bluuebunny/crossref_metadata_2025_split huggingface dataset:
Diversity and characterisation of polymorphic 3' untranslated region haplotypes of MICA and MICB genes
Authors: Cox Steven T. , Hernandez Diana , Danby Robert , Turner Thomas R. , Madrigal J. Alejandro 
Published: November 2018

MICA and MICB genes encode ligands that interact with the natural killer (NK) cell activating receptor, NKG2D. These ligands display a highly polymorphic allelic repertoire, although the true functional significance of this polymorphism remains elusive. We previously reported additional polymorphism in the 5' untranslated region (UTR) proximal promoter region of these genes by sequencing international histocompatibility workshop (IHW) cell line DNA promoter and coding regions. The present study extends this analysis by further characterising the 3'UTR region of the same IHW reference panel to achieve a more complete understanding of MICA and MICB haplotype diversity and possible functional relevance.We found 17 extended MICA haplotypes encompassing the coding region and 3'UTR, including four novel haplotypes identified in IHW cell line DNA. This increased to 21 when also considering the 5'UTR proximal promoter region. Analysis of the MICB 3'UTR revealed two novel sequences in cell lines KLO and WIN designated MICB‐UTR8 and UTR9, respectively. A total of 11 MICB haplotypes were identified in this study and five were unique. The present study, characterising MICA/B 3'UTR polymorphism utilising IHW reference cell lines, could be useful for future studies investigating the role of microRNA in post‐transcriptional repression of gene expression and for immunotherapy strategies to combat cancer progression.
Frequent blood donations alter susceptibility of red blood cells to storage‐ and stress‐induced hemolysis
Authors: Kanias Tamir , Stone Mars , Page Grier P. , Guo Yuelong , Endres‐Dighe Stacy M. , Lanteri Marion C. , Spencer Bryan R. , Cable Ritchard G. , Triulzi Darrell J. , Kiss Joseph E. , Murphy Edward L. , Kleinman Steve , Gladwin Mark T. , Busch Michael P. , Mast Alan E. ,   for the NHLBI Recipient Epidemiology Donor Evaluation Study (REDS)‐III Program
Published: November 2018

BACKGROUNDFrequent whole blood donations increase the prevalence of iron depletion in blood donors, which may subsequently interfere with normal erythropoiesis. The purpose of this study was to evaluate the associations between donation frequency and red blood cell (RBC) storage stability in a racially/ethnically diverse population of blood donors.STUDY DESIGNLeukoreduced RBC concentrate–derived samples from 13,403 donors were stored for 39 to 42 days (1–6°C) and then evaluated for storage, osmotic, and oxidative hemolysis. Iron status was evaluated by plasma ferritin measurement and self‐reported intake of iron supplements. Donation history in the prior 2 years was obtained for each subject.RESULTSFrequent blood donors enrolled in this study were likely to be white, male, and of older age (56.1 ± 5.0 years). Prior donation intensity was negatively associated with oxidative hemolysis (p < 0.0001) in multivariate analyses correcting for age, sex, and race/ethnicity. Increased plasma ferritin concentration was associated with increased RBC susceptibility to each of the three measures of hemolysis (p < 0.0001 for all), whereas self‐reported iron intake was associated with reduced susceptibility to osmotic and oxidative hemolysis (p < 0.0001 for both).CONCLUSIONSFrequent blood donations may alter the quality of blood components by modulating RBC predisposition to hemolysis. RBCs collected from frequent donors with low ferritin have altered susceptibility to hemolysis. Thus, frequent donation and associated iron loss may alter the quality of stored RBC components collected from iron‐deficient donors. Further investigation is necessary to assess posttransfusion safety and efficacy in patients receiving these RBC products.
Validation of Sysmex XT‐2000iV analyzer‐generated quantitative bone marrow differential counts in cynomolgus monkeys, Beagle dogs, and CD‐1 mice
Authors: Criswell Kay A. , Bock Jeffrey H. , Johnson Kjell , Criswell Ryan A. , Giovanelli Richard P. 
Published: November 2018

BackgroundIn a previous study, the validation of rat bone marrow (BM) collection, processing, and analysis using the Sysmex XT‐2000iV (Sysmex Corporation, Kobe, Japan) hematology analyzer showed that the Sysmex hematology analyzer produced BM differential counts that were comparable to those obtained with microscopic differential counts.ObjectiveThis study was conducted to expand the validation of the Sysmex TNCC (total nucleated cell count) and 5‐part BM differential in cynomolgus monkeys, Beagle dogs, and CD‐1 mice, which are alternate species that are also frequently used in preclinical safety studies.MethodsThe Sysmex 5‐part BM differential counts were generated with a two‐step process, whereby proliferating and maturing erythroid and myeloid cells were determined by preset gating and lymphocytes were determined using species‐specific B‐ and T‐lymphocyte antibodies and a magnetic cell‐sorting method (MACS). Agreement with microscopic myelograms with 500‐cell differential counts was determined from BM suspensions of 62 cynomolgus monkeys, 47 Beagle dogs, and 44 CD‐1 mice.ResultsThe correlation coefficients between methods for myeloid to erythroid (M:E) ratios in all three species was > 0.928. The Bland‐Altman differences between methods were approximately ± 0.3 units for the M:E ratio in dogs and mice, and +0.6 and −0.4 in monkeys. The upper limits of agreement for all three species were ≤7% for maturing myeloid cells, ≤6% for maturing erythroid cells, and ≤4% for proliferating myeloid cells, proliferating erythroid cells, and lymphocytes.ConclusionsThe Sysmex XT‐2000iV produces an automated M:E ratio and a 5‐part differential count equivalent to microscopic differential counts in cynomolgus monkeys, Beagle dogs, and CD‐1 mice.
Bone marrow lesions of the distal condyles of the third metacarpal bone are common and not always related to lameness in sports and pleasure horses
Authors: De Guio Cécile , Ségard‐Weisse Emilie , Thomas‐Cancian Aurélie , Schramme Michael 
Published: November 2018

AbstractThe metacarpophalangeal joint is a common site of pain in horses. Little information is available about bone marrow lesions in the distal condyles of the third metacarpal bone in sports and pleasure horses. Aims of this prospective, retrospective, observational study were to evaluate the prevalence of bone marrow lesions in the distal condyles of the third metacarpal bone, to describe their anatomic distribution and to correlate lesions with the presence of lameness and the level and type of activity. All sports and pleasure horses undergoing standing low‐field MRI of the front fetlock region between 2009 and 2016 were included and divided into three lameness groups according to the results of diagnostic analgesia. Bone marrow lesions were analyzed and graded by one reader. Grades were compared between anatomical locations and between lameness groups. A total of 166 horses were sampled. The prevalence of bone marrow lesions was 76.5% (127/166). The dorsal aspects of the medial condyle (31%, 39/127) and of the sagittal ridge (28%, 36/127) were the most commonly affected locations. There was no significant difference between both forelimbs (lame limb and non‐lame limb) of the same horse. Lesion severity was neither significantly associated with the lameness group nor with the type or level of activity. The prevalence of bone marrow lesions in the distal condyles of the third metacarpal bone is high in this population and the clinical significance is not always clear. Further studies are required to elucidate the clinical significance of this finding in sports and pleasure horses.
Challenges and advances in atomistic simulations of potassium and sodium ion channel gating and permeation
Authors: DeMarco Kevin R. , Bekker Slava , Vorobyov Igor 
Published: November 2018

AbstractIon channels are implicated in many essential physiological events such as electrical signal propagation and cellular communication. The advent of K+ and Na+ ion channel structure determination has facilitated numerous investigations of molecular determinants of their behaviour. At the same time, rapid development of computer hardware and molecular simulation methodologies has made computational studies of large biological molecules in all‐atom representation tractable. The concurrent evolution of experimental structural biology with biomolecular computer modelling has yielded mechanistic details of fundamental processes unavailable through experiments alone, such as ion conduction and ion channel gating. This review is a short survey of the atomistic computational investigations of K+ and Na+ ion channels, focusing on KcsA and several voltage‐gated channels from the KV and NaV families, which have garnered many successes and engendered several long‐standing controversies regarding the nature of their structure–function relationship. We review the latest advancements and challenges facing the field of molecular modelling and simulation regarding the structural and energetic determinants of ion channel function and their agreement with experimental observations.
Analytical Description of the Static and Dynamic Behaviour of a Pressure Relief Valve
Authors: Osterland Sven , Weber Jürgen 
Published: November 2018

The paper presents an explicitly straightforward formulation of the stationary and dynamic behaviour of a pressure relief valve (PRV). This makes it possible to consider the static, dynamic and robustness properties of a PRV during the analysis or design process.
A PRV can be understood as a self-regulating, cross-domain system. The governing equations are well known and widely used in literature. Usually, these include: a geometrical description of the flow area and the pressure surface, a flow equation, the pressure build-up equations, a spring-like counterforce, a flow force, a term for viscous friction and the inertia force. Together they form a system of ordinary non-linear differential equations of third order. So far, these equations had to be solved numerically in order to analyse or adapt the static or dynamic properties of a particular PRV.
In this paper, direct analytical solutions for stationary and dynamic cases are derived. This results in an explicit equation for the respective p-Q characteristic curve. In addition, a simple criterion for the stability of a PRV was found. As it turns out, the minimum requirement for viscous damping is directly anti-proportional to the gradient of the p-Q characteristic curve. It is empirically known that decreasing the gradient of the p-Q curve makes the system more susceptible to oscillations. However, this has not yet been shown mathematically elegant.
The method presented here calculates the static p-Q curve, the stability and natural frequencies of a PRV in a simple procedure using only elementary mathematics — no numerical scheme is required. Thus, the new method offers four main advantages. First, it is several orders of magnitude faster because it is not necessary to solve the differential equation system numerically. Secondly, the user does not require any special knowledge or advanced calculation tools — a simple spreadsheet program is sufficient. This eliminates licensing and training costs. Third, sensitivity and robustness analyses can be carried out easily because the dependencies are explicitly known. Last but not least, the understanding of a PRV is improved by knowing directly which parameters have what influence. The new method is tested and verified by comparison with conventional non-linear numerical simulations.
Use of PVDF Wires As Sensors for Non Intrusive Pressure Measurement
Authors: Journaix Richard , Ancian Loïc , Salanon Rémi 
Published: November 2018

One of the most challenging aspects when performing on-site piping troubleshooting is to obtain the most pertinent information possible regarding piping behavior: acceleration, stress, pressure levels, etc. This last parameter is always difficult to obtain because when pressure taps are available on the line, they are rarely in the area of interest.
PVDF (PolyVinyliDene Fluoride) wire makes it possible to perform non-intrusive pressure measurements but needs to be calibrated in order to have a good representation of phenomenon occurring inside the pipe. After development of a dedicated calibrator and calculation of the fluid/structure coupling coefficient, VibraTec is able to assess PVDF sensor sensitivity according to client’s installation characteristics.
Non-intrusive measurements provide a good accuracy regarding phenomenon amplitude and frequency localization even though some temperature restrictions apply to PVDF measurements.
Although PVDF sensors seem to be simple to implement, particular attention must be paid during installation as this has a direct influence on the PVDF response.
Comparison of DSMC and CFD Models of Heat Transfer in a Rarefied Two-Dimensional Geometry
Authors: Maharjan Dilesh , Hadj-Nacer Mustafa , Greiner Miles , Stefanov Stefan K. 
Published: November 2018

During vacuum drying of used nuclear fuel (UNF) canisters, helium pressure is reduced to as low as 67 Pa to promote evaporation and removal of remaining water after draining process. At such low pressure, and considering the dimensions of the system, helium is mildly rarefied, which induces a thermal-resistance temperature-jump at gas–solid interfaces that contributes to the increase of cladding temperature. It is important to maintain the temperature of the cladding below roughly 400 °C to avoid radial hydride formation, which may cause cladding embrittlement during transportation and long-term storage.
Direct Simulation Monte Carlo (DSMC) method is an accurate method to predict heat transfer and temperature under rarefied condition. However, it is not convenient for complex geometry like a UNF canister. Computational Fluid Dynamics (CFD) simulations are more convenient to apply but their accuracy for rarefied condition are not well established. This work seeks to validate the use of CFD simulations to model heat transfer through rarefied gas in simple two-dimensional geometry by comparing the results to the more accurate DSMC method. The geometry consists of a circular fuel rod centered inside a square cross-section enclosure filled with rarefied helium. The validated CFD model will be used later to accurately estimate the temperature of an UNF canister subjected to vacuum drying condition.
Analysis of the Influence of the Cooling Patterns and the Shape of the Bulges on the Levels of Stress in the Cylindrical Section of Delayed Coke Drums
Authors: Vivas Gabriel A. , Moret Armando J. , Bello Roberto E. , Melian Luis M. , Bedoya Julian J. 
Published: November 2018

Coke drums are thin-walled pressure vessels that experience low cycle fatigue due to thermal loadings. The delayed coking process is comprised by three major stages: heating, coking and cooling, which repeat at intervals between 20 and 48 hours. The cyclic changes of temperature increase the growth of bulges and cracks which with the passing of time, propagate and eventually cause failures due to the loss of containment. A better understanding of the phenomena of the thermal gradients and their influence on the generated stresses would reduce the effects of the damage mechanisms afflicting coke drums, for example; a continuous monitoring system could be implemented in order to control the cooling ramp to obtain a more homogeneous quenching around the cylinder of the coke drum and consequently increase its lifetime. It is been widely accepted that there is a relationship between high cooling rates in isolated zones and high axial stresses. However, this relationship has not been fully validated, since there are also been reported events of low cooling rates and high stresses. This study shows a predictable behavior (trend) that relates the spatial thermal gradients and the axial and circumferential stresses generated.
A coke drum in an upgrader facility was instrumented with two arrays or grids, each of them having 24 thermocouples and 2 strain gauges in zones with distinct bulges. One arrangement was located at an inward bulge while the other was located at an outward bulge. Computational models were carried out to reproduce the behavior of the instrumented zones with their actual deformations obtained from laser scanning. Finite element models were developed using a sequentially coupled thermo-mechanical analysis to determine the transient temperature and stress distributions. The effect of the circumferential thermal gradients on the stress levels in the instrumented cylindrical sections were analyzed, considering two cases; the first of them a perfect cylinder (without deformation) and the second one considering the presence of bulges in the area of interest.
The results indicate that there is a relationship between the circumferential thermal gradients [°C/m] or [°F/ft] and the axial stress levels, i.e., cold zones generate axial tensile stresses, and hot zones produce compressive axial stresses. This relationship is affected — exacerbated or counteracted — by the presence of the bulges. Additionally, the results obtained in this paper confirm those of previous investigations showing that outward bulges subject to pressure and thermal loading generate high stresses on its internal surface and low stresses on its external face whereas inward bulges produce the opposite effect.
Management of severe bronchiolitis: impact of NICE guidelines
Authors: Griffiths Benedict , Riphagen Shelley , Lillie Jon 
Published: November 2018

ObjectiveTo understand the impact of the National Institute for Health and Care Excellence (NICE) bronchiolitis guidelines on the management of children referred to paediatric intensive care unit (PICU) with bronchiolitis.Design and settingData were collected on all children referred to a regional PICU transport service with the clinical diagnosis of bronchiolitis during the winter prior to the NICE consultation period (2011–2012) and during the winter after publication (2015–2016). Management initiated by the referring hospital was assessed.ResultsThere were 165 infants referred with bronchiolitis in epoch 1 and 187 in epoch 2. Nebuliser use increased from 28% in epoch 1 to 53% in epoch 2. Increased use of high-flow nasal cannula oxygen and reduction in continuous positive airway pressure use were observed. The use of antibiotics did not change between epochs.ConclusionThe use of nebulised therapies has increased in the management of severe bronchiolitis despite national guidance to the contrary.
Musculoskeletal anomalies in children with Down syndrome: an observational study
Authors: Foley Charlene , Killeen Orla G 
Published: November 2018

BackgroundMusculoskeletal complications of Down syndrome (DS) are common but infrequently reported. The combination of ligamentous laxity and low muscle tone contributes to increased risk of a number of musculoskeletal disorders and a delay in acquisition of motor milestones. The primary aim of this study was to describe musculoskeletal anomalies reported in a national cohort of children with DS.MethodsThis was an observational study. Children with DS, aged 0–21 years, were invited to attend a musculoskeletal assessment clinic conducted by a paediatric physician. Relevant musculoskeletal history and clinical findings were documented.ResultsOver an 18-month period, 503 children with DS were examined (56% male). The median age was 8.1 years (0.6–19.2). Pes planus was almost universal, occurring in 91% of the cohort. A range of other musculoskeletal anomalies were observed, with inflammatory arthritis (7%) and scoliosis (4.8%) occurring most frequently after pes planus. Delay in ambulation was common; the median age to walk was 28 months (12–84).ConclusionChildren with DS are at increased risk of a number of potentially debilitating musculoskeletal problems. These conditions can present in variable manners or be completely asymptomatic. Pes planus is common; therefore, early consideration of orthotics and lifelong appropriate supportive footwear should be considered. Delayed ambulation is frequently noted. A significant proportion of children with DS have arthritis; however, despite a high prevalence, it is often missed, leading to delayed diagnosis. An annual musculoskeletal assessment for all children with DS could potentially enable early detection of problems, allowing for timely multidisciplinary team intervention and better clinical outcomes.
Economic cost of congenital CMV in the UK
Authors: Retzler Jenny , Hex Nick , Bartlett Chris , Webb Anne , Wood Sharon , Star Caroline , Griffiths Paul , Jones Christine E 
Published: November 2018

ObjectiveCongenital cytomegalovirus (cCMV) is the most common infectious cause of congenital disability. It can disrupt neurodevelopment, causing lifelong impairments including sensorineural hearing loss and developmental delay. This study aimed, for the first time, to estimate the annual economic burden of managing cCMV and its sequelae in the UK.DesignThe study collated available secondary data to develop a static cost model.SettingThe model aimed to estimate costs of cCMV in the UK for the year 2016.PatientsIndividuals of all ages with cCMV.Main outcome measuresDirect (incurred by the public sector) and indirect (incurred personally or by society) costs associated with management of cCMV and its sequelae.ResultsThe model estimated that the total cost of cCMV to the UK in 2016 was £732 million (lower and upper estimates were between £495 and £942 million). Approximately 40% of the costs were directly incurred by the public sector, with the remaining 60% being indirect costs, including lost productivity. Long-term impairments caused by the virus had a higher financial burden than the acute management of cCMV.ConclusionsThe cost of cCMV is substantial, predominantly stemming from long-term impairments. Costs should be compared against investment in educational strategies and vaccine development programmes that aim to prevent virus transmission, as well as the value of introducing universal screening for cCMV to both increase detection of children who would benefit from treatment, and to build a more robust evidence base for future research.