Miracle-dz/UniFAR-FTUs huggingface dataset:
Neurofibrillary tangle-bearing neurons are functionally integrated in cortical circuits in vivo

Significance Alzheimer's disease is pathologically characterized by extracellular amyloid-β plaques and intracellular neurofibrillary tangles (NFTs). It has long been assumed that the accumulation of tau into NFTs causes neuronal dysfunction and death, and is a proximate cause of dementia in patients with Alzheimer’s disease. This assumption underlies the NFT-busting drugs currently in clinical trials and research efforts aimed at understanding tau aggregation. Our study tested the dogma that NFT-bearing neurons are indeed impaired in their ability to respond to complex sensory stimuli. Using two-photon imaging in awake mice with NFT pathology, we found that individual neurons with NFTs respond to visual stimuli and do not impair local circuits. These unexpected results suggest that the presence of an NFT does not inevitably lead to gross physiological alterations. Alzheimer's disease (AD) is pathologically characterized by the deposition of extracellular amyloid-β plaques and intracellular aggregation of tau protein in neurofibrillary tangles (NFTs) (1, 2). Progression of NFT pathology is closely correlated with both increased neurodegeneration and cognitive decline in AD (3) and other tauopathies, such as frontotemporal dementia (4, 5). The assumption that mislocalization of tau into the somatodendritic compartment (6) and accumulation of fibrillar aggregates in NFTs mediates neurodegeneration underlies most current therapeutic strategies aimed at preventing NFT formation or disrupting existing NFTs (7, 8). Although several disease-associated mutations cause both aggregation of tau and neurodegeneration, whether NFTs per se contribute to neuronal and network dysfunction in vivo is unknown (9). Here we used awake in vivo two-photon calcium imaging to monitor neuronal function in adult rTg4510 mice that overexpress a human mutant form of tau (P301L) and develop cortical NFTs by the age of 7–8 mo (10). Unexpectedly, NFT-bearing neurons in the visual cortex appeared to be completely functionally intact, to be capable of integrating dendritic inputs and effectively encoding orientation and direction selectivity, and to have a stable baseline resting calcium level. These results suggest a reevaluation of the common assumption that insoluble tau aggregates are sufficient to disrupt neuronal function.
Role of CD152 genetic polymorphisms in the susceptibility to breast cancer

Background The polymorphisms in cluster of differentiation 152 (CD152) gene have been reported to be associated with breast cancer (BC), but relevant findings were far from conclusive. Therefore, we carried out this meta-analysis to combine those results for a clearer perspective on this issue. Results In our meta-analysis, a total of 8 eligible publications of 19 case-control studies were selected, which totally contained 7,442 BC cases and 7,376 normal controls. Among the five polymorphisms of CD152 gene, +49 G/A, −1661 A/G and −318 C/T significantly increased the risk of BC under corresponding genetic comparisons; while CT60 G/A polymorphism was negatively related to the cancer susceptibility. In addition, −1772 T/C polymorphism of CD152 gene was not associated with the development of BC. Materials and methods Online databases and other sources were searched for published studies on the relationship between BC susceptibility and CD152 polymorphisms (+49 G/A, −1661 A/G, −1722 T/C, −318 C/T and CT60 G/A). The strength of association was evaluated with pooled odds ratios (ORs) and their corresponding 95% confidence intervals (95% CIs). Heterogeneity evaluation was conducted via Q test. Sensitivity analysis was used to detect the stability of our results. Begg's funnel plot and Egger's test were applied to investigate publication bias among selected studies. Conclusions The polymorphisms +49 G/A, −1661 A/G and −318 C/T may elevate the susceptibility to BC, but the polymorphism CT60 G/A may offer protection against the cancer.
Partial discharge and dielectric response behaviour of insulation systems for high voltage rotating machines under electrical stress

In order to understand how the partial discharge (PD), dissipation factor and dielectric response measurements can reflect the changes in the groundwall insulation of high voltage rotating machines due to electrical stress, which lead to insulation degradation, an electrical stress has been applied to the insulation systems of high voltage rotating machines and the change of PD pattern, dissipation factor as a function of the applied test voltage and dielectric response in the time and frequency domain were studied. As test objects, actual stator bars were used, which are based on the epoxy VPI technology, according to the manufacturer's standard.
Within-Range Translocations and Their Consequences in European Larch

In contrast to biological invasions, translocations of individuals within a species range are understudied, due to difficulties in systematically detecting them. This results in limited knowledge about the corresponding processes and uncertainties regarding the status of extant populations. European larch, a forest tree whose fragmented native distribution is restricted to the Alps and to other Central European mountains, has been massively planted for at least 300 years. Here we focus on the genetic characterization of translocations having taken place within its native range. Microsatellite variation at 13 nuclear loci and sequence data of two mitochondrial DNA fragments were analyzed on the basis of a comprehensive range-wide population sample. Two complementary methods (Geneclass and Structure) were used to infer translocation events based on nuclear data whereas mitochondrial data were used for validation of these inferences. Using Geneclass, we found translocation events in a majority of populations. Additional cases of translocation and many instances of admixture were identified using Structure, thanks to the clear-cut ancestral genetic structure detected in this species. In particular, a strong divide between Alpine and Central European populations, also apparent at mitochondrial markers, helped uncover details on translocation events and related processes. Translocations and associated admixture events were found to be heterogeneously distributed across the species range, with a particularly high frequency in Central Europe. Furthermore, translocations frequently involved multiple geographic sources, some of which were over-represented. Our study illustrates the importance of range-wide investigations for tracing translocations back to their origins and for revealing some of their consequences. It provides some first clues for developing suitable conservation and management strategies.
Visual function in menopause: the role of hormone replacement therapy

Objective To assess the effects of hormone replacement therapy (HRT) on visual function after menopause. Design This study was conducted on 80 postmenopausal women aged 52 to 70 years. Women were randomly divided into two groups: 40 women were treated by oral HRT (equine conjugated estrogens 0.625 mg/day + dydrogesterone 5 mg/day in a continuous combined regimen), and 40 women were not treated with hormones (control group). Each woman underwent a contrast sensitivity test, a Schirmer test, and an evaluation of intraocular pressure before starting the study and 1 year after the beginning of the study. Statistical analysis was performed by Student's t test and Fisher's exact test. Results Contrast sensitivity function was significantly improved in all spatial frequencies (1.5, 3, 6, and 12 cycles per degree) with the exception of 18 cycles per degree in the HRT group 1 year after the beginning of treatment, whereas the control group demonstrated significant impairment at the lowest spatial frequencies (1.5, 3, and 6 cycles per degree). Tear production was significantly improved in the HRT group 1 year after the beginning of treatment, and intraocular pressure was similar in the two groups before and after the beginning of the study. Conclusions HRT improves visual function, promoting a better contrast sensitivity and a higher tear production, but does not modify intraocular pressure.
Monoclonal antibodies to the spike protein of feline infectious peritonitis virus mediate antibody-dependent enhancement of infection of feline macrophages

Antibody-dependent enhancement of virus infection is a process whereby virus-antibody complexes initiate infection of cells via Fc receptor-mediated endocytosis. We sought to investigate antibody-dependent enhancement of feline infectious peritonitis virus infection of primary feline peritoneal macrophages in vitro. Enhancement of infection was assessed, after indirect immunofluorescent-antibody labelling of infected cells, by determining the ratio between the number of cells infected in the presence and absence of virus-specific antibody. Infection enhancement was initially demonstrated by using heat-inactivated, virus-specific feline antiserum. Functional compatibility between murine immunoglobulin molecules and feline Fc receptors was demonstrated by using murine anti-sheep erythrocyte serum and an antibody-coated sheep erythrocyte phagocytosis assay. Thirty-seven murine monoclonal antibodies specific for the nucleocapsid, membrane, or spike proteins of feline infectious peritonitis virus or transmissible gastroenteritis virus were assayed for their ability to enhance the infectivity of feline infectious peritonitis virus. Infection enhancement was mediated by a subset of spike protein-specific monoclonal antibodies. A distinct correlation was seen between the ability of a monoclonal antibody to cause virus neutralization in a routine cell culture neutralization assay and its ability to mediate infection enhancement of macrophages. Infection enhancement was shown to be Fc receptor mediated by blockade of antibody-Fc receptor interaction using staphylococcal protein A. Our results are consistent with the hypothesis that antibody-dependent enhancement of feline infectious peritonitis virus infectivity is mediated by antibody directed against specific sites on the spike protein.
Decision Support Alerts for Medication Ordering in a Computerized Provider Order Entry (CPOE) System

Summary Objective: We sought to determine the frequency and type of decision support alerts by location and ordering provider role during Computerized Provider Order Entry (CPOE) medication ordering. Using these data we adjusted the decision support tools to reduce the number of alerts. Design: Retrospective analyses were performed of dose range checks (DRC), drug-drug interaction and drug-allergy alerts from our electronic medical record. During seven sampling periods (each two weeks long) between April 2006 and October 2008 all alerts in these categories were analyzed. Another audit was performed of all DRC alerts by ordering provider role from November 2008 through January 2009. Medication ordering error counts were obtained from a voluntary error reporting system. Measurement/Results: Between April 2006 and October 2008 the percent of medication orders that triggered a dose range alert decreased from 23.9% to 7.4%. The relative risk (RR) for getting an alert was higher at the start of the interventions versus later (RR= 2.40, 95% CI 2.28-2.52; p< 0.0001). The percentage of medication orders that triggered alerts for drug-drug interactions also decreased from 13.5% to 4.8%. The RR for getting a drug interaction alert at the start was 1.63, 95% CI 1.60-1.66; p< 0.0001. Alerts decreased in all clinical areas without an increase in reported medication errors. Conclusion: We reduced the quantity of decision support alerts in CPOE using a systematic approach without an increase in reported medication errors
Duet

Load balancing is a foundational function of datacenter infrastructures and is critical to the performance of online services hosted in datacenters. As the demand for cloud services grows, expensive and hard-to-scale dedicated hardware load balancers are being replaced with software load balancers that scale using a distributed data plane that runs on commodity servers. Software load balancers offer low cost, high availability and high flexibility, but suffer high latency and low capacity per load balancer, making them less than ideal for applications that demand either high throughput, or low latency or both. In this paper, we present Duet, which offers all the benefits of software load balancer, along with low latency and high availability -- at next to no cost. We do this by exploiting a hitherto overlooked resource in the data center networks -- the switches themselves. We show how to embed the load balancing functionality into existing hardware switches, thereby achieving organic scalability at no extra cost. For flexibility and high availability, Duet seamlessly integrates the switch-based load balancer with a small deployment of software load balancer. We enumerate and solve several architectural and algorithmic challenges involved in building such a hybrid load balancer. We evaluate Duet using a prototype implementation, as well as extensive simulations driven by traces from our production data centers. Our evaluation shows that Duet provides 10x more capacity than a software load balancer, at a fraction of a cost, while reducing latency by a factor of 10 or more, and is able to quickly adapt to network dynamics including failures.
Orbital magnetization in crystalline solids: Multi-band insulators, Chern insulators, and metals

We derive a multi-band formulation of the orbital magnetization in a normal periodic insulator (i.e., one in which the Chern invariant, or in two dimensions (2D) the Chern number, vanishes). Following the approach used recently to develop the single-band formalism [Thonhauser, Ceresoli, Vanderbilt, and Resta, Phys. Rev. Lett. 95, 137205 (2005)], we work in the Wannier representation and find that the magnetization is comprised of two contributions, an obvious one associated with the internal circulation of bulklike Wannier functions in the interior and an unexpected one arising from net currents carried by Wannier functions near the surface. Unlike the single-band case, where each of these contributions is separately gauge invariant, in the multi-band formulation only the sum of both terms is gauge invariant. Our final expression for the orbital magnetization can be rewritten as a bulk property in terms of Bloch functions, making it simple to implement in modern code packages. The reciprocal-space expression is evaluated for 2D model systems and the results are verified by comparing to the magnetization computed for finite samples cut from the bulk. Finally, while our formal proof is limited to normal insulators, we also present a heuristic extension to Chern insulators (having nonzero Chern invariant) and to metals. The validity of this extension is again tested by comparing to the magnetization of finite samples cut from the bulk for 2D model systems. We find excellent agreement, thus providing strong empirical evidence in favor of the validity of the heuristic formula.
Scilla: a Smart Contract Intermediate-Level LAnguage

This paper outlines key design principles of Scilla---an intermediate-level language for verified smart contracts. Scilla provides a clean separation between the communication aspect of smart contracts on a blockchain, allowing for the rich interaction patterns, and a programming component, which enjoys principled semantics and is amenable to formal verification. Scilla is not meant to be a high-level programming language, and we are going to use it as a translation target for high-level languages, such as Solidity, for performing program analysis and verification, before further compilation to an executable bytecode. We describe the automata-based model of Scilla, present its programming component and show how contract definitions in terms of automata streamline the process of mechanised verification of their safety and temporal properties.
GaN Photonic-Crystal Surface-Emitting Laser at Blue-Violet Wavelengths

Shorter-wavelength surface-emitting laser sources are important for a variety of fields, including photonics, information processing, and biology. We report on the creation of a current-driven blue-violet photonic-crystal surface-emitting laser. We have developed a fabrication method, named “air holes retained over growth,” in order to construct a two-dimensional gallium nitride (GaN)/air photonic-crystal structure. The resulting periodic structure has a photonic-crystal band-edge effect sufficient for the successful operation of a current-injection surface-emitting laser. This represents an important step in the development of laser sources that could be focused to a size much less than the wavelength and be integrated two-dimensionally at such short wavelengths.
Effectiveness of computerized cognitive rehabilitation training on symptomatological, neuropsychological and work function in patients with schizophrenia

There has been plenty of interest in cognitive rehabilitation for schizophrenia here in Korea since the year 2000. But the efficacy studies of cognitive remediation intervention are still deficient. The primary purpose of this study was to develop a computer‐assisted cognitive remediation program and conduct a clinical trial in a group of schizophrenic patients.
Five-Member Gene Family of Bartonella quintana

ABSTRACT Bartonella quintana, the agent of trench fever and an etiologic agent of bacillary angiomatosis, has an extraordinarily high hemin requirement for growth compared to other bacterial pathogens. We previously identified the major hemin receptor of the pathogen as a 30-kDa surface protein, termed HbpA. This report describes four additional homologues that share approximately 48% amino acid sequence identity with hbpA. Three of the genes form a paralagous cluster, termed hbpCAB, whereas the other members, hbpD and hbpE, are unlinked. Secondary structure predictions and other evidence suggest that Hbp family members are β-barrels located in the outer membrane and contain eight transmembrane domains plus four extracellular loops. Homologs from a variety of gram-negative pathogens were identified, including Bartonella henselae Pap31, Brucella Omp31, Agrobacterium tumefaciens Omp25, and neisserial opacity proteins (Opa). Family members expressed in vitro-synthesized proteins ranging from ca. 26.5 to 35.1 kDa, with the exception of HbpB, an ∼55.9-kDa protein whose respective gene has been disrupted by a ∼510 GC-rich element containing variable-number tandem repeats. Transcription analysis by quantitative reverse transcriptase-PCR (RT-PCR) indicates that all family members are expressed under normal culture conditions, with hbpD and hbpB transcripts being the most abundant and the rarest, respectively. Mutagenesis of hbpA by allelic exchange produced a strain that exhibited an enhanced hemin-binding phenotype relative to the parental strain, and analysis by quantitative RT-PCR showed elevated transcript levels for the other hbp family members, suggesting that compensatory expression occurs.
Parental Education and Family Characteristics: Educational Opportunities Across Cohorts in Italy and Spain

Drawing on data contained in the 2005 EU-SILC, this paper investigates the disparities in educational opportunities in Italy and Spain. Its main objective is to analyse the predicted probabilities of successfully completing upper-secondary and tertiary education for individuals with different parental backgrounds, and the changes in these probabilities across birth cohorts extending from 1940 to 1980. The results suggest that the disparities in tertiary education opportunities in Italy tend to increase over time. By contrast, the gap in educational opportunity in Spain shows a marked decrease across the cohorts. Moreover, by using an intuitive decomposition strategy, the paper shows that a large part of the educational gap between individuals of different backgrounds is �composed� of the difference in the endowment of family characteristics. Specifically, it seems that more highly educated parents are more able to endow their children with a better composition of family characteristics, which accounts for a significant proportion of the disparities in educational opportunity
Prognostic value of venoarterial carbon dioxide gradient in patients with severe sepsis and septic shock.

AIM To investigate the changes in the venoarterial carbon-dioxide gradient (V-a Pco(2)) and its prognostic value for survival of patients with severe sepsis and septic shock. METHODS The study was conducted in General Hospital Holy Spirit from January 2004 to December 2007 and included 71 conveniently sampled adult patients (25 women and 46 men), who fulfilled the severe sepsis and septic shock criteria and were followed for a median of 8 days (interquartile range, 12 days). The patients were divided in two groups depending on whether or not they had been mechanically ventilated. Both groups of patients underwent interventions with an aim to achieve hemodynamic stability. Mechanical ventilation was applied in respiratory failure. Venoarterial carbon dioxide gradient was calculated from the difference between the partial pressure of arterial CO(2) and the partial pressure of mixed venous CO(2), which was measured with a pulmonary arterial Swan-Ganz catheter. The data were analyzed using Kaplan-Meier survival analysis, along with a calculation of the hazard ratios. RESULTS There was a significant difference between non-ventilated and ventilated patients, with almost 4-fold greater hazard ratio for lethal outcome in ventilated patients (3.85; 95% confidence interval, 1.64-9.03). Furthermore, the pattern of changes of many other variables was also different in these two groups (carbon dioxide-related variables, variables related to acid-base status, mean arterial pressure, systemic vascular resistance, lactate, body mass index, Acute Physiology and Chronic Health Evaluation II, Simplified Acute Physiology II Score, and Sepsis-related Organ Failure Assessment score). Pco(2) values (with a cut-off of 0.8 kPa) were a significant predictor of lethal outcome in non-ventilated patients (P=0.015) but not in ventilated ones (P=0.270). CONCLUSION V-a Pco(2) was a significant predictor of fatal outcome only in the non-ventilated group of patients. Ventilated patients are more likely to be admitted with a less favorable clinical status, and other variables seem to have a more important role in their outcome.
Dyadic Profiles of Parental Disciplinary Behavior and Links With Parenting Context

Using data from couples (N = 1,195) who participated in a large community-based study of families, we used maternal reports of parental discipline to examine mothers’ and fathers’ use of and patterns related to aggressive and nonviolent discipline of their 3-year-old child. First, we separately examined mothers’ and fathers’ patterns, or classes, of disciplinary behaviors. Second, we identified joint mother–father class profiles. Maternal reports indicated that the patterns among fathers and mothers were similar, but fathers were more likely to be in the low-aggression classes than mothers; and mothers were more likely to be in the high-aggression classes than fathers. Dyads in which both parents employed high levels of aggressive discipline were characterized by higher parenting stress, poorer parental relationship, and lower quality community context. The majority (81.2%) of dyads used congruent disciplinary behaviors. Discordant dyads were similar to dyads in which both parents were high in aggressive discipline, in that these groups had children with the highest levels of aggressive behavior. Implications highlight the need to target both mothers and fathers with parent education efforts to reinforce positive parenting.