Miracle-dz/UniFAR-FTUs huggingface dataset:
Salmonella typhimurium translocates flagellin across intestinal epithelia, inducing a proinflammatory response.

This study investigated whether soluble paracrine factors mediated Salmonella-induced IL-8 expression in polarized model intestinal epithelia. We found that the basolateral media of model epithelia that had been apically infected with Salmonella typhimurium for a short period (10 minutes) could activate IL-8 secretion in virgin model epithelia, demonstrating that a proinflammatory factor (PIF) was indeed present. Initial characterization found that PIF was a heat-stable protein with a molecular mass of about 50 kDa that acts on the basolateral, but not apical, surface of model intestinal epithelia to elicit IL-8 secretion. PIF was not present in the media of model epithelia stimulated with other inducers of IL-8 secretion (TNF-alpha or carbachol) but was present in S. typhimurium supernatants, indicating PIF is of bacterial origin. PIF was purified from bacterial culture supernatants by anion/cation exchange chromatography and SDS-PAGE and found by using microsequencing to be the protein flagellin. In support of this finding, flagellin-deficient S. typhimurium mutants did not secrete detectable levels of PIF (i.e., a bioactivity that induced IL-8 secretion when placed basolaterally on model epithelia). Furthermore, viable flagellin-deficient mutant organisms (fliC/fljB and flhD) failed to elicit IL-8 secretion when added apically to model intestinal epithelia. These findings indicate that translocation of flagellin across epithelia, subsequent to apical epithelial-S. typhimurium interaction, is likely a major means of activating a mucosal inflammatory response.
Primary care physicians' attitudes and practices regarding complementary and alternative medicine

Abstract Data were gathered from 423 osteopathic primary care physicians who are members of the Michigan Osteopathic Association, assessing their attitudes and practices regarding complementary and alternative medicine (CAM). Family physicians and general internists were more likely than pediatricians to talk to their patients about CAM. Similarly, female physicians were more likely than male physicians to talk to their patients about CAM or refer their patients for CAM. Finally, physicians aged 35 years and younger were more likely than those 60 years and older to use CAM for themselves or their families. Predominant among the conditions for which the physicians would refer for CAM were long-term problems, traditional therapy failures, psychiatric disorders, and behavioral problems. Results reveal wide variations in the way osteopathic primary care physicians view and use complementary and alternative care.
Tissue engineering with the aid of inkjet printers

Tissue engineering holds the promise to create revolutionary new therapies for tissue and organ regeneration. This emerging field is extremely broad and eclectic in its various approaches. However, all strategies being developed are based on the therapeutic delivery of one or more of the following types of tissue building-blocks: cells; extracellular matrices or scaffolds; and hormones or other signaling molecules. So far, most work has used essentially homogenous combinations of these components, with subsequent self-organization to impart some level of tissue functionality occurring during in vitro culture or after transplantation. Emerging ‘bioprinting’ methodologies are being investigated to create tissue engineered constructs initially with more defined spatial organization, motivated by the hypothesis that biomimetic patterns can achieve improved therapeutic outcomes. Bioprinting based on inkjet and related printing technologies can be used to fabricate persistent biomimetic patterns that can be used both to study the underlying biology of tissue regeneration and potentially be translated into effective clinical therapies. However, recapitulating nature at even the most primitive levels such that printed cells, extracellular matrices and hormones become integrated into hierarchical, spatially organized three-dimensional tissue structures with appropriate functionality remains a significant challenge.
Symmetry-Breaking as a Paradigm to Design Highly-Sensitive Sensor Systems

A large class of dynamic sensors have nonlinear input-output characteristics, often corresponding to a bistable potential energy function that controls the evolution of the sensor dynamics. These sensors include magnetic field sensors, e.g., the simple fluxgate magnetometer and the superconducting quantum interference device (SQUID), ferroelectric sensors and mechanical sensors, e.g., acoustic transducers, made with piezoelectric materials. Recently, the possibilities offered by new technologies and materials in realizing miniaturized devices with improved performance have led to renewed interest in a new generation of inexpensive, compact and low-power fluxgate magnetometers and electric-field sensors. In this article, we review the analysis of an alternative approach: a symmetry-based design for highly-sensitive sensor systems. The design incorporates a network architecture that produces collective oscillations induced by the coupling topology, i.e., which sensors are coupled to each other. Under certain symmetry groups, the oscillations in the network emerge via an infinite-period bifurcation, so that at birth, they exhibit a very large period of oscillation. This characteristic renders the oscillatory wave highly sensitive to symmetry-breaking effects, thus leading to a new detection mechanism. Model equations and bifurcation analysis are discussed in great detail. Results from experimental works on networks of fluxgate magnetometers are also included.
Instantons in Non-Critical Strings from the Two-Matrix Model

We derive the non-perturbative corrections to the free energy of the two-matrix model in terms of its algebraic curve. The eigenvalue instantons are associated with the vanishing cycles of the curve. For the (p,q) critical points our results agree with the geometrical interpretation of the instanton effects recently discovered in the CFT approach. The form of the instanton corrections implies that the linear relation between the FZZT and ZZ disc amplitudes is a general property of the 2D string theory and holds for any classical background. We find that the agreement with the CFT results holds in presence of infinitesimal perturbations by order operators and observe that the ambiguity in the interpretation of the eigenvalue instantons as ZZ-branes (four different choices for the matter and Liouville boundary conditions lead to the same result) is not lifted by the perturbations. We find similar results to the c = 1 string theory in presence of tachyon perturbations.
Metabolic Syndrome and the Risk of Ischemic Heart Disease and Stroke Among Japanese Men and Women

Background and Purpose— Limited evidence was available on the metabolic syndrome and risk of cardiovascular disease in Asia. The purpose of this study is to examine the association of the metabolic syndrome and risk of ischemic cardiovascular disease in Japanese men and women. Methods— We conducted an 18-year prospective study of 9087 Japanese people aged 40 to 69 years (3595 men and 5492 women), initially free of ischemic heart disease or stroke. During follow-up, there were 116 (74 men and 42 women) cases of ischemic heart disease and 256 (144 men and 112 women) ischemic strokes. Metabolic syndrome was defined by the modified criteria of the National Cholesterol Education Program Adult Treatment Panel III (NCEP/ATPIII), with the presence of ≥3 of the following factors: (1) serum triglycerides ≥1.69 mmol/L (150 mg/dL); (2) HDL-cholesterol <1.03 mmol/L (40 mg/dL) for men and <1.29 mmol/L (50 mg/dL) for women; (3) glucose ≥6.11 mmol/L (110 mg/dL) fasting or ≥7.77 mmol/L (140 mg/dL) nonfasting, or on treatment; (4) blood pressure ≥130/85 mm Hg or medication use, and (5) body mass index ≥25.0 kg/m2. Results— For both sexes, high blood pressure, high triglycerides and low HDL cholesterol were associated with increased risks of ischemic heart disease or stroke after adjustment for cardiovascular risk factors. A dose-response relationship was found between the number of metabolic risk factors and incidence of these cardiovascular end points. The multivariable hazard ratio (95% CI) associated with metabolic syndrome was 2.4 (1.4 to 4.0) in men and 2.3 (1.2 to 4.3) in women for ischemic heart disease, and 2.0 (1.3 to 3.1) and 1.5 (1.0 to 2.3), respectively, for ischemic stroke. The contribution of metabolic syndrome to the risks was independent of serum total cholesterol levels but stronger among smokers. Conclusions— The metabolic syndrome is a major determinant of ischemic cardiovascular disease among middle-aged Japanese men and women, in particular among smokers.
Effect of barriers on the Clifton suspension bridge, England, on local patterns of suicide: implications for prevention

Summary We assessed the effect of the installation of barriers on the Clifton suspension bridge, Bristol, England, in 1998 on local suicides by jumping. Deaths from this bridge halved from 8.2 per year (1994–1998) to 4.0 per year (1999–2003; P=0.008). Although 90% of the suicides from the bridge were by males, there was no evidence of an increase in male suicide by jumping from other sites in the Bristol area after the erection of the barriers. This study provides evidence for the effectiveness of barriers on bridges in preventing site-specific suicides and suicides by jumping overall in the surrounding area.
Using Dynamic and Contextual Features to Predict Issue Lifetime in GitHub Projects

Methods for predicting issue lifetime can help software project managers to prioritize issues and allocate resources accordingly. Previous studies on issue lifetime prediction have focused on models built from static features, meaning features calculated at one snapshot of the issue's lifetime based on data associated to the issue itself. However, during its lifetime, an issue typically receives comments from various stakeholders, which may carry valuable insights into its perceived priority and difficulty and may thus be exploited to update lifetime predictions. Moreover, the lifetime of an issue depends not only on characteristics of the issue itself, but also on the state of the project as a whole. Hence, issue lifetime prediction may benefit from taking into account features capturing the issue's context (contextual features). In this work, we analyze issues from more than 4000 GitHub projects and build models to predict, at different points in an issue's lifetime, whether or not the issue will close within a given calendric period, by combining static, dynamic and contextual features. The results show that dynamic and contextual features complement the predictive power of static ones, particularly for long-term predictions.
Adenovirus Vector Expressing Stx1/Stx2-Neutralizing Agent Protects Piglets Infected with Escherichia coli O157:H7 against Fatal Systemic Intoxication

ABSTRACT Hemolytic-uremic syndrome (HUS), caused by Shiga toxin (Stx)-producing Escherichia coli (STEC), remains untreatable. Production of human monoclonal antibodies against Stx, which are highly effective in preventing Stx sequelae in animal models, is languishing due to cost and logistics. We reported previously that the production and evaluation of a camelid heavy-chain-only VH domain (VHH)-based neutralizing agent (VNA) targeting Stx1 and Stx2 (VNA-Stx) protected mice from Stx1 and Stx2 intoxication. Here we report that a single intramuscular (i.m.) injection of a nonreplicating adenovirus (Ad) vector carrying a secretory transgene of VNA-Stx (Ad/VNA-Stx) protected mice challenged with Stx2 and protected gnotobiotic piglets infected with STEC from fatal systemic intoxication. One i.m. dose of Ad/VNA-Stx prevented fatal central nervous system (CNS) symptoms in 9 of 10 animals when it was given to piglets 24 h after bacterial challenge and in 5 of 9 animals when it was given 48 h after bacterial challenge, just prior to the onset of CNS symptoms. All 6 placebo animals died or were euthanized with severe CNS symptoms. Ad/VNA-Stx treatment had no impact on diarrhea. In conclusion, Ad/VNA-Stx treatment is effective in protecting piglets from fatal Stx2-mediated CNS complications following STEC challenge. With a low production cost and further development, this could presumably be an effective treatment for patients with HUS and/or individuals at high risk of developing HUS due to exposure to STEC.
Contextual Alignment of Cognitive and Neural Dynamics Daniel

■ Effective real-world communication requires the alignment of multiple individuals to a common perspective or mental framework. To study how this alignment occurs at the level of the brain, we measured BOLD response during fMRI while participants (n = 24) listened to a series of vignettes either in the presence or absence of a valid contextual cue. The valid contextual cue was necessary to understand the information in each vignette. We then examined where and to what extent the shared valid context led to greater intersubject similarity of neural processing. Regions of the default mode network including posterior cingulate cortex and medial pFC became more aligned when participants shared a valid contextual framework, whereas other regions, including primary sensory cortices, responded to the stimuli reliably regardless of contextual factors. Taken in conjunction with previous research, the present results suggest that default mode regions help the brain to organize incoming verbal information in the context of previous
Breaking ground in cross-cultural research on the fear of being laughed at (gelotophobia): A multi-national study involving 73 countries

Abstract The current study examines whether the fear of being laughed at (gelotophobia) can be assessed reliably and validly by means of a self-report instrument in different countries of the world. All items of the GELOPH (Ruch and Titze, GELOPH〈46〉, University of Düsseldorf, 1998; Ruch and Proyer, Swiss Journal of Psychology 67:19–27, 2008b) were translated to the local language of the collaborator (42 languages in total). In total, 22,610 participants in 93 samples from 73 countries completed the GELOPH. Across all samples the reliability of the 15-item questionnaire was high (mean alpha of .85) and in all samples the scales appeared to be unidimensional. The endorsement rates for the items ranged from 1.31% through 80.00% to a single item. Variations in the mean scores of the items were more strongly related to the culture in a country and not to the language in which the data were collected. This was also supported by a multidimensional scaling analysis with standardized mean scores of the items from the GELOPH〈15〉. This analysis identified two dimensions that further helped explaining the data (i.e., insecure vs. intense avoidant-restrictive and low vs. high suspicious tendencies towards the laughter of others). Furthermore, multiple samples derived from one country tended to be (with a few exceptions) highly similar. The study shows that gelotophobia can be assessed reliably by means of a self-report instrument in cross-cultural research. This study enables further studies of the fear of being laughed at with regard to differences in the prevalence and putative causes of gelotophobia in comparisons to different cultures.
Gender and Negotiation in the Small: Are Women (Perceived to Be) More Cooperative than Men?

We surveyed research by experimental economists that examines gender differences in negotiation in the context of two simple, two-player games. Our purpose is to uncover empirical regularities in the results that might be useful to teachers or practitioners of negotiation. In the dictator game, one player unilaterally determines the division of a fixed amount of money. In the ultimatum game, one player offers a division and the other must accept or reject that offer; if rejected, both players receive a zero payoff. The results have shown that, on balance, women tend to be more egalitarian than men, to expect and ask for less in the negotiation. Women also seem to be more responsive to the context of a negotiation and are less likely to fail to reach an agreement than men. These differences are small, however, in comparison with differences in expectations about what women and men will do. We conclude that stereotyping is alive and well in negotiations and that this can help or hinder negotiation outcomes, depending on the context.
ON THE REGULARITY OF THREE-DIMENSIONAL ROTATING EULER–BOUSSINESQ EQUATIONS

The 3-D rotating Boussinesq equations (the "primitive" equations of geophysical fluid flows) are analyzed in the asymptotic limit of strong stable stratification. The resolution of resonances and a nonstandard small divisor problem are the basis for error estimates for such fast singular oscillating limits. Existence on infinite time intervals of regular solutions to the viscous 3-D "primitive" equations is proven for initial data in Hα, α≥ 3/4. Existence on a long-time interval T* of regular solutions to the 3-D inviscid equations is proven for initial data in Hα, α > 5/2 (T*→∞ as the frequency of gravity waves →∞).
Vitamin D deficiency is associated with sudden cardiac death, combined cardiovascular events, and mortality in haemodialysis patients.

It is known that patients with dialysis experience an excess mortality, mostly due to sudden cardiac death (SCD). Accumulated data suggest a role of vitamin D in all cause mortality, in general, and in cardiovascular mortality, in particular, as vitamin D appears to be crucial for cardiovascular health; it is also able to protect against infectious diseases. In patients with chronic kidney disease (CKD), limited sunlight exposure, reduced capacity of the skin to synthesize vitamin D, as well as the loss of vitamin D-binding protein in the urine are mainly responsible for the high prevalence of depressed 25(OH)D levels, which are used to assess vitamin D status. The kidney is the main source for circulating 1,25(OH)2D; in CKD the level of 1,25(OH)2D and its analogues are decreased and it is already a routine to supplement vitamin D in many end-stage CKD patients. This therapy was observed to be associated with improved survival. The study commented investigated the impact of vitamin D status on cardiovascular outcomes and fatal infections in haemodialysis patients. 25-hydroxyvitamin D was measured in 1108 diabetic haemodialysis patients who participated in the German Diabetes and Dialysis Study and were monitored for a period of 4 years. The endpoints established for this study were sudden cardiac death (SCD), myocardial infarction (MI), stroke and cardiovascular events (CE), death due to heart failure, fatal infections and all cause mortality. Patients had a mean age of 66 +/- 8 years, 54% of them were males and the average 25-hydroxyvitamin D level at baseline was 39 nmol/L. Patients with severe vitamin D deficiency [25(OH)D of≤ 25 nmol/L] had a 3-fold higher risk of SCD compared with those with sufficient 25(OH)D levels >75 nmol/L [HR: 2.99, 95% confidence interval (CI): 1.39–6.40]. In addition, cardiovascular events and all cause mortality were highly increased (HR: 1.78, 95% CI: 1.18–2.69, and HR: 1.74, 95% CI: 1.22–2.47, respectively). The vitamin D deficiency did not correlate with stroke and fatal infection, also myocardial infarction and deaths due to heart failure were not meaningfully affected. The researchers concluded that severe vitamin D deficiency was strongly associated with SCD, CVE and mortality and there were borderline associations with stroke and fatal infections. For establishing whether vitamin D supplementation decreases adverse outcomes are needed further evaluations. ❑
CCL 2 and CXCL 2 enhance the survival of primary chronic lymphocytic leukaemia cells in vitro .

Chronic lymphocytic leukaemia (CLL) is predominantly a disease of accumulation rather than rapid proliferation. To date no cell lines exist as CLL cells undergo rapid apoptosis when cultured in vitro, suggesting a favourable in vivo microenvironment is required. To identify survival signals we have cultured primary CLL PBMCs at high density, which has previously been shown to dramatically improve survival. Using antibody arrays we measured the level of 42 cytokines in culture supernatants and show that IL-6, IL-8, CXCL2 and CCL2 were highly up-regulated in culture. This is the first report to describe a role for CCL2 and CXCL2 in CLL cell survival. Importantly, CXCL2, IL6 and IL8 were significantly unregulated in primary patient plasma. Addition of either CXCL2 or CCL2 enhanced CLL cell survival while antibodies blocking these chemokines reduced survival. Co-culture of CLL cells and PBMC accessory cells separated by transwells provided a similar degree of survival protection compared to normal culture whereas CLL cells cultured alone died rapidly. Interestingly, CCL2 and CXCL2 appeared to be produced by 2 CLL cells but only when co-cultured with accessory cells. Thus, we speculate that that accessory cells release soluble factors that promote the production of these pro-survival chemokines from CLL cells and physical interactions were not required. Our data support the concept that the CLL microenvironment is critical and suggests that soluble factors are more important than physical interactions.
Turbulence structure in a boundary layer with two-dimensional roughness

Turbulence measurements for a zero pressure gradient boundary layer over a two-dimensional roughness are presented and compared to previous results for a smooth wall and a three-dimensional roughness (Volino, Schultz & Flack, J. Fluid Mech., vol. 592, 2007, p. 263). The present experiments were made on transverse square bars in the fully rough flow regime. The turbulence structure was documented through the fluctuating velocity components, two-point correlations of the fluctuating velocity and swirl strength and linear stochastic estimation conditioned on the swirl and Reynolds shear stress. The two-dimensional bars lead to significant changes in the turbulence in the outer flow. Reynolds stresses, particularly $\overline {{v'}^2} ^ +$ and $ - \overline {{u}'{v}'} ^ + $, increase, although the mean flow is not as significantly affected. Large-scale turbulent motions originating at the wall lead to increased spatial scales in the outer flow. The dominant feature of the outer flow, however, remains hairpin vortex packets which have similar inclination angles for all wall conditions. The differences between boundary layers over two-dimensional and three-dimensional roughness are attributable to the scales of the motion induced by each type of roughness. This study has shown three-dimensional roughness produces turbulence scales of the order of the roughness height k while the motions generated by two-dimensional roughness may be much larger due to the width of the roughness elements. It is also noted that there are fundamental differences in the response of internal and external flows to strong wall perturbations, with internal flows being less sensitive to roughness effects.