Non‐natural Peptide Triazole Antagonists of HIV‐1 Envelope gp120

We investigated the derivation of non‐natural peptide triazole dual receptor site antagonists of HIV‐1 Env gp120 to establish a pathway for developing peptidomimetic antiviral agents. Previously we found that the peptide triazole HNG‐156 [R‐I‐N‐N‐I‐X‐W‐S‐E‐A‐M‐M‐CONH₂, in which X=ferrocenyltriazole‐Pro (FtP)] has nanomolar binding affinity to gp120, inhibits gp120 binding to CD4 and the co‐receptor surrogate mAb 17b, and has potent antiviral activity in cell infection assays. Furthermore, truncated variants of HNG‐156, typified by UM‐24 (Cit‐N‐N‐I‐X‐W‐S‐CONH₂) and containing the critical central stereospecific ^LX‐^LW cluster, retain the functional characteristics of the parent peptide triazole. In the current work, we examined the possibility of replacing natural with unnatural residue components in UM‐24 to the greatest extent possible. The analogue with the critical “hot spot” residue Trp 6 replaced with L ‐3‐benzothienylalanine (Bta) (KR‐41), as well as a completely non‐natural analogue containing D ‐amino acid substitutions outside the central cluster (KR‐42, ^DCit‐^DN‐^DN‐^DI‐X‐Bta‐^DS‐CONH₂), retained the dual receptor site antagonism/antiviral activity signature. The results define differential functional roles of subdomains within the peptide triazole and provide a structural basis for the design of metabolically stable peptidomimetic inhibitors of HIV‐1 Env gp120.     

Putative Pheromones in Urine of Rutting Male Moose (Alces alces): Evolution of Honest Advertisement?

We tested hypotheses about how olfactory communication was related to mating behavior in Alaskan moose (Alces alces gigas). Males dig rutting pits where they deposit odiferous urine; females are strongly attracted to and often wallow in those pits. Moreover, mating and parturition are highly synchronized in moose. Consequently, male urine may play an important role in the mating system and in synchronizing reproduction in moose. Urine samples were collected from captive moose on the Kenai Peninsula, Alaska. Samples included those from the mating season and from the nonrutting period for two adult males, one yearling male, and one male and one female less than 1 year old. After pH adjustment, samples were extracted with methylene chloride to yield three fractions (acidic, neutral, and basic), which were analyzed by gas chromatography–mass spectrometry. Potential pheromones included unsaturated alcohols and homologs of tetrahydro-6-methyl pyranone and 2-nonen-4-one. We hypothesize that these compounds are related to hypophagia and catabolism of body reserves by rutting males, and thereby provide an honest advertisement of body condition by male moose during the mating season.     

Optical Basicity of Titanium(IV) Oxide and Zirconium(IV) Oxide

The relationship between electronic polarizability of oxide(—II), α_O²⁻, and the electron donor power, expressed as the optical basicity, ∧, indicates that ∧(TiO₂) is much greater than ∧(SiO₂) and is approximately the same as ∧(CaO). Such a high basicity is supported by the trend in the Racah B parameter for the Ni²⁺ ion in crystalline hosts and is also indicated from α_O²⁻ values of glasses containing TiO₂. Electronic polarizability and other data for zirconium(IV) media indicate that ZrO₂ also has a high basicity, but that ∧(ZrO₂) is somewhat less than ∧(TiO₂).     

Modelling swift heavy ion irradiation in iron

Swift heavy ions moving in metals lose most of their energy to inelastic scattering of electrons. The energy deposited in the electronic system is transferred into the atomic system via electron-ion interactions and can lead to melting and creation of new damage and also annealing of pre-existing atomic defects. Using a combination of molecular dynamics and a consistent treatment of electron energy transfer and transport we have modelled experiments performed in Fe to investigate the annealing effect and damage creation under electronic excitations. We observe both annealing and new damage creation at low and high electronic stopping, respectively. Rapid separation of interstitial atoms and vacant lattice sites is seen due to efficient transport via replacement collision sequences. Our results suggest that the role of electronic excitation can be significant in modeling of the behaviour of metals under swift heavy ion irradiation and attempts to modify metals via ion implantation.     

Asymptotic and numerical analysis of a simple model for blade coating

Motivated by the industrial process of blade coating, the two-dimensional flow of a thin film of Newtonian fluid on a horizontal substrate moving parallel to itself with constant speed under a fixed blade of finite length in which the flows upstream and downstream of the blade are coupled via the flow under the blade is analysed. A combination of asymptotic and numerical methods is used to investigate the number and nature of the steady solutions that exist. Specifically, it is found that in the presence of gravity there is always at least one, and (depending on the parameter values) possibly as many as three, steady solutions, and that when multiple solutions occur they are identical under and downstream of the blade, but differ upstream of it. The stability of these solutions is investigated, and their asymptotic behaviour in the limits of large and small flux and weak and strong gravity effects, respectively, determined.     

Adjuvant nitrosourea therapy for glioblastoma

An attempt was made to evaluate the potential advantages of chemotherapy in the treatment of 62 patients with glioblastoma. Twenty-four of the 62 patients received adjuvant nitrosourea chemotherapy with carmustine (BCNU), lomustine (CCNU), or semustine (methyl CCCNU) in addition to surgery and radiotherapy. Thirty-three of the 62 patients were involved in a controlled, prospective, randomly allocated study. Quality or quantity of survival was not prolonged in patients who received chemotherapy. Age greater than 64 years, a severe postoperative neurological deficit, or the onset of symptoms less than 12 months prior to surgery were associated with a worse prognosis. The valid evaluation of the effect of a form of treatment on survival in patients with glioblastoma is contingent on the regorous avoidance of preselected factors that may predispose the treated group to a more favorable prognosis.     

Prevalence and concentration of verocytotoxigenic Escherichia coli,Salmonella enterica and Listeria monocytogenes in the beef production chain: A review

This review examines the prevalence of three important pathogens, verocytotoxigenic Escherichia coli (VTEC), Salmonella enterica and Listeria monocytogenes, in cattle and beef from the farm to the final, ready-to-eat product. Factors affecting prevalence of pathogens in the beef chain, such as the season and cattle rearing method, are examined. Data from many key surveys are summarized in table form.     

An under-met and over-met expectations model of employee reactions to merit raises.

The authors developed a model of how raise expectations influence the relationship between merit pay raises and employee reactions and tested it using a sample of hospital employees. Pay-for-performance (PFP) perceptions were consistently related to personal reactions (e.g., pay raise happiness, pay-level satisfaction, and turnover intentions). Merit pay raises were strongly related to reactions only among employees with high raise expectations and high PFP perceptions. The interactive effects of under-met/over-met expectations and PFP perceptions were mediated by the extent to which participants saw the raise as generous and they were happy with the raises they received. The authors discuss the implications of these findings for expectation-fulfillment theories, merit pay research, and the administration of incentives. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Behavioral profile of a heterozygous mutant mouse model for EGF-like domain neuregulin 1.

Human genetic studies have demonstrated that the neuregulin 1 gene (NRG1) is involved in the development of schizophrenia. Alternative splicing of NRG1 results in at least 15 distinct isoforms and all contain an extracellular epidermal growth factor (EGF)-like domain, which is sufficient for Nrg1's biological activity. Here, we characterize a heterozygous mutant model for mouse EGF-like domain neuregulin 1 (Nrg1) regarding schizophrenia-related behavioral domains. A comprehensive, multitiered phenotyping strategy was used to investigate locomotion, exploration, anxiety-related behaviors, and sensorimotor gating. Nrg1 mutant mice exhibited a hyper-locomotive phenotype and an improved ability to habituate to a new environment. Extensive analysis of anxiety-related behaviors revealed a wild type-like phenotype in this domain. However, a moderate impairment in sensorimotor gating was found after pharmacological challenge using psychoactive substances. Our study adds to the increasing behavioral data available from a variety of animal models for Nrg1 isoforms. We suggest a standardized and comprehensive behavioral phenotyping approach to distinguish between the different models and to clarify their relevance for schizophrenia research. Future behavioral investigations will focus on the negative and cognitive symptoms of schizophrenia. (PsycINFO Database Record (c) 2010 APA, all rights reserved)