Miracle-dz/UniFAR-FTUs huggingface dataset:
G1 cyclin degradation: the PEST motif of yeast Cln2 is necessary, but not sufficient, for rapid protein turnover

The 545-residue Cln2 protein, like the other G1 cyclins of Saccharomyces cerevisiae, is a very unstable protein. This instability is thought to play a critical role in regulating cell cycle progression. The carboxyl-terminal domains of Cln2 and the other G1 cyclins contain sequences rich in Pro, Glu (and Asp), Ser, and Thr (so-called PEST motifs) that have been postulated to make up the signals that are responsible for the rapid degradation of these and other unstable proteins. To test this hypothesis, the carboxyl-terminal 178 residues of Cln2 were fused to the C terminus of a reporter enzyme, a truncated form of human thymidine kinase (hTK delta 40). The resulting chimeric protein (hTK delta 40-Cln2) retained thymidine kinase activity but was markedly less stable than hTK, hTK delta 40, or an hTK-beta-galactosidase fusion protein, as judged by enzyme assay, immunoblotting with anti-hTK antibodies, pulse-chase analysis of the radiolabeled polypeptides, and ability to support the growth of a thymidylate auxotroph (cdc21 mutant) on thymidine-containing medium. Thus, the presence of the Cln2 PEST domain was sufficient to destabilize a heterologous protein. Furthermore, the half-life of hTK delta 40-Cln2 was similar to that of authentic Cln2, and the rate of degradation of neither protein was detectably enhanced by treatments known to cause G1 arrest, including exposure of MATa haploids to alpha-factor mating pheromone and shifting cdc28ts and cdc34ts mutants to the restrictive temperature. These results suggest that the major signals responsible for Cln2 instability are confined to its C-terminal third. Because hTK delta 40-Cln2 and Cln2 were expressed from heterologous promoters yet their half-lives both in asynchronous cultures and when arrested at various cell cycle stages were always similar, the Cln2 PEST domain contains a signal for rapid protein turnover that is constitutively active and operative throughout the cell cycle. Removal of the 37 codons that encode the most prominent PEST-like segment from either hTK delta 40-Cln2 or Cln2 decreased the turnover rate of the resulting proteins, as expected; however, an hTK delta 40 chimera containing only this 37-residue segment was not detectably destabilized, suggesting that this PEST sequence, when removed from its normal context, is not a self-contained determinant of protein instability.
Ubiquity of lignin-degrading peroxidases among various wood-degrading fungi

Phanerochaete chrysosporium is rapidly becoming a model system for the study of lignin biodegradation. Numerous studies on the physiology, biochemistry, chemistry, and genetics of this system have been performed. However, P. chrysosporium is not the only fungus to have a lignin-degrading enzyme system. Many other ligninolytic species of fungi, as well as other distantly related organisms which are known to produce lignin peroxidases, are described in this paper. In this study, we demonstrated the presence of the peroxidative enzymes in nine species not previously investigated. The fungi studied produced significant manganese peroxidase activity when they were grown on an oak sawdust substrate supplemented with wheat bran, millet, and sucrose. Many of the fungi also exhibited laccase and/or glyoxal oxidase activity. Inhibitors present in the medium prevented measurement of lignin peroxidase activity. However, Western blots (immunoblots) revealed that several of the fungi produced lignin peroxidase proteins. We concluded from this work that lignin-degrading peroxidases are present in nearly all ligninolytic fungi, but may be expressed differentially in different species. Substantial variability exists in the levels and types of ligninolytic enzymes produced by different white not fungi.
Transformations and representations supporting spatial perspective taking

ABSTRACT Spatial perspective taking is the ability to reason about spatial relations relative to another’s viewpoint. Here, we propose a mechanistic hypothesis that relates mental representations of one’s viewpoint to the transformations used for spatial perspective taking. We test this hypothesis using a novel behavioral paradigm that assays patterns of response time and variation in those patterns across people. The results support the hypothesis that people maintain a schematic representation of the space around their body, update that representation to take another’s perspective, and thereby to reason about the space around their body. This is a powerful computational mechanism that can support imitation, coordination of behavior, and observational learning.
MulVAL: A Logic-based Network Security Analyzer

To determine the security impact software vulnerabilities have on a particular network, one must consider interactions among multiple network elements. For a vulnerability analysis tool to be useful in practice, two features are crucial. First, the model used in the analysis must be able to automatically integrate formal vulnerability specifications from the bug-reporting community. Second, the analysis must be able to scale to networks with thousands of machines. We show how to achieve these two goals by presenting MulVAL, an end-to-end framework and reasoning system that conducts multihost, multistage vulnerability analysis on a network. MulVAL adopts Datalog as the modeling language for the elements in the analysis (bug specification, configuration description, reasoning rules, operating-system permission and privilege model, etc.). We easily leverage existing vulnerability-database and scanning tools by expressing their output in Datalog and feeding it to our MulVAL reasoning engine. Once the information is collected, the analysis can be performed in seconds for networks with thousands of machines. We implemented our framework on the Red Hat Linux platform. Our framework can reason about 84% of the Red Hat bugs reported in OVAL, a formal vulnerability definition language. We tested our tool on a real network with hundreds of users. The tool detected a policy violation caused by software vulnerabilities and the system administrators took remediation measures.
Forensic Facial Reconstruction Using Mesh Template Deformation with Detail Transfer over HRBF

Forensic facial reconstruction is the application of anthropology, art and forensic science to recreate the face of an individual from his skull. It is usually done manually by a sculptor with clay and is considered a subjective technique as it relies upon an artistic interpretation of the skull features. In this work, we propose a computerized method based on anatomical rules that systematically generates the surface of the face through a HRBF deformation procedure over a mesh template. Our main contributions are a broader set of anatomical rules being applied over the soft tissue structures and a new deformation method that dissociates the details from the overall shape of the model.
Development of an autonomous flying robot and its verification via flight control experiment

This paper presents development of an autonomous flying robot (unmanned aerial vehicle) and its verification via flight control experiment. The autonomous flying robot has a global positioning system (GPS) sensor to control its altitude and also a wireless camera to gather visual information from the air. First, we construct a longitudinal model of the autonomous flying robot to design a stable controller using a common Lyapunov approach. The longitudinal model has three degree of freedom, i.e., the altitude, the horizontal position and the pitch angle. A stable controller is designed so as to guarantee the stability of the trajectory tracking control system for the three-degree-of-freedom model. The experimental result demonstrates the viability of the stable trajectory tracking control.
The Effect of Sodium Valproate on Sleep, Reaction Times, and Visual Evoked Potential in Normal Subjects

L'effet du Valproate de sodium entérique àétéévalué chez dix volontaires sains à l'aide de temps de réaction simples, de potentiels évoqués visuels (VEP) et d'enregistrements de sommeil. L'effet d'un placebo, d'une faible dose (500 mg), d'une forte dose (1,000 mg) du médicament et du sevrage ont étéétudiés. On n'a trouvé aucun effet significatif du traitement sur les temps de réaction simples ni sur la latence et l'amplitude des VEP. Les enregistrements de sommeil ont été analysés visuellement selon la méthode de Rechtschaffen et Kales (1968) et automatiquement selon la technique de l'analyse de période simple. Les résultats de l'analyse automatique suggéraient qu'il y avait une diminution de l'activité REM et une augmentation de l'activité delta sous forte dose du médicament. Les données de l'analyse visuelle n'étaient pas significatives bien qu'elles suivissent les mêmes tendances que celles de l'analyse automatique. Il est possible que les résultats de cette dernière reflètent plutôt des modifications de la fréquence de l'EEG que des modifications dans le cycle du sommeil lui‐môme, dues au traitement par le valproate de sodium.
Stochastic simulation of the impact of antiretroviral therapy and HIV vaccines on HIV transmission; Rakai, Uganda

Objective: To model the effects of antiretroviral therapy (ART) and HIV vaccines on HIV transmission using empirical data from studies in Rakai, Uganda. Design: A stochastic simulation model estimated HIV incidence, probabilities of transmission per coital act and the reproductive number (R0) with ART and HIV vaccines. Model inputs included Rakai data on HIV transmission probabilities per coital act by HIV viral load, age and gender, and sexual behaviors. The impacts of therapy were derived from US programs, and vaccine assumptions included preventive efficacies ranging from 25 to 75%. Component projection models estimated the numbers of HIV-infected persons over 20 years. Results: The model incidence [1.57/100 person years (PY)] closely fitted empirical data (1.5/100 PY). Simulations of ART using DHHS treatment guidelines, predicted declines in HIV incidence, but R0 remained > 1.0, and the numbers of HIV-positive persons did not change substantially over 20 years. Preventive vaccines with > 50% efficacy and > 50% population coverage could reduce R0 to < 1.0, and substantially reduce the number of HIV-infected persons over 20 years. Concurrent ART and a preventive vaccine can have substantial impact at lower levels of population coverage and would markedly reduce the HIV infected population over 20 years. However, behavioral disinhibition with increased numbers of sexual partners in either ART or vaccine recipients, increased HIV incidence and diminished intervention impact. Conclusion: ART alone cannot control the HIV epidemic in mature epidemics such as Rakai, and persons in need of therapy will increase over time. ART in combination with a low efficacy vaccine could control the epidemic, if behavioral disinhibition is prevented.
Evaluation of risk for graft-versus-host disease in children who receive less than the full doses of mini-dose methotrexate for graft-versus-host disease prophylaxis in allogeneic hematopoietic stem cell transplantation

Purpose The use of cyclosporine and mini-dose methotrexate (MTX) is a common strategy for graft-versus-host disease (GVHD) prophylaxis in allogeneic transplants. We investigated whether patients who receive fewer than the planned MTX doses are at increased risk for GVHD. Methods The study cohort included 103 patients who received allogeneic transplants at the Department of Pediatrics of The Catholic University of Korea College of Medicine, from January 2010 to December 2011. MTX was administered on days 1, 3, 6, and 11 after transplant at a dose of 5 mg/m2 each. Within the cohort, 76 patients (74%) received all 4 doses of MTX [MTX(4) group], while 27 patients (26%) received 0-3 doses [MTX(0-3) group]. Results Although there was no difference in neutrophil engraftment between the 2 groups, platelet engraftment was significantly faster in the MTX(4) group (median, 15 days), compared to the MTX(0-3) group (median, 25 days; P=0.034). The incidence of grades II-IV acute GVHD was not different between the MTX(4) and MTX(0-3) groups (P=0.417). In the multivariate study, human leukocyte antigen mismatch was the most significant factor causing grades II-IV acute GVHD (P=0.002), followed by female donor to male recipient transplant (P=0.034). No difference was found between the MTX(4) and MTX (0-3) groups regarding grades III-IV acute GVHD, chronic GVHD, and disease-free survival. Conclusion Our results indicate that deviations from the full dose schedule of MTX for GVHD prophylaxis do not lead to increased incidence of either acute or chronic GVHD.
Digital Grid: Communicative electrical grids of the future

To support a high penetration of intermittent solar and wind power generation, many regions are planning to add new high capacity transmission lines. These additional transmission lines strengthen grid synchronization, but will also increase the grid's short circuit capacity, and furthermore will be very costly. With a highly interconnected grid and variable renewable generation, a small grid failure can easily start cascading outages, resulting in large scale blackout. We introduce the “Digital Grid”, where large synchronous grids are divided into smaller segmented grids which are connected asynchronously, via multi-leg IP addressed ACs/DC/ACs converters called Digital Grid Routers. These routers communicate with each other and send power among the segmented grids through existing transmission lines, which have been re-purposed as digital grid transmission lines. The Digital Grid can accept high penetrations of renewable power, prevent cascading outages, accommodate identifiable tagged electricity flows, record those transactions and trade electricity as a commodity.
Effect of the Ketone Body Beta-Hydroxybutyrate on the Innate Defense Capability of Primary Bovine Mammary Epithelial Cells

Negative energy balance and ketosis are thought to cause impaired immune function and to increase the risk of clinical mastitis in dairy cows. The present in vitro study aimed to investigate the effect of elevated levels of the predominant ketone body β-hydroxybutyrate on the innate defense capability of primary bovine mammary epithelial cells (pbMEC) challenged with the mastitis pathogen Escherichia coli (E. coli). Therefore, pbMEC of healthy dairy cows in mid- lactation were isolated from milk and challenged in culture with 3 mM BHBA and E. coli. pbMEC stimulated with E. coli for 6 h or 30 h showed an up-regulation of several innate immune genes, whereas co-stimulation of pbMEC with 3 mM BHBA and E. coli resulted in the down-regulation of CCL2, SAA3, LF and C3 gene expression compared to the challenge with solely the bacterial stimulus. These results indicated that increased BHBA concentrations may be partially responsible for the higher mastitis susceptibility of dairy cows in early lactation. Elevated levels of BHBA in blood and milk during negative energy balance and ketosis are likely to impair innate immune function in the bovine mammary gland by attenuating the expression of a broad range of innate immune genes.
Immunoglobulin G Subclass Profile of Antimeasles Response in Vaccinated Children and in Adults with Measles History

ABSTRACT The aim of this study was to investigate measles-specific immunoglobulin G (IgG) subclass profile in vaccinated children and in adults with natural infection. Serum samples were collected before and 30 days after vaccination. The sera from 51 late convalescent adults and seven adults with natural measles infection at the 12th day after onset of rash have been also investigated. Measles IgG antibodies and specific IgG subclasses were tested by enzyme-linked immunosorbent techniques. In children younger than 3 years, the predominant subclass was IgG3, which contributed, on average, 63.3% of the total IgG response. The contributions of specific IgG1 and IgG4 to the total IgG antimeasles response were lower (19.9% and 16.8%, respectively), whereas IgG2 was not found. In contrast, in the group of children older than 4 years, just IgG2 was a predominant subclass; it contributed 42.6% of the total IgG response. Other subclasses were also present but the contribution was much lower. In adult volunteers with measles history, IgG2 was a predominant subclass of total IgG. Thus, in early convalescence IgG2 contributed 62% of the total IgG response, whereas in late convalescence the contribution was lower (41.4%). There were no visible differences in IgG subclass composition between subjects with natural infection and vaccinated children except those below 3 years of age. The humoral immune response of such subjects is immature and the IgG2 subclass of virus-specific antibodies has not been revealed in the sera.
Infections on the move: how transient phases of host movement influence disease spread

Animal movement impacts the spread of human and wildlife diseases, and there is significant interest in understanding the role of migrations, biological invasions and other wildlife movements in spatial infection dynamics. However, the influence of processes acting on infections during transient phases of host movement is poorly understood. We propose a conceptual framework that explicitly considers infection dynamics during transient phases of host movement to better predict infection spread through spatial host networks. Accounting for host transient movement captures key processes that occur while hosts move between locations, which together determine the rate at which hosts spread infections through networks. We review theoretical and empirical studies of host movement and infection spread, highlighting the multiple factors that impact the infection status of hosts. We then outline characteristics of hosts, parasites and the environment that influence these dynamics. Recent technological advances provide disease ecologists unprecedented ability to track the fine-scale movement of organisms. These, in conjunction with experimental testing of the factors driving infection dynamics during host movement, can inform models of infection spread based on constituent biological processes.
International Journal of Health Geographics a Flexibly Shaped Space-time Scan Statistic for Disease Outbreak Detection and Monitoring

Background: Early detection of disease outbreaks enables public health officials to implement disease control and prevention measures at the earliest possible time. A time periodic geographical disease surveillance system based on a cylindrical space-time scan statistic has been used extensively for disease surveillance along with the SaTScan software. In the purely spatial setting, many different methods have been proposed to detect spatial disease clusters. In particular, some spatial scan statistics are aimed at detecting irregularly shaped clusters which may not be detected by the circular spatial scan statistic.
Service Users’ and Caregivers’ Perspectives on Continuity of Care in Out-of-Hours Primary Care

Modernization policies in primary care, such as the introduction of out-of-hours general practice cooperatives, signify a marked departure from many service users’ traditional experiences of continuity of care. We report on a case study of accounts of service users with chronic conditions and their caregivers of continuity of care in an out-of-hours general practice cooperative in Ireland. Using Strauss and colleagues’ Chronic Illness Trajectory Framework, we explored users’ and caregivers’ experiences of continuity in this context. Whereas those dealing with “routine trajectories” were largely satisfied with their experiences, those dealing with “problematic trajectories” (characterized by the presence of, for example, multimorbidity and complex care regimes) had considerable concerns about continuity of experiences in this service. Results highlight that modernization policies that have given rise to out-of-hours cooperatives have had a differential impact on service users with chronic conditions and their caregivers, with serious consequences for those who have “problematic” trajectories.
Differences in the mechanism of tolerance to dinitrophenylated bovine gamma globulin when induced in normal adult mice or in reconstituted irradiated mice: dependence of the mechanism of tolerance on the structural organization of the lymphoid system

Tolerance can be induced in adult mice by a single intravenous injection of 0.5 mg dinitrophenylated bovine gamma globulin. The cellular mechanism of the unresponsive state is different depending upon whether the tolerance is induced in normal intact adult mice or in reconstituted, irradiated mice. The tolerant state induced in intact mice is characterized by a high avidity of the residual antibody- forming cells in partially tolerant animals and a prompt reversibility on cell transfer. The overall properties of this unresponsive state are consistent with the hypothesis that it is mediated by the production of small amounts of high affinity antibody in response to the tolerance- inducing injection of antigen. In contrast, the unresponsiveness induced in reconstituted, irradiated mice by the same procedure was characterized by a low avidity of the residual antibody-forming cells in partially tolerant animals and stability on transfer of spleen cells from unresponsive into irradiated recipients. No suppressor cell activity was detected and mixed cell transfer studies were consitent with the view that this unresponsive state represented a B-lymphocyte clonal deletion. The presence or absence of T lymphocytes in the population of cells used for reconstituting the irradiated recipients did not effect the ease of tolernace induction or the cellular mechanism of the tolerant state which was produced. If irradiated mice reconstituted with B and T lymphocytes were rested for 2 wk before tolerance induction then a reversible "high affinity"-type tolerance is obtained such as is typical of normal intact animals. Restorationof a "normal" response to the tolerance-inducing injection of antigen is dependent upon the presence of thymus cells in the population of cells used for reconstitution. It is suggested that the structural integrity of the lymphoid tissue is critical in determining whether B cell will be rendered tolerant after exposure to antigen in vivo.
Genotyping by PCR and High-Throughput Sequencing of Commercial Probiotic Products Reveals Composition Biases

Recent advances in microbiome research have brought renewed focus on beneficial bacteria, many of which are available in food and dietary supplements. Although probiotics have historically been defined as microorganisms that convey health benefits when ingested in sufficient viable amounts, this description now includes the stipulation “well defined strains,” encompassing definitive taxonomy for consumer consideration and regulatory oversight. Here, we evaluated 52 commercial dietary supplements covering a range of labeled species using plate counting and targeted genotyping. Strain identities were assessed using methods recently published by the United States Pharmacopeial Convention. We also determined the relative abundance of individual bacteria by high-throughput sequencing (HTS) of the 16S rRNA sequence using paired-end 2 × 250 bp Illumina MiSeq technology. Using these methods, we tested the hypothesis that products do contain the quantitative and qualitative list of labeled microbial species. We found that 17 samples (33%) were below label claim for CFU prior to their expiration dates. A multiplexed-PCR scheme showed that only 30/52 (58%) of the products contained a correctly labeled classification, with issues encompassing incorrect taxonomy, missing species, and un-labeled species. The HTS revealed that many blended products consisted predominantly of Lactobacillus acidophilus and Bifidobacterium animalis subsp. lactis. These results highlight the need for reliable methods to determine the correct taxonomy and quantify the relative amounts of mixed microbial populations in commercial probiotic products.