Miracle-dz/UniFAR-FTUs huggingface dataset:
EP 3 receptor-mediated contraction of human pulmonary arteries and inhibition of neurogenic tachycardia in pithed rats

Background: The aim of our study was (1) the pharmacological characterization of EP3 receptors in human pulmonary arteries and (2) the examination of the potential involvement of these receptors in the regulation of neurogenic tachycardia in pithed rats. L-826266 served as the EP3 receptor antagonist. Methods: Experiments were performed on isolated human pulmonary arteries and pithed rats. Results: The prostanoid EP1/EP3 receptor agonist sulprostone (1 nM – 100 μM) concentration-dependently contracted isolated human pulmonary arteries (pEC50, 6.88 ± 0.10). The EP1 receptor antagonist SC 19920 (100 μM) did not affect the vasoconstriction induced by sulprostone, the TP receptor antagonist sulotroban (10 μM) only slightly attenuated the effects elicited by sulprostone > 3 μM, whereas L-826266 (10 μM) shifted its concentration-response curve to the right (apparent pA2 value 6.18; incubation time 0.5 h). In rings exposed to L-826266 (0.1, 1 or 10 μM) for 3 h, a concentration-dependent inhibitory effect against the sulprostone-induced vasoconstriction was obtained, yielding a Schild plot-based pA2 value of 7.39. In pithed rats, sulprostone (10 – 1,000 nmol/kg), but not the IP/EP1 receptor agonist iloprost (1–100 nmol/kg), inhibited the electrically evoked increase in heart rate (HR) dosedependently, maximally by at least 80%. L-826266 (3 μmol/kg) did not affect basal HR and diastolic blood pressure, but reduced the inhibitory effect of sulprostone 1,000 nmol/kg by about 20%. Conclusion: EP3 receptors (1) located postsynaptically strongly contract human pulmonary arteries and (2) located presynaptically on sympathetic nerve fibers supplying the heart of pithed rats strongly inhibit the neurogenic tachycardia.
An official American Thoracic Society/European Respiratory Society statement: Update of the international multidisciplinary classification of the idiopathic interstitial pneumonias.

BACKGROUND In 2002 the American Thoracic Society/European Respiratory Society (ATS/ERS) classification of idiopathic interstitial pneumonias (IIPs) defined seven specific entities, and provided standardized terminology and diagnostic criteria. In addition, the historical "gold standard" of histologic diagnosis was replaced by a multidisciplinary approach. Since 2002 many publications have provided new information about IIPs. PURPOSE The objective of this statement is to update the 2002 ATS/ERS classification of IIPs. METHODS An international multidisciplinary panel was formed and developed key questions that were addressed through a review of the literature published between 2000 and 2011. RESULTS Substantial progress has been made in IIPs since the previous classification. Nonspecific interstitial pneumonia is now better defined. Respiratory bronchiolitis-interstitial lung disease is now commonly diagnosed without surgical biopsy. The clinical course of idiopathic pulmonary fibrosis and nonspecific interstitial pneumonia is recognized to be heterogeneous. Acute exacerbation of IIPs is now well defined. A substantial percentage of patients with IIP are difficult to classify, often due to mixed patterns of lung injury. A classification based on observed disease behavior is proposed for patients who are difficult to classify or for entities with heterogeneity in clinical course. A group of rare entities, including pleuroparenchymal fibroelastosis and rare histologic patterns, is introduced. The rapidly evolving field of molecular markers is reviewed with the intent of promoting additional investigations that may help in determining diagnosis, and potentially prognosis and treatment. CONCLUSIONS This update is a supplement to the previous 2002 IIP classification document. It outlines advances in the past decade and potential areas for future investigation.
CHAPTER 13:Spider Silk: The Toughest Natural Polymer

In this chapter we review the properties and characterization of spider silk, particularly dragline silk, which is attracting increasing interest due to its marvelous properties. The spider's unique protein dope and natural spinning process play important roles in providing this unrivalled material with its characteristic structure that determines its strong and tough properties. In general, dragline silk is a semicrystalline material composed of crystallites embedded in an amorphous matrix. We introduce the widely applied techniques used to probe the structural characteristics of dragline silk. The inherent excellent mechanical properties of dragline silk, as well as the influence of silking conditions its mechanical properties, are reviewed. Models relating the structure to the mechanical properties are discussed, aiming to unravel the structural base for the unique mechanical properties. Supercontraction and cyclic contraction are two other interesting inherent properties of dragline silk; the former can maintain tension in a web after deformation by natural elements and the latter has the ability to perform work by subjecting the silk fibre to periodic cycling at high and low humidity. Current advances in possible applications of dragline silk in the biomedical and clinical fields using biomaterials of different forms, based on recombinant and reconstituted silk proteins, are discussed finally.
Physical Fitness Characteristics of High vs. Low Performers on an Occupationally Specific Physical Agility Test for Patrol Officers

Abstract Dawes, JJ, Lindsay, K, Bero J, Elder C, Kornhauser C, and Holmes, R. Physical fitness characteristics of high vs. low performers on an occupationally specific physical agility test for patrol officers. J Strength Cond Res 31(10): 2808–2815, 2017—Law enforcement agencies frequently use physical ability tests (PATs) as a method of evaluating occupational performance. These tests are designed to replicate essential occupational tasks frequently performed by officers in the field. The purpose of this study was to determine whether significant relationships exist between the selected physical fitness tests and PAT performance and to determine which of these tests best differentiates between high and low PAT performers. Full-time highway patrol officers (n = 495) submitted self-reported anthropometric data (mean age = 39.6 + 7.7 years) along with fitness assessments taken from their organization's yearly fitness tests. All subjects completed a series of field-based fitness tests, as well as an occupationally specific PAT. Results of the study indicated that the selected tests accounted for almost 69% of the total variance on PAT performance. Overall, the 20-m meter multistage fitness test, 1-minute sit-up performance, and vertical jump height best predicted PAT performance. Furthermore, it was revealed that high performers were significantly more fit in all measures of dynamic fitness when compared with lower performers. No significant differences were discovered in static strength between groups. Strength and conditioning specialists should focus on developing aerobic capacity, trunk muscular endurance, and whole-body anaerobic power to improve PAT and occupational performance.
Global and local visual processing in autism: An objective assessment approach

We examined global and local visual processing in autism spectrum disorder (ASD) via a match‐to‐sample task using Kanizsa illusory contours (KIC). School‐aged children with ASD (n = 28) and age‐matched typically developing controls (n = 22; 7–13 years) performed a sequential match‐to‐sample between a solid shape (sample) and two illusory alternatives. We tracked eye gaze and behavioral performance in two task conditions: one with and one without local interference from background noise elements. While analyses revealed lower accuracy and longer reaction time in ASD in the condition with local interference only, eye tracking robustly captured ASD‐related global atypicalities across both conditions. Specifically, relative to controls, children with ASD showed decreased fixations to KIC centers, indicating reduced global perception. Notably, they did not differ from controls in regard to fixations to local elements or touch response location. These results indicate impaired global perception in the absence of heightened local processing in ASD. They also underscore the utility of eye‐tracking measures as objective indices of global/local visual processing strategies in ASD. Autism Res 2017, 10: 1392–1404. © 2017 International Society for Autism Research, Wiley Periodicals, Inc.
Neuromodulation with single‐element transcranial focused ultrasound in human thalamus

Transcranial focused ultrasound (tFUS) has proven capable of stimulating cortical tissue in humans. tFUS confers high spatial resolutions with deep focal lengths and as such, has the potential to noninvasively modulate neural targets deep to the cortex in humans. We test the ability of single‐element tFUS to noninvasively modulate unilateral thalamus in humans. Participants (N = 40) underwent either tFUS or sham neuromodulation targeted at the unilateral sensory thalamus that contains the ventro‐posterior lateral (VPL) nucleus of thalamus. Somatosensory evoked potentials (SEPs) were recorded from scalp electrodes contralateral to median nerve stimulation. Activity of the unilateral sensory thalamus was indexed by the P14 SEP generated in the VPL nucleus and cortical somatosensory activity by subsequent inflexions of the SEP and through time/frequency analysis. Participants also under went tactile behavioral assessment during either the tFUS or sham condition in a separate experiment. A detailed acoustic model using computed tomography (CT) and magnetic resonance imaging (MRI) is also presented to assess the effect of individual skull morphology for single‐element deep brain neuromodulation in humans. tFUS targeted at unilateral sensory thalamus inhibited the amplitude of the P14 SEP as compared to sham. There is evidence of translation of this effect to time windows of the EEG commensurate with SI and SII activities. These results were accompanied by alpha and beta power attenuation as well as time‐locked gamma power inhibition. Furthermore, participants performed significantly worse than chance on a discrimination task during tFUS stimulation.
Large-Scale Transposition Mutagenesis of Streptomyces coelicolor Identifies Hundreds of Genes Influencing Antibiotic Biosynthesis

ABSTRACT Gram-positive Streptomyces bacteria produce thousands of bioactive secondary metabolites, including antibiotics. To systematically investigate genes affecting secondary metabolism, we developed a hyperactive transposase-based Tn5 transposition system and employed it to mutagenize the model species Streptomyces coelicolor, leading to the identification of 51,443 transposition insertions. These insertions were distributed randomly along the chromosome except for some preferred regions associated with relatively low GC content in the chromosomal core. The base composition of the insertion site and its flanking sequences compiled from the 51,443 insertions implied a 19-bp expanded target site surrounding the insertion site, with a slight nucleic acid base preference in some positions, suggesting a relative randomness of Tn5 transposition targeting in the high-GC Streptomyces genome. From the mutagenesis library, 724 mutants involving 365 genes had altered levels of production of the tripyrrole antibiotic undecylprodigiosin (RED), including 17 genes in the RED biosynthetic gene cluster. Genetic complementation revealed that most of the insertions (more than two-thirds) were responsible for the changed antibiotic production. Genes associated with branched-chain amino acid biosynthesis, DNA metabolism, and protein modification affected RED production, and genes involved in signaling, stress, and transcriptional regulation were overrepresented. Some insertions caused dramatic changes in RED production, identifying future targets for strain improvement. IMPORTANCE High-GC Gram-positive streptomycetes and related actinomycetes have provided more than 100 clinical drugs used as antibiotics, immunosuppressants, and antitumor drugs. Their genomes harbor biosynthetic genes for many more unknown compounds with potential as future drugs. Here we developed a useful genome-wide mutagenesis tool based on the transposon Tn5 for the study of secondary metabolism and its regulation. Using Streptomyces coelicolor as a model strain, we found that chromosomal insertion was relatively random, except at some hot spots, though there was evidence of a slightly preferred 19-bp target site. We then used prodiginine production as a model to systematically survey genes affecting antibiotic biosynthesis, providing a global view of antibiotic regulation. The analysis revealed 348 genes that modulate antibiotic production, among which more than half act to reduce production. These might be valuable targets in future investigations of regulatory mechanisms, for strain improvement, and for the activation of silent biosynthetic gene clusters.
Evolution of Pectobacterium Bacteriophage ΦM1 To Escape Two Bifunctional Type III Toxin-Antitoxin and Abortive Infection Systems through Mutations in a Single Viral Gene

ABSTRACT Some bacteria, when infected by their viral parasites (bacteriophages), undergo a suicidal response that also terminates productive viral replication (abortive infection [Abi]). This response can be viewed as an altruistic act protecting the uninfected bacterial clonal population. Abortive infection can occur through the action of type III protein-RNA toxin-antitoxin (TA) systems, such as ToxINPa from the phytopathogen Pectobacterium atrosepticum. Rare spontaneous mutants evolved in the generalized transducing phage ΦM1, which escaped ToxINPa-mediated abortive infection in P. atrosepticum. ΦM1 is a member of the Podoviridae and a member of the “KMV-like” viruses, a subset of the T7 supergroup. Genomic sequencing of ΦM1 escape mutants revealed single-base changes which clustered in a single open reading frame. The “escape” gene product, M1-23, was highly toxic to the host bacterium when overexpressed, but mutations in M1-23 that enabled an escape phenotype caused M1-23 to be less toxic. M1-23 is encoded within the DNA metabolism modular section of the phage genome, and when it was overexpressed, it copurified with the host nucleotide excision repair protein UvrA. While the M1-23 protein interacted with UvrA in coimmunoprecipitation assays, a UvrA mutant strain still aborted ΦM1, suggesting that the interaction is not critical for the type III TA Abi activity. Additionally, ΦM1 escaped a heterologous type III TA system (TenpINPl) from Photorhabdus luminescens (reconstituted in P. atrosepticum) through mutations in the same protein, M1-23. The mechanistic action of M1-23 is currently unknown, but further analysis of this protein may provide insights into the mode of activation of both systems. IMPORTANCE Bacteriophages, the viral predators of bacteria, are the most abundant biological entities and are important factors in driving bacterial evolution. In order to survive infection by these viruses, bacteria have evolved numerous antiphage mechanisms. Many of the studies involved in understanding these interactions have led to the discovery of biotechnological and gene-editing tools, most notably restriction enzymes and more recently the clustered regularly interspaced short palindromic repeats (CRISPR)-Cas systems. Abortive infection is another such antiphage mechanism that warrants further investigation. It is unique in that activation of the system leads to the premature death of the infected cells. As bacteria infected with the virus are destined to die, undergoing precocious suicide prevents the release of progeny phage and protects the rest of the bacterial population. This altruistic suicide can be caused by type III toxin-antitoxin systems, and understanding the activation mechanisms involved will provide deeper insight into the abortive infection process.
Reliability and Au embrittlement of lead free solders for BGA applications

Pb-free solder for electronics assemblies is fast becoming a reality, primarily because of market driven forces. This affects the entire electronic manufacturing industry, from component supplier to equipment manufacturer. While the industry has identified possible alternates to Sn-Pb solder alloy, much work still needs to be done, especially in the area of component and board level reliability, solder/surface interactions, and assembly process development. The reliability of Pb-free solder joints for BGA applications under temperature cycle conditions for three different packages is compared in this paper. Two Sn-Ag-Cu compositions are considered and their reliability is compared with Sn-Pb alloy. In addition, ball shear testing was performed after 0, 24, 48, 96, 192, 384, and 504 hours of high temperature aging. The results indicate that the solder joint reliability generally improves when Pb-free solder is used; however, the degree of improvement is package dependent. The ball shear data also favors Sn-Ag-Cu alloy over Sn-Pb alloy. The data also indicates that using Sn-Ag-Cu alloy for solder balls can possibly eliminate the Au embrittlement issue, often encountered in BGA type packages with Sn-Pb balls.
Development of Durable Superhydrophobic Aluminium Surfaces Synthesized by Chemical Etching Process

In this paper, the superhydrophobic coatings on aluminium surfaces were prepared by two-step (chemical etching followed by coating) and one-step (chemical etching and coating in a single step) processes using potassium hydroxide and lauric acid. Besides, surface immersion time in solutions was varied in both processes. Wettability and surface morphologies of treated aluminium surfaces were characterized using contact angle measurement technique and scanning electron microscopy, respectively. Microstructures are formed on the treated aluminium surfaces which lead to increase in contact angle of the surface (>150°). Also on increasing immersion time, contact angle further increases due to increase in size and depth of microstructures. Additionally, these superhydrophobic coatings show excellent self-cleaning and corrosion-resistant behaviour. Water jet impact, floatation on water surface, and low temperature condensation tests assert the excellent water-repellent nature of coatings. Further, coatings are to be found mechanically, thermally, and ultra-violet stable. Along with, these coatings are found to be excellent regeneration ability as verified experimentally. Although aforesaid both processes generate durable and regenerable superhydrophobic aluminium surfaces with excellent self-cleaning, corrosion-resistant, and water-repellent characteristics, but one-step process is proved more efficient and less time consuming than two-step process and promises to produce superhydrophobic coatings for industrial applications.
Cohort Profile Cohort Profile : The Breast Cancer Prospective Family Study Cohort ( ProF-SC )

Cohort Profile: The Breast Cancer Prospective Family Study Cohort (ProF-SC) Mary Beth Terry,* Kelly-Anne Phillips, Mary B Daly, Esther M John, Irene L Andrulis, Saundra S Buys, David E Goldgar, Julia A Knight, Alice S Whittemore, Wendy K Chung, Carmel Apicella and John L Hopper* Department of Epidemiology, Columbia University Mailman School of Public Health, New York, NY, USA, Herbert Irving Comprehensive Cancer Center, Columbia University Medical Center, New York, NY, USA, Peter MacCallum Cancer Centre and Sir Peter MacCallum Department of Oncology, School of Population and Global Health, St Vincent’s Hospital, University of Melbourne, Melbourne, VIC, Australia, Department of Clinical Genetics, Fox Chase Cancer Center, Philadelphia, PA, USA, Cancer Prevention Institute of California, Fremont, CA, USA, Department of Health Research & Policy, Stanford University School of Medicine, Stanford, CA, USA, Lunenfeld-Tanenbaum Research Institute, University of Toronto, Toronto, ON, Canada, Department of Medicine, Department of Dermatology, Huntsman Cancer Institute, University of Utah School of Medicine, Salt Lake City, UT, USA, Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, ON, Canada, Dalla Lana School of Public Health, University of Toronto, Toronto, ON, Canada and Departments of Pediatrics and Medicine, Columbia University, New York, NY, USA
Cinnamon Oil Inhibits Shiga Toxin Type 2 Phage Induction and Shiga Toxin Type 2 Production in Escherichia coli O157:H7

ABSTRACT This study evaluated the inhibitory effect of cinnamon oil against Escherichia coli O157:H7 Shiga toxin (Stx) production and further explored the underlying mechanisms. The MIC and minimum bactericidal concentration (MBC) of cinnamon oil against E. coli O157:H7 were 0.025% and 0.05% (vol/vol), respectively. Cinnamon oil significantly reduced Stx2 production and the stx 2 mRNA expression that is associated with diminished Vero cell cytotoxicity. Consistently, induction of the Stx-converting phage where the stx 2 gene is located, along with the total number of phages, decreased proportionally to cinnamon oil concentration. In line with decreased Stx2 phage induction, cinnamon oil at 0.75× and 1.0× MIC eliminated RecA, a key mediator of SOS response, polynucleotide phosphorylase (PNPase), and poly(A) polymerase (PAP I), which positively regulate Stx-converting phages, contributing to reduced Stx-converting phage induction and Stx production. Furthermore, cinnamon oil at 0.75× and 1.0× MIC strongly inhibited the qseBC and luxS expression associated with decreased AI-2 production, a universal quorum sensing signaling molecule. However, the expression of oxidative stress response genes oxyR, soxR, and rpoS was increased in response to cinnamon oil at 0.25× or 0.5× MIC, which may contribute to stunted bacterial growth and reduced Stx2 phage induction and Stx2 production due to the inhibitory effect of OxyR on prophage activation. Collectively, cinnamon oil inhibits Stx2 production and Stx2 phage induction in E. coli O157:H7 in multiple ways. IMPORTANCE This study reports the inhibitory effect of cinnamon oil on Shiga toxin 2 phage induction and Shiga toxin 2 production. Subinhibitory concentrations (concentrations below the MIC) of cinnamon oil reduced Stx2 production, stx 2 mRNA expression, and cytotoxicity on Vero cells. Subinhibitory concentrations of cinnamon oil also dramatically reduced both the Stx2 phage and total phage induction in E. coli O157:H7, which may be due to the suppression of RNA polyadenylation enzyme PNPase at 0.25× to 1.0× MIC and the downregulation of bacterial SOS response key regulator RecA and RNA polyadenylation enzyme PAP I at 0.75× or 1.0× MIC. Cinnamon oil at higher levels (0.75× and 1.0× MIC) eliminated quorum sensing and oxidative stress. Therefore, cinnamon oil has potential applications as a therapeutic to control E. coli O157:H7 infection through inhibition of bacterial growth and virulence factors.
Relationship between depressive symptoms, alcohol use, and antiretroviral therapy adherence among HIV-infected, clinic-attending patients in South Africa

Despite the prevalence of depression and alcohol use among HIV-infected individuals, few studies have examined their association together in relation to nonadherence to antiretroviral therapy in sub-Saharan Africa. This study examined depressive symptoms, alcohol use, and other psychosocial factors (stigma, demographic characteristics) in relation to nonadherence to antiretroviral therapy among clinic-attending, HIV-infected individuals in South Africa (n = 101). Nonadherence was assessed using event-level measurement (missed doses over the past weekend). Multivariable logistic regression analyses revealed that only alcohol use, over and above depressive symptoms and education level, was associated with antiretroviral therapy nonadherence(AOR = 1.15; 95%CI = 1.02–1.29; p < .05). Findings point to the independent association of alcohol use and nonadherence to antiretroviral therapy above and beyond depressive symptoms.