Miracle-dz/UniFAR-FTUs huggingface dataset:
Atomistic aspects of screw dislocation behavior in α-iron and the derivation of microscopic yield criterion

The plastic deformation of body-centered cubic iron at low temperatures is governed by slip behavior of screw dislocations. Their non-planar core structure gives rise to a strong temperature dependence of the yield stress and overall plastic behavior that does not follow the Schmid law common to most close-packed metals. In this work,we carry out a systematic study of the screw dislocation behavior in α-Fe by means of atomistic simulations using a state-of-the-art magnetic bond-order potential. Based on the atomistic simulations of the screw dislocations under various external loadings, we formulate an analytical yield criterion that correctly captures the non-Schmid plastic response of iron single crystals under general loading conditions. The theoretical predictions of operative slip systems for uniaxial loadings agree well with available experimental observations, and demonstrate the robustness and reliability of such atomistically based yield criterion. In addition, this bottom-up approach can be directly utilized to formulate dislocation mobility rules in mesoscopic discrete dislocation dynamics simulations.
Effect of protein binding on unbound atazanavir and darunavir cerebrospinal fluid concentrations

HIV‐1 protease inhibitors (PIs) exhibit different protein binding affinities and achieve variable plasma and tissue concentrations. Degree of plasma protein binding may impact central nervous system penetration. This cross‐sectional study assessed cerebrospinal fluid (CSF) unbound PI concentrations, HIV‐1 RNA, and neopterin levels in subjects receiving either ritonavir‐boosted darunavir (DRV), 95% plasma protein bound, or atazanavir (ATV), 86% bound. Unbound PI trough concentrations were measured using rapid equilibrium dialysis and liquid chromatography/tandem mass spectrometry. Plasma and CSF HIV‐1 RNA and neopterin were measured by Ampliprep/COBAS® Taqman® 2.0 assay (Roche) and enzyme‐linked immunosorbent assay (ALPCO), respectively. CSF/plasma unbound drug concentration ratio was higher for ATV, 0.09 [95% confidence interval (CI) 0.06–0.12] than DRV, 0.04 (95%CI 0.03–0.06). Unbound CSF concentrations were lower than protein adjusted wild‐type inhibitory concentration‐50 (IC50) in all ATV and 1 DRV‐treated subjects (P < 0.001). CSF HIV‐1 RNA was detected in 2/15 ATV and 4/15 DRV subjects (P = 0.65). CSF neopterin levels were low and similar between arms. ATV relative to DRV had higher CSF/plasma unbound drug ratio. Low CSF HIV‐1 RNA and neopterin suggest that both regimens resulted in CSF virologic suppression and controlled inflammation.
Monoclonal antibodies against the nonhemagglutinating fimbrial antigen 1C (pseudotype 1) of Escherichia coli

Hybridoma-derived monoclonal antibodies were produced with fimbrial preparations from Escherichia coli 20025 (04:K12:H-) with fimbrial (F) antigens 1C, 13, one related to 12, and one preliminarily termed y and from E. coli 2980 (018ac:K5:H-) with F antigens 1C and 8. Two clones of subclonal hybrid cells were studied which produced monoclonal antibodies (mc-20025-F2b, immunoglobulin G2b [IgG2b]; mc-2980-F2, IgG1) that were reactive with E. coli 20025, 2980, and a number of additional strains which exhibited the F1C antigen. Results of enzyme-linked immunosorbent assay and Western blot analysis indicated that the antibodies had F1C specificity, and competitive enzyme-linked immunosorbent assay with 125I-labeled antibodies showed that they recognized different epitopes on the fimbrial subunit. Neither of the antibodies agglutinated F1C-fimbriated E. coli but bound to the bacteria. There was no binding to E. coli without F1C fimbriae.
Allelic Imbalances in Radiation—Associated Acute Myeloid Leukemia

Acute myeloid leukemia (AML) can develop as a secondary malignancy following radiotherapy, but also following low-dose environmental or occupational radiation exposure. Therapy-related AML frequently carries deletions of chromosome 5q and/or 7, but for low-dose exposure associated AML this has not been described. For the present study we performed genome-wide screens for loss-of-heterozygosity (LOH) in a set of 19 AML cases that developed after radiation-exposure following the Chernobyl accident. Using Affymetrix SNP arrays we found large regions of LOH in 16 of the cases. Eight cases (42%) demonstrated LOH at 5q and/or 7, which is a known marker of complex karyotypic changes and poor prognosis. We could show here for the first time that exposure to low-dose ionizing radiation induces AML with molecular alterations similar to those seen in therapy-related cases.
Membrane lysis during biological membrane fusion: collateral damage by misregulated fusion machines

In the canonical model of membrane fusion, the integrity of the fusing membranes is never compromised, preserving the identity of fusing compartments. However, recent molecular simulations provided evidence for a pathway to fusion in which holes in the membrane evolve into a fusion pore. Additionally, two biological membrane fusion models—yeast cell mating and in vitro vacuole fusion—have shown that modifying the composition or altering the relative expression levels of membrane fusion complexes can result in membrane lysis. The convergence of these findings showing membrane integrity loss during biological membrane fusion suggests new mechanistic models for membrane fusion and the role of membrane fusion complexes.
Identification of a Ca2+-Pectate Binding Site on an Apoplastic Peroxidase

An apoplastic isoperoxidase from zucchini (APRX) was shown to bind strongly to polygalacturonic acid in their Ca2+-induced conformation. By homology modeling, we were able to identify a motif of four clustered arginines (positions 117, 262, 268, and 271) that could be responsible for this binding. To verify the role of these arginine residues in the binding process, we prepared three mutants of APRX (M1, R117S; M2, R262Q/R268S; and M3, R262Q/R268S/R271Q). APRX and the three mutants were expressed as recombinant glycoproteins by the baculovirus–insect cell system. This procedure yielded four active enzymes with similar molecular masses that were tested for their ability to bind Ca2+-pectate. Recombinant wild-type APRX exhibited an affinity for the pectic structure comparable to that of the native plant isoperoxidase. The mutations impaired binding depending on the number of arginine residues that were replaced. M1 and M2 showed intermediate affinities, whereas M3 did not bind at all. This was demonstrated using an in vitro binding test and on cell walls of hypocotyl cross-sections. It can be concluded that APRX bears a Ca2+-pectate binding site formed by four clustered arginines. This site could ensure that APRX is properly positioned in cell walls, using unesterified domains of pectins as a scaffold.
Children's Motivations for Video Game Play in the Context of Normal Development

Electronic games are now an everyday part of childhood and adolescence. The debate has moved from whether children should play video games to how to maximize potential benefits and to identify and minimize potential harms. To do this, we must understand what motivates children to play electronic games and what needs the games meet. Drawing on a survey of 1,254 middle school children, focus groups with boys and their parents, and findings from other quantitative and qualitative research, the author describes a variety of motivations for video game play (including games with violent content) and how these may vary based on factors such as mood, environment, personality, and developmental stage. The findings are put into the context of normal development, and suggestions are given for parents, educators, and researchers.
Long-term Follow-up of Patients with Malignant Pleural Mesothelioma Receiving High-Dose Adenovirus Herpes Simplex Thymidine Kinase/Ganciclovir Suicide Gene Therapy

Purpose: Delineation of the long-term follow-up data on a series of patients with malignant mesothelioma, who received a single intrapleural dose of a nonreplicative adenoviral (Ad) vector encoding the herpes simplex virus thymidine kinase “suicide gene” (Ad.HSVtk) in combination with systemic ganciclovir. Experimental Design: This report focuses on the 21 patients receiving “high-dose” therapy, defined by an intrapleural dose of vector (≥1.6 × 1013 viral particles), where transgene-encoded tk protein was reliably identified on immunohistochemical staining. In 13 patients, the vector was deleted in the E1 and E3 regions of the Ad; in the other eight patients, the vector had deletions in the Ad genes E1 and E4. Safety, immunologic responses, transgene expression, and clinical responses were evaluated. Results: Both the E1/E3-deleted vector and the E1/E4-deleted vector were well tolerated and safe, although production of the E1/E4 vector was more difficult. Posttreatment antibody responses against the tumors were consistently seen. Interestingly, we observed a number of clinical responses in our patients, including two long-term (>6.5 year) survivors, both of whom were treated with the E1/E4-deleted vector. Conclusions: Intrapleural Ad.HSVtk/ganciclovir is safe and well tolerated in mesothelioma patients and resulted in long-term durable responses in two patients. Given the limited amount of gene transfer observed, we postulate that Ad.HSVtk may have been effective due to induction of antitumor immune responses. We hypothesize that approaches aiming to augment the immune effects of Ad gene transfer (i.e., with the use of cytokines) may lead to increased numbers of therapeutic responses in otherwise untreatable pleural malignancies.
Humoral Immunity in Atherosclerosis

Atherosclerosis is a chronic inflammatory disease of largeand medium-sized arteries. It is characterized by the deposition and trapping of low-density lipoproteins (LDLs) in the artery wall, which then undergo a variety of changes, both enzymatic and nonenzymatic, that lead to a cascade of inflammatory responses followed by the recruitment of mostly macrophages and T cells. The accumulation of LDL in the subendothelial space makes it susceptible to oxidation by various processes, and the resultant formation of oxidized LDL (OxLDL) has been suggested to be the key event in driving the subsequent inflammation that characterizes atherosclerosis. Infiltrating macrophages take up OxLDL via scavenger receptors leading to the formation of lipid-laden foam cells, which are the hallmark cells of atherosclerotic lesions. With plaque progression, many foam cells undergo apoptosis resulting in the formation of an acellular necrotic core that is full of lipid gruel and cellular debris. Once the fibrous cap covering the necrotic core erodes or ruptures, allowing contact between the exposed material and the circulating coagulation system, thrombus formation is triggered, resulting in clinical events such as stroke and myocardial infarction, which are leading causes of death globally. Inflammation is the response of the immune system to the presence of exogenous and endogenous antigens, and it is now widely accepted that immune mechanisms are involved in all phases of lesion development. However, knowledge Review
Insufficient APC Capacities of Dendritic Cells in Gene Gun-Mediated DNA Vaccination1

Gene gun-mediated DNA immunization is a powerful mode of vaccination against infectious diseases and tumors. Many studies have identified dendritic cells (DC) as the central players in inducing immunity upon biolistic DNA vaccination; however, none of these studies directly quantify DC-mediated responses in comparison with immunity triggered by all Ag- and MHC-expressing cells. In this study we use two different approaches to decipher the relative role of DC vs other cell types in gene gun-induced immunity. First, we directly compared the immunization efficacy of different DNA constructs, which allow Ag expression ubiquitously (CMV promoter) or specifically in DC (CD11c promoter) and would encode either for soluble or membrane bound forms of Ag. Second, we immunized transgenic mice in which only DC can present MHC-restricted Ag, and directly compared the magnitudes of CTL activation with those obtained in wild-type mice. Surprisingly, our combined data suggest that, although DC-specific Ag expression is sufficient to induce humoral responses, DC alone cannot trigger optimal CD4 and CD8 T cell responses upon gene gun vaccination. Therefore, we conclude that DC alone are insufficient to mediate optimal induction of T cell immunity upon gene gun DNA vaccination and that broad Ag expression rather than DC-restricted approaches are necessary for induction of complete immune responses.
p‐Jigsaw: a cluster‐based Web server with cooperative caching support

Clustering provides a viable approach to building scalable Web systems with increased computing power and abundant storage space for data and contents. In this paper, we present a pure‐Java‐based parallel Web server system, p‐Jigsaw, which operates on a cluster and uses the technique of cooperative caching to achieve high performance. We introduce the design of an in‐memory cache layer, called Global Object Space (GOS), for dynamic caching of frequently requested Web objects. The GOS provides a unified view of cluster‐wide memory resources for achieving location‐transparent Web object accesses. The GOS relies on cooperative caching to minimize disk accesses. A requested Web object can be fetched from a server node's local cache or a peer node's local cache, with the disk serving only as the last resort. A prototype system based on the W3C Jigsaw server has been implemented on a 16‐node PC cluster. Three cluster‐aware cache replacement algorithms were tested and evaluated. The benchmark results show good speedups with a real‐life access log, proving that cooperative caching can have significant positive impacts on the performance of cluster‐based parallel Web servers. Copyright © 2003 John Wiley & Sons, Ltd.
Circulating Levels of Insulin-like Growth Factors, their Binding Proteins, and Breast Cancer Risk

Background: Earlier data support the hypothesis that the relation between circulating insulin-like growth factor-I (IGF-I) levels and breast cancer risk differs by menopausal status. The strong association of IGF-I with height in childhood and weak or no association between adult levels and adult height also suggest that IGF levels in young women may better reflect an exposure time period of importance to breast cancer. Few studies have assessed IGF binding protein-1 (IGFBP-1) or free IGF and breast cancer risk. Materials and Methods: We conducted a large case-control study nested within the prospective Nurses' Health Study. Plasma concentrations of IGF-I, free IGF, IGFBP-3, and IGFBP-1 were measured in blood samples collected in 1989 to 1990. Eight hundred women were identified who had a diagnosis of invasive or in situ breast cancer after blood collection, up to 1998, 27% of whom were premenopausal at blood collection. To those 800 women, one to two controls were age-matched for a total of 1,129 controls. We used logistic regression models to estimate the relative risk (RR) of breast cancer associated with IGF levels. Findings: Among postmenopausal women, neither IGF-I, IGFBP-3, IGFBP-1, nor free IGF was associated with breast cancer risk [RRs, top versus bottom quintile: IGF-I, 1.0; 95% confidence interval (95% CI), 0.7-1.4; IGFBP-3, 0.8; 95% CI, 0.6-1.1; IGFBP-1, 0.9; 95% CI, 0.6-1.5; and free IGF, 1.0; 95% CI, 0.6-1.4]. Among premenopausal women, IGFBP-3, IGFBP-1, and free IGF similarly were not associated with breast cancer risk (RRs, top versus bottom quintile: IGFBP-3, 1.2; 95% CI, 0.8-2.3; IGFBP-1, 1.5; 95% CI, 0.8-3.0; and free IGF, 1.1; 95% CI, 0.7-2.1). Higher IGF-I plasma levels, however, were associated with a modestly elevated breast cancer risk (RR, 1.6; 95% CI, 1.0-2.6) among the premenopausal women, with a stronger association among premenopausal women ages ≤50 (RR, 2.5; 95% CI, 1.4-4.3); further adjustment for IGFBP-3 did not greatly change these estimates. Interpretation: Circulating IGF-I levels seem to be modestly associated with breast cancer risk among premenopausal women, but not among postmenopausal women. IGFBP-3, IGFBP-1, and free IGF are not associated with breast cancer risk in either premenopausal or postmenopausal women in this cohort.
On The Limits of Mutation Reduction Strategies

Although mutation analysis is considered the best way to evaluate the effectiveness of a test suite, hefty computational cost often limits its use. To address this problem, various mutation reduction strategies have been proposed, all seeking to reduce the number of mutants while maintaining the representativeness of an exhaustive mutation analysis. While research has focused on the reduction achieved, the effectiveness of these strategies in selecting representative mutants, and the limits in doing so have not been investigated, either theoretically or empirically. We investigate the practical limits to the effectiveness of mutation reduction strategies, and provide a simple theoretical framework for thinking about the absolute limits. Our results show that the limit in improvement of effectiveness over random sampling for real-world open source programs is a mean of only 13.078%. Interestingly, there is no limit to the improvement that can be made by addition of new mutation operators. Given that this is the maximum that can be achieved with perfect advance knowledge of mutation kills, what can be practically achieved may be much worse. We conclude that more effort should be focused on enhancing mutations than removing operators in the name of selective mutation for questionable benefit.
Genetic Variation within Native Populations of Endemic Silkmoth Antheraea assamensis (Helfer) from Northeast India Indicates Need for In Situ Conservation

A. assamensis is a phytophagous Lepidoptera from Northeast India reared on host trees of Lauraceae family for its characteristic cocoon silk. Source of these cocoons are domesticated farm stocks that crash frequently and/or wild insect populations that provide new cultures. The need to reduce dependence on wild populations for cocoons necessitates assessment of genetic diversity in cultivated and wild populations. Molecular markers based on PCR of Inter-simple sequence repeats (ISSR) and simple sequence repeats (SSR) were used with four populations of wild insects and eleven populations of cultivated insects. Wild populations had high genetic diversity estimates (Hi = 0.25; HS = 0.28; HE = 0.42) and at least one population contained private alleles. Both marker systems indicated that genetic variability within populations examined was significantly high. Among cultivated populations, insects of the Upper Assam region (Hi = 0.19; HS = 0.18; HE = 0) were genetically distinct (F ST = 0.38 with both marker systems) from insects of Lower Assam (Hi = 0.24; HS = 0.25; HE = 0.3). Sequencing of polymorphic amplicons suggested transposition as a mechanism for maintaining genomic diversity. Implications for conservation of native populations in the wild and preserving in-farm diversity are discussed.
Prediction of Ownership and Control Concentration in German and UK Initial Public Offerings

The paper investigates why the corporate landscapes of Germany and UK are so different in terms of control by analyzing ownership and control evolution in recent IPOs. We report the control evolution of a sample of size- and industry-matched German and UK companies six years subsequent to the flotation. The initial shareholders in the average German IPO lose majority control six years after going public, whereas the initial owners of UK IPOs decrease their holding to less than the majority two years after going public. Acquisitions are frequent in the UK with 35% of IPOs being taken over versus only one German sample company. Partial take-overs are common in German firms: in one third of the sample a large controlling shareholder acquires control from the existing controlling shareholder. In order to predict the state of ownership and control six years after going public, a multinomial logit model is used. We distinguish four possible states of control: the company is (i) still controlled by the shareholders who controlled the company prior to the flotation, (ii) acquired by a closely held shareholder (i.e. an individual or family), (iii) acquired by a shareholder with diffuse ownership and (iv) widely held. We find that if the founder still owns a stake at the flotation, the probability that the company will be controlled by this founder after six years is large. For risky and poorly performing German and UK companies, the odds of ending up with concentrated ultimate control increase. In the case of German IPOs, the chance of substantial control concentration augments when non-voting shares have been issued at flotation and when the company experiences a high growth rate subsequent to the IPO. Profitable, low-risk, and large companies tend to be widely held six years after being listed.
Cooperative Binding of Transcription Factors Promotes Bimodal Gene Expression Response

In the present work we extend and analyze the scope of our recently proposed stochastic model for transcriptional regulation, which considers an arbitrarily complex cis-regulatory system using only elementary reactions. Previously, we determined the role of cooperativity on the intrinsic fluctuations of gene expression for activating transcriptional switches, by means of master equation formalism and computer simulation. This model allowed us to distinguish between two cooperative binding mechanisms and, even though the mean expression levels were not affected differently by the acting mechanism, we showed that the associated fluctuations were different. In the present generalized model we include other regulatory functions in addition to those associated to an activator switch. Namely, we introduce repressive regulatory functions and two theoretical mechanisms that account for the biphasic response that some cis-regulatory systems show to the transcription factor concentration. We have also extended our previous master equation formalism in order to include protein production by stochastic translation of mRNA. Furthermore, we examine the graded/binary scenarios in the context of the interaction energy between transcription factors. In this sense, this is the first report to show that the cooperative binding of transcription factors to DNA promotes the “all-or-none” phenomenon observed in eukaryotic systems. In addition, we confirm that gene expression fluctuation levels associated with one of two cooperative binding mechanism never exceed the fluctuation levels of the other.
The Silence of the LANs: Efficient Leakage Resilience for IPsec VPNs

Virtual private networks (VPNs) are increasingly used to build logically isolated networks. However, existing VPN designs and deployments neglected the problem of traffic analysis and covert channels. Hence, there are many ways to infer information from VPN traffic without decrypting it. Many proposals have been made to mitigate network covert channels, but previous works remained largely theoretical or resulted in prohibitively high padding overhead and performance penalties. In this paper, we: 1) analyse the impact of covert channels in IPsec; 2) present several improved and novel approaches for covert channel mitigation in IPsec; 3) propose and implement a system for dynamic performance trade-offs; and 4) implement our design in the Linux IPsec stack and evaluate its performance for different types of traffic and mitigation policies. At only 24% overhead, our prototype enforces tight information-theoretic bounds on information leakage. To encourage further research, we put our prototype code and data in the public domain.