Modulation of human lymphocyte function by C3a and C3a(70-77).

Human C3a and the synthetic octapeptide C3a (70-77), which retains the activities of an anaphylatoxin, inhibit in a concentration-dependent manner the generation of leukocyte inhibitory factor (LIF) activity by human mononuclear leukocytes and T lymphocytes cultured with the mitogens phytohemagglutinin (PHA) or concanavalin A (Con A) or the antigen streptokinase-streptodornase (SK-SD). The generation of LIF activity was inhibited by 50% by 10(-8) M C3a or C3a(70-77) with PHA or Con A as the stimulus, whereas a more than 10-fold higher concentration of C3a(70-77) than C3a was required to achieve the same level of suppression with SK-SD as the stimulus. Similar concentrations of C3a(70-77) inhibited to the same extent the migration of T lymphocytes stimulated by alpha-thioglycerol of Con A. Neither C3a nor C3a(70-77) altered significantly the uptake of [3H]thymidine by human mononuclear cells exposed to PHA, Con A, or SK-SD. The capacity of C3a(70-77)-Sepharose,m but not Sepharose alone, to adsorb or inactivate mononuclear leukocytes required for the generation of LIF activity established a direct interaction. Analysis of the lymphocytes in the effluent from C3a(70-77)-Sepharose columns, using monoclonal antibodies to surface antigens, showed a selective depletion of the helper/inducer population of lymphocytes. C3a might represent an important mediator of the functionally selective regulation of human T lymphocyte activities by the complement system

Exploiting the full power of temporal gene expression profiling through a new statistical test: Application to the analysis of muscular dystrophy data

Background: The identification of biologically interesting genes in a temporal expression profiling dataset is challenging and complicated by high levels of experimental noise. Most statistical methods used in the literature do not fully exploit the temporal ordering in the dataset and are not suited to the case where temporal profiles are measured for a number of different biological conditions. We present a statistical test that makes explicit use of the temporal order in the data by fitting polynomial functions to the temporal profile of each gene and for each biological condition. A Hotelling T2-statistic is derived to detect the genes for which the parameters of these polynomials are significantly different from each other. Results: We validate the temporal Hotelling T2-test on muscular gene expression data from four mouse strains which were profiled at different ages: dystrophin-, beta-sarcoglycan and gammasarcoglycan deficient mice, and wild-type mice. The first three are animal models for different muscular dystrophies. Extensive biological validation shows that the method is capable of finding genes with temporal profiles significantly different across the four strains, as well as identifying potential biomarkers for each form of the disease. The added value of the temporal test compared to an identical test which does not make use of temporal ordering is demonstrated via a simulation study, and through confirmation of the expression profiles from selected genes by quantitative PCR experiments. The proposed method maximises the detection of the biologically interesting genes, whilst minimising false detections. Conclusion: The temporal Hotelling T2-test is capable of finding relatively small and robust sets of genes that display different temporal profiles between the conditions of interest. The test is simple, it can be used on gene expression data generated from any experimental design and for any number of conditions, and it allows fast interpretation of the temporal behaviour of genes. The R code is available from V.V. The microarray data have been submitted to GEO under series GSE1574 and GSE3523

Rotational symmetry and degeneracy: a cotangent-perturbed rigid rotator of unperturbed level multiplicity

We predict level degeneracy of the rotational type in diatomic molecules described by means of a cotangent-hindered rigid rotator. The problem is shown to be exactly solvable in terms of non-classical Romanovski polynomials. The energies of such a system are linear combinations of t(t+1) and 1/[t(t+1)+1/4] terms with the non-negative integer principal quantum number t=n+|/bar{m}| being the sum of the degree n of the polynomials and the absolute value, |/bar{m}|, of the square root of the separation constant between the polar and azimuthal motions. The latter obeys, with respect to t, the same branching rule, |/bar{m}|=0,1,..., t, as does the magnetic quantum number with respect to the angular momentum, l, and, in this fashion, the t quantum number presents itself indistinguishable from l. In effect, the spectrum of the hindered rotator has the same (2t+1)-fold level multiplicity as the unperturbed one. For small t values, the wave functions and excitation energies of the perturbed rotator differ from the ordinary spherical harmonics, and the l(l+1) law, respectively, while approaching them asymptotically with increasing t. In this fashion the breaking of the rotational symmetry at the level of the representation functions is opaqued by the level degeneracy. The model provides a tool for the description of rotational bands with anomalously large gaps between the ground state and its first excitation.Comment: 10 pages, 6 figures; Molecular Physics 201

The use of dried blood spots and a modified particle agglutination test for cost-effective sero-epidemiological HIV surveys

No Abstract

Approaches used to evaluate the social Impacts of protected areas

Protected areas are a key strategy in conserving biodiversity, and there is a pressing need to evaluate their social impacts. Though the social impacts of development interventions are widely assessed, the conservation literature is limited and methodological guidance is lacking. Using a systematic literature search, which found 95 relevant studies, we assessed the methods used to evaluate the social impacts of protected areas. Mixed methods were used by more than half of the studies. Almost all studies reported material aspects of wellbeing, particularly income; other aspects were included in around half of studies. The majority of studies provided a snapshot, with only one employing a before-after-control-intervention design. Half of studies reported respondent perceptions of impacts, while impact was attributed from researcher inference in 1/3 of cases. Although the number of such studies is increasing rapidly, there has been little change in the approaches used over the last 15 years, or in the authorship of studies, which is predominantly academics. Recent improvements in understanding of best practice in social impact evaluation need to be translated into practice if a true picture of the effects of conservation on local people is to be obtained

Resident Perception of Academic Skills Training and Impact on Academic Career Choice

Objectives: 1) To evaluate residents' perceptions of the quality of training in basic academic skills and the availability and quality of research resources during residency; 2) to evaluate the association between these attitudes and choice of an academic career; and 3) to assess residents' attitudes toward the importance of postgraduate fellowship training for success in an academic career. Methods: A 15-item survey was administered to all U.S. emergency medicine (EM) residents in conjunction with the February 1997 American Board of Emergency Medicine (ABEM) In-service Examination. The survey assessed resident interest in a career in academic EM, and resident perception of the general quality of training in academic (research and teaching) skills. Residents were also asked to rate the quality of their training in the following specific academic skills: medical and grant writing, bedside teaching, lecturing, the use of computers, study design, statistics, and the use of audiovisual aids. Resident perceptions of the availability of the following resources were also assessed: teaching and research role models, data collection and analysis support, laboratory facilities, financial support of research, research fundamentals lectures, and computers. Results: The response rate was 93%. Forty-four percent of the respondents were interested in academic EM, 36.6% were undecided, and 19.6% were not interested in an academic career. On a scale of 1 (unprepared) to 5 (well prepared), the residents rated their overall preparedness for an academic career fairly high (3.97 [0.86]). In contrast, they perceived the quality of their training in the specific academic skill areas assessed and research resource availability to be only fair. Despite resident perception of relatively inadequate training in basic academic skills, only 24% of the respondents indicated that they believed fellowship training was important for success in an academic career. Logistic regression analyses demonstrated that participation in a research project in medical school, the length of the training program (4- vs 3-year), being a first-year resident, and a better perception of one's overall academic skill preparation were factors independently associated with having a greater interest in an academic career. Conclusions: A relatively high percentage of residents initially express an interest in an academic career, but this interest wanes as residency progresses. A minority of residents believe that their training provides them with the specific skills needed to succeed in academics, or with adequate exposure to research resources or mentors. Emergency medicine may be able to increase the number of qualified academic faculty by recruiting medical students with prior research experience, and providing residents with better research training and role models.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/72196/1/j.1553-2712.2000.tb00499.x.pd

Local charge carrier mobility in disordered organic field-effect transistors

In conventional field-effect transistors, the extracted mobility does not take into account the distribution of charge carriers. However, in disordered organic field-effect transistors, the local charge carrier mobility decreases from the semiconductor/insulator interface into the bulk, due to its dependence on the charge carrier density. It is demonstrated that the conventional field-effect mobility is a good approximation for the local mobility of the charge carriers at the interface, (C) 2003 Elsevier Science B.V. All rights reserved

Modulation of amygdala response to task-irrelevant emotion

It has been shown that as cognitive demands of a non-emotional task increase, amygdala response to task-irrelevant emotional stimuli is reduced. However, it remains unclear whether effects are due to altered task demands, or altered perceptual input associated with task demands. Here, we present fMRI data from 20 adult males during a novel cognitive conflict task in which the requirement to scan emotional information was necessary for task performance and held constant across levels of cognitive conflict. Response to fearful facial expressions was attenuated under high (vs. low) conflict conditions, as indexed by both slower reaction times (RTs) and reduced right amygdala response. Psychophysiological interaction (PPI) analysis showed that increased amygdala response to fear in the low conflict condition was accompanied by increased functional coupling with middle frontal gyrus, a prefrontal region previously associated with emotion regulation during cognitive task performance. These data suggest that amygdala response to emotion is modulated as a function of task demands, even when perceptual inputs are closely matched across load conditions. PPI data also show that, in particular emotional contexts, increased functional coupling of amygdala with prefrontal cortex can paradoxically occur when executive demands are lower