Search results for "Replica"
showing 10 items of 576 documents
Overcoming drug resistance in HSV, CMV, HBV and HCV infection.
2015
Although vaccination has provided as a very efficient preventive tool, antiviral therapy is still needed to control viral infections not avoidable by prophylaxis with vaccines; those caused by viruses for which a vaccine is available, but vaccination is not universally implemented or does not result in complete, long-term protection; and in immunocompromised individuals with reduced immune control of viral replication. After more than 50 years of the first licensing for an antiherpetic drug, novel compounds for herpes-simplex viruses and human cytomegalovirus will open new strategies for better control and management of these two recurrent viral infections. Besides, the development and use…
Chronic hepatitis B: who to treat and which choice of treatment?
2009
The goal of antiviral therapy in patients with chronic hepatitis B is to prevent, through persistent suppression of HBV replication, cirrhosis and hepatocellular carcinoma. Currently, seven drugs are available: IFN-alpha, pegylated interferon, lamivudine, adefovir dipivoxil, entecavir, telbivudine and tenofovir. The choice of the drugs should always take into consideration the clinical features of patients, the antiviral efficacy of each drug, the risk of developing resistance, the long-term safety profile, the method of administration and the cost of therapy. Ideal candidates for treatment are hepatitis B e antigen-positive patients with a prolonged phase of immune clearance and hepatitis …
Evolutionary history conditions the timing of transmission in vesicular stomatitis virus.
2001
It has been postulated that early transmitted viruses would evolve to be more virulent than late transmitted ones. The reason for this prediction is that early transmission selects for rapid viral replication and, consequently, rapid host death, whereas late transmission would select for slow-replicating viruses that permit longer survival to the host. To test this prediction, experimental lineages of vesicular stomatitis virus (VSV) had been adapted to three different transmission dynamics during more than 100 generations. Transmission dynamic differed in the stage of infection at which transmission took place: early, intermediate or late. Regardless the timing of transmission imposed duri…
Investing for the Long Run
2017
This paper studies long term investing by an investor that maximizes either expected utility from terminal wealth or from consumption. We introduce the concepts of a generalized stochastic discount factor (SDF) and of the minimum price to attain target payouts. The paper finds that the dynamics of the SDF needs to be captured and not the entire market dynamics, which simplifies significantly practical implementations of optimal portfolio strategies. We pay particular attention to the case where the SDF is equal to the inverse of the growth-optimal portfolio in the given market. Then, optimal wealth evolution is closely linked to the growth optimal portfolio. In particular, our concepts allo…
Yet Another Note on the Leland's Option Hedging Strategy with Transaction Costs
2005
In a market with transaction costs the option hedging is costly. The idea presented by Leland (1985) was to include the expected transaction costs in the cost of a replicating portfolio. The resulting Leland's pricing and hedging method is an adjusted Black-Scholes method where one uses a modified volatility in the Black-Scholes formulas for the option price and delta. The Leland's method has been criticized on different grounds. Despite the critique, the risk-return tradeoff of the Leland's strategy is often better than that of the Black-Scholes strategy even in the case when a hedger starts with the same initial value of a replicating portfolio. This implies that the Leland's modification…
Mitochondrial DNA Replication in Health and Disease
2011
Mitochondria are dynamic, semi-autonomous organelles that play a diverse role in cellular physiopathology, being involved in bioenergetics, ROS generation/signaling and redox balance, β-oxidation of free fatty acids, Ca2+ homeostasis, thermogenesis, and essential anabolic pathways (fatty acids, cholesterol, urea, haem and bile acids). They contain their own, mitochondrial DNA (mtDNA) which is one of the main points in favor of the hypothesis of the endosymbiotic origin of these organelles (Lang et al., 1999). The human mitochondrial genome, a 16.5 kb circular DNA consisting of a heavy and a light chain, contains 37 genes, 13 of which encode proteins involved in the mitochondrial electron tr…
Effect of ATP Binding and Hydrolysis on Dynamics of Canine Parvovirus NS1▿ †
2010
ABSTRACT The replication protein NS1 is essential for genome replication and protein production in parvoviral infection. Many of its functions, including recognition and site-specific nicking of the viral genome, helicase activity, and transactivation of the viral capsid promoter, are dependent on ATP. An ATP-binding pocket resides in the middle of the modular NS1 protein in a superfamily 3 helicase domain. Here we have identified key ATP-binding amino acid residues in canine parvovirus (CPV) NS1 protein and mutated amino acids from the conserved A motif (K406), B motif (E444 and E445), and positively charged region (R508 and R510). All mutations prevented the formation of infectious viruse…
Cis autocatalytic cleavage of glycine-linked Zika virus NS2B-NS3 protease constructs.
2019
The flaviviral heterodimeric serine protease NS2B-NS3, consisting of the NS3 protease domain and the NS2B co-factor, is essential for ZIKA virus maturation and replication in cells. For in vitro studies a 'linked' construct, where a polyglycine linker connects NS2BCF and NS3pro , is often used. This construct undergoes autocatalytic cleavage. Here, we show that linked ZIKV NS2BCF -NS3pro is cleaved in cis in the NS2BCF exclusively at position R95 and not at the previously proposed alternate cleavage site at residue R29 in the NS3pro . Cleavage neither affects protease stability nor activity, despite some observed differences in spectroscopic behavior. This minimally modified construct may t…
Genomic determinants of protein folding thermodynamics in prokaryotic organisms.
2004
Here we investigate how thermodynamic properties of orthologous proteins are influenced by the genomic environment in which they evolve. We performed a comparative computational study of 21 protein families in 73 prokaryotic species and obtained the following main results. (i) Protein stability with respect to the unfolded state and with respect to misfolding are anticorrelated. There appears to be a trade-off between these two properties, which cannot be optimized simultaneously. (ii) Folding thermodynamic parameters are strongly correlated with two genomic features, genome size and G+C composition. In particular, the normalized energy gap, an indicator of folding efficiency in statistical…
Candidate Targets for Hepatitis C Virus-Specific Antiviral Therapy
1997
The hepatitis C virus (HCV) was identified as the major causative agent of posttransfusion and community-acquired non-A, non-B hepatitis throughout the world. It is an enveloped virus with a plus-strand RNA genome encoding a polyprotein of about 3,010 amino acids. This polyprotein is cleaved co- and posttranslationally into mature viral proteins by host cell signal peptidases and 2 viral enzymes designated the NS2-3 proteinase and the NS3/4A proteinase complex. It is assumed that virus replication takes place in a membrane-associated complex containing at least 2 viral enzymatic activities: the NS3 nucleoside triphosphatase (NTPase)/helicase and the NS5B RNA-dependent RNA polymerase (RdRp).…