Miracle-dz/UniFAR-FTUs huggingface dataset:
Comprehensive assessment of cancer missense mutation clustering in protein structures

Significance Tumor sequencing efforts have enabled the identification of cancer genes based on an excess of mutations in the gene or clustering of mutations along the (one-dimensional) DNA sequence of the gene. Here, we show that this approach can be extended to identify cancer genes based on clustering of mutations relative to the 3D structure of the protein product. By analyzing the PanCancer compendium of somatic mutations in nearly 5,000 tumors, we identified known cancer genes and previously unidentified candidates based on clustering of missense mutations in protein structures or at interfaces with binding partners. In addition, we found that 3D clustering is present in both oncoproteins and tumor suppressors—contrary to the view that such clustering is a hallmark of oncoproteins. Large-scale tumor sequencing projects enabled the identification of many new cancer gene candidates through computational approaches. Here, we describe a general method to detect cancer genes based on significant 3D clustering of mutations relative to the structure of the encoded protein products. The approach can also be used to search for proteins with an enrichment of mutations at binding interfaces with a protein, nucleic acid, or small molecule partner. We applied this approach to systematically analyze the PanCancer compendium of somatic mutations from 4,742 tumors relative to all known 3D structures of human proteins in the Protein Data Bank. We detected significant 3D clustering of missense mutations in several previously known oncoproteins including HRAS, EGFR, and PIK3CA. Although clustering of missense mutations is often regarded as a hallmark of oncoproteins, we observed that a number of tumor suppressors, including FBXW7, VHL, and STK11, also showed such clustering. Beside these known cases, we also identified significant 3D clustering of missense mutations in NUF2, which encodes a component of the kinetochore, that could affect chromosome segregation and lead to aneuploidy. Analysis of interaction interfaces revealed enrichment of mutations in the interfaces between FBXW7-CCNE1, HRAS-RASA1, CUL4B-CAND1, OGT-HCFC1, PPP2R1A-PPP2R5C/PPP2R2A, DICER1-Mg2+, MAX-DNA, SRSF2-RNA, and others. Together, our results indicate that systematic consideration of 3D structure can assist in the identification of cancer genes and in the understanding of the functional role of their mutations.
Cytoplasmic Localization of Human cdc25C during Interphase Requires an Intact 14-3-3 Binding Site

ABSTRACT cdc25C induces mitosis by activating the cdc2-cyclin B complex. The intracellular localization of cyclin B1 is regulated in a cell cycle-specific manner, and its entry into the nucleus may be required for the initiation of mitosis. To determine the cellular localization of cdc25C, monoclonal antibodies specific for cdc25C were developed and used to demonstrate that in human cells, cdc25C is retained in the cytoplasm during interphase. A deletion analysis identified a 58-amino-acid region (amino acids 201 to 258) in cdc25C that was required for the cytoplasmic localization of cdc25C. This region contained a specific binding site for 14-3-3 proteins, and mutations in cdc25C that disrupted 14-3-3 binding also disrupted the cytoplasmic localization of cdc25C during interphase. cdc25C proteins that do not contain a binding site for 14-3-3 proteins showed a pancellular localization and an increased ability to induce premature chromosome condensation. The cytoplasmic localization of cdc25C was not altered by γ irradiation or treatment with the nuclear export inhibitor leptomycin B. These results suggest that 14-3-3 proteins may negatively regulate cdc25C function by sequestering cdc25C in the cytoplasm.
Cognitive deficits in chronic fatigue syndrome and their relationship to psychological status, symptomatology, and everyday functioning.

OBJECTIVE To examine cognitive deficits in people with chronic fatigue syndrome (CFS) and their relationship to psychological status, CFS symptoms, and everyday functioning. METHOD The current study compared the cognitive performance (reaction time, attention, memory, motor functioning, verbal abilities, and visuospatial abilities) of a sample with CFS (n = 50) with that of a sample of healthy controls (n = 50), all of whom had demonstrated high levels of effort and an intention to perform well, and examined the extent to which psychological status, CFS symptoms, and everyday functioning were related to cognitive performance. RESULTS The CFS group showed impaired information processing speed (reaction time), relative to the controls, but comparable performance on tests of attention, memory, motor functioning, verbal ability, and visuospatial ability. Moreover, information processing speed was not related to psychiatric status, depression, anxiety, the number or severity of CFS symptoms, fatigue, sleep quality, or everyday functioning. CONCLUSION A slowing in information processing speed appears to be the main cognitive deficit seen in persons with CFS whose performance on effort tests is not compromised. Importantly, this slowing does not appear to be the consequence of other CFS-related variables, such as depression and fatigue, or motor speed.
Lumbar spine loads during the lifting of extremely heavy weights.

The reaction moments at the knee, hip, and L4/L5 joints, and the compressive and shearing forces on L4/L5 are documented in powerlifters competing in a national powerlifting championship. Analyses were made of 13 female and 44 male competitors. The joint moments and forces were estimated from a linked segment model (WATBAK) that incorporated functional low back extensor musculature with a moment arm of 6 cm and a line action that was oriented 5 degrees posteriorly to the L4/L5 compression axis. This oblique orientation of the extensor muscles reduced the anterior shearing load on the vertebral motion unit. Average compressive loads on L4/L5 were estimated up to 17,192 N while the highest average L4/L5 and hip moments were 988 and 1047 N.m, respectively. The sumo deadlift style resulted in a 10% reduction in the joint moment and 8% reduction in the load shear force at the L4/L5 level when compared with the conventional lifting style. Formulation of linear regression equations to predict the load lifted using reaction joint moments yielded substantial unexplained variability, though significant relationships were found. This analysis suggested that there is large variability in the pattern of loading joints among national class powerlifters.
ML based QoE enhancement in SDN context: Video streaming case

In today's world, video streaming rose above all other types of traffic. In fact, providing this service with a high quality presents the most challenging task among the advancements in networking technologies. Researchers are trying to help creating a more efficient network where congestion, broadband limitations and skyrocketing number of users present ever-diminishing obstacles. When it comes to us, we present in this paper a machine learning approach combined with adaptive coding in order to provide a better QoE for video streaming services. This solution will be established using SDN architecture. We can justify this choice because we need a centralized architecture, where the totality of the network is known, to predict its status. So, we will implement a machine learning algorithm in the controller: this algorithm, called ML based SSIM, will calculate approximately the quality needed for a video to be streamed. Finally, the quality found by the ML-based SSIM Algorithm will be combined with the network situation to choose the right coding. First part of the paper deals with a brief introduction of SDN networks, QoE requirement and ML algorithms. Secondly, we expose the SSIM approach and explain how our proposed one is based on. The last part of the paper deals with experiments: we describe SDN environment deployment, describe scenarios and give at the end results and values. We highlight at the end the future of our proposition.
Steady-state and transient-state analyses of aerobic fermentation in Saccharomyces kluyveri.

Some yeasts, such as Saccharomyces cerevisiae, produce ethanol at fully aerobic conditions, whereas other yeasts, such as Kluyveromyces lactis, do not. In this study we investigated the occurrence of aerobic alcoholic fermentation in the petite-negative yeast Saccharomyces kluyveri that is only distantly related to S. cerevisiae. In aerobic glucose-limited continuous cultures of S. kluyveri, two growth regimens were observed: at dilution rates below 0.5 h(-1) the metabolism was purely respiratory, and at dilution rates above 0.5 h(-1) the metabolism was respiro-fermentative. The dilution rate at which the switch in metabolism occurred, i.e. the critical dilution rate, was 66% higher than the typical critical dilution rate of S. cerevisiae. The maximum specific oxygen consumption rate around the critical dilution rate was found to 13.6 mmol (g dry weight)(-1) h(-1) and the capacity of the pyruvate dehydrogenase-bypass pathway was estimated to be high from in vitro enzyme activities; especially the specific activity of acetyl-CoA synthetase was much higher than in S. cerevisiae at all tested conditions. Addition of glucose to respiring cells of S. kluyveri led to ethanol formation after a delay of 20-50 min (depending on culture conditions prior to the pulse), which is in contrast to S. cerevisiae that ferments immediately after glucose addition.
Arrhythmia detection and classification using morphological and dynamic features of ECG signals

Computer-assisted cardiac arrhythmia detection and classification can play a significant role in the management of cardiac disorders. In this paper, we propose a new approach for arrhythmia classification based on a combination of morphological and dynamic features. Wavelet Transform (WT) and Independent Component Analysis (ICA) are applied separately to each heartbeat to extract corresponding coefficients, which are categorized as ‘morphological’ features. In addition, RR interval information is also obtained characterizing the ‘rhythm’ around the corresponding heartbeat providing ‘dynamic’ features. These two different types of features are then concatenated and Support Vector Machine (SVM) is utilized for the classification of heartbeats into 15 classes. The procedure is applied to the data from two ECG leads independently and the two results are fused for the final decision. Compare the two classification results and the classification result is kept if the two are identical or the one with greater classification confidence is picked up if the two are inconsistent. The proposed method was tested over the entire MIT-BIH Arrhythmias Database [1] and it yields an overall accuracy of 99.66% on 85945 heartbeats, better than any other published results.
Neurotransmitter and neuromodulator genes associated with a history of depressive symptoms in individuals with alcohol dependence.

BACKGROUND Depressive symptoms are common among individuals with alcohol use disorders and impact treatment outcome. Substantial overlap exists among the neurobiological systems proposed in the pathophysiology of depressive and alcohol use disorders; however, specific genetic effects contributing to risk for depressive comorbidity remain poorly understood. METHODS This study examines the association of depressive symptom scores for lifetime depression (the sum of DSM-IV major depression co-endorsed criteria for lifetime depression) with markers in 120 candidate genes in 554 alcohol-dependent individuals. The candidate genes code for molecules involved in dopamine, serotonin, glutamate, gamma-aminobutyric acid (GABA), and opioid neurotransmission, cell signaling, pharmacokinetics, stress biology, and behavioral control. Analyses were conducted at the single marker level with experimentwise permutation to control for multiple testing. RESULTS Results revealed nominal associations for markers in 20 genes. Following experimentwise permutation, markers in the corticotropin-releasing hormone-binding protein (CRHBP) the μ-opioid receptor (OPRM1) and the β1 subunit of GABA A (GABA(A)) receptors (GABRB1) met or exceeded the significance threshold. None of the markers associated with depressive symptom scores were significantly associated with alcohol dependence symptom scores. CONCLUSION These findings suggest potential risk genes for depressive symptoms in alcohol-dependent individuals.
Prolonged dormancy of human liposarcoma is associated with impaired tumor angiogenesis

The disease state of cancer appears late in tumor development. Before being diagnosed, a tumor can remain for prolonged periods of time in a dormant state. Dormant human cancer is commonly defined as a microscopic tumor that does not expand in size and remains asymptomatic. Dormant tumors represent an early stage in tumor development and may therefore be a potential target for nontoxic, antiangiogenic therapy that could prevent tumor recurrence. Here, we characterize an experimental model that recapitulates the clinical dormancy of human tumors in mice. We demonstrate that these microscopic dormant cancers switch to the angiogenic phenotype at a predictable time. We further show that while angiogenic liposarcomas expand rapidly after inoculation of tumor cells in mice, nonangiogenic dormant liposarcomas remain microscopic up to one‐third of the normal severe combined immune deficiency (SCID) mouse life span, although they contain proliferating tumor cells. Nonangiogenic dormant tumors follow a similar growth pattern in subcutaneous (s.c.) and orthotopic environments. Throughout the dormancy period, development of intratumoral vessels is impaired. In nonangogenic dormant tumors, small clusters of endothelial cells without lumens are observed early after tumor cell inoculation, but the nonangiogenic tumor cannot sustain these vessels, and they disappear within weeks. There is a concomitant decrease in microvessel density, and the nonangiogenic dormant tumor remains harmless to the host. In contrast, microvessel density in tumors increases rapidly after the angiogenic switch and correlates with rapid expansion of tumor mass. Both tumor types cultured in vitro contain fully transformed cells, but only cells from the nonangiogenic human liposarcoma secrete relatively high levels of the angiogenesis inhibitors thrombospondin‐1 and TIMP‐1. This model suggests that as improved blood or urine molecular biomarkers are developed, the microscopic, nonangiogenic, dormant phase of human cancer may be vulnerable to antiangiogenic therapy years before symptoms, or before anatomical location of a tumor can be detected, by conventional methods. —Almog, N. , Henke, V. , Flores, L. , Hlatky, L. , Kung, A. L. , Wright, R. D. , Berger, R. , Hutchinson, L. , Naumov, G. , Bender, E. , Akslen, L. , Achilles, E. ‐G. , Folkman, J. Prolonged dormancy of human liposarcoma is associated with impaired tumor angiogenesis. FASEB J. 20, E1–E10 (2006)
Experimental Demonstration of Segment Routing

Segment routing (SR) technology has been recently proposed to enforce effective routing strategies without relying on signaling protocols. So far, the SR technology has received limited attention within the scientific community. In this paper, two SR implementations are presented and successfully demonstrated in two different network testbeds. The first implementation focuses on a software defined networking (SDN) scenario where nodes consist of OpenFlow switches and the SR controller is a specifically designed enhanced version of an OpenFlow controller. The second implementation includes a novel path computation element (PCE) scenario where nodes consist of commercially available IP/MPLS routers and the SR controller is a new extended version of a PCE solution. Both implementations have been successfully applied to demonstrate dynamic traffic rerouting. In particular, by enforcing different segment list configurations at the ingress node, rerouting is effectively achieved with no packet loss and without requiring the use of signaling protocols. Effective scalability performance is achieved in both proposed implementations, under different segment list conditions.
Gas-Phase Ion–Molecule Reactions of Small Nitroalkanes and Their Deprotonated Anions

Gas-phase reactions of nitromethane (1), nitroethane (2), 2-nitropropane (3), 2-methyl-2-nitropropane (4) and nitrocyclopropane (5) were studied at 300 K using the flowing afterglow technique. These nitroalkanes react with gas-phase bases HO−, CH3O− and HOO− very rapidly with rate coefficients of (2.5–4.3) × 10−9 cm3 s−1 and reaction efficiencies of 60–100%, for example, k = 3.2 × 10−9 cm3 s−1 (86%) for 5 reacting with hydroperoxide anion. Proton transfer (PT) is the only reaction observed for 1 while elimination (E2) is the exclusive pathway for 4 yielding isobutene and NO2−. Both PT and E2 reactions are observed for 2, 3 and 5, the former being the major pathway. Deprotonated anions of 1, 2, 3 and 5 were subjected to reactivity studies with CH3I, CO2, CS2 and SO2. Nucleophilic substitution (SN2) reaction occurs with CH3I, while characteristic products CS2O− and SO3− are formed from CS2 and SO2, respectively, along with competing adduct formation. The SN2 rate is greater, whereas the reactivities with the triatomic reagents are smaller for deprotonated nitrocyclopropane than for the other acyclic anions. These observations strongly suggest that the reactions of nitroalkane [M – H]− anions occur through initial attack from the terminal oxygen; the nitrocyclopropane carbanion is more strained and, thus, less stabilized by resonance [R2C−−NO2 ↔ R2C=NO2−] resulting in the greater basicity/nucleophilicy and the less negative charge on the oxygen site.
Relationship between Vitamin D Status and Striae Distensae: A Case-Referent Study

Vitamin D (VD) plays a role in the skin regulation. Striae Distensae (SD) are manifestations of epidermal atrophy that occurs after tissue tearing due to overstretching or rapid growth. The objective of this study was to investigate the relation between serum VD and occurrence of SD in women who had undergone mammaplasty with silicone implants. A case-referent study was conducted. The blood values of 25-hydroxyvitamin D (25OHD) were measured before the surgery. For each patient postoperatively diagnosed with SD, four other participants submitted to the same surgery, without the development of SD, were enrolled as the healthy controls. 67 women with SD after the surgery entered the study. 268 formed the control group. In the serum of healthy controls 25OHD mean was 27 ng/mL, and SD cases presented 20 ng/mL (P = 0.01). Scarce values of VD have been observed in 56.71% of the cases presenting SD and in 39.91% without SD (P = 0.002). Chance of having VD values lower than 20 ng/mL amongst cases with SD is 2.38 (P = 0.0001). Lower serum levels of VD are linked to a higher occurrence of SD.
Characterization of a human monoclonal antibody obtained after immunization with plasma vaccine and a booster with recombinant‐DNA hepatitis B vaccine

A human monoclonal antibody type IgG4, designated 1Ff4, was obtained by Epstein Barr virus transformation of peripheral blood lymphocytes from a hepatitis B vaccinee (HB‐VAX: plasma‐derived vaccine) after one boost of yeast recombinant DNA derived vaccine (Engerix‐B). 1Ff4 binds preferentially to HBsAg/adw2 and HBsAg/ayw1. In binding experiments, it competes with antibodies induced by vaccination with HB‐VAX‐DNA (yeast recombinant) and HB‐VAX (plasma‐derived vaccine). 1Ff4 competes in part with a monoclonal antibody for the w/r region. Partial inhibition of binding of HBsAg/adw2 to solid phase anti‐HBs was detected, resembling inhibition obtained using other human monoclonal specific for the “a”‐loop. 1Ff4 does not bind to linear peptides covering the two “a”‐loops or to an adw2/G145R mutant, its binding to wild type HBsAg strongly depends on the presence of disulphide bonds. In a large series of HBsAg‐positive samples from an endemic area, 1Ff4 antibodies were successfully used to discriminate between an adw2 and an adrq+ strain. The characterisation of 1Ff4 and other human monoclonal anti‐HBs antibodies may help to understand the fine specificity of protective antibodies elicited by immunization. J. Med. Virol. 66:304‐311, 2002. © 2002 Wiley‐Liss, Inc.
Direct Analysis of Samples of Various Origin and Composition Using Specific Types of Mass Spectrometry

ABSTRACT One of the major sources of error that occur during chemical analysis utilizing the more conventional and established analytical techniques is the possibility of losing part of the analytes during the sample preparation stage. Unfortunately, this sample preparation stage is required to improve analytical sensitivity and precision. Direct techniques have helped to shorten or even bypass the sample preparation stage; and in this review, we comment of some of the new direct techniques that are mass-spectrometry based. The study presents information about the measurement techniques using mass spectrometry, which allow direct sample analysis, without sample preparation or limiting some pre-concentration steps. MALDI – MS, PTR – MS, SIFT – MS, DESI – MS techniques are discussed. These solutions have numerous applications in different fields of human activity due to their interesting properties. The advantages and disadvantages of these techniques are presented. The trends in development of direct analysis using the aforementioned techniques are also presented.
Morphology of human neutrophils: A comparison of cryofixation, routine gluteraldehyde fixation, and the effects of dimethyl sulfoxide

Cell shape and density are critical to the evaluation of neutrophil function and/or activation. Dimethyl sulfoxide‐cryofixation‐freeze‐substitution processing (DCF) instantly preserves cell processes and ultrastructural elements with fewer artifacts than routine chemical fixation with glutaraldehyde and postfixation osmium tetroxide (GO). This study morphometrically examined density‐separated neutrophils to assess differences in DCF and GO processing procedures and studied the effect of dimethyl sulfoxide followed by GO fixation (DGO) on morphology.
Acclimation of life‐history traits to experimental changes in environmental contaminant concentrations in brown bullhead (Ameiurus nebulosus)

One adaptive mechanism aquatic populations use to facilitate tolerance to environmental contaminants is acclimation. Polychlorinated biphenyls (PCBs) are a globally ubiquitous class of persistent organic contaminants that have been linked to reproductive impairments in fish. The authors used female brown bullhead (Ameiurus nebulosus) to test whether acclimation of reproductive life‐history traits occurs in response to changes in sum PCB exposure. They compared egg diameter, gonadosomatic index (GSI), and fecundity of fish directly caught from wild populations exposed to a range of contaminant concentrations (acute), to those collected from the same populations a year before, which were placed in a clean environment to clear their contaminants throughout that year (cleared). Sum PCB concentrations were also determined for each individual. Brown bullhead from acute treatments had significantly greater sum PCB concentrations compared with cleared treatments. Egg diameter and GSI metrics were greater in cleared treatments compared with acute treatments (by 6 and 14%, respectively). Treatment effect (i.e., acute or cleared), as opposed to where the fish were collected from, accounts for 72 to 89% of the variation in the reproductive life‐history trait variables. No difference in fecundity was found between acute and cleared treatments. The authors found support that acclimation of reproductive life‐history traits occurs to changes in sum PCB concentration. To their knowledge, the present study is the first experimental test of acclimation responses of female life‐history traits to contaminants in wild populations. Environ. Toxicol. Chem. 2012;31:863–869. © 2012 SETAC