Miracle-dz/UniFAR-FTUs huggingface dataset:
Test generation and design-for-testability for flow-based mVLSI microfluidic biochips

Advances in flow-based microfluidic biochips offer tremendous potential for biochemical analyses and clinical diagnostics. However, the adoption of flow-based biochips is hampered by defects that are especially common for chips fabricated using soft lithography techniques. Recently published work on fault detection in flow-based biochips is based on logic-circuit modeling of the microfluidic channels and control valves, followed by classical test generation for digital circuits. However, this approach is not applicable to realistic designs because the circuit model is generated manually and many real defects are mapped to undetectable faults in the logic-circuit model. We present a technique for automated and hierarchical generation of the logic-circuit model from the layout of a flow-based microfluidic chip. Moreover, based on the analysis of untestable faults in the logic-circuit model, we present a design-for-testability (DfT) technique that can achieve 100% fault coverage. Two microfluidic VLSI (mVLSI) chips, each containing over 1500 valves, are used to demonstrate the automated model generation and DfT solutions.
The Ena/VASP enigma

Ena/VASP proteins are actin-binding proteins that localize to actin stress fibres, the tips of filopodia and the lamellipodial leading edge. In the past few years, a number of seemingly conflicting studies have confused the Ena/VASP field, pointing to roles for these proteins in both promotion and inhibition of actin-dependent processes. Recent discoveries resolve these contradictions and suggest a novel mechanism of Ena/VASP function, in which the proteins function as `anti-capping' proteins that antagonize capping proteins at the barbed end of actin filaments.
Two common mutations (D9N, N291S) in lipoprotein lipase: a cumulative analysis of their influence on plasma lipids and lipoproteins in men and women

We assessed the effect of two common mutations in the lipoprotein lipase gene (LPL), D9N and N291S, which have been shown to modulate plasma lipids in a wide spectrum of patients.A total of 1 114 men and 1 144 women from the Framingham Offspring Study (FOS) were analyzed for these two LPL variants. Subsequently, the association with fasting plasma lipids and risk of coronary artery disease (CHD) was determined. We extended our study by calculating weighed means of lipids and lipoproteins in carriers and non‐carriers for these LPL mutations in patients with genetic dyslipidemias, CHD patients and healthy controls.In the FOS sample, the D9N and N291S alleles were associated with lower high‐density lipoprotein‐cholesterol (HDL‐C) (Δ=−0.07 mmol/l, p=0.03) and a trend towards increased triglycerides (Δ=0.25 mmol/l, p=0.07). In women, a trend towards the high triglyceride, low HDL‐C phenotype was evident (Δ=−0.02 mmol/l for HDL‐C and Δ=0.14 mmol/l for triglycerides, respectively). Cumulative analysis of other studies of male carriers of the D9N and N291S revealed higher levels of triglycerides (D291N; 2.60(1.85) mmol/l vs. 1.62(1.18) mmol/l: p<0.0001) (D9N; 1.94 (1.19) mmol/l vs. 1.74(1.17) mmol/l: p<0.001) and lower HDL‐C (N291S; 1.04(0.32) mmol/l vs. 1.15(0.28) mmol/l: p<0.0001) (D9N; 1.08(0.24) mmol/l vs. 1.16(0.28) mmol/l: p<0.0001). In females, results differed with higher TG levels (N291S; 1.70(0.99) mmol/l vs. 1.10(0.63) mmol/l: p<0.001) (D9N; 1.08(0.76) mmol/l vs. 0.96(0.51) mmol/l: p<0.01) and lower HDL‐C levels (N291S; 1.27(0.33) mmol/l vs. 1.51(0.32) mmol/l: p<0.0001); however, the HDL‐C levels for D9N carriers were similar to non‐carriers (D9N; 1.52(0.29) mmol/l vs. 1.53(0.35) mmol/l: p=0.83). Our data provide evidence that common variants of the LPL gene are significant modulators of lipid and lipoprotein levels in both men and women.
The Influence of Dialytic Modality on Arterial Stiffness, Pulse Wave Reflections, and Vasomotor Function

Background Measurements of aortic stiffness [aortic pulse wave velocity (PWV) and augmentation index (AIx)] have been established as powerful predictors of survival on hemodialysis (HD). Abnormal endothelial-dependent and endothelial-independent vascular reactivity and increased arterial stiffness are commonly described in HD patients. There is, however, a lack of information on the comparative impact of different renal replacement therapies (RRTs) on PWV and AIx, and how these different methods might influence endothelial-dependent abnormal vasodilatation. Objective To describe in a cross-sectional design arterial compliance and distensibility in continuous ambulatory peritoneal dialysis (CAPD) versus HD versus renal transplant (RTx) patients, compared with age- and blood pressure-matched essential hypertensive controls. The PWV and aortic AIx were determined from contour analysis of arterial waveforms recorded by applanation tonometry in 40 CAPD, 41 HD, 20 RTx patients (with normal serum creatinine), and 20 controls with essential hypertension (all normotensive under treatment). Endothelial-dependent and endothelial-independent vascular reactivities were assessed by changes in AIx following challenges with inhaled salbutamol and sublingual nitroglycerin respectively. Results CAPD patients had significantly stiffer arteries than all other categories. The PWV was 8.29 ± 1.09 m/second in CAPD patients, significantly higher (p < 0.05) compared to HD subjects (7.19 ± 1.87 m/s). Both dialysis subgroups had significantly higher PWV values compared to RTx patients (6.59 ± 1.62 m/s) and essential hypertensive controls (6.34 ± 1.32 m/s), p < 0.05. The AIx had a profile similar to PWV in different RRTs. All groups with the exception of CAPD subjects had a significant decrease in AIx following salbutamol. Moreover, the vasodilatation induced by either nitroglycerin or salbutamol was significantly blunted compared to HD. Overall, both dialysis categories had more abnormal responses compared to RTx patients and essential hypertensive controls. Conclusion CAPD is associated with stiffer arteries and more profoundly abnormal endothelial-dependent vasomotor function, compared to matched HD subjects. These differences in arterial physical properties might explain differences seen in cardiac structure and function between the RRTs.
Response of inbred mice to aerosol challenge with Mycobacterium tuberculosis

An autosomal dominant gene (Bcg), which maps to mouse chromosome 1, has been shown to confer on mice resistance to attenuated Mycobacterium bovis BCG Montreal, Salmonella typhimurium, and Leishmania donovani. Most animal models used for the study of the Bcg gene have involved intravenous injection of a large number of microorganisms (greater than 10(4) CFU). The present study examines the effect of the Bcg gene on the resistance of inbred mice to challenge via the respiratory route with 5 to 10 CFU of virulent Mycobacterium tuberculosis. The number of tubercle bacilli recovered from the lung lobes indicates that the growth kinetics of the microorganism did not differ between BCG-resistant and BCG-susceptible strains of mice. The number of tubercle bacilli recovered from the spleen was also similar among strains. Although there were reproducible differences in the time of first recovery of bacilli from the spleen, these differences appeared to be unrelated to the expression of the Bcg gene. When mice were challenged with purified protein derivative, all strains responded similarly as observed by measurements of footpad swelling.
Sulfur globule oxidation in green sulfur bacteria is dependent on the dissimilatory sulfite reductase system.

Green sulfur bacteria (GSB) oxidize sulfide and thiosulfate to sulfate, with extracellular globules of elemental sulfur as an intermediate. Here we investigated which genes are involved in the formation and consumption of these sulfur globules in the green sulfur bacterium Chlorobaculum tepidum. We show that sulfur globule oxidation is strictly dependent on the dissimilatory sulfite reductase (DSR) system. Deletion of dsrM/CT2244 or dsrT/CT2245, or the two dsrCABL clusters (CT0851-CT0854, CT2247-2250), abolished sulfur globule oxidation and prevented formation of sulfate from sulfide, whereas deletion of dsrU/CT2246 had no effect. The DSR system also seems to be involved in the formation of thiosulfate, because thiosulfate was released from wild-type cells during sulfide oxidation, but not from the dsr mutants. The dsr mutants incapable of complete substrate oxidation oxidized sulfide and thiosulfate about twice as fast as the wild-type, while having only slightly lower growth rates (70-80 % of wild-type). The increased oxidation rates seem to compensate for the incomplete substrate oxidation to satisfy the requirement for reducing equivalents during growth. A mutant in which two sulfide : quinone oxidoreductases (sqrD/CT0117 and sqrF/CT1087) were deleted exhibited a decreased sulfide oxidation rate (~50 % of wild-type), yet formation and consumption of sulfur globules were not affected. The observation that mutants lacking the DSR system maintain efficient growth suggests that the DSR system is dispensable in environments with sufficiently high sulfide concentrations. Thus, the DSR system in GSB may have been acquired by horizontal gene transfer as a response to a need for enhanced substrate utilization in sulfide-limiting habitats.
A Statistical Model for Testing the Pleiotropic Control of Phenotypic Plasticity for a Count Trait

The differences of a phenotypic trait produced by a genotype in response to changes in the environment are referred to as phenotypic plasticity. Despite its importance in the maintenance of genetic diversity via genotype-by-environment interactions, little is known about the detailed genetic architecture of this phenomenon, thus limiting our ability to predict the pattern and process of microevolutionary responses to changing environments. In this article, we develop a statistical model for mapping quantitative trait loci (QTL) that control the phenotypic plasticity of a complex trait through differentiated expressions of pleiotropic QTL in different environments. In particular, our model focuses on count traits that represent an important aspect of biological systems, controlled by a network of multiple genes and environmental factors. The model was derived within a multivariate mixture model framework in which QTL genotype-specific mixture components are modeled by a multivariate Poisson distribution for a count trait expressed in multiple clonal replicates. A two-stage hierarchic EM algorithm is implemented to obtain the maximum-likelihood estimates of the Poisson parameters that specify environment-specific genetic effects of a QTL and residual errors. By approximating the number of sylleptic branches on the main stems of poplar hybrids by a Poisson distribution, the new model was applied to map QTL that contribute to the phenotypic plasticity of a count trait. The statistical behavior of the model and its utilization were investigated through simulation studies that mimic the poplar example used. This model will provide insights into how genomes and environments interact to determine the phenotypes of complex count traits.
Development of an electromyographic controlled biomimetic prosthetic hand

This paper presents the development of an electromyogram controlled extreme upper limb prosthetic hand prototype following a biomimetic approach. The biomimetic approach is followed to harmonise both physical and functional aspects of the human hand. The prototype with tendon driven fingers possesses 15 degrees of freedom. It can perform grasping operations involved during 70% of daily living activities. The control is in two stages: superior hand control SHC and local hand control LHC. The SHC involves a grasp recognition module responsible for recognition of the grasp type indented by the user. The LHC involves a translation module responsible for emulating the identified grasp type into the prototype. The results obtained for finger joint trajectories during a precision grasp through the two stage control architecture in conformity to the human hand finger.
Escherichia coli Serotype O15:K52:H1 as a Uropathogenic Clone

ABSTRACT To clarify the clinical and bacteriological correlates of urinary-tract infection (UTI) due to Escherichia coliO15:K52:H1, during a 1-year surveillance period we prospectively screened all 1,871 significant E. coli urine isolates at the Hospital de la Santa Creu i Sant Pau, Barcelona, Spain, for this serotype and assessed the epidemiological features of community-acquired UTI due to E. coli O15:K52:H1 versus other E. coli serotypes. We also compared the 25 O15:K52:H1 UTI isolates from the present study with 22 O15:K52:H1 isolates from other, diverse geographic locales and with 23 standard control strains (8 strains from the ECOR reference collection and 15 strains of nonpathogenic O:K:H serotypes) with respect to multiple phenotypic and genotypic traits. Although E. coli O15:K52:H1 caused only 1.4% of community-acquired E. coli UTIs during the surveillance period, these UTIs were more likely to present as pyelonephritis and to occur in younger hosts, with similar risk factors, than were UTIs due to other E. coli serotypes. Irrespective of geographic origin, E. coli O15:K52:H1 strains exhibited a comparatively restricted repertoire of distinctive virulence factor profiles (typically, they were positive forpapG allele II, papA allele F16, andaer and negative for sfa, afa,hly, and cnf1), biotypes, ribotypes, and amplotypes, consistent with a common clonal origin. In contrast, their antimicrobial resistance profiles were more extensive and more diverse than those of control strains. These findings indicate that E. coli O15:K52:H1 constitutes a broadly distributed and clinically significant uropathogenic clone with fluid antimicrobial resistance capabilities.
Infant Formula Supplementation With Long-chain Polyunsaturated Fatty Acids Has No Effect on Bayley Developmental Scores at 18 Months of Age—IPD Meta-analysis of 4 Large Clinical Trials

Objectives: To find out whether supplementation of formula milk by long-chain polyunsaturated fatty acids (LCPUFA) affects neurodevelopment at 18 months of age in term or preterm infants by an individual patient data (IPD) meta-analysis. Materials and Methods: Data of 870 children from 4 large randomised clinical trials for formula milk with and without LCPUFAs allowed for assessing the effect of LCPUFA with adjustment for potential confounders and extensive subgroup analysis on prematurity, LCPUFA source, and dosage. Any additional clinical trials examining the effect of LCPUFA supplementation on Bayley Scales of Infant Development at 18 months were regarded as relevant. Two relevant studies were identified by MEDLINE, but were not available to us. An IPD meta-analysis was performed with subgroup analyses by preterm delivery, very low birth weight (<1500 g), trials with higher amounts of docosahexaenoic acid (DHA) and arachidonic acid (AA), and specific sources of LCPUFA. The sample size of 870 children was sufficient to detect clinically relevant differences in Bayley Scales even in subgroups. Results: There were no significant differences in mental or psychomotor developmental indexes between LCPUFA-supplemented and control groups for all children or in subgroups. This was confirmed with adjustment for the possible confounders: sex, gestational age, birth weight, maternal age, and maternal smoking. The adjusted mean differences in mental developmental index and psychomotor developmental index for all of the children were −0.8 (95% confidence interval −2.8 to 1.2) and −1.0 (−2.7 to 0.7), respectively. Conclusions: These data based on considerable sample size provide substantial evidence that LCPUFA supplementation of infant formula does not have a clinically meaningful effect on the neurodevelopment as assessed by Bayley scores at 18 months. Inclusion of all relevant data should not have led to differing conclusions except, possibly, for very-low-birth-weight infants.
C5aR and C3aR antagonists each inhibit diet‐induced obesity, metabolic dysfunction, and adipocyte and macrophage signaling

Mammalian survival depends on metabolizing nutrients, storing energy, and combating infection. Complement activation in blood triggers energy‐depleting immune responses to fight infections. Here we identify surprising energy‐conserving roles for complement proteins C5a and C3a and their receptors, C5aR and C3aR, roles that are contraindicated in complement biology. Rats fed a high‐carbohydrate high‐fat diet developed obesity, visceral adiposity, adipose inflammation, glucose/insulin intolerance, and cardiovascular dysfunction that correlated with increased plasma C3a, adipose C5aR, and C3aR. These in vivo changes were dramatically attenuated by receptor‐selective antagonists of either C5aR (5 mg/kg/d p.o.) or C3aR (30 mg/kg/d p.o.), which both reduced proinflammatory adipokines and altered expression of inflammatory genes in adipose tissue. In vitro C5a and C3a (100 nM) exhibited novel insulin‐like effects on 3T3‐L1 adipocytes, promoting energy conservation by increasing glucose and fatty acid uptake while inhibiting cAMP signaling and lipolysis, and induced PGE2 release from macrophages, effects all blocked by each respective antagonist (10 μM). These studies reveal important new links between complement signaling and metabolism, highlight new complement functions on adipocytes and in adipose tissue, demonstrate how aberrant immune responses may exacerbate obesity and metabolic dysfunction, and show that targeting C3aR or C5aR with antagonists is a new strategy for treating metabolic dysfunction. —Lim, J., Iyer, A. , Suen, J. Y. , Seow, V. , Reid, R. C. , Brown, L. , Fairlie, D. P. C5aR and C3aR antagonists each inhibit diet‐induced obesity, metabolic dysfunction, and adipocyte and macrophage signaling. FASEB J. 27, 822–831 (2013). www.fasebj. org
Regulation of Gap Junction Coupling Through the Neuronal Connexin Cx35 by Nitric Oxide and cGMP

Gap-junctional coupling among neurons is subject to regulation by a number of neurotransmitters including nitric oxide. We studied the mechanisms by which NO regulates coupling in cells expressing Cx35, a connexin expressed in neurons throughout the central nervous system. NO donors caused potent uncoupling of HeLa cells stably transfected with Cx35. This effect was mimicked by Bay 21-4272, an activator of guanylyl cyclase. A pharmacological analysis indicated that NO-induced uncoupling involved both PKG-dependent and PKG-independent pathways. PKA was involved in both pathways, suggesting that PKG-dependent uncoupling may be indirect. In vitro, PKG phosphorylated Cx35 at three sites: Ser110, Ser276, and Ser289. A mutational analysis indicated that phosphorylation on Ser110 and Ser276, sites previously shown also to be phosphorylated by PKA, had a significant influence on regulation. Ser289 phosphorylation had very limited effects. We conclude that NO can regulate coupling through Cx35 and that regulation is indirect in HeLa cells.
T-Cell mRNA Expression in Response to Mycobacterium bovis BCG Vaccination and Mycobacterium bovis Infection of White-Tailed Deer

ABSTRACT Understanding immune responses of white-tailed deer (WTD) to infection with Mycobacterium bovis provides insight into mechanisms of pathogen control and may provide clues to development of effective vaccine strategies. WTD were vaccinated with either M. bovis BCG strain Pasteur or BCG strain Danish. Both vaccinees and unvaccinated controls were subsequently inoculated with virulent M. bovis via the intratonsillar route. Real-time PCR was used to assess T-cell mRNA expression in peripheral blood leukocytes (PBL) from animals following vaccination and infection. Recall T-cell responses were measured by assessing the relative expression of gamma interferon (IFN-γ), T-cell-specific T-box transcription factor (Tbet), interleukin 12p40 (IL-12p40), IL-12p35, IL-23p19, FoxP3, IL-17, and GATA3 in PBL stimulated in vitro with purified protein derivative (PPD) of M. bovis or a recombinant fusion protein, ESAT6-CFP10. Animals vaccinated with BCG Danish expressed more IFN-γ and Tbet than either BCG Pasteur-vaccinated animals or unvaccinated controls. BCG Pasteur-vaccinated animals expressed more GATA3 than either group. After infection, unvaccinated controls expressed more Tbet and IL-12p40 than vaccinated animals. BCG Pasteur-vaccinated animals expressed more GATA3 than either the unvaccinated controls or the BCG Danish-vaccinated animals after infection. Animals were divided into pathology groups to correlate gene expression with severity of pathology. Animals in the visible lesion group expressed more Tbet and IFN-γ than animals that were culture negative, while Tbet and IFN-γ expression in the culture-positive, no-visible-lesion group was intermediate. GATA3 expression inversely correlated with pathology. Overall, expression of immune response genes correlated more closely with pathology than vaccination treatment.
The timeline of lamellar basement membrane changes during equine laminitis development.

REASONS FOR PERFORMING STUDY The timing of lamellar basement membrane (BM) changes occurring during laminitis development is incompletely understood. OBJECTIVES To determine the temporal progression of lamellar BM changes and whether laminin-332 (Ln-332) γ2 cleavage products are generated during laminitis development. METHODS Eight clinically normal Standardbred horses were allocated into treatment (n = 5) or sham (n = 3) groups. The treatment group received, via nasogastric intubation, an oligofructose (OF) bolus (10 g/kg bwt) while the sham group was given water. Laminitis induction proceeded for 48 h followed by euthanasia. Lamellar biopsies were obtained prior to dosing and at intervals during the treatment period for analysis (at 12, 18, 24, 30 and 36 h and at 48 h following euthanasia). RESULTS Changes in lamellar collagen type IV and Ln-332 were first observed at 12 h post dosing. A unique pattern of reactivity for the Ln-332 γ2 antibody D4B5 occurred, in which reactivity was observed only in lamellar tissue affected by laminitis. No bioactive Ln-332 γ2 proteolytic fragments were detected in lamellar samples. CONCLUSIONS Basement membrane changes occurred early during the laminitis process. Direct Ln-332 γ2 cleavage to release biologically active products did not appear to occur. Thus loss of stability or protein interaction of the BM is probably responsible for the γ2 specific reactivity observed. POTENTIAL RELEVANCE Basement membrane changes may a first step in lamellar failure occurring prior to detection with conventional methods. Thus, more sensitive detection methods of BM changes are required to study laminitis development.