gebhart/patrepeval huggingface dataset:
Targeting Gene Therapy for Osteogenesis Imperfecta (2004)

Targeting the collagen gene in bone mesenchymal stem cells can prevent the synthesis of mutant collagen and therefore represents a potential strategy for the treatment of diseases such as osteogenesis imperfecta.
Molecular analysis of human forearm superficial skin bacterial biota (2007)

The microbial ecology of human skin is complex, but little is known about its species composition. We examined the diversity of the skin biota from the superficial volar left and right forearms in six healthy subjects using broad-range small subunit rRNA genes (16S rDNA) PCR-based sequencing of randomly selected clones. For the initial 1,221 clones analyzed, 182 species-level operational taxonomic units (SLOTUs) belonging to eight phyla were identified, estimated as 74.0% [95% confidence interval (C.I.), approximately 64.8-77.9%] of the SLOTUs in this ecosystem; 48.0 +/- 12.2 SLOTUs were found in each subject. Three phyla (Actinobacteria, Firmicutes, and Proteobacteria) accounted for 94.6% of the clones. Most (85.3%) of the bacterial sequences corresponded to known and cultivated species, but 98 (8.0%) clones, comprising 30 phylotypes, had <97% similarity to prior database sequences. Only 6 (6.6%) of the 91 genera and 4 (2.2%) of the 182 SLOTUs, respectively, were found in all six subjects. Analysis of 817 clones obtained 8-10 months later from four subjects showed additional phyla (numbering 2), genera (numbering 28), and SLOTUs (numbering 65). Only four (3.4%) of the 119 genera (Propionibacteria, Corynebacteria, Staphylococcus, and Streptococcus) were observed in each subject tested twice, but these genera represented 54.4% of all clones. These results show that the bacterial biota in normal superficial skin is highly diverse, with few well conserved and well represented genera, but otherwise low-level interpersonal consensus.
Novel blood group H glycolipid antigens exclusively expressed in blood group A and AB erythrocytes (type 3 chain H). I. Isolation and chemical characterization. (1986)

A series of blood group H antigens reacting with monoclonal antibody MBrl has been found in human blood group A and AB erythrocytes, but not in O or B erythrocytes. These H antigens are clearly different from the globo-H structure (Fuc alpha 1----2Gal beta 1----3GalNAc beta 1----3Gal alpha 1----4Gal beta 1----4Glc beta 1----1Cer), which was previously isolated from O erythrocytes and is also reactive with the MBrl antibody. The new series of H antigens associated with blood group A has been characterized as having TLC mobilities which approximately coincide with those of H2, H3, and H4 glycolipids. One of these A-associated H antigens, having a similar TLC mobility as the H2 glycolipid, was isolated from A erythrocytes and was characterized by 1H NMR spectroscopy, methylation analysis, and enzymatic degradation as having the structure shown below: (formula, see text). The structure represents a precursor of the repetitive A epitope attached to type 2 chain, previously called type 3 chain A (Clausen, H., Levery, S. B., Nudelman, E., Tsuchiya, S., and Hakomori, S. (1985) Proc. Natl. Acad. Sci. U.S.A. 82, 1199-1203). This A-associated H structure is hereby called type 3 chain H.
Internal field engineering in CdZnO/MgZnO quantum well structures (2009)

Electronic and optical properties of CdZnO/MgZnO quantum well (QW) structures with the depolarization of an internal field are investigated by using the non-Markovian gain model. The Mg composition is selected to give zero internal field for a given Cd composition. The Mg content to give zero internal field is found to increase with increasing Cd content. The peak gain is improved with increasing Cd composition in a range of Cd&amp;lt;0.07 because a quasi-Fermi-level separation rapidly increases with the Cd composition. However, it begins to decrease when the Cd composition exceeds 0.07.
Well‐Defined Silica‐Supported Mo–Alkylidene Catalyst Precursors Containing One OR Substituent: Methods of Preparation and Structure–Reactivity Relationship in Alkene Metathesis (2009)

Abstract Silica supports : Well‐defined silica‐supported Mo–alkylidene complexes containing one alkoxy/aryloxy substituent are selectively obtained by grafting onto silica either well‐defined molecular bis(alkoxy) or alkoxyamido complexes (see scheme). These silica‐supported complexes are highly efficient catalyst precursors for the metathesis of acyclic alkenes. However, they display poor performances in ring‐closing metathesis reactions, possibly due to the relatively large siloxy ligand (silica) inducing a greater rigidity. magnified image The monosiloxy surface complexes [(SiO)Mo(NAr)(=CHCMe 2 R′)(OR)] (R′=Me or Ph; OR=O t Bu, OCMe(CF 3 ) 2 or OAr) are obtained by grafting onto SiO 2−(700) either symmetric Mo–alkylidene derivatives [Mo(NAr)(=CHCMe 2 R′)(OR) 2 ] or asymmetric derivatives, that is, with two different pendant ligands, one amido and one alkoxy/aryloxy, [Mo(NAr)(=CHCMe 2 R′)(OR)(NC 6 H 8 )]. The formation of these complexes was confirmed by mass‐balance analysis, and infrared (IR) and NMR spectroscopies. These systems are highly efficient catalyst precursors for the metathesis of acyclic alkenes; the best results were seen when OR=OCMe(CF 3 ) 2 . Nevertheless, they display poor performances in ring‐closing metathesis, possibly due to the rigidity of the metal center (as evidenced by NMR spectroscopy), which therefore slows the rate of the metathesis.
Ingestion of Yogurt Containing Lactobacillus acidophilus as Prophylaxis for Candidal Vaginitis (1992)

Daily ingestion of 8 ounces of yogurt containing Lactobacillus acidophilus decreased both candidal colonization and infection.
Using integrated color and texture features for automatic hair detection (2008)

Hair is one of the most challenging facial features, playing important role in human appearance. This paper introduces novel approach to human hair extraction, based on integration of texture, shape and color features. This approach allows robust hair detection in complex background under various illumination and hairstyles. This study deals with color images and hair detection aims hair re-colorization to simulate different hair colors. The process starting with typical facial features extraction such as open skin, eyes and mouth and finishing with fuzzy hair mask. Fuzzy hair representation allows overcoming hair appearance problems around hair roots and close to outer line of hairstyle. Fuzzy hair mask building involves binary hair mask detection, background detection and matting procedure. Experiments caring in cosmetic store environment for 354 images show 75% of correct detection for complex background and illumination and 85% for homogeneous background and illumination.
Regulation of Endothelial Nitric Oxide Synthase in Pathophysiological Conditions (2011)

The nitric oxide (NO) cascade and endothelial NO synthase (eNOS) are best known for their role in endothelium-mediated relaxation of vascular smooth muscle (VSM). NO generated by eNOS has been established as a key regulatory signaling molecule in the vasculature. The activities of eNOS are controlled by intracellular calcium/calmodulin (CaM) and by binding of the molecular chaperone heat-shock protein 90 (Hsp90). A number of studies have demonstrated a close association between insulin resistance (IR) and NO bioactivity. Some recent studies demonstrate that insulin signaling is essential for normal cardiovascular (CV) function and lack of it such as IR result in CV dysfunction and disease. A key step in the initiation and progression of atherosclerosis is a reduction in the bioactivity of endothelial cell-derived NO. Multiple changes in endothelial function and eNOS activity accompany the onset and development of Type 2 diabetes mellitus (T2DM) and contribute to the development of cardiovascular disease (CVD). This review focuses on recent findings about regulation of eNOS in pathophysiological conditions such are: IR, T2DM and CVD.
Novel Method to Control Pathogenic Bacteria on Human Mucous Membranes (2003)

Nearly all infections begin at a mucous membrane site. Also, the human mucous membranes are a reservoir for many pathogenic bacteria found in the environment (that is, pneumococci, staphylococci, streptococci), some of which are resistant to antibiotics. Clearly, if this human reservoir can be reduced or eliminated, the incidence of disease will be markedly reduced. However, compounds designed to eliminate this reservoir are not available. Towards this goal, we have exploited the highly lethal effects of bacteriophage lytic enzymes (lysins) to specifically destroy disease bacteria on mucous membranes. Such lysins are used by the phage to release their progeny at the end of their replicative cycle. We have identified and purified these enzymes and found that when applied externally to gram-positive bacteria, they are killed seconds after contact. For example, 10(7) S. pyogenes are reduced to undetectable levels 10 s after enzyme addition. A feature of these enzymes is their high specificity; that is, streptococcal lysins kill streptococci and pneumococcal lysins kill pneumococci without effects on the normal flora organisms. In vivo, an oral colonization model for S. pyogenes and a nasal colonization model for S. pneumoniae were developed to test the capacity of the lysins to kill organisms on these surfaces. In both cases, when the animals were pre-colonized with their respective bacteria then treated with a small amount of lysin, specific for the colonizing organism, all the animals were found to be free of colonizing bacteria shortly after lysin treatment. Thus, lysins may be added to our armamentarium to control antibiotic-resistant bacteria.
Body Orientation and the Perception of Spatial Auditory and Tactile Cues (2005)

This study investigated the effects of five body orientations (supine, kneeling, sitting, standing, and prone) on perception of spatial auditory and spatial tactile cues along eight equidistant points (45° separation) of the azimuth, using a within-participant design. Participants (N = 30) used a graphics tablet and stylus to indicate the perceived direction indicated by either vibrotactile stimuli applied to the abdomen, or spatial auditory stimuli presented via headphones. Response time data show responses to spatial tactile cues were significantly faster than spatial auditory cues at each body position and for each point along the azimuth, with no significant effects of body orientation. Absolute angle differences between presented and perceived cues were significantly smaller in the tactile condition for five of the eight stimulus positions, with no significant effects of body orientation. Results are discussed in terms of designing multi-sensory directional cues for reducing visual search space for dismounted soldiers
Specific association of small heat shock proteins with the pathological hallmarks of Alzheimer's disease brains (2006)

The small heat shock protein family (sHsp) comprises molecular chaperones able to interact with incorrectly folded proteins. Alzheimer's disease (AD) is characterized by pathological lesions such as senile plaques (SPs), cerebral amyloid angiopathy (CAA) and neurofibrillary tangles (NFTs), predominantly consisting of the incorrectly folded proteins amyloid-beta (Abeta) and tau respectively. The aim of this study was to investigate the association of the chaperones Hsp20, HspB2, alphaB-crystallin and Hsp27 with the pathological lesions of AD brains. For this purpose, a panel of well-characterized antibodies directed against these sHsps was used in immunohistochemistry and immunoblotting. We observed extracellular expression of Hsp20, Hsp27 and HspB2 in classic SPs, and Hsp20 expression in diffuse SPs. In addition, extracellular expression of HspB2 was observed in CAA. Both Hsp27 and alphaB-crystallin were also observed in astrocytes associated with both SPs and CAA. Furthermore, none of the sHsps were observed in NFTs in AD brains. We conclude that specific sHsp species may be involved in the pathogenesis of either SPs or CAA in AD.
New paradigm for the roles of fungi and eosinophils in chronic rhinosinusitis (2005)

Several classification schemes and diagnostic criteria describe chronic rhinosinusitis and make comparisons difficult. Preselection of patient groups within the chronic rhinosinusitis population and the lack of sensitive diagnostic techniques have prevented a full understanding of the syndrome complex of chronic rhinosinusitis. New results suggest a broader role for fungi in the pathophysiology of chronic rhinosinusitis, linking the eosinophilic inflammation to the presence of certain molds in the nasal and paranasal cavities. Although fungi are commonly found in nearly everyone, only chronic rhinosinusitis patients respond to them with an eosinophilic inflammation. These findings support a shift in the etiologic understanding of chronic rhinosinusitis away from a bacteriologic infectious pathogenesis to a fungal-driven inflammatory pathophysiology. Herein, the authors review earlier studies and describe an updated view on an old paradigm.
Phosphorylation of E2F-1 by cyclin A-cdk2. (1995)

Transcription factor E2F-1 has a putative consensus sequence for phosphorylation by cyclin dependent kinase (Ser-Pro-X-Lys/Arg). Therefore, we studied the phosphorylation of E2F-1 in vivo and in vitro and its biological functions. E2F-1 was prepared by immunoprecipitation with anti-E2F-1 antibody from IMR32 lysates and was effectively phosphorylated by human cyclin A-cdk2 which was expressed in insect cells using baculovirus system. GST-E2F-1 was phosphorylated by cyclin A-cdk2 more efficiently than by cyclin E-cdk2. Cyclin D1-cdk4 phosphorylated pRB but scarcely phosphorylated GST-E2F-1 or H1 histone. The 60 kd protein precipitated with anti-E2F-1 antibody was phosphorylated in vivo. Phospho-peptide mapping indicated that its cleavage profile was identical with that of E2F-1 phosphorylated by cyclin A-cdk2 in vitro. This 60 kd protein, which is likely to be E2F-1, was not phosphorylated during the G0 and early G1 phase. Phosphorylation of E2F-1 began from the S phase while phosphorylation of pRB started nearly at G1/S. The in vivo phosphorylation of E2F-1 was inhibited by butyrolactone I, a cyclin-dependent kinase inhibitor (Kitagawa et al., 1993, Oncogene, 8, 2425-2432). The binding of E2F-1 to E2 promoter was found to be reduced by phosphorylation of E2F-1 by cyclin A-cdk2, suggesting that phosphorylation of E2F-1 may induce shut off of gene expression at the transcriptional level. These results suggest that E2F-1 is phosphorylated by cyclin A-cdk2 in the S phase in vivo as well as in vitro and that its phosphorylation by cyclin A-cdk2 may modulate its activity.
Direction finding using a switched parasitic antenna array (2002)

An electronically controlled antenna array consisting of one active element and a number of parasitic elements can be used for direction finding. Array directivity is controlled by exchanging the position of the feed and the parasitic elements. An array of four monopoles on a ground plane provides 360 degree azimuthal coverage with no moving parts, provides excellent directional resolution and can be controlled using a simple microcontroller. The antenna design, its application to direction finding and reliability in noisy environments are presented.
A Novel Glucokinase Activator Modulates Pancreatic Islet and Hepatocyte Function (2005)

The glucose-sensing enzyme glucokinase (GK) plays a key role in glucose metabolism. We report here the effects of a novel glucokinase activator, LY2121260. The activator enhanced GK activity via binding to the allosteric site located in the hinge region of the enzyme. LY2121260 stimulated insulin secretion in a glucose-dependent manner in pancreatic beta-cells and increased glucose use in rat hepatocytes. In addition, incubation of beta-cells with the GK activator resulted in increased GK protein levels, suggesting that enhanced insulin secretion on chronic treatment with a GK activator may be due to not only changed enzyme kinetics but also elevated enzyme levels. Animals treated with LY2121260 showed an improved glucose tolerance after oral glucose challenge. These results support the concept that GK activators represent a new class of compounds that increase both insulin secretion and hepatic glucose use and in doing so may prove to be effective agents for the control of blood glucose levels in patients with type 2 diabetes.
Efficient Sleeping Beauty DNA Transposition From DNA Minicircles (2013)

DNA transposon-based vectors have emerged as new potential delivery tools in therapeutic gene transfer. Such vectors are now showing promise in hematopoietic stem cells and primary human T cells, and clinical trials with transposon-engineered cells are on the way. However, the use of plasmid DNA as a carrier of the vector raises safety concerns due to the undesirable administration of bacterial sequences. To optimize vectors based on the Sleeping Beauty (SB) DNA transposon for clinical use, we examine here SB transposition from DNA minicircles (MCs) devoid of the bacterial plasmid backbone. Potent DNA transposition, directed by the hyperactive SB100X transposase, is demonstrated from MC donors, and the stable transfection rate is significantly enhanced by expressing the SB100X transposase from MCs. The stable transfection rate is inversely related to the size of circular donor, suggesting that a MC-based SB transposition system benefits primarily from an increased cellular uptake and/or enhanced expression which can be observed with DNA MCs. DNA transposon and transposase MCs are easily produced, are favorable in size, do not carry irrelevant DNA, and are robust substrates for DNA transposition. In accordance, DNA MCs should become a standard source of DNA transposons not only in therapeutic settings but also in the daily use of the SB system.Molecular Therapy - Nucleic Acids (2013) 2, e74; doi:10.1038/mtna.2013.1; published online 26 February 2013.
Androgen receptor targeted therapies in castration‐resistant prostate cancer: Bench to clinic (2016)

The androgen receptor is a transcription factor and validated therapeutic target for prostate cancer. Androgen deprivation therapy remains the gold standard treatment, but it is not curative, and eventually the disease will return as lethal castration-resistant prostate cancer. There have been improvements in the therapeutic landscape with new agents approved, such as abiraterone acetate, enzalutamide, sipuleucel-T, cabazitaxel and Ra-223, in the past 5 years. New insight into the mechanisms of resistance to treatments in advanced disease is being and has been elucidated. All current androgen receptor-targeting therapies inhibit the growth of prostate cancer by blocking the ligand-binding domain, where androgen binds to activate the receptor. Persuasive evidence supports the concept that constitutively active androgen receptor splice variants lacking the ligand-binding domain are one of the resistant mechanisms underlying advanced disease. Transcriptional activity of the androgen receptor requires a functional AF-1 region in its N-terminal domain. Preclinical evidence proved that this domain is a druggable target to forecast a potential paradigm shift in the management of advanced prostate cancer. This review presents an overview of androgen receptor-related mechanisms of resistance as well as novel therapeutic agents to overcome resistance that is linked to the expression of androgen receptor splice variants in castration-resistant prostate cancer.
Interferon-gamma induced exacerbation of systemic lupus erythematosus. (1990)

A patient with presumed rheumatoid arthritis based on clinical and serological evidence was subjected by her physician to interferon-gamma (IFN-gamma) therapy and developed a life threatening multiorgan flare of systemic lupus erythematosus (SLE). Pulse cyclophosphamide therapy in conjunction with plasmapheresis led to complete remission. Retrospective analysis of serum drawn before IFN-gamma was started revealed high DNA binding capacity. Thus, similar to observations in lupus-prone animals, IFN-gamma may have induced an exacerbation of preexisting SLE.
A Novel, Selective Inhibitor of Fibroblast Growth Factor Receptors That Shows a Potent Broad Spectrum of Antitumor Activity in Several Tumor Xenograft Models (2011)

The fibroblast growth factor receptors (FGFR) are tyrosine kinases that are present in many types of endothelial and tumor cells and play an important role in tumor cell growth, survival, and migration as well as in maintaining tumor angiogenesis. Overexpression of FGFRs or aberrant regulation of their activities has been implicated in many forms of human malignancies. Therefore, targeting FGFRs represents an attractive strategy for development of cancer treatment options by simultaneously inhibiting tumor cell growth, survival, and migration as well as tumor angiogenesis. Here, we describe a potent, selective, small-molecule FGFR inhibitor, (R)-(E)-2-(4-(2-(5-(1-(3,5-Dichloropyridin-4-yl)ethoxy)-1H-indazol-3yl)vinyl)-1H-pyrazol-1-yl)ethanol, designated as LY2874455. This molecule is active against all 4 FGFRs, with a similar potency in biochemical assays. It exhibits a potent activity against FGF/FGFR-mediated signaling in several cancer cell lines and shows an excellent broad spectrum of antitumor activity in several tumor xenograft models representing the major FGF/FGFR relevant tumor histologies including lung, gastric, and bladder cancers and multiple myeloma, and with a well-defined pharmacokinetic/pharmacodynamic relationship. LY2874455 also exhibits a 6- to 9-fold in vitro and in vivo selectivity on inhibition of FGF- over VEGF-mediated target signaling in mice. Furthermore, LY2874455 did not show VEGF receptor 2-mediated toxicities such as hypertension at efficacious doses. Currently, this molecule is being evaluated for its potential use in the clinic.
Immunologic and Clinical Effects of Injecting Mature Peptide-Loaded Dendritic Cells by Intralymphatic and Intranodal Routes in Metastatic Melanoma Patients (2006)

Injections into the lymphatic system of mature peptide-loaded dendritic cells with potential TH1 polarization capacities did not result in marked clinical results, despite immunologic responses in some patients. This highlights the need to improve our understanding of dendritic cell physiology.
Anticoagulant therapy and central nervous system complications in patients with prosthetic valve endocarditis. (1978)

Among 52 cases of prosthetic valve endocarditis, adequate anticoagulant therapy was administered in 38 and discontinued or given in subtherapeutic dosage in 14. Our data suggest that anticoagulant therapy does not appreciably increase morbidity or mortality in patients with prosthetic valve endocarditis. On the contrary, in our patients the incidence of major clinical CNS (central nervous system) complications was increased and the mortality was higher if anticoagulant therapy was discontinued. CNS complications occurred in 10 of the 14 patients without adequate anticoagulant therapy and in three of the 38 with adequate anticoagulant therapy. Mortality was 57% among those treated without adequate anticoagulation and 47% among those with adequate anticoagulation. At autopsy, CNS complications were thought to be the primary cause of five of the eight deaths in cases without adequate anticoagulation.
A novel method for the preparation of zeolite ZSM-5 (1990)

The zeolite ZSM-5 has been synthesized from amorphous aluminosilicate gels in a vapour of ethylenediamine, triethylamine, and water and characterized by XRD and chemical analysis.