Miracle-dz/UniFAR-FTUs huggingface dataset:
B and T Lymphocyte Attenuator-Mediated Signal Transduction Provides a Potent Inhibitory Signal to Primary Human CD4 T Cells That Can Be Initiated by Multiple Phosphotyrosine Motifs1

The B and T lymphocyte attenuator (BTLA) is a recently identified member of the CD28 family of cell receptors. Initial reports demonstrated that mice deficient in BTLA expression were more susceptible to experimental autoimmune encephalomyelitis, indicating that BTLA was likely to function as a negative regulator of T cell activation. However, cross-linking of BTLA only resulted in a 2-fold reduction of IL-2 production, questioning the potency with which BTLA engagement blocks T cell activation. We established a model in which BTLA signaling could be studied in primary human CD4 T cells. We observed that cross-linking of a chimeric receptor consisting of the murine CD28 extracellular domain and human BTLA cytoplasmic tail potently inhibits IL-2 production and completely suppresses T cell expansion. Mutation of any BTLA tyrosine motifs had no effect on the ability of BTLA to block T cell activation. Only mutation of all four tyrosines rendered the BTLA cytoplasmic tail nonfunctional. We performed structure-function studies to determine which factors recruited to the BTLA cytoplasmic tail correlated with BTLA function. Using pervanadate as a means to phosphorylate the BTLA cytoplasmic tail, we observed both Src homology protein (SHP)-1 and SHP-2 recruitment. However, upon receptor engagement, we observed only SHP-1 recruitment, and mutations that abrogated SHP-1 recruitment did not impair BTLA function. These studies question whether SHP-1 or SHP-2 have any role in BTLA function and caution against the use of pervanadate as means to initiate signal transduction cascades in primary cells.
Diabetes and depot medroxyprogesterone contraception in Navajo women.

BACKGROUND Depot medroxyprogesterone acetate contraception is widely used in Navajo women, a high-risk population for diabetes mellitus. However, depot medroxyprogesterone may lead to weight gain and independently decrease insulin sensitivity. We studied the association between depot medroxyprogesterone and development of diabetes in Navajo women. METHODS We studied Navajo women aged 18 to 50 years who had seen a health care provider at a Navajo Area Indian Health Service clinic at least once in 1998. Diabetic cases (n = 284) and nondiabetic controls (n = 570) were matched by age. Medical records were reviewed to determine contraception use before the diagnosis date of diabetes. RESULTS Users of depot medroxyprogesterone were more likely to develop diabetes than patients who had used combination estrogen-progestin oral contraception only (odds ratio [OR], 3.8; 95% confidence interval [CI], 1.8-7.9). The excess risk persisted after adjustment for body mass index (OR, 3.6; 95% CI, 1.6-7.9). Longer use was associated with greater risk of diabetes. Users of depot medroxyprogesterone were also more likely to develop diabetes than patients who had never used hormonal contraception, although excess risk was smaller (OR, 2.4; 95% CI, 1.4-3.6). CONCLUSIONS Depot medroxyprogesterone contraception was associated with a greater risk of diabetes compared with combination oral contraceptive use only. Risk was associated with length of use and persisted after adjustment for body mass index. Additional research is needed for confirmation, but this risk should be considered in contraceptive choice for women at high risk for diabetes.
Polynucleotide phosphorylase has an impact on cell biology of Campylobacter jejuni

Polynucleotide phosphorylase (PNPase), encoded by the pnp gene, is known to degrade mRNA, mediating post-transcriptional regulation and may affect cellular functions. The role of PNPase is pleiotropic. As orthologs of the two major ribonucleases (RNase E and RNase II) of Escherichia coli are missing in the Campylobacter jejuni genome, in the current study the focus has been on the C. jejuni ortholog of PNPase. The effect of PNPase mutation on C. jejuni phenotypes and proteome was investigated. The inactivation of the pnp gene reduced significantly the ability of C. jejuni to adhere and to invade Ht-29 cells. Moreover, the pnp mutant strain exhibited a decrease in C. jejuni swimming ability and chick colonization. To explain effects of PNPase on C. jejuni 81-176 phenotype, the proteome of the pnp mutant and parental strains were compared. Overall, little variation in protein production was observed. Despite the predicted role of PNPase in mRNA regulation, the pnp mutation did not induce profound proteomic changes suggesting that other ribonucleases in C. jejuni might ensure this biological function in the absence of PNPase. Nevertheless, synthesis of proteins which are involved in virulence (LuxS, PEB3), motility (N-acetylneuraminic acid synthetase), stress-response (KatA, DnaK, Hsp90), and translation system (EF-Tu, EF-G) were modified in the pnp mutant strain suggesting a more specific role of PNPase in C. jejuni. In conclusion, PNPase deficiency induces limited but important consequences on C. jejuni biology that could explain swimming limitation, chick colonization delay, and the decrease of cell adhesion/invasion ability.
Query-feature graphs: bridging user vocabulary and system functionality

This paper introduces query-feature graphs, or QF-graphs. QF-graphs encode associations between high-level descriptions of user goals (articulated as natural language search queries) and the specific features of an interactive system relevant to achieving those goals. For example, a QF-graph for the GIMP graphics manipulation software links the query "GIMP black and white" to the commands "desaturate" and "grayscale. " We demonstrate how QF-graphs can be constructed using search query logs, search engine results, web page content, and localization data from interactive systems. An analysis of QF-graphs shows that the associations produced by our approach exhibit levels of accuracy that make them eminently usable in a range of real-world applications. Finally, we present three hypothetical user interface mechanisms that illustrate the potential of QF-graphs: search-driven interaction, dynamic tooltips, and app-to-app analogy search.
The father: his role in child development

Researchers in the field of mother-child relationships and maternal deprivation have become household names in child welfare during the last 20 years. The findings of Spitz, Goldfarb, Bowlby, Ainsworth and Rutter have profoundly influenced professional attitudes and practices. By contrast, father-child interactions have been less well analysed and still less well publicised. Lynn's scholarly examination of available research data, including his own studies, goes a long way to correct this imbalance. His message is clear and unequivocal — fathers have roles to play in child development, as important and wide-ranging in their consequences as those played by mothers.
Usefulness of the Neuroform Stent for the Treatment of Cerebral Aneurysms: Results at Initial (3–6-mo) Follow-up

OBJECTIVE: The Neuroform microstent, a flexible, self-expanding, nitinol stent specifically designed for use in the cerebral vasculature, became available in North America for aneurysm treatment in November 2002. The present report details our experience with the Neuroform stent over the past 2 years, with an emphasis on evolving treatment strategies and treatment durability at initial (3–6 mo) follow-up. METHODS: All patients included in this report were registered in a prospectively maintained database. We assessed the clinical history, indications for stent use, aneurysm dimensions, technical details of the procedures, degree of aneurysm occlusion, angiographic and clinical findings at follow-up, and complications. RESULTS: Over a 20-month period, 64 patients with 74 aneurysms were treated with 86 Neuroform stents. Of 64 patients, 16 (25%) were treated in the context of subarachnoid hemorrhage (8 acute, 7 subacute, 1 remote). Indications for stent use included broad aneurysm neck (n = 51 stents; average neck, 5.1 mm; aneurysm size, 8.2 mm), fusiform/dissecting morphology (n = 17), salvage/bailout for coils prolapsed into the parent vessel (n = 7), and giant aneurysm (n = 11). Sixty-one aneurysms were stented and coiled with complete or near complete (>95%) occlusion in 28 patients (45.9%) and partial occlusion (<95%) in 33 patients (54%). Follow-up angiographic (n = 43) or magnetic resonance angiographic (n = 5) data (average follow-up, 4.6 mo; median, 4 mo; range, 1.5–13 mo) for 48 aneurysms (46 patients) after stent-supported coil embolization demonstrated progressive thrombosis in 25 patients (52%), recanalization in 11 patients (23%) (8 of whom were retreated), and no change in 12 patients (25%). Follow-up angiography in 5 additional patients with dissecting aneurysms treated with stents alone demonstrated interval vascular remodeling with decreased aneurysm size in all patients. Delayed, severe, in-stent stenosis was observed in 3 patients, 1 of whom was symptomatic and required angioplasty and subsequently superficial temporal artery-to-middle cerebral artery bypass surgery. Using the second-generation Neuroform2 delivery system (n = 53), very few technical problems with stent delivery and deployment have been encountered (n = 2). CONCLUSION: The Neuroform stent facilitates adequate embolization of complex cerebral aneurysms, which would not otherwise be amenable to endovascular therapy. Initial follow-up data indicate favorable progressive thrombosis and recanalization rates for aneurysms after Neuroform stent-assisted embolization. These advantages of stenting were most evident for small aneurysms with wide necks.
Pathological functions of the small GTPase Arf6 in cancer progression: Tumor angiogenesis and metastasis

ABSTRACT Although several lines of evidence have shown that the small GTPase ADP-ribosylation factor 6 (Arf6) plays pivotal roles in cancer progression of several types of cancers, little is known about the functions of Arf6 in tumor microenvironment. We demonstrated that Arf6 in vascular endothelial cells (VECs) plays a crucial role in tumor angiogenesis and growth using endothelial cell-specific Arf6 conditional knockout mice into which B16 melanoma and Lewis lung carcinoma cells were implanted. It was also found that Arf6 in VECs positively regulates hepatocyte growth factor (HGF)-induced β1 integrin recycling, which is a critical event for tumor angiogenesis by promoting cell migration. Importantly, pharmacological inhibition of HGF-induced Arf6 activation significantly suppresses tumor angiogenesis and growth in mice, suggesting that Arf6 signaling would be a potential target for anti-angiogenic therapy. In this manuscript, we summarize the multiple roles of Arf6 in cancer progression, particularly in cancer cell invasion/metastasis and our recent findings on tumor angiogenesis, and discuss a possible approach to develop innovative anti-cancer drugs.
Cultural Models and Somatic Syndromes

Objectives: To review the relevance of cultural models in the generation and amplification of somatic symptoms and syndromes. Methods: Based on a selective review of literature, we examine evidence that cultural and personal explanatory models can contribute to the pathogenesis, symptomatology, and chronicity of medically unexplained symptoms and functional somatic syndromes. Results: In the contemporary world, culture involves flows of information, roles, and institutions that offer individuals multiple models for understanding illness. Cultural models include 1) explanatory models, which make causal attributions and impute specific mechanisms or processes of pathophysiology; 2) prototypes, which are salient images or exemplars drawn from personal experience, family, friends, mass media, and popular culture that are used to reason analogically about one’s own condition; and 3) implicit models and procedural knowledge that may be difficult to articulate because they are embedded in body practices and ways of experiencing distress. Symptom attributions and explanations can participate in vicious circles of symptom amplification that give rise to culture-specific varieties of panic disorder, hypochondriacal worry, and medically unexplained symptoms. Conclusions: Clinical research using the methods of experimental cognitive and social psychology as well as community-based ethnographic and ecological research are needed to advance our understanding of the impact of personal and cultural models on somatic distress. Nevertheless, the current state of knowledge on social and cultural dimensions of somatic syndromes suggests a typology of forms of psychosomatic and sociosomatic looping that has implications for the nosology of somatoform disorders.
Pragmatic Neuroethics: Improving Treatment and Understanding of the Mind-Brain

Today the measurable health burden of neurological and mental health disorders matches or even surpasses any other cluster of health conditions. At the same time, the clinical applications of recent advances in neuroscience are hardly straightforward. In Pragmatic Neuroethics, Eric Racine argues that the emerging field of neuroethics offers a way to integrate such specialties as neurology, psychiatry, and neurosurgery with the humanities and social sciences, neuroscience research, and related healthcare professions, with the goal of tackling key ethical challenges and improving patient care. Racine provides a survey of the often diverging perspectives within neuroethics, offers a theoretical framework supported by empirical data, and discusses the neuroethical implications of such issues as media coverage of neuroscience innovation and the importance of public concerns and lay opinion; nonmedical use of pharmaceuticals for performance enhancement; and the discord between intuitive notions about consciousness and behavior and the scientific understanding of them. Racine proposes a pragmatic neuroethics that combines pluralistic approaches, bottom-up research perspectives, and a focus on practical issues (in contrast to other more theoretical and single-discipline approaches to the field). [He discusses ethical issues related to powerful neuroscience insights into the mechanisms underlying moral reasoning, cooperative behavior, and such emotional processes as empathy. ] In addition, he outlines a pragmatic framework for neuroethics, based on the philosophy of emergentism, which identifies conditions for the meaningful contribution of neuroscience to ethics, and sketches new directions and strategies for meeting future challenges for neuroscience and society. Basic Bioethics series
Edge Provisioning with Flexible Server Placement

We present <inline-formula><tex-math notation="LaTeX">$\sf {Tentacle}$</tex-math><alternatives> <inline-graphic xlink:href="zhang-ieq1-2604803.gif"/></alternatives></inline-formula>, a decision support framework to provision edge servers for online services providers (OSPs). <inline-formula><tex-math notation="LaTeX">$\sf {Tentacle}$</tex-math><alternatives><inline-graphic xlink:href="zhang-ieq2-2604803.gif"/></alternatives> </inline-formula> takes advantage of the increasingly flexible edge server placement, which is enabled by new technologies such as edge computing platforms, cloudlets and network function virtualization, to optimize the overall performance and cost of edge infrastructures. The key difference between <inline-formula><tex-math notation="LaTeX"> $\sf {Tentacle}$</tex-math><alternatives><inline-graphic xlink:href="zhang-ieq3-2604803.gif"/></alternatives> </inline-formula> and traditional server placement approaches lies on that <inline-formula><tex-math notation="LaTeX"> $\sf {Tentacle}$</tex-math><alternatives><inline-graphic xlink:href="zhang-ieq4-2604803.gif"/></alternatives> </inline-formula> can discover proper unforeseen edge locations which significantly improve the efficiency and reduce the cost of edge provisioning. We show how <inline-formula><tex-math notation="LaTeX">$\sf {Tentacle}$</tex-math> <alternatives><inline-graphic xlink:href="zhang-ieq5-2604803.gif"/></alternatives></inline-formula> effectively identifies promising edge locations which are close to a collection of users merely with inaccurate network distance estimation methods, e.g., geographic coordinate (GC) and network coordinate systems (NC). We also show how <inline-formula><tex-math notation="LaTeX">$\sf {Tentacle}$</tex-math><alternatives> <inline-graphic xlink:href="zhang-ieq6-2604803.gif"/></alternatives></inline-formula> comprehensively considers various pragmatic concerns in edge provisioning, such as traffic limits by law or ISP policy, edge site deployment and resource usage cost, over-provisioning for fault tolerance, etc., with a simple optimization model. We simulate <inline-formula><tex-math notation="LaTeX">$\sf {Tentacle}$</tex-math><alternatives> <inline-graphic xlink:href="zhang-ieq7-2604803.gif"/></alternatives></inline-formula> using real network data at global and county-wide scales. Measurement-driven simulations show that with a given cost budget <inline-formula> <tex-math notation="LaTeX">$\sf {Tentacle}$</tex-math><alternatives> <inline-graphic xlink:href="zhang-ieq8-2604803.gif"/></alternatives></inline-formula> can improve user performance by around 10-45 percent at global scale networks and 15-35 percent at a country-wide scale network.
Efficient rotation invariant object detection using boosted Random Ferns

We present a new approach for building an efficient and robust classifier for the two class problem, that localizes objects that may appear in the image under different orientations. In contrast to other works that address this problem using multiple classifiers, each one specialized for a specific orientation, we propose a simple two-step approach with an estimation stage and a classification stage. The estimator yields an initial set of potential object poses that are then validated by the classifier. This methodology allows reducing the time complexity of the algorithm while classification results remain high. The classifier we use in both stages is based on a boosted combination of Random Ferns over local histograms of oriented gradients (HOGs), which we compute during a preprocessing step. Both the use of supervised learning and working on the gradient space makes our approach robust while being efficient at run-time. We show these properties by thorough testing on standard databases and on a new database made of motorbikes under planar rotations, and with challenging conditions such as cluttered backgrounds, changing illumination conditions and partial occlusions.
Hsp 15 : a ribosome-associated heat shock protein

is essential to the cell not only after heat shock but Philipp Korber, Jennifer M.Stahl, also under normal conditions. We decided that the Knud H.Nierhaus1 and James C.A. Bardwell2 uncharacterized heat shock proteins recently uncovered Department of Biology, University of Michigan, Ann Arbor, by genomic expression screening technology represent MI 48109-1048, USA and 1Max-Planck-Institut für Molekulare a promising source of new chaperones, proteases and Genetik, AG Ribosomen, Ihnestrasse 74, D-14195 Berlin, Germany possibly other important cellular functions as well. 2Corresponding author Very recently, a global screening of the 4290 ORFs in e-mail: jbardwel@umich.edu E.coli by ‘gene chip’ array technology revealed a total of This publication is dedicated to Thomas O.Golda and Kathrin Pongratz 77 ORFs that are induced 5-fold at the RNA level upon on the occasion of their reunion anniversary temperature upshift (Richmond et al., 1999). The function of at least one-third of these proteins is unknown (Gross, We are analyzing highly conserved heat shock genes 1996; Richmond et al., 1999). of unknown or unclear function with the aim of We are investigating the function of three highly condetermining their cellular role. Hsp15 has previously served, very heat-inducible ORFs: yrfH/hslR, yrfI/hslO been shown to be an abundant nucleic acid-binding and ftsJ. The gene for Hsp15 (yrfH/hslR) shows a 43-fold protein whose synthesis is induced massively at the induction as assayed by radioactivity, making it the fifth RNA level upon temperature upshift. We have now most highly heat inducible of the 4290 genes in E.coli identified that the in vivo target of Hsp15 action is the (Richmond et al., 1999). Seventy-seven ORFs showed a free 50S ribosomal subunit. Hsp15 binds with very 5-fold induction with this assay. This makes the gene high affinity (KD <5 nM) to this subunit, but only when for Hsp15 more highly heat inducible than nearly all well 50S is free, not when it is part of the 70S ribosome. In studied heat shock genes including groEL, groES dnaK, addition, the binding of Hsp15 appears to correlate dnaJ, clpA, clpP, rpoD, rpoH and lon. When assayed by with a specific state of the mature, free 50S subunit, using a fluorescent microarray gene chip, Hsp15 RNA which contains bound nascent chain. This provides the showed a similar, 51-fold induction. first evidence for a so far unrecognized abortive event In a previous report (Korber et al., 1999), we described in translation. Hsp15 is suggested to be involved in the the purification of the gene product of yrfH/hslR, Hsp15, recycling of free 50S subunits that still carry a nascent and its in vitro characterization as a nucleic acid-binding chain. This gives Hsp15 a very different functional role protein. This activity is different from that of most heat from all other heat shock proteins and points to a new shock proteins, which function at the protein level as aspect of translation. chaperones or proteases. We are interested in determining
Inferring social ties in academic networks using short-range wireless communications

WiFi base stations are increasingly deployed in both public spaces and private companies, and the increase in their density poses a significant threat to the privacy of connected users. Prior studies have provided evidence that it is possible to infer the social ties of users from their location and co-location traces but they lack one important component: the comparison of the inference accuracy between an internal attacker (e.g., a curious application running on a mobile device) and a realistic external eavesdropper in the same field trial. In this paper, we experimentally show that such an eavesdropper is able to infer the type of social relationships between mobile users better than an internal attacker. Moreover, our results indicate that by exploiting the underlying social community structure of mobile users, the accuracy of the inference attacks doubles. Based on our findings, we propose countermeasures to help users protect their privacy against eavesdroppers.