Miracle-dz/UniFAR-FTUs huggingface dataset:
A novel role for the NLRC 4 inflammasome in mucosal defenses against the fungal pathogen Candida albicans

Candida sp. are opportunistic fungal pathogens that colonize the skin and oral cavity and, when overgrown under permissive conditions, cause inflammation and disease. Previously, we identified a central role for the NLRP3 inflammasome in regulating IL-1b production and resistance to dissemination from oral infection with Candida albicans. Here we show that mucosal expression of NLRP3 and NLRC4 is induced by Candida infection, and up-regulation of these molecules is impaired in NLRP3 and NLRC4 deficient mice. Additionally, we reveal a role for the NLRC4 inflammasome in anti-fungal defenses. NLRC4 is important for control of mucosal Candida infection and impacts inflammatory cell recruitment to infected tissues, as well as protects against systemic dissemination of infection. Deficiency in either NLRC4 or NLRP3 results in severely attenuated pro-inflammatory and antimicrobial peptide responses in the oral cavity. Using bone marrow chimeric mouse models, we show that, in contrast to NLRP3 which limits the severity of infection when present in either the hematopoietic or stromal compartments, NLRC4 plays an important role in limiting mucosal candidiasis when functioning at the level of the mucosal stroma. Collectively, these studies reveal the tissue specific roles of the NLRP3 and NLRC4 inflammasome in innate immune responses against mucosal Candida infection. Citation: Tomalka J, Ganesan S, Azodi E, Patel K, Majmudar P, et al. (2011) A Novel Role for the NLRC4 Inflammasome in Mucosal Defenses against the Fungal Pathogen Candida albicans. PLoS Pathog 7(12): e1002379. doi:10.1371/journal.ppat. 1002379 Editor: Scott G. Filler, David Geffen School of Medicine at University of California Los Angeles, United States of America Received May 10, 2011; Accepted September 30, 2011; Published December 8, 2011 Copyright: 2011 Tomalka et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Funding: This work was supported by NIH R01DE018279 (AGH). JT was supported during a portion of the period of this study by NIH T32GM008056. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Competing Interests: The authors have declared that no competing interests exist. * E-mail: amy.hise@case.edu
Spatio-Temporal Modeling and Prediction of Visual Attention in Graphical User Interfaces

We present a computational model to predict users' spatio-temporal visual attention on WIMP-style (windows, icons, menus, pointer) graphical user interfaces. Like existing models of bottom-up visual attention in computer vision, our model does not require any eye tracking equipment. Instead, it predicts attention solely using information available to the interface, specifically users' mouse and keyboard input as well as the UI components they interact with. To study our model in a principled way, we further introduce a method to synthesize user interface layouts that are functionally equivalent to real-world interfaces, such as from Gmail, Facebook, or GitHub. We first quantitatively analyze attention allocation and its correlation with user input and UI components using ground-truth gaze, mouse, and keyboard data of 18 participants performing a text editing task. We then show that our model predicts attention maps more accurately than state-of-the-art methods. Our results underline the significant potential of spatio-temporal attention modeling for user interface evaluation, optimization, or even simulation.
Does the restart method work? Preliminary Results on Efficiency Improvements for Interactions of Web-agents

With the wide adoption of web-agents, improving the efficiency of their interactions is of great importance. The restart method aims to reduce overall completion times of such interactions by using the distribution of completion times to determine a best timeout after which it is more promising to re-issue a request than to wait for completion. In this paper, we review existing work on the restart method and self-similarity of internet traffic. We extend existing work by analysing the restart method for the four interaction phases connection, request, processing, reply. We obtain results for web-agents retrieving statically and dynamically generated webpages and discuss implications for agents based on middleware such as RPC, Corba, or mobile agents. Regarding the connection phase, previous work [9, 11] by Huberman et al. found a lognormal distribution in UDP connections. In contrast to the simpler UDP, we focus on the more complex and more widely used TCP/IP connections, for which we obtain more complicated distributions, which lead nonetheless to improvements in 65% of our experiments. Furthermore, in contrast to previous work we relate document size to reply times.
Cyclosporin A induces apoptosis in childhood acute lymphoblastic leukemia cells.

In an effort to identify novel antileukemic agents that can bypass the mechanisms of multidrug resistance, we found that cyclosporin A ([CyA] 5 mumol/L) produced a median cell kill of 69% (range, 47% to 85%) in seven B-lineage acute lymphoblastic leukemia (ALL) cell lines (OP-1, SUP-B15, KOPN-55bi, RS4;11, NALM6, REH, and 380) and three T-lineage ALL cell lines (MOLT4, CCRF-CEM, and CEM-C7) after 4 days of culture. At 10 mumol/L, median CyA toxicity was 99% (range, 88% to > 99%). CyA was equally toxic to both a multidrug-resistant cell line, CEM-VLB100, which overexpresses gp-170 P-glycoprotein, and one resistant to topoisomerase II inhibitors, CEM-VM1-5, which has a mutation in the topoisomerase II gene. CyA was also toxic to primary leukemic cells maintained in stroma-based culture, a system that substantially prolongs in vitro cell survival. Against lymphoblasts from 21 patients with B-lineage ALL, the compound (at 5 mumol/L) reduced the leukemic cell number by a median of 87% (range, 27% to > 99%) compared with results for parallel control cultures lacking CyA. Seven of these samples were from cases with unfavorable genetic features (e.g., Philadelphia-chromosome or MLL gene rearrangements); three were obtained at relapse. Against T lymphoblasts (from six patients), the median reduction in cell number was 79% (range, 30% to > 99%). At 10 mumol/L, the cell kill exceeded 97% in all cases studied. The mechanism of CyA cytotoxicity was found to be the activation of apoptosis, which was suppressed by phorbol myristate acetate but not by inhibitors of ceramide-mediated apoptosis, phosphatidyl inositol-3 kinase activity, or tyrosine kinase activity. These findings demonstrate high levels of CyA-induced toxicity against ALL cells at concentrations achievable in vivo, thus providing a strong rationale for clinical testing of this agent in patients with ALL.
Occurrence of a fetal fibroblast phenotype in familial breast cancer

We have previously shown that fetal and adult human skin fibroblasts display distinctive migratory phenotypes when cultured on 3‐dimensional collagen gels in vitro. In the present study, we have used this information to assess the migratory behavior of fibroblasts obtained from patients with either benign or malignant breast disease, and correlated this with the presence of a family history of breast cancer. We have observed that fibroblasts from 17/34 patients with no previous family history of breast cancer displayed fetal‐type behavior in our assay system; in contrast, fibroblasts from 15/16 patients with a positive family history of breast cancer behaved abnormally. This apparently increased probability of expressing a fetaltype migratory phenotype in the patients with a family history is statistically significant (p > 0.008). Skin fibroblasts obtained from 2 healthy and unaffected first‐degree relatives (one male and one female) of patients with a family history of breast cancer also exhibited a fetal‐type migratory phenotype.
The Voice That Challenged a Nation: Marian Anderson and the Struggle for Equal Rights

Biography Bridges, Ruby. 1999. Through My Eyes. Illustrated with photographs, newspaper articles, and other quotes from the late 1950s and early 1960s. Scholastic. (63 pp.) (ISBN 0590189239) Ruby Bridges recalls her experience as the six-year-old African American child who integrated her New Orleans elementary school and was escorted to class by federal marshals, taunted by angry mobs, taught one-on-one by a brave, young white teacher, and supported by the faith of her parents.
Micro-Virtualization Memory Tracing to Detect and Prevent Spraying Attacks

Spraying is a common payload delivery technique used by attackers to execute arbitrary code in presence of Address Space Layout Randomisation (ASLR). In this paper we present Graffiti, an efficient hypervisorbased memory analysis framework for the detection and prevention of spraying attacks. Compared with previous solutions, our system is the first to offer an efficient, complete, extensible, and OS independent protection against all spraying techniques known to date. We developed a prototype open source framework based on our approach, and we thoroughly evaluated it against all known variations of spraying attacks on two operating systems: Linux and Microsoft Windows. Our tool can be applied out of the box to protect any application, and its overhead can be tuned according to the application behavior and to the desired level of protection.
Clinical and Experimental Evidence of Supernormal Excitability and Conduction

True supernormality of excitability and conduction has been demonstrated in normal Purkinje fibers in in vitro studies. In the clinical setting, supernormality of conduction is manifested better than expected. This phenomenon is much more common than previously thought, particularly in the presence of certain clinical conditions. If a careful scanning of the cardiac cycle is performed on all patients with intermittent bundle branch block and second degree or advanced infranodal AV block, accessory pathways and mulfunctioning pacemakers, it is anticipated that a much larger amount of supernormal excitability and conduction will be unmasked.
Chronic Drinking, Binge Drinking and Drunk Driving

Data from the Brief Risk Factor Surveillance System on 47 states were examined in an ecological analysis of the relationship between rates of binge drinking, chronic drinking, and driving while intoxicated (DWI). DWI rates were significantly associated with rates of binge drinking but not with chronic heavy drinking. This finding has implications for the nature and targets of efforts toward prevention.
Emerging Technologies and Cognitive Disability

Despite the potential of emerging technologies to assist persons with cognitive disabilities, significant practical impediments remain to be overcome in commercialization, consumer abandonment, and in the design and development of useful products. Barriers also exist in terms of the financial and organizational feasibility of specific envisioned products, and their limited potential to reach the consumer market. Innovative engineering approaches, effective needs analysis, user-centered design, and rapid evolutionary development are essential to ensure that technically feasible products meet the real needs of persons with cognitive disabilities. Efforts must be made by advocates, designers and manufacturers to promote better integration of future software and hardware systems so that forthcoming iterations of personal support technologies and assisted care systems technologies do not quickly become obsolete. They will need to operate seamlessly across multiple real-world environments in the home, school, community, and workplace.
Inhibition of Apoptosis in Chlamydia-infected Cells: Blockade of Mitochondrial Cytochrome c Release and Caspase Activation

We report that chlamydiae, which are obligate intracellular bacterial pathogens, possess a novel antiapoptotic mechanism. Chlamydia-infected host cells are profoundly resistant to apoptosis induced by a wide spectrum of proapoptotic stimuli including the kinase inhibitor staurosporine, the DNA-damaging agent etoposide, and several immunological apoptosis-inducing molecules such as tumor necrosis factor-α, Fas antibody, and granzyme B/perforin. The antiapoptotic activity was dependent on chlamydial but not host protein synthesis. These observations suggest that chlamydia may encode factors that interrupt many different host cell apoptotic pathways. We found that activation of the downstream caspase 3 and cleavage of poly (ADP-ribose) polymerase were inhibited in chlamydia-infected cells. Mitochondrial cytochrome c release into the cytosol induced by proapoptotic factors was also prevented by chlamydial infection. These observations suggest that chlamydial proteins may interrupt diverse apoptotic pathways by blocking mitochondrial cytochrome c release, a central step proposed to convert the upstream private pathways into an effector apoptotic pathway for amplification of downstream caspases. Thus, we have identified a chlamydial antiapoptosis mechanism(s) that will help define chlamydial pathogenesis and may also provide information about the central mechanisms regulating host cell apoptosis.
From Conditioning to Conscious Recollection Memory Systems of the Brain. Oxford Psychology Series, Volume 35.

The authors conceptualize these memory systems from both behavioural and neurobiological perspectives, guided by three related principles: * First, that our understanding of a wide range of memory phenomena can be advanced by breaking down memory into multiple forms with different operating characteristics. * Second, that different forms of memory representation are supported by distinct brain pathways with circuitry and neural coding properties. * Third, that the contributions of different brain systems can be compared and contrasted by distinguishing between dedicated (or specific) and elaborate (or general) memory systems. A primary goal of this work is to relate the neurobiological properties of dedicated and elaborate systems to their neuropsychological counterparts, and in so doing, account for the phenomenology of memory, from conditioning to conscious recollection.
Subtypes of depression and comorbid disorders

Subtypes of Depression: Biology of Bipolar Disorder A.C. Swann. The Biology of Depression in Children and Adolescents N.D. Ryan, R.E. Dahl. The Biology of Late Life Depression C.B. Nemeroff, et al. The Biology of Chronic Depression J.H. Kocsis. Biological Relationships of Comorbid Disorder: The Biology of Personality Disorders O. Kalus, L.J. Siever. Depression in Alcoholism A. Roy, M. Linnoila. Serotonin and Norepinephrine Activity in Anorexia and Bulimia Nervosa W.H. Kaye, et al. The Biology of Panic Disorder J.D. Coplan, et al. Index.
Values in global health governance

Abstract In the 60 years since the Universal Declaration of Human Rights was promulgated, the promise of achieving respect for the human rights, health and well being of all is becoming an ever more distant prospect. We have not even remotely met the challenge of improving health for a large proportion of the world's population, and the prospects for improving global health seem to be receding in the current deteriorating economic and political climate. As global health remains one of the most pressing problems of our time, we must question the values that direct our actions and current approaches, which proclaim ‘human rights to health’ but which subsume these rights to a broader paradigm of unregulated global market economics and national politics, rather than working to make these oft-contradictory goals mutually compatible through justifiable and accountable global governance processes. We suggest that a new balance of values and new ways of thinking and acting are needed. These must transcend national and institutional boundaries and recognise that health in the most privileged nations is closely linked to health and disease in impoverished countries. Sustainable development of health and well-being is a necessity for all, and values for health should permeate every area of social and economic activity.
Enhancing traffic sampling scope and efficiency

Traffic sampling is a crucial step towards scalable network measurements, enclosing manifold challenges. The wide variety of foreseeable sampling scenarios demands for a modular view of sampling components and features, grounded on a consistent architecture. Articulating the measurement scope, the required information model and the adequate sampling strategy is a major design issue for achieving an encompassing and efficient sampling solution. This is the main focus of the present work, where a layered architecture, a taxonomy of existing sampling techniques distinguishing their inner characteristics and a flexible framework able to combine these characteristics are introduced. In addition, a new multi-adaptive technique proposal, based on linear prediction, allows to reduce the measurement overhead significantly, while assuring that traffic samples reflect the statistical behavior of the global traffic under analysis.
Threonine dehydratases of Corynebacterium glutamicum with altered allosteric control: their generation and biochemical and structural analysis

Threonine dehydratase is the key enzyme in L‐isoleucine synthesis, since it is allosterically feedback‐inhibited by L‐isoleucine. With the aim of obtaining regulatorily altered mutants of the threonine dehydratase of Corynebacterium glutamicum, amino acids were specifically exchanged and a new biological system of mutant selection was developed, based on the intoxication of Escherichia coli by ketobutyrate, which is the dehydratase reaction product. A collection of 19 mutant enzymes was generated and genetically and biochemically characterized comprising a whole range of regulatorily and catalytically altered enzymes. Of particular interest is the mutant Val‐323‐Ala, which is characterized by the fact that the L‐isoleucine inhibition is entirely abolished so that the enzyme is always present in a relaxed, high‐activity state. Correspondingly, the Hill coefficient is 1.4, in contrast to the value of 3.4 characteristic of the wild‐type enzyme. Another peculiar mutant generated is the double mutant His‐278‐Arg‐Leu‐351‐Ser. Here, again, L‐isoleucine no longer inhibits catalytic activity, but the effector still promotes major structural changes of the protein, as ascertained from the L‐isoleucine‐dependent loss of pyridoxal‐5 ‐phosphate from this mutant enzyme. Further enzymes obtained are reduced in L‐isoleucine inhibition to a varying degree. Detailed studies on the structure of the enzyme revealed a partially very high similarity of the secondary structure to the mechanistically identical β‐subunit of the tryptophan synthase. This provides further indications concerning the localization of the regulatory and catalytic domain of threonine dehydratase.
LOPHOTOXIN BLOCKS SYNAPTIC ACETYLCHOLINE RECEPTORS IN THE COCKROACH PERIPLANETA AMERICANA

The actions of lophotoxin on synaptic acetylcholine receptors were investigated, using the cholinergic synapse between the lateral filiform hair sensory neurone and giant interneurone 3 in the first-instar cockroach Periplaneta americana. Lophotoxin (1-Oxl0~moll~) blocked transmission without affecting the passive or active membrane properties of the preand postsynaptic neurones, and without affecting non-cholinergic synaptic inputs. Micromolar concentrations of lophotoxin also blocked the depolarizing response of giant interneurone 3 to carbamylcholine, when applied ionophoretically to its dendritic branches. The toxin shifted , the dose-response curve to the right by two orders of magnitude, suggesting that it was acting as a competitive antagonist. Lophotoxin is a diterpene lactone isolated from gorgonian corals of the genus Lophogorgia (Fenical et al. 1981). It has recently been shown to block nicotinic neuromuscular transmission in vertebrates at micromolar concentrations (Culver & Jacobs, 1981; Langdon & Jacobs, 1983; Atchison, Narahashi & Vogel, 1984), and binding studies have shown that it blocks transmission by binding to the acetylcholine recognition sites of muscle nicotinic receptors (Culver, Fenical & Taylor, 1984). Recently, lophotoxin has emerged as a selective, high-affinity antagonist at neuronal nicotinic receptors, blocking transmission in autonomic ganglia of the chick and rat at concentrations in the range 1-Oxl0~moll~ to 3-2xlO~moll~ (Sorenson, Culver & Chiappinelli, 1987). However, the toxin has not been tested on invertebrate nervous tissues. There is considerable evidence that cereal afferent, giant interneurone synapses of the cockroach Periplaneta americana are cholinergic (Sattelle, 1985), and the nicotinic antagonist a'-bungarotoxin blocks transmission at nanomolar concentrations (Sattelle et al. 1983). The first-instar terminal abdominal ganglion is a useful preparation for studies of axonal and synaptic physiology since the
MOSFET stacked-pair test structure for mismatch evaluation by estimating the on-resistance ratio

This work describes a procedure for evaluating the mismatch between MOSFET transistors in a test array and connected as stacked-pairs. The transistor mismatch is characterized by measuring the gate voltage dependence of the DC voltage established at the middle node of the common-gate MOSFET stacked-pair. This procedure is modeled as the on-resistance ratio of these two transistors and it is performed by two simple measurements. Various pieces of information on the MOSFET mismatch characteristics (e.g., channel length variation and threshold voltage variation) can be extracted. The test structure was manufactured in 180nm CMOS technology, and the test array was designed to allow a large number of MOSFET stacked-pairs, from transistors placed in different parts of the layout to vary gradually the distance of the paired FETs.
Muscle glycogen accumulation after endurance exercise in trained and untrained individuals.

Muscle glycogen accumulation was determined in six trained cyclists (Trn) and six untrained subjects (UT) at 6 and either 48 or 72 h after 2 h of cycling exercise at approximately 75% peak O2 uptake (VO2 peak), which terminated with five 1-min sprints. Subjects ate 10 g carbohydrate . kg-1 . day-1 for 48-72 h postexercise. Muscle glycogen accumulation averaged 71 +/- 9 (SE) mmol/kg (Trn) and 31 +/- 9 mmol/kg (UT) during the first 6 h postexercise (P < 0.01) and 79 +/- 22 mmol/kg (Trn) and 60 +/- 9 mmol/kg (UT) between 6 and 48 or 72 h postexercise (not significant). Muscle glycogen concentration was 164 +/- 21 mmol/kg (Trn) and 99 +/- 16 mmol/kg (UT) 48-72 h postexercise (P < 0.05). Muscle GLUT-4 content immediately postexercise was threefold higher in Trn than in UT (P < 0.05) and correlated with glycogen accumulation rates (r = 0.66, P < 0.05). Glycogen synthase in the active I form was 2.5 +/- 0.5, 3.3 +/- 0.5, and 1.0 +/- 0.3 micromol . g-1 . min-1 in Trn at 0, 6, and 48 or 72 h postexercise, respectively; corresponding values were 1.2 +/- 0.3, 2.7 +/- 0.5, and 1.6 +/- 0.3 micromol . g-1 . min-1 in UT (P < 0.05 at 0 h). Plasma insulin and plasma C-peptide area under the curve were lower in Trn than in UT over the first 6 h postexercise (P < 0.05). Plasma creatine kinase concentrations were 125 +/- 25 IU/l (Trn) and 91 +/- 9 IU/l (UT) preexercise and 112 +/- 14 IU/l (Trn) and 144 +/- 22 IU/l (UT; P < 0.05 vs. preexercise) at 48-72 h postexercise (normal: 30-200 IU/l). We conclude that endurance exercise training results in an increased ability to accumulate muscle glycogen after exercise.