Miracle-dz/UniFAR-FTUs huggingface dataset:
Mechanism of negative lusitropic effect of alpha 1-adrenoceptor stimulation in cat papillary muscles.

Experiments were performed in cat papillary muscles to explore the mechanisms by which alpha 1-adrenoceptor stimulation affects myocardial relaxation. Phenylephrine (PE; 10 microM) + atenolol (1 microM; n = 8 experiments) produced a negative lusitropic effect, i.e., a prolongation of half-relaxation time (t1/2; time to 50% relaxation) by 30 +/- 10% (P < 0.05) and a proportionally smaller increase in maximal velocity of relaxation (-T) than in maximal velocity of contraction (+T), which significantly increased the ratio +T/-T. A similar increase in contractility, produced by increasing calcium, failed to significantly change t1/2 and +T/-T. PE-induced negative lusitropic effect was significantly inhibited by two protein kinase C (PKC) inhibitors, staurosporine (0.1 microM) and chelerythrine (10 microM). PE also increased intracellular pH by 0.18 +/- 0.05 pH units (P < 0.05, n = 4), as measured by the fluorescent dye 2'-7'-bis(2-carboxyethyl)-5(6)-carboxyfluorescein. Intracellular alkalosis and the negative lusitropic effect of PE were prevented by the Na+/H+ exchanger inhibitor ethylisopropylamiloride (10 microM). No significant changes in calcium myofilament sensitivity and maximal tension were detected in trabeculae treated with PE either before or after chemical skinning. These results indicate that a Na+/H+ exchanger-induced intracellular alkalosis, possibly mediated by PKC activation, may fully account for the negative lusitropism of alpha 1-adrenoceptor stimulation.
Transcriptional Profiling of Host Cell Responses to Virulent Haemophilus parasuis: New Insights into Pathogenesis

Haemophilus parasuis is the causative agent of Glässer’s disease in pigs. H. parasuis can cause vascular damage, although the mechanism remains unclear. In this study, we investigated the host cell responses involved in the molecular pathway interactions in porcine aortic vascular endothelial cells (PAVECs) induced by H. parasuis using RNA-Seq. The transcriptome results showed that when PAVECs were infected with H. parasuis for 24 h, 281 differentially expressed genes (DEGs) were identified; of which, 236 were upregulated and 45 downregulated. The 281 DEGs were involved in 136 KEGG signaling pathways that were organismal systems, environmental information processing, metabolism, cellular processes, and genetic information processing. The main pathways were the Rap1, FoxO, and PI3K/Akt signaling pathways, and the overexpressed genes were determined and verified by quantitative reverse transcription polymerase chain reaction. In addition, 252 genes were clustered into biological processes, molecular processes, and cellular components. Our study provides new insights for understanding the interaction between bacterial and host cells, and analyzed, in detail, the possible mechanisms that lead to vascular damage induced by H. parasuis. This may lead to development of novel therapeutic targets to control H. parasuis infection.
Fast and accurate modeling of protein–protein interactions by combining template‐interface‐based docking with flexible refinement

The similarity between folding and binding led us to posit the concept that the number of protein–protein interface motifs in nature is limited, and interacting protein pairs can use similar interface architectures repeatedly, even if their global folds completely vary. Thus, known protein–protein interface architectures can be used to model the complexes between two target proteins on the proteome scale, even if their global structures differ. This powerful concept is combined with a flexible refinement and global energy assessment tool. The accuracy of the method is highly dependent on the structural diversity of the interface architectures in the template dataset. Here, we validate this knowledge‐based combinatorial method on the Docking Benchmark and show that it efficiently finds high‐quality models for benchmark complexes and their binding regions even in the absence of template interfaces having sequence similarity to the targets. Compared to “classical” docking, it is computationally faster; as the number of target proteins increases, the difference becomes more dramatic. Further, it is able to distinguish binders from nonbinders. These features allow performing large‐scale network modeling. The results on an independent target set (proteins in the p53 molecular interaction map) show that current method can be used to predict whether a given protein pair interacts. Overall, while constrained by the diversity of the template set, this approach efficiently produces high‐quality models of protein–protein complexes. We expect that with the growing number of known interface architectures, this type of knowledge‐based methods will be increasingly used by the broad proteomics community. Proteins 2012; © 2011 Wiley Periodicals, Inc.
Developmental Exposure to a Mixture of 23 Chemicals Associated With Unconventional Oil and Gas Operations Alters the Immune System of Mice

Chemicals used in unconventional oil and gas (UOG) operations have the potential to cause adverse biological effects, but this has not been thoroughly evaluated. A notable knowledge gap is their impact on development and function of the immune system. Herein, we report an investigation of whether developmental exposure to a mixture of chemicals associated with UOG operations affects the development and function of the immune system. We used a previously characterized mixture of 23 chemicals associated with UOG, and which was demonstrated to affect reproductive and developmental endpoints in mice. C57Bl/6 mice were maintained throughout pregnancy and during lactation on water containing two concentrations of this 23-chemical mixture, and the immune system of male and female adult offspring was assessed. We comprehensively examined the cellularity of primary and secondary immune organs, and used three different disease models to probe potential immune effects: house dust mite-induced allergic airway disease, influenza A virus infection, and experimental autoimmune encephalomyelitis (EAE). In all three disease models, developmental exposure altered frequencies of certain T cell sub-populations in female, but not male, offspring. Additionally, in the EAE model disease onset occurred earlier and was more severe in females. Our findings indicate that developmental exposure to this mixture had persistent immunological effects that differed by sex, and exacerbated responses in an experimental model of autoimmune encephalitis. These observations suggest that developmental exposure to complex mixtures of water contaminants, such as those derived from UOG operations, could contribute to immune dysregulation and disease later in life.
Food allergy and allergic rhinitis in 435 asian patients - A descriptive review.

OBJECTIVE To describe the prevalence of food allergy in Asian patients with allergic rhinitis. STUDY DESIGN A non-randomized prospectively collected patients over a three year period, with complaints of nose congestion, rhinorrhea and/or nasal discharge. RESULTS There were 435 patients enrolled, 213 children and 222 adults. The children group had a high prevalence of allergen specific IgE to Dermatophagoides pteryonysinus (70%), Dermatophagoides farina (69%), and Blomia tropicalis (55%); followed by dogs (32%), cats (19%) and cockroaches (19%). In the children food allergy category, the top three allergens were egg white (54%), milk (31%) and soya bean (13%). The adult group had results of Dermatophagoides pteryonysinus (71%), Dermatophagoides farina (72%), and Blomia tropicalis (59%); the adult food allergy category, the top 3 allergens were egg white (13%), milk (6%) and soya bean (5%). There was a statistically significant difference in the child and adult group for Dust, D. pteryonysinus, D. farina, B.tropicalis, egg white, wheat, gluten and soya bean. In the age specific child groups, there was an increased in egg food allergy levels, with a peak at the age of five-nine years old and decreasing thereafter (p=0.04). In the children group, the mean Total Nasal Symptom Score (TNSS) was 10.3 (range of 7 to 13); the adult group was similar, with a mean TNSS of 9.8 (range 5 to 12). CONCLUSION The prevalence of food allergy in paediatric patients with allergic rhinitis is fairly high and should be considered when treating these children.
Farnesol Inhibits L-type Ca2+ Channels in Vascular Smooth Muscle Cells*

Earlier experiments with animal and human arteries have shown that farnesol, a natural 15-carbon (C15) isoprenoid, is an inhibitor of vasoconstriction (Roullet, J.-B., Xue, H., Chapman, J., McDougal, P., Roullet, C. M., and McCarron, D. A. (1996) J. Clin. Invest.97, 2384–2390). We report here that farnesol reduced KCl- and norepinephrine-dependent cytosolic Ca2+ transients in fura-2-loaded intact arteries. An effect on Ca2+signaling was also observed in cultured aortic smooth muscle cells (A10 cells). In these cells, farnesol reduced KCl-induced [Ca2+] i transients and mimicked the inhibitory effect of Ca2+-free medium on the [Ca2+] i response to both 12,13-phorbol myristate acetate, a protein kinase C activator, and thapsigargin, a specific endoplasmic reticulum ATPase inhibitor. Perforated patch-clamp experiments further showed in two vascular smooth muscle cell lines (A10 and A7r5), a reversible, dose-dependent inhibitory effect of farnesol on L-type Ca2+ currents (IC50 = 2.2 μm). Shorter (C10, geraniol) and longer (C20, geranylgeraniol) isoprenols were inactive. L-type Ca2+ channel blockade also occurred under tight (gigaohm) seal configuration using cell-attached, single-channel analysis, thus suggesting a possible action of farnesol from within the intracellular space. We finally demonstrated that farnesol did not affect Ca2+-sensitive pathways implicated in smooth muscle contraction, as tested with α-toxin permeabilized arteries. Altogether, our results indicate that farnesol is an inhibitor of vascular smooth muscle Ca2+ signaling with plasma membrane Ca2+ channel blocker properties. The data have implications for the endogenous and pharmacological regulation of vascular tone by farnesol or farnesol analogues.
The effectiveness of inpatient and outpatient treatment for alcohol abuse: the need to focus on mediators and moderators of setting effects.

Previous reviews have concluded that there was no evidence for the superiority of inpatient over outpatient treatment of alcohol abuse, although particular types of patients might be more effectively treated in inpatient settings. In this review, we first consider the conceptual rationales that have been offered to support inpatient and outpatient treatment. Following that, the results of the relevant research on setting effects are presented. Five studies had significant setting effects favoring inpatient treatment, two studies found day hospital to be significantly more effective than inpatient treatment, and seven studies yielded no significant differences on drinking-related outcome variables. In all but one instance in which a significant effect emerged, patients in the 'superior' setting received more intensive treatment and patients were not 'preselected' for their willingness to accept random assignment to treatment in either setting. Studies finding significant setting effects also conducted more treatment contrasts (18.6 vs. 4.9), on average, and had a mean statistical power level of 0.71 (median 0.79) to detect a medium-sized effect, whereas studies with no significant findings had an average power level of 0.55 (median 0.57). When inpatient treatment was found to be more effective, outpatients did not receive a respite in the form of inpatient detoxification and the studies were slightly less likely to have social stability inclusion criteria and to use random assignment to treatment settings. We consider the implications of our findings for future research, especially the need to examine the conceptual rationales put forward by proponents of inpatient and outpatient treatment, i.e. mediators and moderators of setting effects.
Differential kinetics of circulating angiotensin IV and II after treatment with angiotensin II type 1 receptor antagonist and their plasma levels in patients with chronic renal failure.

BACKGROUND Angiotensin II (Ang II) C-terminal hexapeptide (referred to as Ang IV) possesses the characteristics of a real hormone with specific receptors and biological effects. Clinical application of Ang II type 1 receptor (AT1-R) antagonists cause an increase in plasma Ang II level, which may result in enhanced production of Ang IV. PATIENTS AND METHODS In this study, we measured plasma Ang IV and Ang II levels in patients with chronic renal failure (CRF), and also examined the changes in Ang IV and Ang II levels after administration of an ATI-R antagonist. RESULTS Ang II and Ang IV levels in CRF patients untreated with hemodialysis (n = 16) were 15.8+/-3.6 and 6.0+/-1.1 pg/ml, respectively, which did not differ significantly from Ang II (20.6+/-2.4) and Ang IV levels (8.6+/-1.1) in normal controls (n = 23). The ratio of Ang IV to Ang II was 38%, similar to that in the controls (41%). Ang II or Ang IV levels in CRF patients treated with hemodialysis (n = 12) were also similar to the control values. Ang IV levels had a significant correlation with Ang II levels (r = 0.59). When hypertensive patients were treated with an AT1-R antagonist candesartan for 7 days, Ang II and Ang IV levels were increased 5.5- and 4.1-fold relative to the control levels, respectively. Ang II levels 28 and 56 days after treatment were significantly lower than those 7 days after treatment, whereas Ang IV levels did not differ significantly from those 7 days after treatment. Similar differential kinetics in Ang II and Ang IV levels after long-term (90 days) treatment with an AT1-R antagonist was also confirmed in experiments using rats. Significant decrease in blood pressure continued during long-term treatment with an AT1-R antagonist. CONCLUSION These findings demonstrated that plasma Ang IV levels in patients with CRF did not differ significantly from those in normal subjects, and that treatment with an AT1-R antagonist caused marked increases in both Ang II and Ang IV levels. In contrast, during long-term treatment plasma Ang II levels were more rapidly decreased than Ang IV levels, suggesting longer-lasting enhancement of the action of Ang IV rather than that of Ang II after treatment with an AT1-R antagonist.
Evaluation of Impairment Caused by MPEG Video Frame Loss

This article presents a study on the impact of video frame losses on the quality perceived by users. Video compression standards, such as MPEG, use a sequence of frames called Group of Pictures (GOP), which is a video compression method which a frame is expressed in terms of one or more neighboring frames. This dependence between frames impacts directly in the quality because a loss of a reference frame prevents the decoding of other frames in GOP, thereby reducing the user-perceived quality. The assessment of quality in this article is estimated by Peak Signal Noise Ratio (PSNR), which compares the original and the received images. Computer simulations were used to show that the degradation on the quality may vary for different patterns of GOPs and type of lost frames.
Role of IL-1β in type 2 diabetes

Purpose of reviewTo understand the role of inflammation as the fundamental cause of type 2 diabetes and specifically to examine the contribution of IL-1β. Recent findingsRecent studies from animals, in-vitro cultures and clinical trials provide evidence that support a causative role for IL-1β as the primary agonist in the loss of beta-cell mass in type 2 diabetes. In vitro, IL-1β-mediated autoinflammatory process results in beta-cell death. The autoinflammation is driven by glucose, free fatty acids, leptin, and IL-1β itself. Caspase-1 is required for IL-1β activity and the release of free fatty acids from the adipocyte. An emerging hypothesis gains support from patients with type 2 diabetes in which an imbalance in the amount of IL-1β agonist activity versus the specific countering by the naturally occurring IL-1 receptor antagonist (IL-1Ra) determines the outcome of islet inflammation. An important confirmation comes from clinical trials. Blockade of IL-1 receptor with anakinra, the recombinant form of IL-1Ra, or neutralizing anti-IL-1β antibodies, provides proof-of-principle data that reducing IL-1β activity is sufficient for correcting dysfunctional beta-cell production of insulin in type 2 diabetes, including a possibility that suppression of IL-1β-mediated inflammation in the microenvironment of the islet allows for regeneration. SummaryMonotherapy or add-on therapy targeting IL-1β in type 2 diabetes holds promise for long-term benefits in glycemic control and possibly reducing cardiovascular events.
Angiographic morphology and response to therapy in unstable angina

The coronary anatomy of 69 patients with unstable angina, subgrouped according to response to medical therapy, was investigated. All patients received oral treatment with nitrates, calcium antagonists, and beta‐blocking agents. When combined oral treatment was not effective, an intravenous infusion of nitrates (10–100 m̈g/min) was subsequently administered. Coronary arteriography was performed within hours (14±9 h) from the last episode of chest pain in 28 patients refractory to medical treatment, while in 41 patients who became asymptomatic during medical therapy, angiography was performed after an observation period of several days (8 ± 6 days). On angiography, the nonresponder group was characterized by a prevalence of eccentric and multiple lesions, and by a 46% incidence of thrombi (p <0.001). Recurrent symptoms requiring emergency bypass operation were common in this group. In patients responsive to medical treatment, a high percentage of concentric lesions (37%) and totally occluded (34%) coronary arteries was found (p <0.05). No infarcts and low rate of recurrent angina were noted in these patients during hospitalization. In conclusion, the finding of intracoro‐nary thrombotic material and eccentric or multiple lesions can be an accurate markers of the active phase of the disease, while “silent” occlusion of the involved vessel may be accompanied by relief of symptoms during medical therapy.
Structural brain abnormalities in chronic schizophrenia at the extremes of the outcome spectrum.

OBJECTIVE This study investigated the relationship between outcome and structural brain abnormalities in schizophrenia. METHOD Intracranial volume and volumes of the cerebrum, gray and white matter, lateral and third ventricles, frontal lobes, thalamus, and cerebellum were measured in 20 patients with a poor outcome, 25 with a favorable outcome, and 23 healthy comparison subjects with magnetic resonance imaging. RESULTS Thalamic volume was significantly smaller both in poor-outcome patients and good-outcome patients. In contrast, only poor-outcome patients displayed significantly smaller cerebral gray matter, particularly prefrontal, and enlargement of the lateral and third ventricles. No significant differences were found for intracranial, cerebellar, or cortical CSF volumes. CONCLUSIONS Smaller thalamic volumes in schizophrenia may reflect a greater susceptibility for the disorder and seem unrelated to outcome. In contrast, gray matter volume loss of the cerebrum, particularly in the frontal lobes, and lateral and third ventricular enlargement appear related to outcome in schizophrenia.
Moderately lipophilic carboxylate compounds are the selective inducers of the Saccharomyces cerevisiae Pdr12p ATP‐binding cassette transporter

Saccharomyces cerevisiae displays very strong induction of a single ATP‐binding cassette (ABC) transporter, Pdr12p, when stressed with certain weak organic acids. This is a plasma membrane pump catalysing active efflux of the organic acid anion from the cell. Pdr12p action probably allows S. cerevisiae to maintain lower intracellular levels of several weak organic acid preservatives than would be expected on the basis of the free equilibration of the acid across the cell membrane. This in turn facilitates growth in the presence of these preservatives and therefore yeast spoilage of food materials. Pdr12p appears to confer resistance to those carboxylic acids that, to a reasonable degree, partition into both the lipid bilayer and aqueous phases. Its gene (PDR12) is strongly induced by sorbate, benzoate and certain other moderately lipophilic carboxylate compounds, but not by organic alcohols or high levels of acetate. PDR12 induction reflects the operation of a previously uncharacterized S. cerevisiae stress response, for which the induction signal is probably a high intracellular pool of the organic acid anion. Copyright © 2003 John Wiley & Sons, Ltd.
What Is Better Than Coulomb Failure Stress? A Ranking of Scalar Static Stress Triggering Mechanisms from 105 Mainshock‐Aftershock Pairs

Aftershocks may be triggered by the stresses generated by preceding mainshocks. The temporal frequency and maximum size of aftershocks are well described by the empirical Omori and Bath laws, but spatial patterns are more difficult to forecast. Coulomb failure stress is perhaps the most common criterion invoked to explain spatial distributions of aftershocks. Here we consider the spatial relationship between patterns of aftershocks and a comprehensive list of 38 static elastic scalar metrics of stress (including stress tensor invariants, maximum shear stress, and Coulomb failure stress) from 213 coseismic slip distributions worldwide. The rates of true‐positive and false‐positive classification of regions with and without aftershocks are assessed with receiver operating characteristic analysis. We infer that the stress metrics that are most consistent with observed aftershock locations are maximum shear stress and the magnitude of the second and third invariants of the stress tensor. These metrics are significantly better than random assignment at a significance level of 0.005 in over 80% of the slip distributions. In contrast, the widely used Coulomb failure stress criterion is distinguishable from random assignment in only 51–64% of the slip distributions. These results suggest that a number of alternative scalar metrics are better predictors of aftershock locations than classic Coulomb failure stress change.
Fast estimation of average leakage based on pre-characterizing standard cell

In CMOS circuits, sub-threshold leakage (ISUB) has been an important issue during IC design. As technology keeps on scaling down, new leakage mechanisms such as bound to bound leakage (IBTBT) and gate tunneling leakage (IGATE) can't still be neglected. Estimating the total leakage of a circuit at high level can help the designers to decide whether the design is eligible or should be modified. This paper introduced the main leakage mechanisms, including ISUB, IBTBT and IGATE. The authors have also proposed a method to estimate the average leakage quickly based on pre-characterizing standard cell with BSIM models considering the new mechanisms. The results obtained by experiment on ISCAS benchmark circuits show that the method can be used to get the total leakage value and give a early direction for IC design.
Fast Three Dimensional Magnetic Resonance Imaging

To reduce the scan time in three‐dimensional (3D) imaging, the authors consider alternative trajectories for traversing k‐space. They differ from traditional 3D trajectories, such as 3DFT, in that they employ time‐varying gradients allowing longer readouts and in turn a reduced scan time. Some of these trajectories reduce by an order of magnitude the number of excitations compared with 3DFT and provide flexibility for trading off signal‐to‐noise ratio for scan time. Other concerns are the minimum echo time and flow/motion properties. As examples, the authors show two applications: A 3D data set of the head (field of view of 30 x 30 x 7.5 cm and resolution of 1.5 x 1.5 x 1.5 mm) acquired in 56 s using a stack of spirals in 3D k‐space; and a 3D movie of the heart (20 x 20 x 20 cm field of view, 2 x 2 x 2 mm resolution, and 16 time frames per cardiac cycle) acquired in 11 min using a cones trajectory.