Finite Element Methods against Limit Equilibrium Approaches for Slope Stability Analysis

A number of powerful numerical models, including limit equilibrium and finite element (FE) methods, have been developed for slope stability analysis in recent decades. The limit equilibrium method contains several limitations, yet is considered the most common approach. However, the advancement of technology has increased the use of the finite element method as it embraces a wider range of features. The limit equilibrium software, SLOPE/W, and the FE program PLAXIS are two common software programs currently employed in geotechnical engineering. Slope analysis using the limit equilibrium method involves a series of slip surfaces dividing ground into vertical slices, and using the static equilibrium equations to calculate the factor of safety (FOS) and stresses for each slice. PLAXIS requires the input of soil properties and elastic-plastic parameters of elements. In this study the properties of a heterogeneous slope, consisting of general fill embankment over soft, slightly overconsolidated clay is implemented in each program. The FOS of slopes is determined for subsequent design requirements, and results are analysed and comparisons are conducted. The effect of Youngâs modulus on the FOS is also discussed. Recommendations are provided based on the results and previously published findings. The contribution of this paper is beneficial to geotechnical engineers, as it discusses the suitability and limitations of each method and assesses reliability of model outputs for slope stability analyses

Alternative antiretroviral monitoring strategies for HIV-infected patients in east Africa: opportunities to save more lives?

<p>Abstract</p> <p>Background</p> <p>Updated World Health Organization guidelines have amplified debate about how resource constraints should impact monitoring strategies for HIV-infected persons on combination antiretroviral therapy (cART). We estimated the incremental benefit and cost effectiveness of alternative monitoring strategies for east Africans with known HIV infection.</p> <p>Methods</p> <p>Using a validated HIV computer simulation based on resource-limited data (USAID and AMPATH) and circumstances (east Africa), we compared alternative monitoring strategies for HIV-infected persons newly started on cART. We evaluated clinical, immunologic and virologic monitoring strategies, including combinations and conditional logic (e.g., only perform virologic testing if immunologic testing is positive). We calculated incremental cost-effectiveness ratios (ICER) in units of cost per quality-adjusted life year (QALY), using a societal perspective and a lifetime horizon. Costs were measured in 2008 US dollars, and costs and benefits were discounted at 3%. We compared the ICER of monitoring strategies with those of other resource-constrained decisions, in particular earlier cART initiation (at CD4 counts of 350 cells/mm³rather than 200 cells/mm³).</p> <p>Results</p> <p>Monitoring strategies employing routine CD4 testing without virologic testing never maximized health benefits, regardless of budget or societal willingness to pay for additional health benefits. Monitoring strategies employing virologic testing conditional upon particular CD4 results delivered the most benefit at willingness-to-pay levels similar to the cost of earlier cART initiation (approximately $2600/QALY). Monitoring strategies employing routine virologic testing alone only maximized health benefits at willingness-to-pay levels (>$4400/QALY) that greatly exceeded the ICER of earlier cART initiation.</p> <p>Conclusions</p> <p>CD4 testing alone never maximized health benefits regardless of resource limitations. Programmes routinely performing virologic testing but deferring cART initiation may increase health benefits by reallocating monitoring resources towards earlier cART initiation.</p

Atrophin-1, the Dentato-Rubral and Pallido-Luysian Atrophy Gene Product, Interacts with Eto/Mtg8 in the Nuclear Matrix and Represses Transcription

Dentato-rubral and pallido-luysian atrophy (DRPLA) is one of the family of neurodegenerative diseases caused by expansion of a polyglutamine tract. The drpla gene product, atrophin-1, is widely expressed, has no known function or activity, and is found in both the nuclear and cytoplasmic compartments of neurons. Truncated fragments of atrophin-1 accumulate in neuronal nuclei in a transgenic mouse model of DRPLA, and may underlie the disease phenotype

The Oncoprotein EVI1 and the DNA Methyltransferase Dnmt3 Co-Operate in Binding and De Novo Methylation of Target DNA

EVI1 has pleiotropic functions during murine embryogenesis and its targeted disruption leads to prenatal death by severely affecting the development of virtually all embryonic organs. However, its functions in adult tissues are still unclear. When inappropriately expressed, EVI1 becomes one of the most aggressive oncogenes associated with human hematopoietic and solid cancers. The mechanisms by which EVI1 transforms normal cells are unknown, but we showed recently that EVI1 indirectly upregulates self-renewal and cell-cycling genes by inappropriate methylation of CpG dinucleotides in the regulatory regions of microRNA-124-3 (miR-124-3), leading to the repression of this small gene that controls normal differentiation and cell cycling of somatic cells. We used the regulatory regions of miR-124-3 as a read-out system to investigate how EVI1 induces de novo methylation of DNA. Here we show that EVI1 physically interacts with DNA methyltransferases 3a and 3b (Dnmt3a/b), which are the only de novo DNA methyltransferases identified to date in mouse and man, and that it forms an enzymatically active protein complex that induces de novo DNA methylation in vitro. This protein complex targets and binds to a precise region of miR-124-3 that is necessary for repression of a reporter gene by EVI1. Based on our findings, we propose that in cooperation with Dnmt3a/b EVI1 regulates the methylation of DNA as a sequence-specific mediator of de novo DNA methylation and that inappropriate EVI1 expression contributes to carcinogenesis through improper DNA methylation

Can Broader Diffusion of Value-Based Insurance Design Increase Benefits from US Health Care without Increasing Costs? Evidence from a Computer Simulation Model

Using a computer simulation based on US data, R. Scott Braithwaite and colleagues calculate the benefits of value-based insurance design, in which patients pay less for highly cost-effective services

Role of CBP and SATB-1 in Aging, Dietary Restriction, and Insulin-Like Signaling

Increased transcriptional complex activity, or pharmacological mimics of increased complex activity, predict lifespan in mice and mediate the protective effects of dietary restriction during aging

Amyloid-Mediated Sequestration of Essential Proteins Contributes to Mutant Huntingtin Toxicity in Yeast

BACKGROUND: Polyglutamine expansion is responsible for several neurodegenerative disorders, among which Huntington disease is the most well-known. Studies in the yeast model demonstrated that both aggregation and toxicity of a huntingtin (htt) protein with an expanded polyglutamine region strictly depend on the presence of the prion form of Rnq1 protein ([PIN+]), which has a glutamine/asparagine-rich domain. PRINCIPAL FINDINGS: Here, we showed that aggregation and toxicity of mutant htt depended on [PIN+] only quantitatively: the presence of [PIN+] elevated the toxicity and the levels of htt detergent-insoluble polymers. In cells lacking [PIN+], toxicity of mutant htt was due to the polymerization and inactivation of the essential glutamine/asparagine-rich Sup35 protein and related inactivation of another essential protein, Sup45, most probably via its sequestration into Sup35 aggregates. However, inhibition of growth of [PIN+] cells depended on Sup35/Sup45 depletion only partially, suggesting that there are other sources of mutant htt toxicity in yeast. CONCLUSIONS: The obtained data suggest that induced polymerization of essential glutamine/asparagine-rich proteins and related sequestration of other proteins which interact with these polymers represent an essential source of htt toxicity

Activation of p38MAPK Contributes to Expanded Polyglutamine-Induced Cytotoxicity

The signaling pathways that may modulate the pathogenesis of diseases induced by expanded polyglutamine proteins are not well understood.Herein we demonstrate that expanded polyglutamine protein cytotoxicity is mediated primarily through activation of p38MAPK and that the atypical PKC iota (PKCiota) enzyme antagonizes polyglutamine-induced cell death through induction of the ERK signaling pathway. We show that pharmacological blockade of p38MAPK rescues cells from polyglutamine-induced cell death whereas inhibition of ERK recapitulates the sensitivity observed in cells depleted of PKCiota by RNA interference. We provide evidence that two unrelated proteins with expanded polyglutamine repeats induce p38MAPK in cultured cells, and demonstrate induction of p38MAPK in an in vivo model of neurodegeneration (spinocerebellar ataxia 1, or SCA-1).Taken together, our data implicate activated p38MAPK in disease progression and suggest that its inhibition may represent a rational strategy for therapeutic intervention in the polyglutamine disorders

Duration of viremia and fecal shedding of the virus in hepatitis A infected children

La infección por el virus de hepatitis A (HAV) es endémica en Argentina. El uso de técnicas moleculares permitió extender la detección del RNA del HAV en suero y heces en pacientes con diferentes presentaciones clínicas. Comparamos la sensibilidad del protocolo de RT-PCR que usamos con cebadores dirigidos a distintas regiones del genoma, resultando la detección de la región VP3 C terminal la más sensible. Se obtuvieron prospectivamente muestras de suero y materia fecal de 20 niños con hepatitis aguda autolimitada por HAV. El RNA del HAV fue detectado en 18/20 niños en muestras basales y en 19/20 sumando una muestra posterior. El RNA del HAV fue detectable en 9/20 pacientes hasta 30 días en suero; en materia fecal en 2/20 hasta 60 días y en 1/20 hasta 90 días. La secuencia genómica para la región VP1/2A en 8 muestras demostró que todas pertenecían al subgenotipo IA, aunque eran diferentes entre sí. Solo en 1/11 niños con falla hepática fulminante fue posible la detección del RNA del HAV utilizando la región VP3 C terminal y el genotipo fue I. La reciente introducción de la vacunación universal en niños de 1 año de edad en Argentina podría disminuir drásticamente la circulación del virus emergiendo nuevas fuentes de infección y permitiendo la introducción de nuevos genotipos. Las técnicas moleculares aplicadas al estudio de la historia natural de la infección y a la vigilancia epidemiológica contribuyen al control y la toma de decisiones eficientes en políticas de Salud Pública.Hepatitis A virus (HAV) infection is endemic in Argentina. Molecular tools have allowed HAV RNA detection to be extent to sera and feces from patients with different clinical backgrounds. We compare the sensitivity of the RT-PCR protocol we follow using primers targeting different genomic regions and VP3 C terminal was the most sensitive. Sequential sera and fecal samples were obtained from 20 children with acute self limited Hepatitis A. HAV RNA was detectable in 18/20 children if sera and stool specimens were collected at the onset of symptoms and in 19/20 if a later sample was considered. HAV RNA was detectable in serum from 9/20 patients until day 30 and in feces from 2 patients until day 60 and until day 90 in one. Genomic sequences from VP1/2A region in 8 samples showed they all belong to subgenotype IA although they were different between them. HAV RNA was detectable only in 1/11 sera from children with acute liver failure when VP3 C terminal fragment was searched and it belonged to genotype I. Universal vaccination in one year old children was recently implemented in Argentina and it will dramatically enable the decrease of the viral circulation, making new sources of infection emerge and allowing the introduction of new genotypes. The application of molecular tools to the study of the natural history of infection and to the epidemiologic surveillance may contribute to efficient control and lead to rational decisions in public health policies.Fil: Munné, María Silvina. ANLIS Dr.C.G.Malbrán. Instituto Nacional de Enfermedades Infecciosas. Laboratorio Nacional de Referencia de Hepatitis Virales; Argentina.Fil: Cañero Velasco, María C. Hospital Municipal del Niño de San Justo. Unidad de Gastroenterología y Hepatología; Argentina.Fil: Moreiro, Rita. Hospital Nacional de Pediatría J. P. Garrahan. Laboratorio; Argentina.Fil: Vladimirsky, Sara. ANLIS Dr.C.G.Malbrán. Instituto Nacional de Enfermedades Infecciosas. Laboratorio Nacional de Referencia de Hepatitis Virales; Argentina.Fil: Otegui, Lucio. ANLIS Dr.C.G.Malbrán. Instituto Nacional de Enfermedades Infecciosas. Laboratorio Nacional de Referencia de Hepatitis Virales; Argentina.Fil: Castro, Raúl. ANLIS Dr.C.G.Malbrán. Instituto Nacional de Enfermedades Infecciosas. Laboratorio Nacional de Referencia de Hepatitis Virales; Argentina.Fil: Brajterman, Leonardo. ANLIS Dr.C.G.Malbrán. Instituto Nacional de Enfermedades Infecciosas. Laboratorio Nacional de Referencia de Hepatitis Virales; Argentina.Fil: Soto, Sonia. ANLIS Dr.C.G.Malbrán. Instituto Nacional de Enfermedades Infecciosas. Laboratorio Nacional de Referencia de Hepatitis Virales; Argentina.Fil: Mutti, Jorge. Hospital Municipal del Niño de San Justo. Unidad de Gastroenterología y Hepatología; Argentina.Fil: Nucifora, Silvia. Hospital Municipal del Niño de San Justo. Unidad de Gastroenterología y Hepatología; Argentina.Fil: Lara, Elena. Hospital Municipal del Niño de San Justo. Laboratorio Central; Argentina.Fil: Sosa, Anibal. Hospital Municipal del Niño de San Justo. Laboratorio Central; Argentina.Fil: Godoy, Patricia. Hospital Municipal del Niño de San Justo. Unidad de Gastroenterología y Hepatología; Argentina.Fil: Ciocca, Mirta. Hospital Nacional de Pediatría J. P. Garrahan. Unidad de Hígado; Argentina.Fil: Cuarterolo, Miriam. Hospital Nacional de Pediatría J. P. Garrahan. Unidad de Hígado; Argentina.Fil: Quarleri, Jorge F. Facultad de Medicina. Centro Nacional de Referencia para el SIDA; Argentina.Fil: González, Jorge E. ANLIS Dr.C.G.Malbrán. Instituto Nacional de Enfermedades Infecciosas. Laboratorio Nacional de Referencia de Hepatitis Virales; Argentina

Duration of viremia and fecal shedding of the virus in hepatitis A infected children

La infección por el virus de hepatitis A (HAV) es endémica en Argentina. El uso de técnicas moleculares permitió extender la detección del RNA del HAV en suero y heces en pacientes con diferentes presentaciones clínicas. Comparamos la sensibilidad del protocolo de RT-PCR que usamos con cebadores dirigidos a distintas regiones del genoma, resultando la detección de la región VP3 C terminal la más sensible. Se obtuvieron prospectivamente muestras de suero y materia fecal de 20 niños con hepatitis aguda autolimitada por HAV. El RNA del HAV fue detectado en 18/20 niños en muestras basales y en 19/20 sumando una muestra posterior. El RNA del HAV fue detectable en 9/20 pacientes hasta 30 días en suero; en materia fecal en 2/20 hasta 60 días y en 1/20 hasta 90 días. La secuencia genómica para la región VP1/2A en 8 muestras demostró que todas pertenecían al subgenotipo IA, aunque eran diferentes entre sí. Solo en 1/11 niños con falla hepática fulminante fue posible la detección del RNA del HAV utilizando la región VP3 C terminal y el genotipo fue I. La reciente introducción de la vacunación universal en niños de 1 año de edad en Argentina podría disminuir drásticamente la circulación del virus emergiendo nuevas fuentes de infección y permitiendo la introducción de nuevos genotipos. Las técnicas moleculares aplicadas al estudio de la historia natural de la infección y a la vigilancia epidemiológica contribuyen al control y la toma de decisiones eficientes en políticas de Salud Pública.Hepatitis A virus (HAV) infection is endemic in Argentina. Molecular tools have allowed HAV RNA detection to be extent to sera and feces from patients with different clinical backgrounds. We compare the sensitivity of the RT-PCR protocol we follow using primers targeting different genomic regions and VP3 C terminal was the most sensitive. Sequential sera and fecal samples were obtained from 20 children with acute self limited Hepatitis A. HAV RNA was detectable in 18/20 children if sera and stool specimens were collected at the onset of symptoms and in 19/20 if a later sample was considered. HAV RNA was detectable in serum from 9/20 patients until day 30 and in feces from 2 patients until day 60 and until day 90 in one. Genomic sequences from VP1/2A region in 8 samples showed they all belong to subgenotype IA although they were different between them. HAV RNA was detectable only in 1/11 sera from children with acute liver failure when VP3 C terminal fragment was searched and it belonged to genotype I. Universal vaccination in one year old children was recently implemented in Argentina and it will dramatically enable the decrease of the viral circulation, making new sources of infection emerge and allowing the introduction of new genotypes. The application of molecular tools to the study of the natural history of infection and to the epidemiologic surveillance may contribute to efficient control and lead to rational decisions in public health policies.Fil: Munné, María Silvina. ANLIS Dr.C.G.Malbrán. Instituto Nacional de Enfermedades Infecciosas. Laboratorio Nacional de Referencia de Hepatitis Virales; Argentina.Fil: Cañero Velasco, María C. Hospital Municipal del Niño de San Justo. Unidad de Gastroenterología y Hepatología; Argentina.Fil: Moreiro, Rita. Hospital Nacional de Pediatría J. P. Garrahan. Laboratorio; Argentina.Fil: Vladimirsky, Sara. ANLIS Dr.C.G.Malbrán. Instituto Nacional de Enfermedades Infecciosas. Laboratorio Nacional de Referencia de Hepatitis Virales; Argentina.Fil: Otegui, Lucio. ANLIS Dr.C.G.Malbrán. Instituto Nacional de Enfermedades Infecciosas. Laboratorio Nacional de Referencia de Hepatitis Virales; Argentina.Fil: Castro, Raúl. ANLIS Dr.C.G.Malbrán. Instituto Nacional de Enfermedades Infecciosas. Laboratorio Nacional de Referencia de Hepatitis Virales; Argentina.Fil: Brajterman, Leonardo. ANLIS Dr.C.G.Malbrán. Instituto Nacional de Enfermedades Infecciosas. Laboratorio Nacional de Referencia de Hepatitis Virales; Argentina.Fil: Soto, Sonia. ANLIS Dr.C.G.Malbrán. Instituto Nacional de Enfermedades Infecciosas. Laboratorio Nacional de Referencia de Hepatitis Virales; Argentina.Fil: Mutti, Jorge. Hospital Municipal del Niño de San Justo. Unidad de Gastroenterología y Hepatología; Argentina.Fil: Nucifora, Silvia. Hospital Municipal del Niño de San Justo. Unidad de Gastroenterología y Hepatología; Argentina.Fil: Lara, Elena. Hospital Municipal del Niño de San Justo. Laboratorio Central; Argentina.Fil: Sosa, Anibal. Hospital Municipal del Niño de San Justo. Laboratorio Central; Argentina.Fil: Godoy, Patricia. Hospital Municipal del Niño de San Justo. Unidad de Gastroenterología y Hepatología; Argentina.Fil: Ciocca, Mirta. Hospital Nacional de Pediatría J. P. Garrahan. Unidad de Hígado; Argentina.Fil: Cuarterolo, Miriam. Hospital Nacional de Pediatría J. P. Garrahan. Unidad de Hígado; Argentina.Fil: Quarleri, Jorge F. Facultad de Medicina. Centro Nacional de Referencia para el SIDA; Argentina.Fil: González, Jorge E. ANLIS Dr.C.G.Malbrán. Instituto Nacional de Enfermedades Infecciosas. Laboratorio Nacional de Referencia de Hepatitis Virales; Argentina