expressions of a given type at a given program point. As the basis of our technique we use type inhabitation for lambda calculus terms in long normal form. We introduce a succinct representation for type judgements that merges types into equivalence classes to reduce the search space, then reconstructs any desired number of solutions on demand. Furthermore, we introduce a method to rank solutions based on weights derived from a corpus of code. We implemented the algorithm and deployed it as a plugin for the Eclipse IDE for Scala. We show that the techniques we incorporated greatly increase the effectiveness of the approach. Our evaluation benchmarks are code examples from programming practice; we make them available for future comparisons.