Denaturation of Circular DNA: Supercoil Mechanism

The denaturation transition which takes place in circular DNA is analyzed by extending the Poland-Scheraga model to include the winding degrees of freedom. We consider the case of a homopolymer whereby the winding number of the double stranded helix, released by a loop denaturation, is absorbed by \emph{supercoils}. We find that as in the case of linear DNA, the order of the transition is determined by the loop exponent $c$. However the first order transition displayed by the PS model for $c>2$ in linear DNA is replaced by a continuous transition with arbitrarily high order as $c$ approaches 2, while the second-order transition found in the linear case in the regime $1<c\le2$ disappears. In addition, our analysis reveals that melting under fixed linking number is a \emph{condensation transition}, where the condensate is a macroscopic loop which appears above the critical temperature.Comment: 9 pages, 4 figure

No association for Chinese HBV-related hepatocellular carcinoma susceptibility SNP in other East Asian populations.

published_or_final_versio

New susceptibility and resistance HLA-DP alleles to HBV-related diseases identified by a trans-ethnic association study in Asia

Previous studies have revealed the association between SNPs located on human leukocyte antigen (HLA) class II genes, including HLA-DP and HLA-DQ, and chronic hepatitis B virus (HBV) infection, mainly in Asian populations. HLA-DP alleles or haplotypes associated with chronic HBV infection or disease progression have not been fully identified in Asian populations. We performed trans-ethnic association analyses of HLA-DPA1, HLA-DPB1 alleles and haplotypes with hepatitis B virus infection and disease progression among Asian populations comprising Japanese, Korean, Hong Kong, and Thai subjects. To assess the association between HLA-DP and chronic HBV infection and disease progression, we conducted high-resolution (4-digit) HLA-DPA1 and HLA-DPB1 genotyping in a total of 3,167 samples, including HBV patients, HBV-resolved individuals and healthy controls. Trans-ethnic association analyses among Asian populations identified a new risk allele HLA-DPB1*09 ratio 01 (P = 1.36 x 10(-6); OR= 1.97; 95% CI, 1.50-2.59) and a new protective allele DPB1*02 ratio 01 (P = 5.22 x 10(-6); OR = 0.68; 95% CI, 0.58-0.81) to chronic HBV infection, in addition to the previously reported alleles. Moreover, DPB1*02 ratio 01 was also associated with a decreased risk of disease progression in chronic HBV patients among Asian populations (P = 1.55 x 10(-7); OR = 0.50; 95% CI, 0.39-0.65). Trans-ethnic association analyses identified Asian-specific associations of HLA-DP alleles and haplotypes with HBV infection or disease progression. The present findings will serve as a base for future functional studies of HLA-DP molecules in order to understand the pathogenesis of HBV infection and the development of hepatocellular carcinoma.published_or_final_versio

Vortex State and Field-Angle Resolved Specific Heat Oscillation for H // ab in d-Wave Superconductors

When magnetic field is applied parallel to the ab plane in d_{x^2-y^2}-wave superconductors, the transition of stable vortex lattice structure, spatial structure of local density of states, and specific heat oscillation by rotation of magnetic field orientation are investigated by quantitative calculations based on the selfconsistent Eilenberger theory. We estimate how the vortex state changes depending on the relative angle between the node-direction of the superconducting gap and magnetic field orientation. To reproduce the sign-change of specific heat oscillation observed in CeCoIn_5, our study is done by including strong paramagnetic effect. The quantitative theoretical calculations give decisive information to analyze the experimental data on the field-angle dependence, and establish the angle-resolved specific heat experiment as a spectroscopic means to identify the node-position of the superconducting gap.Comment: 9 pages, 13 figure

Treatment of mechanically-induced vasospasm of the carotid artery in a primate using intra-arterial verapamil: a technical case report

BACKGROUND: Despite improvements in the safety and efficacy of endovascular procedures, considerable morbidity may still be attributed to vasospasm. Vasospasm has proven amenable to pharmacological intervention such as nitrates, intravenous calcium channel blockers (CCBs), and intra-arterial papaverine, particularly in small vessels. However, few studies have focused on medium to large vessel spasm. Here we report the use of an intra-arterial CCB, verapamil, to treat flow-limiting mechanically-induced spasm of the common carotid artery (CCA) in a primate. We believe this to be the first such report of its kind. CASE PRESENTATION: As part of a study assessing the placement feasibility and safety of a catheter capable of delivering intra-arterial cerebroprotective therapy, a female 16 kg baboon prophylaxed with intravenous nitroglycerin underwent transfemoral CCA catheterization with a metallic 6-Fr catheter without signs of acute spasm. The protocol dictated that the catheter remain in the CCA for 12 hours. Upon completion of the protocol, arteriography revealed a marked decrease in CCA size (mean cross-sectional area reduction = 31.6 ± 1.9%) localized along the catheter length. Intra-arterial verapamil (2 mg/2cc) was injected and arteriography was performed 10 minutes later. Image analysis at 6 points along the CCA revealed a 21.0 ± 1.7% mean increase in vessel diameter along the length of the catheter corresponding to a 46.7 ± 4.0% mean increase in cross-sectional area. Mean systemic blood pressure did not deviate more than 10 mm Hg during the procedure. CONCLUSIONS: Intraluminal CCBs like verapamil may constitute an effective endovascular treatment for mechanically-induced vasospasm in medium to large-sized vessels such as the CCA

Lenvatinib versus Sorafenib as first-line treatment in hepatocellular carcinoma: A multi-institutional matched case-control study

Background: Advanced Hepatocarcinoma (HCC) is an important health problem worldwide. Recently, the REFLECT trial demonstrated the non-inferiority of Lenvatinib compared to Sorafenib in I line setting, thus leading to the approval of new first-line standard of care, along with Sorafenib. Aims and methods: With aim to evaluate the optimal choice between Sorafenib and Lenvatinib as primary treatment in clinical practice, we performed a multicentric analysis with the propensity score matching on 184 HCC patients. Results: The median overall survival (OS) were 15.2 and 10.5&nbsp;months for Lenvatinib and Sorafenib arm, respectively. The median progression-free survival (PFS) was 7.0 and 4.5&nbsp;months for Lenvatinib and Sorafenib arm, respectively. Patients treated with Lenvatinib showed a 36% reduction of death risk (p&nbsp;=&nbsp;0.0156), a 29% reduction of progression risk (p&nbsp;=&nbsp;0.0446), a higher response rate (p&nbsp;&lt;&nbsp;0.00001) and a higher disease control rate (p&nbsp;=&nbsp;0.002). Sorafenib showed to be correlated with more hand-foot skin reaction and Lenvatinib with more hypertension and fatigue. We highlighted the prognostic role of Barcelona Clinic Liver Cancer (BCLC) stage, Eastern Cooperative Oncology Group Performance Status (ECOG-PS), bilirubin, alkaline phosphatase and eosinophils for Sorafenib. Conversely, albumin, aspartate aminotransferase (AST), alkaline phosphatase and Neutrophil-Lymphocyte Ratio (NLR) resulted prognostic in Lenvatinib arm. Finally, we highlighted the positive predictive role of albumin&nbsp;&gt;&nbsp;Normal Value (NV), ECOG&nbsp;&gt;&nbsp;0, NLR&nbsp;&lt;&nbsp;3, absence of Hepatitis C Virus positivity, and presence of portal vein thrombosis in favor of Lenvatinib arm. Eosinophil&nbsp;&lt;&nbsp;50 and ECOG&nbsp;&gt;&nbsp;0 negatively predicted the response to Sorafenib. Conclusion: SLenvatinib showed to better perform in a real-word setting compared to Sorafenib. More researches are needed to validate the predictor factors of response to Lenvatinib rather than Sorafenib

Advanced Instrumentation of Frequency Modulation AFM for Subnanometer-Scale 2D/3D Measurements at Solid-Liquid Interfaces

Since the first demonstration of true atomic-resolution imaging by frequency modulation atomic force microscopy (FM-AFM) in liquid, the method has been used for imaging subnanometer-scale structures of various materials including minerals, biological systems and other organic molecules. Rencetly, there have been further advancements in theFM-AFMinstrumentation. Three-dimensional (3D) force measurement techniques are proposed for visualizing 3D hydration structures formed at a solid-liquid interface. Thesemethods further enabled to visualize 3D distributions of flexible surface structures at interfaces between soft materials andwater. Furthermore, the fundamental performance such as force sensitivity and operation speed have been significantly improved using a small cantilever and high-speed phase detector. These technical advancements enabled direct visualization of atomic-scale interfacial phenomena at 1 frame/s. In this chapter, these recent advancements in the FM-AFM instrumentation and their applications to the studies on various interfacial phenomena are presented. © Springer International Publishing Switzerland 201

RecG interacts directly with SSB: implications for stalled replication fork regression

RecG and RuvAB are proposed to act at stalled DNA replication forks to facilitate replication restart. To define the roles of these proteins in fork regression, we used a combination of assays to determine whether RecG, RuvAB or both are capable of acting at a stalled fork. The results show that RecG binds to the C-terminus of single-stranded DNA binding protein (SSB) forming a stoichiometric complex of 2 RecG monomers per SSB tetramer. This binding occurs in solution and to SSB protein bound to single stranded DNA (ssDNA). The result of this binding is stabilization of the interaction of RecG with ssDNA. In contrast, RuvAB does not bind to SSB. Side-by-side analysis of the catalytic efficiency of the ATPase activity of each enzyme revealed that (−)scDNA and ssDNA are potent stimulators of the ATPase activity of RecG but not for RuvAB, whereas relaxed circular DNA is a poor cofactor for RecG but an excellent one for RuvAB. Collectively, these data suggest that the timing of repair protein access to the DNA at stalled forks is determined by the nature of the DNA available at the fork. We propose that RecG acts first, with RuvAB acting either after RecG or in a separate pathway following protein-independent fork regression