A Tight Karp-Lipton Collapse Result in Bounded Arithmetic

Cook and Krajíček [9] have obtained the following Karp-Lipton result in bounded arithmetic: if the theory proves , then collapses to , and this collapse is provable in . Here we show the converse implication, thus answering an open question from [9]. We obtain this result by formalizing in a hard/easy argument of Buhrman, Chang, and Fortnow [3]. In addition, we continue the investigation of propositional proof systems using advice, initiated by Cook and Krajíček [9]. In particular, we obtain several optimal and even p-optimal proof systems using advice. We further show that these p-optimal systems are equivalent to natural extensions of Frege systems

Statin Efficacy and Safety for Lipid Modification in Apparently Healthy Male Military Aircrew

Introduction: Military aircrew men represent an elite group of relatively young, fit, and healthy people. The effectiveness of statin treatment in reducing low-density lipoprotein cholesterol (LDL-C) according to the current National Cholesterol Education Program (NCEP) guidelines, its safety, and compliance in this group of people has not yet been determined. Methods: We prospectively evaluated 84 military aircrew men (mean age 43 Ϯ 7 yr) with LDL-C above the current NCEP guidelines. The patients were divided into two groups according to their coronary risk factors: Group 1, LDL-C goal Ͻ 160 mg ⅐ dL Ϫ1 ; Group 2, LDL-C goal Ͻ 130 mg ⅐ dL Ϫ1 . All patients received statins in addition to therapeutic lifestyle changes and were followed for a mean of 3 Ϯ 1 yr according to a simple flow chart. Lipoprotein levels, liver function tests, creatinine phosphokinase, and subjective adverse reactions were checked periodically. Results: LDL-C significantly declined by 32% (p Ͻ 0.0001) within the first month of treatment and 99% of subjects achieved their LDL-C goal within 114 Ϯ 35 d from statin therapy initiation. The Framingham estimated 10-yr coronary risk showed a reduction at an average of 12 mo after statin therapy initiation from a baseline value of 6.54% to 3.95% (p ϭ 0.003). No subjects were grounded or disqualified from duty, there were no cardiovascular events during follow-up, and compliance to therapy was high [82/84 (98%)]. Discussion: Statin treatment in this highly select, relatively young group of aircrew men significantly and safely lowered LDL-C cholesterol levels

Risk of congenital anomalies in pregnant users of statin drugs

What is already known about this subjectCholesterol is known to be essential for fetal development.Statins, which inhibit cholesterol production, have therefore been considered as potential teratogens and are contraindicated in pregnancy.Data available thus far on the risks of congenital anomalies associated with statin therapy have come from non-analytic postmarketing surveillance studies.Given the increasing use of statins in women of childbearing age, there is a need for a population-based study on the risks of congenital anomalies associated with gestational statin use.What this study addsIn this pharmacoepidemiological study, we determined the risk of congenital anomalies in women who filled prescriptions for statins during the first trimester of pregnancy, compared with women who had stopped statins before pregnancy or those who used fibrates during pregnancy.We found no evidence of an increased risk of fetal anomalies among first-trimester statin users, or any discernable pattern of congenital anomalies among live births.However, in the absence of outcome data on nonlive births, conclusions remain uncertain

A Rapid Flp-In System for Expression of Secreted H5N1 Influenza Hemagglutinin Vaccine Immunogen in Mammalian Cells

Continuing transmissions of highly pathogenic H5N1 viruses in poultry and humans underscores the need for a rapid response to potential pandemic in the form of vaccine. Recombinant technologies for production of immunogenic hemagglutinin (HA) could provide an advantage over the traditional inactivated vaccine manufacturing process. Generation of stably transfected mammalian cells secreting properly folded HA proteins is important for scalable controlled manufacturing.We have developed a Flp-In based 293 stable cell lines through targeted site-specific recombination for expression of secreted hemagglutinin (HA) proteins and evaluated their immunogenicity. H5N1 globular domain HA1(1-330) and HA0(1-500) proteins were purified from the supernatants of 293 Flp-In stable cell lines. Both proteins were properly folded as confirmed by binding to H5N1-neutralizing conformation-dependent human monoclonal antibodies. The HA0 (with unmodified cleavage site) was monomeric, while the HA1 contained oligomeric forms. Upon rabbit immunization, both HA proteins elicited neutralizing antibodies against the homologous virus (A/Vietnam/1203/2004, clade 1) as well as cross-neutralizing antibodies against heterologous H5N1 clade 2 strains, including A/Indonesia/5/2005. These results exceeded the human antibody responses against the inactivated sub-virion H5N1 vaccine.Our data suggest that the 293 Flp-In system could serve as a platform for rapid expression of HA immunogens in mammalian cells from emerging influenza strains

Influenza sequence and epitope database

Influenza epidemics arise through the acquisition of viral genetic changes to overcome immunity from previous infections. An increasing number of complete genomes of influenza viruses have been sequenced in Asia in recent years. Knowledge about the genomes of the seasonal influenza viruses from different countries in Asia is valuable for monitoring and understanding of the emergence, migration and evolution of strains. In order to make full use of the wealth of information from such data, we have developed an integrated user friendly relational database, Influenza Sequence and Epitope Database (ISED), that catalogs the influenza sequence and epitope information obtained in Asia. ISED currently hosts a total of 13 020 influenza A and 2984 influenza B virus sequence data collected in 17 countries including 9 Asian countries, and a total of approximately 545 amantadine-resistant influenza virus sequences collected in Korea. ISED provides users with prebuilt application tools to analyze sequence alignment and different patterns and allows users to visualize epitope-matching structures, which is freely accessible at http://influenza.korea.ac.kr and http://influenza.cdc.go.kr

Isoperimetric Inequalities in Simplicial Complexes

In graph theory there are intimate connections between the expansion properties of a graph and the spectrum of its Laplacian. In this paper we define a notion of combinatorial expansion for simplicial complexes of general dimension, and prove that similar connections exist between the combinatorial expansion of a complex, and the spectrum of the high dimensional Laplacian defined by Eckmann. In particular, we present a Cheeger-type inequality, and a high-dimensional Expander Mixing Lemma. As a corollary, using the work of Pach, we obtain a connection between spectral properties of complexes and Gromov's notion of geometric overlap. Using the work of Gunder and Wagner, we give an estimate for the combinatorial expansion and geometric overlap of random Linial-Meshulam complexes

Comparative analysis of the lambda-interferons IL-28A and IL-29 regarding their transcriptome and their antiviral properties against hepatitis C virus.

Specific differences in signaling and antiviral properties between the different Lambda-interferons, a novel group of interferons composed of IL-28A, IL-28B and IL-29, are currently unknown. This is the first study comparatively investigating the transcriptome and the antiviral properties of the Lambda-interferons IL-28A and IL-29. Expression studies were performed by microarray analysis, quantitative PCR (qPCR), reporter gene assays and immunoluminometric assays. Signaling was analyzed by Western blot. HCV replication was measured in Huh-7 cells expressing subgenomic HCV replicon. All hepatic cell lines investigated as well as primary hepatocytes expressed both IFN-λ receptor subunits IL-10R2 and IFN-λR1. Both, IL-28A and IL-29 activated STAT1 signaling. As revealed by microarray analysis, similar genes were induced by both cytokines in Huh-7 cells (IL-28A: 117 genes; IL-29: 111 genes), many of them playing a role in antiviral immunity. However, only IL-28A was able to significantly down-regulate gene expression (n = 272 down-regulated genes). Both cytokines significantly decreased HCV replication in Huh-7 cells. In comparison to liver biopsies of patients with non-viral liver disease, liver biopsies of patients with HCV showed significantly increased mRNA expression of IL-28A and IL-29. Moreover, IL-28A serum protein levels were elevated in HCV patients. In a murine model of viral hepatitis, IL-28 expression was significantly increased. IL-28A and IL-29 are up-regulated in HCV patients and are similarly effective in inducing antiviral genes and inhibiting HCV replication. In contrast to IL-29, IL-28A is a potent gene repressor. Both IFN-λs may have therapeutic potential in the treatment of chronic HCV

Risk for Infection with Highly Pathogenic Influenza A Virus (H5N1) in Chickens, Hong Kong, 2002

Infection was spread to commercial poultry farms through retail marking of live birds