Miracle-dz/UniFAR-FTUs huggingface dataset:
A Self-Fulfilling Prophecy: C-Reactive Protein Attenuates Nitric Oxide Production and Inhibits Angiogenesis

Background—Given the central importance of nitric oxide (NO) in the development and clinical course of cardiovascular diseases, we sought to determine whether the powerful predictive value of C-reactive protein (CRP) might be explained through an effect on NO production. Methods and Results—Endothelial cells (ECs) were incubated with recombinant CRP (0 to 100 &mgr;g/mL, 24 hours), and NO and cyclic guanosine monophosphate (cGMP) production was assessed. The effects of CRP on endothelial NO synthase (eNOS) protein, mRNA expression, and mRNA stability were also examined. In a separate study, the effects of CRP (25 &mgr;g/mL) on EC cell survival, apoptosis, and in vitro angiogenesis were evaluated. Incubation of ECs with CRP resulted in a significant inhibition of basal and stimulated NO release, with concomitant reductions in cGMP production. CRP caused a marked downregulation of eNOS mRNA and protein expression. Actinomycin D studies suggested that eNOS downregulation was related to decreased mRNA stability. In conjunction with a decrease in NO production, CRP inhibited both basal and vascular endothelial growth factor–stimulated angiogenesis as assessed by EC migration and capillary-like tube formation. CRP did not induce EC survival but did, however, promote apoptosis in a NO-dependent fashion. Conclusions—CRP, at concentrations known to predict adverse vascular events, directly quenches the production of the NO, in part, through posttranscriptional effect on eNOS mRNA stability. Diminished NO bioactivity, in turn, inhibits angiogenesis, an important compensatory mechanism in chronic ischemia. Through decreasing NO synthesis, CRP may facilitate the development of diverse cardiovascular diseases. Risk reduction strategies designed to lower plasma CRP may be effective by improving NO bioavailability.
Is Social Network Diversity Associated with Tooth Loss among Older Japanese Adults?

Background We sought to examine social network diversity as a potential determinant of oral health, considering size and contact frequency of the social network and oral health behaviors. Methods Our cross-sectional study was based on data from the 2010 Japan Gerontological Evaluation Study. Data from 19,756 community-dwelling individuals aged 65 years or older were analyzed. We inquired about diversity of friendships based on seven types of friends. Ordered logistic regression models were developed to determine the association between the diversity of social networks and number of teeth (categorized as ≥20, 10–19, 1–9, and 0). Results Of the participants, 54.1% were women (mean age, 73.9 years; standard deviation, 6.2). The proportion of respondents with ≥20 teeth was 34.1%. After adjusting for age, sex, socioeconomic status (income, education, and occupation), marital status, health status (diabetes and mental health), and size and contact frequency of the social network, an increase in the diversity of social networks was significantly associated with having more teeth (odds ratio = 1.08; 95% confidence interval, 1.04–1.11). Even adjusted for oral health behaviors (smoking, curative/preventive dental care access, use of dental floss/fluoride toothpaste), significant association was still observed (odds ratio = 1.05 (95% confidence interval, 1.02–1.08)). Conclusion Social connectedness among people from diverse backgrounds may increase information channels and promote the diffusion of oral health behaviors and prevent tooth loss.
On the transition from initial data to travelling waves in the Fisher-KPP equation

The Fisher-KPP equation has a travelling wave solution for all speeds . Initial data that decrease monotonically from 1 to 0 on , with as , are known to evolve to a travelling wave, whose speed depends on . Here, it is shown that the relationship between wave speed and , can be recovered by linearizing the Fisher-KPP equation about and explicitly solving the linear equation. Moreover, the calculation predicts that in the case , the solution for itself evolves to a transition wave, moving ahead of the (minimum speed) u wave at the greater speed of . Behind this transition , while ahead of it . The paper goes on to discuss the potential applications of the method to systems of coupled reaction-diffusion equations
Lipoxin A4 and B4 are potent stimuli for human monocyte migration and adhesion: selective inactivation by dehydrogenation and reduction

Monocyte recruitment and adherence are important events in inflammatory and vascular diseases. Here, we evaluated the actions of lipoxin A4 (LXA4) and LXB4, a series of lipoxygenase products from arachidonic acid generated by cell-cell interactions, on human monocytes. LXA4 and LXB4 (10(-7) M) each increased monocyte migration in chamber chemotaxis assays and, in migration under agarose, exhibited chemotactic indices similar to those of the chemotactic peptide formyl-methionyl-leucyl- phenylalanine at 10(-10)-10(-8) M and to the chemokine macrophage inflammatory protein-1 alpha (MIP-1 alpha) at 10(-8)-10(-7) M with a rank order of potency: Monocyte chemotactic protein-1 alpha > LXA4 approximately LXB4 approximately MIP-1 alpha. Lipoxins also stimulated monocyte adherence to laminin. In addition, human monocytes rapidly transformed LXA4 and LXB4 to several metabolites. LXB4 (> 80%) was converted within 30 s to new products, in a trend similar to that of LXA4. The novel monocyte-derived LXB4 products were identified as 5-oxo- 6,7-dihydro-LXB4 and 6,7-dihydro-LXB4, indicating a role for site- selective dehydrogenation and reduction. Unlike monocytes, intact polymorphonuclear leukocytes (PMN) did not metabolize LXA4 in significant quantities, and only approximately 12% of exogenous LXB4 was omega-oxidized to 20-OH-LXB4 and 20-COOH-LXB4 by PMN. To determine if lipoxin conversion altered bioactivity, we evaluated the actions of these metabolites on monocytes. Each of the novel products of LXA4 and LXB4 from monocytes, namely oxo- and dihydrolipoxins, were essentially inactive in stimulating monocyte adherence. In contrast, the omega- oxidation products of LXB4 isolated from PMN were equipotent with LXB4 for monocyte adherence. Dehydrogenation of LXA4 in monocytes appears to be carried out by a 15-hydroxyprostaglandin dehydrogenase, which is present in human monocytes as determined by reverse transcription PCR and Western blots. Together, these results provide the first evidence that LXA4 and LXB4 are both potent stimulants for migration and adherence of human monocytes. Moreover, they underscore the importance of the major route of lipoxin metabolism in leukocytes, namely, the rapid dehydrogenation and inactivation carried out by monocytes.
Genome-wide association of white blood cell counts in Hispanic/Latino Americans: the Hispanic Community Health Study/Study of Latinos

Circulating white blood cell (WBC) counts (neutrophils, monocytes, lymphocytes, eosinophils, basophils) differ by ethnicity. The genetic factors underlying basal WBC traits in Hispanics/Latinos are unknown. We performed a genome-wide association study of total WBC and differential counts in a large, ethnically diverse US population sample of Hispanics/Latinos ascertained by the Hispanic Community Health Study and Study of Latinos (HCHS/SOL). We demonstrate that several previously known WBC-associated genetic loci (e.g. the African Duffy antigen receptor for chemokines null variant for neutrophil count) are generalizable to WBC traits in Hispanics/Latinos. We identified and replicated common and rare germ-line variants at FLT3 (a gene often somatically mutated in leukemia) associated with monocyte count. The common FLT3 variant rs76428106 has a large allele frequency differential between African and non-African populations. We also identified several novel genetic loci involving or regulating hematopoietic transcription factors (CEBPE-SLC7A7, CEBPA and CRBN-TRNT1) associated with basophil count. The minor allele of the CEBPE variant associated with lower basophil count has been previously associated with Amerindian ancestry and higher risk of acute lymphoblastic leukemia in Hispanics. Together, these data suggest that germline genetic variation affecting transcriptional and signaling pathways that underlie WBC development and lineage specification can contribute to inter-individual as well as ethnic differences in peripheral blood cell counts (normal hematopoiesis) in addition to susceptibility to leukemia (malignant hematopoiesis).
Possible Involvement of Rho-Kinase in the Pathogenesis of Hypertension in Humans

Rho-kinase plays an important role in modulating Ca2+ sensitivity of vascular smooth muscle and has been suggested to be involved in the increased systemic vascular resistance in hypertensive animals. However, it remains to be examined whether this is also the case in patients with essential hypertension. Recently, it has been shown that fasudil is a specific Rho-kinase inhibitor. The aim of this study was to examine whether Rho-kinase is involved in the pathogenesis of hypertension in humans by using this Rho-kinase inhibitor. Studies were performed in hypertensive patients (HT group, n=14) and age-matched normotensive subjects (NT group, n=12). Forearm blood flow was measured by a strain-gauge plethysmograph during intra-arterial infusion of graded doses of fasudil (3.2, 6.4, 12.8, and 25.6 &mgr;g/min) or sodium nitroprusside (0.4, 0.8, 1.6, and 3.2 &mgr;g/min). Resting forearm vascular resistance was significantly higher in the HT group than in the NT group (22±4 versus 17±5 U, respectively; P<0.05). The extent of the increase in forearm blood flow evoked by fasudil was significantly greater in the HT group than in the NT group (12.3±1.4 versus 6.0±0.6 mL · min−1 · 100 mL−1, respectively;P <0.01). The percent decrease in forearm vascular resistance was significantly greater in the HT group than in the NT group (63.6±4.7% versus 29.6±3.9%, respectively;P <0.01). By contrast, forearm vasodilator response evoked by sodium nitroprusside was comparable between the 2 groups. These results provide the first evidence that Rho-kinase may be involved in the pathogenesis of the increased peripheral vascular resistance in hypertension in humans.
GPU-based dynamic search on adaptive resolution grids

This paper presents a GPU-based wave-front propagation technique for multi-agent path planning in extremely large, complex, dynamic environments. Our work proposes an adaptive subdivision of the environment with efficient indexing, update, and neighbor-finding operations on the GPU to address several known limitations in prior work. In particular, an adaptive environment representation reduces the device memory requirements by an order of magnitude which enables for the first time, GPU-based goal path planning in truly large-scale environments (> 2048 m2) for hundreds of agents with different targets. We compare our approach to prior work that uses an uniform grid on several challenging navigation benchmarks and report significant memory savings, and up to a 1000X computational speedup.
Serum lipoprotein(a) and lipid profile in polycystic ovarian syndrome

Background: Polycystic ovarian syndrome (PCOS) is associated with dyslipidaemia and may render the affected women “at risk” of developing cardiovascular disease. Lipoprotein(a) [Lp(a)] is an independent risk factor for development of atherosclerosis and along with dyslipidaemia may add to cardiovascular risk. In this background the levels of Lp(a) and lipid profile are assessed in PCOS patients. Material and Methods: The study was carried out on 30 newly diagnosed PCOS subjects aged 18-35 years and 30 age-matched healthy women. Blood samples were collected in a fasting state and serum Lp(a), lipid parameters were estimated. Results: The lipid profile parameters were comparable between patients and control subjects. There was no statistically significant difference in the median [interquartile range (IQR)] Lp(a) levels between patients with PCOS and normal controls. However, the proportion of subjects with elevated (> 30 mg/dL) Lp(a) levels were significantly higher in patients with PCOS compared to control subjects.
Conceptual entropy and its effect on class hierarchies

All systems that undergo frequent change characteristically tend toward disorder. This is known as entropy and is recognized in all branches of science. Class hierarchies are shared structures which, if useful, undergo frequent change in the form of additional subclassing, modification to existing classes, and sometimes the restructuring of the hierarchy itself. Given this frequent change, we can expect class hierarchies to exhibit entropic tendencies, which we term conceptual entropy. Conceptual entropy is manifested by increasing conceptual inconsistency as we travel down the hierarchy. That is, the deeper the level of the hierarchy, the greater the probability that a subclass will not consistently extend and/or specialize the concept of its superclass. Constructing and maintaining consistent class hierarchies is one of the most difficult activities of object-oriented design. The article describes an automated classification tool that helps minimize conceptual entropy. <<ETX>>
Novel Aspects Concerning the Functional Cross-Talk between the Insulin/IGF-I System and Estrogen Signaling in Cancer Cells

The insulin/IGF system plays an important role in cancer progression. Accordingly, elevated levels of circulating insulin have been associated with an increased cancer risk as well as with aggressive and metastatic cancer phenotypes. Numerous studies have documented that estrogens cooperate with the insulin/IGF system in multiple pathophysiological conditions. The biological responses to estrogens are mainly mediated by the estrogen receptors (ER)α and ERβ, which act as transcription factors; however, several studies have recently demonstrated that a member of the G protein-coupled receptors, named GPR30/G-protein estrogen receptor (GPER), is also involved in the estrogen signaling in normal and malignant cells as well as in cancer-associated fibroblasts (CAFs). In this regard, novel mechanisms linking the action of estrogens through GPER with the insulin/IGF system have been recently demonstrated. This review recapitulates the relevant aspects of this functional cross-talk between the insulin/IGF and the estrogenic GPER transduction pathways, which occurs in various cell types and may account for cancer progression.
Poly-logarithmic Frege depth lower bounds via an expander switching lemma

We show that any polynomial-size Frege refutation of a certain linear-size unsatisfiable 3-CNF formula over n variables must have depth Ω(√logn). This is an exponential improvement over the previous best results (Pitassi et al. 1993, Krajíček et al. 1995, Ben-Sasson 2002) which give Ω(loglogn) lower bounds. The 3-CNF formulas which we use to establish this result are Tseitin contradictions on 3-regular expander graphs. In more detail, our main result is a proof that for every d, any depth-d Frege refutation of the Tseitin contradiction over these n-node graphs must have size nΩ((logn)/d2). A key ingredient of our approach is a new switching lemma for a carefully designed random restriction process over these expanders. These random restrictions reduce a Tseitin instance on a 3-regular n-node expander to a Tseitin instance on a random subgraph which is a topological embedding of a 3-regular n′-node expander, for some n′ which is not too much less than n. Our result involves Ω(√logn) iterative applications of this type of random restriction.
Study on Interconnect Test Generation of MCM Based on Particle Swarm Optimization Algorithm and Genetic Algorithm

The paper proposes a new interconnect test generation approach based on particle swarm optimization algorithm (PSO) and genetic algorithm (GA) for multi-chip module (MCM) applications. By combing the characteristics of interconnect test and constructing particle expression of test generation, the velocity updating equation and position updating equation of discrete PSO is presented in tins paper. GA is employed to evolve the candidates generated by PSO. in order to improve the fault coverage of the test vector. The experimental results for MCM benchmark circuits show that the proposed algorithm can improve the performance of interconnect test generation in test set. fault coverage and CPU time when compared to other interconnect test generation algorithms.
Assessment of appropriateness of indications for CT enterography in younger patients

Background: The small potential risk of radiation‐induced cancer is increased in younger patients undergoing serial imaging with computed tomography enterography (CTE). We sought to determine the appropriateness of CTEs based on clinical indication in patients ≤35 years old, and the potential impact of evolution of practice to alternative magnetic resonance enterography (MRE). Methods: Over a 7‐year period, the medical records of all patients ≤35 years old undergoing CTE were reviewed to determine the clinical indications for each CTE exam. An interdisciplinary consensus panel evaluated the appropriateness of all CTE exams based on American College of Radiology appropriateness criteria and peer‐reviewed literature, classifying indications into “appropriate” or “inappropriate. ” For repeat CTEs, an “alternative MRE suggested” pathway was created. Criteria for evolution of practice to “alternative MRE” were suspicion of obstruction and evaluation of disease activity/therapeutic response in the absence of new symptoms. Results: In all, 2022 patients ≤35 years old underwent 2295 CTEs. Ninety‐nine percent (2008/2022) of first‐time CTE exams were “appropriate” by the defined criteria. A total of 197 patients (9.7%) underwent multiple exams, with 73% of these patients having Crohn's disease. Repeat exams occurred in 9% (18/197) with obstructive symptoms and evaluation of disease activity/therapeutic response in the absence of new symptoms in 41% (80/197). Conclusions: A multidisciplinary expert panel concluded that the vast majority of young patients underwent clinically appropriate first‐time CTE exams. However, a shift in clinical practice to MRE appears warranted for approximately half of young patients undergoing repeat CTE examinations. Inflamm Bowel Dis 2009
Neuroprotection of Ischemic Postconditioning by Downregulating the Postsynaptic Signaling Mediated by Kainate Receptors

Background and Purpose— Ischemic postconditioning, a brief episode of ischemia after a prolonged ischemic insult, has been found to reduce the delayed neuronal loss after stroke. However, the mechanisms underlying such endogenous neuroprotective strategy remain obscure. In this study, we try to explore the excitatory postsynaptic signal events associated with neuroprotective effect of ischemic postconditioning. Methods— Global cerebral ischemia was induced for 15 minutes by the 4-vessel occlusion method in male Sprague–Dawley rats. Ischemic postconditioning was conducted 10 minutes later by a single reocclusion for 3 minutes. Results— A severe global cerebral ischemia after 5 days of reperfusion destroyed almost all hippocampal CA1 pyramidal neurons. A brief ischemic postconditioning robustly reduced the neuronal loss after ischemia. Preadministration of phosphoinositide 3-kinase inhibitor LY294002 blocked the neuroprotection of postconditioning, whereas mitogen-activated protein kinase kinase 1 inhibitor PD98059 had no effect. Ischemic postconditioning significantly increased the Akt phosphorylation (Ser473). In addition, postconditioning not only perturbed the binding of postsynaptic density protein-95 with glutamatergic kainate receptor subunit 2 and mixed lineage kinase 3 but also suppressed the downstream activation of mixed lineage kinase 3, mitogen-activated protein kinase kinase 7, and c-Jun N-terminal kinase 3. LY294002, but not PD98059, abolished the postconditioning-induced decreases in the assembly of glutamatergic kainate receptor subunit 2–postsynaptic density protein-95–mixed lineage kinase 3 complex and in the mixed lineage kinase 3–c-Jun N-terminal kinase 3 signaling. Akt inhibitor IV, a specific Akt inhibitor, showed the same effects as LY294002. Conclusions— Ischemic postconditioning protects neurons against stroke by attenuating the postsynaptic glutamatergic kainate receptor subunit 2–postsynaptic density protein-95–mixed lineage kinase 3–c-Jun N-terminal kinase 3 signal cascade via phosphoinositide 3-kinase–Akt pathway. (Stroke. 2013;44:2031-2035.)
Modifying transients for efficient coding of audio

We propose a method for efficient representation of transients in audio signals. We estimate the transient component of an original audio signal and modify the locations of the transients in such a way that the transients can occur only at locations defined by a relatively coarse time grid. This procedure allows an efficient representation of transients with damped sinusoids. We also verify that the introduced modifications do not result in a perceptual difference between the original and the modified audio signals.
Social Environmental Influences on Physical Activity of Children With Autism Spectrum Disorders.

BACKGROUND Children with Autism Spectrum Disorders (ASD) may be at greater risk for not meeting physical activity (PA) guidelines than neurotypical children (NT). The purpose of this study was to explore setting (free play versus organized) and social group composition influences on PA of children with ASD during summer camp. METHODS Data were collected on 6 ASD and 6 NT boys (aged 5 to 6 years) attending an inclusive summer camp. During free play and organized activity, research assistants observed the camp's social environment and children's PA using a modified version of the Observational System for Recording Physical Activity of Children-Preschool version. RESULTS In free play, children with ASD spent significantly less time in Moderate-Vigorous PA (MVPA) while with a peer (1.2%), compared with a peer group (11.5%) or alone (13.2%). They demonstrated significantly more Light-Moderate-Vigorous PA (LMVPA) while in a solitary social context (68.2%) compared with alone with an adult (25.8%), alone with a peer (34.8%), or with a peer group (28.2%). No significant differences were noted during organized activity. CONCLUSION Features of the social environment may influence PA levels of children with ASD. Specifically, certain social group contexts may be more PA-promoting than others depending on the setting.
Changes in Root Cap pH Are Required for the Gravity Response of the Arabidopsis Root

Although the columella cells of the root cap have been identified as the site of gravity perception, the cellular events that mediate gravity signaling remain poorly understood. To determine if cytoplasmic and/or wall pH mediates the initial stages of root gravitropism, we combined a novel cell wall pH sensor (a cellulose binding domain peptide–Oregon green conjugate) and a cytoplasmic pH sensor (plants expressing pH-sensitive green fluorescent protein) to monitor pH dynamics throughout the graviresponding Arabidopsis root. The root cap apoplast acidified from pH 5.5 to 4.5 within 2 min of gravistimulation. Concomitantly, cytoplasmic pH increased in columella cells from 7.2 to 7.6 but was unchanged elsewhere in the root. These changes in cap pH preceded detectable tropic growth or growth-related pH changes in the elongation zone cell wall by 10 min. Altering the gravity-related columella cytoplasmic pH shift with caged protons delayed the gravitropic response. Together, these results suggest that alterations in root cap pH likely are involved in the initial events that mediate root gravity perception or signal transduction.