Endometriosis and the neoplastic process

Endometriosis is a frequent disorder that commonly presents with infertility and pelvic pain. Although the precise aetiology of endometriosis is unclear, it is generally considered to involve multiple genetic, environmental, immunological, angiogenic and endocrine processes. Genetic factors have been implicated in endometriosis but the susceptibility genes remain largely unknown. Although endometriosis is a benign disorder, recent studies of endometriosis suggest endometriosis could be viewed as a neoplastic process. Evidence to support this hypothesis includes the increased susceptibility to develop ovarian clear-cell and endometrioid cancers in the presence of endometriosis, and molecular similarities between endometriosis and cancer. In this article we discuss (i) the evidence suggesting that endometriosis might be viewed as a neoplastic process, and (ii) the implications of this hypothesis for elucidating the pathogenesis of endometriosis and developing novel methods of diagnostic classification and individualised treatments.     

Blood donation is an act of benevolence rather than altruism.

Objectives: Blood donation is described as an archetypal altruistic behavior, and recruitment/retention campaigns emphasize altruism. Here, a benevolence hypothesis for blood donation (both the donor and recipient benefit) rather than the altruism hypothesis (only the recipient gains) is proposed. Design: Three United Kingdom-based studies contrasted benevolence and altruism: (a) a 6-month prospective study of blood donor behavior (Study 1: N = 957), (b) a cross-sectional study of blood donors' intentions (Study 2: N = 333), and (c) an experimental study examining the effect of benevolent and altruistic messages on willingness to help across high- and low-cost helping behaviors for committed and noncommitted blood donors (Study 3: N = 200). Main Outcome: Donor behavior and intentions-willingness. Measures: Beliefs in personal and societal benefit (Time 1) and actual donations (Time 2) were assessed in Study 1; beliefs in benevolence, altruism, hedonism, and kinship along with donation intentions were assessed in Study 2; and empathy, donor commitment, and willingness to donate blood, money, fund-raise, and staff a telephone helpline were assessed in Study 3. Results: Beliefs in personal rather than societal benefit predicted actual future donation. A path model showed that only beliefs in benevolence were associated with intentions to donate. Committed blood donors were more willing to donate blood when exposed to a benevolent message rather than an altruistic one. This effect was not observed for other forms of helping. Conclusions: The benevolence hypothesis is supported, suggesting that blood donor motivation is partly selfish. Blood donation campaigns should focus on benevolent rather than purely altruistic messages. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

The UCR Time Series Archive

The UCR time series archive – introduced in 2002, has become an important resource in the time series data mining community, with at least one thousand published papers making use of at least one data set from the archive. The original incarnation of the archive had sixteen data sets but since that time, it has gone through periodic expansions. The last expansion took place in the summer of 2015 when the archive grew from 45 to 85 data sets. This paper introduces and will focus on the new data expansion from 85 to 128 data sets. Beyond expanding this valuable resource, this paper offers pragmatic advice to anyone who may wish to evaluate a new algorithm on the archive. Finally, this paper makes a novel and yet actionable claim: of the hundreds of papers that show an improvement over the standard baseline (1-nearest neighbor classification), a fraction might be mis-attributing the reasons for their improvement. Moreover, the improvements claimed by these papers might have been achievable with a much simpler modification, requiring just a few lines of code.      

Crystal structures of high affinity human T-cell receptors bound to peptide major histocompatibility complex reveal native diagonal binding geometry

Naturally selected T-cell receptors (TCRs) are characterised by low binding affinities, typically in the range 1-100 microM. Crystal structures of syngeneic TCRs bound to peptide major histocompatibility complex (pMHC) antigens exhibit a conserved mode of binding characterised by a distinct diagonal binding geometry, with poor shape complementarity (SC) between receptor and ligand. Here, we report the structures of three in vitro affinity enhanced TCRs that recognise the pMHC tumour epitope NY-ESO(157-165) (SLLMWITQC). These crystal structures reveal that the docking mode for the high affinity TCRs is identical to that reported for the parental wild-type TCR, with only subtle changes in the mutated complementarity determining regions (CDRs) that form contacts with pMHC; both CDR2 and CDR3 mutations act synergistically to improve the overall affinity. Comparison of free and bound TCR structures for both wild-type and a CDR3 mutant reveal an induced fit mechanism arising from restructuring of CDR3 loops which allows better peptide binding. Overall, an increased interface area, improved SC and additional H-bonding interactions are observed, accounting for the increase in affinity. Most notably, there is a marked increase in the SC for the central methionine and tryptophan peptide motif over the native TCR.     

Optical tweezers in a new light

Abstract

Optical tweezers were invented in the mid-1980s by Arthur Ashkin and co-workers at the Bell Telephone Laboratories. Since then there has been a steady stream of developments and applications, particularly in the biological field. In the last five years, work using optical tweezers has increased significantly and they are becoming a mainstream tool within biological and nanotechnological fields. This introductory article seeks to explain the underpinning mechanism behind optical tweezers, present some recent technological advances and speculate on future applications within both biological and non-biological fields.     

Time series shapelets: a novel technique that allows accurate, interpretable and fast classification

Classification of time series has been attracting great interest over the past decade. While dozens of techniques have been introduced, recent empirical evidence has strongly suggested that the simple nearest neighbor algorithm is very difficult to beat for most time series problems, especially for large-scale datasets. While this may be considered good news, given the simplicity of implementing the nearest neighbor algorithm, there are some negative consequences of this. First, the nearest neighbor algorithm requires storing and searching the entire dataset, resulting in a high time and space complexity that limits its applicability, especially on resource-limited sensors. Second, beyond mere classification accuracy, we often wish to gain some insight into the data and to make the classification result more explainable, which global characteristics of the nearest neighbor cannot provide. In this work we introduce a new time series primitive, time series shapelets, which addresses these limitations. Informally, shapelets are time series subsequences which are in some sense maximally representative of a class. We can use the distance to the shapelet, rather than the distance to the nearest neighbor to classify objects. As we shall show with extensive empirical evaluations in diverse domains, classification algorithms based on the time series shapelet primitives can be interpretable, more accurate, and significantly faster than state-of-the-art classifiers.     

Factors controlling volatile organic compounds in dwellings in Melbourne,Australia

This study characterized indoor volatile organic compounds (VOCs) and investigated the effects of the dwelling characteristics, building materials, occupant activities, and environmental conditions on indoor VOC concentrations in 40 dwellings located in Melbourne, Australia, in 2008 and 2009. A total of 97 VOCs were identified. Nine VOCs, n‐butane, 2‐methylbutane, toluene, formaldehyde, acetaldehyde, d‐limonene, ethanol, 2‐propanol, and acetic acid, accounted for 68% of the sum of all VOCs. The median indoor concentrations of all VOCs were greater than those measured outdoors. The occupant density was positively associated with indoor VOC concentrations via occupant activities, including respiration and combustion. Terpenes were associated with the use of household cleaning and laundry products. A petroleum‐like indoor VOC signature of alkanes and aromatics was associated with the proximity of major roads. The indoor VOC concentrations were negatively correlated (P < 0.05) with ventilation. Levels of VOCs in these Australian dwellings were lower than those from previous studies in North America and Europe, probably due to a combination of an ongoing temporal decrease in indoor VOC concentrations and the leakier nature of Australian dwellings.     

Effect of selenium status and supplementation with high-selenium yeast on plasma homocysteine and B vitamin concentrations in the UK elderly

The level of plasma total homocysteine (tHcy), long known to be B vitamin dependent, has recently been shown to be inversely associated with plasma selenium (Se) concentration in human subjects. We therefore, chose to investigate the interaction between Se, tHcy and B vitamins in a double-blind, placebo-controlled trial where 501 healthy UK elderly volunteers were randomly allocated to receive 100, 200, or 300 microg Se/day as high-Se-yeast, or placebo-yeast for 6 months. Plasma Se, tHcy, folate, vitamin B-12, pyridoxal-5'-phosphate (PLP) and its catabolite, 4-pyridoxic acid, were measured in all participants at baseline and in samples from the placebo, 100 and 300 microg Se/day groups, at follow-up. At baseline, Se was inversely correlated with tHcy but only in males (p < 0.001). Before supplementation, tHcy concentration was significantly lower in the highest compared to the lowest Se tertile in males (p < 0.05), and in females when folate concentrations were also in the top tertile (p < 0.05). The effect of folate, PLP and vitamin B-12 concentrations on plasma tHcy correlated with Se concentration at baseline. After 6 months of Se supplementation, only Se concentration had changed significantly. Supplementation with Se does not affect tHcy concentration in the UK elderly population.     

Recurrent nonalcoholic steatohepatitis and cirrhosis after liver transplantation

Necrotizing fasciitis is a rare condition, but has a devastating clinical course if it is not diagnosed early and treated aggressively. There are usually a number of organisms implicated in its pathogenesis, but in this case report a patient is presented in whom the only organism isolated from both tissue and blood cultures was Clostridium septicum. This organism almost always causes a myonecrosis, but in this case only the superficial and deep fascial layers were affected, sparing the underlying muscle. Clostridium septicum resulting in a true necrotizing fasciitis with no myonecrosis and being the only isolate from both blood and tissue cultures has not been previously reported in literature.