Miracle-dz/UniFAR-FTUs huggingface dataset:
IL-27 Receptor Signaling Regulates CD4+ T Cell Chemotactic Responses during Infection

IL-27 exerts pleiotropic suppressive effects on naive and effector T cell populations during infection and inflammation. Surprisingly, however, the role of IL-27 in restricting or shaping effector CD4+ T cell chemotactic responses, as a mechanism to reduce T cell–dependent tissue inflammation, is unknown. In this study, using Plasmodium berghei NK65 as a model of a systemic, proinflammatory infection, we demonstrate that IL-27R signaling represses chemotaxis of infection-derived splenic CD4+ T cells in response to the CCR5 ligands, CCL4 and CCL5. Consistent with these observations, CCR5 was expressed on significantly higher frequencies of splenic CD4+ T cells from malaria-infected, IL-27R–deficient (WSX-1−/−) mice than from infected wild-type mice. We find that IL-27 signaling suppresses splenic CD4+ T cell CCR5-dependent chemotactic responses during infection by restricting CCR5 expression on CD4+ T cell subtypes, including Th1 cells, and also by controlling the overall composition of the CD4+ T cell compartment. Diminution of the Th1 response in infected WSX-1−/− mice in vivo by neutralization of IL-12p40 attenuated CCR5 expression by infection-derived CD4+ T cells and also reduced splenic CD4+ T cell chemotaxis toward CCL4 and CCL5. These data reveal a previously unappreciated role for IL-27 in modulating CD4+ T cell chemotactic pathways during infection, which is related to its capacity to repress Th1 effector cell development. Thus, IL-27 appears to be a key cytokine that limits the CCR5-CCL4/CCL5 axis during inflammatory settings.
Characterization of structural and immunological properties of specific domains of Friend ecotropic and dual-tropic murine leukemia virus gp70s

A detailed comparison of the gp70 proteins of cloned ecotropic Friend murine leukemia virus (FLV) and dual-tropic Friend mink focus-forming virus (FrMCF) was performed by analyzing the structural and immunological properties of amino- and carboxy-terminal domains of these molecules generated upon controlled trypsinization. The two gp70s gave characteristic fragmentation patterns; the amino-terminal fragments of FrMCF gp70 were smaller than the corresponding fragments of FLV and contained a trypsin site which resulted in a 19,000-dalton amino-terminal fragment not observed for FLV, whereas both molecules yielded an identically sized carboxy-terminal fragment. All amino-terminal fragments of both gp70 molecules contained an endo H-sensitive oligosaccharide chain; for FrMCF, a second endo H-sensitive carbohydrate was present as well at a carboxy-terminal site for approximately 50% of the molecules. Several aspects of the disulfide interactions of the two gp70s were conserved; in both cases the carboxy-terminal fragments were disulfide bonded to p15(E), there were no disulfide bonds between amino- and carboxy-terminal fragments, and the amino-terminal fragments exhibited a significant increase in mobility upon analysis by sodium dodecyl sulfate-polyacrylamide gel electrophoresis under nonreducing conditions. Analysis of the immunoreactivity of the different domains of the proteins by immunoprecipitation of the fragments with antisera prepared against xenotropic murine leukemia virus and feline leukemia virus gp70s indicated major differences in antigenicity for the amino-terminal domains of FLV and FrMCF gp70, whereas the carboxy-terminal domains were immunologically conserved. Similar analyses with antibodies specific for p15(E) and Pr15(E) demonstrate that these components are conserved as well. These data provide direct evidence that p15(E) and the C-terminal gp70 domain of FrMCF gp70 are related to the corresponding regions of the ecotropic FLV parent and indicate that the acquisition of MCF-specific properties is due to the replacement of the ecotropic amino-terminal gp70 domain with sequences related to those of xenotropic gp70s.
Insights from mouse models of heparin-induced thrombocytopenia and thrombosis

Heparin-induced thrombocytopenia/thrombosis (HIT/T) is the most frequent cause of drug-induced antibody-mediated thrombocytopenia, a common cause of life-and limb-threatening platelet activation and thrombosis. Although antibodies to heparin–platelet factor 4 (PF4) complexes are found in essentially all patients with HIT/T, it is unclear how antibody formation is initiated, why only a small subset of these antibodies cause disease, or the mechanism by which they initiate thrombosis. The recent development of a transgenic mouse model of HIT/T showed, for the first time in vivo, that heparin, PF4, antibodies to the heparin–PF4 complex, and Fc&ggr;RIIA are necessary and sufficient to recapitulate the severe thrombocytopenia and thrombosis seen in patients. This model can be expanded to systematically study individual factors important to HIT/T development in vivo, to determine their contribution to the spectrum of human disease. Several recent papers have examined the role of other contributors, such as monocyte tissue factor, endothelial cell activation, and leukocyte-platelet aggregates in the pathogenesis of the disease. Mouse models will provide a means to test new diagnostic and therapeutic approaches.
Sex differences in cortisol response to reboxetine

This study examined the cortisol response to reboxetine in a sample of healthy men and women. Forty healthy volunteers were randomly allocated to one of two treatment groups: placebo or 4 mg reboxetine under double-blind conditions. Saliva cortisol was measured pre, 1 and 1.5 h post-treatment. Mood and side-effects were also measured. A single oral dose of 4 mg reboxetine did not affect positive or negative mood but did produce some side-effects. It was also sufficient to increase cortisol release 1.5 h post-treatment compared to placebo. In addition, reboxetine lead to a significantly increased cortisol release in male compared to female volunteers. The results suggest that healthy male volunteers are more responsive to challenge with a noradrenergic compound than females.
Elaborating actual lead time with both management and execution data

Many lean management initiatives are achieved worldwide. Most often the focus of these projects is to reduce lead time in order to improve enterprise responsiveness and financial health. Usually, lead time is estimated by drawing up a value stream map and by estimating inventories and flow times all along it. This current practice is not accurate, exhaustive and relevant enough to us when managing a real ongoing improvement project. We suggest in this paper a new way of elaborating lead time for each product, taking into account all its components and using genealogy and purchasing costs data.
Use of tricyclic antidepressants as analgesic adjuvants results in nonhazardous prolongation of the QTc interval.

BACKGROUND Tricyclic antidepressants (TCAs) are known to prolong QTc interval. However, little is known about the QTc lengthening effect of TCAs at analgesic dosages and the predictive factors for abnormal QTc prolongation. METHODS We conducted a single-center, retrospective observational study, and evaluated 87 patients (65 amitriptyline, 22 nortriptyline) who underwent 12-lead electrocardiogram (ECG) examinations both before and after receiving TCAs for herpes zoster pain or postherpetic neuralgia from May 2007 to January 2012. Data on QTc interval, age, gender, the type and daily dosage of TCAs, the medication period until the second ECG examination, and ECG findings were obtained from electronic medical charts. RESULTS The median daily dosages were 25 mg/day for amitriptyline and 10 mg/day for nortriptyline. The median medication period for all participants was 62 days. TCAs significantly prolonged the QTc interval (before, 413.2 +/-17.0 ms; after, 419.9 +/- 18.9 ms, p < 0.01). Three patients showed marked QTc prolongation, but it did not exceed 500 ms, or deltaQTc of 60 ms, and none had an episode of fatal arrhythmia. Univariate logistic regression analysis revealed left ventricular hypertrophy (LVH) to be the sole risk factor for abnormal QTc prolongation. The adjusted odds ratio was 4.09 (95% CI, 1.01-16.55, p < 0.05) by multivariate logistic regression analysis. CONCLUSIONS TCAs as analgesic adjuvant significantly prolonged the QTc interval, but within an acceptable range. LVH was a significant predictor of abnormal QTc prolongation.
Posttranslational control of transcription factor FixK2, a key regulator for the Bradyrhizobium japonicum–soybean symbiosis

Rhizobial FixK-like proteins play essential roles in activating genes for endosymbiotic life in legume root nodules, such as genes for micro-oxic respiration. In the facultative soybean symbiont, Bradyrhizobium japonicum, the FixK2 protein is the key player in a complex regulatory network. The fixK2 gene itself is activated by the 2-component regulatory system FixLJ in response to a moderate decrease of the oxygen tension, and the FixK2 protein distributes and amplifies this response to the level of approximately 200 target genes. Unlike other members of the cAMP receptor protein family, to which FixK2 belongs, the FixK2 protein does not appear to be modulated by small effector molecules. Here, we show that a critical, single cysteine residue (C183) near the DNA-binding domain of FixK2 confers sensitivity to oxidizing agents and reactive oxygen species. Oxidation-dependent inactivation occurs not only in vitro, as shown with cell-free transcription assays, but also in vivo, as shown by microarray-assisted transcriptome analysis of the FixK2 regulon. The oxidation mechanism may involve a reversible dimerization by intermolecular disulfide-bridge formation and a direct, irreversible oxidation at the cysteine thiol, depending on the oxidizing agent. Mutational exchange of C183 to alanine renders FixK2 resistant to oxidation, yet allows full activity, shown again both in vitro and in vivo. We hypothesize that posttranslational modification by reactive oxygen species is a means to counterbalance the cellular pool of active FixK2, which would otherwise fill unrestrictedly through FixLJ-dependent synthesis.
The optimal balancing of the robotic manipulators

In the present work, the static balancing of the forearm of a robot is analyzed; the advantages and disadvantages of using a mass or a spring for the balancing are discussed and their effects on the system natural frequencies are illusrated using numerical examples. The three-dimensional finite element analysis has been used as a mathematical tool for finding the natural frequencies.
[Mental disorders in patients with spinocerebellar ataxia type 2 in Cuba].

INTRODUCTION Of the different hereditary ataxias present in Cuba, spinocerebellar ataxia type 2 (SCA2) is the most prevalent molecular type. Over the last years a great amount of progress has been made in clinical, epidemiological, molecular and neurophysiological research. Yet, the main psychiatric disorders that appear in these patients remain unknown. Their proper diagnosis will help to draw up a program of individualized therapeutic interventions for each disorder and will allow the patient to cope better with his or her illness and to take part in an effective physical and psychological rehabilitation program. AIMS. To identify the mental disorders that appear in patients suffering from SCA2. PATIENTS AND METHODS We conducted a descriptive study of series of cases in 150 patients with SCA2. Data was obtained by means of a semi structured interview with patients and their relatives, as well as a thorough psychiatric exploration, which enabled us to sort the symptoms according to spheres. A battery of psychometric tests and the diagnostic and research criteria for the international classification of mental illnesses were also used. RESULTS Findings showed that 88% of those studied present at least one clinical manifestation related with mental disorders. These included, essentially, disorders involving adaptation, sleep, mood and sexual disorders. Mental retardation and dementia were other alterations that were diagnosed. CONCLUSIONS Disorders in the psychic sphere are a part of the SCA2 phenotype
Research Challenges and Bioethics Responsibilities in the Aftermath of the Presidential Apology to the Survivors of the U. S. Public Health Services Syphilis Study at Tuskegee

In 1997 President Clinton apologized to the survivors of the U.S. Public Health Service Syphilis Study. Since then, two of his recommendations have received little attention. First, he emphasized the need to remember the shameful past so we can build a better future for racial'ethnic minority populations. Second, he directed the creation in partnership with higher education to prepare training materials that would instruct biomedical researchers on the application of ethical principles to research with racial/ethnic minority populations. This article proposes the inclusion of these issues in the implementation of the Affordable Care Act. It asks, What is the right or good thing to do? What are our obligations to one another? Two challenges are examined: (a) Conducting research with African Americans without knowledge of bioethics specific to this population, and (b) the ethical dilemma of conducting research that does not adequately take into account the diversity within the Black population that is a contributing factor in health disparities. Training and policy recommendations responsive to President Clinton's Apology are presented.
LATE ESL LEARNERS ’ DIFFICULTIES OF DISTINCTION BETWEEN LAX AND TENSE VOWELS

The present research is to analyze the production of English lax and tense vowels by early learners of English and late learners of English (namely, Early Bilinguals and Late Bilinguals). According to Flege, Munro, and McKay’s research in 1995, they discovered that Italian speakers who arrived in Canada late tended to have a noticeable foreign accent in English, whereas early Italian arrivals in Canada performed better at English pronunciation tasks. This suggests that older second language learners may have more difficulties in pronouncing native-like sounds in speech. Therefore, given that acoustic cues of vowels varied by the formant frequencies and perceived by speakers, it is likely to conclude that age of acquisition (AOA) might be the important factor that prohibits language learners to perceive, distinguish, and produce these formant frequencies correctly.
The Demographics of Cool: Popularity and Recommender Performance for Different Groups of Users

ABSTRACT Typical recommender evaluations treat users as an homogeneous unit. However, user subgroups often differ in their tastes, which can result more broadly in diverse recommender needs. Thus, these groups may have different degrees of satisfaction with the provided recommendations. We explore the offline top-N performance of collaborative filtering algorithms across two domains. We find that several strategies achieve higher accuracy for dominant demographic groups, thus increasing the overall performance for the strategy, without providing increased benefits for other users.
Robust and scalable sampling algorithms for network measurement

Recent growth of the Internet in both scale and complexity has imposed a number of difficult challenges on existing measurement techniques and approaches, which are essential for both network management and many ongoing research projects. For any measurement algorithm, achieving both accuracy and scalability is very challenging given hard resource constraints (e.g., bandwidth, delay, physical memory, and CPU speed). My dissertation research tackles this problem by first proposing a novel mechanism called residual sampling, which intentionally introduces a predetermined amount of bias into the measurement process. We show that such biased sampling can be extremely scalable; moreover, we develop residual estimation algorithms that can unbiasedly recover the original information from the sampled data. Utilizing these results, we further develop two versions of the residual sampling mechanism: a continuous version for characterizing the user lifetime distribution in large-scale peer-to-peer networks and a discrete version for monitoring flow statistics (including per-flow counts and the flow size distribution) in high-speed Internet routers. For the former application in P2P networks, this work presents two methods: ResIDual-based Estimator (RIDE), which takes single-point snapshots of the system and assumes systems with stationary arrivals, and Uniform RIDE (U-RIDE), which takes multiple snapshots and adapts to systems with arbitrary (including non-stationary) arrival processes. For the latter application in traffic monitoring, we introduce Discrete RIDE (D-RIDE), which allows one to sample each flow with a geometric random variable. Our numerous simulations and experiments with P2P networks and real Internet traces confirm that these algorithms are able to make accurate estimation about the monitored metrics and simultaneously meet the requirements of hard resource constraints. These results show that residual sampling indeed provides an ideal solution to balancing between accuracy and scalability.
Discovery of Rare Sequential Topic Patterns in Document Stream

Plain text documents created and distributed on the Internet are ever changing in various forms. Mining topics of these documents has significant applications in many domains. Most of the literature is devoted to topic modeling, while sequential patterns of topics in document streams are ignored. Moreover, traditional sequential pattern mining algorithms mainly focused on frequent patterns for deterministic data sets, and thus not suitable for document streams with topic uncertainty and rare patterns. In this paper, we formulate and handle the mining problem of rare Sequential Topic Patterns (STPs) for Internet document streams, which are rare on the whole but relatively often for specific users, so also interesting. Since this type of rare STPs reflects users’ specific behaviors, our work can be applied in many fields, such as personalized context-aware recommendation and real-time monitoring on abnormal user behaviors on the Internet. We propose a novel approach to discovering user-related rare STPs based on the temporal and probabilistic information of concerned topics. After extracting topics from documents by LDA and sorting the document stream into sessions for different users during different time periods, the proposed algorithms discover rare STPs by (1) mining STP candidates for each user through an efficient algorithm based on pattern-growth, and (2) generating userrelated rare STPs by pattern rarity analysis. Experiments on both synthetic and real data sets show that our approach can discover interesting rare STPs very effectively and effi-
The M.EcoRV DNA-(Adenine N6)-methyltransferase Uses DNA Bending for Recognition of an Expanded EcoDam Recognition Site*

The M.EcoRV DNA methyltransferase recognizes GATATC sites. It is related to EcoDam, which methylates GATC sites. The DNA binding domain of M.EcoRV is similar to that of EcoDam suggesting a similar mechanism of DNA recognition. We show that amino acid residue Lys11 of M.EcoRV is involved in recognition of Gua1 and Arg128 contacts the Gua in base pair 6. These residues correspond to Lys9 and Arg124 in EcoDam, which recognize the Gua residues in both strands of the Dam recognition sequence, indicating that M.EcoRV and EcoDam make similar contacts to outermost base pairs of their recognition sequences and M.EcoRV recognizes its target site as an expanded GATC site. In contrast to EcoDam, M.EcoRV considerably bends the DNA (59 ± 4°) suggesting indirect readout of the AT-rich inner sequence. Recognition of an expanded target site by DNA bending is a new principle for changing DNA recognition specificity of proteins during molecular evolution. R128A is inefficient in DNA bending and binding, whereas K11A bends DNA with relaxed sequence specificity. These results suggest a temporal order of the formation of protein-DNA contacts in which the Gua6–Arg128 contact forms early followed by DNA bending and, finally, the formation of the Lys11–Gua1 contact.
Effect of repeated freeze-thaw cycles on routine plasma biochemical constituents in canine plasma.

BACKGROUND The effect of repeated freeze-thaw cycles on plasma constituents has not been assessed in dogs, although such a procedure is not uncommon to use in routine laboratory practice. OBJECTIVE To assess the effect of freeze-thaw cycles on routine plasma constituents in healthy dogs. METHODS Six healthy adult dogs were used. Blood was sampled and placed in heparinized tubes. After centrifugation, plasma was separated into 5 aliquots. One aliquot was considered as the reference aliquot and used immediately for the assay of all of the biochemical constituents. All of the other aliquots were stored at 20 degrees C. Three aliquots underwent 1, 2, or 3 freeze-thaw cycles during a 1- to 3-day period. The last aliquot remained at 20 degrees C throughout the study and was thawed on the third day. The following biochemical constituents were assayed: glucose, urea, creatinine, total proteins, sodium, potassium, chloride, calcium, phosphates, aspartate aminotransferase (AST), alanine aminotransferase (ALT), creatine kinase (CK), and alkaline phosphatase (ALP). RESULTS No clinically relevant change was observed between the different aliquots for all of the constituents. CONCLUSION Repeated freeze-thaw cycles do not cause changes in the biochemical constituents studied in canine plasma.
High Intake of Dietary Long-Chain &ohgr;-3 Fatty Acids Is Associated With Lower Blood Pressure in Children Born With Low Birth Weight: NHANES 2003–2008

Reduced fetal growth is associated with increased systolic blood pressure. Recently, we found an inverse association between serum &ohgr;-3 fatty acids and systolic blood pressure in young adults born with impaired fetal growth. We investigated the associations of dietary intake in childhood of the long-chain &ohgr;-3 fatty acids eicosapentaenoic acid and docosahexaenoic acid with blood pressure parameters in children born with reduced birth weight. We analyzed data from 3457 children aged 8 to 15 years participating in the continuous National Health and Nutrition Examination Survey 2003–2004, 2005–2006, and 2007–2008. Dietary intake was assessed by two 24-hour dietary recalls, birth weight by questionnaire, and blood pressure was measured. Systolic blood pressure was 1.1 mm Hg higher in those with reduced (<10th centile) compared with normal birth weight (≥10th centile), consistent with previous findings, although not statistically significant (P=0.40); however, pulse pressure was significantly higher in these children (3.4 mm Hg). In the 354 participants with reduced birth weight, when compared with children with the lowest tertile of intake, those who had the highest tertile of dietary eicosapentaenoic acid and docosahexaenoic acid intake had significantly lower systolic blood pressure (−4.9 mm Hg [95% confidence interval, −9.7 to −0.1]) and pulse pressure (−7.7 mm Hg [95% confidence interval, −15.0 to −0.4]). High-dietary intakes of eicosapentaenoic acid and docosahexaenoic acid are associated with lower systolic blood pressure and pulse pressure in children born with reduced birth weight. These data are consistent with the hypothesis that long-chain &ohgr;-3 fatty acids reduce blood pressure in those with impaired fetal growth.