1,581 research outputs found
Anorectal malformations
Anorectal malformations comprise a wide spectrum of diseases, which can affect boys and girls, and involve the distal anus and rectum as well as the urinary and genital tracts. They occur in approximately 1 in 5000 live births. Defects range from the very minor and easily treated with an excellent functional prognosis, to those that are complex, difficult to manage, are often associated with other anomalies, and have a poor functional prognosis. The surgical approach to repairing these defects changed dramatically in 1980 with the introduction of the posterior sagittal approach, which allowed surgeons to view the anatomy of these defects clearly, to repair them under direct vision, and to learn about the complex anatomic arrangement of the junction of rectum and genitourinary tract. Better imaging techniques, and a better knowledge of the anatomy and physiology of the pelvic structures at birth have refined diagnosis and initial management, and the analysis of large series of patients allows better prediction of associated anomalies and functional prognosis. The main concerns for the surgeon in correcting these anomalies are bowel control, urinary control, and sexual function. With early diagnosis, management of associated anomalies and efficient meticulous surgical repair, patients have the best chance for a good functional outcome. Fecal and urinary incontinence can occur even with an excellent anatomic repair, due mainly to associated problems such as a poorly developed sacrum, deficient nerve supply, and spinal cord anomalies. For these patients, an effective bowel management program, including enema and dietary restrictions has been devised to improve their quality of life
Heat Capacity of Protein Folding
We construct a Hamiltonian for a single domain protein where the contact
enthalpy and the chain entropy decrease linearly with the number of native
contacts. The hydration effect upon protein unfolding is included by modeling
water as ideal dipoles that are ordered around the unfolded surfaces, where the
influence of these surfaces, covered with an ``ice-like'' shell of water, is
represented by an effective field that directs the water dipoles. An
intermolecular pair interaction between water molecules is also introduced. The
heat capacity of the model exhibits the common feature of small globular
proteins, two peaks corresponding to cold and warm unfolding, respectively. By
introducing vibrational modes, we obtain quantitatively good accordance with
experiments.Comment: 14 pages, LaTex, 4 figure
Optimization and evaluation of a coarse-grained model of protein motion using X-ray crystal data
Simple coarse-grained models, such as the Gaussian Network Model, have been
shown to capture some of the features of equilibrium protein dynamics. We
extend this model by using atomic contacts to define residue interactions and
introducing more than one interaction parameter between residues. We use
B-factors from 98 ultra-high resolution X-ray crystal structures to optimize
the interaction parameters. The average correlation between GNM fluctuation
predictions and the B-factors is 0.64 for the data set, consistent with a
previous large-scale study. By separating residue interactions into covalent
and noncovalent, we achieve an average correlation of 0.74, and addition of
ligands and cofactors further improves the correlation to 0.75. However,
further separating the noncovalent interactions into nonpolar, polar, and mixed
yields no significant improvement. The addition of simple chemical information
results in better prediction quality without increasing the size of the
coarse-grained model.Comment: 18 pages, 4 figures, 1 supplemental file (cnm_si.tex
Long term productivity and collaboration in information science
This is an accepted manuscript of an article published by Springer in Scientometrics on 02/07/2016, available online: https://doi.org/10.1007/s11192-016-2061-8
The accepted version of the publication may differ from the final published version.Funding bodies have tended to encourage collaborative research because it is generally more highly cited than sole author research. But higher mean citation for collaborative articles does not imply collaborative researchers are in general more research productive. This article assesses the extent to which research productivity varies with the number of collaborative partners for long term researchers within three Web of Science subject areas: Information Science & Library Science, Communication and Medical Informatics. When using the whole number counting system, researchers who worked in groups of 2 or 3 were generally the most productive, in terms of producing the most papers and citations. However, when using fractional counting, researchers who worked in groups of 1 or 2 were generally the most productive. The findings need to be interpreted cautiously, however, because authors that produce few academic articles within a field may publish in other fields or leave academia and contribute to society in other ways
Human physiologically based pharmacokinetic model for propofol
BACKGROUND: Propofol is widely used for both short-term anesthesia and long-term sedation. It has unusual pharmacokinetics because of its high lipid solubility. The standard approach to describing the pharmacokinetics is by a multi-compartmental model. This paper presents the first detailed human physiologically based pharmacokinetic (PBPK) model for propofol. METHODS: PKQuest, a freely distributed software routine , was used for all the calculations. The "standard human" PBPK parameters developed in previous applications is used. It is assumed that the blood and tissue binding is determined by simple partition into the tissue lipid, which is characterized by two previously determined set of parameters: 1) the value of the propofol oil/water partition coefficient; 2) the lipid fraction in the blood and tissues. The model was fit to the individual experimental data of Schnider et. al., Anesthesiology, 1998; 88:1170 in which an initial bolus dose was followed 60 minutes later by a one hour constant infusion. RESULTS: The PBPK model provides a good description of the experimental data over a large range of input dosage, subject age and fat fraction. Only one adjustable parameter (the liver clearance) is required to describe the constant infusion phase for each individual subject. In order to fit the bolus injection phase, for 10 or the 24 subjects it was necessary to assume that a fraction of the bolus dose was sequestered and then slowly released from the lungs (characterized by two additional parameters). The average weighted residual error (WRE) of the PBPK model fit to the both the bolus and infusion phases was 15%; similar to the WRE for just the constant infusion phase obtained by Schnider et. al. using a 6-parameter NONMEM compartmental model. CONCLUSION: A PBPK model using standard human parameters and a simple description of tissue binding provides a good description of human propofol kinetics. The major advantage of a PBPK model is that it can be used to predict the changes in kinetics produced by variations in physiological parameters. As one example, the model simulation of the changes in pharmacokinetics for morbidly obese subjects is discussed
Functional Dynamics of PDZ Binding Domains: A Normal Mode Analysis
PDZ (Post-synaptic density-95/discs large/zonula occludens-1) domains are
relatively small (80 to 120 residues) protein binding modules central in the
organization of receptor clusters and in the association of cellular proteins.
Their main function is to bind C-terminals of selected proteins that are
recognized through specific amino-acids in their carboxyl end. Binding is
associated with a deformation of the PDZ native structure and is responsible
for dynamical changes in regions not in direct contact with the target. We
investigate how this deformation is related to the harmonic dynamics of the PDZ
structure and show that one low-frequency collective normal mode, characterized
by the concerted movements of different secondary structures, is involved in
the binding process. Our results suggest that even minimal structural changes
are responsible of communication between distant regions of the protein, in
agreement with recent Nuclear Magnetic Resonance (NMR) experiments. Thus PDZ
domains are a very clear example of how collective normal modes are able to
characterize the relation between function and dynamics of proteins, and to
provide indications on the precursors of binding/unbonding events.Comment: 25 pages, 10 figures, submitted to Biophysical Journa
Human physiologically based pharmacokinetic model for ACE inhibitors: ramipril and ramiprilat
BACKGROUND: The angiotensin-converting enzyme (ACE) inhibitors have complicated and poorly characterized pharmacokinetics. There are two binding sites per ACE (high affinity "C", lower affinity "N") that have sub-nanomolar affinities and dissociation rates of hours. Most inhibitors are given orally in a prodrug form that is systemically converted to the active form. This paper describes the first human physiologically based pharmacokinetic (PBPK) model of this drug class. METHODS: The model was applied to the experimental data of van Griensven et. al for the pharmacokinetics of ramiprilat and its prodrug ramipril. It describes the time course of the inhibition of the N and C ACE sites in plasma and the different tissues. The model includes: 1) two independent ACE binding sites; 2) non-equilibrium time dependent binding; 3) liver and kidney ramipril intracellular uptake, conversion to ramiprilat and extrusion from the cell; 4) intestinal ramipril absorption. The experimental in vitro ramiprilat/ACE binding kinetics at 4°C and 300 mM NaCl were assumed for most of the PBPK calculations. The model was incorporated into the freely distributed PBPK program PKQuest. RESULTS: The PBPK model provides an accurate description of the individual variation of the plasma ramipril and ramiprilat and the ramiprilat renal clearance following IV ramiprilat and IV and oral ramipril. Summary of model features: Less than 2% of total body ACE is in plasma; 35% of the oral dose is absorbed; 75% of the ramipril metabolism is hepatic and 25% of this is converted to systemic ramiprilat; 100% of renal ramipril metabolism is converted to systemic ramiprilat. The inhibition was long lasting, with 80% of the C site and 33% of the N site inhibited 24 hours following a 2.5 mg oral ramipril dose. The plasma ACE inhibition determined by the standard assay is significantly less than the true in vivo inhibition because of assay dilution. CONCLUSION: If the in vitro plasma binding kinetics of the ACE inhibitor for the two binding sites are known, a unique PBPK model description of the Griensven et. al. experimental data can be obtained
Anyonic interferometry and protected memories in atomic spin lattices
Strongly correlated quantum systems can exhibit exotic behavior called
topological order which is characterized by non-local correlations that depend
on the system topology. Such systems can exhibit remarkable phenomena such as
quasi-particles with anyonic statistics and have been proposed as candidates
for naturally fault-tolerant quantum computation. Despite these remarkable
properties, anyons have never been observed in nature directly. Here we
describe how to unambiguously detect and characterize such states in recently
proposed spin lattice realizations using ultra-cold atoms or molecules trapped
in an optical lattice. We propose an experimentally feasible technique to
access non-local degrees of freedom by performing global operations on trapped
spins mediated by an optical cavity mode. We show how to reliably read and
write topologically protected quantum memory using an atomic or photonic qubit.
Furthermore, our technique can be used to probe statistics and dynamics of
anyonic excitations.Comment: 14 pages, 6 figure
Not all international collaboration is beneficial: The Mendeley readership and citation impact of biochemical research collaboration
This is an accepted manuscript of an article published by Wiley Blackwell in Journal of the Association for Information Science and Technology on 13/05/2015, available online: https://doi.org/10.1002/asi.23515
The accepted version of the publication may differ from the final published version.Biochemistry is a highly funded research area that is typified by large research teams and is important for many areas of the life sciences. This article investigates the citation impact and Mendeley readership impact of biochemistry research from 2011 in the Web of Science according to the type of collaboration involved. Negative binomial regression models are used that incorporate, for the first time, the inclusion of specific countries within a team. The results show that, holding other factors constant, larger teams robustly associate with higher impact research, but including additional departments has no effect and adding extra institutions tends to reduce the impact of research. Although international collaboration is apparently not advantageous in general, collaboration with the USA, and perhaps also with some other countries, seems to increase impact. In contrast, collaborations with some other nations associate with lower impact, although both findings could be due to factors such as differing national proportions of excellent researchers. As a methodological implication, simpler statistical models would have found international collaboration to be generally beneficial and so it is important to take into account specific countries when examining collaboration
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