gebhart/patrepeval huggingface dataset:
Increased metalloproteinase activity, oxidant production, and emphysema in surfactant protein D gene-inactivated mice (2000)

Targeted ablation of the surfactant protein D (SP-D) gene caused chronic inflammation, emphysema, and fibrosis in the lungs of SP-D (-/-) mice. Although lung morphology was unperturbed during the first 2 weeks of life, airspace enlargement was observed by 3 weeks and progressed with advancing age. Inflammation consisted of hypertrophic alveolar macrophages and peribronchiolar-perivascular monocytic infiltrates. These abnormalities were associated with increased activity of the matrix metalloproteinases, MMP2 and MMP9, and immunostaining for MMP9 and MMP12 in alveolar macrophages. Hydrogen peroxide production by isolated alveolar macrophages also was increased significantly (10-fold). SP-D plays a critical role in the suppression of alveolar macrophage activation, which may contribute to the pathogenesis of chronic inflammation and emphysema.
Reduced Mortality after Allogeneic Hematopoietic-Cell Transplantation (2010)

We found a substantial reduction in the hazard of death related to allogeneic hematopoietic-cell transplantation, as well as increased long-term survival, over the past decade. Improved outcomes appear to be related to reductions in organ damage, infection, and severe acute GVHD. (Funded by the National Institutes of Health.).
Electroluminescence from trap-limited current transport in vacuum deposited organic light emitting devices (1994)

We investigate the current transport and electroluminescence mechanisms controlling the efficiency of organic heterojunction, green light emitting devices consisting of tris-(8-hydroxyquinoline) aluminum (Alq) and a hole transport layer (HTL). From the dependence of the current-voltage characteristics and luminescence efficiency on layer thickness and HTL composition, we find that current is controlled by trap-limited transport of electrons injected into Alq. Electroluminescence efficiency, on the other hand, is controlled by hole injection from the HTL into Alq. The luminescence is generated by recombination of electrons localized at a high density trap in the Alq, and holes injected from the HTL. These results provide insight into the fundamental processes which control the operating voltage and luminescence efficiency of vacuum deposited organic light emitters.
BCR-ABL point mutants isolated from patients with imatinib mesylate–resistant chronic myeloid leukemia remain sensitive to inhibitors of the BCR-ABL chaperone heat shock protein 90 (2002)

Clinical resistance to imatinib mesylate is commonly observed in patients with advanced Philadelphia chromosome- positive (Ph(+)) leukemias. Acquired resistance is typically associated with reactivation of BCR-ABL due to kinase domain mutations or gene amplification, indicating that BCR-ABL remains a viable target for inhibition in these patients. Strategies for overcoming resistance can be envisioned through exploitation of other molecular features of the BCR-ABL protein, such as its dependence on the molecular chaperone heat shock protein 90 (Hsp90). To determine whether inhibition of Hsp90 could induce degradation of imatinib mesylate-resistant, mutant BCR-ABL proteins, hematopoietic cells expressing 2 mutant BCR-ABL proteins found in imatinib mesylate-resistant patients (T315I and E255K) were examined for sensitivity to geldanamycin and 17-allylaminogeldanamycin (17-AAG). Both compounds induced the degradation of wild-type and mutant BCR-ABL and inhibited cell growth, with a trend indicating more potent activity against mutant BCR-ABL proteins. These data support clinical investigations of 17-AAG in imatinib mesylate-resistant Ph(+) leukemias.
Evaluation of simple and complex sensorimotor behaviours in rats with a partial lesion of the dopaminergic nigrostriatal system (2000)

We have examined the behavioural consequences of a partial unilateral dopaminergic denervation of the rat striatum. This partial lesion was obtained by an intrastriatal 6-hydroxy-dopamine injection (6-OHDA, 20 or 10 microgram divided between two injection sites) and was compared with a unilateral complete lesion resulting from an injection of 6-OHDA (2 x 6 microgram) into the medial forebrain bundle. Quantification of striatal dopamine (DA) and its metabolites, and the immunohistochemical evaluation of the nigrostriatal DA system confirmed the complete and partial lesions. Animals with complete striatal denervation displayed both apomorphine- and amphetamine-induced rotations whereas the partial denervation elicited amphetamine-induced rotations only. However, the rates of amphetamine-induced rotation were not correlated with the size of the lesion. In contrast, the paw-reaching impairments were significantly correlated with the striatal dopaminergic depletion. When evaluated in the staircase test, animals with partial denervation were impaired exclusively for the paw contralateral to the side of the lesion. This motor deficit (50-75%) included all components of the skilled paw use (i.e. attempt, motor coordination and success) and was observed at least 12 weeks after the lesion. However, these animals were able to perform normal stepping adjustments with the impaired paw, indicating that the partial lesion induced a coordination deficit of the paw rather than a deficit of movement initiation. After a complete lesion, stepping adjustments of the contralateral paw were dramatically impaired (by 80%), an akinesia which almost certainly accounted for the great deficit in skilled paw use. The paw-reaching impairments resulting from the partial striatal denervation are proposed as a model of the early symptoms of Parkinson's disease and may be useful for the development of restorative therapies.
N-Acetyltransferases, sulfotransferases and heterocyclic amine activation in the breast (2001)

Heterocyclic amines are mammary carcinogens in rats and their N-hydroxy metabolites are substrates for subsequent metabolic activation by N-acetyltransferases (NAT) and sulfotransferases (SULT) in man. We investigated the expression of these enzymes in human breast tissue and the relationship between NAT genotype and NAT mRNA expression or enzyme activity. Immunohistochemical staining of sections of breast tissue identified expression of NAT1 and NAT2 protein in human mammary epithelial cells, but not in the stroma. We also measured the formation of DNA adducts of the heterocyclic amines 2-amino-3-methylimidazo[4,5-f]quinoline (IQ) and 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine in calf thymus DNA after incubation of their promutagenic N-hydroxy metabolites with mammary cytosols prepared from reduction mammoplasty tissue. Experimental observations gained from use of enzyme cofactors and NAT and/or SULT inhibitors on cytosolic enzyme activity, recombinant NAT1 activity and heterocyclic amine-DNA adduct formation suggest that both NAT1 and SULT1A enzymes contribute significantly to the activation of N-hydroxylated heterocyclic amines in mammary tissue. NAT1 mRNA transcript levels were found to be two- to three-fold higher than mRNA transcripts of the NAT2 gene in reduction mammoplasty tissue and mammary epithelial cells. NAT1-specific p-aminobenzoic acid acetylation activity, but not NAT2-specific sulfamethazine acetylation activity, was detectable in mammary cytosols. There was no association apparent between NAT genotype and the levels of NAT mRNA or NAT enzyme activity, or between NAT1 genotype and IQ-DNA adduct formation mediated by mammary cytosols. Western blot analysis of mammary cytosolic protein showed detectable levels of SULT1A1 and SULT1A3.
Allelic Variants of Melanocortin 3 Receptor Gene (MC3R) and Weight Loss in Obesity: A Randomised Trial of Hypo-Energetic High- versus Low-Fat Diets (2011)

The study provided overall sufficient evidence to support that there is no major effect of genetic variants of MC3R and differential weight loss after a 10-week dietary intervention with hypo-energetic diets in obese Europeans.
Nonlinear Interactions with an Ultrahigh Flux of Broadband Entangled Photons (2005)

We experimentally demonstrate sum-frequency generation with entangled photon pairs, generating as many as 40,000 photons per second, visible even to the naked eye. The nonclassical nature of the interaction is exhibited by a linear intensity dependence of the nonlinear process. The key element in our scheme is the generation of an ultrahigh flux of entangled photons while maintaining their nonclassical properties. This is made possible by generating the down-converted photons as broadband as possible, orders of magnitude wider than the pump. This approach can be applied to other nonlinear interactions, and may become useful for various quantum-measurement tasks.
Photochemical treatment of donor lymphocytes inhibited their ability to facilitate donor engraftment or increase donor chimerism after nonmyeloablative conditioning or establishment of mixed chimerism (2002)

Donor T-cells can provide a graft-versus-leukemia effect and help to promote donor engraftment after allogeneic BMT; however, these benefits can be outweighed by the ability of the cells to induce life-threatening GVHD. Photochemical treatment (PCT) of T-cells with S-59 psoralen and long-wavelength UV-A light can inhibit their proliferative capacity and significantly decrease their ability to induce acute GVHD after allogeneic BMT. PCT donor T-cells have been shown to facilitate donor engraftment in a myeloablative BMT model. In this study, we examined whether donor T-cells subjected to PCT ex vivo could retain the ability to facilitate engraftment or increase donor chimerism after nonmyeloablative BMT or after establishment of mixed hematopoietic chimerism. In a transplantation model in which mice were conditioned for BMT with sublethal (600 cGy) TBI, an infusion of PCT donor T-cells was unable to facilitate engraftment of donor BM. A BMT model was used in which a mixture of allogeneic and syngeneic marrow cells was infused into lethally irradiated recipients for establishment of mixed hematopoietic chimerism. The goal was to determine whether PCT donor splenocytes could increase levels of donor chimerism. Recipients of splenocytes treated with UV-A light only (no S-59 psoralen) and given at the time of BMT or in a donor lymphocyte infusion (DLI) had significantly higher levels of donor chimerism than did recipients of BM only. Although PCT donor splenocytes given at the time of BMT modestly increased donor chimerism, PCT donor splenocytes given in a DLI did not increase donor chimerism. A nonmyeloablative BMT model was employed for determining whether DLI given relatively late after BMT could increase donor chimerism. Recipient mice were conditioned for BMT with a combination of low-dose TBI (50 or 100 cGy) and anti-CD154 (anti-CD40L) monoclonal antibody for achievement of low levels of mixed chimerism. When control mixed chimeras were given a DLI 71 days after BMT, donor chimerism was significantly increased. In contrast, PCT of the donor cells eliminated the ability of the cells to increase donor chimerism after infusion. Together results from these 3 distinct BMT models indicate that PCT of donor T-cells significantly inhibited the ability of the cells to facilitate donor engraftment after nonmyeloablative BMT or to increase donor chimerism in mixed hematopoietic chimeras when the cells were administered in a DLI.
Effects of Cellulolytic Ruminal Bacteria and of Cell Extracts on Germination of Euonymus americanus L. Seeds (1988)

In past attempts, the experimental germination of the seeds of Euonymus americanus L. in vitro has had little success. However, treatment of seeds with ruminal fluid containing viable microflora has been successful in stimulating germination. In the presence of the cellulolytic ruminal bacterium, Clostridium cellobioparum ATCC 15832, seeds of E. americanus were stimulated to germinate. Subsequent studies were designed to determine whether the bacterium synthesized a cellulolytic enzyme responsible for initiating germination. The cell-free endocellulase from C. cellobioparum induced germination of the seeds. To support the hypothesis that the endocellulase from C. cellobioparum was responsible for triggering germination, a 1,4-beta-d-glucan glucanohydrolase (EC 3.2.1.4) from Penicillum funiculosum was used to treat the seeds. In addition, no germination was obtained from seeds treated with a commercial exocellulase enzyme. Also, Ruminococcus flavefaciens FD-1 was found to initiate germination of E. americanus seeds. Thus, cellulase activity is indicated in the degradation of the testa of the seed, allowing imbibition and germination.
ÜBER DIE BISDIPHENYLENFULGIDE UND DIE SPALTUNG DER BISDIPHENYLENFULGENSÄURE IN OPTISCH AKTIVE KOMPONENTEN (1957)

Abstract Die Konstitution der drei Bisdiphenylenfulgide von Stobbe wurde untersucht. Nur das schwarze Bisdiphenylenfulgid, für das eine ergiebige Methode zur Darstellung angegeben wird, entspricht der angenommenen Struktur. Das rote „Allo”︁‐und das gelbe „Iso”︁‐Bisdiphenylenfulgid sind isomere Dihydro‐bis‐diphenylenfulgide mit verschiedener Lage der Doppelbindung. Die Bisdiphenylenfulgensäure läßt sich in optisch aktive Komponenten spalten, die schnell durch Racemisierung inaktiv werden.
affy—analysis of Affymetrix GeneChip data at the probe level (2004)

The affy package is an R package of functions and classes for the analysis of oligonucleotide arrays manufactured by Affymetrix. The package is currently in its second release, affy provides the user with extreme flexibility when carrying out an analysis and make it possible to access and manipulate probe intensity data. In this paper, we present the main classes and functions in the package and demonstrate how they can be used to process probe-level data. We also demonstrate the importance of probe-level analysis when using the Affymetrix GeneChip platform.
Embryonic stem cells: a model to study structural and functional properties in cardiomyogenesis (1997)

Time for primary review 20 days.

In order to study cardiac myocyte development different approaches were established during the last decades. The main purpose of these studies was the differentiation of cardiac precursor cells into specialized, differentiated cell types, as well as the development of functional properties such as Ca2+ handling, rhythm generation and excitation-contraction coupling of cardiomyocytes during development. Although considerable data exist about skeletal myogenesis [1–3], limited knowledge is available with regard to the origin of the commitment and differentiation of cardiac cells. A comprehensive, morphological study on the cytodifferentiation from mesenchymal cells into cardiac myocytes is described in the embryonic murine heart [4]: According to the authors, different stages of myofibrillogenesis are present during embryological myocardial development. Cells with no or only little myofibrillar arrangement develop to myocardial cells with orientated myofibrils [5, 6]. A number of morphological studies have investigated heart development on embryonic, neonatal and adult isolated cardiomyocytes also from different species [7–16].

Although the ultrastructure during cardiac development has been thoroughly investigated [17], still relatively little is known on the development of excitability of the mammalian heart, most importantly: (1): The relation between expression of cardio-specific genes (see review [23]), the formation of cardiac phenotypes and the functional expression of different types of ion channels; (2): The regulation and genetic control of expression of ion channels (e.g. by growth factors, hormones, extracellular matrix); (3): The development of the regulation of ion channels and morphological correlates. The progress in this field is hampered by the inability to study cardiomyocytes from early, embryonal hearts because of their very small size and because of the lack of cardiac cell lines that mimic various stages of cardiac development. The development of ion currents has been studied in cardiomyocytes prepared from mammalian embryos … 

* Corresponding author. Tel.: (+49-221) 4786960; Fax: (+49-221) 4786965.
A Parallel Workflow for Real-time Correlation and Clustering of High-Frequency Stock Market Data (2007)

We investigate the design and implementation of a parallel workflow environment targeted towards the financial industry. The system performs real-time correlation analysis and clustering to identify trends within streaming high-frequency intra-day trading data. Our system utilizes state-of-the-art methods to optimize the delivery of computationally-expensive real-time stock market data analysis, with direct applications in automated/algorithmic trading as well as knowledge discovery in high-throughput electronic exchanges. This paper describes the design of the system including the key online parallel algorithms for robust correlation calculation and clique-based clustering using stochastic local search. We evaluate the performance and scalability of the system, followed by a preliminary analysis of the results using data from the Toronto Stock Exchange.
Heterologous T cell immunity in severe hepatitis C virus infection (2005)

Hepatitis C virus (HCV) can cause liver disease of variable severity. Expansion of preexisting memory CD8 T cells by cross-reactivity with a new heterologous virus infection has been shown in mice to shape the repertoire of the primary response and to influence virus-related immunopathology. To determine whether this mechanism can influence the course of HCV infection, we analyzed the features of the HCV-specific CD8 T cell response in eight patients with acute HCV infection, two of whom had a particularly severe illness. Patients with severe hepatitis, but not those with mild disease, showed an extremely vigorous CD8 T cell response narrowly focused on a single epitope (NS3 1073-1081), which cross-reacted with an influenza neuraminidase sequence. Our results suggest that CD8 T cell cross-reactivity influences the severity of the HCV-associated liver pathology and depicts a model of disease induction that may apply to different viral infections.
Transforming Growth Factor-β1 Represses Bone Morphogenetic Protein–Mediated Smad Signaling in Pulmonary Artery Smooth Muscle Cells via Smad3 (2013)

Previous studies of pulmonary arterial hypertension (PAH) have implicated excessive transforming growth factor (TGF)-β1 signaling and reduced bone morphogenetic protein (BMP) signaling in the disease pathogenesis. Reduced BMP signaling in pulmonary artery smooth muscle cells (PASMCs) from patients with heritable PAH is a consequence of germline mutations in the BMP type II receptor (BMPR-II). We sought to establish whether the TGF-β1 and BMP4 pathways interact in PASMCs, and if this is altered in cells with BMPR-II mutations. Control PASMCs or from patients with PAH harboring BMPR-II mutations were treated with BMP4, TGF-β1, or cotreated with both ligands. Signaling was assessed by examination of Smad phosphorylation, luciferase reporters, and the transcription of BMP4 or TGF-β1-responsive genes. TGF-β1 attenuated BMP4-mediated inhibitors of differentiation 1/2 induction and abolished the response in BMPR-II mutant PASMCs, whereas BMP4 did not alter TGF-β1-mediated transcription. Activin-like kinase 5 inhibition blocked this effect, whereas cycloheximide or pharmacological inhibitors of TGF-β-activated kinase 1, extracellular signal-regulated kinase 1/2, or p38 mitogen-activated protein kinase were ineffective. BMP4 and TGF-β1 cotreatment did not alter the activation or nuclear translocation of their respective Smad signaling proteins. Small interfering RNA for Smad3, but not Smad2, Smad6, or Smad7, reversed the inhibition by TGF-β1. In addition, TGF-β-activated kinase 1 inhibition blocked Smad3 phosphorylation, implying that C-terminal Smad3 phosphorylation is not required for the inhibition of BMP4 signaling by TGF-β1. TGF-β1 reduces BMP4 signaling in PASMCs, a response that is exacerbated on the background of reduced BMP responsiveness due to BMPR-II mutations. These data provide a rationale for therapeutic inhibition of TGF-β1 signaling in PAH.
Cluster of Neisseria gonorrhoeae Isolates With High-level Azithromycin Resistance and Decreased Ceftriaxone Susceptibility, Hawaii, 2016 (2017)

This cluster of genetically related gonococcal isolates with decreased ceftriaxone susceptibility and high-level azithromycin resistance may bring the threat of treatment failure in the United States with the current recommended dual therapy one step closer.
Sacral neuromodulation; does it affect colonic transit time in patients with faecal incontinence? (2006)

SNM in patients with fecal incontinence led to a significant decrease of bowel movements however (segmental) colonic transit time was not influenced.
Convergent themes in X chromosome inactivation and autosomal imprinting (1997)

Abstract X chromosome inactivation (X inactivation) is the genetic silencing of a single X chromosome in XX female mammals, providing the mechanism whereby X-linked gene dosage is equalized relative to XY males (reviewed in ref. 1). X inactivation occurs early in female embryogenesis and there is normally an equal probability that either the maternally-derived (Xm), or paternally-derived (XP) X chromosome will be inactivated. The stochastic nature of X inactivation gives rise to the classical variegated phenotypes observed in females heterozygous for X-linked coat colour mutations, for example the tortoiseshell cat. The pattern of variegation reflects the fact that the initiation of X inactivation occurs in early embryogenesis, and that the inactive state is clonally inherited in subsequent cell divisions. In certain instances X inactivation is non-random. Thus, for example, XP is preferentially inactivated in marsupial species, and also in restricted extra-embryonic lineages in mouse.
MRI in the early identification and classification of high-risk atherosclerotic carotid plaques (2010)

Stroke is a leading cause of mortality and long-term morbidity. As a means for stroke prevention, an estimated 99,000 carotid endarterectomy procedures were performed in the USA in 2006. Traditionally, the degree of luminal stenosis has been used as a marker of the stage of atherosclerosis and as an indication for surgical intervention. However, prospective clinical trials have shown that the majority of patients with a history of recent transient ischemic attack or stroke have mild-to-moderate carotid stenosis. Using stenosis criteria, many of these symptomatic individuals would be considered to have early-stage carotid atherosclerosis. It is evident that improved criteria are needed for identifying the high-risk carotid plaque across a range of stenoses. Histological studies have led to the hypothesis that plaques with larger lipid-rich necrotic cores, thin fibrous cap rupture, intraplaque hemorrhage, plaque neovasculature and vessel wall inflammation are characteristics of the high-risk, 'vulnerable plaque'. Despite the widespread consensus on the importance of these plaque features, testing the vulnerable plaque hypothesis in prospective clinical studies has been hindered by the lack of reliable imaging tools for in vivo plaque characterization. MRI has been shown to accurately identify key carotid plaque features, including the fibrous cap, lipid-rich necrotic core, intraplaque hemorrhage, neovasculature and vascular wall inflammation. Thus, MRI is a histologically validated technique that will permit prospective testing of the vulnerable plaque hypothesis. This article will provide a summary of the histological validation of carotid MRI, and highlight its application in prospective clinical studies aimed at early identification of the high-risk atherosclerotic carotid plaque.