Miracle-dz/UniFAR-FTUs huggingface dataset:
Nitric oxide and noradrenaline contribute to the temperature threshold of the axon reflex response to gradual local heating in human skin

The initial skin blood flow response to rapid local heating is an axon reflex, which may be mediated by calcitonin gene‐related peptide and substance P released from C‐fibres. We investigated the role of nitric oxide (NO) and noradrenaline on the temperature threshold for the axon reflex during gradual local heating. 36 subjects participated in two studies. Using microdialysis, we examined the following interventions: NO synthase inhibition (10 mmNG‐nitro‐l‐arginine methyl ester, l‐NAME); low‐dose NO infusion (1.0 μm sodium nitroprusside, SNP); adrenergic blockade (10 mm bretylium tosylate); and low‐dose (0.1 μm) noradrenaline infusion. Laser‐Doppler flowmetry was used to measure red blood cell flux. Skin was heated at a rate of 0.1°C min−1 from 33°C to 40°C. Compared to control skin sites, the axon reflex response was shifted to a higher temperature in 4 subjects in the l‐NAME sites (control, 37.0 ± 0.3°C, n= 16; l‐NAME, 39.8 ± 0.1°C, n= 4; P < 0.001) and absent in 12 subjects. The response was also absent in l‐NAME plus low‐dose SNP sites and not altered by low‐dose SNP infusion alone. Adrenergic blockade, with and without low‐dose noradrenaline infusion, also abolished the axon reflex response in all subjects. Low‐dose noradrenaline infusion alone shifted the axon reflex to a significantly lower temperature threshold compared to control sites (control, 38.2 ± 0.5°C; noradrenaline, 37.7 ± 0.4°C, P < 0.05, n= 5). These results suggest that endogenous NO and noradrenaline contribute to the temperature threshold of the axon reflex response during gradual local heating of the skin.
Recombinant adeno-associated virus serotype 9 in a mouse model of atherosclerosis: Determination of the optimal expression time in vivo

Adeno-associated virus 9 (AAV9) has been identified as one of the optimal gene transduction carriers for gene therapy. The aim of the present study was to determine the gene transfection efficiency and safety of an AAV9 vector produced using a recombinant baculovirus (rBac)-based system. AAV9-cytomegalovirus (CMV)-green fluorescent protein was produced using an rBac system and the resulting vector particles were injected intravenously into mice. Animals were sacrificed at 14, 21, 28, 35, 60, 90 and 120 days following injection. GFP expression in aortic vasculature and aortic plaques in C57/6B and apolipoprotein E−/− mice was analyzed by fluorescence imaging and western blotting. In vivo analyses of biological markers of liver and heart damage, and renal function, as well as in vitro terminal deoxynucleotidyl transferase dUTP nick end labeling analysis were used to determine the toxicity of the AAV9 carrier. The findings of the present study demonstrated that AAV9 viral vectors packaged using the rBac system functioned appropriately in arteriosclerosis plaques. The CMV promoter significantly induced GFP expression in the vascular plaque in a time-dependent manner. AAV9-CMV viral particles did not lead to heart, liver or renal damage and no change in apoptotic rate was identified. These findings indicated that AAV9-CMV may be effectively and safely used to transfect genes into atherosclerotic plaques.
Automatic psoriasis lesion segmentation in two-dimensional skin images using multiscale superpixel clustering

Abstract. Psoriasis is a chronic skin disease that is assessed visually by dermatologists. The Psoriasis Area and Severity Index (PASI) is the current gold standard used to measure lesion severity by evaluating four parameters, namely, area, erythema, scaliness, and thickness. In this context, psoriasis skin lesion segmentation is required as the basis for PASI scoring. An automatic lesion segmentation method by leveraging multiscale superpixels and K-means clustering is outlined. Specifically, we apply a superpixel segmentation strategy on CIE-L*a*b* color space using different scales. Also, we suppress the superpixels that belong to nonskin areas. Once similar regions on different scales are obtained, the K-means algorithm is used to cluster each superpixel scale separately into normal and lesion skin areas. Features from both a* and b* color bands are used in the clustering process. Furthermore, majority voting is performed to fuse the segmentation results from different scales to obtain the final output. The proposed method is extensively evaluated on a set of 457 psoriasis digital images, acquired from the Royal Melbourne Hospital, Melbourne, Australia. Experimental results have shown evidence that the method is very effective and efficient, even when applied to images containing hairy skin and diverse lesion size, shape, and severity. It has also been ascertained that CIE-L*a*b* outperforms other color spaces for psoriasis lesion analysis and segmentation. In addition, we use three evaluation metrics, namely, Dice coefficient, Jaccard index, and pixel accuracy where scores of 0.783%, 0.698%, and 86.99% have been achieved by the proposed method for the three metrics, respectively. Finally, compared with existing methods that employ either skin decomposition and support vector machine classifier or Euclidean distance in the hue–chrome plane, our multiscale superpixel-based method achieves markedly better performance with at least 20% accuracy enhancement.
Potentiating effect of pyrimethamine and sulfadoxine against dihydrofolate reductase from pyrimethamine-sensitive and pyrimethamine-resistant Plasmodium chabaudi

Dihydrofolate reductase was partially purified from a pyrimethamine-sensitive Plasmodium chabaudi clone and a pyrimethamine-resistant clone derived from it and used in a study of the inhibitory effect of pyrimethamine and sulfadoxine, both alone and in combination. Kinetic analysis of the inhibitory effect of sulfadoxine against the enzyme from pyrimethamine-sensitive and -resistant parasites revealed that the drug inhibited the former enzyme competitively, with an inhibition constant (Kis) of 0.7 +/- 0.4 mM, but inhibited the latter enzyme noncompetitively, with Kis and Kii of 8.9 +/- 1.2 and 4.1 +/- 1.2 mM, respectively. Previous studies also showed competitive inhibition by pyrimethamine on the former enzyme and noncompetitive inhibition on the latter enzyme, with some 200-fold-lower affinity. Sulfadoxine and pyrimethamine exhibited a mutually potentiating effect on the enzyme activity, as revealed by the concave isoboles and the fractional inhibitions of less than unity. A potentiating effect was observed for the enzymes from both sources and was not dependent on the degree of the purification of the enzyme. Our results can be explained by assuming simultaneous binding of two inhibitors on the enzyme.
Application of a novel integrated toxicity testing strategy incorporating “3R” principles of animal research to evaluate the safety of a new agrochemical sulfoxaflor

Abstract Plant protection products (PPPs) and the active substance(s) contained within them are rigorously and comprehensively tested prior to registration to ensure that human health is not impacted by their use. In recent years, there has been a widespread drive to have more relevant testing strategies (e.g., ILSI/HESI-ACSA and new EU Directives), which also take account of animal welfare, including the 3R (replacement, refinement, and reduction) principles. The toxicity potential of one such new active substance, sulfoxaflor, a sulfoximine insecticide (CAS #946578-00-3), was evaluated utilizing innovative testing strategies comprising: (1) an integrated testing scheme to optimize information obtained from as few animals as possible (i.e., 3R principles) through modifications of standard protocols, such as enhanced palatability study design, to include molecular endpoints, additional neurotoxicity and immunotoxicity parameters in a subchronic toxicity study, and combining multiple test guidelines into one study protocol; (2) generation of toxicokinetic data across dose levels, sexes, study durations, species, strains and life stages, without using satellite animals, which was a first for PPP development, and (3) addition of prospective mode of action (MoA) endpoints within repeat dose toxicity studies as well as proactive inclusion of specific MoA studies as an integral part of the development program. These novel approaches to generate key data early in the safety evaluation program facilitated informed decision-making on the need for additional studies and contributed to a more relevant human health risk assessment. This supplement also contains papers which describe in more detail the approach taken to establish the MoA and human relevance framework related to toxicities elicited by sulfoxaflor in the mammalian toxicology studies: developmental toxicity in rats mediated via the fetal muscle nicotinic acetylcholine receptor (nAChR) (12); liver tumors in rodents mediated via CAR/PXR (20); and Leydig cell tumors in Fischer 344 rats (30)
A Novel Approach to Optical Switching for Intradatacenter Networking

In this paper, we propose to apply a novel paradigm called labeled optical burst switching with home circuit (LOBS-HC) for intradatacenter networking to provide a high bisection bandwidth and significantly reduce the cost and energy consumption associated with electronic packet switching. The unique features of LOBS-HC that make it more suitable than either optical circuit switching (OCS) or optical packet/burst switching are exploited to enable all-to-all communications with a guaranteed lossless transmission bandwidth between any given pair of pods, while also supporting bursty transmissions through wavelength-sharing among home circuits (HCs) and statistical multiplexing. As a case study, hypercube-like topologies are considered for the interconnection among the pods within a datacenter. In particular, we first propose a simple but efficient HC assignment scheme called complementary HC for 2-D cube or ring, and then extend our works to n-cube and generalized hypercube by applying the concept of spanning balanced tree (SBT) for their HC assignment. Our analysis results show that with such datacenters, the minimum number of wavelengths needed in each case is significantly reduced from that needed with OCS and also, the network cost in terms of wires and transceivers needed is considerably reduced from that incurs with datacenters using electronic packet switching. We then evaluate the traffic performance of such hypercube-based datacenters using LOBS-HC through simulation experiments via the OPNET simulator. The performance results obtained for a variety of communication patterns and traffic models within a datacenter demonstrate the feasibility of the proposed approach.
Signaling-dependent and coordinated regulation of transcription, splicing, and translation resides in a single coregulator, PCBP1

Transcription, splicing, and translation are potentially coordinately regulatable in a temporospatial-dependent manner, although supporting experimental evidence for this notion is scarce. Yeast two-hybrid screening of a mammary gland cDNA library with human p21-activated kinase 1 (Pak1) as bait identified polyC-RNA-binding protein 1 (PCBP1), which controls translation from mRNAs containing the DICE (differentiation control element). Mitogenic stimulation of human cells phosphorylated PCBP1 on threonines 60 and 127 in a Pak1-sensitive manner. Pak1-dependent phosphorylation of PCBP1 released its binding and translational inhibition from a DICE-minigene. Overexpression of PCBP1 also inhibited the translation of the endogenous L1 cell adhesion molecule mRNA, which contains two DICE motifs in the 3′ untranslated region. We also found that Pak1 activation led to an increased nuclear retention of PCBP1, recruitment to the eukaryotic translation initiation factor 4E (eIF4E) promoter, and stimulation of eIF4E expression in a Pak1-sensitive manner. Moreover, mitogenic stimulation promoted Pak1- and PCBP1-dependent alternative splicing and exon inclusion from a CD44 minigene. The alternative splicing functions of PCBP1 were in turn mediated by its intrinsic interaction with Caper α, a U2 snRNP auxiliary factor-related protein previously implicated in RNA splicing. These findings establish the principle that a single coregulator can function as a signal-dependent and coordinated regulator of transcription, splicing, and translation.
Embracing Corruption Burstiness: Fast Error Recovery for ZigBee under Wi-Fi Interference

The ZigBee communication can be easily and severely interfered by Wi-Fi traffic. Error recovery, as an important means for ZigBee to survive Wi-Fi interference, has been extensively studied in recent years. The existing works add upfront redundancy to in-packet blocks for recovering a certain number of random corruptions. Therefore, the bursty nature of ZigBee in-packet corruptions under Wi-Fi interference is often considered harmful, since some blocks are full of errors which cannot be recovered and some blocks have no errors but are still requiring redundancy. As a result, they often use interleaving to reshape the bursty errors, before applying complex FEC codes to recover the re-shaped random distributed errors. In this paper, we take a different view that burstiness may be helpful. With burstiness, the in-packet corruptions are often consecutive and the requirement for error recovery is reduced as “recovering any k consecutive errors” instead of “recovering any random k errors”. This lowered requirement allows us to design far more efficient code than the existing FEC codes. Motivated by this implication, we exploit the corruption burstiness to design a simple yet effective error recovery code using XOR operations (called ZiXOR). ZiXOR uses XOR code and the delay is significantly reduced. More, ZiXOR uses RSSI-hinted approach to detect in packet corruptions without CRC, incurring almost no extra transmission overhead. The testbed evaluation results show that ZiXOR outperforms the state-of-the-art works in terms of the throughput (by 47 percent) and latency (by 22 percent).
Severity of Mitral Stenosis and Left Ventricular Mechanics: A Speckle Tracking Study

Background: It has been shown that mitral stenosis (MS) impairs left ventricular (LV) systolic function; however, this issue has not been studied comprehensively. We aimed to evaluate the role of 2D strain in the assessment of subclinical LV systolic dysfunction in patients with MS. Methods: Seventy-two patients with isolated MS (mild, moderate and severe) and 31 healthy control subjects constituted the study population. 2D echocardiography images were obtained from LV apical 4-chamber (4C), long axis (LAX), and 2-chamber (2C) views. Peak longitudinal strain and strain rate (Sr) were obtained from 4C, LAX, and 2C views. Global strain and Sr were calculated by averaging the three apical views. Results: There were no significant differences in LV ejection fraction and LV systolic or diastolic dimensions between the groups. Patients with MS had significantly lower LV longitudinal strain and Sr measurements than the control group. In addition, there were no significant differences in MS subgroups with respect to LV strain and Sr measurements. Conclusion: We demonstrated that patients with MS had lower LV functions using 2D strain imaging, and this is independent of the hemodynamic severity of MS. In the detection of subclinical LV dysfunction in patients with MS, 2D strain imaging appears to be useful.
Are there researcher allegiance effects in diagnostic validation studies of the PHQ-9? A systematic review and meta-analysis

Objectives To investigate whether an authorship effect is found that leads to better performance in studies conducted by the original developers of the Patient Health Questionnaire (PHQ-9) (allegiant studies). Design Systematic review with random effects bivariate diagnostic meta-analysis. Search strategies included electronic databases, examination of reference lists and forward citation searches. Inclusion criteria Included studies provided sufficient data to calculate the diagnostic accuracy of the PHQ-9 against a gold standard diagnosis of major depression using the algorithm or the summed item scoring method at cut-off point 10. Data extraction Descriptive information, methodological quality criteria and 2×2 contingency tables. Results Seven allegiant and 20 independent studies reported the diagnostic performance of the PHQ-9 using the algorithm scoring method. Pooled diagnostic OR (DOR) for the allegiant group was 64.40, and 15.05 for non-allegiant studies group. The allegiance status was a significant predictor of DOR variation (p<0.0001). Five allegiant studies and 26 non-allegiant studies reported the performance of the PHQ-9 at recommended cut-off point of 10. Pooled DOR for the allegiant group was 49.31, and 24.96 for the non-allegiant studies. The allegiance status was a significant predictor of DOR variation (p=0.015). Some potential alternative explanations for the observed authorship effect including differences in study characteristics and quality were found, although it is not clear how some of them account for the observed differences. Conclusions Allegiant studies reported better performance of the PHQ-9. Allegiance status was predictive of variation in the DOR. Based on the observed differences between independent and non-independent studies, we were unable to conclude or exclude that allegiance effects are present in studies examining the diagnostic performance of the PHQ-9. This study highlights the need for future meta-analyses of diagnostic validation studies of psychological measures to evaluate the impact of researcher allegiance in the primary studies.
Positive Association Between Limbic Metabotropic Glutamate Receptor 5 Availability and Novelty-Seeking Temperament in Humans: An 18F-FPEB PET Study

Heritable temperament traits have been linked to several neuropsychiatric illnesses, including disorders associated with metabotropic glutamate receptor 5 (mGluR5) and dopaminergic dysfunctions. Considering its modulating effect on neurotransmission, we hypothesized that cerebral mGluR5 availability is associated with temperament traits in healthy humans. Methods: Forty-four nonsmoking healthy volunteers (mean age ± SD, 40 ± 14 y; age range, 22–66 y; 22 women) were included in this cross-sectional investigation. Brain mGluR5 availability was quantified on both a voxel-by-voxel and a volume-of-interest basis using the total distribution volume of the radioligand 18F-3-fluoro-5-[(pyridin-3-yl)ethynyl]benzonitrile (18F-FPEB) with 90-min dynamic PET and arterial input function. Moreover, glutamate–glutamine concentrations in the anterior cingulate cortex were measured using MR spectroscopy. These measures were related to the temperament traits of the 240-item Cloninger temperament and character inventory using a regression analysis with age and sex as nuisance variables. Results: High novelty-seeking temperament was robustly associated with increased mGluR5 availability in various regions including the thalamus (r = 0.71; the strongest association), amygdala, parahippocampus, insula, anterior and posterior cingulate cortex, and several primary sensory areas (all r > 0.58; P < 0.05, corrected for familywise error). These associations were specific because no correlations were found with other temperament scales or with spectroscopic measures of glutamatergic transmission. Conclusion: Overall, these data posit mGluR5 in key paralimbic areas as a strong determinant of the temperament trait novelty seeking. These data add to our understanding of how brain neurochemistry accounts for the variation in human behavior and strongly support further research on mGluR5 as a potential therapeutic target in neuropsychiatric disorders associated with abnormal novelty-seeking behaviors.
Quantifying and predicting recovery after heart surgery.

&NA; The validity of the biopsychosocial approach to the study of health and illness is reaffirmed by the prospective findings of the Recovery Study. This is a multidisciplinary examination, conducted in four teaching hospitals, of the predictors of symptoms of cardiac illness in 463 patients 6 months after coronary artery bypass or cardiac valve surgery. We found that the following preoperative measures predict freedom from cardiac symptoms 6 months after surgery: low levels of all of the following: angina pain, shortness of breath, fatigue and sleep problems, lifetime cigarette usage, and preoperative hospitalization for cardiac treatment; low levels of anxiety, depression, and hostility, and few life change events; high levels of all of the following: self‐esteem, well‐being, vigor; prevalence of activities and hobbies, social participation, and social support. The six variables in bold print contributed independently in a multiple regression equation that accounted for 21% of the variance of the symptoms score and was associated with an estimated 45% difference in success of recovery. The statistical strength and general nature of many of the predictors indicate that the predictors may also be important in recovery from other health crises. Psychosocial and biomedical factors correlate across time (predictively), as well as cross‐sectionally, indicating that psychological, social, and biological mechanisms may be parts of a single general multifaceted process influencing recovery of health. A clinical trial could determine if psychological, social, or behavioral interventions will hasten and improve recovery from physical illness or trauma.
Chitin oligosaccharide binding to a family GH19 chitinase from the moss Bryum coronatum

Substrate binding of a family GH19 chitinase from a moss species, Bryum coronatum (BcChi‐A, 22 kDa), which is smaller than the 26 kDa family GH19 barley chitinase due to the lack of several loop regions (‘loopless’), was investigated by oligosaccharide digestion, thermal unfolding experiments and isothermal titration calorimetry (ITC). Chitin oligosaccharides [β‐1,4‐linked oligosaccharides of N‐acetylglucosamine with a polymerization degree of n, (GlcNAc)n, n = 3–6] were hydrolyzed by BcChi‐A at rates in the order (GlcNAc)6 > (GlcNAc)5 > (GlcNAc)4 >> (GlcNAc)3. From thermal unfolding experiments using the inactive BcChi‐A mutant (BcChi‐A‐E61A), in which the catalytic residue Glu61 is mutated to Ala, we found that the transition temperature (Tm) was elevated upon addition of (GlcNAc)n (n = 2–6) and that the elevation (ΔTm) was almost proportional to the degree of polymerization of (GlcNAc)n. ITC experiments provided the thermodynamic parameters for binding of (GlcNAc)n (n = 3–6) to BcChi‐A‐E61A, and revealed that the binding was driven by favorable enthalpy changes with unfavorable entropy changes. The change in heat capacity (ΔCp°) for (GlcNAc)6 binding was found to be relatively small (−105 ± 8 cal·K−1·mol−1). The binding free energy changes for (GlcNAc)6, (GlcNAc)5, (GlcNAc)4 and (GlcNAc)3 were determined to be −8.5, −7.9, −6.6 and −5.0 kcal·mol−1, respectively. Taken together, the substrate binding cleft of BcChi‐A consists of at least six subsites, in contrast to the four‐subsites binding cleft of the ‘loopless’ family 19 chitinase from Streptomyces coelicolor.
Graphene–boron nitride superlattices: the role of point defects at the BN layer

We investigate, by means of first-principles calculations, the role of hBN point defects on the energetical stability and electronic structure of heterostructures composed of graphene atop hBN, rotated at angles of 13.17°, 9.43° and 7.34°. We consider, as possible point defects, boron and nitrogen vacancies and antisites, substitutional oxygen at the nitrogen site ON, substitutional carbon dimers, and nitrogen interstitials. The electronic and structural properties of all defects were analyzed. Among these, the most stable is ON, with negative formation energies at several possible rotation angles and chemical environments. Under such conditions, ON doping can raise the Fermi level of the neutral system by as much as 1 eV relative to graphene’s Dirac point, reaching the band crossing between adjacent Dirac cones at the M point of the heterostructure Brillouin zone. This could lead to interesting electronic transport properties without the need for electrostatic doping.