gebhart/patrepeval huggingface dataset:
Meniscal Rasping for Repair of Meniscal Tear in the Avascular Zone (1999)

We examined experimentally whether a longitudinal tear in the avascular zone of a rabbit meniscus can be healed by meniscal rasping. A full-thickness longitudinal tear 5-mm long was artificially created in the avascular zone of the anterior segment of both medial menisci. Meniscal rasping was then done on the femoral surface of the right meniscus from the parameniscal synovium to the inner segment including the tear. The left meniscus was left without further treatment as control. Two to 4 weeks after surgery, the hypertrophic synovium was observed invading from the parameniscal region to the injured portion. Eight to 16 weeks after surgery, the tear was almost completely healed. In contrast, neither hypertrophy of the synovium covering the tear nor healing was induced in the control meniscus. The mechanical test showed that there was a significant difference in the tensile strength and the stiffness of the injured portion between the rasped meniscus and the control meniscus. Meniscal rasping is easy to do, is effective, and causes few adverse effects with menisci. This procedure may be a treatment option for clinical cases of meniscal tear in the avascular zone for which we have no effective and clinically applicable methods at present, although further investigation is needed before clinical application.
Octreotide – A Review of its Use in Treating Neuroendocrine Tumours (2013)

Neuroendocrine tumours (NETs) are a heterogeneous group of neoplasms whose incidence has dramatically increased in recent years. Octreotide is a somatostatin analogue used in the treatment of NETs, and its use in clinical trials has been associated with substantially increased survival. Although traditionally used for the relief of symptoms that result from release of peptides and neuroamines, there has been a growing body of evidence that suggest octreotide has antiproliferative effects. A phase III clinical study has demonstrated that the long-acting formulation (LAR), octreotide LAR, lengthens time to tumour progression in patients with well-differentiated metastatic midgut NETs, and that octreotide LAR is a treatment option for patients with metastatic midgut NETs, regardless of functional status. Furthermore, octreotide LAR has demonstrated clinical efficacy in different types of NETs. These data, along with emerging data on somatostatin analogs, may change the way doctors approach this patient population and reinforce the use of these drugs as a treatment option for patients with non-functioning tumours.
Liposomal encapsulation increases the activity of the topoisomerase I inhibitor topotecan. (1995)

Topotecan, a topoisomerase I poison and water-soluble derivative of camptothecin, has shown promise in treating solid tumors; however, the drug is unstable under physiological conditions and converts to an inactive form within 30 minutes. Encapsulating topotecan in liposomes (LIP-TPT) minimizes inactivation. The efficacy of LIP-TPT was examined with a novel in vivo bioassay called ICE for In vivo Complexes of Enzyme. This bioassay uses antibodies to probe DNA for the presence of topoisomerase I covalent complexes and thereby allows direct quantification of topoisomerase I driven DNA adducts in living cells. We report that LIP-TPT was three- to fourfold more effective than free TPT in stabilizing covalent topoisomerase I-DNA intermediates inside tumor cells. These findings reveal that liposomal wrapping permitted effective delivery of camptothecin derivatives to active enzyme in the nucleus of the cell.
Phylogenetic footprinting of transcription factor binding sites in proteobacterial genomes (2001)

Toward the goal of identifying complete sets of transcription factor (TF)-binding sites in the genomes of several gamma proteobacteria, and hence describing their transcription regulatory networks, we present a phylogenetic footprinting method for identifying these sites. Probable transcription regulatory sites upstream of Escherichia coli genes were identified by cross-species comparison using an extended Gibbs sampling algorithm. Close examination of a study set of 184 genes with documented transcription regulatory sites revealed that when orthologous data were available from at least two other gamma proteobacterial species, 81% of our predictions corresponded with the documented sites, and 67% corresponded when data from only one other species were available. That the remaining predictions included bona fide TF-binding sites was proven by affinity purification of a putative transcription factor (YijC) bound to such a site upstream of the fabA gene. Predicted regulatory sites for 2097 E.coli genes are available at http://www.wadsworth.org/resnres/bioinfo/.
Approximation by Quantum Circuits (1995)

In a recent preprint by Deutsch et al. [1995] the authors suggest the possibility of polynomial approximability of arbitrary unitary operations on $n$ qubits by 2-qubit unitary operations. We address that comment by proving strong lower bounds on the approximation capabilities of g-qubit unitary operations for fixed g. We consider approximation of unitary operations on subspaces as well as approximation of states and of density matrices by quantum circuits in several natural metrics. The ability of quantum circuits to probabilistically solve decision problem and guess checkable functions is discussed. We also address exact unitary representation by reducing the upper bound by a factor of n^2 and by formalizing the argument given by Barenco et al. [1995] for the lower bound. The overall conclusion is that almost all problems are hard to solve with quantum circuits.
Genetic characterization and cloning of mothers against dpp, a gene required for decapentaplegic function in Drosophila melanogaster. (1995)

The decapentaplegic (dpp) gene of Drosophila melanogaster encodes a growth factor that belongs to the transforming growth factor-beta (TGF-beta) superfamily and that plays a central role in multiple cell-cell signaling events throughout development. Through genetic screens we are seeking to identify other functions that act upstream, downstream or in concert with dpp to mediate its signaling role. We report here the genetic characterization and cloning of Mothers against dpp (Mad), a gene identified in two such screens. Mad loss-of-function mutations interact with dpp alleles to enhance embryonic dorsal-ventral patterning defects, as well as adult appendage defects, suggesting a role for Mad in mediating some aspect of dpp function. In support of this, homozygous Mad mutant animals exhibit defects in midgut morphogenesis, imaginal disk development and embryonic dorsal-ventral patterning that are very reminiscent of dpp mutant phenotypes. We cloned the Mad region and identified the Mad transcription unit through germline transformation rescue. We sequenced a Mad cDNA and identified three Mad point mutations that alter the coding information. The predicted MAD polypeptide lacks known protein motifs, but has strong sequence similarity to three polypeptides predicted from genomic sequence from the nematode Caenorhabditis elegans. Hence, MAD is a member of a novel, highly conserved protein family.
Inhibition of the Metallo-.BETA.-lactamase Produced from Serratia marcescens by Thiol Compounds. (1997)

Low molecular weight thiol compounds have been found to be strong inhibitors of metallo-beta-lactamase (IMP-1) produced by Serratia marcescens TN9106, which was expressed by Echerichia coli JM109 cells. Mercaptoacetic acid and 2-mercaptopropionic acid strongly and competitively inhibited IMP-1 with Ki of 0.23 and 0.19 microM, respectively. 2-Mercaptoethanol reversibly inhibited IMP-1 but did not show simple competitive inhibition.
Perspectives on Pituitary Adenylate Cyclase Activating Polypeptide (PACAP) in the Neuroendocrine, Endocrine, and Nervous Systems (1998)

PACAP is a pleiotropic neuropeptide that belongs to the secretin/glucagon/VIP family. PACAP functions as a hypothalamic hormone, neurotransmitter, neuromodulator, vasodilator, and neurotrophic factor. Its structure has been remarkably conserved during evolution. The PACAP receptor is G protein-coupled with seven transmembrane domains and also belongs to the VIP receptor family. PACAP, but not VIP, binds to PAC1-R, whereas PACAP and VIP bind to VPAC1-R and VPAC2-R with a similar affinity. Despite the sizable homology of the structures of PACAP and VIP and their receptors, the distribution of these peptides and receptors is quite different. At least eight subtypes of PACAP specific, or PAC1-R, result from alternate splicing. Each subtype is coupled with specific signaling pathways, and its expression is tissue or cell specific. Although PACAP fulfills most requirements for a physiological hypothalamic hypophysiotropic hormone, it does not consistently stimulate secretion of the adenohypophysial hormones, except for stimulation of IL-6 release from the FS cells of the pituitary. The major regulatory role of PACAP in pituitary cells appears to be the regulation of gene expression of pituitary hormones and/or regulatory proteins that control growth and differentiation of the pituitary glandular cells. These effects appear to be exhibited directly and indirectly through a paracrine or autocrine action. Although PACAP stimulates the release of AVP, the physiological role of neurohypophysial PACAP remains unknown. One important action of PACAP in the endocrine system is its role as a potent secretagogue for adrenaline from the adrenal medulla through activation of TH. PACAP also stimulates the release of insulin and increases [Ca2+]i from pancreatic beta-cells at an extremely small concentration. The stage-specific expression of PACAP in testicular germ cells during spermatogenesis suggests its regulatory role in the maturation of germ cells. In the ovary, PACAP is transiently expressed in the granulosa cells of the preovulatory follicles and appears to be involved in the LH-induced cellular events in the ovary, including prevention of follicular apoptosis. In the central nervous system, PACAP acts as a neurotransmitter or neuromodulator, which has been supported by IHC and electrophysiological methods. More important, PACAP is a neurotrophic factor that may play an important role during the development of the brain. In the adult brain, PACAP appears to function as a neuroprotective factor that attenuates the neuronal damage resulting from various insults.
A Functional Variomics Tool for Discovering Drug-Resistance Genes and Drug Targets (2013)

Comprehensive discovery of genetic mechanisms of drug resistance and identification of in vivo drug targets represent significant challenges. Here we present a functional variomics technology in the model organism Saccharomyces cerevisiae. This tool analyzes numerous genetic variants and effectively tackles both problems simultaneously. Using this tool, we discovered almost all genes that, due to mutations or modest overexpression, confer resistance to rapamycin, cycloheximide, and amphotericin B. Most significant among the resistance genes were drug targets, including multiple targets of a given drug. With amphotericin B, we discovered the highly conserved membrane protein Pmp3 as a potent resistance factor and a possible target. Widespread application of this tool should allow rapid identification of conserved resistance mechanisms and targets of many more compounds. New genes and alleles that confer resistance to other stresses can also be discovered. Similar tools in other systems, such as human cell lines, will also be useful.
CATION-DISORDER-ENHANCED MAGNETIZATION IN PULSED-LASER-DEPOSITED CUFE2O4 FILMS (2005)

Copper ferrite films have been deposited on (100) MgO substrates by pulsed-laser deposition. The oxygen pressure used in deposition was varied from 1to120mTorr with the substrate temperature fixed at 700°C. Magnetization values are measured to increase with oxygen pressure, reaching a maximum value of 2480G, which is a 42% increase over the bulk equilibrium value. Extended x-ray absorption spectroscopy shows that the Cu cation inversion δ [defined as (Cu1−δFeδ)tet[CuδFe2−δ]octO4] decreases monotonically from 0.72 to 0.55 with increasing saturation magnetization.
Role of Size and Shape on Biofilm Eradication for Nitric Oxide-Releasing Silica Nanoparticles (2013)

Nitric oxide (NO), a reactive free radical, has proven effective in eradicating bacterial biofilms with reduced risk of fostering antibacterial resistance. Herein, we evaluated the efficacy of NO-releasing silica nanoparticles against Gram-negative Pseudomonas aeruginosa and Gram-positive Staphylococcus aureus biofilms as a function of particle size and shape. Three sizes of NO-releasing silica nanoparticles (i.e., 14, 50, and 150 nm) with identical total NO release (∼0.3 μmol/mg) were utilized to study antibiofilm eradication as a function of size. To observe the role of particle shape on biofilm killing, we varied the aspect ratio of the NO-releasing silica particles from 1 to 8 while maintaining constant particle volume (∼0.02 μm(3)) and NO-release totals (∼0.7 μmol/mg). Nitric oxide-releasing particles with decreased size and increased aspect ratio were more effective against both P. aeruginosa and S. aureus biofilms, with the Gram-negative species exhibiting the greatest susceptibility to NO. To further understand the influence of these nanoparticle properties on NO-mediated antibacterial activity, we visualized intracellular NO concentrations and cell death with confocal microscopy. Smaller NO-releasing particles (14 nm) exhibited better NO delivery and enhanced bacteria killing compared to the larger (50 and 150 nm) particles. Likewise, the rod-like NO-releasing particles proved more effective than spherical particles in delivering NO and inducing greater antibacterial action throughout the biofilm.
Infection in the twenty-first century: predictions and postulates (2000)

The late Paul Garrod, in whose honour this lecture is named, was 'the right man at the right time'. He seized the opportunities offered by the dawning of the chemotherapeutic era with vigour and enthusiasm and was a formidable link between the traditional laboratory-based bacteriologist and the more clinically orientated 'modern' medical microbiologist. Professor Garrod was a founder member of the British Society for Antimicrobial Chemotherapy and I had the privilege of meeting him on many occasions. He would have relished the many challenges facing today's microbiologists, infectious disease physicians and public health experts. These will have major implications for antimicrobial chemotherapy in the twenty-first century. The emergence and prevalence of infectious diseases, and the necessity for discovering therapies to treat them, are influenced by many factors. In this lecture I will discuss four which could have a major influence on infectious diseases in the twenty-first century-global warming, biological warfare/terrorism, the dissemination of infections, including those caused by resistant pathogens, by travellers and certain untreatable zoonotic diseases.
Subunit complementation of thymidylate synthase (1992)

Each of the two active sites of thymidylate synthase contains amino acid residues contributed by the other subunit. For example, Arg-178 of one monomer binds the phosphate group of the substrate dUMP in the active site of the other monomer [Hardy et al. (1987) Science 235, 448-455]. Inactive mutants of such residues should combine with subunits of other inactive mutants to form heterodimeric hybrids with one functional active site. In vivo and in vitro approaches were used to test this hypothesis. In vivo complementation was accomplished by cotransforming plasmid mixtures encoding pools of inactive Arg-178 mutants and pools of inactive Cys-198 mutants into a host strain deficient in thymidylate synthase. Individual inactive mutants of Arg-178 were also cotransformed with the C198A mutant. Subunit complementation was detected by selection or screening for transformants which grew in the absence of thymidine, and hence produced active enzyme. Many mutants at each position representing a wide variety of size and charge supported subunit complementation. In vitro complementation was accomplished by reversible dissociation and unfolding of mixtures of purified individual inactive Arg-178 and Cys-198 mutant proteins. With the R178F + C198A heterodimer, the Km values for dUMP and CH2H4folate were similar to those of the wild-type enzyme. By titrating C198A with R178F under unfolding-refolding conditions, we were able to calculate the kcat value for the active heterodimer. The catalytic efficiency of the single wild-type active site of the C198A + R178F heterodimer approaches that of the wild-type enzyme.
Towards Genomic Drug Therapy with Antisense Oligonucleotides (1996)

Antisense oligonucleotides represent a novel class of potential drugs for highly selective blocking of genes. The basic concept of antisense strategy is simple: an antisense molecule recognizes a complementary mRNA (or DNA) by sequence-specific base pairing, and hence prevents translation (or transcription), resulting in a selective inhibition of protein synthesis. Because of these properties, antisense oligonucleotides have great potential as therapeutic agents in several human diseases, such as viral diseases, malignancies and dominant hereditary diseases. However, technical difficulties have slowed down their use as drugs: structural modifications are needed to increase the stability and potency of synthetic oligonucleotides, specific delivery systems are required to facilitate their entry into target cells, and more information is needed to their mechanism of action. Much of the current research on antisense oligonucleotides takes place at the interface of chemistry and biomedical sciences, a multidisciplinary field where finding a common language is sometimes difficult. The aim of this review is to present an overview of the antisense strategy in terms which should be understandable for chemists, biologists and physicians.
Ultrastructural differences between the cells of the medical collateral and the anterior cruciate ligaments. (1991)

The anterior cruciate ligament (ACL) does not heal after an interstitial tear, in contrast to the medial collateral ligament (MCL), whose interstitial tears heal readily. The light microscopic and ultrastructural differences between the cells of the two ligaments were studied in rabbit knees to observe the healing characteristics of the two ligaments. A rabbit knee was chosen because the rabbit ACL, like that of humans, does not heal following interstitial injury. The cells populating the MCL have the characteristics of fibroblasts. The cells of the ACL resemble fibrocartilage cells. The phenotypic differences in the cells of the two ligaments may be important determinants of the differences in healing.
Fractional Flow Reserve and Coronary Computed Tomographic Angiography (2016)

Invasive fractional flow reserve (FFR) is now the gold standard for intervention. Noninvasive functional imaging analyses derived from coronary computed tomographic angiography (CTA) offer alternatives for evaluating lesion-specific ischemia. CT-FFR, CT myocardial perfusion imaging, and transluminal attenuation gradient/corrected contrast opacification have been studied using invasive FFR as the gold standard. CT-FFR has demonstrated significant improvement in specificity and positive predictive value compared with CTA alone for predicting FFR of ≤0.80, as well as decreasing the frequency of nonobstructive invasive coronary angiography. High-risk plaque characteristics have also been strongly implicated in abnormal FFR. Myocardial computed tomographic perfusion is an alternative method with promising results; it involves more radiation and contrast. Transluminal attenuation gradient/corrected contrast opacification is more controversial and may be more related to vessel diameter than stenosis. Important considerations remain: (1) improvement of CTA quality to decrease unevaluable studies, (2) is the diagnostic accuracy of CT-FFR sufficient? (3) can CT-FFR guide intervention without invasive FFR confirmation? (4) what are the long-term outcomes of CT-FFR-guided treatment and how do they compare with other functional imaging-guided paradigms? (5) what degree of stenosis on CTA warrants CT-FFR? (6) how should high-risk plaque be incorporated into treatment decisions? (7) how will CT-FFR influence other functional imaging test utilization, and what will be the effect on the practice of cardiology? (8) will a workstation-based CT-FFR be mandatory? Rapid progress to date suggests that CTA-based lesion-specific ischemia will be the gatekeeper to the cardiac catheterization laboratory and will transform the world of intervention.
Analyzing near-infrared scattering from human skin to monitor changes in hematocrit (2011)

Probing tissue with near-infrared radiation (NIR) simultaneously produces remitted fluorescence and Raman scattering (IE) plus Rayleigh∕Mie light scattering (EE) that noninvasively give chemical and physical information about the materials and objects within. We model tissue as a three-phase system: plasma and red blood cell (RBC) phases that are mobile and a static tissue phase. In vivo, any volume of tissue naturally experiences spatial and temporal fluctuations of blood plasma and RBC content. Plasma and RBC fractions may be discriminated from each other on the basis of their physical, chemical, and optical properties. Thus, IE and EE from NIR probing yield information about these fractions. Assuming there is no void volume in viable tissue, or that void volume is constant, changes in plasma and RBC volume fractions may be calculated from simultaneous measurements of the two observables, EE and IE. In a previously published analysis we showed the underlying phenomenology but did not provide an algorithm for calculating volume fractions from experimental data. Now, we present a simple analysis that allows monitoring of fluid fraction and hematocrit (Hct) changes by measuring IE and EE, and apply it to some experimental in vivo measurements.
Monoclonal Antibody against T‐Cell Receptor αβ Induces Self‐Tolerance in Chronic Experimental Autoimmune Encephalomyelitis (2006)

The therapeutic effect of monoclonal antibody (H57-597 MoAb) against T-cell receptor (TCR) alphabeta has been investigated on MOG(35-55)-induced experimental autoimmune encephalomyelitis (EAE), as a model system for T-cell-mediated chronic inflammation in the central nervous system (CNS). Short-term administration of the anti-TCR alphabeta immediately after immunization protected the mice from EAE. Furthermore, anti-TCR alphabeta treatment on an established disease restored the self-tolerance which led to a complete remission of EAE and a dramatic reduction of inflammatory cells in the CNS, while treatment with control antibody (hamster IgG) was ineffective. The remission was durable and not associated with disappearance of autoreactive T cells as measured by persistence of MOG-reactive T-cell proliferation in vitro. However, MOG-reactive T cells from anti-TCR-treated animals produced significantly lower amounts of inflammatory TNF-alpha and IFN-gamma. In addition, while a transient deletion of CD4(+) and CD8(+) T cells was observed, a population of T cells expressing CD3, NK1.1 and CD69 (NKT cells) were expanding. By transfer of spleen cells from anti-TCR MoAb-treated animals, we could show that the tolerogenic capacity can be transferred to untreated recipients with EAE. The data indicate therapeutic effect of anti-TCR alphabeta MoAb (H57-597), which represents a promising approach in treatment of T-cell-mediated autoimmune diseases.