Miracle-dz/UniFAR-FTUs huggingface dataset:
Female rat transcriptome response to infraorbital nerve transection differs from that of males: RNA‐seq

The effects of infraorbital nerve (ION) transection on gene expression in the adult female rat barrel cortex were investigated using RNA sequencing. After a 24‐hour survival duration, 28 genes were differentially regulated by ION transection. Differentially expressed genes suggest microglial activity, increased retrograde ciliary transport, and a decrease in inhibition. These changes may be functionally comparable to changes in the male barrel cortex, where changes in genes related to morphology, neuronal activity, and neuronal excitability were observed. However, the patterns in changes in gene expression are vastly different between male and female rats. The results strongly caution against the practice of generalizing data from one sex to both sexes. This cautionary note has potentially profound implications for a range of research lines, including substance abuse and stress, both research domains in which subjects have been predominantly males. Future research needs to employ sex as a classification variable, as sex differences can generally be expected. Future research is also needed to confirm that changes in gene expression observed with RNA‐seq correlate with changes in protein expression. J. Comp. Neurol. 525:140–150, 2017. © 2016 Wiley Periodicals, Inc.
Surface integration of velocity vectors from 3D digital colour Doppler: an angle independent method for laminar flow measurements.

BACKGROUND The study was designed to test the angle independence of a dynamic three-dimensional digital colour Doppler method for laminar flow measurement. The technique acquired three-dimensional data by rotational acquisition and used surface integration of Doppler vector velocities and flow areas in time and space for flow computation. METHOD A series of pulsatile flows (peak flow 55-180 ml/s) through a curved tube were studied with reference flow rates obtained using an ultrasonic flow meter. Colour Doppler imaging was performed at three angles to the direction of flow (20 degrees, 30 degrees, 40 degrees), using a multiplane transoesophageal probe controlled by an ATL HDI5000 system. Integration of digital velocity vectors over a curved three-dimensional surface across the tube for each of the 11 flow rates at each angle was performed off-line to compute peak flow. RESULTS Peak flow rates correlated closely (r=0.99) with the flow meter with the mean difference from the reference being -0.8+/-2 x 4 ml/s, 0.9+/-2.6 ml/s, 1.0+/-2 x 3 ml/s for 20 degrees, 30 degrees and 40 degrees respectively. Comparison of the three angle groups showed no significant differences (P=0.15, ANOVA). When sampled obliquely, the flow area on the curved surface increased while the velocities measured decreased. CONCLUSION Surface integration of velocity vectors to compute three-dimensional Doppler flow data is less angle dependent than conventional Doppler methods.
Structural and Functional Characterization of the Streptococcus pneumoniae RrgB Pilus Backbone D1 Domain*

Streptococcus pneumoniae expresses on its surface adhesive pili, involved in bacterial attachment to epithelial cells and virulence. The pneumococcal pilus is composed of three proteins, RrgA, RrgB, and RrgC, each stabilized by intramolecular isopeptide bonds and covalently polymerized by means of intermolecular isopeptide bonds to form an extended fiber. RrgB is the pilus scaffold subunit and is protective in vivo in mouse models of sepsis and pneumonia, thus representing a potential vaccine candidate. The crystal structure of a major RrgB C-terminal portion featured an organization into three independently folded protein domains (D2–D4), whereas the N-terminal D1 domain (D1) remained unsolved. We have tested the four single recombinant RrgB domains in active and passive immunization studies and show that D1 is the most effective, providing a level of protection comparable with that of the full-length protein. To elucidate the structural features of D1, we solved the solution structure of the recombinant domain by NMR spectroscopy. The spectra analysis revealed that D1 has many flexible regions, does not contain any intramolecular isopeptide bond, and shares with the other domains an Ig-like fold. In addition, we demonstrated, by site-directed mutagenesis and complementation in S. pneumoniae, that the D1 domain contains the Lys residue (Lys-183) involved in the formation of the intermolecular isopeptide bonds and pilus polymerization. Finally, we present a model of the RrgB protein architecture along with the mapping of two surface-exposed linear epitopes recognized by protective antisera.
Does Late 10k Filing Impact Companies’ Financial Reporting Strategy? Evidence from Discretionary Accruals and Real Transaction Management

The study investigates how late 10K filers adapt their financial reporting strategy in the post&#8208;late filing period in their response to bad publicity, negative market sentiment, and higher stakeholders&#8217; scrutiny resulting from reporting delays. Both the level and change regressions show that late 10K filers significantly reduce the use of discretionary accruals from pre&#8208; to post&#8208;late filing year. However, they simultaneously increase real transaction management over the same time period. The trade&#8208;offs between the two earnings management techniques are more prominent when the late filers have a strong incentive to meet or beat earnings benchmarks. Our primary results are robust when late filings are caused by accounting, auditing, and internal control issues, and when the late filers cited no meaningful reason for late 10K filings. It is further evident that late filers with material internal control weaknesses and late filers that subsequently restate their financial statements make relatively higher trade&#8208;offs than the matched non&#8208;late filers. Finally, the trade&#8208;offs between reduced accruals and increased real transaction management are stronger for the accelerated filers, and for the late filers audited by Big 4 auditors.
Effect of Gamma-Oryzanol as Therapeutic Agent to Prevent Cardiorenal Metabolic Syndrome in Animals Submitted to High Sugar-Fat Diet

Background: The high consumption of fat and sugar contributes to the development of obesity and co-morbidities, such as diabetes, and cardiovascular and kidney diseases. Different strategies have been used to prevent these diseases associated with obesity, such as changes in eating habits and/or the addition of dietary components with anti-inflammatory and anti-oxidant properties, such as gamma-oryzanol (γOz) present mainly in bran layers and rice germ. Methods: Animals were randomly divided into four experimental groups and fed ad libitum for 20 weeks with control diet (C, n = 8), control diet + γOz (C + γOz, n = 8), high-sugar and high-fat diet (HSF, n = 8), and high-sugar and high-fat diet + γOz (HSF + γOz, n = 8). HSF groups also received water + sucrose (25%). The dose of γOz was added to diets to reach 0.5% of final concentration (w/w). Evaluation in animals included food and caloric intake, body weight, plasma glucose, insulin, triglycerides, uric acid, HOMA-IR, glomerular filtration rate, protein/creatinine ratio, systolic blood pressure, and Doppler echocardiographic. Results: Animals that consumed the HSF diet had weight gain compared to group C, increased insulin, HOMA, glucose and triglycerides, there were also atrial and ventricular structural alterations, deterioration of systolic and diastolic function, decreased glomerular filtration rate, and proteinuria. Gamma-oryzanol is significantly protective against effects on body weight, hypertriglyceridemia, renal damage, and against structural and functional alteration of the heart. Conclusion: Gamma-oryzanol shows potential as a therapeutic to prevent Cardiorenal Metabolic Syndrome.
Drought stress limits the geographic ranges of two tree species via different physiological mechanisms

Range shifts are among the most ubiquitous ecological responses to anthropogenic climate change and have large consequences for ecosystems. Unfortunately, the ecophysiological forces that constrain range boundaries are poorly understood, making it difficult to mechanistically project range shifts. To explore the physiological mechanisms by which drought stress controls dry range boundaries in trees, we quantified elevational variation in drought tolerance and in drought avoidance‐related functional traits of a widespread gymnosperm (ponderosa pine – Pinus ponderosa) and angiosperm (trembling aspen – Populus tremuloides) tree species in the southwestern USA. Specifically, we quantified tree‐to‐tree variation in growth, water stress (predawn and midday xylem tension), drought avoidance traits (branch conductivity, leaf/needle size, tree height, leaf area‐to‐sapwood area ratio), and drought tolerance traits (xylem resistance to embolism, hydraulic safety margin, wood density) at the range margins and range center of each species. Although water stress increased and growth declined strongly at lower range margins of both species, ponderosa pine and aspen showed contrasting patterns of clinal trait variation. Trembling aspen increased its drought tolerance at its dry range edge by growing stronger but more carbon dense branch and leaf tissues, implying an increased cost of growth at its range boundary. By contrast, ponderosa pine showed little elevational variation in drought‐related traits but avoided drought stress at low elevations by limiting transpiration through stomatal closure, such that its dry range boundary is associated with limited carbon assimilation even in average climatic conditions. Thus, the same climatic factor (drought) may drive range boundaries through different physiological mechanisms – a result that has important implications for process‐based modeling approaches to tree biogeography. Further, we show that comparing intraspecific patterns of trait variation across ranges, something rarely done in a range‐limit context, helps elucidate a mechanistic understanding of range constraints.
Effect of natural infection with minor pathogens on susceptibility to natural infection with major pathogens in the bovine mammary gland.

OBJECTIVE To evaluate the effect of natural udder infection with minor pathogens on subsequent natural infection with major pathogens. SAMPLE POPULATION 7 dairy herds with low bulk milk somatic cell count. PROCEDURE During a 20-month prospective study, milk samples were collected from diary cows at regular intervals and from quarters with clinical signs of mastitis. Incidence of intramammary infection was calculated in uninfected quarters and in quarters infected with minor pathogens. A within-cow, matched case-control analysis was used to evaluate the effect of minor pathogens on subsequent infection with major pathogens. RESULTS Quarters infected with minor pathogens had higher somatic cell count than did uninfected quarters. In quarters infected with Corynebacterium bovis, the rate of infection with major pathogens was lower, whereas in quarters infected with coagulase-negative Micrococcaceae, the rate of infection with major pathogens was higher than that in uninfected quarters. From the within-cow comparison, it appeared that, in quarters infected with minor pathogens, infection with major pathogens was significantly lower than that in comparable control quarters not infected with minor pathogens. CONCLUSIONS Minor pathogens have a protective effect against infection with major pathogens. The protective effect of C bovis against subsequent infection with major pathogens appears to be greater than the effect of coagulase-negative Micrococcaceae.
Protective action of the peroxisome proliferator‐activated receptor‐γ agonist pioglitazone in a mouse model of Parkinson's disease

We examined the effect of pioglitazone, a peroxisome proliferator‐activated receptor‐γ (PPARγ)agonistofthethiazolidinedione class, on dopaminergic nerve cell death and glial activation in the 1‐methyl‐4‐phenyl‐1,2,3,6‐tetrahydropyridine (MPTP) mouse model of Parkinson's disease. The acute intoxication of C57BL/6 mice with MPTP led to nigrostriatal injury, as determined by tyrosine hydroxylase (TH) immunocytochemistry, and HPLC detection of striatal dopamine and metabolites. Damage to the nigrostriatal dopamine system was accompanied by a transient activation of microglia, as determined by macrophage antigen‐1 (Mac‐1) and inducible nitric oxide synthase (iNOS) immunoreactivity, and a prolonged astrocytic response. Orally administered pioglitazone (∼ 20 mg/kg/day) attenuated the MPTP‐inducedglialactivation and prevented the dopaminergic cell loss in the substantia nigra pars compacta (SNpc). In contrast, there was little reduction of MPTP‐induced dopamine depletion, with no detectable effect on loss of TH immunoreactivity and glial response in the striatum of pioglitazone‐treated animals. Low levels of PPARγ expression were detected in the ventral mesencephalon and striatum, and were unaffected by MPTP or pioglitazone treatment. Since pioglitazone affects primarily the SNpc in our model, different PPARγ‐independent mechanisms may regulate glial activation in the dopaminergic terminals compared with the dopaminergic cell bodies after acute MPTP intoxication.
Effects of exposure to low concentrations of carbon monoxide on exercise performance and myocardial perfusion in young healthy men.

OBJECTIVE: To assess the effects of exposure to low concentrations of carbon monoxide (CO), as commonly measured in atmospheric urban air pollution and certain occupational environments, on exercise performance and myocardial perfusion in young healthy men, and the possible need for tighter restrictions on ambient concentrations of CO. METHODS: 15 young, healthy non-smoking men, 18-35 years old, were exposed blindly and randomly to air or to a mixture of CO and air, followed by an exercise treadmill test with thallium heart scintigraphy. Blood was drawn for determination of carboxyhaemoglobin before and at the end of the exposure, and for lactic and pyruvic acid at the beginning and the end of the exercise test. The main outcome measures include the duration of the exercise test, the maximal effort expressed in metabolic equivalent units (METs), the mean plasma lactic to pyruvic acid ratio at the end of the ergometry, ECG changes in the exercise test, and perfusion deficits in thallium heart scintigraphy. RESULTS: At the end of exposure to CO, the mean (SD) blood carboxyhaemoglobin concentration rose from 0.59% (0.08%) to 5.12% (0.65%) (p < 0.0001). At the end of the exercise period, the mean (SD) plasma lactate/pyruvate ratio, which reflects the level of anaerobic metabolism (69.9 (5.9) after air and 75.9 (7.0) after CO), was not significantly different between the two experimental groups. Exercise induced electrocardiographic changes were noted in only one subject after exposure to CO. No arrhythmias were detected in any of the subjects. Significant differences were found in the mean duration of the exercise test (p = 0.0012) and the METs (p = 0.0001). The mean adjusted difference of exercise duration between exposure to air and CO was 1.52 minutes 95% confidence interval (95% CI) 0.73 to 2.32 minutes. The mean adjusted difference of METs between exposure to air and CO was 2.04 95% CI 1.33 to 2.76. The models for duration of exercise and METs showed no significant sequence and period effects. Thallium myocardial perfusion imaging disclosed normal perfusion in all regions of the heart, with no significant differences in perfusion between the two exercise tests (after air or CO). CONCLUSION: Acute exposure to a low concentration of CO which produces blood carboxyhaemoglobin concentrations of 4%-6% significantly decreases exercise performance in young healthy men. No ischaemic electrocardiographic changes or disturbances in myocardial perfusion were found by graded exercise with thallium scintigraphy. Our findings suggest that pollution of atmospheric air by CO at concentrations which are commonly found in urban and industrial environments may exert an adverse effect on skeletal muscles, manifesting as decreased exercise performance.
Pharmacological specificity of conditioned avoidance response inhibition in rats: inhibition by neuroleptics and correlation to dopamine receptor blockade.

The inhibitory effect of 36 neuroleptic compounds on conditioned avoidance response (CAR) and unconditioned escape response (UER) has been studied in rats. All neuroleptics antagonized CAR in doses below those inhibiting UER and below those inducing catalepsy. Stereospecificity was shown in two cases. Significant correlation was found between CAR inhibitory and cataleptogenic potency. Also inhibition of amphetamine induced stereotypy, affinity to 3H-haloperidol binding sites in vitro and clinical potency was significantly correlated to CAR inhibition. CAR and UER inhibition induced by cis(Z)-flupentixol and haloperidol was attenuated by scopolamine, but was only weakly influenced by methysergide and prazosin. Among a wide range of other CNS active compounds tested, CAR was inhibited by alpha 1-adrenergic antagonists, benzodiazepines, a barbiturate, GABA agonists, morphine and a serotonin agonist, but in doses inducing other motor disturbances. It is concluded that CAR inhibition is a sensitive test for dopamine receptor antagonists. However, additional alpha-adrenergic activity found for some neuroleptics (e.g. clozapine, chlorprothixene) may contribute to the CAR inhibitory potency. Additional antimuscarinic activity of neuroleptics may moderately attenuate CAR inhibition whereas serotonin receptor blockade is of minor importance.
Computational modeling of 915 MHz microwave ablation: Comparative assessment of temperature‐dependent tissue dielectric models

Purpose The objective of this study is to develop a computational model for simulating 915 MHz microwave ablation (MWA), and verify the simulation predictions of transient temperature profiles against experimental measurements. Due to the limited experimental data characterizing temperature‐dependent changes of tissue dielectric properties at 915 MHz, we comparatively assess two temperature‐dependent approaches of modeling of dielectric properties: model A‐ piecewise linear temperature dependencies based on existing, but limited, experimental data, and model B‐ similar to model A, but augmented with linear decrease in electrical conductivity above 95 °C, as guided by our experimental measurements. Methods The finite element method was used to simulate MWA procedures in liver with a clinical 915 MHz ablation applicator. A coupled electromagnetic‐thermal solver incorporating temperature‐dependent tissue biophysical properties of liver was implemented. Predictions of the transient temperature profiles and ablation zone dimensions for both model A and model B were compared against experimental measurements in ex vivo bovine liver tissue. Broadband dielectric properties of tissue within different regions of the ablation zone were measured and reported at 915 MHz and 2.45 GHz. Results Model B yielded peak tissue temperatures in closer agreement with experimental measurements, attributed to the inclusion of decrease in electrical conductivity at elevated temperature. The simulated transverse diameters of the ablation zone predicted by both models were greater than experimental measurements, which may be in part due to the lack of a tissue shrinkage model. At both considered power levels, predictions of transverse ablation zone diameters were in closer agreement with measurements for model B (max. discrepancy of 5 mm at 60 W, and 3 mm at 30 W), compared to model A (max. discrepancy of 9 mm at 60 W, and 6 mm at 30 W). Ablation zone lengths with both models were within 2 mm at 30 W, but overestimated by up to 10 mm at 60 W. Conclusions The inclusion of decreased electrical conductivity above 95 °C, implemented with model B as guided by our experimental measurements, may be a good approach for approximating the dynamic changes that occur during MWA at 915 MHz. Although a step toward more effectively modeling MWA at 915 MHz, further investigation of the transition in dielectric properties with temperature and tissue shrinkage, especially at high temperatures is needed for more accurate simulations.
The pharmacology and safety of paliperidone extended-release in the treatment of schizophrenia

Paliperidone extended-release (ER) is a newly commercialised antipsychotic formulated using the principal active metabolite of risperidone, 9-hydroxyrisperidone. It has been developed as an osmotic controlled-release oral delivery system that minimizes peak-trough fluctuations in plasma concentrations, allowing once-daily administration and theoretically leading to a decreased incidence of adverse effects. Available data from preregistration, multicenter, short-term, double-blind, placebo-controlled studies indicate that paliperidone ER, at dosages of 3 – 15 mg/day, is relatively safe and well tolerated in adult patients with schizophrenia. As with risperidone, paliperidone may cause extrapyramidal symptoms and hyperprolactinemia in a dose-dependent manner. Preliminary long-term studies (up to 52 weeks) appear to confirm the findings from short-term trials indicating a low liability for paliperidone ER to cause metabolic effects (i.e., weight gain, hyperglycaemia and lipid dysregulation). Safety data from elderly patients appear to be promising. Due to negligible hepatic biotransformation, paliperidone ER is unlikely to be involved in clinically significant metabolic drug–drug interactions.
Energy minimization of discrete functions with higher-order potentials for depth map generation

Minimization of discrete energy functions considering higher-order potentials is a challenging yet an important problem. In this work, a three-step procedure will be presented and exemplified on a general problem related to the dense depth map computation from multi-view configurations: Achieving a joint reconstruction of structure and semantics with piecewise planarity constraints. The three steps of the procedure are binarization, quadratization, and energy minimization. While the first and the third step are accomplished using procedures based on alpha-expansion and max-flow algorithms, respectively, we propose for the quadratization step a fast and simple module to reformulate the higher-order problem as a quadratic one. This module is based on edge statistics and is particularly useful for regular graphs and for third- or fourth-order potentials.