Miracle-dz/UniFAR-FTUs huggingface dataset:
Seasonal differences in finger skin temperature and microvascular blood flow in healthy men and women are exaggerated in women with primary Raynaud's phenomenon.

AIMS Patients with primary Raynaud's phenomenon (PRP) have more severe symptoms in the winter. The aetiology of this is more complex than simply increased vasoconstriction in response to the immediate ambient temperature. The aim of this study was to investigate differences in skin temperature (Tsk), microvascular blood flow and responses to endothelium-dependent and independent vasodilators in healthy controls, and women with PRP under identical environmental temperatures but in different seasons. METHODS Ten women with PRP were compared with age matched women (10) and men (10). Finger skin responses were recorded immediately on arrival, after stabilizing in a temperature regulated laboratory at 22-24 degrees C, and at matched warm (35 degrees C) and cold (15 degrees C) Tsk in the winter and summer. Baseline red blood cell flux (r.b.c. flux), and the change in flux in response to iontophoresis of acetylcholine (ACh) and sodium nitroprusside (SNP) were recorded by laser Doppler fluxmetry at the warm and cold Tsk. RESULTS Arrival Tsk were significantly cooler for all subjects during the winter (mean seasonal difference -2.6 degrees C, P < 0.0001), and markedly colder in subjects with PRP (mean seasonal difference -3.5 degrees C, P < 0.0005). Statistically significant seasonal differences persisted in all subjects at stable Tsk despite an identical laboratory temperature (mean difference 1.3 degrees C, P < 0.0001). To achieve comparable controlled finger Tsk a significantly colder local environment was required for male controls (mean of -2.1 degrees C, P < 0.0001), and a significantly warmer environment for subjects with PRP (mean of + 2.4 degrees C, P < 0.0001) compared with female controls. This needed to be warmer in the winter, by a mean of 2.4 degrees C, than the summer for all subjects. Vasodilatation in response to ACh, but not SNP, was significantly smaller (P < 0.0001) in the PRP group compared with the female controls for all visits, with most of this difference arising in the winter visits (P < 0.01). CONCLUSIONS There is a seasonal and persistent influence on finger Tsk, and microvascular blood flow in healthy men and women, which modifies the observed responses to immediate changes in finger Tsk. The seasonal differences are greater in women than men, and are further exaggerated in women with PRP, in whom this is associated with reduced endothelium-dependent vasodilatation.
Interaction between virion-bound host intercellular adhesion molecule-1 and the high-affinity state of lymphocyte function-associated antigen-1 on target cells renders R5 and X4 isolates of human immunodeficiency virus type 1 more refractory to neutralization.

The oligomeric nature of the viral envelope proteins has been partly held responsible for the observed differences in neutralization sensitivity between primary and laboratory-adapted strains of human immunodeficiency virus type 1 (HIV-1). However, recent evidence suggests that host factors can also modify the sensitivity of HIV-1 particles to neutralization. Having previously demonstrated that the acquisition of host-encoded intercellular adhesion molecule (ICAM)-1 proteins by newly formed viruses has a functional significance for the life cycle of HIV-1, we investigated whether the acquisition of host-derived ICAM-1 by HIV-1 could affect the virus sensitivity to neutralization. In this study, we have first shown that the physical presence of host cell membrane ICAM-1 on HIV-1 was not modifying virus sensitivity to neutralization by either two different anti-gp120 monoclonal antibodies (0.5beta and 4.8D) or soluble CD4. However, the ability of the F105 anti-gp120 monoclonal antibody (specific for the CD4-binding site) to neutralize ICAM-1-bearing virions was diminished when target cells were pretreated with an lymphocyte function-associated antigen-1 (LFA-1)-activating antibody. Interestingly, ICAM-1/POS progeny viruses were found to be slightly more resistant to neutralization by individual human sera in target cells expressing a low-affinity form of LFA-1 than viruses devoid of host-encoded ICAM-1 proteins. This resistance was markedly enhanced when target cells expressed an activated LFA-1 form on their surface. These results suggest that the interaction between virally embedded host ICAM-1 and target cell surface LFA-1 should be considered a factor modulating neutralization sensitivity of HIV-1 by human sera from HIV-1-infected individuals.
Aortic Dissection Precedes Formation of Aneurysms and Atherosclerosis in Angiotensin II-Infused, Apolipoprotein E-Deficient Mice

Objective—We sought to define the temporal characteristics of angiotensin II (AngII)-induced abdominal aortic aneurysms (AAAs) and to provide mechanistic insight into the development of this vascular pathology in apolipoprotein E-deficient (apoE-/-) mice. Methods and Results—Male apoE-/- mice were infused with AngII for 1 to 56 days. Suprarenal arteries were sequentially sectioned, and cellular features were defined by histologic and immunocytochemical techniques. The initial identified event was medial accumulation of macrophages in regions of elastin degradation. Subsequent medial dissection was associated with luminal dilation and thrombus formation. Thrombi were usually constrained by adventitial tissue, although ≈10% of mice died due to rupture. Thrombi led to profound inflammation that was characterized by infiltration of macrophages and T and B lymphocytes. Remodeling of the tissues was associated with regeneration of elastin fibers and reendothelialization of the dilated luminal surface. Aneurysmal tissue underwent profound neovascularization. Atherosclerotic lesions were only detected after development of the aneurysms. Conclusions—The initial event in AngII-induced AAA is a focal dissection in the suprarenal region. The progression of AAA precedes the development of overt atherosclerotic lesions.
Hardware Generation of Arbitrary Random Number Distributions From Uniform Distributions Via the Inversion Method

We present an automated methodology for producing hardware-based random number generator (RNG) designs for arbitrary distributions using the inverse cumulative distribution function (ICDF). The ICDF is evaluated via piecewise polynomial approximation with a hierarchical segmentation scheme that involves uniform segments and segments with size varying by powers of two which can adapt to local function nonlinearities. Analytical error analysis is used to guarantee accuracy to one unit in the last place (ulp). Compact and efficient RNGs that can reach arbitrary multiples of the standard deviation sigma can be generated. For instance, a Gaussian RNG based on our approach for a Xilinx Virtex-4 XC4VLX100-12 field-programmable gate array produces 16-bit random samples up to 8.2 sigma. It occupies 487 slices, 2 block-RAMs, and 2 DSP-blocks. The design is capable of running at 371 MHz and generates one sample every clock cycle.
Balancing and Step Recovery Capturability via Sums-of-Squares Optimization

A fundamental requirement for legged robots is to maintain balance and prevent potentially damaging falls whenever possible. As a response to outside disturbances, fall prevention can be achieved by a combination of active balancing actions, e.g. through ankle torques and upper-body motion, and through reactive step placement. While it is widely accepted that stepping is required to respond to large disturbances, the limits of active motions on balancing and step recovery are only well understood for the simplest of walking models. Recent advances in convex optimization-based verification and control techniques enable a more complete understanding of the limits and capabilities of more complex models. In this work, we present an algorithmic approach for formal analysis of the viable-capture basins of walking robots, calculating both inner and outer approximations and corresponding push recovery control strategies. Extending beyond the classic Linear Inverted Pendulum Model (LIPM), we analyze a series of centroidal momentum based planar walking models, examining the effects of center of mass height, angular momentum, and impact dynamics during stepping on capturability. This formal analysis enables an explicit calculation of the differences between these models, and assessment of whether the simplest models ultimately sacrifice capability, and thus stability, when designing push recovery control policies.
Effect of influenza vaccination on oxidative stress products in breath

Viral infections cause increased oxidative stress, so a breath test for oxidative stress biomarkers (alkanes and alkane derivatives) might provide a new tool for early diagnosis. We studied 33 normal healthy human subjects receiving scheduled treatment with live attenuated influenza vaccine (LAIV). Each subject was his or her own control, since they were studied on day 0 prior to vaccination, and then on days 2, 7 and 14 following vaccination. Breath volatile organic compounds (VOCs) were collected with a breath collection apparatus, then analyzed by automated thermal desorption with gas chromatography and mass spectroscopy. A Monte Carlo simulation technique identified non-random VOC biomarkers of infection based on their C-statistic values (area under curve of receiver operating characteristic). Treatment with LAIV was followed by non-random changes in the abundance of breath VOCs. 2, 8-Dimethyl-undecane and other alkane derivatives were observed on all days. Conservative multivariate models identified vaccinated subjects on day 2 (C-statistic = 0.82, sensitivity = 63.6% and specificity = 88.5%); day 7 (C-statistic = 0.94, sensitivity = 88.5% and specificity = 92.3%); and day 14 (C-statistic = 0.95, sensitivity = 92.3% and specificity = 92.3%). The altered breath VOCs were not detected in live attenuated influenza vaccine, excluding artifactual contamination. LAIV vaccination in healthy humans elicited a prompt and sustained increase in breath biomarkers of oxidative stress. A breath test for these VOCs could potentially identify humans who are acutely infected with influenza, but who have not yet developed clinical symptoms or signs of disease.
Research on e-Service quality, customer relational benefits and customer satisfaction

In this research, a relationship model among e-Service quality, Customer Relational Benefits and customer satisfaction is constructed and verified from the perspective of e-Service process. Study results show that process-based quality and outcome-based quality of e-Service have significantly positive effects on the confidence benefits, social benefits, special treatment benefits and e-satisfaction of customers. While confidence benefits and special treatment benefits have significantly positive impact on e-satisfaction, the impact of social benefits is not significant.
Temporal Centering

We present a semantic and pragmatic account of the anaphoric properties of past and perfect that improves on previous work by integrating discourse structure, aspectual type, surface structure and commonsense knowledge. A novel aspect of our account is that we distinguish between two kinds of temporal intervals in the interpretation of temporal operators --- discourse reference intervals and event intervals. This distinction makes it possible to develop an analogy between centering and temporal centering, which operates on discourse reference intervals. Our temporal property-sharing principle is a defeasible inference rule on the logical form. Along with lexical and causal reasoning, it plays a role in incrementally resolving underspecified aspects of the event structure representation of an utterance against the current context.
Systematic analysis of yeast strains with possible defects in lipid metabolism

Lipids are essential components of all living cells because they are obligate components of biological membranes, and serve as energy reserves and second messengers. Many but not all genes encoding enzymes involved in fatty acid, phospholipid, sterol or sphingolipid biosynthesis of the yeast Saccharomyces cerevisiae have been cloned and gene products have been functionally characterized. Less information is available about genes and gene products governing the transport of lipids between organelles and within membranes or the turnover and degradation of complex lipids. To obtain more insight into lipid metabolism, regulation of lipid biosynthesis and the role of lipids in organellar membranes, a group of five European laboratories established methods suitable to screen for novel genes of the yeast Saccharomyces cerevisiae involved in these processes. These investigations were performed within EUROFAN (European Function Analysis Network), a European initiative to identify the functions of unassigned open reading frames that had been detected during the Yeast Genome Sequencing Project. First, the methods required for the complete lipid analysis of yeast cells based on chromatographic techniques were established and standardized. The reliability of these methods was demonstrated using tester strains with established defects in lipid metabolism. During these investigations it was demonstrated that different wild‐type strains, among them FY1679, CEN.PK2‐1C and W303, exhibit marked differences in lipid content and lipid composition. Second, several candidate genes which were assumed to encode proteins involved in lipid metabolism were selected, based on their homology to genes of known function. Finally, lipid composition of mutant strains deleted of the respective open reading frames was determined. For some genes we found evidence suggesting a possible role in lipid metabolism. Copyright © 1999 John Wiley & Sons, Ltd.
Studies on the role of the thymus in immunobiology. Reconstitution of immunologic capacity in mice thymectomized at birth

Mice thymectomized immediately after birth are extremely defective in rejecting allogeneic skin or tumor grafts (2, 4, 5) and even xenogeneic skin (6). Their responsive antibody formation is also greatly impaired (6-8), although not necessarily for all antigens (8). These animals often develop a wasting syndrome, with failure of body growth and early mortality (6, 8-10), and are extremely susceptible to the runt disease produced by administration of aUogeneic lymphoid cells (9-11). Furthermore, the lymphoreticular cells derived from neonatally thymectomized mice are defective with respect to their capacity to elicit graft versus host reactions (12, 13). These animals also have a low level of circulating lymphocytes, a depletion of lymphocytes in the tissues, and, to a somewhat lesser degree, a depletion of plasma cells (2, 6, 8-11, 13). The immunologic defect, lymphoid cell depletion, and growth failure of these animals can be prevented by grafting a newborn thymus into the subcutaneous tissue (11) or by administration, shortly after thymectomy, of adult lymph node cells from syngeneic donors (13, 14). Some of the characteristics of the mice thymectomized at birth have also been described in other species subjected to neonatal thymectomy: the rat (15-17), rabbit (3, 10, 18), and hamster (19-22). Particularly interesting are the findings in the thymectomized hamster in which a wasting syndrome associated with hypogammaglobulinemia has been observed (19). Thymectomy after the immediate neonatal period does not cause wasting in mice, although it still has a significant effect on the development of immunologic reactivity as the animal matures. In certain strain combinations, isogenie at the tI-2 histocom-
Dependence of Ricin Toxicity on Translocation of the Toxin A-chain from the Endoplasmic Reticulum to the Cytosol*

Ricin acts by translocating to the cytosol the enzymatically active toxin A-chain, which inactivates ribosomes. Retrograde intracellular transport and translocation of ricin was studied under conditions that alter the sensitivity of cells to the toxin. For this purpose tyrosine sulfation of mutant A-chain in the Golgi apparatus, glycosylation in the endoplasmic reticulum (ER) and appearance of A-chain in the cytosolic fraction was monitored. Introduction of an ER retrieval signal, a C-terminal KDEL sequence, into the A-chain increased the toxicity and resulted in more efficient glycosylation, indicating enhanced transport from Golgi to ER. Calcium depletion inhibited neither sulfation nor glycosylation but inhibited translocation and toxicity, suggesting that the toxin is translocated to the cytosol by the pathway used by misfolded proteins that are targeted to the proteasomes for degradation. Slightly acidified medium had a similar effect. The proteasome inhibitor, lactacystin, sensitized cells to ricin and increased the amount of ricin A-chain in the cytosol. Anti-Sec61α precipitated sulfated and glycosylated ricin A-chain, suggesting that retrograde toxin translocation involves Sec61p. The data indicate that retrograde translocation across the ER membrane is required for intoxication.
Alleviation of a Selective Age-Related Relational Memory Deficit in Mice by Pharmacologically Induced Normalization of Brain Retinoid Signaling

Vitamin A and its derivatives, the retinoids, have been implicated recently in the synaptic plasticity of the hippocampus and might therefore play a role in associated cognitive functions. Acting via transcription factors, retinoids can regulate gene expression via their nuclear receptors [retinoic acid receptors (RARs) and retinoid X receptors]. In a series of experiments, the present study investigated the possible role of age-related downregulation of retinoid-mediated transcription events in the cognitive decline seen in aged mice. We observed that the brain (and hippocampal) levels of retinoid receptors and the expression of specific associated target genes were restored to presenescent (adult) levels in aged mice after acute administration (150 μg/kg, s.c.) of retinoic acid (RA). These effects of RA, however, could be abolished by the coadministration of an RAR antagonist. RA was also demonstrated to alleviate the age-related deficit in the CA1 long-term potentiation efficacy of aged micein vivo. Moreover, RA was found to alleviate completely the performance deficit of aged mice to the control level in a two-stage spatial discrimination paradigm designed to assess relational memory. This promnesic effect of RA was again susceptible to abolition by RAR antagonist treatment. The parallel molecular, cellular, and behavioral correlates associated with the decrease of retinoid receptor expression and its normalization demonstrated here suggest that the fine regulation of retinoid-mediated gene expression is fundamentally important to optimal brain functioning and higher cognition. Specifically, a naturally occurring dysregulation of retinoid-mediated molecular events might be a potential etiological factor for cognitive deterioration during senescence.
Autoflora in the upper respiratory tract of Apollo astronauts

The typical microbial inhabitants of the oral and nasal cavities of Apollo astronauts were identified before space flight and generally found to be similar to those previously reported for healthy male adults. Additional analyses of samples collected immediately after return of the Apollo 13, 14, 15, and 16 crew members to earth were performed to evaluate the effects of space travel on the microbial bioburden of the upper respiratory tract. In-flight cross-contamination and buildup of pathogens such as Staphylococcus aureus were noted, although significant increases in nonpathogenic species were absent. Other proposed alterations, such as dysbacteriosis (flooding of the mouth with a single species) and simplification of the autoflora, did not occur. Generally, the incidence and quantitation of each species after flight was within the preflight range, although the number of viable Haemophilus cells recovered from the mouth decreased significantly after space flight. Except for those minor alterations listed above, the aerobic and anaerobic bacterial components of the upper respiratory autoflora of Apollo astronauts was found to be stable after space flight of up to 295 h.
Improving effector functions of antibodies for cancer treatment: Enhancing ADCC and CDC

As platforms for therapeutic agents, monoclonal antibodies (MAbs) have already been approved, and several MAbs have demonstrated clinical effectiveness in a variety of malignancies. However, several issues have also been emerging in antibody therapy, such as high cost and insufficient drug action. Recently, to improve MAb activity in humans, effector functions have been subjects of focus, especially antibody-dependent cell-mediated cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC). Extensive efforts have been made to enhance these effector functions of MAbs, and successful approaches have been reported by us and others, wherein the binding activity of MAbs to FcγRIIIa or C1q is increased by introducing amino acid mutations into heavy chain constant regions or through glyco-modification of Fc-linked oligosaccharides. In addition, one of the next approaches to optimizing therapeutic antibodies would be to combine multiple enhancing modifications into a single antibody platform to overcome the diverse mechanisms of clinical resistance of tumor cells. For this aim, we have recently developed a successful combination composed of ADCC-enhancing modification by the fucose depletion from Fc-linked oligosaccharides and CDC-enhancing modification by IgG1 and IgG3 isotype shuffling in heavy chains, which could be of great value for the development of third-generation antibody therapeutics.
Feedback stabilization of predator-prey systems for impulsive biological control

Abstract In agricultural applications, the introduction of predators is used to control the prey/pests level so that crop damage is limited; however, though a satisfactory equilibrium between predators and prey may exist, it may be unstable. In order to achieve pest control, its stabilization should then be achieved and, since predator releases occur at discrete time instants, we model them through impulses upon which we will build a positive impulsive feedback control law. Our controller is based on the measurement of the state every T time instants followed by the introduction, when necessary, of predators into the system to instantaneously bring their population up to a prescribed level. The proposed controller is shown to lead to the global asymptotic stability of the desired equilibrium for T small; local stability is shown for some larger periods, and some numerical asymptotic analysis is performed.
The Use of Essential Oils in Ruminants as Modifi ers of Rumen Microbial Fermentation

87 0. Take Home Message The effi ciency of energy and protein utilization in the rumen may be improved through the manipulation of microbial population. Antibiotic ionophores have been very successful in improving these effi ciencies, but its use in animal feeds is facing reduced social acceptance. For this reason, other alternatives to control specifi c microbial populations are currently being investigated. Some essential oils have antimicrobial activities resulting in reduced peptidolysis, deamination and methanogenesis. Because the effects of essential oils are diet and pH dependent, the selection of the appropriate essential oil will depend on the specifi c objectives and target animal. Moreover, because essential oils may act at different levels in the energy and protein metabolic pathways, their careful selection and combination may provide a useful tool to effectively manipulate rumen microbial fermentation.