Generation of a large volume of clinically relevant nanometre-sized ultra-high-molecular-weight polyethylene wear particles for cell culture studies.

It has recently been shown that the wear of ultra-high-molecular-weight polyethylene in hip and knee prostheses leads to the generation of nanometre-sized particles, in addition to micron-sized particles. The biological activity of nanometre-sized ultra-high-molecular-weight polyethylene wear particles has not, however, previously been studied due to difficulties in generating sufficient volumes of nanometre-sized ultra-high-molecular-weight polyethylene wear particles suitable for cell culture studies. In this study, wear simulation methods were investigated to generate a large volume of endotoxin-free clinically relevant nanometre-sized ultra-high-molecular-weight polyethylene wear particles. Both single-station and six-station multidirectional pin-on-plate wear simulators were used to generate ultra-high-molecular-weight polyethylene wear particles under sterile and non-sterile conditions. Microbial contamination and endotoxin levels in the lubricants were determined. The results indicated that microbial contamination was absent and endotoxin levels were low and within acceptable limits for the pharmaceutical industry, when a six-station pin-on-plate wear simulator was used to generate ultra-high-molecular-weight polyethylene wear particles in a non-sterile environment. Different pore-sized polycarbonate filters were investigated to isolate nanometre-sized ultra-high-molecular-weight polyethylene wear particles from the wear test lubricants. The use of the filter sequence of 10, 1, 0.1, 0.1 and 0.015 µm pore sizes allowed successful isolation of ultra-high-molecular-weight polyethylene wear particles with a size range of < 100 nm, which was suitable for cell culture studies

Performance of the CMS Cathode Strip Chambers with Cosmic Rays

The Cathode Strip Chambers (CSCs) constitute the primary muon tracking device in the CMS endcaps. Their performance has been evaluated using data taken during a cosmic ray run in fall 2008. Measured noise levels are low, with the number of noisy channels well below 1%. Coordinate resolution was measured for all types of chambers, and fall in the range 47 microns to 243 microns. The efficiencies for local charged track triggers, for hit and for segments reconstruction were measured, and are above 99%. The timing resolution per layer is approximately 5 ns

The crystal structure of human Rogdi provides insight into the causes of Kohlschutter-Tonz Syndrome

Kohlschutter-T&amp;ouml;nz syndrome (KTS) is a rare autosomal-recessive disorder of childhood onset characterized by global developmental delay, spasticity, epilepsy, and amelogenesis imperfecta. Rogdi, an essential protein, is highly conserved across metazoans, and mutations in Rogdi are linked to KTS. However, how certain mutations in Rogdi abolish its physiological functions and cause KTS is not known. In this study, we determined the crystal structure of human Rogdi protein at atomic resolution. Rogdi forms a novel elongated curved structure comprising the ?? domain, a leucine-zipper-like four-helix bundle, and a characteristic ??-sheet domain. Within the ?? domain, the N-terminal H1 helix (residues 19-45) pairs with the C-terminal H6 helix (residues 252-287) in an antiparallel manner, indicating that the integrity of the four-helix bundle requires both N- and C-terminal residues. The crystal structure, in conjunction with biochemical data, indicates that the ?? domain might undergo a conformational change and provide a structural platform for protein-protein interactions. Disruption of the four-helix bundle by mutation results in significant destabilization of the structure. This study provides structural insights into how certain mutations in Rogdi affect its structure and cause KTS, which has important implications for the development of pharmaceutical agents against this debilitating neurological disease

Performance of CMS muon reconstruction in pp collision events at sqrt(s) = 7 TeV

The performance of muon reconstruction, identification, and triggering in CMS has been studied using 40 inverse picobarns of data collected in pp collisions at sqrt(s) = 7 TeV at the LHC in 2010. A few benchmark sets of selection criteria covering a wide range of physics analysis needs have been examined. For all considered selections, the efficiency to reconstruct and identify a muon with a transverse momentum pT larger than a few GeV is above 95% over the whole region of pseudorapidity covered by the CMS muon system, abs(eta) < 2.4, while the probability to misidentify a hadron as a muon is well below 1%. The efficiency to trigger on single muons with pT above a few GeV is higher than 90% over the full eta range, and typically substantially better. The overall momentum scale is measured to a precision of 0.2% with muons from Z decays. The transverse momentum resolution varies from 1% to 6% depending on pseudorapidity for muons with pT below 100 GeV and, using cosmic rays, it is shown to be better than 10% in the central region up to pT = 1 TeV. Observed distributions of all quantities are well reproduced by the Monte Carlo simulation.Comment: Replaced with published version. Added journal reference and DO

The statistics of natural hand movements.

Humans constantly use their hands to interact with the environment and they engage spontaneously in a wide variety of manual activities during everyday life. In contrast, laboratory-based studies of hand function have used a limited range of predefined tasks. The natural movements made by the hand during everyday life have thus received little attention. Here, we developed a portable recording device that can be worn by subjects to track movements of their right hand as they go about their daily routine outside of a laboratory setting. We analyse the kinematic data using various statistical methods. Principal component analysis of the joint angular velocities showed that the first two components were highly conserved across subjects, explained 60% of the variance and were qualitatively similar to those reported in previous studies of reach-to-grasp movements. To examine the independence of the digits, we developed a measure based on the degree to which the movements of each digit could be linearly predicted from the movements of the other four digits. Our independence measure was highly correlated with results from previous studies of the hand, including the estimated size of the digit representations in primary motor cortex and other laboratory measures of digit individuation. Specifically, the thumb was found to be the most independent of the digits and the index finger was the most independent of the fingers. These results support and extend laboratory-based studies of the human hand

Performance of CMS muon reconstruction in pp collision events at sqrt(s) = 7 TeV

The performance of muon reconstruction, identification, and triggering in CMS has been studied using 40 inverse picobarns of data collected in pp collisions at sqrt(s) = 7 TeV at the LHC in 2010. A few benchmark sets of selection criteria covering a wide range of physics analysis needs have been examined. For all considered selections, the efficiency to reconstruct and identify a muon with a transverse momentum pT larger than a few GeV is above 95% over the whole region of pseudorapidity covered by the CMS muon system, abs(eta) < 2.4, while the probability to misidentify a hadron as a muon is well below 1%. The efficiency to trigger on single muons with pT above a few GeV is higher than 90% over the full eta range, and typically substantially better. The overall momentum scale is measured to a precision of 0.2% with muons from Z decays. The transverse momentum resolution varies from 1% to 6% depending on pseudorapidity for muons with pT below 100 GeV and, using cosmic rays, it is shown to be better than 10% in the central region up to pT = 1 TeV. Observed distributions of all quantities are well reproduced by the Monte Carlo simulation.Comment: Replaced with published version. Added journal reference and DO

The genetic basis and evolution of red blood cell sickling in deer

Crescent-shaped red blood cells, the hallmark of sickle-cell disease, present a striking departure from the biconcave disc shape normally found in mammals. Characterized by increased mechanical fragility, sickled cells promote haemolytic anaemia and vaso-occlusions and contribute directly to disease in humans. Remarkably, a similar sickle-shaped morphology has been observed in erythrocytes from several deer species, without obvious pathological consequences. The genetic basis of erythrocyte sickling in deer, however, remains unknown. Here, we determine the sequences of human β-globin orthologues in 15 deer species and use protein structural modelling to identify a sickling mechanism distinct from the human disease, coordinated by a derived valine (E22V) that is unique to sickling deer. Evidence for long-term maintenance of a trans-species sickling/non-sickling polymorphism suggests that sickling in deer is adaptive. Our results have implications for understanding the ecological regimes and molecular architectures that have promoted convergent evolution of sickling erythrocytes across vertebrates

Search for new physics in the multijet and missing transverse momentum final state in proton-proton collisions at √s=8 Tev

Peer reviewe

Measurement of Higgs boson production and properties in the WW decay channel with leptonic final states

Peer reviewe

Glucagon-Like Peptide 1 Receptor (Glp1r) Deficiency Does Not Appreciably Alter Airway Inflammation or Gut-Lung Microbiome Axis in a Mouse Model of Obese Allergic Airways Disease and Bariatric Surgery

Yeon Ji Kim,1,&ast; Victoria M Ihrie,2,&ast; Pixu Shi,3 Mark D Ihrie,2 Jack T Womble,2 Anna Hill Meares,1 Joshua A Granek,3 Claudia K Gunsch,1 Jennifer L Ingram2 1Department of Civil and Environmental Engineering, Pratt School of Engineering, DukeUniversity, Durham, NC, USA; 2Division of Pulmonary, Allergy and Critical Care Medicine, Department of Medicine, Duke University Medical Center, Durham, NC, USA; 3Biostatistics and Bioinformatics, Division of Integrative Genomics, Department of Medicine, Duke University Medical Center, Durham, NC, USA&ast;These authors contributed equally to this workCorrespondence: Jennifer L Ingram, Department of Medicine, Duke University Medical Center, Box 2641 DUMC, 203 Research Drive, Durham, NC, 27710, USA, Tel +1 919-668-1439, Email [email protected]: High body mass index (≥ 30 kg/m2) is associated with asthma severity, and nearly 40% of asthma patients exhibit obesity. Furthermore, over 40% of patients with obesity and asthma that receive bariatric surgery no longer require asthma medication. Increased levels of glucagon-like peptide 1 (GLP-1) occur after bariatric surgery, and recent studies suggest that GLP-1 receptor (GLP-1R) signaling may regulate the gut microbiome and have anti-inflammatory properties in the lung. Thus, we hypothesized that increased GLP-1R signaling following metabolic surgery in obese and allergen-challenged mice leads to gut/lung microbiome alterations, which together contribute to improved features of allergic airways disease.Methods: Male and female Glp1r-deficient (Glp1r−/−) and replete (Glp1r+/+) mice were administered high fat diet (HFD) to induce obesity with simultaneous intranasal challenge with house dust mite (HDM) allergen to model allergic airway disease with appropriate controls. Mice on HFD received either no surgery, sham surgery, or vertical sleeve gastrectomy (VSG) on week 10 and were sacrificed on week 13. Data were collected with regard to fecal and lung tissue microbiome, lung histology, metabolic markers, and respiratory inflammation.Results: HFD led to metabolic imbalance characterized by lower GLP-1 and higher leptin levels, increased glucose intolerance, and alterations in gut microbiome composition. Prevalence of bacteria associated with short chain fatty acid (SCFA) production, namely Bifidobacterium, Lachnospiraceae UCG-001, and Parasutterella, was reduced in mice fed HFD and positively associated with serum GLP-1 levels. Intranasal HDM exposure induced airway inflammation. While Glp1r−/− genotype affected fecal microbiome beta diversity metrics, its effect was limited.Conclusion: Herein, GLP-1R deficiency had surprisingly little effect on host gut and lung microbiomes and health, despite recent studies suggesting that GLP-1 receptor agonists are protective against lung inflammation.Plain Language Summary: Asthma is a chronic lung disease that affects over 20 million Americans. In addition, obesity is a major worldwide healthcare problem whose impact is increasing each year. Asthma patients with obesity have worse symptoms, use more medications and have reduced asthma control than lean patients. Also, both asthma and obesity are linked to changes in the normal bacteria that live in the gut and the airways. Weight loss, either through bariatric surgery or through diet and exercise, improves asthma symptoms, through unknown mechanisms. One way that bariatric surgery may impact asthma is through the increase in beneficial gut hormones (GLP-1) and restoration of altered bacteria in the gut and airways. Our study shows that overall, obese mice experience changes in hormones involved in weight gain and glucose metabolism as well as gut bacteria, particularly those that may produce important factors that could improve health. We did not find any links between changes in the bacteria in the gut or lung and features of airway disease or effects from bariatric surgery in the mice. Mice that lacked GLP-1 activity did not differ from normal mice for weight, glucose tolerance, or prevalence of bacteria in the lung. Future studies will explore the timeline of these bacterial changes and the role of the gut and lung microbiomes in human obesity-associated asthma.Keywords: vertical sleeve gastrectomy, allergic airways disease, short-chain fatty acids, gut-lung microbiome axi