gebhart/patrepeval huggingface dataset:
A Rapid Molecular Test for Determining Yersinia pestis Susceptibility to Ciprofloxacin by the Quantification of Differentially Expressed Marker Genes (2016)

Standard antimicrobial susceptibility tests used to determine bacterial susceptibility to antibiotics are growth dependent and time consuming. The long incubation time required for standard tests may render susceptibility results irrelevant, particularly for patients infected with lethal bacteria that are slow growing on agar but progress rapidly in vivo, such as Yersinia pestis. Here, we present an alternative approach for the rapid determination of antimicrobial susceptibility, based on the quantification of the changes in the expression levels of specific marker genes following exposure to growth-inhibiting concentrations of the antibiotic, using Y. pestis and ciprofloxacin as a model. The marker genes were identified by transcriptomic DNA microarray analysis of the virulent Y. pestis Kimberley53 strain after exposure to specific concentrations of ciprofloxacin for various time periods. We identified several marker genes that were induced following exposure to growth-inhibitory concentrations of ciprofloxacin, and we confirmed the marker expression profiles at additional ciprofloxacin concentrations using quantitative RT-PCR. Eleven candidate marker transcripts were identified, of which four mRNA markers were selected for a rapid quantitative RT-PCR susceptibility test that correctly determined the Minimal Inhibitory Concentration (MIC) values and the categories of susceptibility of several Y. pestis strains and isolates harboring various ciprofloxacin MIC values. The novel molecular susceptibility test requires just 2 h of antibiotic exposure in a 7-h overall test time, in contrast to the 24 h of antibiotic exposure required for a standard microdilution test.
Ultrasensitive Antibody Detection by Agglutination-PCR (ADAP) (2016)

Antibodies are widely used biomarkers for the diagnosis of many diseases. Assays based on solid-phase immobilization of antigens comprise the majority of clinical platforms for antibody detection, but can be undermined by antigen denaturation and epitope masking. These technological hurdles are especially troublesome in detecting antibodies that bind nonlinear or conformational epitopes, such as anti-insulin antibodies in type 1 diabetes patients and anti-thyroglobulin antibodies associated with thyroid cancers. Radioimmunoassay remains the gold standard for these challenging antibody biomarkers, but the limited multiplexability and reliance on hazardous radioactive reagents have prevented their use outside specialized testing facilities. Here we present an ultrasensitive solution-phase method for detecting antibodies, termed antibody detection by agglutination-PCR (ADAP). Antibodies bind to and agglutinate synthetic antigen-DNA conjugates, enabling ligation of the DNA strands and subsequent quantification by qPCR. ADAP detects zepto- to attomoles of antibodies in 2 μL of sample with a dynamic range spanning 5-6 orders of magnitude. Using ADAP, we detected anti-thyroglobulin autoantibodies from human patient plasma with a 1000-fold increased sensitivity over an FDA-approved radioimmunoassay. Finally, we demonstrate the multiplexability of ADAP by simultaneously detecting multiple antibodies in one experiment. ADAP's combination of simplicity, sensitivity, broad dynamic range, multiplexability, and use of standard PCR protocols creates new opportunities for the discovery and detection of antibody biomarkers.
Cellular approaches to central nervous system remyelination stimulation: thyroid hormone to promote myelin repair via endogenous stem and precursor cells (2009)

Brain and spinal cord repair is a very difficult task in view of the extremely limited repair capability of the mature central nervous system (CNS). Thus, cellular therapies are regarded as a new frontier for both acute and chronic neurological diseases characterized by neuron or oligodendroglia degeneration. Although cell replacement has been considered as the primary goal of such approaches, in recent years greater attention has been devoted to the possibility that new undifferentiated cells in damaged nervous tissue might also act in autocrine-paracrine fashion, regulating the micro-environment through the release of growth factor and cytokines, also regulating immune response and local inflammation. In this review, repair of demyelinating disease using endogenous cells will be discussed in view of the critical role played by thyroid hormones (THs) during developmental myelination, focusing on the following points: 1) endogenous stem and precursor cells during demyelinating diseases; 2) TH homeostasis in the CNS; 3) cellular and molecular mechanism regulated by TH during developmental myelination and 4) a working hypothesis to develop a rationale for the use of THs to improve remyelination through endogenous stem and precursor cells in the course of demyelinating diseases.
The concept of entero‐colonic encephalopathy, autism and opioid receptor ligands (2002)

There is growing awareness that primary gastrointestinal pathology may play an important role in the inception and clinical expression of some childhood developmental disorders, including autism. In addition to frequent gastrointestinal symptoms, children with autism often manifest complex biochemical and immunological abnormalities. The gut-brain axis is central to certain encephalopathies of extra-cranial origin, hepatic encephalopathy being the best characterized. Commonalities in the clinical characteristics of hepatic encephalopathy and a form of autism associated with developmental regression in an apparently previously normal child, accompanied by immune-mediated gastrointestinal pathology, have led to the proposal that there may be analogous mechanisms of toxic encephalopathy in patients with liver failure and some children with autism. Aberrations in opioid biochemistry are common to these two conditions, and there is evidence that opioid peptides may mediate certain aspects of the respective syndromes. The generation of plausible and testable hypotheses in this area may help to identify new treatment options in encephalopathies of extra-cranial origin. Therapeutic targets for this autistic phenotype may include: modification of diet and entero-colonic microbial milieu in order to reduce toxin substrates, improve nutritional status and modify mucosal immunity; anti-inflammatory/immunomodulatory therapy; and specific treatment of dysmotility, focusing, for example, on the pharmacology of local opioid activity in the gut.
Analysis of digitized waveforms using Shannon entropy. II. High-speed algorithms based on Green’s functions (1994)

An improved approach for calculating continuous waveform entropy Hc is described. This approach is based on the use of the Green’s function for the one-dimensional differential operator L[u]=u″ with boundary conditions u(1)=u(0)=0. The method is applied to data acquired from a Plexiglas block having artificial defects in order to produce an entropy image. The defect contrast obtained with the new Green’s function computation is then compared with that obtained from a previously described Fourier series approach. It is found that the new approach produces the same or higher image contrast in a time that is roughly three orders of magnitude smaller than that required by the Fourier series method. This speedup arises from two sources. The Green’s function approach has greater inherent immunity to noise, and the number of calculations required in the Green’s function approach is much smaller than the number required in the Fourier series approach.
Genetic analysis of amino acid transport in the facultatively heterotrophic cyanobacterium Synechocystis sp. strain 6803 (1987)

The existence of active transport systems (permeases) operating on amino acids in the photoautotrophic cyanobacterium Synechocystis sp. strain 6803 was demonstrated by following the initial rates of uptake with 14C-labeled amino acids, measuring the intracellular pools of amino acids, and isolating mutants resistant to toxic amino acids. One class of mutants (Pfa1) corresponds to a regulatory defect in the biosynthesis of the aromatic amino acids, but two other classes (Can1 and Aza1) are defective in amino acid transport. The Can1 mutants are defective in the active transport of three basic amino acids (arginine, histidine, and lysine) and in one of two transport systems operating on glutamine. The Aza1 mutants are not affected in the transport of the basic amino acids but have lost the capacity to transport all other amino acids except glutamate. The latter amino acid is probably transported by a third permease which could be identical to the Can1-independent transport operating on glutamine. Thus, genetic evidence suggests that strain 6803 has only a small number of amino acid transport systems with fairly broad specificity and that, with the exception of glutamine, each amino acid is accumulated by only one major transport system. Compared with heterotrophic bacteria such as Escherichia coli, these permeases are rather inefficient in terms of affinity (apparent Km ranging from 6 to 60 microM) and of Vmax.
URINARY CATECHOLAMINES AND AMPHETAMINE EXCRETION IN HYPERACTIVE AND NORMAL BOYS (1978)

Urinary catecholamines and metabolites and urinary amphetamine excretion were examined for hyperactive and normal boys following a single dose of dextroamphetamine (0.5 mg/kg) and placebo. Hyperactive children showed a significantly faster rate of excretion of amphetamine which could not be accounted for by previous exposure to drug or by signs of neurological involvement. Urinary norepinephrine (NE) was significantly higher for hyperactive than for normal children, but NE excretion did not correlate with motor activity or any measures of arousal. The single dose of amphetamine produced a significant rise in urinary epinephrine excretion (EP) for the normal children but not for the hyperactive group, supporting the notion of a more sluggish catecholamine response to stimulants for hyperkinetic children.
Macrophage cathepsin L, a factor in the erosion of subchondral bone in rheumatoid arthritis (1997)

The cathepsin L-rich macrophages are sufficiently numerous to be considered a major factor in producing the erosion of subchondral bone found in chronic RA lesions.
Direct Observation of a Cytosine Analogue that Forms Five Hydrogen Bonds to Guanosine: Guanidino G-Clamp (2002)

Bound and clamped: A novel heterocyclic base modification, the guanidino G-clamp, is designed to allow two Hoogsteen-type hydrogen bonds to form between the amino and imino nitrogen atoms of a tethered guanidinium group to O6 and N7 of guanosine, which results in a total of five hydrogen bonds (broken lines, see picture). Details of a crystal structure at 1.0-Å resolution of a modified DNA decamer containing this guanidino G-clamp analogue demonstrate its mechanism of binding. Supporting information for this article is available on the WWW under http://www.wiley-vch.de/contents/jc_2002/2002/z17542_s.pdf or from the author. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
Single-neuron RNA-Seq: technical feasibility and reproducibility (2012)

Understanding brain function involves improved knowledge about how the genome specifies such a large diversity of neuronal types. Transcriptome analysis of single neurons has been previously described using gene expression microarrays. Using high-throughput transcriptome sequencing (RNA-Seq), we have developed a method to perform single-neuron RNA-Seq. Following electrophysiology recording from an individual neuron, total RNA was extracted by aspirating the cellular contents into a fine glass electrode tip. The mRNAs were reverse transcribed and amplified to construct a single-neuron cDNA library, and subsequently subjected to high-throughput sequencing. This approach was applied to both individual neurons cultured from embryonic mouse hippocampus, as well as neocortical neurons from live brain slices. We found that the average pairwise Spearman's rank correlation coefficient of gene expression level expressed as RPKM (reads per kilobase of transcript per million mapped reads) was 0.51 between five cultured neuronal cells, whereas the same measure between three cortical layer 5 neurons in situ was 0.25. The data suggest that there may be greater heterogeneity of the cortical neurons, as compared to neurons in vitro. The results demonstrate the technical feasibility and reproducibility of RNA-Seq in capturing a part of the transcriptome landscape of single neurons, and confirmed that morphologically identical neurons, even from the same region, have distinct gene expression patterns.
A comparison of several acoustic representations for speech recognition with degraded and undegraded speech (2003)

Several acoustic representations have been compared in speaker-dependent and independent connected and isolated-word recognition tests with undegraded speech and with speech degraded by adding white noise and by applying a 6-dB/octave spectral tilt. The representations comprised the output of an auditory model, cepstrum coefficients derived from an FFT-based mel-scale filter bank with various weighting schemes applied to the coefficients, cepstrum coefficients augmented with measures of their rates of change with time, and sets of linear discriminant functions derived from the filter-bank output and called IMELDA. The model outperformed the cepstrum representations except in noise-free connected-word tests, where it had a high insertion rate. The best cepstrum weighting scheme was derived from within-class variances. Its behavior may explain the empirical adjustments found necessary with other schemes. IMELDA outperformed all other representations in all conditions and is computationally simple.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
β3-integrin–deficient mice are a model for Glanzmann thrombasthenia showing placental defects and reduced survival (1999)

beta3 integrins have been implicated in a wide variety of functions, including platelet aggregation and thrombosis (alphaIIbbeta3) and implantation, placentation, angiogenesis, bone remodeling, and tumor progression (alphavbeta3). The human bleeding disorder Glanzmann thrombasthenia (GT) can result from defects in the genes for either the alphaIIb or the beta3 subunit. In order to develop a mouse model of this disease and to further studies of hemostasis, thrombosis, and other suggested roles of beta3 integrins, we have generated a strain of beta3-null mice. The mice are viable and fertile, and show all the cardinal features of GT (defects in platelet aggregation and clot retraction, prolonged bleeding times, and cutaneous and gastrointestinal bleeding). Implantation appears to be unaffected, but placental defects do occur and lead to fetal mortality. Postnatal hemorrhage leads to anemia and reduced survival. These mice will allow analyses of the other suggested functions of beta3 integrins and we report that postnatal neovascularization of the retina appears to be beta3-integrin-independent, contrary to expectations from inhibition experiments.
Evidence that Microdeletions in the α Globin Gene Protect Against the Development of Sickle Cell Glomerulopathy in Humans (1999)

There is a large variability in the severity of the clinical manifestations of sickle cell anemia (SSA), including renal involvement. Haplotypes in the beta-globin gene cluster associated with the geographical origin of the sickle mutation, as well as microdeletions in the alpha-globin genes, could provide an epigenetic influence on the heterogeneous outcome in SSA. It has been determined that the cause of progressive renal insufficiency in SSA is a glomerulopathy, clinically detected by the presence of macroalbuminuria (albumin excretion rate >300 mg/g creatinine). To investigate the role of the alpha-globin gene microdeletion and beta-globin gene cluster haplotypes on the degree of glomerular involvement, 76 adult SSA patients (hemoglobin SS) were studied to determine the relationship between these genetic markers and the development of sickle cell glomerulopathy. Macroalbuminuria was present in 22 (29%) of 76 adult SSA patients. The coinheritance of microdeletions in one or two of the four alpha-globin genes (alpha-thalassemia) was associated with a lower prevalence of macroalbuminuria (13%) versus patients with intact alpha-globin genes (40%, P = 0.01). By contrast, there was no association between albuminuria and beta-globin gene haplotypes (Central African Republic [CAR] versus non-CAR haplotypes). Patients with alpha-globin gene microdeletions had lower mean corpuscular volumes and mean corpuscular hemoglobin concentration than patients with all four alpha genes (86+/-2 versus 99+/-3 fl, and 33.9+/-0.2 versus 34.9+/-0.2%, respectively, P<0.05). There were no such hematologic differences between CAR and non-CAR beta-globin haplotypes. There were no differences in duration of disease (age), hemoglobin levels, reticulocyte index, and lactate dehydrogenase levels between those with and without glomerulopathy, but the mean arterial pressure was higher (87+/-1 mm Hg) in patients with intact alpha gene locus versus those with microdeletions (80+/-2 mm Hg, P<0.05). It is concluded that the coinheritance of microdeletions in the alpha-globin gene locus in SSA patients confers "renoprotection" by mechanisms not related to the degree of anemia or the severity of hemolysis, but could be related to a reduced mean corpuscular volume or to a lower erythrocyte hemoglobin concentration.
Sterically HinderedCα,α-Disubstituted α-Amino Acids:  Synthesis from α-Nitroacetate and Incorporation into Peptides (2001)

The preparation of sterically hindered and polyfunctional C(alpha,alpha)-disubstituted alpha-amino acids (alpha alpha AAs) via alkylation of ethyl nitroacetate and transformation into derivatives ready for incorporation into peptides are described. Treatment of ethyl nitroacetate with N,N-diisopropylethylamine (DIEA) in the presence of a catalytic amount of tetraalkylammonium salt, followed by the addition of an activated alkyl halide or Michael acceptor, gives the doubly C-alkylated product in good to excellent yields. Selective nitro reduction with Zn in acetic acid or hydrogen over Raney Ni gives the corresponding amino ester that, upon saponification, can be protected with the fluorenylmethyloxycarbonyl (Fmoc) group. The first synthesis of an orthogonally protected, tetrafunctional C(alpha,alpha)-disubstituted analogue of aspartic acid, 2,2-bis(tert-butylcarboxymethyl)glycine (Bcmg), is described. Also, the sterically demanding C(alpha,alpha)-dibenzylglycine (Dbg) has been incorporated into a peptide using solid-phase synthesis. It was found that once sterically congested Dbg is at the peptide N-terminus, further chain extension becomes very difficult using uronium or phosphonium salts (PyAOP, PyAOP/HOAt, HATU). However, preformed amino acid symmetrical anhydride couples to N-terminal Dbg in almost quantitative yield in nonpolar solvent (dichloroethane-DMF, 9:1).
B-Lymphocyte Stimulator Protein (BLYS) Is Expressed by Bone Marrow Mast and Lymphoplasmacytic Cells in Waldenstrom’s Macroglobulinemia, and Provides Signaling for Growth, Survival and IgM Secretion. (2004)

Abstract B-lymphocyte stimulator protein (BLYS) is a member of the tumor necrosis family of ligands which is expressed by monocytes and neutrophils and regulates B-cell homeostasis and immunoglobulin production through its receptors BCMA, TACI and BAFF-R. In recent studies, we have shown that bone marrow (BM) mast cells (MC) are increased in WM patients and support tumor cell growth. We therefore evaluated sorted WM BM MC (CD117+FceRI+) and lymphoplasmacytic cells (LPC) for BLYS, BCMA, TACI AND BAFF-R by multicolor flow cytometry and RT-PCR. Results were as follows: Flow Cytometry RT-PCR WM MC WM MC BLYS 5/7 (71%) 8/15 (53%) 25/26 (96%) 20/23 (61%) BCMA 4/6 (66%) 7/8 (87%) 20/20 (100%) 8/13 (61%) TACI 15/16 (93%) 7/7 (100%) 20/20 (100%) 12/15 (80%) BAFF-R 11/16 (68%) 5/8 (62%) 20/20 (100%) 11/11 (100%) By RT-PCR, BLYS was detected in MC from 5/7 normal donors. However, in contrast to MC from WM patients, BLYS was not expressed on the cell surface of MC from 7 normal donors using multicolor flow cytometry (p=0.02). Importantly, recombinant human BLYS stimulated proliferation, enhanced survival and/or induced IgM secretion of WM LPC at concentrations of up to 1 ug/mL. Paradoxically, at higher concentrations (5, 10 ug/mL) BLYS induced apoptosis of WM LPC. These studies therefore demonstrate that MC and LPC in WM patients express BLYS and BLYS receptors, and provide the framework for specific targeting of MC-LPC interactions in WM.
ChimerDB 2.0—a knowledgebase for fusion genes updated (2009)

Chromosome translocations and gene fusions are frequent events in the human genome and have been found to cause diverse types of tumor. ChimerDB is a knowledgebase of fusion genes identified from bioinformatics analysis of transcript sequences in the GenBank and various other public resources such as the Sanger cancer genome project (CGP), OMIM, PubMed and the Mitelman's database. In this updated version, we significantly modified the algorithm of identifying fusion transcripts. Specifically, the new algorithm is more sensitive and has detected 2699 fusion transcripts with high confidence. Furthermore, it can identify interchromosomal translocations as well as the intrachromosomal deletions or inversions of large DNA segments. Importantly, results from the analysis of next-generation sequencing data in the short read archives are incorporated as well. We updated and integrated all contents (GenBank, Sanger CGP, OMIM, PubMed publications and the Mitelman's database), and the user-interface has been improved to support diverse types of searches and to enhance the user convenience especially in browsing PubMed articles. We also developed a new alignment viewer that should facilitate examining reliability of fusion transcripts and inferring functional significance. We expect ChimerDB 2.0, available at http://ercsb.ewha.ac.kr/fusiongene, to be a valuable tool in identifying biomarkers and drug targets.
Tissue generation with growth factors. (1993)

In an experimental model that approximates an in vivo tissue culture system, rPDGF-BB can induce a tenfold increase in tissue within the chamber. However, that tissue is labile and its survival necessitates continuous rPDGF-BB delivery. To become useful for reconstructive purposes, means to stabilize this new tissue growth are needed.
ED-B fibronectin as a target for antibody-based cancer treatments (2005)

Chemotherapeutic agents for the treatment of solid cancers do not discriminate between malignant and normal tissue, but rather depend on the increased proliferation of tumour cells versus benign cells. To reach therapeutically active concentrations in the tumour, large doses of these rather unspecific compounds have to be given to the patient, often resulting in severe side effects. Therefore, the goal of modern cancer research is the development of highly selective compounds which are able to discriminate between tumour tissue and normal tissue. One promising approach in this direction is antibody-mediated targeted cancer therapy which may either block an important receptor-ligand interaction or deliver a therapeutically active molecule to an otherwise nonfunctional target. A prerequisite for such an approach is the tumour-selective expression of the respective target structure. This review discusses extra domain-B fibronectin as a promising target which is associated with tumour angiogenesis and tumour growth for the development of novel antibody-mediated therapies.