Miracle-dz/UniFAR-FTUs huggingface dataset:
Major histocompatibility complex heterozygosity enhances reproductive success

We investigated how heterozygosity at the major histocompatibility complex (MHC) affects fitness in wild‐derived (F2) house mice (Mus musculus musculus). To compare and control for potential confounding effects from close inbreeding and genome‐wide heterozygosity, we used mice that were systematically outbred. We assessed how heterozygosity at MHC and background loci (using 15 microsatellite markers on 11 different chromosomes) affects individual survival and reproductive success (RS) in large, semi‐natural population enclosures. We found that overall heterozygosity significantly increased RS, and this correlation was entirely explained by heterozygosity at two MHC loci. Moreover, we found that the effects of MHC heterozygosity depend on the level of background heterozygosity, and the benefits of maximal MHC heterozygosity show a curvilinear effect with increasing background heterozygosity. The enhanced RS from MHC heterozygosity was not because of increased survival, and although MHC heterozygosity was correlated with body mass, body mass did not correlate with RS when heterozygosity is controlled. Breeders were more MHC heterozygous than nonbreeders for both sexes, indicating that MHC heterozygosity enhanced fecundity, mating success or both. Our results show that (i) MHC heterozygosity enhances fitness among wild, outbred as well as congenic laboratory mice; (ii) heterozygosity–fitness correlations can potentially be explained by a few loci, such as MHC; (iii) MHC heterozygosity can increase fitness, even without affecting survival, by increasing mating and RS; and (iv) MHC effects depend on background genes, and maximal MHC heterozygosity is most beneficial at intermediate or optimal levels of background heterozygosity.
Perspective on architecture and assembly of membrane contact sites

Membrane contact sites (MCS) are platforms of physical contact between different organelles. They are formed through interactions involving lipids and proteins, and function in processes such as calcium and lipid exchange, metabolism and organelle biogenesis. In this article, we discuss emerging questions regarding the architecture, organisation and assembly of MCS, such as: What is the contribution of different components to the interaction between organelles? How is the specific composition of different types of membrane contacts sites established and maintained? How are proteins and lipids spatially organised at MCS and how does that influence their function? How dynamic are MCS on the molecular and ultrastructural level? We highlight current state of research and point out experimental approaches that promise to contribute to a spatiomechanistic understanding of MCS functions.
Methamphetamine-like discriminative stimulus effects of bupropion and its two hydroxy metabolites in male rhesus monkeys

The dopamine transporter (DAT) inhibitor and nicotinic acetylcholine (nACh) receptor antagonist bupropion is being investigated as a candidate ‘agonist’ medication for methamphetamine addiction. In addition to its complex pharmacology, bupropion also has two distinct pharmacologically active metabolites. However, the mechanism by which bupropion produces methamphetamine-like ‘agonist’ effects remains unknown. The aim of the present study was to determine the role of DAT inhibition, nACh receptor antagonism, and the hydroxybupropion metabolites in the methamphetamine-like discriminative stimulus effects of bupropion in rhesus monkeys. In addition, varenicline, a partial agonist at the nACh receptor, and risperidone, a dopamine antagonist, were tested as controls. Monkeys (n=4) were trained to discriminate 0.18 mg/kg intramuscular methamphetamine from saline in a two-key food-reinforced discrimination procedure. The potency and time course of methamphetamine-like discriminative stimulus effects were determined for all compounds. Bupropion, methylphenidate, and 2S,3S-hydroxybupropion produced full, at least 90%, methamphetamine-like effects. 2R,3R-Hydroxybupropion, mecamylamine, and nicotine also produced full methamphetamine-like effects, but drug potency was more variable between monkeys. Varenicline produced partial methamphetamine-like effects, whereas risperidone did not. Overall, these results suggest DAT inhibition as the major mechanism of the methamphetamine-like ‘agonist’ effects of bupropion, although nACh receptor antagonism appeared, at least partially, to contribute. Furthermore, the contribution of the 2S,3S-hydroxybupropion metabolite could not be completely ruled out.
Brain mechanisms of speech perception: A preliminary report

David Pesetsky,Ken Wexler, Elron Yellin: Massachusetts Institute of TechnologyDavid Poeppel, Tim Roberts, Howard Rowley: University of California,San Francisco1. IntroductionThis paper is a progress report on our work on speech perception usingbrain imaging techniques. We review our goals, methods, and two experimentalparadigms we have used to study classic categorical perception effects, like theone illustrated in Figure 1. This graph illustrates one subject’s identification ofstimuli from a synthesized /dae/–/tae/ continuum.
An efficient conversion of quantum circuits to a linear nearest neighbor architecture

Several promising implementations of quantum computation rely on a Linear NearestNeighbor (LNN) architecture, which arranges quantum bits on a line, and allows neighborinteractions only. Therefore, several specific circuits have been designed on an LNNarchitecture. However, a general and efficient conversion method for an arbitrary circuithas not been established. Therefore, this paper gives an efficient conversion technique toconvert quantum circuits to an LNN architecture. When a quantum circuit is convertedto an LNN architecture, the objective is to reduce the size of the additional circuit addedby the conversion and the time complexity of the conversion. The proposed methodrequires less additional circuitry and time complexity compared with naive techniques.To develop the method, we introduce two key theorems that may be interesting on theirown. In addition, the proposed method also achieves less overhead than some knowncircuits designed from scratch on an LNN architecture.
Nonlinear dynamics and fluctuations in biological systems

Inspired by the coordinated beating of the flagellar pair of the green algae Chlamydomonas, we study theoretically a simple, mirror-symmetric swimmer, which propels itself at low Reynolds number by a revolving motion of a pair of spheres. We show that perfect synchronization between these two driven spheres can occur due to the motion of the swimmer and local hydrodynamic friction forces. Hydrodynamic interactions, though crucial for net propulsion, contribute little to synchronization for this free-moving swimmer. B. M. Friedrich, F. Jülicher: Flagellar synchronization independent of hydrodynamic interactions. Phys. Rev. Lett. 109(13), 138102, 2012 http://journals.aps. org/prl/abstract/10.1103/PhysRevLett.109. 138102
MukEF Is Required for Stable Association of MukB with the Chromosome

ABSTRACT MukB is a bacterial SMC(structural maintenance of chromosome) protein required for correct folding of the Escherichia coli chromosome. MukB acts in complex with the two non-SMC proteins, MukE and MukF. The role of MukEF is unclear. MukEF disrupts MukB-DNA interactions in vitro. In vivo, however, MukEF stimulates MukB-induced DNA condensation and is required for the assembly of MukB clusters at the quarter positions of the cell length. We report here that MukEF is essential for stable association of MukB with the chromosome. We found that MukBEF forms a stable complex with the chromosome that copurifies with nucleoids following gentle cell lysis. Little MukB could be found with the nucleoids in the absence or upon overproduction of MukEF. Similarly, overproduced MukEF recruited MukB-green fluorescent protein (GFP) from its quarter positions, indicating that formation of MukB-GFP clusters and stable association with the chromosome could be mechanistically related. Finally, we report that MukE-GFP forms foci at the quarter positions of the cell length but not in cells that lack MukB or overproduce MukEF, suggesting that the clusters are formed by MukBEF and not by its individual subunits. These data support the view that MukBEF acts as a macromolecular assembly, a scaffold, in chromosome organization and that MukEF is essential for the assembly of this scaffold.
Path-based next trace prediction

The trace cache is proposed as a mechanism for providing increased fetch bandwidth by allowing the processor to fetch across multiple branches in a single cycle. But to date predicting multiple branches per cycle has meant paying a penalty in prediction accuracy. We propose a next trace predictor that treats the traces as basic units and explicitly predicts sequences of traces. The predictor collects histories of trace sequences (paths) and makes predictions based on these histories. The basic predictor is enhanced to a hybrid configuration that reduces performance losses due to cold starts and aliasing in the prediction table. The Return History Stack is introduced to increase predictor performance by saving path history information across procedure call/returns. Overall, the predictor yields about a 26% reduction in misprediction rates when compared with the most aggressive previously proposed, multiple branch prediction methods.
The dynamic nature of polyploid genomes.

It is well known that polyploidy is a major force in evolution, particularly in plants. Perhaps 50% of all angiosperms are of polyploid origin; estimates for the ferns and fern allies range from 44 to 95% (1, 2). Because of the significant role that it has played in plant evolution, polyploidy has been the focus of great interest and controversy for >50 years. Diverse aspects of polyploidy have been reviewed, including types of polyploids (3-8), ecological and evolutionary attributes of polyploids (810), genetic consequences of polyploid evolution (10-17), and mode of polyploid formation (4, 18, 19). The application of molecular techniques has dramatically increased our understanding of polyploid evolution and has fundamentally reshaped traditional views. The paper by Song et al. (20) in this journal further elucidates the process of polyploid evolution and represents a key breakthrough in our understanding of the evolution of polyploid genomes. To appreciate the great significance of the paper by Song et al. (20), it is important to consider briefly some of the traditional tenets of polyploid evolution.
HEMOSTASIS , THROMBOSIS , AND VASCULAR BIOLOGY 3-Dimensional structure of membrane-bound coagulation factor VIII : modeling of the factor VIII heterodimer within a 3-dimensional density map derived by electron crystallography

Despite recent studies, the organization of coagulation factor VIII (FVIII) on a phospholipid (PL) membrane is not known in detail. Thus, 2-dimensional (2D) crystals of human FVIII lacking the B domain were prepared for electron microscopy onto negatively charged PL monolayers. The 3-dimensional (3D) density map of the PL-bound FVIII protein was calculated at 1.5 nm. Existing atomic data and models for FVIII domains were fitted unambiguously within the 3D density map of the molecule. FVIII domains arrangement followed a compact spiral organization with the A3 domains in close association with the C1 and C2 domains near the PL surface. Viewed toward the membrane the A domains’ heterotrimer is oriented side-on with the pseudo–3-fold axis almost parallel to the PL surface and A1 fully covering C1. The C2 domain is partially overlapped by the A2 domain of an adjacent molecule in the 2D crystal, favoring close packing. Viewed parallel to the membrane, C2 is slightly inclined to the PL surface covering an area of 12 nm 2. Four C2 loops are embedded within the lipid monolayer at about 0.7 to 1.0 nm depth. C1 forms almost a right angle with C2, its long axis nearly parallel to the membrane. The proposed structure for membrane-bound FVIII results from modeling of the FVIII domains within a 3D density map obtained from electron crystallography and accords with the main biochemical and structural information known to date. A model is proposed for FVIIIa and factor IXa assembly within the membrane-bound factor X-activating complex. (Blood. 2002; 99:1215-1223)
Dopamine‐Mediated Inhibition of Renal Na,K‐ATPase Is Reduced by Insulin

Abstract— Recently we have reported that rosiglitazone treatment of obese Zucker rats reduced plasma insulin and restored the ability of dopamine to inhibit Na,K‐ATPase (NKA) in renal proximal tubules. The present study was performed to test the hypothesis that a chronic increase in levels of insulin causes a decrease in expression of the D1 receptor and its uncoupling from G proteins, which may account for the diminished inhibitory effect of dopamine on NKA in obese Zucker rats. We conducted experiments in primary proximal tubule epithelial cells obtained from Sprague‐Dawley rat kidneys. These cells at 80% to 90% confluence were pretreated with insulin (100 nmol/L for 24 hours) in growth factor–/serum‐free medium. SKF‐38393, a D1 receptor agonist, inhibited NKA activity in untreated cells, but the agonist failed to inhibit enzyme activity in insulin‐pretreated cells. Basal NKA activity was similar in untreated and insulin‐pretreated cells. Measurement of D1 receptors in the plasma membranes revealed that [3H]SCH‐23390 binding, a D1 receptor ligand, as well as D1 receptor protein abundance, was significantly reduced in insulin‐pretreated cells compared with untreated cells. SKF‐38393 (10 &mgr;mol/L) elicited significant stimulation of [35S]GTP[gamma]S binding in the membranes from control cells, suggesting that the D1 receptor–G protein coupling was intact. However, the stimulatory effect of SKF‐38393 was absent in membranes from insulin‐pretreated cells. We suggest that chronic exposure of cells to insulin causes both the reduction in D1 receptor abundance and its uncoupling from G proteins. These phenomena might account for the diminished inhibitory effect of dopamine on NKA activity in hyperinsulinemic rats.
Performance evaluation of a new adaptive packet marking scheme for TCP over DiffServ networks

In differentiated services (DiffServ) networks, packets may receive a different treatment according to their differentiated services code point (DSCP) label. As a consequence, packet marking schemes can be devised to differentiate packets belonging to the same TCP flow, with the goal of improving the experienced performance. The paper presents an extensive performance evaluation of a new adaptive packet marking scheme, applied to a traffic scenario composed of TCP flows with different lengths. The proposed marking scheme is most efficient when applied to a scenario composed of all long-lived flows. In a realistic mixed traffic scenario, composed of both long-lived and short-lived TCP flows, our marking scheme provides excellent performance in high utilization conditions, and still provides improved performance in medium utilization conditions, comparable with that achieved by a recently proposed marking algorithm specifically devised for short-lived flows. We also propose a "three colors" marking scheme, which merges this approach with ours to achieve improved performance in all utilization conditions.
Performance analysis of cellular mobile communication networks supporting multimedia services

This paper illustrates the development of an analytical model for a communication network providing integrated services to a population of mobile users, and presents performance results to both validate the analytical approach, and assess the quality of the services offered to the end users. The analytical model is based on continuous‐time multidimensional birth–death processes, and is focused on just one of the cells in the network. The cellular system is assumed to provide three classes of service: the basic voice service, a data service with bit rate higher than the voice service, and a multimedia service with one voice and one data component. In order to improve the overall network performance, some channels can be reserved to handovers, and multimedia calls that cannot complete a handover are decoupled, by transferring to the target cell only the voice component and suspending the data connection until a sufficient number of channels become free. Numerical results demonstrate the accuracy of the approximate model, as well as the effectiveness of the newly proposed multimedia call decoupling approach.
Effects of Etching and Chemo-Mechanical Polishing on the Electrical Properties of CdZnTe Nuclear Detectors

Chemical etching and chemo-mechanical polishing are techniques used to remove surface defects and damages caused by cutting and mechanical polishing of cadmium zinc telluride (CdZnTe) nuclear detector materials. Etching and chemo-mechanical polishing processes often form thin films on the surfaces of the CdZnTe wafers. While several studies have been done on etching and chemo-mechanical polishing using different chemicals, there is a lack of reporting on the uses of the same chemical solution to study the effects of these two-surface processing techniques. This paper focuses on comparing the effects of chemical etching and chemo-mechanical polishing on the electrical properties of CdZnTe detectors using the same chemical solution: bromine-methanol-ethylene glycol. Three CdZnTe samples were cut from the same region of the ingot, mechanically polished, and used to studying the two surface processing techniques. The current-voltage experiments on the samples gave a measured bulk resistivity of 2.6 x 1010 Ω-cm for mechanical polishing, 1.6 x 1010 Ω-cm for chemical etching, and 3.5 x 1010 Ω-cm for chemo-mechanical polishing. The variations in the measured resistivity for the different surface processing techniques are due to the additional contribution of surface currents to the measured bulk current. The spectral response measurements of the 59.5-keV peak of Am-241 gave a full-width-at-half-maximum (FWHM) of 30.4%, 20.7%, and 30.8% for the mechanical polishing, chemical etching, and chemo-mechanical polishing respectively. In this study, the chemo-mechanical polishing process resulted in a lower measured bulk current. The chemical etching process gave a better spectral resolution (FWHM = 20.7%), and a higher charge-carrier mobility–lifetime product of 0.86 x 10-3 cm2/V compared to 0.62 x 10-3 cm2/V and 0.64 x 10-3 cm2/V for mechanical and chemo-mechanical polishing processes respectively.
Characterization of Upper Eyelid Tarsus and Lid Wiper Dimensions

Objectives: To measure various dimensions of the upper tarsal plate and the area of upper lid wiper staining. The repeatability of the method of measurement was investigated. Methods: Thirty-five healthy non–contact lens wearers were enrolled. The following parameters were measured from digital images of the upper eyelid captured with a slitlamp camera: length, height, and total area of the tarsal plate and area of lid wiper staining (lissamine green). Measurements were performed in a randomized and masked fashion on two separate occasions by the same investigator using ImageJ (National Institutes of Health). Coefficients of repeatability (COR) were calculated. Results: The dimensions (mean±SD) of the tarsal plate were 20.6±1.9 mm length, 7.9±0.8 mm height, and 103.3±18.8 mm2 total area. The area of lid wiper staining was 2.7±2.0 mm2. No association was found between tarsal dimensions and lid wiper staining (all P>0.05). Image analysis COR values were 0.6 mm tarsal length, 0.1 mm tarsal height, 1.2 mm2 tarsal area, and 0.4 mm2 lid wiper staining. There was no significant difference between repeated measurements for any parameter (all P>0.05). Limits of agreement were narrow for all parameters, indicating good agreement between repeated measurements. Conclusions: This work has demonstrated that there is a wide range in the dimensions of the upper tarsal plate in an urban UK population. No association was found between the upper tarsal dimensions and lid wiper staining. ImageJ was shown to be a repeatable method to measure the dimensions of the upper tarsal plate and upper lid wiper staining.
Efficiently clustering transactional data with weighted coverage density

It is widely recognized that developing efficient and fully automated algorithms for clustering large transactional datasets is a challenging problem. In this paper, we propose a fast, memory-efficient, and scalable clustering algorithm for analyzing transactional data. Our approach has three unique features. First, we use the concept of Weighted Coverage Density as a categorical similarity measure for efficient clustering of transactional datasets. The concept of weighted coverage density is intuitive and allows the weight of each item in a cluster to be changed dynamically according to the occurrences of items. Second, we develop two transactional data clustering specific evaluation metrics based on the concept of large transactional items and the coverage density respectively. Third, we implement the weighted coverage density clustering algorithm and the two clustering validation metrics using a fully automated transactional clustering framework, called SCALE (Sampling, Clustering structure Assessment, cLustering and domain-specific Evaluation). The SCALE framework is designed to combine the weighted coverage density measure for clustering over a sample dataset with self-configuring methods that can automatically tune the two important parameters of the clustering algorithms: (1) the candidates of the best number K of clusters; and (2) the application of two domain-specific cluster validity measures to find the best result from the set of clustering results. We have conducted experimental evaluation using both synthetic and real datasets and our results show that the weighted coverage density approach powered by the SCALE framework can efficiently generate high quality clustering results in a fully automated manner.
Identification of Human and Animal Adenoviruses and Polyomaviruses for Determination of Sources of Fecal Contamination in the Environment

ABSTRACT The Adenoviridae and Polyomaviridae families comprise a wide diversity of viruses which may be excreted for long periods in feces or urine. In this study, a preliminary analysis of the prevalence in the environment and the potential usefulness as source-tracking tools of human and animal adenoviruses and polyomaviruses has been developed. Molecular assays based on PCR specifically targeting human adenoviruses (HAdV), porcine adenoviruses (PAdV), bovine adenoviruses (BAdV), and bovine polyomaviruses (BPyV) were applied to environmental samples including urban sewage, slaughterhouse, and river water samples. PAdV and BPyV were detected in a very high percentage of samples potentially affected by either porcine or bovine fecal contamination, respectively. However, BAdV were detected in only one sample, showing a lower prevalence than BPyV in the wastewater samples analyzed. The 22 slaughterhouse samples with fecal contamination of animal origin showed negative results for the presence of HAdV. The river water samples analyzed were positive for the presence of both human and animal adenoviruses and polyomaviruses, indicating the existence of diverse sources of contamination. The identities of the viruses detected were confirmed by analyses of the amplified sequences. All BPyV isolates showed a 97% similarity in nucleotide sequences. This is the first time that PAdV5, BAdV6, and BPyV have been reported to occur in environmental samples. Human and porcine adenoviruses and human and bovine polyomaviruses are proposed as tools for evaluating the presence of viral contamination and for tracking the origin of fecal/urine contamination in environmental samples.