Miracle-dz/UniFAR-FTUs huggingface dataset:
Motor cortex localization using functional MRI and transcranial magnetic stimulation.

OBJECTIVE Congenital brain lesions producing focal seizures may be accompanied by reorganization of the areas responsible for motor and sensory functions within the brain due to a phenomenon that has been termed "neuronal plasticity. " This can be studied using functional MRI (fMRI) and transcranial magnetic stimulation (TMS). Using either method, the motor cortex can be localized noninvasively, but to date there have been few studies correlating the level of agreement between the two techniques. METHODS We used fMRI and TMS to localize the motor cortex in a young woman with intractable focal seizures, congenital left arm weakness, and a dysplastic right hemisphere on MRI. RESULTS There was excellent agreement in the localization of motor representation for each hand. Both were predominantly located in the left hemisphere. fMRI also showed an area of posterior activation in the right hemisphere, but there was no evidence of descending corticospinal projections from this site using TMS, direct cortical stimulation, and Wada testing. CONCLUSIONS Functional MRI (fMRI) and transcranial magnetic stimulation (TMS) were successfully used to localize cortical motor function before epilepsy surgery. Each technique demonstrated migration of motor function for the left hand to the left motor cortex. After resection of the dysplastic right precentral gyrus there was no permanent increase in weakness or disability. The two techniques are complementary; fMRI indicates all cortical areas activated by the motor task, whereas TMS identifies only those areas giving rise to corticospinal projections.
Selection, combination, and evaluation of effective software sensors for detecting abnormal computer usage

We present and empirically analyze a machine-learning approach for detecting intrusions on individual computers. Our Winnow-based algorithm continually monitors user and system behavior, recording such properties as the number of bytes transferred over the last 10 seconds, the programs that currently are running, and the load on the CPU. In all, hundreds of measurements are made and analyzed each second. Using this data, our algorithm creates a model that represents each particular computer's range of normal behavior. Parameters that determine when an alarm should be raised, due to abnormal activity, are set on a per-computer basis, based on an analysis of training data. A major issue in intrusion-detection systems is the need for very low false-alarm rates. Our empirical results suggest that it is possible to obtain high intrusion-detection rates (95%) and low false-alarm rates (less than one per day per computer), without "stealing" too many CPU cycles (less than 1%). We also report which system measurements are the most valuable in terms of detecting intrusions. A surprisingly large number of different measurements prove significantly useful.
Acetaldehyde mediation in the mechanism of ethanol-induced changes in norepinephrine metabolism.

The role of acetaldehyde in reducing the oxidative pathway and increasing the reductive route for norepinephrine (NE) metabolism was evaluated. Experiments were performed in which 14 C-NE was injected into rats and its metabolic fate in vivo was monitored in the urine. Ethanol administration failed to alter the biochemical disposition of this amine, whereas, acetaldehyde produced profound aberrations in NE metabolism. The excretion of 14 C-vanillylmandelic acid and dihydroxymandelic acid was decreased as a result of treatment with acetaldehyde, disulfiram, or calcium carbimide. A concomitant increase in labeled 3-methoxy-4-hydroxyphenylglycol was also observed with these treatments. Administration of ethanol to animals previously treated with disulfiram or calcium carbimide potentiated this effect and resulted in elevated acetaldehyde blood levels as measured by a specific gas chromatographic procedure. These findings confirm the hypothesis that competitive inhibition of aldehyde dehydrogenase by acetaldehyde is the quantitatively important mechansim in the genesis of altered neuroamine metabolism by ethanol.
Iodine Intakes of Victorian Schoolchildren Measured Using 24-h Urinary Iodine Excretion

Mandatory fortification of bread with iodized salt was introduced in Australia in 2009, and studies using spot urine collections conducted post fortification indicate that Australian schoolchildren are now replete. However an accurate estimate of daily iodine intake utilizing 24-h urinary iodine excretion (UIE μg/day) has not been reported and compared to the estimated average requirement (EAR). This study aimed to assess daily total iodine intake and status of a sample of primary schoolchildren using 24-h urine samples. Victorian primary school children provided 24-h urine samples between 2011 and 2013, from which urinary iodine concentration (UIC, μg/L) and total iodine excretion (UIE, μg/day) as an estimate of intake was determined. Valid 24-h urine samples were provided by 650 children, mean (SD) age 9.3 (1.8) years (n = 359 boys). The mean UIE of 4–8 and 9–13 year olds was 94 (48) and 111 (57) μg/24-h, respectively, with 29% and 26% having a UIE below the age-specific EAR. The median (IQR) UIC was 124 (83,172) μg/L, with 36% of participants having a UIC < 100 μg/L. This convenience sample of Victorian schoolchildren were found to be iodine replete, based on UIC and estimated iodine intakes derived from 24-h urine collections, confirming the findings of the Australian Health Survey.
Decreased pulmonary arterial proportional pulse pressure is associated with increased mortality in group 1 pulmonary hypertension

This study evaluated the utility of a novel index, pulmonary arterial (PA) proportional pulse pressure (PAPP; range 0–1, defined as [PA systolic pressure – PA diastolic pressure] / PA systolic pressure), in predicting mortality in patients with World Health Organization group 1 pulmonary hypertension (PH).
Causation and Disease: The Henle-Koch Postulates Revisited 1

The Henle-Koch postulates are reviewed in terms of their full validity in Koch's day and in light of subsequent developments. The changing guidelines developed for viral diseases, for viruses in relation to cancer and to chronic central nervous system infection, and for causative agents in chronic diseases are discussed chronologically. A set of guidelines for both acute infectious and chronic diseases is presented. The need for recognizing the role of the host and the spectrum of host responses, for sound biologic sense in evaluating causal roles of agents in disease, and for flexibility in adapting our guidelines to new knowledge are emphasized. ImagesFIG. 1FIG. 2FIG. 3FIG. 4FIG. 5FIG. 6FIG. 7FIG. 8
Association between initial type of hemodialysis access used in the elderly and mortality

We hypothesized that certain subpopulations (elderly and those with greater comorbidity) may not have significant benefit from “fistula first” initiative. A cohort of incident hemodialysis patients from 2005 to 2007, who were ≥70 years old, was derived from the United States Renal Data System. Primary variable of interest was type of vascular access used at first outpatient hemodialysis (i.e., fistula, graft, or central catheter), with primary outcome of all‐cause mortality (time to death measured from the first outpatient hemodialysis). A cohort of 82,202 patients was stratified by age (70 to ≤80, 81 to ≤90, and >90). Each group demonstrated a survival benefit with the use of an arterio‐venous fistula compared with catheter (hazard ratio [HR] 0.56 [P < 0.001], HR 0.55 [P < 0.001], and HR 0.69 [P = 0.007], respectively). Comparing graft to with a catheter, both groups, 70 to ≤80 and 81 to ≤90, had significant benefit compared with catheter (HR 0.73, P < 0.001 and HR 0.74, P < 0.001, respectively). However, significance was lost in those ≥90 (HR 0.83, P = 0.354). When substratified by comorbidity, those 81 to ≤90 years old with a history of malignancy or peripheral vascular disease also did not reach significant benefit compared with a catheter (HR 0.88, P = 0.423 and HR 0.85, P = 0.221, respectively). While specific subgroups in the hemodialysis population exist where use of fistulas and grafts at time of dialysis initiation is not of proven statistical benefit to survival, elderly hemodialysis patients with comorbidities still appear to benefit from the use of fistulas and grafts.
Metabolic Activation of Nevirapine in Human Liver Microsomes: Dehydrogenation and Inactivation of Cytochrome P450 3A4

Nevirapine, a non-nucleoside HIV-1 reverse transcriptase inhibitor, has been associated with incidences of skin rash and hepatotoxicity in patients. Although the mechanism of idiosyncratic hepatotoxicity remains unknown, it is proposed that metabolic activation of nevirapine and subsequent covalently binding of reactive metabolites to cellular proteins play a causative role. Studies were initiated to determine whether nevirapine undergoes cytochrome P450 (P450)-mediated bioactivation in human liver microsomes to electrophilic intermediates. Liquid chromatography-tandem mass spectrometry analysis of incubations containing nevirapine and NADPH-supplemented microsomes in the presence of glutathione (GSH) revealed the formation of a GSH conjugate derived from the addition of the sulfydryl nucleophile to nevirapine. No other GSH conjugates were detected, including conjugates of oxidized metabolites of nevirapine. These findings are consistent with a bioactivation sequence involving initial P450-catalyzed dehydrogenation of the aromatic nucleus with a 4-methyl group in nevirapine to an electrophilic quinone methide intermediate, which is subsequently attacked by glutathione yielding the sulfydryl conjugate. Formation of the nevirapine GSH conjugate was primarily catalyzed by heterologously expressed recombinant CYP3A4 and, to a lesser extent, CYP2D6, CYP2C19, and CYP2A6. In addition, the quinone methide reactive metabolite was a mechanism-based inactivator of CYP3A4, with inactivation parameters KI = 31 μM and kinact = 0.029 min–1, respectively. It is proposed that formation of the quinone methide intermediate may represent a rate-limiting step in the initiation of nevirapine-mediated hepatotoxicity.
A High‐Yield, High‐Purity Elutriation Method for Preparing Human Granulocytes Demonstrating Enhanced Experimental Lifetimes

A counterflow centrifugal elutriation procedure for preparing human granulocytes is described. This method permits isolation of 1‐2 × 109 granulocytes with a yield of 70% ± 7% from a unit of whole blood in 3 h. These cells are 99% ±1% pure and 95‐99% viable. When compared to cells prepared by a conventional procedure employing hypotonic lysis to remove red cells, the elutriated cells show enhanced oxidative responses resulting from enhanced longevity. Other responses including receptor‐mediated uptake of chemoattractant were not significantly different from those of conventionally prepared cells after incubation at 37° prior to stimulation. The population of elutriated granulocytes, however, was significantly more homogeneous and pure than cells prepared conventionally.
Modern HVDC PLUS application of VSC in Modular Multilevel Converter topology

This paper presents an actual view into the development of High Voltage Direct Current (HVDC) converter stations build in Modular Multilevel Converter (MMC) topology. Explanations are given how voltage sourced converters (VSC) of large active power transmission capacity and independent controlled reactive power exchange capability are designed for terminals of HVDC Links. This modern type of self-commutated converters has been developed under brand name HVDC PLUS by Siemens for use in electric power systems.
Akkermansia muciniphila induces gut microbiota remodelling and controls islet autoimmunity in NOD mice

Objective Intestinal microbiota is implicated in the pathogenesis of autoimmune type 1 diabetes in humans and in non-obese diabetic (NOD) mice, but evidence on its causality and on the role of individual microbiota members is limited. We investigated if different diabetes incidence in two NOD colonies was due to microbiota differences and aimed to identify individual microbiota members with potential significance. Design We profiled intestinal microbiota between two NOD mouse colonies showing high or low diabetes incidence by 16S ribosomal RNA gene sequencing and colonised the high-incidence colony with the microbiota of the low-incidence colony. Based on unaltered incidence, we identified a few taxa which were not effectively transferred and thereafter, transferred experimentally one of these to test its potential significance. Results Although the high-incidence colony adopted most microbial taxa present in the low-incidence colony, diabetes incidence remained unaltered. Among the few taxa which were not transferred, Akkermansia muciniphila was identified. As A. muciniphila abundancy is inversely correlated to the risk of developing type 1 diabetes-related autoantibodies, we transferred A. muciniphila experimentally to the high-incidence colony. A. muciniphila transfer promoted mucus production and increased expression of antimicrobial peptide Reg3γ, outcompeted Ruminococcus torques from the microbiota, lowered serum endotoxin levels and islet toll-like receptor expression, promoted regulatory immunity and delayed diabetes development. Conclusion Transfer of the whole microbiota may not reduce diabetes incidence despite a major change in gut microbiota, but single symbionts such as A. muciniphila with beneficial metabolic and immune signalling effects may reduce diabetes incidence when administered as a probiotic.
The Slip Transfer Process Through Grain Boundaries in HCP Ti

Information on the mechanisms of slip transfer across grain boundaries in an HCP α-Ti alloy has been obtained from deformation experiments performed In situ in the transmission electron microscope. Initially, lattice dislocations are accommodated within the grain boundary until a critical local dislocation density is reached. The boundary then responds by activating slip in the adjoining grain on the slip system experiencing the highest local resolved shear stress and producing the residual grain-boundary dislocation with the smallest Burgers vector. Slip on secondary slip systems may be initiated provided they reduce the magnitude of the Burgers vector of, or eliminate, the residual grainboundary dislocation. The selection rules used to predict the slip system activated by the grain boundary are the same as apply in ordered and disordered FCC materials.
Extracellular Matrix Metalloproteinase Inducer (CD147) Confers Resistance of Breast Cancer Cells to Anoikis through Inhibition of Bim*

Overexpression of extracellular matrix metalloproteinase inducer (EMMPRIN or CD147), a member of the immunoglobulin family and a glycoprotein enriched on the surface of tumor cells, promotes invasion, metastasis, and growth and survival of malignant cells and confers resistance to some chemotherapeutic drugs. However, the molecular mechanisms underlying the actions of EMMPRIN are not fully understood. In this study we sought to determine whether EMMPRIN contributes to the malignant phenotype of breast cancer by inhibiting anoikis, a form of apoptosis induced by loss or alteration of cell-cell or cell-matrix anchorage, and to explore the signaling pathways involved. We found that in the absence of attachment, human breast carcinoma cells expressing high levels of EMMPRIN formed less compact aggregates with larger surface area and less fibronectin matrix assembly, had higher viability, and were resistant to anoikis. Knockdown of EMMPRIN expression by RNA interference (small interfering RNA or short hairpin RNA) sensitized cancer cells to anoikis, as demonstrated by activation of caspase-3, increased DNA fragmentation, and decreased cellular viability. Furthermore, we observed that the accumulation of Bim, a proapoptotic BH3-only protein, was reduced in EMMPRIN-expressing cells and that silencing of EMMPRIN expression elevated Bim protein levels and enhanced cellular sensitivity to anoikis. Treatment of cells with a MEK inhibitor (U0126) or proteasome inhibitor (epoxomicin) also up-regulated Bim accumulation and rendered cells more sensitive to anoikis. These results indicated that expression of EMMPRIN protects cancer cells from anoikis and that this effect is mediated at least in part by a MAP kinase-dependent reduction of Bim. Because anoikis deficiency is a key feature of neoplastic transformation and invasive growth of epithelial cancer cells, our study on the role of EMMPRIN in anoikis resistance and the mechanism involved underscores the potential of EMMPRIN expression as a prognostic marker and novel target for cancer therapy.
Roles of DNA repair and reductase activity in the cytotoxicity of the hypoxia-activated dinitrobenzamide mustard PR-104A

PR-104 is a dinitrobenzamide mustard currently in clinical trial as a hypoxia-activated prodrug. Its major metabolite, PR-104A, is metabolized to the corresponding hydroxylamine (PR-104H) and amine (PR-104M), resulting in activation of the nitrogen mustard moiety. We characterize DNA damage responsible for cytotoxicity of PR-104A by comparing sensitivity of repair-defective hamster Chinese hamster ovary cell lines with their repair-competent counterparts. PR-104H showed a repair profile similar to the reference DNA cross-linking agents chlorambucil and mitomycin C, with marked hypersensitivity of XPF−/−, ERCC1−/−, and Rad51D−/− cells but not of XPD−/− or DNA-PKCS−/− cells. This pattern confirmed the expected dependence on the ERCC1-XPF endonuclease, implicated in unhooking DNA interstrand cross-links at blocked replication forks, and homologous recombination repair (HRR) in restarting collapsed forks. However, even under anoxia, the hypersensitivity of XPF−/−, ERCC1−/−, and Rad51D−/− cells to PR-104A itself was lower than for chlorambucil. To test whether this reflects inefficient PR-104A reduction, a soluble form of human NADPH:cytochrome P450 oxidoreductase was stably expressed in Rad51D−/− cells and their HRR-restored counterpart. This expression increased hypoxic metabolism of PR-104A to PR-104H and PR-104M as well as hypoxia-selective cytotoxicity of PR-104A and its dependence on HRR. We conclude that PR-104A cytotoxicity is primarily due to DNA interstrand cross-linking by its reduced metabolites, although under conditions of inefficient PR-104A reduction (low reductase expression or aerobic cells), a second mechanism contributes to cell killing. This study shows that hypoxia, reductase activity, and DNA interstrand cross-link repair proficiency are key variables that interact to determine PR-104A sensitivity. [Mol Cancer Ther 2009;8(6):1714–23]
Dependability Issues of INPE's ESA/CCSDS Telecommand/Telemetry Subsystem

This paper introduces and discusses dependability features of a Telecomm and and Telemetry subsystem designed under a Brazilian Space Program contract. The whole subsystem has been developed in a hardware description language (HDL), targeting anti-fuse programmable once FPGA devices. The discussed features include device redundancy, at hardware level, and several adopted strategies at the HDL level.
Estrogens Can Disrupt Amphibian Mating Behavior

The main component of classical contraceptives, 17α-ethinylestradiol (EE2), has high estrogenic activity even at environmentally relevant concentrations. Although estrogenic endocrine disrupting compounds are assumed to contribute to the worldwide decline of amphibian populations by adverse effects on sexual differentiation, evidence for EE2 affecting amphibian mating behaviour is lacking. In this study, we demonstrate that EE2 exposure at five different concentrations (0.296 ng/L, 2.96 ng/L, 29.64 ng/L, 2.96 µg/L and 296.4 µg/L) can disrupt the mating behavior of adult male Xenopus laevis. EE2 exposure at all concentrations lowered male sexual arousal, indicated by decreased proportions of advertisement calls and increased proportions of the call type rasping, which characterizes a sexually unaroused state of a male. Additionally, EE2 at all tested concentrations affected temporal and spectral parameters of the advertisement calls, respectively. The classical and highly sensitive biomarker vitellogenin, on the other hand, was only induced at concentrations equal or higher than 2.96 µg/L. If kept under control conditions after a 96 h EE2 exposure (2.96 µg/L), alterations of male advertisement calls vanish gradually within 6 weeks and result in a lower sexual attractiveness of EE2 exposed males toward females as demonstrated by female choice experiments. These findings indicate that exposure to environmentally relevant EE2 concentrations can directly disrupt male mate calling behavior of X. laevis and can indirectly affect the mating behavior of females. The results suggest the possibility that EE2 exposure could reduce the reproductive success of EE2 exposed animals and these effects might contribute to the global problem of amphibian decline.
MOEA/D with Adaptive Weight Adjustment

Recently, MOEA/D (multi-objective evolutionary algorithm based on decomposition) has achieved great success in the field of evolutionary multi-objective optimization and has attracted a lot of attention. It decomposes a multi-objective optimization problem (MOP) into a set of scalar subproblems using uniformly distributed aggregation weight vectors and provides an excellent general algorithmic framework of evolutionary multi-objective optimization. Generally, the uniformity of weight vectors in MOEA/D can ensure the diversity of the Pareto optimal solutions, however, it cannot work as well when the target MOP has a complex Pareto front (PF; i.e., discontinuous PF or PF with sharp peak or low tail). To remedy this, we propose an improved MOEA/D with adaptive weight vector adjustment (MOEA/D-AWA). According to the analysis of the geometric relationship between the weight vectors and the optimal solutions under the Chebyshev decomposition scheme, a new weight vector initialization method and an adaptive weight vector adjustment strategy are introduced in MOEA/D-AWA. The weights are adjusted periodically so that the weights of subproblems can be redistributed adaptively to obtain better uniformity of solutions. Meanwhile, computing efforts devoted to subproblems with duplicate optimal solution can be saved. Moreover, an external elite population is introduced to help adding new subproblems into real sparse regions rather than pseudo sparse regions of the complex PF, that is, discontinuous regions of the PF. MOEA/D-AWA has been compared with four state of the art MOEAs, namely the original MOEA/D, Adaptive-MOEA/D, -MOEA/D, and NSGA-II on 10 widely used test problems, two newly constructed complex problems, and two many-objective problems. Experimental results indicate that MOEA/D-AWA outperforms the benchmark algorithms in terms of the IGD metric, particularly when the PF of the MOP is complex.