Shaping Thermal Transport and Temperature Distribution via Anisotropic Carbon Fiber Reinforced Composites.

With the ongoing electrification of vehicles, thermal management is on everyone's lips. To prevent overheating in electronic systems, new design strategies for thermal dissipation are needed. Thermally anisotropic materials enable targeted directional heat transport due to their anisotropic thermal conduction.

Preclinical Evidence for the Role of Botulinum Neurotoxin A (BoNT/A) in the Treatment of Peripheral Nerve Injury.

Traumatic peripheral nerve injuries tend to be more common in younger, working age populations and can lead to long-lasting disability. Peripheral nerves have an impressive capacity to regenerate; however, successful recovery after injury depends on a number of factors including the mechanism and severity of the trauma, the distance from injury to the reinnervation target, connective tissue sheath integrity, and delay between injury and treatment. Even though modern surgical procedures have greatly improved the success rate, many peripheral nerve injuries still culminate in persistent neuropathic pain and incomplete functional recovery.

A Systems Perspective of DoD Global Health Engagement.

Introduction: A systems perspective was used to describe U.S. Department of Defense (DoD) Global Health Engagement (GHE).

Government Cloud Computing Policies: Potential Opportunities for Advancing Military Biomedical Research.

Introduction: This position paper summarizes the development and the present status of Department of Defense (DoD) and other government policies and guidances regarding cloud computing services. Due to the heterogeneous and growing biomedical big datasets, cloud computing services offer an opportunity to mitigate the associated storage and analysis requirements. Having on-demand network access to a shared pool of flexible computing resources creates a consolidated system that should reduce potential duplications of effort in military biomedical research.

Yesterday and Today: The Impact of Research Conducted at Camp Detrick on Botulinum Toxin.

Introduction: This review summarizes the research conducted on botulinum toxin (BoTx) from 1943 to 1956 by a small group of Camp Detrick investigators and their staff. A systematic, cross-disciplinary approach was used to develop effective vaccines against this biological warfare threat agent. In response to the potential need for medical countermeasures against BoTx during World War II, the refinement of isolation and purification techniques for BoTx successfully led to the large-scale production of botulinum toxoid vaccines.

Collaborative Systems Biology Projects for the Military Medical Community.

Introduction: This pilot study was conducted to examine, for the first time, the ongoing systems biology research and development projects within the laboratories and centers of the U.S. Army Medical Research and Materiel Command (USAMRMC).

Differential regulation of oxidative burst by distinct β-glucan-binding receptors and signaling pathways in human peripheral blood mononuclear cells.

β-Glucans possess broad immunomodulatory properties, including activation of innate immune functions such as oxidative burst activity. The differential roles of complement receptor type 3 (CR3) and Dectin-1, the known β-glucan receptors, and their associated signaling pathways in the generation of oxidative burst induced by different physical forms of Saccharomyces cerevisiae-derived β-glucan were examined in human peripheral blood mononuclear cells (PBMC). In this study whole glucan particle (WGP) or immobilized soluble β-glucan (ISG) was used to represent the phagocytizable or the nonphagocytizable form of a fungus, respectively.

Decay-accelerating factor limits hemorrhage-instigated tissue injury and improves resuscitation clinical parameters.

Background: Complement is invariably activated during trauma and contributes to tissue injury. Recombinant human decay-accelerating factor (DAF), a complement regulatory protein that inhibits both classical and alternative pathways, improves survival and reduces tissue damage in animal models of tissue injury. The extent to which DAF may facilitate resuscitation in hemorrhaged large animals is not known.

Kinetic and reaction pathway analysis in the application of botulinum toxin a for wound healing.

A relatively new approach in the treatment of specific wounds in animal models and in patients with type A botulinum toxin is the focus of this paper. The indications or conditions include traumatic wounds (experimental and clinical), surgical (incision) wounds, and wounds such as fissures and ulcers that are signs/symptoms of disease or other processes. An objective was to conduct systematic literature searches and take note of the reactions involved in the healing process and identify corresponding pharmacokinetic data.

The zinc-dependent protease activity of the botulinum neurotoxins.

The botulinum neurotoxins (BoNT, serotypes A-G) are some of the most toxic proteins known and are the causative agents of botulism. Following exposure, the neurotoxin binds and enters peripheral cholinergic nerve endings and specifically and selectively cleaves one or more SNARE proteins to produce flaccid paralysis. This review centers on the kinetics of the Zn-dependent proteolytic activities of these neurotoxins, and briefly describes inhibitors, activators and factors underlying persistence of toxin action.

Temporal characteristics of botulinum neurotoxin therapy.

Botulinum neurotoxin is a pharmaceutical treatment used for an increasing number of neurological and non-neurological indications, symptoms and diseases. Despite the wealth of clinical reports that involve the timing of the therapeutic effects of this toxin, few studies have attempted to integrate these data into unified models. Secondary reactions have also been examined including the development of adverse events, resistance to repeated applications, and nerve terminal sprouting.

Fold prediction of VP24 protein of Ebola and Marburg viruses using de novo fragment assembly.

Virus particle 24 (VP24) is the smallest protein of the Ebola and Marburg virus genomes. Recent experiments show that Ebola VP24 blocks binding of tyrosine-phosphorylated STAT-1 homodimer (PY-STAT1) to the NPI-1 subfamily of importin alpha, thereby preventing nuclear accumulation of this interferon-promoting transcription factor which, in turn, reduces the innate immune response of the host target. Lacking an experimental structure for VP24, we applied de novo protein structure prediction using the fragment assembly-based Rosetta method to classify its fold topology and better understand its biological function.

IC50-to-Ki: a web-based tool for converting IC50 to Ki values for inhibitors of enzyme activity and ligand binding.

A new web-server tool estimates K(i) values from experimentally determined IC(50) values for inhibitors of enzymes and of binding reactions between macromolecules (e.g. proteins, polynucleic acids) and ligands.

Onset dynamics of type A botulinum neurotoxin-induced paralysis.

Experimental studies have demonstrated that botulinum neurotoxin serotype A (BoNT/A) causes flaccid paralysis by a multi-step mechanism. Following its binding to specific receptors at peripheral cholinergic nerve endings, BoNT/A is internalized by receptor-mediated endocytosis. Subsequently its zinc-dependent catalytic domain translocates into the neuroplasm where it cleaves a vesicle-docking protein, SNAP-25, to block neurally evoked cholinergic neurotransmission.

botXminer: mining biomedical literature with a new web-based application.

This paper outlines botXminer, a publicly available application to search XML-formatted MEDLINE data in a complete, object-relational schema implemented in Oracle XML DB. An advantage offered by botXminer is that it can generate quantitative results with certain queries that are not feasible through the Entrez-PubMed interface. After retrieving citations associated with user-supplied search terms, MEDLINE fields (title, abstract, journal, MeSH and chemical) and terms (MeSH qualifiers and descriptors, keywords, author, gene symbol and chemical), these citations are grouped and displayed as tabulated or graphic results.

Characterization of botulinum progenitor toxins by mass spectrometry.

Botulinum toxin analysis has renewed importance. This study included the use of nanochromatography-nanoelectrospray-mass spectrometry/mass spectrometry to characterize the protein composition of botulinum progenitor toxins and to assign botulinum progenitor toxins to their proper serotype and strain by using currently available sequence information. Clostridium botulinum progenitor toxins from strains Hall, Okra, Stockholm, MDPH, Alaska, and Langeland and 89 representing serotypes A through G, respectively, were reduced, alkylated, digested with trypsin, and identified by matching the processed product ion spectra of the tryptic peptides to proteins in accessible databases.

BotDB: A database resource for the clostridial neurotoxins.

BotDB is a database designed to encapsulate the rapidly expanding amount of information about the structure and function of the botulinum (BoNT) and tetanus neurotoxins and to track a variety of basic and applied research efforts. The AceDB management system was chosen for this project because of its flexibility in manipulating semistructured data sets and for its information retrieval query languages. In addition to storing amino and nucleic acid sequences of the clostridial neurotoxin genes and proteins, BotDB provides sequence data for new classes of objects, including neurotoxin mutants, substrates and their mutants, associated nontoxic proteins, and C-fragment vaccine candidates.

Mechanism of action of sodium cyanide on rat diaphragm muscle.

The effects of sodium cyanide (NaCN) were investigated on the contractile and electrophysiological properties of rat diaphragm muscles in vitro. Sodium cyanide (0.1-1.

Prediction of a conserved, neutralizing epitope in ribosome-inactivating proteins.

The secondary structures, side-chain solvent accessibilities, and superpositioned crystal structures of the A-chain of ricin and four other plant rRNA N-glycosidases (ribosome-inactivating proteins, RIPs) were examined. Previously, a 26-residue fragment from the A-chain of ricin was determined to bind to a neutralizing monoclonal antibody. The region in the native ricin A-chain, to which this peptide corresponds, is solvent-exposed and contains a negatively charged residue that has been hypothesized to participate in the toxin's function, namely, rRNA binding and/or enzymatic activity.

Identifying the principal protective antigenic determinants of type A botulinum neurotoxin.

The neurotoxins from Clostridium botulinum (BoNT serotypes A-G) exert their lethal effect by preventing the release of acetylcholine at the neuromuscular junction. As with tetanus toxin, immunization with a non-toxic fragment, the 50 kDa C-terminal portion of BoNT/A (Hc; residues 861-1296), protects mice against lethal challenges with the intact toxin. To locate the neutralizing epitopes, several protective monoclonal antibodies (mAbs) against BoNT/A-Hc were isolated and cloned.

Predictions of secondary structure and solvent accessibility of the light chain of the clostridial neurotoxins.

Predictions were made of the secondary, two-dimensional (2-D) structures and side-chain solvent accessibilities of the light (L) chains of the clostridial neurotoxins (botulinum neurotoxin serotypes A-G and tetanus neurotoxin). An artificial neural network was used to make these predictions from a multiple alignment of their primary structures and was the approach used in making successful predictions for the C-fragments of these neurotoxins (Lebeda et al., J.

Accuracy of secondary structure and solvent accessibility predictions for a clostridial neurotoxin C-fragment.

Earlier studies used Rost and Sander's artificial neural network [(1993a), J. Mol. Biol.

Suppression of drug-induced epileptiform discharges by cyclic AMP in rat hippocampus.

The effect of cyclic adenosine 3',5'-monophosphate (cAMP) on epileptiform activity in rat hippocampal slices was investigated. Bath-applied cAMP reversibly decreased the frequency of extracellularly recorded discharges in the CA3 subfield induced by bethanechol- or theophylline-containing solutions. Because cAMP was presumed to be relatively membrane impermeant, we developed and tested the hypothesis that this cAMP-mediated effect occurred extracellularly through the catabolic conversion of cAMP to 5'-AMP and, in turn, to adenosine, a known inhibitory neuromodulator.

Predicting differential antigen-antibody contact regions based on solvent accessibility.

A novel computational approach was examined for predicting epitopes from primary structures of the seven immunologically distinct botulinum neurotoxins (BoNT/A-G) and tetanus toxin (TeTX). An artificial neural network [Rost and Sander (1994), Proteins 20, 216] was used to estimate residue solvent accessibilities in multiple aligned sequences. A similar network trained to predict secondary structures was also used to examine this protein family, whose tertiary fold is presently unknown.