Search

We report measurements of single-asperity wear on sodium trisilicate glass in basic solution using atomic force microscopy (AFM), where the silicon nitride tip was used both to tribologically load and image the surface. Single-asperity micron-square polishing was performed by rastering the AFM tip in a square pattern. More localized, “nano”-machining was performed by drawing the AFM tip back and forth across the substrate in a linear fashion. In both modes, the wear rate gradually slowed during prolonged scanning. Changes in contact stress due to the wear of the AFM tip dramatically affect the observed wear rates. The changes in surface elevation for both the tip and the substrate display the same dependence on true stress and time for the case of square-raster scanning over micron dimensions. In the case of linear reciprocal scanning, conformal wear substantially modifies the rates and morphology of the wear of both the tip and the substrate. [ABSTRACT FROM AUTHOR]

Nanometer scale single asperity tribochemical wear of silicon nitride was examined by measuring the wear of atomic force microscope tips translated against a variety of substrates in aqueous solutions. We show that the chemical nature of the substrate plays an important role: significant wear was observed only when the substrate surface is populated with appropriate metal-hydroxide bonds. Mica and calcite substrates, whose water-exposed cleavage surfaces lack these bonds, produced little if any tip wear. As a function of contact force F[SUBN] and scan duration t, the length of the tips in this work decreases approximately as (F[SUBN]t)[SUP0.5]. We propose that pressure-induced intermediate states involving hydroxyl groups form on both the tip and the substrate; chemical reactions subsequently form transient bridging chemical bonds that are responsible for tip wear. [ABSTRACT FROM AUTHOR]

Background. Many healthcare education programmes embody methods of 'active learning' in authentic contexts. What students learn from authentic early experiences when exposed to healthcare in local communities is less clear. Objectives. We explored medical students' learning in South African communities by analysing their reflection on and meaning given to interactions with patients. Methods. A directed content analysis was done on a sample of 58 students' reflection reports with regard to the meaning of disease. Four different perspectives were coded, and labelled as positivist, compassionate, moralist and spiritualist. Results. Students documented their greater understanding of their patients' circumstances and their compassion and respect for patients and their diseases. Overall, the positivist biomedical perspective was observed, followed by the compassionate perspective. In their reflections, students expressed combined perspectives, i.e. the positivist perspective together with one or more of the others. Moralist and spiritualist perspectives were also observed in the data. The students indicated the benefits they had experienced, i.e. by visiting a patient in his/her home environment, they were able to construct and contextualise the patients' lives more holistically. Conclusions. Raising medical students' awareness of the realities of seeing patients in primary health clinics, district hospitals and at home, may contribute to their understanding of the meaning of disease and illness and their ability to better serve communities in need. [ABSTRACT FROM AUTHOR]

The heterogeneity of the spatial distribution of soil organic carbon ( SOC) at the landscape scale is generally not considered in regional or national SOC dynamics models. In cropland this heterogeneity is controlled largely by topography, which influences the distribution of water, energy and sediments, and thus the SOC dynamics. Sediment redistribution rates have increased strongly since the mechanization of agriculture. The over-simplification of landscape processes in regional models of C dynamics may add to the uncertainty in C balances. Therefore, a better characterization of the importance of landscape-scale effects on the SOC distribution throughout a region is needed. This study characterized the relative importance of geomorphology in the SOC horizontal and vertical variability across croplands in the Belgian loess belt region. A large legacy dataset of soil horizons was exploited together with 147 recently sampled profiles. Mean SOC depth profiles for different soil types were compared. Various topographic attributes were computed from a digital elevation model, and their influence on SOC was quantified through simple linear models. Finally, SOC content was mapped at three depth layers through multiple linear models, and results were cross-validated. The legacy dataset allowed identification of significant differences in the mean SOC profile according to texture, drainage or profile development classes. A clear relationship between SOC content and topographic attributes was demonstrated, but only for the recently sampled profiles. This may be explained by a substantial error in the location of the profiles of the legacy dataset. This study thus shows evidence that the major control of the vertical distribution of SOC is related to topography in a region where observed heterogeneities for other commonly involved factors are limited. However, the large amount of unexplained variability still limits the usefulness of the spatial prediction of SOC content, and suggests the importance of additional influencing factors. [ABSTRACT FROM AUTHOR]

Atomic force microscopy (AFM) is used to examine chemical–mechanical processes on Si(100) surfaces. The AFM tip serves as a single asperity contact to exert tribological forces as well as an imaging tool. By scanning in chemically aggressive solutions, material removal can be observed directly. In the silicon system, high-force scans are used to remove oxide and initiate etching in selected locations, followed by low-force scans to image the resulting surfaces. Material removal rates were measured as a function of applied load, number of scans, solution composition, and time. In basic solution, places where the underlying silicon is exposed etch rapidly, producing structures 100 nm or less in size. Although the surface roughness initially increases during etching, the final surfaces are smooth. The oxide is extremely sensitive to applied stress: even very light scanning accelerates oxide dissolution. Once the oxide is removed, chemical etching proceeds through the underlying silicon with or without AFM scanning; but the silicon etches more rapidly if AFM scanning is continued, due to true chemical–mechanical (tribochemical) effects. [ABSTRACT FROM AUTHOR]

Objective Clinical experiences and gender have been shown to influence medical students' specialty choices. It remains unclear, however, which aspects of experiences make students favour some specialties and reject others. This study aimed to clarify the effects of clerkships on specialty choice and to identify explanatory factors. Methods We carried out a longitudinal cohort study to collect data on career preferences and attitudes towards future careers among 3 cohorts of students before and after clerkships in surgery (n = 200), internal medicine (n = 277) and general practice (n = 184). Regression analyses were performed to identify the determinants of career choice and the role of gender. Results Exposure to clinical settings encourages students to opt for a career in the corresponding specialty. Men were more stimulated than women by the general practice clerkship. Gender had no clear role as a predictor of career preference. The major predictor of career choice in all 3 specialties was positive evaluation of work-intrinsic factors. A preference for working with acute patients and technology-oriented work, prestige orientation and insignificance of a controllable lifestyle were determinants of a preference for surgery. Students with a preference for general practice had almost opposite preferences. Those who chose internal medicine favoured a controllable lifestyle. Discussion Factors other than gender appear to drive specialty decisions. Work content, type of patients and lifestyle options play major roles. Consequently, along with teaching about the practice of medicine, the matching of specialty preferences with reality is an essential outcome of clerkships. [ABSTRACT FROM AUTHOR]

Chromosomal passenger proteins have emerged as key players in the regulation of mitosis and cytokinesis. Histone deacetylase inhibitors (HDACi) are a class of anticancer drugs that induce aberrant mitosis and can overcome the spindle assembly checkpoint. Here, we investigate the mechanism by which HDACi disrupt normal mitotic progression and checkpoint function. We demonstrate that HDACi treatment temporarily delays mitotic progression through prometaphase due to activation of the spindle assembly checkpoint. Despite failing to congress chromosomes to the metaphase plate, cells aberrantly segregate their chromosomes and exit mitosis to undergo a failed cytokinesis. We show that this premature exit from mitosis is a form of mitotic slippage. Chromosomal passenger proteins fail to accumulate at the centromere following HDACi treatment. This results in inadequate concentrations of chromosomal passenger proteins at the centromere, which are insufficient to regulate the phosphorylation of the kinetochore checkpoint component BubR1, and an inability to maintain the mitotic arrest. Thus, the centromeric accumulation of chromosomal passenger complex components is critical for regulating kinetochore but not centromeric processes, and failure of this accumulation underlies the HDACi-induced mitotic slippage.Oncogene (2008) 27, 1345–1354; doi:10.1038/sj.onc.1210779; published online 10 September 2007 [ABSTRACT FROM AUTHOR]

Abstract: The synthesis and biological evaluation of a series of oxindole β3 adrenergic receptor agonists is described. A modulation of rat atrial tachycardia was observed with substitution at the 3-position of the oxindole moiety. [Copyright &y& Elsevier]

Density functional theory techniques are used to investigate the defect structure of X- (X = O, S, Se) ions in MZ (M = Na, K, Rb and Z = Cl, Br) alkali halides which exhibit monoclinic-I g-tensor symmetry, using cluster in vacuo, embedded cluster, and periodic embedding schemes. Although a perturbed interstitial defect model was suggested from electron paramagnetic resonance experiments (EPR), the nature of the perturbation is still unknown. An appropriate defect model is developed theoretically by comparing structural and energetical properties of various defect configurations. Further validation is achieved by cross referencing experimental and computed EPR data. On the basis of the computational results, the following defect model is proposed: the X- ion is located interstitially with a charge compensating halide vacancy in its first coordination shell. [ABSTRACT FROM AUTHOR]

Monoatomic X- (X = O, S) chalcogen centers in MZ (M = Na, K, Rb and Z = Cl, Br, I) alkali halide lattices are investigated within the framework of density functional theory with the principal aim to establish defect models. In electron paramagnetic resonance (EPR) experiments, X- defects with tetragonal, orthorhombic, and monoclinic g-tensor symmetry have been observed. In this paper, models in which X- replaces a single halide ion, with a next nearest neighbor and a nearest neighbor halide vacancy, are validated for the X- centers with tetragonal and orthorhombic symmetry, respectively. As such defect models are extended, the ability to reproduce experimental data is a stringent test for various computational approaches. Cluster in vacuo and embedded cluster schemes are used to calculate energy and EPR parameters for the two vacancy configurations. The final assignment of a defect structure is based on the qualitative and quantitative reproduction of experimental g and (super)hyperfine tensors. [ABSTRACT FROM AUTHOR]

Abstract: Bond distances, vibrational frequencies and dipole moments of the RhX (X=C, N, O, F, P and Cl) molecules were studied by density functional theory (DFT) methods. For all molecules under consideration, spectroscopic properties are computed using various functionals. This study is the first systematic ab initio investigation of the RhX molecules and in those cases where comparison with experimental data can be made, good quantitative agreement is achieved when using the BP86 functional. [Copyright &y& Elsevier]

Calculations using density functional theory are performed to study the electron paramagnetic resonance (EPR) and electron nuclear double resonance (ENDOR) properties of S3- and Se3- impurities in alkali halide lattices. Cluster in vacuo models are used to describe the defect and the lattice surroundings. The trivacancy defect model proposed in the literature is able to reproduce both the experimental principal values and directions of the g tensor for S3- and Se3- defects doped in alkali halides. The alternative monovacancy model gives rise to important discrepancies with experiment and can be discarded. For the KCl lattice, the hyperfine tensors of the S3- and Se3- molecular ions also agree well with the available experimental data, giving further evidence to the trivacancy model. In addition, for NaCl:S3- and KCl:S3- computational results for the 23Na and 35Cl superhyperfine and quadrupole tensors are compared with experimental ENDOR parameters. [ABSTRACT FROM AUTHOR]

A substantial fraction of protein sequences derived from genomic analyses is currently classified as representing 'hypothetical proteins of unknown function'. In part, this reflects the limitations of methods for comparison of sequences with very low identity. We evaluated the effectiveness of a Psi-BLAST search strategy to identify proteins of similar fold at low sequence identity. Psi-BLAST searches for structurally characterized low-sequence-identity matches were carried out on a set of over 300 proteins of known structure. Searches were conducted in NCBI's non-redundant database and were limited to three rounds. Some 614 potential homologs with 25% or lower sequence identity to 166 members of the search set were obtained. Disregarding the expect value, level of sequence identity and span of alignment, correspondence of fold between the target and potential homolog was found in more than 95% of the Psi-BLAST matches. Restrictions on expect value or span of alignment improved the false positive rate at the expense of eliminating many true homologs. Approximately three-quarters of the putative homologs obtained by three rounds of Psi-BLAST revealed no significant sequence similarity to the target protein upon direct sequence comparison by BLAST, and therefore could not be found by a conventional search. Although three rounds of Psi-BLAST identified many more homologs than a standard BLAST search, most homologs were undetected. It appears that more than 80% of all homologs to a target protein may be characterized by a lack of significant sequence similarity. We suggest that conservative use of Psi-BLAST has the potential to propose experimentally testable functions for the majority of proteins currently annotated as 'hypothetical proteins of unknown function';. Copyright © 2004 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Based on a study involving structural comparisons of proteins sharing 25% or less sequence identity, three rounds of Psi-BLAST appear capable of identifying remote evolutionary homologs with greater than 95% confidence provided that more than 50% of the query sequence can be aligned with the target sequence. Since it seems that more than 80% of all homologous protein pairs may be characterized by a lack of significant sequence similarity, the experimental biologist is often confronted with a lack of guidance from conventional homology searches involving pair-wise sequence comparisons. The ability to disregard levels of sequence identity and expect value in Psi-BLAST if at least 50% of the query sequence has been aligned allows for generation of new hypotheses by consideration of matches that are conventionally disregarded. In one example, we suggest a possible evolutionary linkage between the cupredoxin and immunoglobulin fold families. A thermostable hypothetical protein of unknown function may be a circularly permuted homolog to phosphotriesterase, an enzyme capable of detoxifying organophosphate nerve agents. In a third example, the amino acid sequence of another hypothetical protein of unknown function reveals the ATP binding-site, metal binding site, and catalytic sidechain consistent with kinase activity of unknown specificity. This approach significantly expands the utility of existing sequence data to define the primary structure degeneracy of binding sites for substrates, cofactors and other proteins. Copyright © 2004 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Abstract: Electron paramagnetic resonance experiments have shown that, depending on the doping procedure, two different S2- centers may coexist in KCl. These centers have the 2B2g and the 2B3g ground state, respectively. As no experimental ligand hyperfine data are available, it could not be determined whether the S2- molecular ion replaces a single halide ion (mono-vacancy site) or two nearest neighbor halide ions (di-vacancy site). Also, other defect models could a priory be considered. In this work, cluster in vacuo density functional theory calculations of the g and 33S hyperfine tensors show that the S2- ion at a mono-vacancy site has the 2B2g ground state, whereas S2- in a di-vacancy exhibits a 2B3g ground state. For the latter center, the possibility of charge compensation by a cation vacancy is also considered. The calculations indicate that a possible vacancy is not in the direct vicinity (nearest or next-nearest neighbor) of the S2- ion. [Copyright &y& Elsevier]

Low molecular weight peptidomimetic compounds based on O-malonyl tyrosine and O-carboxymethyl salicylic acid are potent inhibitors of PTP1B. Modifications of the N-terminal Boc-Phe moiety were undertaken in an effort to improve physical chemical properties and to achieve cellular activity. Although Phe ultimately proved to be the optimal N-terminal amino acid, several viable replacements for the Boc group were identified, two of which afforded analogues that were effective at enhancing the insulin-stimulated uptake of 2-deoxyglucose by L6 myocytes. [Copyright &y& Elsevier]

Background: Female medical students often prefer primary care specialties, while male students appear to be attracted to hospital specialties. Notwithstanding the steady feminisation of medicine, in many countries there are still difficulties in recruiting trainees for general practice. This seeming paradox raises the question on what specific role gender plays in a specialty choice. The authors looked at the (a) the role of gender in general practice specialty choice of Dutch medical students, (b) the decisive factors in career choice and relation of gender to these, and (c) differences in how male and female students are influenced by the GP clerkship.Methods: A cohort of 206 final year medical students at the Maastricht University, the Netherlands were asked to complete a questionnaire focusing on career preferences before and after a 12-week general practice clerkship and at graduation, a couple of months later.Results: Gender was significantly related to willingness to become a GP in bivariate analysis. Adding variables in multivariate analysis made this effect disappear. While females expressed overall higher preference for general practice than males, after the GP clerkship likelihood of choosing general practice increased with 38% among male and 22% among female students. After graduation, interest in general practice had dropped, mainly among females. Attitudes predicting a GP career choice were: extrinsic career motivation before the clerkship, and the content of GP work (patient contacts, treatments) and motivation to work with chronic and palliative patients after the clerkship.Conclusion: Gender 'as such' appeared not to be a distinctive predictor of specialty choice. It is students' attitudes towards GP work and preferred patient category that determine the career choice in general practice. However, more male students were positively influenced by the GP clerkship than female students. The motivating effect of the clerkship is not long lasting. Especially female graduates change their interest in favour of other specialties, which may explain why eventually few students choose general practice. It might be worthwhile to reinforce an initial preference for general practice by motivational guidance throughout the whole period of clerkships. [ABSTRACT FROM AUTHOR]

Theoretical calculations are presented to determine the structure of radical defects in crystalline lattices. The applications are concentrated on radical defects as they are induced by irradiation in organic crystals and paramagnetic molecular ions embedded in alkali halide lattices. Various approaches are possible to model the molecular environment: the single-molecule approach, the cluster approach, and periodic calculations. The latter are based on a Car—Parrinello formalism in which the molecular orbitals are expanded in a plane-wave basis set and in which the optimized structures at 0 K are obtained by a simulated annealing technique. The pros and cons of the various approaches are highlighted, and where possible comparison with experimental electron paramagnetic resonance data are given. Due to the different natures of ionic and organic crystals, specific computational procedures are needed to get good correspondence with the experimental data. In various cases there is experimental evidence that some radical structures are submitted to noticeable changes with increasing temperature. [ABSTRACT FROM AUTHOR]

• Robustness of models is essential to generate accurate phenotypes at a large scale. • Variability in the reference and spectral data is a key element of robustness. • In most cases, complexity of models is in contradiction with robustness. • Models development should consider absorbance reliability of spectral regions. • Quality assurance methods are necessary to evaluate models and predictions. Methods and technologies enabling the estimation at large scale of important traits for the dairy sector are of great interest. Those phenotypes are necessary to improve herd management, animal genetic evaluation, and milk quality control. In the recent years, the research was very active to predict new phenotypes from the mid-infrared (MIR) analysis of milk. Models were developed to predict phenotypes such as fine milk composition, milk technological properties or traits related to cow health, fertility and environmental impact. Most of models were developed within research contexts and often not designed for routine use. The implementation of models at a large scale to predict new traits of interest brings new challenges as the factors influencing the robustness of models are poorly documented. The first objective of this work is to highlight the impact on prediction accuracy of factors such as the variability of the spectral and reference data, the spectral regions used and the complexity of models. The second objective is to emphasize methods and indicators to evaluate the quality of models and the quality of predictions generated under routine conditions. The last objective is to outline the issues and the solutions linked with the use and transfer of models on large number of instruments. Based on partial least square regression and 10 datasets including milk MIR spectra and reference quantitative values for 57 traits of interest, the impact of the different factors is illustrated by evaluating the influence on the validation root mean square error of prediction (RMSEP). In the displayed examples, all factors, when well set up, increase the quality of predictions, with an improvement of the RMSEP ranging from 12% to 43%. This work also aims to underline the need for and the complementarity between different validation procedures, statistical parameters and quality assurance methods. Finally, when using and transferring models, the impact of the spectral standardization on the prediction reproducibility is highlighted with an improvement up to 86% with the tested models, and the monitoring of individual spectrometer stability over time appears essential. This list inspired from our experience is of course not exhaustive. The displayed results are only examples and not general rules and other aspects play a role in the quality of final predictions. However, this work highlights good practices, methods and indicators to increase and evaluate quality of phenotypes predicted at a large scale. The results obtained argue for the development of guidelines at international levels, as well as international collaborations in order to constitute large and robust datasets and enable the use of models in routine conditions. [ABSTRACT FROM AUTHOR]

Unmanned Aerial Systems (UAS) have emerged as a platform capable of providing valuable data on vegetation structure, health, and productivity. The platform provides maximum temporal flexibility in data collection and customizability of spatial footprints which is important for mapping and monitoring vegetation conditions especially for high spectrally and structurally heterogeneous landscapes. In this letter, we investigate the potential improvement in structural information when using sensor payloads that include infrared bands (730–810 nm) in addition to the typical visible bands of many UAS sensor payloads. Specifically, we use derived point clouds and imagery collected from UAS-mounted sensors at a test site in Louisville, Kentucky, USA to assess whether multispectral sensors improve estimates of vegetation structure for plant greenness (leaf-on) and senescence (leaf-off) periods. Results indicate that including detailed multispectral reflectance information beyond the visible portion of the electromagnetic spectrum aids in estimating structural characteristics of woody vegetation, regardless of season. While both leaf-on and leaf-off periods result in reasonable crown height estimates, leaf-on conditions also improve radial estimates, likely due to continuous canopy surfaces. These findings advance research for remote sensing analyses assessing structural composition in heterogeneous landscapes where varying levels of vegetation structure have implications on land use and land function. [ABSTRACT FROM AUTHOR]

Transmembrane AMPA receptor regulatory proteins (TARPs) are a family of scaffolding proteins that regulate AMPA receptor trafficking and function. TARP γ-8 is one member of this family and is highly expressed within the hippocampus relative to the cerebellum. A selective TARP γ-8-dependent AMPA receptor antagonist (TDAA) is an innovative approach to modulate AMPA receptors in specific brain regions to potentially increase the therapeutic index relative to known non-TARP-dependent AMPA antagonists. We describe here, for the first time, the discovery of a noncompetitive AMPA receptor antagonist that is dependent on the presence of TARP γ-8. Three major iteration cycles were employed to improve upon potency, CYP1A2-dependent challenges, and in vivo clearance. An optimized molecule, compound (-)-25 (LY3130481), was fully protective against pentylenetetrazole-induced convulsions in rats without the motor impairment associated with non-TARP-dependent AMPA receptor antagonists. Compound (-)-25 could be utilized to provide proof of concept for antiepileptic efficacy with reduced motor side effects in patients. [ABSTRACT FROM AUTHOR]

OBJECTIVE: To gain caregivers' insights into the decision-making process in dementia patients with regard to treatment and care. METHODS: Four focus group interviews (n=29). RESULTS: The decision-making process consists of three elementary components: (1) identifying an individual's needs; (2) exploring options; and (3) making a choice. The most important phase is the exploration phase as it is crucial for the acceptance of the disease. Furthermore, the decision is experienced more as an emotional choice than a rational one. It is influenced by personal preferences whereas practical aspects do not seem to play a substantial role. CONCLUSION: Several aspects make decision-making in dementia different from decision-making in the context of other chronic diseases: (1) the difficulty accepting dementia; (2) the progressive nature of dementia; (3) patient's reliance on surrogate decision-making; and (4) strong emotions. Due to these aspects, the decision-making process is very time-consuming, especially the crucial exploration phase. PRACTICE IMPLICATIONS: A more active role is required of both the caregiver and the health care professional especially in the exploration phase, enabling easier acceptance and adjustment to the disease. Acceptance is an important condition for reducing anxiety and resistance to care that may offer significant benefits in the future. [ABSTRACT FROM AUTHOR]

BACKGROUND AND PURPOSE Spreading depression (SD) is a local, temporary disruption of cellular ionic homeostasis that propagates slowly across the cerebral cortex and other neural tissues such as the retina. Spreading depolarization associated with SD occurs in different types of stroke, and this phenomenon correlates also with the initiation of classical migraine aura. The aim of this study was to investigate how NMDA receptor antagonists with different subtype selectivity alter SD. EXPERIMENTAL APPROACH Immunoblotting was applied to the chick retina for NMDA receptor subunit protein analysis, and an efficient in vitro chick retinal model used with SD imaging for NMDA receptor pharmacology. KEY RESULTS The prominent NMDA receptor subtypes GluN1, GluN2A and GluN2B were found highly expressed in the chick retina. Nanomolar concentrations of NVP-AAM077 (GluN2A-preferring receptor antagonist) markedly suppressed high K+-induced SD; that is, ∼30 times more effectively than MK801. At sub-micromolar concentrations, Ro 25-6981 (GluN2B-preferring receptor antagonist) produced a moderate SD inhibition, whereas CP-101,606 (also GluN2B-preferring receptor antagonist) and UBP141 (GluN2C/2D-preferring receptor antagonist) had no effect. CONCLUSIONS AND IMPLICATIONS The expression of major NMDA receptor subtypes, GluN1, GluN2A and GluN2B in the chick retina makes them pertinent targets for pharmacological inhibition of SD. The high efficacy of NVP-AAM077 on SD inhibition suggests a critical role of GluN2A-containing receptors in SD genesis. Such high anti-SD potency suggests that NVP-AAM077, and other GluN2A-selective drug-like candidates, could be potential anti-migraine agents. [ABSTRACT FROM AUTHOR]

Cyclin A/cdk2 has a role in progression through S phase, and a large pool is also activated in G2 phase. Here we report that this G2 phase pool regulates the timing of progression into mitosis. Knock down of cyclin A by siRNA or addition of a specific cdk2 small molecule inhibitor delayed entry into mitosis by delaying cells in G2 phase. The G2 phase-delayed cells contained elevated levels of inactive cyclin B/cdk1. However, increased microtubule nucleation at the centrosomes was observed, and the centrosomes stained for markers of cyclin B/cdk1 activity. Both microtubule nucleation at the centrosomes and the phosphoprotein markers were lost with short-term treatment of the cdk1/2 inhibitor roscovitine but not the Mek1/2 inhibitor U0126. Cyclin A/cdk2 localized at the centrosomes in late G2 phase after separation of the centrosomes but before the start of prophase. Thus G2 phase cyclin A/cdk2 controls the timing of entry into mitosis by controlling the subsequent activation of cyclin B/cdk1, but also has an unexpected role in coordinating the activation of cyclin B/cdk1 at the centrosome and in the nucleus.Oncogene (2008) 27, 4261–4268; doi:10.1038/onc.2008.74; published online 31 March 2008 [ABSTRACT FROM AUTHOR]

Abstract: The synthesis and biological evaluation of novel tetrahydroisoquinoline, tetrahydroquinoline, and tetrahydroazepine antagonists of the human and rat H3 receptors are described. The substitution around these rings as well as the nature of the substituent on nitrogen is explored. Several compounds with high affinity and selectivity for the human and rat H3 receptors are reported. [Copyright &y& Elsevier]

Chromosomal region 2q33 encodes the immune regulatory genes, CTLA4, ICOS and CD28, which are involved in regulation of T-cell activity and has been studied as a candidate gene locus in autoimmune diseases, including coeliac disease (CD). We have investigated whether an association exists between this region and CD in the Irish population using a comprehensive analysis for genetic variation. Using a haplotype-tagging approach, this gene cluster was investigated for disease association in a case–control study comprising 394 CD patients and 421 ethnically matched healthy controls. Several SNPs, including CTLA4_CT60, showed association with disease; however, after correction for multiple-testing, CTLA4−658C/T was the only polymorphism found to show significant association with disease when allele, genotype, or carrier status frequency were analysed (carrier status (Allele C), P=0.0016). Haplotype analysis revealed a haplotype incorporating the CD28/CTLA4 and two 5′ ICOS polymorphisms to be significantly associated with disease (patients 24.1%; controls 31.5%; P=0.035), as was a shorter haplotype composed of the CTLA4 markers only (30.9 vs 34.9%; P=0.042). The extended haplotype incorporating CD28/CTLA4 and 5′ ICOS is more strongly associated with disease than haplotypes of individual genes. This suggests a causal variant associated with this haplotype may be associated with disease in this population.Genes and Immunity (2006) 7, 19–26. doi:10.1038/sj.gene.6364265; published online 20 October 2005 [ABSTRACT FROM AUTHOR]

The prevalence rate of Alzheimer's disease (AD) in people with down's syndrome (DS) increases significantly with age. However, the nature of the early clinical presentation, course and incidence rates of dementia are uncertain. The aims of the present study were to investigate the characteristics of age‐related clinical changes and incidence rates for dementia in a population‐based sample of people with DS aged 30 years and older at the age of risk for dementia. A modified version of the cambridge examination for mental disorders of the elderly informant interview was used to determine the extent and nature of changes in memory, personality, general mental functioning and daily living skill 18 months after a similar assessment. At the time of the first assessment, the initial changes reported were predominately in behaviour and personality. At the second assessment, overall estimated incidence rates for frontal‐like dementia were high (0.24), mainly in the younger groups, with incidence rates of AD, meeting both ICD‐10 and DSM‐IV criteria, of 0.04 predominately in the older groups. The present authors have hypothesized that the observed personality changes and the high estimated incidence rates of frontal‐like dementia in the younger groups may indicate that functions served by the frontal lobes are the first to be compromised with the progressive development of Alzheimer‐like neuropathology in people with DS. [ABSTRACT FROM AUTHOR]

Presents abstract of several studies on old age psychiatry. Information on alcohol consumption and risk of dementia in older adults in the U.S.; Relationship between behavioral problems in patients with dementia and changes in marital relationship; Differentiation of geriatric major depression from Alzheimer's disease.

Examines the humoral response of patients with coeliac disease and enteropathy associated T cell lymphoma on wheat protein. Ratio of women to men in he group with coeliac disease; Characterization of coeliac disease; Comparison between gliadin antibody levels in patients with coeliac disease.