Pliocene summer sea surface temperature reconstruction using silicoflagellates from Southern Ocean ODP Site 1165

In the modern marine environment the silicoflagellate genus Dictyocha is rare, or absent, south of the Antarctic polar front (APF); the genus Distephanus, in contrast, is dominant. In sediments recovered from ODP Site 1165, 1600 km south of the front, however, three intervals where Dictyocha is abundant are interpreted to represent Pliocene warm events. Comparison of our data with Ciesielski and Weaver’s [1974] modern core top silicoflagellate relationship with sea surface temperature (SST) indicates that at Site 1165 mean annual SST was approximately 5C at 3.7 Ma (event I), and approximately 4C at 4.3–4.4 Ma (event II) and 4.55–4.8 Ma (event III). Event I represents a 5.5C warming, and events II and III represents a 4.5C warming relative to modern mean annual SST. Dictyocha is absent from other Site 1165 Pliocene intervals, which suggests that cooler SST

Probability of Detection Study for Visual Inspection of Steel Bridges: Volume 2—Full Project Report

An inspector’s ability to correctly identify surface and internal defects in steel bridge components is critical to protecting public safety. Ensuring that inspectors are properly trained and adequately equipped to detect these defects in locations that are difficult to access and/or in unfavorable environmental conditions must be a high priority. While the Federal Highway Administration and individual state departments of transportation have guidelines for inspector qualifications, trainings, and certifications, there is very little emphasis placed on evaluating or “testing: a given inspector’s capability to characterize defects in the field. As a result, there is also very little, if any, data on how well a given inspector actually performs or the variability which can be expected between inspectors. This comprehensive Probability of Detection (POD) study was conducted to establish the ability of an inspector with the current required training to locate and quantify cracks in steel bridge components. This study is believed to be the first statistically-significant study of its kind in the United States

Probability of Detection Study for Visual Inspection of Steel Bridges: Volume 1—Executive Summary

An inspector’s ability to correctly identify surface and internal defects in steel bridge components is critical to protecting public safety. Ensuring that inspectors are properly trained and adequately equipped to detect these defects in locations that are difficult to access and/or in unfavorable environmental conditions must be a high priority. While the Federal Highway Administration and individual state departments of transportation have guidelines for inspector qualifications, trainings, and certifications, there is very little emphasis placed on evaluating or “testing” a given inspector’s capability to characterize detect defects in the field. As a result, there is also very little if any data on how well a given inspector actually performs or the variability which can be expected between various inspectors. This comprehensive Probability of Detection (POD) study was conducted to establish the ability of an inspector with the current required training to locate cracks in steel bridge components using typical visual inspection techniques

Jorge R. Navas (1921-2009)

Con el fallecimiento del Dr. Jorge R. Navas, ocurrido el 12 de septiembre de 2009 en la localidad bonaerense de Temperley, desaparece no solo un nombre fundamental de la ornitología argentina sino también un verdadero pionero de esta rama de la biología en el ámbito latinoamericano. Todos los que trabajamos en aves durante las últimas décadas del siglo XX sentimos que se nos fue un referente fundamental, a quien recurríamos en forma constante para aclarar dudas o para solicitar una opinión autorizada.Facultad de Ciencias Naturales y Muse

Differential engulfment of Staphylococcus aureus and Pseudomonas aeruginosa by monocyte-derived macrophages is associated with altered phagocyte biochemistry and morphology

Knowledge of changes in macrophages following bacterial engulfment is limited. U937-derived macrophages were incubated with Staphylococcus aureus or Pseudomonas aeruginosa. Morphological and biochemical changes in macrophages following host-pathogen interactions were visualized using Scanning Electron Microscopy (SEM) and Fourier-Transform Infrared Spectroscopy (FTIR) respectively. Principal Component Analysis (PCA) was used to assess the variability in the FTIR spectra. Following host-pathogen interactions, survival of S. aureus was significantly lower than P. aeruginosa (P 99 % of variability in the FTIR spectra explained by the first two principal components. These findings demonstrated that there were clear morphological and biochemical changes in macrophages following engulfment of two different bacterial types suggesting that the biochemical components of the bacterial cell wall influenced the biochemical characteristics and hence the morphology of macrophages in distinct ways

Multifunctional Roles for the PH Domain of Dbs in Regulating Rho GTPase Activation

Dbl family members are guanine nucleotide exchange factors specific for Rho guanosine triphosphatases (GTPases) and invariably possess tandem Dbl (DH) and pleckstrin homology (PH) domains. Dbs, a Dbl family member specific for Cdc42 and RhoA, exhibits transforming activity when overexpressed in NIH 3T3 mouse fibroblasts. In this study, the PH domain of Dbs was mutated to impair selectively either guanine nucleotide exchange or phosphoinositide binding in vitro and resulting physiological alterations were assessed. As anticipated, substitution of residues within the PH domain of Dbs integral to the interface with GTPases reduced nucleotide exchange and eliminated the ability of Dbs to transform NIH 3T3 cells. More interestingly, substitutions within the PH domain that prevent interaction with phosphoinositides yet do not alter in vitro activation of GTPases also do not transform NIH 3T3 cell and fail to activate RhoA in vivo despite proper subcellular localization. Therefore, the PH domain of Dbs serves multiple roles in the activation of GTPases and cannot be viewed as a simple membrane-anchoring device. In particular, the data suggest that binding of phosphoinositides to the PH domain within the context of membrane surfaces may direct orientations or conformations of the linked DH and PH domains to regulate GTPases activation

Contesting the psychiatric framing of ME / CFS

ME/CFS is a medically contested illness and its understanding, framing and treatment has been the subject of heated debate. This paper examines why framing the condition as a psychiatric issue—what we refer to as ‘psychiatrisation’—has been so heavily contested by patients and activists. We argue that this contestation is not simply about stigmatising mental health conditions, as some have suggested, but relates to how people diagnosed with mental illness are treated in society, psychiatry and the law. We highlight the potentially harmful consequences of psychiatrisation which can lead to people’s experiential knowledge being discredited. This stems, in part, from a psychiatric-specific form of ‘epistemic injustice’ which can result in unhelpful, unwanted and forced treatments. This understanding helps explain why the psychiatrisation of ME/CFS has become the focus of such bitter debate and why psychiatry itself has become such a significant field of contention, for both ME/CFS patients and mental health service users/survivors. Notwithstanding important differences, both reject the way psychiatry denies patient explanations and understandings, and therefore share a collective struggle for justice and legitimation. Reasons why this shared struggle has not resulted in alliances between ME and mental health activists are noted

Ecological Modeling of Aedes aegypti (L.) Pupal Production in Rural Kamphaeng Phet, Thailand

Background - Aedes aegypti (L.) is the primary vector of dengue, the most important arboviral infection globally. Until an effective vaccine is licensed and rigorously administered, Ae. aegypti control remains the principal tool in preventing and curtailing dengue transmission. Accurate predictions of vector populations are required to assess control methods and develop effective population reduction strategies. Ae. aegypti develops primarily in artificial water holding containers. Release recapture studies indicate that most adult Ae. aegypti do not disperse over long distances. We expect, therefore, that containers in an area of high development site density are more likely to be oviposition sites and to be more frequently used as oviposition sites than containers that are relatively isolated from other development sites. After accounting for individual container characteristics, containers more frequently used as oviposition sites are likely to produce adult mosquitoes consistently and at a higher rate. To this point, most studies of Ae. aegypti populations ignore the spatial density of larval development sites. Methodology - Pupal surveys were carried out from 2004 to 2007 in rural Kamphaeng Phet, Thailand. In total, 84,840 samples of water holding containers were used to estimate model parameters. Regression modeling was used to assess the effect of larval development site density, access to piped water, and seasonal variation on container productivity. A varying-coefficients model was employed to account for the large differences in productivity between container types. A two-part modeling structure, called a hurdle model, accounts for the large number of zeroes and overdispersion present in pupal population counts. Findings - The number of suitable larval development sites and their density in the environment were the primary determinants of the distribution and abundance of Ae. aegypti pupae. The productivity of most container types increased significantly as habitat density increased. An ecological approach, accounting for development site density, is appropriate for predicting Ae. aegypti population levels and developing efficient vector control program

Modeling Mechanisms of In Vivo Variability in Methotrexate Accumulation and Folate Pathway Inhibition in Acute Lymphoblastic Leukemia Cells

Methotrexate (MTX) is widely used for the treatment of childhood acute lymphoblastic leukemia (ALL). The accumulation of MTX and its active metabolites, methotrexate polyglutamates (MTXPG), in ALL cells is an important determinant of its antileukemic effects. We studied 194 of 356 patients enrolled on St. Jude Total XV protocol for newly diagnosed ALL with the goal of characterizing the intracellular pharmacokinetics of MTXPG in leukemia cells; relating these pharmacokinetics to ALL lineage, ploidy and molecular subtype; and using a folate pathway model to simulate optimal treatment strategies. Serial MTX concentrations were measured in plasma and intracellular MTXPG concentrations were measured in circulating leukemia cells. A pharmacokinetic model was developed which accounted for the plasma disposition of MTX along with the transport and metabolism of MTXPG. In addition, a folate pathway model was adapted to simulate the effects of treatment strategies on the inhibition of de novo purine synthesis (DNPS). The intracellular MTXPG pharmacokinetic model parameters differed significantly by lineage, ploidy, and molecular subtypes of ALL. Folylpolyglutamate synthetase (FPGS) activity was higher in B vs T lineage ALL (p<0.005), MTX influx and FPGS activity were higher in hyperdiploid vs non-hyperdiploid ALL (p<0.03), MTX influx and FPGS activity were lower in the t(12;21) (ETV6-RUNX1) subtype (p<0.05), and the ratio of FPGS to γ-glutamyl hydrolase (GGH) activity was lower in the t(1;19) (TCF3-PBX1) subtype (p<0.03) than other genetic subtypes. In addition, the folate pathway model showed differential inhibition of DNPS relative to MTXPG accumulation, MTX dose, and schedule. This study has provided new insights into the intracellular disposition of MTX in leukemia cells and how it affects treatment efficacy

In Vivo Comparison of Two Human Norovirus Surrogates for Testing Ethanol-Based Handrubs: The Mouse Chasing the Cat!

Human noroviruses (HuNoV), a major cause of acute gastroenteritis worldwide, cannot be readily cultured in the lab. Therefore, a feline calicivirus (FCV) is often used as its surrogate to, among other things, test alcohol-based handrubs (ABHR). The more recent laboratory culture of a mouse norovirus (MNV) provides an alternative. While MNV is closer to HuNoV in several respects, to date, no comparative testing of FCV and MNV survival and inactivation on human hands has been performed. This study was designed to address the knowledge gap. The rates of loss in viability during drying on hands were −1.91 and −1.65% per minute for FCV and MNV, respectively. When the contaminated skin was exposed for 20 s to either a commercial ABHR with 62% (v/v) ethanol or to 75% (v/v) ethanol in water, FCV infectivity was reduced by <1 log10 while that of MNV by nearly 2.8 log10. Extending the contact time to 30 s reduced the FCV titer by almost 2 log10 by both test substances and that of MNV by >3.5 log10 by the commercial ABHR while 75% ethanol did not show any noticeable improvement in activity as compared to the 20 s contact. An 80% (v/v) aqueous solution of ethanol gave only a 1.75 log10 reduction in MNV activity after 20 s. The results show significant differences in the ethanol susceptibility of FCV and MNV in contact times relevant to field use of ABHR and also that 62% ethanol was a more effective virucide than either 75% or 80% ethanol. These findings indicate the need for a review of the continuing use of FCV as a surrogate for HuNoV