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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
Progress in heterogeneously integrated silicon-InP laser diodes for on-chip all-optical networks and signal processing
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
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