Endovascular repair of type B aortic dissection: a study by computational fluid dynamics

Aortic dissection is a dangerous pathological condi-tion where blood intrudes into the layers of the arte-rial walls, creating an artificial channel (false lumen). In the absence of thrombosis or surgical intervention, blood will enter the false lumen through the proximal tear, and join the true lumen again through a distal tear. Rupture of the weakened outer wall will result in extremely high mortality rates. Type B thoracic aortic dissection (TAD), occurring along the de-scending aorta, can be repaired surgically by the de-ployment of an endovascular stent graft, concealing the proximal entry tear. Blood might still flow into the false lumen (FL) through the distal tear. The do-main of such flow should be minimized, as complete thrombosis of the FL is generally believed to be more beneficial for the patient. The dependence on the area ratios of the lumens and size of these tears is studied by computational fluid dynamics.published_or_final_versio

Successful endovascular infrarenal aneurysm repair in a patient with situs inversus totalis

Situs inversus totalis is a rare autosomal recessive developmental anomaly. There are very few reports in the published literature of abdominal aortic aneurysm in patient with situs inversus totalis, all of whom underwent open aneurysm repair. This is the first case in the world's literature to describe a patient with situs inversus totalis who had a successful endovascular infrarenal aneurysm repair. Although endovascular infrarenal aneurysm repair should not be more challenging, the endovascular approach may decrease risk of potential errors because of unfamiliar anatomy. Technical considerations in performing endovascular procedures in patients with situs inversus totalis are discussed in this article. © Annals of Vascular Surgery Inc.postprin

Wavelength-multiplexed duplex transceiver based on III-V/Si hybrid integration for off-chip and on-chip optical interconnects

A six-channel wavelength-division-multiplexed optical transceiver with a compact footprint of 1.5 x 0.65 mm(2) for off-chip and on-chip interconnects is demonstrated on a single silicon-on-insulator chip. An arrayed waveguide grating is used as the (de)multiplexer, and III-V electroabsorption sections fabricated by hybrid integration technology are used as both modulators and detectors, which also enable duplex links. The 30-Gb/s capacity for each of the six wavelength channels for the off-chip transceiver is demonstrated. For the on-chip interconnect, an electrical-to-electrical 3-dB bandwidth of 13 GHz and a data rate of 30 Gb/s per wavelength are achieved

Determination of the number of J/ψ events with J/ψ → inclusive decays

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Two-photon widths of the χ c0,2 states and helicity analysis for χ c2→γγ

Based on a data sample of 106×106 ψ ′ events collected with the BESIII detector, the decays ψ ′→γχ c0,2, χ c0,2→γγ are studied to determine the two-photon widths of the χ c0,2 states. The two-photon decay branching fractions are determined to be B(χ c0→γγ)=(2. 24±0.19±0.12±0.08)×10 -4 and B(χ c2→γγ)=(3.21±0.18±0. 17±0.13)×10 -4. From these, the two-photon widths are determined to be Γ γγ(χ c0)=(2. 33±0.20±0.13±0.17)keV, Γ γγ(χ c2)=(0.63±0.04±0. 04±0.04)keV, and R=Γ γγ(χ c2)/ Γ γγ(χ c0)=0.271±0. 029±0.013±0.027, where the uncertainties are statistical, systematic, and those from the PDG B(ψ ′→γχ c0,2) and Γ(χ c0,2) errors, respectively. The ratio of the two-photon widths for helicity λ=0 and helicity λ=2 components in the decay χ c2→γγ is measured for the first time to be f 0/2=Γγγλ= 0(χ c2)/Γγγλ=2(χ c2)=0. 00±0.02±0.02. © 2012 American Physical Society.published_or_final_versio

Association of HLA-A, B, DRB1 alleles and haplotypes with HIV-1 infection in Chongqing, China

<p>Abstract</p> <p>Background</p> <p>The human immunodeficiency virus type 1(HIV-1) epidemic in Chongqing, China, is increasing rapidly with the dominant subtype of CRF07_BC over the past 3 years. Since human leukocyte antigen (HLA) polymorphisms have shown strong association with susceptibility/resistance to HIV-1 infection from individuals with different ethnic backgrounds, a recent investigation on frequencies of HLA class I and class II alleles in a Chinese cohort also indicated that similar correlation existed in HIV infected individuals from several provinces in China, however, such information is unavailable in Chongqing, southwest China.</p> <p>Methods</p> <p>In this population-based study, we performed polymerase chain reaction analysis with sequence-specific oligonucleotide probes (PCR-SSOP) for intermediate-low-resolution HLA typing in a cohort of 549 HIV-1 infected individuals, another 2475 healthy subjects from the Han nationality in Chongqing, China, were selected as population control. We compared frequencies of HLA-A, B, DRB1 alleles, haplotypes and genotypes between the two groups, and analyzed their association with HIV-1 susceptibility or resistance.</p> <p>Results</p> <p>The genetic profile of HLA (A, B, DRB1) alleles of HIV-1 infected individuals from Chongqing Han of China was obtained. Several alleles of HLA-B such as B*46 (P = 0.001, OR = 1.38, 95%CI = 1.13-1.68), B*1501G(B62) (P = 0.013, OR = 1.42, 95%CI = 1.08-1.88), B*67 (P = 0.022, OR = 2.76, 95%CI = 1.16-6.57), B*37 (P = 0.014, OR = 1.93, 95%CI = 1.14-3.28) and B*52 (P = 0.038, OR = 1.64, 95%CI = 1.03-2.61) were observed to have association with susceptibility to HIV-1 infection in this population. In addition, the haplotype analysis revealed that A*11-B*46, A*24-B*54 and A*01-B*37 for 2-locus, and A*11-B*46-DRB1*09, A*02-B*46-DRB1*08, A*11-B*4001G-DRB1*15, A*02-B*4001G-DRB1*04, A*11-B*46-DRB1*08 and A*02-B*4001G-DRB1*12 for 3-locus had significantly overrepresented in HIV-1 infected individuals, whereas A*11-B*1502G, A*11-B*1502G-DRB1*12 and A*33-B*58-DRB1*13 were underrepresented. However, the low-resolution homozygosity of HLA-A, B, DRB1 loci and HLA-Bw4/Bw6 genotypes did not differ significantly between the two groups.</p> <p>Conclusion</p> <p>These results may contribute to the database of HLA profiles in HIV-1 infected Chinese population, consequently, the association of certain HLA alleles with susceptibility or resistance to HIV-1 infection would provide with clues in choosing proper preventive strategies against HIV-1 infection and developing effective HIV-1 vaccines in Chinese population, especially for those in southwest China.</p

Inhibition of Enterovirus 71 (EV-71) Infections by a Novel Antiviral Peptide Derived from EV-71 Capsid Protein VP1

Enterovirus 71 (EV-71) is the main causative agent of hand, foot and mouth disease (HFMD). In recent years, EV-71 infections were reported to cause high fatalities and severe neurological complications in Asia. Currently, no effective antiviral or vaccine is available to treat or prevent EV-71 infection. In this study, we have discovered a synthetic peptide which could be developed as a potential antiviral for inhibition of EV-71. Ninety five synthetic peptides (15-mers) overlapping the entire EV-71 capsid protein, VP1, were chemically synthesized and tested for antiviral properties against EV-71 in human Rhabdomyosarcoma (RD) cells. One peptide, SP40, was found to significantly reduce cytopathic effects of all representative EV-71 strains from genotypes A, B and C tested, with IC50 values ranging from 6–9.3 µM in RD cells. The in vitro inhibitory effect of SP40 exhibited a dose dependent concentration corresponding to a decrease in infectious viral particles, total viral RNA and the levels of VP1 protein. The antiviral activity of SP40 peptide was not restricted to a specific cell line as inhibition of EV-71 was observed in RD, HeLa, HT-29 and Vero cells. Besides inhibition of EV-71, it also had antiviral activities against CV-A16 and poliovirus type 1 in cell culture. Mechanism of action studies suggested that the SP40 peptide was not virucidal but was able to block viral attachment to the RD cells. Substitutions of arginine and lysine residues with alanine in the SP40 peptide at positions R3A, R4A, K5A and R13A were found to significantly decrease antiviral activities, implying the importance of positively charged amino acids for the antiviral activities. The data demonstrated the potential and feasibility of SP40 as a broad spectrum antiviral agent against EV-71

Direct Binding of a Hepatitis C Virus Inhibitor to the Viral Capsid Protein

Over 130 million people are infected chronically with hepatitis C virus (HCV), which, together with HBV, is the leading cause of liver disease. Novel small molecule inhibitors of Hepatitis C virus (HCV) are needed to complement or replace current treatments based on pegylated interferon and ribavirin, which are only partially successful and plagued with side-effects. Assembly of the virion is initiated by the oligomerization of core, the capsid protein, followed by the interaction with NS5A and other HCV proteins. By screening for inhibitors of core dimerization, we previously discovered peptides and drug-like compounds that disrupt interactions between core and other HCV proteins, NS3 and NS5A, and block HCV production. Here we report that a biotinylated derivative of SL209, a prototype small molecule inhibitor of core dimerization (IC50 of 2.80 µM) that inhibits HCV production with an EC50 of 3.20 µM, is capable of penetrating HCV-infected cells and tracking with core. Interaction between the inhibitors, core and other viral proteins was demonstrated by SL209–mediated affinity-isolation of HCV proteins from lysates of infected cells, or of the corresponding recombinant HCV proteins. SL209-like inhibitors of HCV core may form the basis of novel treatments of Hepatitis C in combination with other target-specific HCV drugs such as inhibitors of the NS3 protease, the NS5B polymerase, or the NS5A regulatory protein. More generally, our work supports the hypothesis that inhibitors of viral capsid formation might constitute a new class of potent antiviral agents, as was recently also shown for HIV capsid inhibitors

Discovery of a Non-Peptidic Inhibitor of West Nile Virus NS3 Protease by High-Throughput Docking

An estimated 2.5 billion people are at risk of diseases caused by dengue and West Nile virus. As of today, there are neither vaccines to prevent nor drugs to cure the severe infections caused by these viruses. The NS3 protease is one of the most promising targets for drug development against West Nile virus because it is an essential enzyme for viral replication and because success has been demonstrated with the closely related hepatitis C virus protease. We have discovered a small molecule that inhibits the NS3 protease of West Nile virus by computer-aided high-throughput docking, and validated it using three experimental techniques. The inhibitor has potential to be developed to a drug candidate to combat West Nile virus infections