The effect of S-substitution at the O6-guanine site on the structure and dynamics of a DNA oligomer containing a G:T mismatch

The effect of S-substitution on the O6 guanine site of a 13-mer DNA duplex containing a G:T mismatch is studied using molecular dynamics. The structure, dynamic evolution and hydration of the S-substituted duplex are compared with those of a normal duplex, a duplex with Ssubstitution on guanine, but no mismatch and a duplex with just a G:T mismatch. The S-substituted mismatch leads to cell death rather than repair. One suggestion is that the G:T mismatch recognition protein recognises the S-substituted mismatch (GS:T) as G:T. This leads to a cycle of futile repair ending in DNA breakage and cell death. We find that some structural features of the helix are similar for the duplex with the G:T mismatch and that with the S-substituted mismatch, but differ from the normal duplex, notably the helical twist. These differences arise from the change in the hydrogen-bonding pattern of the base pair. However a marked feature of the S-substituted G:T mismatch duplex is a very large opening. This showed considerable variability. It is suggested that this enlarged opening would lend support to an alternative model of cell death in which the mismatch protein attaches to thioguanine and activates downstream damage-response pathways. Attack on the sulphur by reactive oxygen species, also leading to cell death, would also be aided by the large, variable opening

Uniform regularity for the Navier-Stokes equation with Navier boundary condition

We prove that there exists an interval of time which is uniform in the vanishing viscosity limit and for which the Navier-Stokes equation with Navier boundary condition has a strong solution. This solution is uniformly bounded in a conormal Sobolev space and has only one normal derivative bounded in $L^\infty$. This allows to get the vanishing viscosity limit to the incompressible Euler system from a strong compactness argument

Viral genotype correlates with distinct liver gene transcription signatures in chronic hepatitis C virus infection

BACKGROUND: Chronic hepatitis C virus (HCV) infection of the liver with either genotype 1 or genotype 3 gives rise to distinct pathologies, and the two viral genotypes respond differently to antiviral therapy. METHODS: To understand these clinical differences, we compared gene transcription profiles in liver biopsies from patients infected with either gt1 or gt3, and uninfected controls. RESULTS: Gt1-infected biopsies displayed elevated levels of transcripts regulated by type I and type III interferons (IFN), including genes that predict response to IFN-α therapy. In contrast, genes controlled by IFN-γ were induced in gt3-infected biopsies. Moreover, IFN-γ levels were higher in gt3-infected biopsies. Analysis of hepatocyte-derived cell lines confirmed that the genes upregulated in gt3 infection were preferentially induced by IFN-γ. The transcriptional profile of gt3 infection was unaffected by IFNL4 polymorphisms, providing a rationale for the reduced predictive power of IFNL genotyping in gt3-infected patients. CONCLUSIONS: The interactions between HCV genotypes 1 and 3 and hepatocytes are distinct. These unique interactions provide avenues to explore the biological mechanisms that drive viral genotype-specific differences in disease progression and treatment response. A greater understanding of the distinct host-pathogen interactions of the different HCV genotypes is required to facilitate optimal management of HCV infection

The Inviscid Limit and Boundary Layers for Navier-Stokes Flows

The validity of the vanishing viscosity limit, that is, whether solutions of the Navier-Stokes equations modeling viscous incompressible flows converge to solutions of the Euler equations modeling inviscid incompressible flows as viscosity approaches zero, is one of the most fundamental issues in mathematical fluid mechanics. The problem is classified into two categories: the case when the physical boundary is absent, and the case when the physical boundary is present and the effect of the boundary layer becomes significant. The aim of this article is to review recent progress on the mathematical analysis of this problem in each category.Comment: To appear in "Handbook of Mathematical Analysis in Mechanics of Viscous Fluids", Y. Giga and A. Novotn\'y Ed., Springer. The final publication is available at http://www.springerlink.co

Quasar accretion disk sizes from continuum reverberation mapping in the DES standard-star fields

Measurements of the physical properties of accretion disks in active galactic nuclei are important for better understanding the growth and evolution of supermassive black holes. We present the accretion disk sizes of 22 quasars from continuum reverberation mapping with data from the Dark Energy Survey (DES) standard star fields and the supernova C fields. We construct continuum lightcurves with the \textit{griz} photometry that span five seasons of DES observations. These data sample the time variability of the quasars with a cadence as short as one day, which corresponds to a rest frame cadence that is a factor of a few higher than most previous work. We derive time lags between bands with both JAVELIN and the interpolated cross-correlation function method, and fit for accretion disk sizes using the JAVELIN Thin Disk model. These new measurements include disks around black holes with masses as small as $\sim10^7$ $M_{\odot}$, which have equivalent sizes at 2500\AA \, as small as $\sim 0.1$ light days in the rest frame. We find that most objects have accretion disk sizes consistent with the prediction of the standard thin disk model when we take disk variability into account. We have also simulated the expected yield of accretion disk measurements under various observational scenarios for the Large Synoptic Survey Telescope Deep Drilling Fields. We find that the number of disk measurements would increase significantly if the default cadence is changed from three days to two days or one day.Comment: 33 pages, 24 figure

Mammography Services Quality Assurance: Baseline Standards for Latin America and the Caribbean

Fil: Barr, Helen. No especifíca;Fil: Blanco, Susana Alicia Ana. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Ministerio de Salud. Instituto Nacional del Cáncer; ArgentinaFil: Butler, Priscilla. No especifíca;Fil: da Paz, María Angela. No especifíca;Fil: Fleitas, Ileana. No especifíca;Fil: Craig, George. No especifíca;Fil: Jimenez, Pablo. No especifíca;Fil: Luciani, Silvana. No especifíca;Fil: Manrique, Javier. No especifíca;Fil: Mazal, Jonathan. No especifíca;Fil: Medlen, Kayiba. No especifíca;Fil: MIller, Colie. No especifíca;Fil: Mora, Patricia. No especifíca;Fil: Valdez Moreno, Martha Elena. No especifíca;Fil: Mosodeen, Murrie. No especifíca;Fil: Mysler, Gustavo. No especifíca;Fil: Nuche-Berenguer, Bernardo. No especifíca;Fil: Pastel, Mary. No especifíca;Fil: Pinochet, Miguel. No especifíca;Fil: Sisney, Gale. No especifíca;Fil: Ruiz Trejo, Cesar. No especifíca;Fil: Saraiya, Mona. No especifíca;Fil: Solis, Esteban. No especifíca;Fil: Swann, Phillip. No especifíca

Uneven focal shoe deterioration in Tourette syndrome.

A 31-year-old single man (AB) sought neuropsychiatric consultation for treatment-resistant motor and vocal tics. He described himself expressing a total of 24 different tics, mainly facial twitches (eye blinking, raising eyebrows, mouth opening, lips licking, stereotyped grimacing) and inappropriate utterances (grunting, throat clearing, sniffing), since the age of 7. There appeared to be no family history of tic disorder. He reported occasional utterance of swear words in contextually inappropriate situations (coprolalia), and the urge to copy other people’s movements (echopraxia). Other tic-associated symptoms included self-injurious behaviours and forced touching of objects. A.B. met both DSM-IV-tr and ICD-10 criteria for Tourette syndrome, and also DSM-IV-tr criteria for attention deficit hyperactivity disorder (combined type) in childhood