New Vector Boson Near the Z-pole and the Puzzle in Precision Electroweak Data

We show that a Z' with suppressed couplings to the electron compared to the Z-boson, with couplings to the b-quark, and with a mass close to the mass of the Z-boson, provides an excellent fit to forward-backward asymmetry of the b-quark and R_b measured on the Z-pole and $\pm 2$ GeV off the Z-pole, and to A_e obtained from the measurement of left-right asymmetry for hadronic final states. It also leads to a significant improvement in the total hadronic cross section on the Z-pole and R_b measured at energies above the Z-pole. In addition, with a proper mass, it can explain the excess of $Zb\bar b$ events at LEP in the 90-105 GeV region of the $b\bar b$ invariant mass.Comment: 10 pages, 1 figur

Z' near the Z-pole

We present a fit to precision electroweak data in the standard model extended by an additional vector boson, Z', with suppressed couplings to the electron compared to the Z boson, with couplings to the b-quark, and with mass close to the mass of the Z boson. This scenario provides an excellent fit to forward-backward asymmetry of the b-quark measured on the Z-pole and \pm 2 GeV off the Z-pole, and to lepton asymmetry, A_e, obtained from the measurement of left-right asymmetry for hadronic final states, and thus it removes the tension in the determination of the weak mixing angle from these two measurements. It also leads to a significant improvement in the total hadronic cross section on the Z-pole and R_b measured at energies above the Z-pole. We explore in detail properties of the Z' needed to explain the data and present a model for Z' with required couplings. The model preserves standard model Yukawa couplings, it is anomaly free and can be embedded into grand unified theories. It allows a choice of parameters that does not generate any flavor violating couplings of the Z' to standard model fermions. Out of standard model couplings, it only negligibly modifies the left-handed bottom quark coupling to the Z boson and the 3rd column of the CKM matrix. Modifications of standard model couplings in the charged lepton sector are also negligible. It predicts an additional down type quark, D, with mass in a few hundred GeV range, and an extra lepton doublet, L, possibly much heavier than the D quark. We discuss signatures of the Z' at the Large Hadron Collider and calculate the Z'b production cross section which is the dominant production mechanism for the Z'.Comment: 26 pages, 18 figures, minor modifications, one fig. added, results unchange

Identification of serpins specific for activated protein C using a lysate-based screening assay.

Activated protein C (APC) is a powerful anticoagulant enzyme that proteolytically inactivates the cofactors of the Xase and prothrombinase complexes, factors VIIIa and Va. A common mutation in factor V, fVLeiden, confers resistance to APC leading to an increased risk of thrombosis in the normal population. However, when coinherited with haemophilia, fVLeiden reduces bleeding severity, suggesting that inhibition of APC may be a useful strategy for treatment of haemophilia. We previously reported on serpins that were rationally designed for improved specificity for APC over other coagulation serine proteases. Based on structural differences in the substrate binding pockets to either side of the P1 Arg, we mutated the P2 and P1' residues to Lys. Although this approach achieved APC specificity, it resulted in a reduction in the rate of APC inhibition relative to the parent containing only the P1 Arg. Here we conduct site-specific random mutagenesis at the P2 and P1' positions to determine if improvements could be made in the rate of APC inhibition. In addition to our original Lys mutations, we found that Arg and Gln also confer specificity for APC. However, in all cases specificity for APC resulted in a reduction in inhibition rate

Subcellular Epithelial HMGB1 Expression Is Associated with Colorectal Neoplastic Progression, Male Sex, Mismatch Repair Protein Expression, Lymph Node Positivity, and an 'Immune Cold' Phenotype Associated with Poor Survival.

New treatment targets are needed for colorectal cancer (CRC). We define expression of High Mobility Group Box 1 (HMGB1) protein throughout colorectal neoplastic progression and examine the biological consequences of aberrant expression. HMGB1 is a ubiquitously expressed nuclear protein that shuttles to the cytoplasm under cellular stress. HMGB1 impacts cellular responses, acting as a cytokine when secreted. A total of 846 human tissue samples were retrieved; 6242 immunohistochemically stained sections were reviewed. Subcellular epithelial HMGB1 expression was assessed in a CRC Tissue Microarray (n = 650), normal colonic epithelium (n = 75), adenomatous polyps (n = 52), and CRC polyps (CaP, n = 69). Stromal lymphocyte phenotype was assessed in the CRC microarray and a subgroup of CaP. Normal colonic epithelium has strong nuclear and absent cytoplasmic HMGB1. With progression to CRC, there is an emergence of strong cytoplasmic HMGB1 (p < 0.001), pronounced at the leading cancer edge within CaP (p < 0.001), and reduction in nuclear HMGB1 (p < 0.001). In CRC, absent nuclear HMGB1 is associated with mismatch repair proteins (p = 0.001). Stronger cytoplasmic HMGB1 is associated with lymph node positivity (p < 0.001) and male sex (p = 0.009). Stronger nuclear (p = 0.011) and cytoplasmic (p = 0.002) HMGB1 is associated with greater CD4+ T-cell density, stronger nuclear HMGB1 is associated with greater FOXP3+ (p < 0.001) and ICOS+ (p = 0.018) lymphocyte density, and stronger nuclear HMGB1 is associated with reduced CD8+ T-cell density (p = 0.022). HMGB1 does not directly impact survival but is associated with an 'immune cold' tumour microenvironment which is associated with poor survival (p < 0.001). HMGB1 may represent a new treatment target for CRC

Ixodes ricinus Salivary Serpin Iripin-8 Inhibits the Intrinsic Pathway of Coagulation and Complement.

Tick saliva is a rich source of antihemostatic, anti-inflammatory, and immunomodulatory molecules that actively help the tick to finish its blood meal. Moreover, these molecules facilitate the transmission of tick-borne pathogens. Here we present the functional and structural characterization of Iripin-8, a salivary serpin from the tick Ixodes ricinus, a European vector of tick-borne encephalitis and Lyme disease. Iripin-8 displayed blood-meal-induced mRNA expression that peaked in nymphs and the salivary glands of adult females. Iripin-8 inhibited multiple proteases involved in blood coagulation and blocked the intrinsic and common pathways of the coagulation cascade in vitro. Moreover, Iripin-8 inhibited erythrocyte lysis by complement, and Iripin-8 knockdown by RNA interference in tick nymphs delayed the feeding time. Finally, we resolved the crystal structure of Iripin-8 at 1.89 Å resolution to reveal an unusually long and rigid reactive center loop that is conserved in several tick species. The P1 Arg residue is held in place distant from the serpin body by a conserved poly-Pro element on the P' side. Several PEG molecules bind to Iripin-8, including one in a deep cavity, perhaps indicating the presence of a small-molecule binding site. This is the first crystal structure of a tick serpin in the native state, and Iripin-8 is a tick serpin with a conserved reactive center loop that possesses antihemostatic activity that may mediate interference with host innate immunity

Seasonal variations in carbon, nitrogen and phosphorus concentrations and C:N:P stoichiometry in different organs of a Larix principis-rupprechtii Mayr. plantation in the Qinling Mountains, China

Understanding how concentrations of elements and their stoichiometry change with plant growth and age is critical for predicting plant community responses to environmental change. Weusedlong-term field experiments to explore how the leaf, stem and root carbon (C), nitrogen (N) and phosphorous (P) concentrations and their stoichiometry changed with growth and stand age in a L.principis-rupprechtii Mayr. plantation from 2012–2015 in the Qinling Mountains, China. Our results showed that the C, N and P concentrations and stoichiometric ratios in different tissues of larch stands were affected by stand age, organ type andsampling month and displayed multiple correlations with increased stand age in different growing seasons. Generally, leaf C and N concentrations were greatest in the fast-growing season, but leaf P concentrations were greatest in the early growing season. However, no clear seasonal tendencies in the stem and root C, N and P concentrations were observed with growth. In contrast to N and P, few differences were found in organ-specific C concentrations. Leaf N:P was greatest in the fast-growing season, while C:N and C:P were greatest in the late-growing season. No clear variations were observed in stem and root C:N, C:P andN:Pthroughout the entire growing season, but leaf N:P was less than 14, suggesting that the growth of larch stands was limited by N in our study region. Compared to global plant element concentrations and stoichiometry, the leaves of larch stands had higher C, P, C:NandC:PbutlowerNandN:P,andtherootshadgreater PandC:NbutlowerN,C:Pand N:P. Our study provides baseline information for describing the changes in nutritional elements with plant growth, which will facilitates plantation forest management and restoration, and makes avaluable contribution to the global data pool on leaf nutrition and stoichiometry

Flow through a circular tube with a permeable Navier slip boundary

For Newtonian fluid flow in a right circular tube, with a linear Navier slip boundary, we show that a second flow field arises which is different to conventional Poiseuille flow in the sense that the corresponding pressure is quadratic in its dependence on the length along the tube, rather than a linear dependence which applies for conventional Poiseuille flow. However, assuming that the quadratic pressure is determined, say from known experimental data, then the new solution only exists for a precisely prescribed permeability along the boundary. While this cannot occur for conventional pipe flow, for fluid flow through carbon nanotubes embedded in a porous matrix, it may well be an entirely realistic possibility, and could well explain some of the high flow rates which have been reported in the literature. Alternatively, if the radial boundary flow is prescribed, then the new flow field exists only for a given quadratic pressure. Our primary purpose here is to demonstrate the existence of a new pipe flow field for a permeable Navier slip boundary and to present a numerical solution and two approximate analytical solutions. The maximum flow rate possible for the new solution is precisely twice that for the conventional Poiseuille flow, which occurs for constant inward directed flow across the boundary

Importance of the intersection of age and sex to understand variation in incidence and survival for primary malignant gliomas

BACKGROUND: Gliomas are the most common type of malignant brain and other CNS tumors, accounting for 80.8% of malignant primary brain and CNS tumors. They cause significant morbidity and mortality. This study investigates the intersection between age and sex to better understand variation of incidence and survival for glioma in the United States. METHODS: Incidence data from 2000 to 2017 were obtained from CBTRUS, which obtains data from the NPCR and SEER, and survival data from the CDC\u27s NPCR. Age-adjusted incidence rate ratios (IRR) per 100 000 were generated to compare male-to-female incidence by age group. Cox proportional hazard models were performed by age group, generating hazard ratios to assess male-to-female survival differences. RESULTS: Overall, glioma incidence was higher in males. Male-to-female incidence was lowest in ages 0-9 years (IRR: 1.04, 95% CI: 1.01-1.07, P = .003), increasing with age, peaking at 50-59 years (IRR: 1.56, 95% CI: 1.53-1.59, P \u3c .001). Females had worse survival for ages 0-9 (HR: 0.93, 95% CI: 0.87-0.99), though male survival was worse for all other age groups, with the difference highest in those 20-29 years (HR: 1.36, 95% CI: 1.28-1.44). Incidence and survival differences by age and sex also varied by histological subtype of glioma. CONCLUSIONS: To better understand the variation in glioma incidence and survival, investigating the intersection of age and sex is key. The current work shows that the combined impact of these variables is dependent on glioma subtype. These results contribute to the growing understanding of sex and age differences that impact cancer incidence and survival

Population genomics of domestic and wild yeasts

The natural genetics of an organism is determined by the distribution of sequences of its genome. Here we present one- to four-fold, with some deeper, coverage of the genome sequences of over seventy isolates of the domesticated baker&#x27;s yeast, _Saccharomyces cerevisiae_, and its closest relative, the wild _S. paradoxus_, which has never been associated with human activity. These were collected from numerous geographic locations and sources (including wild, clinical, baking, wine, laboratory and food spoilage). These sequences provide an unprecedented view of the population structure, natural (and artificial) selection and genome evolution in these species. Variation in gene content, SNPs, indels, copy numbers and transposable elements provide insights into the evolution of different lineages. Phenotypic variation broadly correlates with global genome-wide phylogenetic relationships however there is no correlation with source. _S. paradoxus_ populations are well delineated along geographic boundaries while the variation among worldwide _S. cerevisiae_ isolates show less differentiation and is comparable to a single _S. paradoxus_ population. Rather than one or two domestication events leading to the extant baker&#x27;s yeasts, the population structure of _S. cerevisiae_ shows a few well defined geographically isolated lineages and many different mosaics of these lineages, supporting the notion that human influence provided the opportunity for outbreeding and production of new combinations of pre-existing variation