1,198 research outputs found
Neural Dynamics in Parkinsonian Brain:The Boundary Between Synchronized and Nonsynchronized Dynamics
Synchronous oscillatory dynamics is frequently observed in the human brain.
We analyze the fine temporal structure of phase-locking in a realistic network
model and match it with the experimental data from parkinsonian patients. We
show that the experimentally observed intermittent synchrony can be generated
just by moderately increased coupling strength in the basal ganglia circuits
due to the lack of dopamine. Comparison of the experimental and modeling data
suggest that brain activity in Parkinson's disease resides in the large
boundary region between synchronized and nonsynchronized dynamics. Being on the
edge of synchrony may allow for easy formation of transient neuronal
assemblies
Rapid turnover of T cells in acute infectious mononucleosis.
During acute infectious mononucleosis (AIM), large clones of Epstein-Barr virus-specific T lymphocytes are produced. To investigate the dynamics of clonal expansion, we measured cell proliferation during AIM using deuterated glucose to label DNA of dividing cells in vivo, analyzing cells according to CD4, CD8 and CD45 phenotype. The proportion of labeled CD8(+)CD45R0(+) T lymphocytes was dramatically increased in AIM subjects compared to controls (mean 17.5 versus 2.8%/day; p<0.005), indicating very rapid proliferation. Labeling was also increased in CD4(+)CD45R0(+) cells (7.1 versus 2.1%/day; p<0.01), but less so in CD45RA(+) cells. Mathematical modeling, accounting for death of labeled cells and changing pool sizes, gave estimated proliferation rates in CD8(+)CD45R0(+) cells of 11-130% of cells proliferating per day (mean 47%/day), equivalent to a doubling time of 1.5 days and an appearance rate in blood of about 5 x 10(9) cells/day (versus 7 x 10(7) cells/day in controls). Very rapid death rates were also observed amongst labeled cells (range 28-124, mean 57%/day),indicating very short survival times in the circulation. Thus, we have shown direct evidence for massive proliferation of CD8(+)CD45R0(+) T lymphocytes in AIM and demonstrated that rapid cell division continues concurrently with greatly accelerated rates of cell disappearance
Guidelines (1988) for training in clinical laboratory management
Trainees in laboratory medicine must develop skills in laboratory
management. Guidelines are detailed for laboratory staff in
training, directors responsible for staff development and professional
bodies wishing to generate material appropriate to their
needs. The syllabus delineates the knowledge base required and
includes laboratory planning and organization, control of operations,
methodology and instrumentation, data management and
statistics, financial management, clinical use of tests, communication,
personnel management and training and research and
development. Methods for achievement of the skills required are
suggested. A bibliography of IFCC publications and other
material is provided to assist in training in laboratory management
Predicting toxicity through computers: a changing world
The computational approaches used to predict toxicity are evolving rapidly, a process hastened on by the emergence of new ways of describing chemical information. Although this trend offers many opportunities, new regulations, such as the European Community's 'Registration, Evaluation, Authorisation and Restriction of Chemicals' (REACH), demand that models be ever more robust
BMQ
BMQ: Boston Medical Quarterly was published from 1950-1966 by the Boston University School of Medicine and the Massachusetts Memorial Hospitals
Interpolated wave functions for nonadiabatic simulations with the fixed-node quantum Monte Carlo method
Simulating nonadiabatic effects with many-body wave function approaches is an
open field with many challenges. Recent interest has been driven by new
algorithmic developments and improved theoretical understanding of properties
unique to electron-ion wave functions. Fixed-node diffusion Monte Caro is one
technique that has shown promising results for simulating electron-ion systems.
In particular, we focus on the CH molecule for which previous results suggested
a relatively significant contribution to the energy from nonadiabatic effects.
We propose a new wave function ansatz for diatomic systems which involves
interpolating the determinant coefficients calculated from configuration
interaction methods. We find this to be an improvement beyond previous wave
function forms that have been considered. The calculated nonadiabatic
contribution to the energy in the CH molecule is reduced compared to our
previous results, but still remains the largest among the molecules under
consideration.Comment: 7 pages, 3 figure
The challenge of reconciling bottom-up agricultural methane emissions inventories with top-down measurements
Agriculture is estimated to produce more than 40% of anthropogenic methane (CH4) emissions, contributing to global climate change. Bottom-up, IPCC based methodologies are typically used to estimate the agriculture sector\u2019s contribution, but these estimates are rarely verified beyond the farm gate, due to the challenge of separating interspersed sources. We present flux measurements of CH4, using eddy covariance (EC), relaxed eddy accumulation (REA) and wavelet covariance obtained using an aircraft-based measurement platform and compare these top-down estimates with bottom-up footprint adjusted inventory estimates of CH4 emissions for an agricultural region in eastern Ontario, Canada. Top-down CH4 fluxes agree well (mean \ub1 1 standard error: EC = 17 \ub1 4 mg CH4 m 122 d 121; REA = 19 \ub1 3 mg CH4 m 122 d 121, wavelet covariance = 16 \ub1 3 mg CH4 m 122 d 121), and are not statistically different, but significantly exceed bottom-up inventory estimates of CH4 emissions based on animal husbandry (8 \ub1 1 mg CH4 m 122 d 121). The discrepancy between top-down and bottom-up estimates was found to be related to both increasing fractional area of wetlands in the flux footprint, and increasing surface temperature. For the case when the wetland area in the flux footprint was less than 10% fractional coverage, the top-down and bottom-up estimates were within the measurement error. This result provides the first independent verification of agricultural methane emissions inventories at the regional scale. Wavelet analysis, which provides spatially resolved fluxes, was used to attempt to separate CH4 emissions from managed and unmanaged CH4 sources. Opportunities to minimize the challenges of verifying agricultural CH4 emissions inventories using aircraft flux measuring systems are discussed.Peer reviewed: YesNRC publication: Ye
InternationaL cross-sectIonAl and longItudinal assessment on aSthma cONtrol in European adult patients : the LIAISON study protocol
The study is funded by Chiesi Farmaceutici S.p.A., Parma, ItalyPeer reviewedPublisher PD
FragmentStore—a comprehensive database of fragments linking metabolites, toxic molecules and drugs
Consideration of biomolecules in terms of their molecular building blocks provides valuable new information regarding their synthesis, degradation and similarity. Here, we present the FragmentStore, a resource for the comparison of fragments found in metabolites, drugs or toxic compounds. Starting from 13 000 metabolites, 16 000 drugs and 2200 toxic compounds we generated 35 000 different building blocks (fragments), which are not only relevant to their biosynthesis and degradation but also provide important information regarding side-effects and toxicity. The FragmentStore provides a variety of search options such as 2D structure, molecular weight, rotatable bonds, etc. Various analysis tools have been implemented including the calculation of amino acid preferences of fragments’ binding sites, classification of fragments based on the enzyme classification class of the enzyme(s) they bind to and small molecule library generation via a fragment-assembler tool. Using the FragmentStore, it is now possible to identify the common fragments of different classes of molecules and generate hypotheses about the effects of such intersections. For instance, the co-occurrence of fragments in different drugs may indicate similar targets and possible off-target interactions whereas the co-occurrence of fragments in a drug and a toxic compound/metabolite could be indicative of side-effects. The database is publicly available at: http://bioinformatics.charite.de/fragment_store
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