Creep behavior of copper-chromium in-situ composite

Creep deformation and fracture behaviors were investigated on a deformation-processed Cu-Cr in-situ composite over a temperature range of 200 °C to 650 °C. It was found that the creep resistance increases significantly with the introduction of Cr fibers into Cu. The stress exponent and the activation energy for creep of the composite at high temperatures (≥400 °C) were observed to be 5.5 and 180 to 216 kJ/mol, respectively. The observation that the stress exponent and the activation energy for creep of the composite at high temperatures (≥400 °C) are close to those of pure Cu suggests that the creep deformation of the composite is dominated by the deformation of the Cu matrix. The high stress exponent at low temperatures (200 °C and 300 °C) is thought be associated with the as-swaged microstructure, which contains elongated dislocation cells and subgrains that are stable and act as strong athermal obstacles at low temperatures. The mechanism of damage was found to be similar for all the creep tests performed, but the distribution and extent of damage were found to be very sensitive to the test temperature

Effect of possible rotor deformation on the probability of face contact for a liquid film bearing

The possibility of face contact is examined for a coaxial rotor-stator bearing in dynamic motion constrained by a highly rotating very thin liquid film. A modified Reynolds equation for pressurised flow is coupled to the bearing structure leading to determination of the bearing gap from solving a nonlinear second-order non-autonomous ordinary differential equation. Periodic solutions are found via a mapping solver. Rotor deformation is parametrised by a coning angle and considered a random variable. The method of derived distributions is used to quantify variation in coning angle and examine the probability of rotor-stator contact. Additionally, effects of possible destabilising random aspects on the axial rotor oscillations are investigated. Exact solutions for probability of contact are obtained for various bearing configurations

Search for solar axions in XMASS, a large liquid-xenon detector

XMASS, a low-background, large liquid-xenon detector, was used to search for solar axions that would be produced by bremsstrahlung and Compton effects in the Sun. With an exposure of 5.6ton days of liquid xenon, the model-independent limit on the coupling for mass $\ll$ 1keV is $|g_{aee}|< 5.4\times 10^{-11}$ (90% C.L.), which is a factor of two stronger than the existing experimental limit. The bounds on the axion masses for the DFSZ and KSVZ axion models are 1.9 and 250eV, respectively. In the mass range of 10-40keV, this study produced the most stringent limit, which is better than that previously derived from astrophysical arguments regarding the Sun to date

The Society for Immunotherapy of Cancer consensus statement on immunotherapy for the treatment of squamous cell carcinoma of the head and neck (HNSCC)

Head and neck cancers, including those of the lip and oral cavity, nasal cavity, paranasal sinuses, oropharynx, larynx and nasopharynx represent nearly 700,000 new cases and 380,000 deaths worldwide per annum, and account for over 10,000 annual deaths in the United States alone. Improvement in outcomes are needed for patients with recurrent and or metastatic squamous cell carcinoma of the head and neck (HNSCC). In 2016, the US Food and Drug Administration (FDA) granted the first immunotherapeutic approvals - the anti-PD-1 immune checkpoint inhibitors nivolumab and pembrolizumab - for the treatment of patients with recurrent squamous cell carcinoma of the head and neck (HNSCC) that is refractory to platinum-based regimens. The European Commission followed in 2017 with approval of nivolumab for treatment of the same patient population, and shortly thereafter with approval of pembrolizumab monotherapy for the treatment of recurrent or metastatic HNSCC in adults whose tumors express PD-L1 with a 65 50% tumor proportion score and have progressed on or after platinum-containing chemotherapy. Then in 2019, the FDA granted approval for PD-1 inhibition as first-line treatment for patients with metastatic or unresectable, recurrent HNSCC, approving pembrolizumab in combination with platinum and fluorouracil for all patients with HNSCC and pembrolizumab as a single agent for patients with HNSCC whose tumors express a PD-L1 combined positive score 65 1. These approvals marked the first new therapies for these patients since 2006, as well as the first immunotherapeutic approvals in this disease. In light of the introduction of these novel therapies for the treatment of patients with head and neck cancer, The Society for Immunotherapy of Cancer (SITC) formed an expert committee tasked with generating consensus recommendations for emerging immunotherapies, including appropriate patient selection, therapy sequence, response monitoring, adverse event management, and biomarker testing. These consensus guidelines serve as a foundation to assist clinicians' understanding of the role of immunotherapies in this disease setting, and to standardize utilization across the field for patient benefit. Due to country-specific variances in approvals, availability and regulations regarding the discussed agents, this panel focused solely on FDA-approved drugs for the treatment of patients in the U.S

A comprehensive TALEN-based knockout library for generating human induced pluripotent stem cell-based models for cardiovascular diseases

Rationale: Targeted genetic engineering using programmable nucleases such as transcription activator-like effector nucleases (TALENs) is a valuable tool for precise, site-specific genetic modification in the human genome. Objective: The emergence of novel technologies such as human induced pluripotent stem cells (iPSCs) and nuclease-mediated genome editing represent a unique opportunity for studying cardiovascular diseases in vitro. Methods and Results: By incorporating extensive literature and database searches, we designed a collection of TALEN constructs to knockout (KO) eighty-eight human genes that are associated with cardiomyopathies and congenital heart diseases. The TALEN pairs were designed to induce double-strand DNA break near the starting codon of each gene that either disrupted the start codon or introduced a frameshift mutation in the early coding region, ensuring faithful gene KO. We observed that all the constructs were active and disrupted the target locus at high frequencies. To illustrate the general utility of the TALEN-mediated KO technique, six individual genes (TNNT2, LMNA/C, TBX5, MYH7, ANKRD1, and NKX2.5) were knocked out with high efficiency and specificity in human iPSCs. By selectively targeting a dilated cardiomyopathy (DCM)-causing mutation (TNNT2 p.R173W) in patient-specific iPSC-derived cardiac myocytes (iPSC-CMs), we demonstrated that the KO strategy ameliorates the DCM phenotype in vitro. In addition, we modeled the Holt-Oram syndrome (HOS) in iPSC-CMs in vitro and uncovered novel pathways regulated by TBX5 in human cardiac myocyte development. Conclusions: Collectively, our study illustrates the powerful combination of iPSCs and genome editing technology for understanding the biological function of genes and the pathological significance of genetic variants in human cardiovascular diseases. The methods, strategies, constructs and iPSC lines developed in this study provide a validated, readily available resource for cardiovascular research

On the Role of Higher Twist in Polarized Deep Inelastic Scattering

The higher twist corrections $h^N(x)/Q^2$ to the spin dependent proton and neutron structure functions $g_1^N(x, Q^2)$ are extracted in a model independent way from experimental data on $g_1^N$ and found to be non-negligible. It is shown that the NLO QCD polarized parton densities determined from the data on g1, including higher twist effects, are in good agreement with those found earlier from our analysis of the data on g1/F1 and A1 where higher twist effects are negligible. On the contrary, the LO QCD polarized parton densities obtained from the data on g1, including higher twist, differ significantly from our previous results.Comment: 18 pages, latex, 6 figures, final version which will be published in Phys. Rev. D, fig. 5 is changed, misprints in Table 2 are remove

A unified Witten-Reshetikhin-Turaev invariant for integral homology spheres

We construct an invariant J_M of integral homology spheres M with values in a completion \hat{Z[q]} of the polynomial ring Z[q] such that the evaluation at each root of unity \zeta gives the the SU(2) Witten-Reshetikhin-Turaev invariant \tau_\zeta(M) of M at \zeta. Thus J_M unifies all the SU(2) Witten-Reshetikhin-Turaev invariants of M. As a consequence, \tau_\zeta(M) is an algebraic integer. Moreover, it follows that \tau_\zeta(M) as a function on \zeta behaves like an ``analytic function'' defined on the set of roots of unity. That is, the \tau_\zeta(M) for all roots of unity are determined by a "Taylor expansion" at any root of unity, and also by the values at infinitely many roots of unity of prime power orders. In particular, \tau_\zeta(M) for all roots of unity are determined by the Ohtsuki series, which can be regarded as the Taylor expansion at q=1.Comment: 66 pages, 8 figure

TGF-beta triggers rapid fibrillogenesis via a Novel T beta RII-Dependent Fibronectin-Trafficking Mechanism

Fibronectin (FN) is a critical regulator of extracellular matrix (ECM) remodeling through its availability and stepwise polymerization for fibrillogenesis. Availability of FN is regulated by its synthesis and turnover, and fibrillogenesis is a multistep, integrin-dependent process essential for cell migration, proliferation, and tissue function. Transforming growth factor β (TGF-β) is an established regulator of ECM remodeling via transcriptional control of ECM proteins. Here we show that TGF-β, through increased FN trafficking in a transcription- and SMAD-independent manner, is a direct and rapid inducer of the fibrillogenesis required for TGF-β–induced cell migration. Whereas TGF-β signaling is dispensable for rapid fibrillogenesis, stable interactions between the cytoplasmic domain of the type II TGF-β receptor (TβRII) and the FN receptor (α5β1 integrin) are required. We find that, in response to TGF-β, cell surface–internalized FN is not degraded by the lysosome but instead undergoes recycling and incorporation into fibrils, a process dependent on TβRII. These findings are the first to show direct use of trafficked and recycled FN for fibrillogenesis, with a striking role for TGF-β in this process. Given the significant physiological consequences associated with FN availability and polymerization, our findings provide new insights into the regulation of fibrillogenesis for cellular homeostasis

Search for exotic neutrino-electron interactions using solar neutrinos in XMASS-I

We have searched for exotic neutrino-electron interactions that could be produced by a neutrino millicharge, by a neutrino magnetic moment, or by dark photons using solar neutrinos in the XMASS-I liquid xenon detector. We observed no significant signals in 711 days of data. We obtain an upper limit for neutrino millicharge of 5.4 × 10−12e at 90% confidence level assuming all three species of neutrino have common millicharge. We also set flavor-dependent limits assuming the respective neutrino flavor is the only one carrying a millicharge, 7.3 × 10−12e for νe , 1.1 × 10−11e for νμ, and 1.1 × 10−11e for ντ . These limits are the most stringent yet obtained from direct measurements. We also obtain an upper limit for the neutrino magnetic moment of 1.8 × 10−10 Bohr magnetons. In addition, we obtain upper limits for the coupling constant of dark photons in the U(1)B−L model of 1.3 × 10−6 if the dark photon mass is 1 × 10−3 MeV/c2, and 8.8 × 10−5 if it is 10 MeV/c2