Miracle-dz/UniFAR-FTUs huggingface dataset:
Treatment With Tetrahydrobiopterin Overcomes Brain Death–Associated Injury in a Murine Model of Pancreas Transplantation

Brain death (BD) has been associated with an immunological priming of donor organs and is thought to exacerbate ischemia reperfusion injury (IRI). Recently, we showed that the essential nitric oxide synthase co‐factor tetrahydrobiopterin (BH4) abrogates IRI following experimental pancreas transplantation. We therefore studied the effects of BD in a murine model of syngeneic pancreas transplantation and tested the therapeutic potential of BH4 treatment. Compared with sham‐operated controls, donor BD resulted in intragraft inflammation reflected by induced IL‐1ß, IL‐6, VCAM‐1, and P‐selectin mRNA expression levels and impaired microcirculation after reperfusion (p < 0.05), whereas pretreatment of the BD donor with BH4 significantly improved microcirculation after reperfusion (p < 0.05). Moreover, BD had a devastating impact on cell viability, whereas BH4‐treated grafts showed a significantly higher percentage of viable cells (p < 0.001). Early parenchymal damage in pancreatic grafts was significantly more pronounced in organs from BD donors than from sham or non‐BD donors (p < 0.05), but BH4 pretreatment significantly ameliorated necrotic lesions in BD organs (p < 0.05). Pretreatment of the BD donor with BH4 resulted in significant recipient survival (p < 0.05). Our data provide novel insights into the impact of BD on pancreatic isografts, further demonstrating the potential of donor pretreatment strategies including BH4 for preventing BD‐associated injury after transplantation.
Distribution and Medical Impact of Loss-of-Function Variants in the Finnish Founder Population

Exome sequencing studies in complex diseases are challenged by the allelic heterogeneity, large number and modest effect sizes of associated variants on disease risk and the presence of large numbers of neutral variants, even in phenotypically relevant genes. Isolated populations with recent bottlenecks offer advantages for studying rare variants in complex diseases as they have deleterious variants that are present at higher frequencies as well as a substantial reduction in rare neutral variation. To explore the potential of the Finnish founder population for studying low-frequency (0.5–5%) variants in complex diseases, we compared exome sequence data on 3,000 Finns to the same number of non-Finnish Europeans and discovered that, despite having fewer variable sites overall, the average Finn has more low-frequency loss-of-function variants and complete gene knockouts. We then used several well-characterized Finnish population cohorts to study the phenotypic effects of 83 enriched loss-of-function variants across 60 phenotypes in 36,262 Finns. Using a deep set of quantitative traits collected on these cohorts, we show 5 associations (p<5×10−8) including splice variants in LPA that lowered plasma lipoprotein(a) levels (P = 1.5×10−117). Through accessing the national medical records of these participants, we evaluate the LPA finding via Mendelian randomization and confirm that these splice variants confer protection from cardiovascular disease (OR = 0.84, P = 3×10−4), demonstrating for the first time the correlation between very low levels of LPA in humans with potential therapeutic implications for cardiovascular diseases. More generally, this study articulates substantial advantages for studying the role of rare variation in complex phenotypes in founder populations like the Finns and by combining a unique population genetic history with data from large population cohorts and centralized research access to National Health Registers.
Data Quality from a Community-Based, Water-Quality Monitoring Project in
 the Yukon River Basin

This paper examines the quality of data collected by the Indigenous Observation Network, a community-based water-quality project in the Yukon River Basin of Alaska and Canada. The Indigenous Observation Network relies on community technicians to collect surface-water samples from as many as fifty locations to achieve their goals of monitoring the quality of the Yukon River and major tributaries in the basin and maintaining a long-term record of baseline data against which future changes can be measured. This paper addresses concerns about the accuracy, precision, and reliability of data collected by non-professionals. The Indigenous Observation Network data are examined in the context of a standard data life cycle: plan, collect, assure, and describe; as compared to professional scientific activities. Field and laboratory protocols and procedures of the Indigenous Observation Network are compared to those utilized by professional scientists. The data of the Indigenous Observation Network are statistically compared to those collected by professional scientists through a retrospective analysis of a set of water-quality parameters reported by all three projects over a number of years. No statistical differences were found among the three projects for pH, Calcium, Magnesium, or Alkalinity, although statistically significant differences were found for Sodium, Chloride, Sulfate, and Potassium concentrations. The statistical differences found were small and likely not significant in terms of interpreting the data for a variety of uses. Our results suggest that Indigenous Observation Network data are of high quality, and with consistent protocols and participant training, community based monitoring projects can collect data that are accurate, precise, and reliable.
Auctioning Incentive Contracts: An Experimental Study

In this note, we experimentally examine the relative performance of price-only auctions and multi-attribute auctions. We do so in procurement settings where the buyer can give the winning bidder incentives to exert effort on non-price dimensions after the auction. Both auctions theoretically implement the surplus maximizing mechanism. Our experiment confirms this result. Moreover, we observe that the “pie” is shared the same in both auctions between buyer and suppliers both in theory and in the lab (after accounting for learning effects).
Atypical Sensory Modulation and Psychological Distress in the General Population.

OBJECTIVE Atypical sensory modulation (ASM) is characterized by over- or underresponsiveness to sensory stimuli in one or more sensory systems. Faulty sensory information processing could result in anxiety. Because the relation between ASM and psychological distress has not been examined, we explored psychological distress and ASM in the general population. METHOD A community-based sample of 204 adults (105 men; mean age = 27.4 yr, standard deviation = 3.71) completed the Sensory Responsiveness Questionnaire--Intensity Scale (SRQ-IS; Bar-Shalita, Seltzer, Vatine, Yochman, & Parush, 2009); the Brief Symptom Inventory (BSI; Derogatis & Coons, 1993); and the Short Form--36 Health Survey, Version 2 (SF-36; Ware, Kosinski, & Gandek, 2005). RESULTS The ASM group displayed considerably more distress symptoms than the comparison group. Multivariate linear regression showed SRQ-IS and SF-36 scores as significant predictors of BSI score (r = .64). CONCLUSION ASM may be a risk factor for developing other mental health concerns.
Perishable commodities? : management consultancies and product replacement

This paper explores the process of product replacement within management consultancies. Drawing on product marketing literature we argue that main knowledge suppliers do not simply regard their knowledge commodities as inherently perishable during an alleged downturn phase on the knowledge market. Rather, our study reveals that management consultants may follow a variety of alternative strategies to extend the life of their knowledge products. This provides support for the notion that there is more continuity within the supply system than management fashion theorists would suggest and identifies some key elements that play a role in shaping this process. Our discussion aims to provide some clues for further studying the evolution of management knowledge within the system of knowledge supply.
Aging and Genome Maintenance: Lessons from the Mouse?

Recent progress in the science of aging is driven largely by the use of model systems, ranging from yeast and nematodes to mice. These models have revealed conservation in genetic pathways that balance energy production and its damaging by-products with pathways that preserve somatic maintenance. Maintaining genome integrity has emerged as a major factor in longevity and cell viability. Here we discuss the use of mouse models with defects in genome maintenance for understanding the molecular basis of aging in humans.
Genotype by Planting Date Effects on Cowpea in Humid Fringes, Southeast Nigeria

A two-year factorial arranged field experiment in randomized complete block design with three replications was carried out in 2014 and 2015 at Michael Okpara University of Agriculture Teaching and Research Farm, Umudike (latitude 05° 29'N; longitude 07° 33'E; altitude 122 m above sea level), Nigeria. The objectives were to assess growth and yield response of twenty newly released cowpea genotypes to different planting dates (July, August and September). Plant height, number of leaves/plant, number of branches/plant, shoot biomass, total dry matter, number of nodules/plant, weight of pod, number of seeds/pod, seed weight/pod and grain yield varied amongst the genotypes and across the different planting dates in both years. The association between grain yield and other variables analysed across both years was significant and positive except 100-seed weight and the phenological characters of the plant. Path coefficients analysis across two years indicated that seed weight/pod followed by number of branches/plant and number of seeds/pod had positive direct effect on grain yield of cowpea in contrast to characters that exhibited negative but direct effect on yield. The other traits had relatively negligible to low indirect effects that were positive through other component traits. The grain yield sequence of interaction between genotype and date of planting was in this order: IT06K-141 planted in July ＞ IT11K-61-82 planted in September ＞ IT99K-573-1-1 planted in August. IT06K-141 genotype was considered to be better endowed genetically while the mean across both years indicated August as appropriate planting date to ensure high and sustainable grain yield.
Edinburgh Research Explorer Estrogen Receptor Related Beta Is Expressed in Human Endometrium throughout the Normal Menstrual Cycle

Estrogen receptor related beta is expressed in human endometrium throughout the normal menstrual cycle receptor related beta is expressed in human endometrium throughout the normal menstrual cycle' Human Reproduction, vol 23, no. The online version of this article has been published under an open access model. Users are entitled to use, reproduce, disseminate, or display the open access version of this article for non-commercial purposes provided that: the original authorship is properly and fully attributed: the Journal and Oxford University Press are attributed as the original place of publication with the correct citation details given: if an article is subsequently reproduced or disseminated not in its entirety but only in part or as a derivative word this must be clearly indicated. For commercial re-use, please contact journals.permissions@oxfordjournals.org General rights Copyright for the publications made accessible via the Edinburgh Research Explorer is retained by the author(s) and / or other copyright owners and it is a condition of accessing these publications that users recognise and abide by the legal requirements associated with these rights. Take down policy The University of Edinburgh has made every reasonable effort to ensure that Edinburgh Research Explorer content complies with UK legislation. If you believe that the public display of this file breaches copyright please contact openaccess@ed.ac. uk providing details, and we will remove access to the work immediately and investigate your claim. BACKGROUND: Estrogen receptor related beta (ERRb, ESRRB/NR3B2) is an orphan receptor that shares significant sequence homology with estrogen receptors ERa and ERb. ERR family members are reported to exhibit consti-tutive transcriptional activity; however, little is known about the biological function of ERRb. In an attempt to delineate its role, we examined expression of ERRb in normal human endometrium, a tissue that undergoes cyclic remodelling under the influence of estrogen and progesterone. METHODS: Well-characterized endometrial tissue (n 5 31), including full-thickness biopsies, was obtained from women with regular menstrual cycles. RT –PCR was used to measure mRNA encoding ERRb, the peroxisome proliferator activated receptor gamma coactivators (PGC)-1a and b and to determine whether ERRb splice variant mRNAs were expressed. ERRb was immunolocalized using both single and double antibody immunohistochemistry. RESULTS: Total ERRb mRNA appeared higher in proliferative phase samples but results did not reach significance. Transcripts corresponding to the long-and short-splice variants of ERRb as well as PGC1a and b were detected but ERRbD10 was absent. ERRb protein was localized to cell nuclei within multiple …
Archaeal phylogenomics provides evidence in support of a methanogenic origin of the Archaea and a thaumarchaeal origin for the eukaryotes

We have developed a machine-learning approach to identify 3537 discrete orthologue protein sequence groups distributed across all available archaeal genomes. We show that treating these orthologue groups as binary detection/non-detection data is sufficient to capture the majority of archaeal phylogeny. We subsequently use the sequence data from these groups to infer a method and substitution-model-independent phylogeny. By holding this phylogeny constrained and interrogating the intersection of this large dataset with both the Eukarya and the Bacteria using Bayesian and maximum-likelihood approaches, we propose and provide evidence for a methanogenic origin of the Archaea. By the same criteria, we also provide evidence in support of an origin for Eukarya either within or as sisters to the Thaumarchaea.
Neurofilament proteins of rat peripheral nerve and spinal cord

Intact neurofilaments were isolated in parallel from rat peripheral nerve and spinal cord by osmotic shock into hypotonic media containing divalent cation chelators. Isolated neurofilaments were washed and separated by multiple centrifugations in 0.1 M NaCl. Abundant intact neurofilaments were identified in the washed pellets by negative staining techniques. Their origin from neurofilaments was confirmed by immune electron microscopy. Washed neurofilaments were extracted from lipid and membranous components with 8 M urea. Analyses of neurofilament isolates on sodium dodecyl sulfate gels showed that proteins of 200,000, 150,000, and 69,000 mol wt were the major components of intact neurofilaments derived from rat peripheral and central nervous systems. These same proteins were identified in whole tissue homogenates of both sources and became enriched during the isolation of intact neurofilaments. A minor component of 64,000 mol wt arose during isolation. Other proteins were identified as contaminants. Small amounts of proteins with electrophoretic migration of tubulin and actin remain in neurofilament isolates.
Radius estimation of subsurface cylindrical objects from ground-penetrating-radar data using full-waveform inversion

Ray-based radius estimations of subsurface cylindrical objects such as rebars and pipes from ground-penetrating-radar (GPR) measurements are not accurate because of their approximations. We have developed a novel full-waveform inversion (FWI) approach that uses a full-waveform 3D finite-difference time-domain (FDTD) forward-modeling program to estimate the radius including other object parameters. By using the full waveform of the common-offset GPR data, the shuffled complex evolution (SCE) approach is able to reliably extract the radius of the subsurface cylindrical objects. A combined optimization of radius, medium properties, and the effective source wavelet is necessary. Synthetic and experimental data inversion returns an accurate reconstruction of the cylinder properties, medium properties, and the effective source wavelet. Combining FWI of GPR data using SCE and a 3D FDTD forward model makes the approach easily adaptable for a wide range of other GPR FWI approaches.
Menière's disease.

INTRODUCTION Menière's disease causes recurrent vertigo, hearing loss, tinnitus, and fullness or pressure in the ear, which mainly affects adults aged 40-60 years. Menière's disease is at first progressive but fluctuating, and episodes can occur in clusters. Vertigo usually resolves but hearing deteriorates, and symptoms other than hearing loss and tinnitus usually improve regardless of treatment. METHODS AND OUTCOMES We conducted a systematic review and aimed to answer the following clinical questions: What are the effects of treatments for acute attacks of Menière's disease; and of interventions to prevent attacks and delay disease progression of Menière's disease? We searched: Medline, Embase, The Cochrane Library and other important databases up to January 2006 (Clinical Evidence reviews are updated periodically, please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA). RESULTS We found 17 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions. CONCLUSIONS In this systematic review we present information relating to the effectiveness and safety of the following interventions: anticholinergics, benzodiazepines, betahistine, cinnarizine, dietary modification, diuretics, phenothiazines, psychological support, trimetazidine, vestibular rehabilitation.
Kinematics and Kinetics of Elite Windmill Softball Pitching

Background A significant number of time-loss injuries to the upper extremity in elite windmill softball pitchers has been documented. The number of outings and pitches thrown in 1 week for a softball pitcher is typically far in excess of those seen in baseball pitchers. Shoulder stress in professional baseball pitching has been reported to be high and has been linked to pitching injuries. Shoulder distraction has not been studied in an elite softball pitching population. Hypothesis The stresses on the throwing shoulder of elite windmill pitchers are similar to those found for professional baseball pitchers. Study Design Descriptive laboratory study. Methods Three-dimensional, high-speed (120 Hz) video data were collected on rise balls from 24 elite softball pitchers during the 1996 Olympic Games. Kinematic parameters related to pitching mechanics and resultant kinetics on the throwing shoulder were calculated. Multiple linear regression analysis was used to relate shoulder stress and pitching mechanics. Results Shoulder distraction stress averaged 80% of body weight for the Olympic pitchers. Sixty-nine percent of the variability in shoulder distraction can be explained by a combination of 7 parameters related to pitching mechanics. Conclusion Excessive distraction stress at the throwing shoulder is similar to that found in baseball pitchers, which suggests that windmill softball pitchers are at risk for overuse injuries. Normative information regarding upper extremity kinematics and kinetics for elite softball pitchers has been established.
Biocontrol of the Sugarcane Borer Eldana saccharina by Expression of the Bacillus thuringiensis cry1Ac7 andSerratia marcescens chiA Genes in Sugarcane-Associated Bacteria

ABSTRACT The cry1Ac7 gene of Bacillus thuringiensisstrain 234, showing activity against the sugarcane borer Eldana saccharina, was cloned under the control of the tacpromoter. The fusion was introduced into the broad-host-range plasmid pKT240 and the integration vector pJFF350 and without thetac promoter into the broad-host-range plasmids pML122 and pKmM0. These plasmids were introduced into a Pseudomonas fluorescens strain isolated from the phylloplane of sugarcane and the endophytic bacterium Herbaspirillum seropedicae found in sugarcane. The ptac-cry1Ac7 construct was introduced into the chromosome of P. fluorescens using the integration vector pJFF350 carrying the artificial interposon Omegon-Km. Western blot analysis showed that the expression levels of the integratedcry1Ac7 gene were much higher under the control of thetac promoter than under the control of its endogenous promoter. It was also determined that multicopy expression in P. fluorescens and H. seropedicae of ptac-cry1Ac7 carried on pKT240 caused plasmid instability with no detectable protein expression. In H. seropedicae, more Cry1Ac7 toxin was produced when the gene was cloned under the control of the Nmr promoter on pML122 than in the opposite orientation and bioassays showed that the former resulted in higher mortality of E. saccharina larvae than the latter. P. fluorescens 14::ptac-tox resulted in higher mortality of larvae than did P. fluorescens14::tox. An increased toxic effect was observed when P. fluorescens 14::ptac-tox was combined with P. fluorescens carrying the Serratia marcescens chitinase gene chiA, under the control of the tac promoter, integrated into the chromosome.
Association of Atherosclerosis With Expression of the LILRB1 Receptor By Human NK and T-Cells Supports the Infectious Burden Hypothesis

Objective—The contribution of human cytomegalovirus (HCMV) to vascular disease may depend on features of the immune response not reflected by the detection of specific antibodies. Persistent HCMV infection in healthy blood donors has been associated with changes in the distribution of NK cell receptors (NKR). The putative relationship among HCMV infection, NKR distribution, subclinical atherosclerosis, and coronary heart disease was assessed. Methods and Results—NKR expression was compared in acute myocardial infarction (AMI) patients (n=70) and a population-based control sample (n=209). The relationship between NKR expression and carotid intima-media thickness (CIMT) in controls (n=149) was also studied. HCMV infection was associated with higher proportions of NKG2C+ and LILRB1+ NK and T-cells. In contrast, only LILRB1+ NK and CD56+ T-cells were found to be increased in AMI patients, independent of age, sex, conventional vascular risk factors, and HCMV seropositivity. Remarkably, LILRB1 expression in NK and T-cells significantly correlated with CIMT in controls. Conclusion—The association of overt and subclinical atherosclerotic disease with LILRB1+ NK and T-cells likely reflects a relationship between the immune challenge by infections and cardiovascular disease risk, without attributing a dominant role for HCMV. Our findings may lead to the identification of novel biomarkers of vascular disease.