25 research outputs found
Superconducting gap variations induced by structural supermodulation in BSCCO
We discuss the possibility that the strain field introduced by the structural
supermodulation in Bi-2212 and certain other cuprate materials may modulate the
superconducting pairing interaction. We calculate the amplitude of this effect,
visible in scanning tunneling spectroscopy experiments, and thereby relate a
change in the local superconducting gap with the change in the local dopant
displacements induced by the supermodulation. In principle, since this
modulation is periodic, sufficiently accurate x-ray measurements or ab initio
calculations should enable one to determine which atomic displacements enhance
pairing and therefore T_c.Comment: 4 pages, 3 figure
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DOE Field Operations Program EV and HEV Testing
The United States Department of Energy’s (DOE) Field Operations Program tests advanced technology vehicles (ATVs) and disseminates the testing results to provide fleet managers and other potential ATV users with accurate and unbiased information on vehicle performance. The ATVs (including electric, hybrid, and other alternative fuel vehicles) are tested using one or more methods - Baseline Performance Testing (EVAmerica and Pomona Loop), Accelerated Reliability Testing, and Fleet Testing. The Program (http://ev.inel.gov/sop) and its nine industry testing partners have tested over 30 full-size electric vehicle (EV) models and they have accumulated over 4 million miles of EV testing experience since 1994. In conjunction with several original equipment manufacturers, the Program has developed testing procedures for the new classes of hybrid, urban, and neighborhood EVs. The testing of these vehicles started during 2001. The EVS 18 presentation will include (1) EV and hybrid electric vehicle (HEV) test results, (2) operating experience with and performance trends of various EV and HEV models, and (3) experience with operating hydrogen-fueled vehicles. Data presented for EVs will include vehicle efficiency (km/kWh), average distance driven per charge, and range testing results. The HEV data will include operating considerations, fuel use rates, and range testing results
When the optimal is not the best: parameter estimation in complex biological models
Background: The vast computational resources that became available during the
past decade enabled the development and simulation of increasingly complex
mathematical models of cancer growth. These models typically involve many free
parameters whose determination is a substantial obstacle to model development.
Direct measurement of biochemical parameters in vivo is often difficult and
sometimes impracticable, while fitting them under data-poor conditions may
result in biologically implausible values.
Results: We discuss different methodological approaches to estimate
parameters in complex biological models. We make use of the high computational
power of the Blue Gene technology to perform an extensive study of the
parameter space in a model of avascular tumor growth. We explicitly show that
the landscape of the cost function used to optimize the model to the data has a
very rugged surface in parameter space. This cost function has many local
minima with unrealistic solutions, including the global minimum corresponding
to the best fit.
Conclusions: The case studied in this paper shows one example in which model
parameters that optimally fit the data are not necessarily the best ones from a
biological point of view. To avoid force-fitting a model to a dataset, we
propose that the best model parameters should be found by choosing, among
suboptimal parameters, those that match criteria other than the ones used to
fit the model. We also conclude that the model, data and optimization approach
form a new complex system, and point to the need of a theory that addresses
this problem more generally
Regulation of neutrophil senescence by microRNAs
Neutrophils are rapidly recruited to sites of tissue injury or infection, where they protect against invading pathogens. Neutrophil functions are limited by a process of neutrophil senescence, which renders the cells unable to respond to chemoattractants, carry out respiratory burst, or degranulate. In parallel, aged neutrophils also undergo spontaneous apoptosis, which can be delayed by factors such as GMCSF. This is then followed by their subsequent removal by phagocytic cells such as macrophages, thereby preventing unwanted inflammation and tissue damage. Neutrophils translate mRNA to make new proteins that are important in maintaining functional longevity. We therefore hypothesised that neutrophil functions and lifespan might be regulated by microRNAs expressed within human neutrophils. Total RNA from highly purified neutrophils was prepared and subjected to microarray analysis using the Agilent human miRNA microarray V3. We found human neutrophils expressed a selected repertoire of 148 microRNAs and that 6 of these were significantly upregulated after a period of 4 hours in culture, at a time when the contribution of apoptosis is negligible. A list of predicted targets for these 6 microRNAs was generated from http://mirecords.biolead.org and compared to mRNA species downregulated over time, revealing 83 genes targeted by at least 2 out of the 6 regulated microRNAs. Pathway analysis of genes containing binding sites for these microRNAs identified the following pathways: chemokine and cytokine signalling, Ras pathway, and regulation of the actin cytoskeleton. Our data suggest that microRNAs may play a role in the regulation of neutrophil senescence and further suggest that manipulation of microRNAs might represent an area of future therapeutic interest for the treatment of inflammatory disease
The XMM Cluster Survey: X-ray analysis methodology
The XMM Cluster Survey (XCS) is a serendipitous search for galaxy clusters
using all publicly available data in the XMM-Newton Science Archive. Its main
aims are to measure cosmological parameters and trace the evolution of X-ray
scaling relations. In this paper we describe the data processing methodology
applied to the 5,776 XMM observations used to construct the current XCS source
catalogue. A total of 3,675 > 4-sigma cluster candidates with > 50
background-subtracted X-ray counts are extracted from a total non-overlapping
area suitable for cluster searching of 410 deg^2. Of these, 993 candidates are
detected with > 300 background-subtracted X-ray photon counts, and we
demonstrate that robust temperature measurements can be obtained down to this
count limit. We describe in detail the automated pipelines used to perform the
spectral and surface brightness fitting for these candidates, as well as to
estimate redshifts from the X-ray data alone. A total of 587 (122) X-ray
temperatures to a typical accuracy of < 40 (< 10) per cent have been measured
to date. We also present the methodology adopted for determining the selection
function of the survey, and show that the extended source detection algorithm
is robust to a range of cluster morphologies by inserting mock clusters derived
from hydrodynamical simulations into real XMM images. These tests show that the
simple isothermal beta-profiles is sufficient to capture the essential details
of the cluster population detected in the archival XMM observations. The
redshift follow-up of the XCS cluster sample is presented in a companion paper,
together with a first data release of 503 optically-confirmed clusters.Comment: MNRAS accepted, 45 pages, 38 figures. Our companion paper describing
our optical analysis methodology and presenting a first set of confirmed
clusters has now been submitted to MNRA
Cynomolgus Macaque as an Animal Model for Severe Acute Respiratory Syndrome
BACKGROUND: The emergence of severe acute respiratory syndrome (SARS) in 2002 and 2003 affected global health and caused major economic disruption. Adequate animal models are required to study the underlying pathogenesis of SARS-associated coronavirus (SARS-CoV) infection and to develop effective vaccines and therapeutics. We report the first findings of measurable clinical disease in nonhuman primates (NHPs) infected with SARS-CoV. METHODS AND FINDINGS: In order to characterize clinically relevant parameters of SARS-CoV infection in NHPs, we infected cynomolgus macaques with SARS-CoV in three groups: Group I was infected in the nares and bronchus, group II in the nares and conjunctiva, and group III intravenously. Nonhuman primates in groups I and II developed mild to moderate symptomatic illness. All NHPs demonstrated evidence of viral replication and developed neutralizing antibodies. Chest radiographs from several animals in groups I and II revealed unifocal or multifocal pneumonia that peaked between days 8 and 10 postinfection. Clinical laboratory tests were not significantly changed. Overall, inoculation by a mucosal route produced more prominent disease than did intravenous inoculation. Half of the group I animals were infected with a recombinant infectious clone SARS-CoV derived from the SARS-CoV Urbani strain. This infectious clone produced disease indistinguishable from wild-type Urbani strain. CONCLUSIONS: SARS-CoV infection of cynomolgus macaques did not reproduce the severe illness seen in the majority of adult human cases of SARS; however, our results suggest similarities to the milder syndrome of SARS-CoV infection characteristically seen in young children
Initial sequencing and analysis of the human genome
The human genome holds an extraordinary trove of information about human development, physiology, medicine and evolution. Here we report the results of an international collaboration to produce and make freely available a draft sequence of the human genome. We also present an initial analysis of the data, describing some of the insights that can be gleaned from the sequence.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/62798/1/409860a0.pd
Finishing the euchromatic sequence of the human genome
The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead
Electric and Hybrid Vehicle Testing
Today’s advanced-technology vehicles (ATVs) feature hybrid-electric engines, regenerative braking, advanced electric drive motors and batteries, and eventually fuel cell engines. There is considerable environmental and regulatory pressure on fleets to adopt these vehicles, resulting in high-risk purchase decisions on vehicles that do not have documented performance histories. The Department of Energy’s Field Operations Program tests ATVs and disseminates the results to provide accurate and unbiased information on vehicle performanc
Axiom Microbiome Array, the next generation microarray for high-throughput pathogen and microbiome analysis.
Microarrays have proven to be useful in rapid detection of many viruses and bacteria. Pathogen detection microarrays have been used to diagnose viral and bacterial infections in clinical samples and to evaluate the safety of biological drug materials. In this study, the Axiom Microbiome Array was evaluated to determine its sensitivity, specificity and utility in microbiome analysis of veterinary clinical samples. The array contains probes designed to detect more than 12,000 species of viruses, bacteria, fungi, protozoa and archaea, yielding the most comprehensive microbial detection platform built to date. The array was able to detect Shigella and Aspergillus at 100 genome copies, and vaccinia virus DNA at 1,000 genome copies. The Axiom Microbiome Array made correct species-level calls in mock microbial community samples. When tested against serum, tissue, and fecal samples from pigs experimentally co-infected with porcine reproductive and respiratory syndrome virus and porcine circovirus type 2, the microarray correctly detected these two viruses and other common viral and bacterial microbiome species. This cost-effective and high-throughput microarray is an efficient tool to rapidly analyze large numbers of clinical and environmental samples for the presence of multiple viral and bacterial pathogens