Variational Monte Carlo Study of the Kondo Necklace Model with Geometrical Frustration

We investigate the ground state of the Kondo necklace model on geometrically-frustrated lattices by the variational Monte Carlo simulation. To explore the possibility of a partially-ordered phase, we employ an extension of the Yosida-type wave function as a variational state, which can describe a coexistence of spin-singlet formation due to the Kondo coupling and magnetic ordering by the Ruderman-Kittel-Kasuya-Yosida interaction. We show the benchmark of the numerical simulation to demonstrate the high precision brought by the optimization of a large number of variational parameters. We discuss the ground-state phase diagram for the model on the kagome lattice in comparison with that for the triangular-lattice case.Comment: 3 pages, proceedings for ICHE201

Cooperation of DNA-PKcs and WRN helicase in the maintenance of telomeric D-loops

Werner syndrome is an inherited human progeriod syndrome caused by mutations in the gene encoding the Werner Syndrome protein, WRN. It has both 3'-5' DNA helicase and exonuclease activities, and is suggested to have roles in many aspects of DNA metabolism, including DNA repair and telomere maintenance. The DNA-PK complex also functions in both DNA double strand break repair and telomere maintenance. Interaction between WRN and the DNA-PK complex has been reported in DNA double strand break repair, but their possible cooperation at telomeres has not been reported. This study analyzes thein vitro and in vivo interaction at the telomere between WRN and DNA-PKcs, the catalytic subunit of DNA-PK. The results show that DNA-PKcs selectively stimulates WRN helicase but not WRN exonuclease in vitro, affecting that WRN helicase unwinds and promotes the release of the full-length invading strand of a telomere D-loop model substrate. In addition, the length of telomeric G-tails decreases in DNA-PKcs knockdown cells, and this phenotype is reversed by overexpression of WRN helicase. These results suggest that WRN and DNA-PKcs may cooperatively prevent G-tail shortening in vivo

Imaging With the Past: Revealing the Complexity of Chimaeroid Pelvic Musculature Anatomy and Development

Chondrichthyans are now widely adopted as models for examining the development and evolution of the stem gnathostome body plan. The fins of some cartilaginous fish are recognized for their plesiomorphic form and mode of muscular development, i.e., epithelial extension. Despite detailed molecular and descriptive examinations of these developmental mechanisms, there has been little contemporary examination of the ontogeny and morphology of the musculature in chondrichthyans including that of the paired fins. This gap represents a need for further examination of the developmental morphology of these appendicular musculatures to gain insight into their evolution in gnathostomes. The elephant shark is a Holocephalan, the sister group of all other chondrichthyans (Holocephali: Callorhinchus milii). Here, we use nano-CT imaging and 3D reconstructions to describe the development of the pelvic musculature of a growth series of elephant shark embryos. We also use historical descriptions from the nineteenth century and traditional dissection methods to describe the adult anatomy. This combined approach, using traditional methods and historical knowledge with modern imaging techniques, has enabled a more thorough examination of the anatomy and development of the pelvic musculature revealing that chimaeroid musculatures are more complex than previously thought. These data, when compared to extant and extinct sister taxa, are essential for interpreting and reconstructing fossil musculatures as well as understanding the evolution of paired fins

Cisplatin and fluorouracil with or without panitumumab in patients with recurrent or metastatic squamous-cell carcinoma of the head and neck (SPECTRUM): an open-label phase 3 randomised trial

Background: Previous trials have shown that anti-EGFR monoclonal antibodies can improve clinical outcomes of patients with recurrent or metastatic squamous-cell carcinoma of the head and neck (SCCHN). We assessed the efficacy and safety of panitumumab combined with cisplatin and fluorouracil as first-line treatment for these patients. Methods: This open-label phase 3 randomised trial was done at 126 sites in 26 countries. Eligible patients were aged at least 18 years; had histologically or cytologically confi rmed SCCHN; had distant metastatic or locoregionally recurrent disease, or both, that was deemed to be incurable by surgery or radiotherapy; had an Eastern Cooperative Oncology Group performance status of 1 or less; and had adequate haematological, renal, hepatic, and cardiac function. Patients were randomly assigned according to a computer-generated randomisation sequence (1:1; stratifi ed by previous treatment, primary tumour site, and performance status) to one of two groups. Patients in both groups received up to six 3-week cycles of intravenous cisplatin (100 mg/m(2) on day 1 of each cycle) and fl uorouracil (1000 mg/m(2) on days 1-4 of each cycle); those in the experimental group also received intravenous panitumumab (9 mg/kg on day 1 of each cycle). Patients in the experimental group could choose to continue maintenance panitumumab every 3 weeks. The primary endpoint was overall survival and was analysed by intention to treat. In a prospectively defi ned retrospective analysis, we assessed tumour human papillomavirus (HPV) status as a potential predictive biomarker of outcomes with a validated p16-INK4A (henceforth, p16) immunohistochemical assay. Patients and investigators were aware of group assignment; study statisticians were masked until primary analysis; and the central laboratory assessing p16 status was masked to identifi cation of patients and treatment. This trial is registered with ClinicalTrials. gov, number NCT00460265. Findings: Between May 15, 2007, and March 10, 2009, we randomly assigned 657 patients: 327 to the panitumumab group and 330 to the control group. Median overall survival was 11.1 months (95% CI 9.8-12.2) in the panitumumab group and 9.0 months (8.1-11.2) in the control group (hazard ratio [HR] 0.873, 95% CI 0.729-1.046; p = 0.1403). Median progression-free survival was 5.8 months (95% CI 5.6-6.6) in the panitumumab group and 4.6 months (4.1-5.4) in the control group (HR 0.780, 95% CI 0.659-0.922; p = 0.0036). Several grade 3 or 4 adverse events were more frequent in the panitumumab group than in the control group: skin or eye toxicity (62 [19%] of 325 included in safety analyses vs six [2%] of 325), diarrhoea (15 [5%] vs four [1%]), hypomagnesaemia (40 [12%] vs 12 [4%]), hypokalaemia (33 [10%] vs 23 [7%]), and dehydration (16 [5%] vs seven [2%]). Treatment-related deaths occurred in 14 patients (4%) in the panitumumab group and eight (2%) in the control group. Five (2%) of the fatal adverse events in the panitumumab group were attributed to the experimental agent. We had appropriate samples to assess p16 status for 443 (67%) patients, of whom 99 (22%) were p16 positive. Median overall survival in patients with p16-negative tumours was longer in the panitumumab group than in the control group (11.7 months [95% CI 9.7-13.7] vs 8.6 months [6.9-11.1]; HR 0.73 [95% CI 0.58-0.93]; p = 0.0115), but this difference was not shown for p16-positive patients (11.0 months [7.3-12.9] vs 12.6 months [7.7-17.4]; 1.00 [0.62-1.61]; p = 0.998). In the control group, p16-positive patients had numerically, but not statistically, longer overall survival than did p16-negative patients (HR 0.70 [95% CI 0.47-1.04]). Interpretation: Although the addition of panitumumab to chemotherapy did not improve overall survival in an unselected population of patients with recurrent or metastatic SCCHN, it improved progression-free survival and had an acceptable toxicity profile. p16 status could be a prognostic and predictive marker in patients treated with panitumumab and chemotherapy. Prospective assessment will be necessary to validate our biomarker findings

Microstructure and mechanical behavior of superelastic Ti-24Nb-0.5O and Ti-24Nb-0.5N biomedical alloys

International audienceIn this study, the microstructure and the mechanical properties of two new biocompatible superelastic alloys, Ti-24Nb-0.5O and Ti-24Nb-0.5N (at.%), were investigated. Special attention was focused on the role of O and N addition on α″ formation, supereleastic recovery and mechanical strength by comparison with the Ti-24Nb and Ti-26Nb (at.%) alloy compositions taken as references. Microstructures were characterized by optical microscopy, X-ray diffraction and transmission electron microscopy before and after deformation. The mechanical properties and the superelastic behavior were evaluated by conventional and cyclic tensile tests. High tensile strength, low Young's modulus, rather high superelastic recovery and excellent ductility were observed for both superelastic Ti-24Nb-0.5O and Ti-24Nb-0.5N alloys. Deformation twinning was shown to accommodate the plastic deformation in these alloys and only the {332}〈113〉 twinning system was observed to be activated by electron backscattered diffraction analyses

Quantitative Imaging of Protein-Protein Interactions by Multiphoton Fluorescence Lifetime Imaging Microscopy using a Streak camera

Fluorescence Lifetime Imaging Microscopy (FLIM) using multiphoton excitation techniques is now finding an important place in quantitative imaging of protein-protein interactions and intracellular physiology. We review here the recent developments in multiphoton FLIM methods and also present a description of a novel multiphoton FLIM system using a streak camera that was developed in our laboratory. We provide an example of a typical application of the system in which we measure the fluorescence resonance energy transfer between a donor/acceptor pair of fluorescent proteins within a cellular specimen.Comment: Overview of FLIM techniques, StreakFLIM instrument, FRET application

Field-Dependent Critical Current in Type-II Superconducting Strips: Combined Effect of Bulk Pinning and Geometrical Edge Barrier

Recent theoretical and experimental research on low-bulk-pinning superconducting strips has revealed striking dome-like magnetic-field distributions due to geometrical edge barriers. The observed magnetic-flux profiles differ strongly from those in strips in which bulk pinning is dominant. In this paper we theoretically describe the current and field distributions of a superconducting strip under the combined influence of both a geometrical edge barrier and bulk pinning at the strip's critical current Ic, where a longitudinal voltage first appears. We calculate Ic and find its dependence upon a perpendicular applied magnetic field Ha. The behavior is governed by a parameter p, defined as the ratio of the bulk-pinning critical current Ip to the geometrical-barrier critical current Is0. We find that when p > 2/pi and Ip is field-independent, Ic vs Ha exhibits a plateau for small Ha, followed by the dependence Ic-Ip ~ 1/Ha in higher magnetic fields.Comment: 4 pages, 2 figures, Fig. 1 revised, submitted to Phys. Rev.