gebhart/patrepeval huggingface dataset:
Energetic Polymers and Plasticisers for Explosive Formulations - A Review of Recent Advances (2000)

In an effort to comply with Insensitive Munitions (IM) criteria, energetic binders comprising polymer and plasticiser(s) are finding use in cast-cured polymer bonded explosives and cast composite rocket propellants. Energetic binders can be considered as cross-linked polymers that provide a matrix to bind explosive ingredients together with a plasticiser. Once cured, the polymeric binder is a tough elastomeric rubber capable of absorbing and dissipating energy from hazardous stimuli, lending itself well to IM applications. This general document outlines the most promising energetic polymers and plasticisers being considered today. Attention is focussed on several energetic polymers including glycidyl azide polymer, GAP, poly(3-nitratomethyl-3-methyloxetane), polyNIMMO and poly(glycidyl nitrate), polyGLYN, although several other energetic polymers will also be reviewed. Energetic plasticisers including oligomers (low molecular weight) of the polymers mentioned above, as well as a variety of nitrate esters, nitroaromatics and azido plasticisers, will also be reviewed. Finally, the review will recommend binder systems for DSTO's future energetic binder programs.
Orthopedic outcomes of long-term daily corticosteroid treatment in Duchenne muscular dystrophy (2007)

Although boys with Duchenne muscular dystrophy on long-term corticosteroid treatment have a significantly decreased risk of scoliosis and an extension of more than 3 years' independent ambulation, they are at increased risk of vertebral and lower limb fractures compared with untreated boys.
Self-optimizing AST interpreters (2012)

An abstract syntax tree (AST) interpreter is a simple and natural way to implement a programming language. However, it is also considered the slowest approach because of the high overhead of virtual method dispatch. Language implementers therefore define bytecodes to speed up interpretation, at the cost of introducing inflexible and hard to maintain bytecode formats. We present a novel approach to implementing AST interpreters in which the AST is modified during interpretation to incorporate type feedback. This tree rewriting is a general and powerful mechanism to optimize many constructs common in dynamic programming languages. Our system is implemented in Java and uses the static typing and primitive data types of Java elegantly to avoid the cost of boxed representations of primitive values in dynamic programming languages.
Selective photothermolysis of lipid-rich tissues: A free electron laser study (2006)

Selective photothermal targeting of fatty tissues is feasible using infrared lipid absorption bands. Potential clinical applications are suggested by this FEL study.
Towards Absolute Quantification of Therapeutic Monoclonal Antibody in Serum by LC−MS/MS Using Isotope-Labeled Antibody Standard and Protein Cleavage Isotope Dilution Mass Spectrometry (2008)

Although LC-MS methods are increasingly used for the absolute quantification of proteins, the lack of appropriate internal standard (IS) hinders the development of rapid and standardized analytical methods for both in vitro and in vivo studies. Here, we have developed a novel method for the absolute quantification of a therapeutic protein, which is monoclonal antibody (mAb). The method combines liquid chromatography tandem mass spectrometry (LC-MS/MS) and protein cleavage isotope dilution mass spectrometry with the isotope-labeled mAb as IS. The latter was identical to the analyzed mAb with the exception that each threonine contains four (13)C atoms and one (15)N atom. Serum samples were spiked with IS prior to the overnight trypsin digestion and subsequent sample cleanup. Sample extracts were analyzed on a C18 ACE column (150 mm x 4.6 mm) using an LC gradient time of 11 min. Endogenous mAb concentrations were determined by calculating the peak height ratio of its signature peptide to the corresponding isotope-labeled peptide. The linear dynamic range was established between 5.00 and 1000 microg/mL mAb with accuracy and precision within +/-15% at all concentrations and below +/-20% at the LLOQ (lower limit of quantification). The overall method recovery in terms of mAb was 14%. The losses due to sample preparation (digestion and purification) were 72% from which about 32% was due to the first step of the method, the sample digestion. This huge loss during sample preparation strongly emphasizes the necessity to employ an IS right from the beginning. Our method was successfully applied to the mAb quantification in marmoset serum study samples, and the precision obtained on duplicate samples was, in most cases, below 20%. The comparison with enzyme-linked immunosorbent assay (ELISA) showed higher exposure in terms of AUC and Cmax with the LC-MS/MS method. Possible reasons for this discrepancy are discussed in this study. The results of this study indicate that our LC-MS/MS method is a simple, rapid, and precise approach for the therapeutic mAb quantification to support preclinical and clinical studies.
Clinical diagnosis of the Usher syndromes (1994)

The Usher syndromes are genetically distinct disorders which share specific phenotypic characteristics. This paper describes a set of clinical criteria recommended for the diagnosis of Usher syndrome type I and Usher syndrome type II. These criteria have been adopted by the Usher Syndrome Consortium and are used in studies reported by members of this Consortium.
Effects of in vivo administration of anti-T3 monoclonal antibody on T cell function in mice. I. Immunosuppression of transplantation responses. (1988)

Anti-T3 mAb are being increasingly used clinically in the treatment of organ graft rejection. However, there has not previously been a murine model in which the effects of these mAb on the immune system could be studied in vivo. We have established such a model using the anti-murine-T3 mAb, 145-2C11. Administration of 145-2C11 led to rapid depletion of T cells from peripheral blood and suppression of skin graft rejection. However, depletion of T cells from spleen and lymph node was both delayed and incomplete. Full recovery of T cell number was dependent on the presence of a thymus, but treatment of thymectomized animals revealed that depletion was not the mechanism by which the mAb induced immunosuppression. Rather, alterations in TCR expression may play a more important role. TCR had modulated from T cells in spleen and lymph node early after treatment, and TCR expression remained subnormal for at least 51 days posttreatment. However, subnormal TCR expression alone could not fully explain the observed T cell dysfunction, inasmuch as a period of time existed after TCR re-expression during which T cells appeared to be anergic to CTL and MLR reactivity. These findings implicate T cell dysfunction as an important element in the induction of immunosuppression after anti-T3 administration.
Discovery of Aryloxy Tetramethylcyclobutanes as Novel Androgen Receptor Antagonists (2011)

An aryloxy tetramethylcyclobutane was identified as a novel template for androgen receptor (AR) antagonists via cell-based high-throughput screening. Follow-up to the initial "hit" established 5 as a viable lead. Further optimization to achieve full AR antagonism led to the discovery of 26 and 30, both of which demonstrated excellent in vivo tumor growth inhibition upon oral administration in a castration-resistant prostate cancer (CRPC) animal model.
Crystal structure of Clostridium botulinum neurotoxin protease in a product-bound state: Evidence for noncanonical zinc protease activity (2004)

Clostridium botulinum neurotoxins (BoNTs), the most potent toxins known, disrupt neurotransmission through proteolysis of proteins involved in neuroexocytosis. The light chains of BoNTs are unique zinc proteases that have stringent substrate specificity and require exceptionally long substrates. We have determined the crystal structure of the protease domain from BoNT serotype A (BoNT/A). The structure reveals a homodimer in a product-bound state, with loop F242-V257 from each monomer deeply buried in its partner's catalytic site. The loop, which acts as a substrate, is oriented in reverse of the canonical direction for other zinc proteases. The Y249-Y250 peptide bond of the substrate loop is hydrolyzed, leaving the Y249 product carboxylate coordinated to the catalytic zinc. From the crystal structure of the BoNT/A protease, detailed models of noncanonical binding and proteolysis can be derived which we propose are also consistent with BoNT/A binding and proteolysis of natural substrate synaptosome-associated protein of 25 kDa (SNAP-25). The proposed BoNT/A substrate-binding mode and catalytic mechanism are markedly different from those previously proposed for the BoNT serotype B.
Circadian Variability of Insulin Sensitivity: Physiological Input for In Silico Artificial Pancreas (2014)

The incorporation of a time-varying SI into the simulator makes this technology suitable for running multiple-meal scenarios, thus enabling a more robust design of artificial pancreas algorithms.
Cell-Surface Expression and Alloantigenic Function of a Human Nonclassical Class I Molecule (HLA-E) in Transgenic Mice (1999)

We have introduced the gene (E*01033) encoding the heavy chain of the human nonclassical MHC class I Ag, HLA-E, into the mouse genome. Two founder mice carry a 21-kb fragment, the others bear an 8-kb fragment. Each of the founder mice was mated to mice of an already established C57BL/10 transgenic line expressing human beta2-microglobulin (beta2m). Cell surface HLA-E was detected on lymph node cells by flow cytometry only in the presence of endogenous human beta2m. However, HLA-E-reactive mouse CTL (H-2-unrestricted) lysed efficiently the target cells originating from HLA-E transgenic mice without human beta2m, showing that the HLA-E protein can be transported to the cell surface in the absence of human beta2m, presumably by association with murine beta2m. Rejection of skin grafts from HLA-E transgenic mice demonstrates that HLA-E behaves as a transplantation Ag in mice. HLA-E transgenic spleen cells are effective in stimulating an allogeneic CTL response in normal and human classical class I (HLA-B27) transgenic mice. Furthermore, results from split-well analysis indicate that the majority of the primary in vivo-induced CTL recognizes HLA-E as an intact molecule (H-2-unrestricted recognition) and not as an HLA-E-derived peptide presented by a mouse MHC molecule, although a small fraction (ranging from 4 to 21%) of the primary in vivo-induced CTL is able to recognize HLA-E in an H-2-restricted manner. Based on these observations, we conclude that HLA-E exhibits alloantigenic properties that are indistinguishable from classical HLA class I molecules when expressed in transgenic mice.
Performance analysis of different algorithms for cdma2000 antenna array system and a new multi user beamforming (MUB) algorithm (2002)

In this paper, the use of base station antenna arrays in wireless code division multiple access (CDMA) systems is studied. Different beamforming algorithms are simulated based on the cdma2000 uplink physical layer specifications. The performance of these algorithms is compared as a function of the number of active users under realistic conditions. The paper also presents a post-processing multi-user-beamforming (MUB) algorithm to be applied at the base station. Simulation results show an improvement in performance after applying MUB.
Biosynthesis of the Validamycins:  Identification of Intermediates in the Biosynthesis of Validamycin A by Streptomyces hygroscopicus var. limoneus (2001)

To study the biosynthesis of the pseudotrisaccharide antibiotic, validamycin A (1), a number of potential precursors of the antibiotic were synthesized in (2)H-, (3)H-, or (13)C-labeled form and fed to cultures of Streptomyces hygroscopicus var. limoneus. The resulting validamycin A from each of these feeding experiments was isolated, purified and analyzed by liquid scintillation counting, (2)H- or (13)C NMR or selective ion monitoring mass spectrometry (SIM-MS) techniques. The results demonstrate that 2-epi-5-epi-valiolone (9) is specifically incorporated into 1 and labels both cyclitol moieties. This suggests that 9 is the initial cyclization product generated from an open-chain C(7) precursor, D-sedoheptulose 7-phosphate (5), by a DHQ synthase-like cyclization mechanism. A more proximate precursor of 1 is valienone (11), which is also incorporated into both cyclitol moieties. The conversion of 9 into 11 involves first epimerization to 5-epi-valiolone (10), which is efficiently incorporated into 1, followed by dehydration, although a low level of incorporation of 2-epi-valienone (15) is also observed. Reduction of 11 affords validone (12), which is also incorporated specifically into 1, but labels only the reduced cyclitol moiety. The mode of introduction of the nitrogen atom linking the two pseudosaccharide moieties is not clear yet. 7-Tritiated valiolamine (8), valienamine (2), and validamine (3) were all not incorporated into 1, although each of these amines has been isolated from the fermentation, with 3 being most prevalent. Demonstration of in vivo formation of [7-(3)H]validamine ([7-(3)H]-3) from [7-(3)H]-12 suggests that 3 may be a pathway intermediate and that the nonincorporation of [7-(3)H]-3 into 1 is due to a lack of cellular uptake. We thus propose that 3, formed by amination of 12, and 11 condense to form a Schiff base, which is reduced to the pseudodisaccharide unit, validoxylamine A (13). Transfer of a D-glucose unit to the 4'-position of 13 then completes the biosynthesis of 1. Other possibilities for the mechanism of formation of the nitrogen bridge between the two pseudosaccharide units are also discussed.
Efforts toward Expansion of the Genetic Alphabet:  Optimization of Interbase Hydrophobic Interactions (2000)

Six novel unnatural nucleobases have been characterized that form stable base pairs in duplex DNA, relying not on hydrogen bonds, but rather on interbase hydrophobic interactions. These nucleobases are derivatives of the hydrophobic base pair between 7-azaindole (7AI) and isocarbostyril (ICS). Derivatives of 7AI and ICS were examined that have increased hydrophobic surface area, as well as increased polarizability. As observed with 7AI and ICS, these derivatives are recognized as substrates by Klenow fragment of Escherichia coli DNA polymerase I. The unnatural base pair between pyrrolopyrizine (PP) and C3-methylisocarbostyril (MICS) is enzymatically incorporated into DNA with high efficiency (kcat/KM = 106 M-1 min-1) and moderate selectivity. These studies represent a significant step toward the generation of a stable, orthogonal base pair that can be enzymatically incorporated into DNA with good fidelity.
Chronic overload of SEPT4, a parkin substrate that aggregates in Parkinson’s disease, causes behavioral alterations but not neurodegeneration in mice (2013)

Together, these data indicate that septin dysregulations commonly found in postmortem human brains with Parkinson's disease, schizophrenia and bipolar disorders may be responsible for a subset of behavioral abnormalities in the patients.
A brief history of angiogenesis assays (2011)

The major problem with angiogenesis research is the choice of an appropriate assay. Currently, many in vitro and in vivo techniques are available for research into the functions of endothelial cells during angiogenesis. In this historical review article, we describe and evaluate the methodology and specific features of some of the most frequently used of these assays.
Prolactin-Releasing Peptides Do Not Stimulate Prolactin Release in vivo (2000)

The prolactin (PRL)-releasing activity of the novel prolactin-releasing peptides (PrRPs) was studied in vivo using male and lactating female rats. Whereas thyrotropin-releasing hormone effectively stimulated PRL and thyrotropin release as expected, PrRP in both animal models neither stimulated PRL secretion nor affected the release of other pituitary hormones. At the anterior pituitary level, in situ hybridization (ISH) histochemistry and Northern blot analysis revealed significantly higher expression levels of PrRP receptor (UHR-1) transcripts in female compared to male rats but not between lactating and nonlactating animals. By ISH, expression of UHR-1 mRNA was also detected in the intermediate lobe but not in the posterior pituitary. UHR-1 transcripts were also readily detectable in various hypothalamic brain areas whereas expression of PrRP mRNA was restricted to the ventral part of the dorsomedial hypothalamic nucleus but was not detected in neuroendocrine hypothalamic nuclei (e.g. PVN, SON). We thus assume that in the central nervous system, PrRP may likely have functions as a neuromodulator. However, together with the detailed cytochemical studies of various investigators that failed to detect PrRP-immunopositive nerve endings in the median eminence, our results strongly suggest that the hypothalamic PrRPs cannot be classified as hypophysiotrophic factors.
Specific growth factors and the healing of chronic wounds (2001)

Part II of this two-part review focuses on the function of specific growth factors in wound healing and considers the results of clinical trials of their use in chronic wounds.
Neurobiology (2002)

The most complex feature of the human body is the brain. Of all the genes in the human genome, as many as 50% may be exclusively expressed in the brain. In this section we consider the molecular basis of brain and nervous system function in health and disease.
Growth performance and antioxidant status of growing rabbits fed on diets supplemented with Eucommia ulmoides leaves (2018)

&lt;p&gt;The present study evaluated the effect of dietary &lt;em&gt;Eucommia ulmoides leaves&lt;/em&gt; (EUL) on growth performance and antioxidant status of growing rabbits under heat stress condition. Four hundred and fifty weaned New Zealand male rabbits (6 wk old) were randomly divided into 3 equal groups (150 rabbits/group) and fed with a basal diet (control, digestible energy (DE): 15.92 MJ/kg and crude protein (CP): 19.24%) or the basal diet supplemented with 1 or 5 g of EUL/kg of diet (EUL1 and EUL5), in which the same quantity of barley meal was replaced. During the 21 d of experiment (43 to 63 d of age), the temperature and relative humidity of the rabbit house ranged from 27.5 to 32.5°C and from 65 to 73%, respectively. We analysed feed intake, growth performance and antioxidant status of growing rabbits. Compared with the control group, at the end of the experimental period, EUL supplementation significantly reduced the average daily feed intake (92.0, 92.8 and 100.7 g/d for EUL1, EUL5 and control, respectively; P&amp;lt;0.05), improved the feed conversion ratio (3.80, 3.81 and 4.59 for EUL1, EUL5 and control, respectively; P&amp;lt;0.05), increased the activities of glutathione peroxidase (+35.5 and +35.0% in plasma and liver of rabbits in EUL5 vs. control group, respectively; P&amp;lt;0.05) and reduced those of malondialdehyde (–12.0 and –46.0% in plasma and liver of rabbits in EUL5 vs. control group, respectively; P&amp;lt;0.05). These results suggest that inclusion of EUL in the diet of growing rabbits improved the growth performance and antioxidant status in growing rabbits.&lt;/p&gt;
Conjugation of Lipid and CpG-Containing Oligonucleotide Yields an Efficient Method for Liposome Incorporation (2011)

For optimal stimulation of T cells, protein-based vaccines must deliver protein antigens to antigen-presenting cells while simultaneously providing immunostimulatory signals. Listeriolysin O (LLO)-containing liposomes have been utilized to efficiently deliver protein antigens to the cytosolic pathway for antigen processing and major histocompatibility complex class I-dependent presentation while codelivering immunostimulatory CpG-oligodeoxyribonuceotides (ODNs). In this report, we describe the synthesis of lipid-CpG-ODN conjugates utilizing maleimide-phosphatidylethanolamine (PE) lipids and 5'-sulfhdryl-containing CpG-ODNs as a method for facile incorporation of CpG-ODNs in liposomal vaccine carriers, an alternative to co-encapsulation inside liposomes and as a means to enhance delivery of CpG-ODNs to their major receptor, Toll-like receptor 9 (TLR9), in the endosome. The characterization and biological evaluation of the vaccine delivery system made of liposomes, which contain the lipid-CpG-ODN conjugates inserted in the liposomal membrane, is described. We demonstrate in vitro in bone marrow derived macrophages that the lipid-CpG-ODN conjugates incorporated onto the liposome bilayers interact with their receptor TLR9 as readily as liposome-encapsulated ODNs and exert their immunostimulatory capabilities. The liposomal vaccine delivery systems were evaluated in mice using ovalbumin (OVA) as a model antigen, and the results indicate equally robust OVA-specific cytotoxic T lymphocyte responses and similar Th1 immune skewing capabilities between liposomes containing lipid-conjugated or encapsulated CpG-ODNs. Overall, this work indicates that conjugating PE lipids and CpG-ODNs results in an efficient method that allows facile incorporation of CpG-ODNs into a liposome-based delivery platform while retaining the immune-stimulating capabilities of CpG-ODNs.
Laser capture microdissection of fluorescently labeled embryonic cranial neural crest cells (2004)

This study is the first to report a unique genetic strategy to permanently label mammalian neural crest cells (NCC) with a fluorescent marker, selectively isolate the labeled NCC or their derivatives during murine ontogenesis by laser capture microdissection (LCM), and prepare molecular components, such as RNA, for selective gene expression analyses. Through utilization of a Cre recombinase/loxP system, a genetic strategy that has been used repeatedly to achieve tissue-specific activation of reporter transgenes in mice, a novel two-component mouse model was created in which neural crest cells (and their progeny) are indelibly marked throughout the pre- and postnatal lifespan of the organism. To generate this mouse model, a Wnt1-Cre transgenic line was crossed with a mouse line expressing a conditional reporter transgene ("floxed" enhanced green fluorescent protein). Resulting offspring, expressing both the Wnt1-Cre and "floxed" EGFP alleles, demonstrated EGFP expression in the NCC and all of their derivatives throughout embryonic, postnatal, and adult stages. In the present study, EGFP-labeled cranial NCC from the first branchial arch of gestational day 9.5 murine embryos were visualized in frozen tissue sections and isolated by LCM under epifluorescence optics. RNA was extracted from "captured" cells and amplified by double-stranded cDNA synthesis and in vitro transcription. Amplified mRNA samples from "captured" cells were evaluated by TaqMan quantitative, real-time PCR for the expression of a panel of NCC gene markers. The molecular genetic strategy delineated in this report will facilitate future embryo-genomic and -proteomic analyses of mammalian NCC that will serve to further our understanding of these pluripotent embryonic progenitor cells.