Miracle-dz/UniFAR-FTUs huggingface dataset:
Excretion of infectious hepatitis E virus into milk in cows imposes high risks of zoonosis

Hepatitis E virus (HEV) represents the main cause of acute hepatitis worldwide. HEV infection in immunocompromised patients involves a high risk for the development of chronic hepatitis. Because HEV is recognized as a zoonotic pathogen, it is currently believed that swine is the primary reservoir. However, this is not sufficient to justify the strikingly high seroprevalence of HEV in both developing and Western countries. Thus, this study aimed to identify new zoonotic sources that bear a high risk of transmission to humans. We collected fecal, blood, and milk samples of cows in a typical rural region of Yunnan Province in southwest China, where mixed farming of domestic animals is a common practice. HEV RNA was quantified by quantitative real‐time polymerase chain reaction, and the whole genome was sequenced. HEV infectivity was assessed in rhesus macaques. We found a high prevalence of active HEV infection in cows as determined by viral RNA positivity in fecal samples. Surprisingly, we discovered that HEV is excreted into milk that is produced by infected cows. Phylogenetic analysis revealed that all HEV isolates from cow/milk belong to genotype 4 and subtype 4h. Gavage with HEV‐contaminated raw and even pasteurized milk resulted in active infection in rhesus macaques. Importantly, a short period of boiling, but not pasteurization, could completely inactivate HEV. Conclusion: Infectious HEV‐contaminated cow milk is recognized as a new zoonotic source that bears a high risk of transmission to humans; these results call attention to understanding and establishing proper measurement and control of HEV zoonotic transmission, particularly in the setting of mixed farming of domestic animals. (Hepatology 2016;64:350‐359)
Wideband MIMO Channel Capacity Analysis in Multiprobe Anechoic Chamber Setups

This paper discusses over-the-air (OTA) testing for multiple-input-multiple-output (MIMO) capable terminals with emphasis on wideband MIMO channel capacity analysis in a multiprobe anechoic chamber setup. In the literature, the spatial correlation simulation accuracy at the receiver (Rx) side has been used to determine the test area size for a limited number of probes. However, it is desirable that the test area size is defined in terms of data rate deviation of the simulated channel in the laboratory from that of the target channel model. This paper reports MIMO capacity analysis results for wideband spatiotemporal channel models, with emphasis on the impact of the spatial correlation at the transmit (Tx) side, the channel model, and the spatial correlation at the Rx side on the capacity simulation accuracy. Simulation results show that the number of probes is irrelevant to capacity simulation accuracy when the spatial correlation at the Tx side is in the high region (e.g., ρ > 0.7). Furthermore, when correlation at the Tx side is low, the spatial correlation accuracy is less critical with small correlation at the Rx side. The simulation results are further supported by measurements in a practical multiprobe anechoic chamber setup. The capacity simulation accuracy is shown to be a valid measure to determine the test area size.
Altruism Heterogeneity and Quality Competition Among Healthcare Providers

New empirical evidence shows substantial heterogeneity in the altruism of healthcare providers. Spurred by this evidence, we build a spatial quality competition model with altruism heterogeneity. We find that more altruistic healthcare providers supply relatively higher quality levels and position themselves closer to the center. Whether the social planner prefers more or less horizontal differentiation is in general ambiguous and depends on the level of altruism. The more altruistic healthcare providers are, the more likely it is that the social planner prefers greater horizontal differentiation to offset costly quality competition.
Improving Enterprise VM Consolidation with High-Dimensional Load Profiles

Modern enterprise data centers take advantage of virtual machine consolidation to allocate virtual machines to virtualized servers to increase energy efficiency. One key problem is to minimize the number of virtualized servers required while maintaining service quality. A promising approach is to exploit recurring load patterns exhibited by enterprise VMs for increased allocation efficiency. This paper shows that bin packing heuristics can deliver the same allocation quality as integer linear programs if calculation time is constrained. There were no significant differences between vector bin packing heuristics in simulations based on CPU load profiles obtained from enterprise data centers. We further show that consolidating in clusters of a few hundred virtual machines is sufficient as solution quality does not improve with larger clusters.
Components of Torpedo electric organ and muscle that cause aggregation of acetylcholine receptors on cultured muscle cells

The synaptic portion of a muscle fiber's basal lamina sheath has molecules tightly bound to it that cause aggregation of acetylcholine receptors (AChRs) on regenerating myofibers. Since basal lamina and other extracellular matrix constituents are insoluble in isotonic saline and detergent solutions, insoluble detergent-extracted fractions of tissues receiving cholinergic input may provide an enriched source of the AChR-aggregating molecules for detailed characterization. Here we demonstrate that such an insoluble fraction from Torpedo electric organ, a tissue with a high concentration of cholinergic synapses, causes AChRs on cultured chick muscle cells to aggregate. We have partially characterized the insoluble fraction, examined the response of muscle cells to it, and devised ways of extracting the active components with a view toward purifying them and learning whether they are similar to those in the basal lamina at the neuromuscular junction. The insoluble fraction from the electric organ was rich in extracellular matrix constituents; it contained structures resembling basal lamina sheaths and had a high density of collagen fibrils. It caused a 3- to 20-fold increase in the number of AChR clusters on cultured myotubes without significantly affecting the number or size of the myotubes. The increase was first seen 2-4 h after the fraction was added to cultures and it was maximal by 24 h. The AChR-aggregating effect was dose dependent and was due, at least in part, to lateral migration of AChRs present in the muscle cell plasma membrane at the time the fraction was applied. Activity was destroyed by heat and by trypsin. The active component(s) was extracted from the insoluble fraction with high ionic strength or pH 5.5 buffers. The extracts increased the number of AChR clusters on cultured myotubes without affecting the number or degradation rate of surface AChRs. Antiserum against the solubilized material blocked its effect on AChR distribution and bound to the active component. Insoluble fractions of Torpedo muscle and liver did not cause AChR aggregation on cultured myotubes. However a low level of activity was detected in pH 5.5 extracts from the muscle fraction. The active component(s) in the muscle extract was immunoprecipitated by the antiserum against the material extracted from the electric organ insoluble fraction. This antiserum also bound to extracellular matrix in frog muscles, including the myofiber basal lamina sheath. Thus the insoluble fraction of Torpedo electric organ is rich in AChR-aggregating molecules that are also found in muscle and has components antigenically similar to those in myofiber basal lamina.
Phytochemical and antibacterial properties of Parkia biglobosa and Parkia bicolor leaf extracts

The comparative studies of different extracts of the leaves of Parkia biglobosa (Jacq) Benth and Parkia bicolor A. Chev (Mimosaceae) with respect to their photochemical and antimicrobial properties was carried out. Preliminary phytochemical screening showed that both plants had similar constituents namely cardiac glycosides, steroids, tannins and alkaloids. The thin layer chromatography of the hexane and ethanol extracts of both plants were also investigated and two of the components of the ethanol extracts of both plants were found to display similar properties. The antimicrobial screening of the hexane, ethyl acetate, ethanol and water extracts of both plant leaves were done using standard strains of Staphylococcus aureus, Bacillus cereus, Esherichia coli, Pseudomonas aeruginosa, Aspergillus niger and Candida utilis. The ethyl acetate, ethanol and water extracts exhibited a concentration dependent antibacterial, inhibiting the growth of the gram-positive bacteria used in the study. Extracts of P. bicolor were slightly more active than those of P. biglobosa.
The DIPMETER ADVISOR: Interpretation of Geologic Signals

The DIPMETER ADVISOR program is an application of AI and Expert System techniques to the problem of inferring subsurface geologic structure. It synthesizes techniques developed in two previous lines of work, rulte-based systems and signal understanding programs. This report on the prototype system has four main concerns. First, we describe the task and characterize the various bodies of knowledge required. Second, we describe the design of the system we have built and the level of performance it has currently reached. Third, we use this task as a case study and examine it in the light of other, related efforts, showing how particular characteristics of this problem have dictated a number of design decisions. We consider the character of the interpretation hypotheses generated and the sources of the expertise involved. Finally, we discuss future directions of this early effort. We describe the problem of "shallow knowledge" in expert systems and explain why this task appears to provide an attractive setting for exploring the use of deeper models.
A comparative study of the turbulent Rayleigh-Taylor (RT) instability using high-resolution 3D numerical simulations: The Alpha-Group collaboration

The turbulent RT instability is investigated in the limit of strong mode-coupling using a variety of high-resolution, multi-mode, three dimensional (3D) numerical simulations (NS). The perturbations are initialized with only short wavelength modes so that the self-similar evolution (i. e. bubble diameter D b µ amplitude h b) occurs solely by the nonlinear coupling (merger) of saturated modes. After an initial transient, it is found that h b ~ a b Agt 2 where A = Atwood number, g = gravity and t = time. The NS yield D b ~ h b /3 in agreement with experiment but the simulation value a b ~ 0.025 ± 0.003 is smaller than the experimental value a b ~ 0.057 ± 0.008. By analyzing the dominant bubbles, it is found that the small value of a b can be attributed to a density dilution due to fine-scale mixing in our NS without interface reconstruction (IR) or an equivalent entrainment in our NS with IR. This may be characteristic of the mode coupling limit studied here and the associated a b may represent a lower bound that is insensitive to the initial conditions. Larger values of a b can be obtained in the presence of additional long wavelength perturbations and this may be more characteristic of experiments. Here, the data from the NS are also analyzed in terms of bubble dynamics, energy balance and the spectra of density fluctuation.
Altered-Function p53 Missense Mutations Identified in Breast Cancers Can Have Subtle Effects on Transactivation

Mutations of the sequence-specific master regulator p53 that alter transactivation function from promoter response elements (RE) could result in changes in the strength of gene activation or spectra of genes regulated. Such mutations in this tumor suppressor might lead to dramatic phenotypic changes and diversification of cell responses to stress. We have determined “functional fingerprints” of sporadic breast cancer–related p53 mutants, many of which are also associated with familial cancer proneness such as the Li-Fraumeni syndrome and germline BRCA1/2 mutant-associated cancers. The ability of p53, wild-type and mutants, to transactivate from 11 human target REs has been assessed at variable expression levels using a cellular, isogenomic yeast model system that allows for the rapid analysis of p53 function using a qualitative and a quantitative reporter. Among 50 missense mutants, 29 were classified as loss of function. The remaining 21 retained transactivation toward at least one RE. At high levels of galactose-induced p53 expression, 12 of 21 mutants that retain transactivation seemed similar to wild-type. When the level of galactose was reduced, transactivation defects could be revealed, suggesting that some breast cancer–related mutants can have subtle changes in transcription. These findings have been compared with clinical data from an ongoing neoadjuvant chemotherapy treatment trial for locally advanced breast tumors. The functional and nonfunctional missense mutations may distinguish tumors in terms of demographics, appearance, and relapse, implying that heterogeneity in the functionality of specific p53 mutations could affect clinical behavior and outcome. Mol Cancer Res; 8(5); 701–16. ©2010 AACR.
Investigation of a pseudo-outbreak of Nocardia asteroides infection by pulsed-field gel electrophoresis and randomly amplified polymorphic DNA PCR

Molecular strain typing by pulsed-field gel electrophoresis and by randomly amplified polymorphic DNA analysis was used to investigate a cluster of four Nocardia asteroides isolates associated with the BACTEC 460 TB system. An instrument motor drive misalignment resulted in inadequate needle sterilization and cross-contamination of BACTEC vials. This pseudo-outbreak illustrates the importance of proper BACTEC 460 needle sterilization and maintenance and confirms the usefulness of molecular typing methods for epidemiologic investigations.
Mechanism-based inactivator of isocitrate lyases 1 and 2 from Mycobacterium tuberculosis

Significance Tuberculosis, caused by Mycobacterium tuberculosis (Mtb) bacteria, is the most prevalent infectious disease, affecting one-third of the global population, especially in developing countries. First-line therapies to treat this disease are losing efficacy due to the emergence of drug resistance. Accordingly, new therapeutic agents of novel mechanisms of action remain an urgent medical need. The isocitrate lyases (ICL1 and ICL2) comprise metabolically essential enzymes of Mtb, are absent in mammals, and thereby provide therapeutically important drug targets for tuberculosis. Here, we describe the first example of a mechanism-based inactivator of ICL1 and ICL2 that could provide a starting point for the development of new drugs to treat tuberculosis. Isocitrate lyase (ICL, types 1 and 2) is the first enzyme of the glyoxylate shunt, an essential pathway for Mycobacterium tuberculosis (Mtb) during the persistent phase of human TB infection. Here, we report 2-vinyl-d-isocitrate (2-VIC) as a mechanism-based inactivator of Mtb ICL1 and ICL2. The enzyme-catalyzed retro-aldol cleavage of 2-VIC unmasks a Michael substrate, 2-vinylglyoxylate, which then forms a slowly reversible, covalent adduct with the thiolate form of active-site Cys191. 2-VIC displayed kinetic properties consistent with covalent, mechanism-based inactivation of ICL1 and ICL2 with high efficiency (partition ratio, <1). Analysis of a complex of ICL1:2-VIC by electrospray ionization mass spectrometry and X-ray crystallography confirmed the formation of the predicted covalent S-homopyruvoyl adduct of the active-site Cys191.
Bladder neck mobility evaluated by vaginal ultrasonography.

Factors involved in monitoring bladder neck mobility were studied by means of vaginal ultrasonography. Thirty-three continent, 28 incontinent and 39 patients who had undergone surgery for incontinence were examined in the supine and sitting positions during rest, the Valsalva manoeuvre and withholding urine. Bladder neck mobility can be described as a semicircular movement with the tip of the symphysis pubis as the centre and a line from the tip to the bladder neck as the radius (BS). Movement can be measured by 2 independent factors: BS distance and size of the angle between the BS line and the midline of the symphysis, at rest, during the Valsalva manoeuvre and withholding urine. The continent controls were characterised by a 90 degrees angle at rest, a long BS (2.4 cm) and a fixed bladder neck. The incontinent patients had a shorter BS (2.1 cm), angles at rest of approximately 100 degrees--the angle increased with the grade of incontinence--and a mobile bladder neck. If 2 of the 3 criteria (angle at rest > or = 95 degrees, BS < or = 2.3 cm and mobility > or = 20 degrees) are regarded as diagnostic of incontinence, diagnostic sensitivity was 84% and specificity 82%. In the surgical group, patients who failed to respond to treatment had a shorter BS, larger angles and greater bladder neck mobility than their successfully treated counterparts.
Preclinical validation of a multiplex real-time assay to quantify SMN mRNA in patients with SMA

Objective: To determine whether survival motor neuron (SMN) expression was stable over time. Methods: We developed a multiplex real-time reverse transcriptase (RT)-PCR assay to quantify SMN transcripts in preclinical blood samples from 42 patients with spinal muscular atrophy (SMA) drawn for three time points per patient; most blood samples were shipped to a centralized laboratory. Results: We obtained a sufficient amount (9.7 ± 5.6 μg) of good-quality total RNA, and RNAs were stable for up to a 3-year interval. This allowed RNA samples collected during a 9- to 12-month period to be analyzed in a single run, thus minimizing interexperimental variability. SMN expression was stable over time; intersample variability for baseline measures, collected during a 17-month interval, was less than 15% for 38 of 42 SMA patients analyzed. This variability was well below the 1.95-fold increase in full-length SMN (flSMN) transcripts detected in SMA fibroblasts treated with 10 mM valproic acid. Conclusion: Real-time quantification of SMN messenger RNA expression may be a biomarker that is amenable to multicenter SMA clinical trials.
Why Is the Shape of the Web a Bowtie

The first time in Graph Theory a graph was characterized as “Bowtie” was in the seminal paper by Broder et. al. Though no textbook had ever mentioned this type of graph before, no less an important network than the Web Graph itself is supposed to resemble this shape. In two large collections of crawled Web pages and in numerous smaller collections, researchers discovered Bowties and Bowtie-looking graphs by studying millions of web pages. But why do collections of Web pages resemble a Bowtie? The short answer is “because, given the way the Web is created, that’s the only shape it could have”. This paper shows why this is the case and presents an algorithm and software to visualize Bowtie graphs.
Exploring large-scale peer-to-peer live streaming topologies

Real-world live peer-to-peer (P2P) streaming applications have been successfully deployed in the Internet, delivering live multimedia content to millions of users at any given time. With relative simplicity in design with respect to peer selection and topology construction protocols and without much algorithmic sophistication, current-generation live P2P streaming applications are able to provide users with adequately satisfying viewing experiences. That said, little existing research has provided sufficient insights on the time-varying internal characteristics of peer-to-peer topologies in live streaming. This article presents Magellan, our collaborative work with UUSee Inc., Beijing, China, for exploring and charting graph theoretical properties of practical P2P streaming topologies, gaining important insights in their topological dynamics over a long period of time. With more than 120 GB worth of traces starting September 2006 from a commercially deployed P2P live streaming system that represents UUSee's core product, we have completed a thorough and in-depth investigation of the topological properties in large-scale live P2P streaming, as well as their evolutionary behavior over time, for example, at different times of the day and in flash crowd scenarios. We seek to explore real-world P2P streaming topologies with respect to their graph theoretical metrics, such as the degree, clustering coefficient, and reciprocity. In addition, we compare our findings with results from existing studies on topological properties of P2P file sharing applications, and present new and unique observations specific to streaming. We have observed that live P2P streaming sessions demonstrate excellent scalability, a high level of reciprocity, a clustering phenomenon in each ISP, and a degree distribution that does not follow the power-law distribution.
A R2R3-MYB Transcription Factor Regulates the Flavonol Biosynthetic Pathway in a Traditional Chinese Medicinal Plant, Epimedium sagittatum

Flavonols as plant secondary metabolites with vital roles in plant development and defense against UV light, have been demonstrated to be the main bioactive components (BCs) in the genus Epimedium plants, several species of which are used as materials for Herba Epimedii, an important traditional Chinese medicine. The flavonol biosynthetic pathway genes had been already isolated from Epimedium sagittatum, but a R2R3-MYB transcription factor regulating the flavonol synthesis has not been functionally characterized so far in Epimedium plants. In this study, we isolated and characterized the R2R3-MYB transcription factor EsMYBF1 involved in regulation of the flavonol biosynthetic pathway from E. sagittatum. Sequence analysis indicated that EsMYBF1 belongs to the subgroup 7 of R2R3-MYB family which contains the flavonol-specific MYB regulators identified to date. Transient reporter assay showed that EsMYBF1 strongly activated the promoters of EsF3H (flavanone 3-hydroxylase) and EsFLS (flavonol synthase), but not the promoters of EsDFRs (dihydroflavonol 4-reductase) and EsANS (anthocyanidin synthase) in transiently transformed Nicotiana benthamiana leaves. Both yeast two-hybrid assay and transient reporter assay validated EsMYBF1 to be independent of EsTT8, or AtTT8 bHLH regulators of the flavonoid pathway as cofactors. Ectopic expression of EsMYBF1 in transgenic tobacco resulted in the increased flavonol content and the decreased anthocyanin content in flowers. Correspondingly, the structural genes involved in flavonol synthesis were upregulated in the EsMYBF1 overexpression lines, including NtCHS (chalcone synthase), NtCHI (chalcone isomerase), NtF3H and NtFLS, whereas the late biosynthetic genes of the anthocyanin pathway (NtDFR and NtANS) were remarkably downregulated, compared to the controls. These results suggest that EsMYBF1 is a flavonol-specific R2R3-MYB regulator, and involved in regulation of the biosynthesis of the flavonol-derived BCs in E. sagittatum. Thus, identification and functional characterization of EsMYBF1 provide insight into understanding the biosynthesis and regulation of the flavonol-derived BCs in Epimedium plants, and also provide an effective tool gene for genetic manipulation to improve the flavonol synthesis.