Anomalous Chromomagnetic Moments of Quarks and Large Transverse Energy Jets

We consider the jet cross sections for gluons coupling to quarks with an anomalous chromomagnetic moment. We then apply this to the deviation and bounds from QCD found in the CDF and D0 Fermilab data, respectively, to find a range of possible values for the anomalous moments. The quadratic and quartic terms in the anomalous moments can fit to the rise of a deviation with transverse energy. Since previous analyses have been done on the top quark total cross section, here we assume the same moment on all quarks except the top and find the range $|\kappa'| \equiv |\kappa/(2 m_q)| = 1.0\pm 0.3$ TeV$^{-1}$ for the CDF data. Assuming the anomalous moment is present only on a charm or bottom quark which is pair produced results in a range $|\kappa'_{b,c}| = 3.5 \pm 1.0$ TeV$^{-1}$. The magnitudes here are compared with anomalous magnetic moments that could account for $R_b$ and found to be in the same general range, as well as not inconsistent with LEP and SLD bounds on $\Delta \Gamma_{\text{had}}$.Comment: REVTeX, 11 pages, 2 postscript figure

Selectivity, efficacy and toxicity studies of UCCB01-144, a dimeric neuroprotective PSD-95 inhibitor

Inhibition of postsynaptic density protein-95 (PSD-95) decouples N-methyl-d-aspartate (NMDA) receptor downstream signaling and results in neuroprotection after focal cerebral ischemia. We have previously developed UCCB01-144, a dimeric PSD-95 inhibitor, which binds PSD-95 with high affinity and is neuroprotective in experimental stroke. Here, we investigate the selectivity, efficacy and toxicity of UCCB01-144 and compare with the monomeric drug candidate Tat-NR2B9c. Fluorescence polarization using purified proteins and pull-downs of mouse brain lysates showed that UCCB01-144 potently binds all four PSD-95-like membrane-associated guanylate kinases (MAGUKs). In addition, UCCB01-144 affected NMDA receptor signaling pathways in ischemic brain tissue. UCCB01-144 reduced infarct size in young and aged male mice at various doses when administered 30 min after permanent middle cerebral artery occlusion, but UCCB01-144 was not effective in young male mice when administered 1 h post-ischemia or in female mice. Furthermore, UCCB01-144 was neuroprotective in a transient stroke model in rats, and in contrast to Tat-NR2B9c, high dose of UCCB01-144 did not lead to significant changes in mean arterial blood pressure or heart rate. Overall, UCCB01-144 is a potent MAGUK inhibitor that reduces neurotoxic PSD-95-mediated signaling and improves neuronal survival following focal brain ischemia in rodents under various conditions and without causing cardiovascular side effects, which encourages further studies towards clinical stroke trials

Association of a marker of N-acetylglucosamine with progressive multiple sclerosis and neurodegeneration

IMPORTANCE: N-glycan branching modulates cell surface receptor availability, and its deficiency in mice promotes inflammatory demyelination, reduced myelination, and neurodegeneration. N-acetylglucosamine (GlcNAc) is a rate-limiting substrate for N-glycan branching, but, to our knowledge, endogenous serum levels in patients with multiple sclerosis (MS) are unknown. OBJECTIVE: To investigate a marker of endogenous serum GlcNAc levels in patients with MS. DESIGN, SETTING, AND PARTICIPANTS: A cross-sectional discovery study and cross-sectional confirmatory study were conducted at 2 academic MS centers in the US and Germany. The discovery study recruited 54 patients with MS from an outpatient clinic as well as 66 healthy controls between April 20, 2010, and June 21, 2013. The confirmatory study recruited 180 patients with MS from screening visits at an academic MS study center between April 9, 2007, and February 29, 2016. Serum samples were analyzed from December 2, 2013, to March 2, 2015. Statistical analysis was performed from February 23, 2020, to March 18, 2021. MAIN OUTCOMES AND MEASURES: Serum levels of GlcNAc plus its stereoisomers, termed N-acetylhexosamine (HexNAc), were assessed using targeted tandem mass spectroscopy. Secondary outcomes (confirmatory study) comprised imaging and clinical disease markers. RESULTS: The discovery cohort included 66 healthy controls (38 women; mean [SD] age, 42 [20] years), 33 patients with relapsing-remitting MS (RRMS; 25 women; mean [SD] age, 50 [11] years), and 21 patients with progressive MS (PMS; 14 women; mean [SD] age, 55 [7] years). The confirmatory cohort included 125 patients with RRMS (83 women; mean [SD] age, 40 [9] years) and 55 patients with PMS (22 women; mean [SD] age, 49 [80] years). In the discovery cohort, the mean (SD) serum level of GlcNAc plus its stereoisomers (HexNAc) was 710 (174) nM in healthy controls and marginally reduced in patients with RRMS (mean [SD] level, 682 [173] nM; P = .04), whereas patients with PMS displayed markedly reduced levels compared with healthy controls (mean [SD] level, 548 [101] nM; P = 9.55 × 10(-9)) and patients with RRMS (P = 1.83 × 10(-4)). The difference between patients with RRMS (mean [SD] level, 709 [193] nM) and those with PMS (mean [SD] level, 405 [161] nM; P = 7.6 × 10(-18)) was confirmed in the independent confirmatory cohort. Lower HexNAc serum levels correlated with worse expanded disability status scale scores (ρ = -0.485; P = 4.73 × 10(-12)), lower thalamic volume (t = 1.7; P = .04), and thinner retinal nerve fiber layer (B = 0.012 [SE = 7.5 × 10(-11)]; P = .008). Low baseline serum HexNAc levels correlated with a greater percentage of brain volume loss at 18 months (t = 1.8; P = .04). CONCLUSIONS AND RELEVANCE: This study suggests that deficiency of GlcNAc plus its stereoisomers (HexNAc) may be a biomarker for PMS. Previous preclinical, human genetic, and ex vivo human mechanistic studies revealed that N-glycan branching and/or GlcNAc may reduce proinflammatory responses, promote myelin repair, and decrease neurodegeneration. Combined, the data suggest that GlcNAc deficiency may be associated with progressive disease and neurodegeneration in patients with MS

Observation of exclusive DVCS in polarized electron beam asymmetry measurements

We report the first results of the beam spin asymmetry measured in the reaction e + p -> e + p + gamma at a beam energy of 4.25 GeV. A large asymmetry with a sin(phi) modulation is observed, as predicted for the interference term of Deeply Virtual Compton Scattering and the Bethe-Heitler process. The amplitude of this modulation is alpha = 0.202 +/- 0.028. In leading-order and leading-twist pQCD, the alpha is directly proportional to the imaginary part of the DVCS amplitude.Comment: 6 pages, 5 figure

Complete measurement of three-body photodisintegration of 3He for photon energies between 0.35 and 1.55 GeV

The three-body photodisintegration of 3He has been measured with the CLAS detector at Jefferson Lab, using tagged photons of energies between 0.35 GeV and 1.55 GeV. The large acceptance of the spectrometer allowed us for the first time to cover a wide momentum and angular range for the two outgoing protons. Three kinematic regions dominated by either two- or three-body contributions have been distinguished and analyzed. The measured cross sections have been compared with results of a theoretical model, which, in certain kinematic ranges, have been found to be in reasonable agreement with the data.Comment: 22 pages, 25 eps figures, 2 tables, submitted to PRC. Modifications: removed 2 figures, improvements on others, a few minor modifications to the tex

eta-prime photoproduction on the proton for photon energies from 1.527 to 2.227 GeV

Differential cross sections for the reaction gamma p -> eta-prime p have been measured with the CLAS spectrometer and a tagged photon beam with energies from 1.527 to 2.227 GeV. The results reported here possess much greater accuracy than previous measurements. Analyses of these data indicate for the first time the coupling of the etaprime N channel to both the S_11(1535) and P_11(1710) resonances, known to couple strongly to the eta N channel in photoproduction on the proton, and the importance of j=3/2 resonances in the process.Comment: 6 pages, 3 figure

A mutation update for the FLNC gene in myopathies and cardiomyopathies

Filamin C (FLNC) variants are associated with cardiac and muscular phenotypes. Originally, FLNC variants were described in myofibrillar myopathy (MFM) patients. Later, high-throughput screening in cardiomyopathy cohorts determined a prominent role for FLNC in isolated hypertrophic and dilated cardiomyopathies (HCM and DCM). FLNC variants are now among the more prevalent causes of genetic DCM. FLNC-associated DCM is associated with a malignant clinical course and a high risk of sudden cardiac death. The clinical spectrum of FLNC suggests different pathomechanisms related to variant types and their location in the gene. The appropriate functioning of FLNC is crucial for structural integrity and cell signaling of the sarcomere. The secondary protein structure of FLNC is critical to ensure this function. Truncating variants with subsequent haploinsufficiency are associated with DCM and cardiac arrhythmias. Interference with the dimerization and folding of the protein leads to aggregate formation detrim

SARS-CoV-2 is transmitted via contact and via the air between ferrets

SARS-CoV-2, a coronavirus that emerged in late 2019, has spread rapidly worldwide, and information about the modes of transmission of SARS-CoV-2 among humans is critical to apply appropriate infection control measures and to slow its spread. Here we show that SARS-CoV-2 is transmitted efficiently via direct contact and via the air (via respiratory droplets and/or aerosols) between ferrets, 1 to 3 days and 3 to 7 days after exposure respectively. The pattern of virus shedding in the direct contact and indirect recipient ferrets is similar to that of the inoculated ferrets and infectious virus is isolated from all positive animals, showing that ferrets are productively infected via either route. This study provides experimental evidence of robust transmission of SARS-CoV-2 via the air, supporting the implementation of community-level social distancing measures currently applied in many countries in the world and informing decisions on infection control measures in healthcare settings

Lack of Middle East Respiratory Syndrome Coronavirus Transmission in Rabbits

Middle East respiratory syndrome coronavirus (MERS-CoV) transmission from dromedaries to humans has resulted in major outbreaks in the Middle East. Although some other livestock animal species have been shown to be susceptible to MERS-CoV, it is not fully understood why the spread of the virus in these animal species has not been observed in the field. In this study, we used rabbits to further characterize the transmission potential of MERS-CoV. In line with the presence of MERS-CoV receptor in the rabbit nasal epithelium, high levels of viral RNA were shed from the nose following virus inoculation. However, unlike MERS-CoV-infected dromedaries, these rabbits did not develop clinical manifestations including nasal discharge and did shed only limited amounts of infectious virus from the nose. Consistently, no transmission by contact or airborne routes was observed in rabbits. Our data indicate that despite relatively high viral RNA levels produced, low levels of infectious virus are excreted in the upper respiratory tract of rabbits as compared to dromedary cam

Breast cancer risks associated with missense variants in breast cancer susceptibility genes

BACKGROUND: Protein truncating variants in ATM, BRCA1, BRCA2, CHEK2, and PALB2 are associated with increased breast cancer risk, but risks associated with missense variants in these genes are uncertain. METHODS: We analyzed data on 59,639 breast cancer cases and 53,165 controls from studies participating in the Breast Cancer Association Consortium BRIDGES project. We sampled training (80%) and validation (20%) sets to analyze rare missense variants in ATM (1146 training variants), BRCA1 (644), BRCA2 (1425), CHEK2 (325), and PALB2 (472). We evaluated breast cancer risks according to five in silico prediction-of-deleteriousness algorithms, functional protein domain, and frequency, using logistic regression models and also mixture models in which a subset of variants was assumed to be risk-associated. RESULTS: The most predictive in silico algorithms were Helix (BRCA1, BRCA2 and CHEK2) and CADD (ATM). Increased risks appeared restricted to functional protein domains for ATM (FAT and PIK domains) and BRCA1 (RING and BRCT domains). For ATM, BRCA1, and BRCA2, data were compatible with small subsets (approximately 7%, 2%, and 0.6%, respectively) of rare missense variants giving similar risk to those of protein truncating variants in the same gene. For CHEK2, data were more consistent with a large fraction (approximately 60%) of rare missense variants giving a lower risk (OR 1.75, 95% CI (1.47-2.08)) than CHEK2 protein truncating variants. There was little evidence for an association with risk for missense variants in PALB2. The best fitting models were well calibrated in the validation set. CONCLUSIONS: These results will inform risk prediction models and the selection of candidate variants for functional assays and could contribute to the clinical reporting of gene panel testing for breast cancer susceptibility