Esmolol potentiates reduction of minimum alveolar isoflurane concentration by alfentanil

The beta subunit of human chorionic gonadotropin is potentially encoded by six genes, which can be categorized into two types based on a sequence change at codon 117: GCC for the type I and GAC for the type II genes. We previously showed that, whereas type I genes were exclusively expressed in normal breast tissues, expression of type II genes was associated with malignant transformation (Bellet, D., et al. Cancer Res., 57: 516-523, 1997). We designed a simple and robust test (the CG117 assay) that measures the percentage of type II over both types of chorionic gonadotropin beta mRNAs. Normal breast tissues consistently had a negative CG117 index, whereas cancer breast tissues showed indexes ranging from 0 to 100%. The prognostic significance of the CG117 index was investigated in a series of 99 unilateral invasive primary breast cancer patients with known long-term outcome (median follow-up, 9 years). The CG117 index was positive in 48 (48.5%) of the 99 tumor mRNA samples. The index was not significantly associated with standard prognostic parameters, including clinical and macroscopic tumor size, histopathological grade, and lymph node status or steroid receptor status. Patients with a positive CG117 index in primary tumor mRNA had significantly shorter metastasis-free survival (P = 0.014) and overall survival (P = 0.038) after surgery, compared to patients with a negative index. The prognostic significance of the CG117 index persisted in Cox multivariate regression analysis, both for metastasis-free survival (P = 0.008) and overall survival (P = 0.016), together with lymph node status (P = 0.027 and P = 0.009, respectively). These findings indicate that the CG117 index may contribute to the identification of high-risk breast cancer patients.     

Biflavonoid-Induced Disruption of Hydrogen Bonds Leads to Amyloid-β Disaggregation

Deposition of amyloid β (Aβ) fibrils in the brain is a key pathologic hallmark of Alzheimer’s disease. A class of polyphenolic biflavonoids is known to have anti-amyloidogenic effects by inhibiting aggregation of Aβ and promoting disaggregation of Aβ fibrils. In the present study, we further sought to investigate the structural basis of the Aβ disaggregating activity of biflavonoids and their interactions at the atomic level. A thioflavin T (ThT) fluorescence assay revealed that amentoflavone-type biflavonoids promote disaggregation of Aβ fibrils with varying potency due to specific structural differences. The computational analysis herein provides the first atomistic details for the mechanism of Aβ disaggregation by biflavonoids. Molecular docking analysis showed that biflavonoids preferentially bind to the aromatic-rich, partially ordered N-termini of Aβ fibril via the π–π interactions. Moreover, docking scores correlate well with the ThT EC₅₀ values. Molecular dynamic simulations revealed that biflavonoids decrease the content of β-sheet in Aβ fibril in a structure-dependent manner. Hydrogen bond analysis further supported that the substitution of hydroxyl groups capable of hydrogen bond formation at two positions on the biflavonoid scaffold leads to significantly disaggregation of Aβ fibrils. Taken together, our data indicate that biflavonoids promote disaggregation of Aβ fibrils due to their ability to disrupt the fibril structure, suggesting biflavonoids as a lead class of compounds to develop a therapeutic agent for Alzheimer’s disease.     

Trustworthy keyword search for compliance storage

Intense regulatory focus on secure retention of electronic records has led to a need to ensure that records are trustworthy, i.e., able to provide irrefutable proof and accurate details of past events. In this paper, we analyze the requirements for a trustworthy index to support keyword-based search queries. We argue that trustworthy index entries must be durable—the index must be updated when new documents arrive, and not periodically deleted and rebuilt. To this end, we propose a scheme for efficiently updating an inverted index, based on judicious merging of the posting lists of terms. Through extensive simulations and experiments with two real world data sets and workloads, we demonstrate that the scheme achieves online update speed while maintaining good query performance. We also present and evaluate jump indexes, a novel trustworthy and efficient index for join operations on posting lists for multi-keyword queries. Jump indexes support insert, lookup and range queries in time logarithmic in the number of indexed documents.     

Cuticular Extracts from Acromis sparsa (Coleoptera: Cassidinae) Mediate Arrestment Behavior of the Commensal Canestriniid Mite Grandiella rugosita

Astigmatid mites in the family Canestriniidae are often closely associated with tortoise leaf beetles (Chrysomelidae: Cassidinae). For example, the survival of the commensal canestriniid mite Grandiella rugosita depends on dispersal to the cassidine beetle Acromis sparsa. Here, we tested whether the beetle cuticle provides chemical cues for host recognition for G. rugosita. In two-choice assays with cuticular extracts from A. sparsa and the co-occurring, non-host cassidine Chelymorpha alternans offered simultaneously, mites clearly preferred the area treated with extract from their host. In no-choice assays, G. rugosita spent three times longer and moved three times slower on host cuticular extracts compared to non-host extracts and the solvent control. Analyses of the chemical composition of cuticular extracts from males and females of A. sparsa and C. alternans revealed complex mixtures of mainly methyl branched hydrocarbons, which clearly separated both species in a principal component analysis. We found no qualitative difference between males and females of either species, but in C. alternans quantitative differences between males and females were detected. Our results demonstrate that G. rugosita is able to discriminate between cuticular extracts from its host A. sparsa and the non-host C. alternans. The components eliciting the observed arrestment behavior remain to be determined.     

Eicosapentaenoic acid is primarily responsible for hypotriglyceridemic effect of fish oil in humans

The aim of this study was to determine whether eicosapentaenoic acid (EPA) or docosahexaenoic acid (DHA), or both, were responsible for the triglyceride (TG)-lowering effects of fish oil. EPA (91% pure) and DHA (83% pure), a fish oil concentrate (FOC; 41% EPA and 23% DHA) and an olive oil (OO) placebo (all ethyl esters) were tested. A total of 49 normolipidemic subjects participated. Each subject was given placebo for 2–3 wk and one of the n-3 supplements for 3 wk in randomized, blinded trials. The target n-3 fatty acid (FA) intake was 3 g/day in all studies. Blood samples were drawn twice at the end of each supplementation phase and analyzed for lipids, lipoproteins, and phospholipid FA composition. In all groups, the phospholipid FA composition changed to reflect the n-3 FA given. On DHA supplementation, EPA levels increased to a small but significant extent, suggesting that some retroconversion may have occurred. EPA supplementation did not raise DHA levels, however, FOC and EPA produced significant decreases in both TG and very low density lipoprotein (VLDL) cholesterol (C) levels (P<0.01) and increases in low density lipoprotein (LDL) cholesterol levels (P<0.05). DHA supplementation did not affect cholesterol, triglyceride, VLDL, LDL, or high density lipoprotein (HDL) levels, but it did cause a significant increase in the HDL₂/HDL₃ cholesterol ratio. We conclude that EPA appears to be primarily responsible for TG-lowering (and LDL-C raising) effects of fish oil.     

"Age differences in psychosocial predictors of positive and negative affect: A longitudinal investigation of young, midlife, and older adults": Correction to Windsor and Anstey (2010).

Reports an error in "Age differences in psychosocial predictors of positive and negative affect: A longitudinal investigation of young, midlife, and older adults" by Tim D. Windsor and Kaarin J. Anstey (Psychology and Aging, 2010[Sep], Vol 25[3], 641-652). Contains an error in Figure 3, on page 649. The correction discusses where to find the correct data. (The following abstract of the original article appeared in record 2010-18944-009.) Research has consistently shown that despite aging-related losses, older adults have high levels of emotional well-being relative to those in young and midlife adults. We aimed to contribute to knowledge around the factors that predict emotional well-being over the life course by examining age group differences in associations of positive and negative social exchanges and mastery beliefs with positive and negative affect in a sample of 7,472 young, midlife, and older adults assessed on 2 measurement occasions, 4 years apart. Results from structural equation models indicated lower levels of negative affect with advancing age. Mastery was consistently related to higher well-being, with the strongest associations evident for young adults. Older adults reported the most frequent positive and least frequent negative social exchanges; however, associations of social relations with affect tended to be stronger among young and midlife adults relative to older adults. Results are discussed in the context of life course perspectives on goal orientations and self-regulatory processes. (PsycINFO Database Record (c) 2011 APA, all rights reserved)     

Spontaneous propeptide processing of mini-stromelysin-1 mutants blocked by APMA ((4-Aminophenyl)mercuric acetate)

Human stromelysin-1 (SL-1) is a member of the stromelysin subfamily of matrix metalloproteinases (MMPs). The MMPs play a major role in the degradation of the extracellular matrix (ECM) during normal and pathological conditions. SL-1 like the other MMPs can be activated in vitro by the stepwise removal of the propeptide that contains a single unpaired cysteine which coordinates the active site zinc. Other residues in the propeptide also play a role in maintaining the latency of the enzymes. Deletion mutants and single-site amino acid replacements within the propeptide of a carboxyl-terminally truncated stromelysin-1 (mini-SL-1) were constructed and expressed in Escherichia coli to further examine what amino acids within the propeptide of SL-1 are important for maintaining latency. While the natural enzyme displayed some limited tendency to spontaneously (autolytically) convert to lower Mr in a stepwise manner and finally to the fully processed form, all of the truncation mutants of more than 19 amino acids generated in E. coli showed greatly accelerated self-cleavage indicative of diminished stability and/or resistance to proteolysis of the residual propeptide. Mutant Delta63 as well as other mutants in which most of the propeptide had been deleted no longer responded to exposure to the organomercurial APMA by accelerated autolytic processing. Rather, APMA inhibited the autolytic processing in these mutants, further confirming the complexity of the action of this organomercurial in the activation of pro-MMPs.     

In‐dependence: Otto Koenigsberger and modernist urban resettlement in India

This article investigates the universalist problematic in Modern Movement town planning predominantly through the Indian phase of the career of Otto Koenigsberger (1909–99). Educated in Germany during the Weimar Republic but subjected to Nazi persecution, Koenigsberger migrated via Egypt to Bangalore and employment by the Tata Dynasty in 1939. Upon independence, he was appointed to Director of Housing in charge of New Town Development across India, including the organization of the Chandigarh commission. Koenigsberger’s architecture and town planning, in particular for Jamshedpur, mobilized current transatlantic modernist practice. It was predicated on the potential of abstract aesthetic and functionalist form to embody radical socio‐political change that surmounted both pre‐colonial and imperial conventions. While accommodating some features of Indian architectural tradition, Koenigsberger espoused non‐sectarian and standard solution, especially for housing. This thinking was most evident in his partially realized scheme for pan‐regional prefabricated dwelling units. The failure of this enterprise and ensuing political controversy caused him to resign and move to London. It is argued here that Koenigsberger’s experience in India informed his inauguration in 1957 of the School of Tropical Architectures at the Architectural Association and the department of Development Planning at University College London in 1972; these teaching posts coincided with successive reconsideration of his concept of urban design that culminated in the locally conditioned concept of Action Planning. The analytic is discursive, reading shifts in design thought out of Koenigsberger’s photographic and textual archive as well as his architectural and urban design work in India.