Miracle-dz/UniFAR-FTUs huggingface dataset:
A Modification-Specific Peptide-Based immunization Approach Using CRM197 Carrier Protein: Development of a Selective Vaccine Against Pyroglutamate Aβ Peptides

Strategies aimed at reducing cerebral accumulation of the amyloid-β (Aβ) peptides have therapeutic potential in Alzheimer’s disease (AD). Aβ immunization has proven to be effective at promoting Aβ clearance in animal models, but adverse effects have hampered its clinical evaluation. The first anti-Aβ immunization clinical trial, which assessed a full-length Aβ1-42 vaccine, showed an increased risk of encephalitis, most likely because of autoimmune proinflammatory T helper 1 (Th1) response against all forms of Aβ. Immunization against less abundant but potentially more pathologically relevant Aβ products, such as N-terminally truncated pyroglutamate-3 Aβ (AβpE3), could provide efficacy and improve tolerability in Aβ immunotherapy. Here, we describe a selective vaccine against AβpE3 that uses the diphtheria toxin mutant CRM197 as a carrier protein for epitope presentation. CRM197 is currently used in licensed vaccines and has demonstrated excellent immunogenicity and safety in humans. In mice, our AβpE3:CRM197 vaccine triggered the production of specific anti-AβpE3 antibodies that did not cross-react with Aβ1-42, non-cyclized AβE3 or N-terminally truncated pyroglutamate-11 Aβ (AβpE11). AβpE3:CRM197 antiserum strongly labeled AβpE3 in insoluble protein extracts and decorated cortical amyloid plaques in human AD brains. Anti-AβpE3 antibodies were almost exclusively of the IgG1 isotype, suggesting an antiinflammatory Th2 response bias to the AβpE3:CRM197 vaccine. To the best of our knowledge, this study shows for the first time that CRM197 has potential as a safe and suitable vaccine carrier for active and selective immunization against specific protein sequence modifications or conformations such as AβpE3.
Early Predictors of In-Hospital Death in Infective Endocarditis

Background—Data on early determinants of outcome in infective endocarditis (IE) are limited. We evaluated the prognostic significance of early clinical characteristics in a large, prospective cohort of patients with IE. Methods and Results—Two hundred sixty-seven consecutive patients with definite or possible IE by modified Duke criteria and echocardiography performed within 7 days of presentation were evaluated. Acute physiology was assessed by the Acute Physiology, Age, Chronic Health Evaluation II (APACHE II) score at the time of presentation, and early heart failure was diagnosed by Framingham criteria. In-hospital mortality rate in the cohort was 19% and similar for patients with definite or possible IE (20% versus 16%, respectively; P =0.464). Independent predictors of death determined by logistic regression modeling were diabetes mellitus (OR 2.48; 95% CI, 1.24 to 4.96), Staphylococcus aureus as causative organism (OR, 2.06; 95% CI, 1.01 to 4.20), APACHE II score (OR, 1.07; 95% CI, 1.01 to 1.12), and embolic event (OR, 2.79; 95% CI, 1.15 to 6.80). Early echocardiographic findings of the Duke criteria were not predictive of death. Conclusions—Early in the course of IE, readily available clinical characteristics that reflect the host-pathogen interaction are predictive of in-hospital death. These factors may identify those patients with IE for more aggressive treatment.
Carotid Baroreceptor Stimulation, Sympathetic Activity, Baroreflex Function, and Blood Pressure in Hypertensive Patients

In animals, electric field stimulation of carotid baroreceptors elicits a depressor response through sympathetic inhibition. We tested the hypothesis that the stimulation acutely reduces sympathetic vasomotor tone and blood pressure in patients with drug treatment–resistant arterial hypertension. Furthermore, we tested whether the stimulation impairs the physiological baroreflex regulation. We studied 7 men and 5 women (ages 43 to 69 years) with treatment-resistant arterial hypertension. A bilateral electric baroreflex stimulator at the level of the carotid sinus (Rheos) was implanted ≥1 month before the study. We measured intra-arterial blood pressure, heart rate, muscle sympathetic nerve activity (microneurography), cardiac baroreflex sensitivity (cross-spectral analysis and sequence method), sympathetic baroreflex sensitivity (threshold technique), plasma renin, and norepinephrine concentrations. Measurements were performed under resting conditions, with and without electric baroreflex stimulation, for ≥6 minutes during the same experiment. Intra-arterial blood pressure was 193±9/94±5 mm Hg on medications. Acute electric baroreflex stimulation decreased systolic blood pressure by 32±10 mm Hg (range: +7 to −108 mm Hg; P=0.01). The depressor response was correlated with a muscle sympathetic nerve activity reduction (r2=0.42; P<0.05). In responders, muscle sympathetic nerve activity decreased sharply when electric stimulation started. Then, muscle sympathetic nerve activity increased but remained below the baseline level throughout the stimulation period. Heart rate decreased 4.5±1.5 bpm with stimulation (P<0.05). Plasma renin concentration decreased 20±8% (P<0.05). Electric field stimulation of carotid sinus baroreflex afferents acutely decreased arterial blood pressure in hypertensive patients, without negative effects on physiological baroreflex regulation. The depressor response was mediated through sympathetic inhibition.
Perilesional blood flow and edema formation in acute intracerebral hemorrhage: a SPECT study.

BACKGROUND AND PURPOSE Secondary brain injury and edema formation contribute significantly to morbidity and mortality after intracerebral hemorrhage (ICH). The pathogenesis of this process is poorly understood. We sought to characterize alterations in perilesional blood flow that occur during the acute phase of ICH and to determine whether progressive enlargement of edema surrounding ICH is related to increased or decreased perfusion. METHODS We performed paired consecutive CT and 99mTc-hexamethylpropylenamine oxime single-photon emission computed tomography (SPECT) scans during the acute (mean, 18 hours) and subacute (mean, 72 hours) phase of ICH in 23 patients. Hematoma and edema volumes were traced and calculated from CT images. SPECT-derived hypothetical flow deficit volumes (FDV) around each hematoma were calculated by measuring a "zero-flow" volume within a large perilesional region of interest (based on percent tracer count loss compared with the contralateral side) and subtracting the corresponding ICH volume. Patients with significant midline shift (>5 mm) or global blood flow reduction were excluded from the analysis. RESULTS ICH volume (18 mL) did not change, mean edema volume increased by 36% (from 19 to 25 mL, P<0.0001), and mean FDV decreased by 55% (from 14 to 6 mL, P=0.0004) between the acute and subacute phases. Edema volume on the second CT scan correlated positively with FDV on the first SPECT scan (Spearman's p=0.48, P=0.02), and with the volume of reperfused perilesional tissue (FDVacute-FDVsubacute) (Spearman's p=0.41, P=0.05). Perilesional edema on CT always corresponded topographically with perfusion deficits on SPECT. In 4 patients, delayed focal hyperemia was identified in more peripheral cortical regions, but these areas appeared normal on CT. CONCLUSIONS Perilesional blood flow normalizes from initially depressed levels as edema forms during the first 72 hours after ICH, and the eventual extent of edema correlates with the volume of reperfused tissue. These results suggest that the potential for perilesional ischemia is highest in the earliest hours after ICH onset and implicate reperfusion injury in the pathogenesis of perihematoma edema formation.
Viscosity-Induced Crossing of the Phantom Barrier

We show explicitly, by using astrophysical data plus reasonable assumptions for the bulk viscosity in the cosmic fluid, how the magnitude of this viscosity may be high enough to drive the fluid from its position in the quintessence region at present time t = 0 across the barrier w = −1 into the phantom region in the late universe. The phantom barrier is accordingly not a sharp mathematical divide, but rather a fuzzy concept. We also calculate the limiting forms of various thermodynamical quantities, including the rate of entropy production, for a dark energy fluid near the future Big Rip singularity.
Erythrocyte thiopurine methyl transferase assessment prior to azathioprine use in the UK.

BACKGROUND Individuals with low activity of a key metabolic enzyme, thiopurine methyl transferase (TPMT), are more susceptible to azathioprine-induced myelosuppression. AIM To determine the pattern of use of TPMT activity estimation, with respect to azathioprine use, by medical practitioners in the UK. DESIGN Retrospective analysis of assay use. METHODS We analysed all test results (n=3291), and patient and practitioner details, from inception of TPMT assay in 1990 to the end of December 2000, held at the Purine Research Laboratory, Guy's Hospital, London. Patient details were anonymized. Repeat analyses and requests from outside the UK were excluded. RESULTS The male:female ratio was approximately equal and the mean age was 46.6 (range 0.5-97) years. Thirteen different medical specialities requested assays; Dermatology and Gastroenterology were the most frequent users, together accounting for 86% of requests. The numbers of centres requesting the assay varied widely both within and between different specialities. Some 80% of individuals had normal TPMT activity, 9% enzymic activity above normal, and 10% low activity. Fifteen had no detectable enzymic activity: 0.45% (1:220) of the study population. DISCUSSION This incidence of undetectable enzyme activity is significantly higher than the previously reported level of 1:300 derived from smaller studies, and makes the economics of screening more attractive.
OPA 1 Processing Reconstituted in Yeast Depends on the Subunit Composition of the mAAA Protease in Mitochondria

*Institute for Physiological Chemistry, Ludwig Maximilians University, 81377 Munich, Germany; ‡Institute for Genetics and Center for Molecular Medicine, University of Cologne, D-50674 Cologne, Germany; §Protein Analysis Unit, Ludwig Maximilians University, 80336 Munich, Germany; Division of Biochemistry and Genetics, National Neurological Institute, 20133 Milan, Italy; ¶Institute of Developmental Genetics, Forschungszentrum für Umwelt und Gesundheit–National Research Center for Environment and Health, 85764 Munich-Neuherberg, Germany; and #Department of Neuroscience and Medical Biotechnologies, University of Milano-Bicocca, 20126 Milan, Italy
Elucidation of the genetic and epigenetic landscape alterations in RNA binding proteins in glioblastoma

RNA binding proteins (RBPs) have been implicated in cancer development. An integrated bioinformatics analysis of RBPs (n = 1756) in various datasets (n = 11) revealed several genetic and epigenetically altered events among RBPs in glioblastoma (GBM). We identified 13 mutated and 472 differentially regulated RBPs in GBM samples. Mutations in AHNAK predicted poor prognosis. Copy number variation (CNV), DNA methylation and miRNA targeting contributed to RBP differential regulation. Two sets of differentially regulated RBPs that may be implicated in initial astrocytic transformation and glioma progression were identified. We have also identified a four RBP (NOL3, SUCLG1, HERC5 and AFF3) signature, having a unique expression pattern in glioma stem-like cells (GSCs), to be an independent poor prognostic indicator in GBM. RBP risk score derived from the signature also stratified GBM into low-risk and high-risk groups with significant survival difference. Silencing NOL3, SUCLG1 and HERC5 inhibited GSC maintenance. Gene set enrichment analysis of differentially regulated genes between high-risk and low-risk underscored the importance of inflammation, EMT and hypoxia in high-risk GBM. Thus, we provide a comprehensive overview of genetic and epigenetic regulation of RBPs in glioma development and progression.
Clustering very large multi-dimensional datasets with MapReduce

Given a very large moderate-to-high dimensionality dataset, how could one cluster its points? For datasets that don't fit even on a single disk, parallelism is a first class option. In this paper we explore MapReduce for clustering this kind of data. The main questions are (a) how to minimize the I/O cost, taking into account the already existing data partition (e.g., on disks), and (b) how to minimize the network cost among processing nodes. Either of them may be a bottleneck. Thus, we propose the Best of both Worlds -- BoW method, that automatically spots the bottleneck and chooses a good strategy. Our main contributions are: (1) We propose BoW and carefully derive its cost functions, which dynamically choose the best strategy; (2) We show that BoW has numerous desirable features: it can work with most serial clustering methods as a plugged-in clustering subroutine, it balances the cost for disk accesses and network accesses, achieving a very good tradeoff between the two, it uses no user-defined parameters (thanks to our reasonable defaults), it matches the clustering quality of the serial algorithm, and it has near-linear scale-up; and finally, (3) We report experiments on real and synthetic data with billions of points, using up to 1,024 cores in parallel. To the best of our knowledge, our Yahoo! web is the largest real dataset ever reported in the database subspace clustering literature. Spanning 0.2 TB of multi-dimensional data, it took only 8 minutes to be clustered, using 128 cores.
Mechanical Properties and Wear Behavior of Polypropylene/Carbon Nanotube Nanocomposites

Polypropylene(PP)/carbon nanotube(CNTs) nanocomposites with different CNTs fraction were prepared by the melting blend method. The effects of CNTs content on the wear properties and mechanical properties were mainly investigated. The results show that the friction coefficient of the nanocomposites decreased as the concentration of CNTs is increased. With increasing CNTs content, tensile strength, ultimate strain, compact strength and Young’s modules increase firstly and then decrease. For the composite with an effective CNTs content of 3 wt, its tensile strength, ultimate strain, compact strength and Young's modules were improved by 72, 44.4,88 and 37 %, respectively, as compared to PP.
Olfactory experience shapes the evaluation of odour similarity in ants: a behavioural and computational analysis

Perceptual similarity between stimuli is often assessed via generalization, the response to stimuli that are similar to the one which was previously conditioned. Although conditioning procedures are variable, studies on how this variation may affect perceptual similarity remain scarce. Here, we use a combination of behavioural and computational analyses to investigate the influence of olfactory conditioning procedures on odour generalization in ants. Insects were trained following either absolute conditioning, in which a single odour (an aldehyde) was rewarded with sucrose, or differential conditioning, in which one odour (the same aldehyde) was similarly rewarded and another odour (an aldehyde differing in carbon-chain length) was punished with quinine. The response to the trained odours and generalization to other aldehydes were assessed. We show that olfactory similarity, rather than being immutable, varies with the conditioning procedure. Compared with absolute conditioning, differential conditioning enhances olfactory discrimination. This improvement is best described by a multiplicative interaction between two independent processes, the excitatory and inhibitory generalization gradients induced by the rewarded and the punished odour, respectively. We show that olfactory similarity is dramatically shaped by an individual's perceptual experience and suggest a new hypothesis for the nature of stimulus interactions underlying experience-dependent changes in perceptual similarity.
Peripheral CD8+CD25+ T Lymphocytes from MHC Class II-Deficient Mice Exhibit Regulatory Activity1

We characterized CD8+ T cells constitutively expressing CD25 in mice lacking the expression of MHC class II molecules. We showed that these cells are present not only in the periphery but also in the thymus. Like CD4+CD25+ T cells, CD8+CD25+ T cells appear late in the periphery during ontogeny. Peripheral CD8+CD25+ T cells from MHC class II-deficient mice also share phenotypic and functional features with regulatory CD4+CD25+ T cells: in particular, they strongly express glucocorticoid-induced TNFR family-related gene, CTLA-4 and Foxp3, produce IL-10, and inhibit CD25− T cell responses to anti-CD3 stimulation through cell contacts with similar efficiency to CD4+CD25+ T cells. However, unlike CD4+CD25+ T cells CD8+CD25+ T cells from MHC class II-deficient mice strongly proliferate and produce IFN-γ in vitro in response to stimulation in the absence of exogenous IL-2.
Manure fertilization alters the population of ammonia‐oxidizing bacteria rather than ammonia‐oxidizing archaea in a paddy soil

Manure fertilizers are widely used in agriculture and highly impacted the soil microbial communities such as ammonia oxidizers. However, the knowledge on the communities of archaeal versus bacterial ammonia oxidizers in paddy soil affected by manure fertilization remains largely unknown, especially for a long‐term influence. In present work, the impact of manure fertilization on the population of ammonia oxidizers, related potential nitrification rates (PNRs) and the key factors manipulating the impact were investigated through studying two composite soil cores (long‐term fed with manure fertilization versus undisturbed). Moreover, soil incubated with NH4+ for 5 weeks was designed to verify the field research. The results showed that the copy numbers of bacterial amoA gene in the manure fed soil were significant higher than those in the unfed soil (p < 0.05), suggesting a clear stimulating effect of long‐term manure fertilization on the population of ammonia‐oxidizing bacteria (AOB). The detected PNRs in the manure fed soil core (14–218 nmol L−1 N g−1 h−1) were significant higher than those in the unfed soil core (5–72 nmol L−1 N g−1 h−1; p < 0.05). Highly correlations between the PNRs and the bacterial amoA gene copies rather than archaeal amoA gene were observed, indicating strong nitrification capacity related to bacterial ammonia oxidizers. The NH4+‐N significantly correlated to the abundance of AOB (p < 0.01) and explained 96.1% of the environmental variation, showing the NH4+‐N was the main factor impacting the population of AOB. The incubation experiment demonstrated a clear increase of the bacterial amoA gene abundance (2.0 × 106 to 8.4 × 106 g−1 d.w.s. and 1.6 × 104 to 4.8 × 105 g−1 d.w.s.) in both soil but not for the archaeal amoA gene, in agreement with the field observation. Overall, our results suggested that manure fertilization promoted the population size of bacterial ammonia oxidizers rather than their archaeal counterparts whether in long‐term or short‐term usage and the NH4+‐N was the key impact factor.
A double-sampling pseudo-two-path bandpass /spl Delta//spl Sigma/ modulator

A double-sampling pseudo-two-path bandpass /spl Delta//spl Sigma/ modulator is proposed. This modulator has an output rate equal to twice the clock rate, uses n/2 operational amplifiers (op-amps) for an nth-older noise transfer function, and has reduced clock feedthrough in the signal path band. The required clocks can be simpler to implement than the conventional pseudo-two-path techniques. The measured signal-to-noise ratio and dynamic range of the fourth-order double-sampling pseudo-two-path bandpass /spl Delta//spl Sigma/ modulator in a 30-kHz bandwidth at a center frequency of 2.5 MHz (at a clock frequency of 5 MHz) are 62 and 68 dB, respectively.
Crosslinked SPEEK membranes: Mechanical, thermal, and hydrothermal properties

The thermal and mechanical behavior, the water uptake (WU), and water diffusion coefficient of sulfonated poly(ether ether ketone) (SPEEK) membranes annealed at 180 °C for different times were explored by high-resolution thermogravimetric analysis, mechanical tensile tests, dynamic mechanical analysis, and WU measurements. The mechanical and thermal stability increased with the thermal treatment time, i.e., with the degree of crosslinking. The effect of residual casting solvent, dimethyl sulfoxide (DMSO), on the WU within SPEEK was probed. In presence of residual DMSO, crosslinked SPEEK exhibited higher water sorption at low and medium relative humidity (RH), and lower water sorption at high RH. These membranes have properties well adapted to fuel cell applications.
Sex and boldness explain individual differences in spatial learning in a lizard

Understanding individual differences in cognitive performance is a major challenge to animal behaviour and cognition studies. We used the Eastern water skink (Eulamprus quoyii) to examine associations between exploration, boldness and individual variability in spatial learning, a dimension of lizard cognition with important bearing on fitness. We show that males perform better than females in a biologically relevant spatial learning task. This is the first evidence for sex differences in learning in a reptile, and we argue that it is probably owing to sex-specific selective pressures that may be widespread in lizards. Across the sexes, we found a clear association between boldness after a simulated predatory attack and the probability of learning the spatial task. In contrast to previous studies, we found a nonlinear association between boldness and learning: both ‘bold’ and ‘shy’ behavioural types were more successful learners than intermediate males. Our results do not fit with recent predictions suggesting that individual differences in learning may be linked with behavioural types via high–low-risk/reward trade-offs. We suggest the possibility that differences in spatial cognitive performance may arise in lizards as a consequence of the distinct environmental variability and complexity experienced by individuals as a result of their sex and social tactics.
Preventing HIV among adolescents with oral PrEP: observations and challenges in the United States and South Africa

Adolescents and young adults aged <25 are a key population in the HIV epidemic, with very high HIV incidence rates in many geographic settings and a large number who have limited access to prevention services. Thus, any biomedical HIV prevention approach should prepare licensure and implementation strategies for young populations. Oral pre‐exposure prophylaxis (PrEP) is the first antiretroviral‐based prevention intervention with proven efficacy across many settings and populations, and regulatory and policy approvals at global and national levels are occurring rapidly. We discuss available data from studies in the United States and South Africa on the use of oral PrEP for HIV prevention in adolescent minors, along with some of the implementation challenges.