gebhart/patrepeval huggingface dataset:
Systemic Delivery of MicroRNA Using Recombinant Adeno-associated Virus Serotype 9 to Treat Neuromuscular Diseases in Rodents (2018)

RNA interference via the endogenous miRNA pathway regulates gene expression by controlling protein synthesis through post-transcriptional gene silencing. In recent years, miRNA-mediated gene regulation has shown potential for treatment of neurological disorders caused by a toxic gain of function mechanism. However, efficient delivery to target tissues has limited its application. Here we used a transgenic mouse model for spinal and bulbar muscular atrophy (SBMA), a neuromuscular disease caused by polyglutamine expansion in the androgen receptor (AR), to test gene silencing by a newly identified AR-targeting miRNA, miR-298. We overexpressed miR-298 using a recombinant adeno-associated virus (rAAV) serotype 9 vector to facilitate transduction of non-dividing cells. A single tail-vein injection in SBMA mice induced sustained and widespread overexpression of miR-298 in skeletal muscle and motor neurons and resulted in amelioration of the neuromuscular phenotype in the mice.
Chimerization of antitumor antibodies via homologous recombination conversion vectors. (1994)

Homologous recombination vectors were designed to convert murine hybridoma cell lines expressing IgG3, IgG1, or IgG2a heavy chains into chimeric human IgG1 producers. These conversion vectors included homology both upstream and downstream of the target sequences and consistently resulted in a higher frequency of successful gene targeting than an insertion vector bearing a single region of homology. A human kappa light chain conversion vector was also constructed and used to complete chimerization of the anticarcinoma hybridoma cell line BR96. The resulting cell line expressed antigen-specific chimeric antibody at comparable levels to those found in the murine parental cell line. Southern blots confirm that recombination occurred within the upstream and downstream regions of homology for both vectors, resulting in the loss of murine constant region sequences.
Expression of the B7-related molecule B7-H1 by glioma cells: a potential mechanism of immune paralysis. (2003)

Human glioblastoma is a highly lethal tumor that is known for its immune inhibitory capabilities. B7-homologue 1 (B7-H1), a recently identified homologue of B7.1/2 (CD80/86), has been described to exert costimulatory and immune regulatory functions. We investigated the expression and the functional activity of B7-H1 in human glioma cells in vitro and in vivo. Although lacking B7.1/2 (CD80/86), all 12 glioma cell lines constitutively expressed B7-H1 mRNA and protein. Exposure to IFN-gamma strongly enhanced B7-H1 expression. Immunohistochemical analysis of malignant glioma specimens revealed strong B7-H1 expression in all 10 samples examined, whereas no B7-H1 expression could be detected on normal brain tissues. To elucidate the functional significance of glioma cell-related B7-H1 expression, we performed coculture experiments of glioma cells with alloreactive CD4+ and CD8+ T cells. Glioma-related B7-H1 was identified as a strong inhibitor of CD4+ as well as CD8+ T-cell activation as assessed by increased cytokine production (IFN-gamma, interleukin-2, and interleukin-10) and expression levels of the T-cell activation marker (CD69) in the presence of a neutralizing antibody against B7-H1 (mAb 5H1). B7-H1 expression may thus significantly influence the outcome of T-cell tumor cell interactions and represents a novel mechanism by which glioma cells evade immune recognition and destruction.
An efficient method for isolating putative promoters and 5'-transcribed sequences from large genomic clones. (1996)

Efficient strategies to isolate promoters and flanking exons from large genomic clones would facilitate the assembly of transcription units, complement existing techniques to isolate expressed sequences, and provide 5' regulatory elements. We have developed a rapid and simple method to isolate promoters from large mammalian genomic DNA clones by exploiting the abundance of binding sites for the ubiquitous transcription factor Sp1 in gene promoters. Using this method, putative promoter sequences with Sp1-binding sites are enriched approximately 100-fold from fragmented P1 clone DNA. Based on the abundance of Sp1-binding motifs in promoters, we predict that a significant subset of vertebrate promoters could be isolated by this method.
Epidemiology and medical management of stone disease (2003)

Recurrent stone formation in the urinary tract is a common and important problem that must be considered in daily urological practice. With a prevalence of> 10% and an expected recurrence rate of approximately 50%, stone disease has an important effect on the healthcare system. It is generally agreed that patients with uric acid/urate, cystine or infection stones always should be treated pharmacologically. For calcium stone formers the treatment should be chosen according to the severity of the disease. Recurrence in patients with calcium-stone disease can be prevented with general or specific dietary and drinking advice, and with pharmacological therapy. For idiopathic calcium stone formers the most convincing therapeutic effects have been reported with thiazide and alkaline citrate.
High-Throughput Screening in Drug Metabolism and Pharmacokinetic Support of Drug Discovery (2000)

The application of rapid methods currently used for screening discovery drug candidates for metabolism and pharmacokinetic characteristics is discussed. General considerations are given for screening in this context, including the criteria for good screens, the use of counterscreens, the proper sequencing of screens, ambiguity in the interpretation of results, strategies for false positives and negatives, and the special difficulties encountered in drug metabolism and pharmacokinetic screening. Detailed descriptions of the present status of screening are provided for absorption potential, blood-brain barrier penetration, inhibition and induction of cytochrome P450, pharmacokinetics, biotransformation, and computer modeling. Although none of the systems currently employed for drug metabolism and pharmacokinetic screening can be considered truly high-throughput, several of them are rapid enough to be a practical part of the screening paradigm for modern, fast-moving discovery programs.
Human Obesity Associated with an Intronic SNP in the Brain-Derived Neurotrophic Factor Locus (2015)

Brain-derived neurotrophic factor (BDNF) plays a key role in energy balance. In population studies, SNPs of the BDNF locus have been linked to obesity, but the mechanism by which these variants cause weight gain is unknown. Here, we examined human hypothalamic BDNF expression in association with 44 BDNF SNPs. We observed that the minor C allele of rs12291063 is associated with lower human ventromedial hypothalamic BDNF expression (p < 0.001) and greater adiposity in both adult and pediatric cohorts (p values < 0.05). We further demonstrated that the major T allele for rs12291063 possesses a binding capacity for the transcriptional regulator, heterogeneous nuclear ribonucleoprotein D0B, knockdown of which disrupts transactivation by the T allele. Binding and transactivation functions are both disrupted by substituting C for T. These findings provide a rationale for BDNF augmentation as a targeted treatment for obesity in individuals who have the rs12291063 CC genotype.
The Candida albicans HYR1 gene, which is activated in response to hyphal development, belongs to a gene family encoding yeast cell wall proteins (1996)

A hyphally regulated gene (HYR1) from the dimorphic human pathogenic fungus Candida albicans was isolated and characterized. Northern (RNA) analyses showed that the HYR1 mRNA was induced specifically in response to hyphal development when morphogenesis was stimulated by serum addition and temperature elevation, increases in both culture pH and temperature, or N-acetylglucosamine addition. The HYR1 gene sequence revealed a 937-codon open reading frame capable of encoding a protein with an N-terminal signal sequence, a C-terminal glycosylphosphatidylinositol-anchoring domain, 17 potential N glycosylation sites, and a large domain rich in serine and threonine (51% of 230 residues). These features are observed in many yeast cell wall proteins, but no homologs are present in the databases. In addition, Hyr1p contained a second domain rich in glycine, serine, and asparagine (79% of 239 residues). The HYR1 locus in C. albicans CAI4 was disrupted by "Ura-blasting," but the resulting homozygous delta hyr1/delta hyr1 null mutant displayed no obvious morphological phenotype. The growth rates for yeast cells and hyphae and the kinetics of germ tube formation in the null mutant were unaffected. Aberrant expression of HYR1 in yeast cells, when an ADH1-HYR1 fusion was used, did not stimulate hyphal formation in C. albicans or pseudohyphal growth in Saccharomyces cerevisiae. HYR1 appears to encode a nonessential component of the hyphal cell wall.
Plane - sweep algorithms for intersecting geometric figures (1981)

Algorithms in computational geometry are of increasing importance in computer-aided design, for example, in the layout of integrated circuits. The efficient computation of the intersection of several superimposed figures is a basic problem. Plane figures defined by points connected by straight line segments are considered, for example, polygons (not necessarily simple) and maps (embedded planar graphs). The regions into which the plane is partitioned by these intersecting figures are to be processed in various ways such as listing the boundary of each region in cyclic order or sweeping the interior of each region. Let m be the total number of points of all the figures involved and s be the total number of intersections of all line segments. A two plane-sweep algorithm that solves the problems above is presented; in the general case (non convexity) in time O((n+s)log-n) and space O(n+s); when the regions of each given figure are convex, the same can be achieved in time O(n log n +s) and space O(n)
A WDM-PON-Compatible System for Simultaneous Distribution of Gigabit Baseband and Wireless Ultrawideband Services With Flexible Bandwidth Allocation (2010)

In this paper, a novel and simple scheme to realize flexible access for gigabit wireline and impulse radio ultrawideband (IR-UWB) wireless services is proposed. The UWB signals are generated by multi-carrier upconverting and reshaping the baseband signals. The proposed system was experimentally demonstrated with the performances of 2.0-Gb/s data in both baseband and UWB formats after 46-km single mode fiber transmission and further 0.5-m wireless for UWB data. The flexibility of the system is confirmed by investigating the system performance at different data rates including 1.0 and 1.6 Gb/s. Optical wavelength independency and data-rate variability of UWB signal generation makes the system attractive for potential wireline and wireless applications in existing wavelength division multiplexing (WDM)-passive optical network (PON) systems.
Posterior capsule opacification in rabbit eyes implanted with 1-piece and 3-piece hydrophobic acrylic intraocular lenses (2005)

The square, truncated optic edge is the most important IOL design feature for PCO prevention. The optic-haptic junctions of the 1-piece designs appear to be sites where the barrier effect of the truncated optic edge is less effective.
Quantum cascade lasers with a heterogeneous cascade: Two-wavelength operation (2001)

A quantum cascade (QC) laser with a heterogeneous cascade containing two substacks previously optimized to emit at 5.2 μm and 8.0 μm wavelengths, respectively, is presented. The low-temperature performance of the two-wavelength laser is comparable to the respective homogeneous stack lasers, indicating no penalty from the heterogeneity of the cascade. Each substack is apportioned the optimum fraction of the applied bias. This demonstrates the general applicability of this scheme. In addition, an etch-stop layer inserted between the two substacks allowed fabrication of a “tap” into the cascade. The latter was used to selectively manipulate the laser threshold of one substack, turning the 8.0 μm laser on and off while the adjacent 5.2 μm QC laser was operating undisturbed.
Insights into the specificity of RNA cleavage by the Escherichia coli MazF toxin (2004)

The mazEF (chpA) toxin-antitoxin system of Escherichia coli is involved in the cell response to nutritional and antibiotic stresses as well as in bacterial-programmed cell death. Valuable information on the MazF toxin was derived from the determination of the crystal structure of the MazE/MazF complex and from in vivo data, suggesting that MazF promoted ribosome-dependent cleavage of messenger RNA. However, it was concluded from recent in vitro analyses using a MazF-(His6) fusion protein that MazF was an endoribonuclease that cleaved messenger RNA specifically at 5'-ACA-3' sites situated in single-stranded regions. In contrast, our work reported here shows that native MazF protein cleaves RNA at the 5' side of residue A in 5'-NAC-3' sequences (where N is preferentially U or A). MazF-dependent cleavage occurred at target sequences situated either in single- or double-stranded RNA regions. These activities were neutralized by a His6-MazE antitoxin. Although essentially consistent with previous in vivo reports on the substrate specificity of MazF, our results strongly suggest that the endoribonuclease activity of MazF may be modulated by additional factors to cleave messenger and other cellular RNAs.
Neurosurgical Applications of Fibrin Glue: Augmentation of Dural Closure in 134 Patients (1990)

In a wide variety of neurosurgical procedures performed on 134 patients over a 3-year period, fibrin glue has been applied as an adjunct to dural closure. Overall success at preventing cerebrospinal fluid (CSF) leakage was 90% (121 of 134, 90% effective). In patients considered to be at high risk for CSF leakage intraoperatively but without pre-established fistulae (Group 1), the success rate was higher (111 of 119, 93% effective). In patients with pre-established CSF fistulae (Group 2), the success rate was lower (10 of 15, 67% effective). As single donor sources of concentrated fibrinogen are now available with reduced risks of blood-borne disease transmission, fibrin glue may be a valuable clinical tool for the neurosurgeon.
Automatic detection, segmentation and classification of abdominal aortic aneurysm using deep learning (2016)

In this paper, an automated method for the detection, segmentation and classification of Abdominal Aortic Aneurysm (AAA) region in computed tomography (CT) images is introduced. Deep Belief Network (DBN) is applied for the purpose of AAA detection and severity classification in this study. Optimum parameters for training the DBN are determined for the training data from the selected dataset. AAA region can be successfully segmented from the CT images and the result is comparable to the existing methods.
Epileptic Seizure Following IV Tramadol in a Patient with Mental Retardation and Cerebellar Ataxia (2011)

Even in recommended doses, IV tramadol may cause epileptic seizures on predisposed patients.
Toward a Social Semantic Web (2007)

The semantic Web embodies a vision for a new era in the management and exploitation of Web content by people and machines. Although it poses great research challenges, the Web industry and user community have not yet embraced this vision. At the same time, Web 2.0 is increasingly gaining ground despite its unsophisticated nature or, more likely, because of it. Despite the apparent tension between the semantic Web and the social Web, they are essentially compatible and call coexist.
[mRNA detection of beta-myosin heavy chain gene in the autopsy cases of hypertrophic cardiomyopathy]. (2000)

A known trigger of sudden cardiac death, hypertrophic cardiomyopathy (HCM) is associated with a point mutation in or overexpression of MYH7, which encodes the sarcomere protein beta-myosin heavy chain. We used nested RT-PCR to detect MYH7 mRNA in left ventricular myocardial tissue. We extracted total RNA from tissue samples that had been obtained after autopsy of 8 people who had died from HCM-related sudden death and that had been fixed in 10% formalin solution for as long as 4 years. The abundance of total RNA extracted from the 100 mg samples of cardiac muscle ranged from 10 to 24 mg/ml. The products of the nested RT-PCR were electrophoresed on a denaturing 8% polyacrylamide gel, and the MYH7 mRNA product was detected as a 424 bp band. MYH7 mRNA was easier to detect in tissue that had been fixed for shorter rather than longer periods. In addition, the greater the cardiac weight, the higher was the yield of the MYH7 mRNA product. Although mRNA had been detected by using RT-PCR on formalin-fixed paraffin-embedded tissue, no one previously had identified by using RT-PCR or nested RT-PCR on formalin-fixed tissue. By using nested RT-PCR, we were able to detect MYH7 mRNA in myocardial tissue that had been fixed in formalin solution for 4 years. Our results are applicable to retrospective examination into the cause of death in cases of sudden cardiac failure.
Fluorous Affinity Purification of Oligonucleotides (2005)

[structure: see text] Nucleoside phosphoramidites bearing a fluorous dimethoxytrityl (FDMT) group were used to synthesize fluorous-tagged oligonucleotides, which were subjected to solid-phase extraction using a pH-stable fluorinated adsorbent. On-column detritylation afforded the purified oligonucleotides. The fluorous affinity purification method offers one-pass loading without ammonia removal, high selectivity for the removal of failure sequences, high recoveries (typically 70-100%), and the ability to purify long oligonucleotides (e.g., 50-100-mers).
2-(3-{1-Carboxy-5-[(6-[18F]Fluoro-Pyridine-3-Carbonyl)-Amino]-Pentyl}-Ureido)-Pentanedioic Acid, [18F]DCFPyL, a PSMA-Based PET Imaging Agent for Prostate Cancer (2011)

These data suggest [(18)F]DCFPyL as a viable, new positron-emitting imaging agent for PSMA-expressing tissues.
Synthesis, in Vitro Evaluation, and Intraocular Pressure Effects of Water-Soluble Prodrugs of Endocannabinoid Noladin Ether (2003)

The poor aqueous solubility of 2-arachidonyl glyceryl ether (noladin ether) 2 hinders both pharmacological studies and pharmaceutical development. The synthesized mono- and diphosphate esters of noladin ether (4 and 6) considerably increased the aqueous solubility of noladin ether (>40000-fold), showed high stability against chemical hydrolysis in buffer solutions, and were rapidly converted to the parent drug via enzymatic hydrolysis. The monophosphate ester of noladin ether reduced intraocular pressure in normotensive rabbits.
Recombinant Human Erythropoietin and Renal Anemia: Molecular Biology, Clinical Efficacy, and Nervous System Effects (1991)

Anemia (hematocrit less than 25%) predictably accompanies chronic renal failure and is present in over 90% of patients on chronic dialysis. Relative erythropoietin deficiency is the proximate cause. Recombinant human erythropoietin recently became available for research and clinical use. Erythropoietin production is regulated by a single copy gene located on chromosome 7; its expression has been shown in the kidney, liver, and macrophages. It is glycosylated protein of 166 amino acids with a molecular weight of 34,000 D. When given to patients with the anemia of renal failure, erythropoietin causes a dose-dependent rise in hematocrit to the normal range within 8 to 14 weeks. Complications of this response are minimal except for a significant incidence of hypertension. When the anemia is corrected, the patient's quality of life, cognitive function, and brain electrophysiology improve dramatically. Recombinant human erythropoietin represents a major breakthrough in the treatment of patients with chronic renal failure. Current reimbursement constraints limit its full application.
An Evaluation of the Beta-1 Adrenergic Receptor Arg389Gly Polymorphism in Individuals with Heart Failure: A MERIT-HF Sub-Study (2003)

In contrast to the benefits of beta-1 selective blockade, we have demonstrated that the Gly389 allele does not confer a significant mortality/morbidity benefit in heart failure patients. We have found no evidence of a pharmacogenetic effect of this biochemically functional polymorphism.
The cytokine network in asthma and chronic obstructive pulmonary disease (2008)

Asthma and chronic obstructive pulmonary disease (COPD) are very common inflammatory diseases of the airways. They both cause airway narrowing and are increasing in incidence throughout the world, imposing enormous burdens on health care. Cytokines play a key role in orchestrating the chronic inflammation and structural changes of the respiratory tract in both asthma and COPD and have become important targets for the development of new therapeutic strategies in these diseases.
Self-Ordered Nanocolumnar Pore Formation in the Photoelectrochemical Etching of 6H SiC (2007)

A columnar mesoporous structure was obtained in single-crystalline n-type by photoelectrochemical etching. The diameter cylindrical pores were about long, parallel, and distributed in a self-ordered manner. The pore morphologies and etching curves under different experimental conditions for both Si and C-face samples are discussed. It is found that constant voltage etching on C-face is crucial for the columnar pore formation.
Laminin Nanofiber Meshes That Mimic Morphological Properties and Bioactivity of Basement Membranes (2008)

The basement membrane protein, laminin I, has been used broadly as a planar two-dimensional film or in a three-dimensional form as a reconstituted basement membrane gel such as Matrigel to support cellular attachment, growth, and differentiation in vitro. In basement membranes in vivo, laminin exhibits a fibrillar morphology, highlighting the electrospinning process as an ideal method to recreate such fibrous substrates in vitro. Electrospinning was employed to fabricate meshes of murine laminin I nanofibers (LNFs) with fiber size, geometry, and porosity of authentic basement membranes. Purified laminin I was solubilized and electrospun in parametric studies of fiber diameters as a function of polymer solution concentration, collecting distance, and flow rate. Resulting fiber diameters ranged from 90 to 300 nm with mesh morphologies containing beads. Unlike previously described nanofibers (NFs) synthesized from proteins such as collagen, meshes of LNFs retain their structural features when wetted and do not require fixation by chemical crosslinking, which often destroys cell attachment and other biological activity. The LNF meshes maintained their geometry for at least 2 days in culture without chemical crosslinking. PC12 cells extended neurites without nerve growth factor stimulation on LNF substrates. Additionally, LNFs significantly enhance both the rate and quantity of attachment of human adipose stem cells (ASCs) compared to laminin films. ASCs were viable and maintained attachment to LNF meshes in serum-free media for at least 3 days in culture and extended neurite-like processes after 24 h in serum-free media conditions without media additives to induce differentiation. LNF meshes are a novel substrate for cell studies in vitro, whose properties may be an excellent scaffold material for delivering cells in tissue engineering applications in vivo.