gebhart/patrepeval huggingface dataset:
High Prevalence of Symptoms of Meniere's Disease in three Families With a Mutation in the COCH Gene (1999)

We report the genetic analysis of one large Belgian and two small Dutch families with autosomal dominant non-syndromic progressive sensorineural hearing loss associated with vestibular dysfunction. Linkage studies in the Belgian family mapped the disease to the DFNA9 locus on chromosome 14. Mutation analysis of the COCH gene, which is responsible for DFNA9, revealed a missense mutation changing a highly conserved residue. One of the patients, who had an earlier age of onset in comparison with most of the affected family members, was shown to be homozygous for the mutation. After the mutation was found in the Belgian family, we discovered that the same missense mutation was also present in two Dutch families with similar cochleo-vestibular symptoms. In all three families with hearing loss and imbalance problems, >25% of the patients showed additional symptoms, including episodes of vertigo, tinnitus, aural fullness and hearing loss. Clinically, these symptoms are consistent with the criteria for Menière's disease. The importance of genetic factors in Menière's disease has been suggested on many occasions, but this study is the first report of a mutation in a gene leading to the symptoms of Menière's disease in a significant portion of the carriers. The COCH gene may be one of the genetic factors contributing to Menière's disease and the possibility of a COCH mutation should be considered in patients with Menière's disease symptoms.
Different 3' end points of deletions causing delta beta-thalassemia and hereditary persistence of fetal hemoglobin: implications for the control of gamma-globin gene expression in man. (1983)

DNA at the end point of the gene deletion associated with one form of hereditary persistence of fetal hemoglobin (HPFH) was cloned and used as a probe in gene mapping experiments to analyze the extent and approximate 3' end points of various deletions associated with HPFH and delta beta-thalassemia. The deletions in the two known forms of deletion-type HPFH were shown to be considerably more extensive than in the two cases of delta beta-thalassemia studied. The overall extents of the deletions in the two types of HPFH were quite similar in both cases and the 3' end points were located at a minimum distance of approximately equal to 52 and 57 kilobases from the 3' extremity of the beta-globin gene. In contrast, the 3' end points of the deletions in the two forms of delta beta-thalassemia were located approximately equal to 5 and 10 kilobases to the 3' side of the beta-globin gene. The extent of these deletions and the nature of the DNA brought into the vicinity of the gamma-globin genes by the deletions may therefore be a more important influence on the phenotype of the deletions than the specific nature of the DNA sequences that are deleted within the non-alpha-globin gene cluster as a result of the mutations.
A Phase I/IIa Clinical Trial of a Recombinant Rho Protein Antagonist in Acute Spinal Cord Injury (2011)

Multiple lines of evidence have validated the Rho pathway as important in controlling the neuronal response to growth inhibitory proteins after central nervous system (CNS) injury. A drug called BA-210 (trademarked as Cethrin(®)) blocks activation of Rho and has shown promise in pre-clinical animal studies in being used to treat spinal cord injury (SCI). This is a report of a Phase I/IIa clinical study designed to test the safety and tolerability of the drug, and the neurological status of patients following the administration of a single dose of BA-210 applied during surgery following acute SCI. Patients with thoracic (T2-T12) or cervical (C4-T1) SCI were sequentially recruited for this dose-ranging (0.3 mg to 9 mg Cethrin), multi-center study of 48 patients with complete American Spinal Injury Association assessment (ASIA) A. Vital signs; clinical laboratory tests; computed tomography (CT) scans of the spine, head, and abdomen; magnetic resonance imaging (MRI) of the spine, and ASIA assessment were performed in the pre-study period and in follow-up periods out to 1 year after treatment. The treatment-emergent adverse events that were reported were typical for a population of acute SCI patients, and no serious adverse events were attributed to the drug. The pharmacokinetic analysis showed low levels of systemic exposure to the drug, and there was high inter-patient variability. Changes in ASIA motor scores from baseline were low across all dose groups in thoracic patients (1.8±5.1) and larger in cervical patients (18.6±19.3). The largest change in motor score was observed in the cervical patients treated with 3 mg of Cethrin in whom a 27.3±13.3 point improvement in ASIA motor score at 12 months was observed. Approximately 6% of thoracic patients converted from ASIA A to ASIA C or D compared to 31% of cervical patients and 66% for the 3-mg cervical cohort. Although the patient numbers are small, the observed motor recovery in this open-label trial suggests that BA-210 may increase neurological recovery after complete SCI. Further clinical trials with Cethrin in SCI patients are planned, to establish evidence of efficacy.
Design and Analysis of Active Hypertext Views on Databases (2003)

The design and maintenance of data-intensive Web sites is a demanding task. The effort can be significantly lowered by using two verified technologies: databases and hypertexts. The first is well suited to administrate a large amount of data; the second has proven to be an easy to use and efficient means of accessing information. The task can be made even easier by using a declarative approach, i.e., the data structure and hypertext structure are both explicitly defined, and the specification is expressed in terms of structure transformation. In addition to the specification language, we provide a design technique: starting with the database structure, the designer applies refinement heuristics that eventually yield an efficient hypertext structure for the final user. The hypertext thus obtained can be seen as a view on the database. A fully functional hypertextual interface should also enable the user to perform update operations on the database. Our system provides this facility, including mechanisms to tackle the well-known update-through-views problem by providing specific mechanisms. Finally, the nonprocedural approach has a supplementary advantage: it offers the possibility of analyzing the hypertext structure before setting it in production, in particular, analyzing the reachability of information or determining the length of the navigation path.
A selectable marker using cytochrome P450 monooxygenases for Arabidopsis transformation (2005)

We have developed a selection system for transformation of Arabidopsis thaliana via Agrobacterium tumefaciens. This selection system uses human cytochrome P450 monooxygenases that metabolize herbicides. Herbicide-tolerant seedlings transformed with CYP1A1, CYP2B6, CYP2C9, or CYP2C19 were selected with the herbicides acetochlor, amiprophos-methyl, chlorpropham, chlorsulfuron, norflurazon, and pendimethalin. The herbicide-tolerant plants transformed with CYP1A1, CYP2B6, and CYP2C19 expressed the corresponding P450 cDNAs. Inheritance and segregation of the P450 genes were analyzed in T2 progeny of herbicide-tolerant T1 seedlings. Metabolism of [14C]norflurazon by transgenic T2 seedlings expressing CYP1A1 produced non-toxic N-demethylated norflurazon. This result suggests that the P450 species expressed in transgenic Arabidopsis plants coordinately functioned as selectable markers because of active metabolism of the herbicides.
Trapping Moving Targets with Small Molecules (2009)

Structure-based drug design traditionally uses static protein models as inspirations for focusing on "active" site targets. Allosteric regulation of biological macromolecules, however, is affected by both conformational and dynamic properties of the protein or protein complex and can potentially lead to more avenues for therapeutic development. We discuss the advantages of searching for molecules that conformationally trap a macromolecule in its inactive state. Although multiple methodologies exist to probe protein dynamics and ligand binding, our current discussion highlights the use of nuclear magnetic resonance spectroscopy in the drug discovery and design process.
“Giant” Multishell CdSe Nanocrystal Quantum Dots with Suppressed Blinking (2008)

Semiconductor nanocrystal quantum dots (NQDs) comprise an important class of inorganic fluorophores for applications from optoelectronics to biology. Unfortunately, to date, NQD optical properties (e.g., their efficient and particle-size-tunable photoluminescence) have been susceptible to instabilities at the bulk and single-particle levels. Specifically, ensemble quantum yields (QYs) in emission are dependent upon NQD surface chemistry and chemical environment, while at the single-particle level, NQDs are characterized by significant fluorescence intermittency (blinking) that hinders applications as single-photon light sources for quantum informatics and biolabels for real-time monitoring of single biomolecules. Furthermore, while NQDs are significantly more photostable than their organic dye counterparts, traditional NQDs photobleach over periods of seconds to many minutes. Here, we demonstrate for the first time that by encapsulating the NQD core in a sufficiently thick inorganic shell, we are able to divorce NQD function from NQD surface chemistry and chemical environment. We show that our "giant" NQDs (g-NQDs) are functionally distinct from standard core-only, core/shell and even core/multishell NQDs. g-NQDs are substantially less sensitive to changes in surface chemistry. They do not photobleach under continuous laser excitation over periods of several hours repeated over several days, and they exhibit markedly different blinking behavior; >20% of the g-NQDs do not blink, while >40% have on-time fractions of >80%. All of these observations are in stark contrast with control samples comprising core-only and standard, thinner core/multishell NQDs.
Inorganic polyphosphate stimulates mammalian TOR, a kinase involved in the proliferation of mammary cancer cells (2003)

Inorganic polyphosphate (poly P), chains of hundreds of phosphate residues linked by "high-energy" bonds as in ATP, has been conserved from prebiotic times in all cells. Poly P is essential for a wide variety of functions in bacteria, including virulence in pathogens. In this study, we observe the unique and many-fold stimulation by poly P in vitro of the protein kinase mTOR (mammalian target of rapamycin). To explore the role of poly P in mammalian cells, a yeast polyphosphatase, PPX1, was inserted into the chromosomes of MCF-7 mammary cancer cells. The transfected cells are markedly deficient in their response to mitogens, such as insulin and amino acids, as seen in their failure to activate mTOR to phosphorylate one of its substrates, PHAS-I (the initiation factor 4E-binding protein). In addition, the transfected cells are severely reduced in their growth in a serum-free medium. On the basis of these findings, we suggest that poly P (and/or PPX1) serves as a regulatory factor in the activation of mTOR in the proliferative signaling pathways of animal cells.
A1-adenosine receptor antagonists block endotoxin-induced lung injury (1997)

Endotoxin produces a variety of biological effects on different cell types, such as priming of neutrophils and macrophages, which then release a number of important mediators of endotoxin-induced lung injury. However, the specific mechanism by which endotoxin initiates its cascade of pathophysiological events in the lung has not been described. Both A1 adenosine receptor activation and endotoxin induce the release of thromboxane A2 from the lung and inhibit adenylate cyclase. By acting on A1 adenosine receptors, adenosine promotes neutrophil chemotaxis and adherence to endothelial cells. We hypothesized that A1 adenosine receptor activation is essential to endotoxin-induced lung injury, and we used the highly selective A1-adenosine receptor antagonists, 8-cyclopentyl-1,3-dipropylxanthine (DPCPX) and 8-benzyl-7,[2-[ethyl(2-hydroxyethyl)amino]-ethyl] theophylline (bamiphylline), to investigate whether selective blocking of the A1 adenosine receptor would prevent endotoxin-induced acute lung injury. An intralobar arterial infusion of endotoxin (15 mg/kg) into the left lower lobe of the lung in intact-chest, spontaneously breathing cats produced lung injury characterized by the presence of neutrophils, macrophages, and red blood cells (RBCs) in alveoli, and alveolar edema and necrosis. Lower doses of endotoxin (5 or 10 mg/kg) produced less severe and dose-dependent lung injury. Endotoxin (15 mg/kg)-induced alveolar injury was blocked in a highly significant manner by A1-adenosine receptor antagonists, DPCPX and bamiphylline. An intravenous bolus of DPCPX 30 min before endotoxin infusion or a continuous intravenous infusion of bamiphylline 30 min before, during, and 30 min after endotoxin reduced the percent injured alveoli (defined as the presence of 2 or more inflammatory cells or RBCs, or edematous fluid) from 57 +/- 31% (endotoxin 15 mg/kg) to 9 +/- 1% (DPCPX) or 21 +/- 14% (bamiphylline), which were not significantly different from control (1-h perfusion only) (4 +/- 1%) (P < 0.05). These data represent the first evidence that A1-adenosine receptor antagonism blocks the capacity of endotoxin to cause lung injury. A1-adenosine receptor antagonists may be useful in preventing adult respiratory distress syndrome associated with septicemia.
A General Solid-Phase Synthesis Strategy for the Preparation of 2-Pyrrolidinemethanol Ligands (1995)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTA General Solid-Phase Synthesis Strategy for the Preparation of 2-Pyrrolidinemethanol LigandsGuangcheng Liu and Jonathan A. EllmanCite this: J. Org. Chem. 1995, 60, 24, 7712–7713Publication Date (Print):December 1, 1995Publication History Published online1 May 2002Published inissue 1 December 1995https://pubs.acs.org/doi/10.1021/jo00129a002https://doi.org/10.1021/jo00129a002research-articleACS PublicationsRequest reuse permissionsArticle Views558Altmetric-Citations140LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-AlertscloseSupporting Info (2)»Supporting Information Supporting Information Get e-Alerts
Mode excitation in a multimode optical-fibre waveguide (1973)

For normal incidence of a Gaussian beam on a multimode optical fibre, theory predicts that only HE1m, modes are excited, and this is confirmed experimentally for a liquid-core fibre of normalised frequency v = 125. Discrete-mode propagation is observed, indicating that the amount of mode conversion due to fibre imperfections is thus very small.
DNA Microarray Technology: Devices, Systems, and Applications (2002)

In this review, recent advances in DNA microarray technology and their applications are examined. The many varieties of DNA microarray or DNA chip devices and systems are described along with their methods for fabrication and their use. This includes both high-density microarrays for high-throughput screening applications and lower-density microarrays for various diagnostic applications. The methods for microarray fabrication that are reviewed include various inkjet and microjet deposition or spotting technologies and processes, in situ or on-chip photolithographic oligonucleotide synthesis processes, and electronic DNA probe addressing processes. The DNA microarray hybridization applications reviewed include the important areas of gene expression analysis and genotyping for point mutations, single nucleotide polymorphisms (SNPs), and short tandem repeats (STRs). In addition to the many molecular biological and genomic research uses, this review covers applications of microarray devices and systems for pharmacogenomic research and drug discovery, infectious and genetic disease and cancer diagnostics, and forensic and genetic identification purposes. Additionally, microarray technology being developed and applied to new areas of proteomic and cellular analysis are reviewed.
Golimumab in patients with active rheumatoid arthritis despite treatment with methotrexate: A randomized, double‐blind, placebo‐controlled, dose‐ranging study (2008)

Golimumab plus MTX effectively reduces the signs and symptoms of RA and is generally well tolerated in patients with an inadequate response to MTX.
Association of the inflammatory state in active juvenile rheumatoid arthritis with hypo-high-density lipoproteinemia and reduced lipoprotein-associated platelet-activating factor acetylhydrolase activity (1999)

This is the first study to show that patients with active JRA exhibit low levels of HDL2 and HDL3 and are deficient in plasma PAF-AH activity. These alterations suggest that active JRA is associated with partial loss of the antiinflammatory activity of plasma Apo B- and Apo A-I-containing lipoproteins.
Reactions of the articular capsule to wear products of artificial joint prostheses (1977)

Examination of a great number of tissue samples taken from the newly formed capsules surrounding artificial joints reveals small particles of prosthetic material. Abraded from the joint by wear and tear, these particles of plastic, metal, and acrylic cement initiate a foreign-body reaction and result in the formation of granulation tissue, including macrophages and foreign-body giant cells. Typical features of tissue reactions exist for each of the materials from which prostheses are made. The consequent formation of scar tissue produces a thickening of the capsule, which, in turn, may cause a reduction in the mobility of the joint. In small amounts, the foreign-body particles are eliminated via the perivascular lymph spaces. Where this transport system is insufficient to handle the volume, however, the foreign-body response may extend to the whole environment surrounding the joint. In such cases, there may be loosening of the cemented prosthetic parts because of deterioration of contiguous bone anchors by the tissue membrane lining the bone cement.
True 3‐D scanned voxel displays using single or multiple light sources (2006)

Abstract— Conventional stereoscopic displays require viewers to unnaturally keep eye accommodation fixed at one focal distance while they dynamically change vergence to view objects at different distances. This forced decoupling of reflexively linked processes fatigues eyes, causes discomfort, compromises image quality, and may lead to pathologies in developing visual systems. Volumetric displays can overcome this conflict, but only for small objects placed within a limited range of viewing distances and accommodation levels, and cannot render occlusion cues correctly. Our multi‐planar True 3‐D displays generate accommodation cues that match vergence and stereoscopic retinal disparity demands and can display images and objects at viewing distances throughout the full range of human accommodation (from 6.25 cm to infinity), better mimicking natural vision and minimizing eye fatigue.
Anisotropic reflection models (1985)

We present a new set of lighting models derived from the questions of electromagnetism. These models describe the reflection and refraction of light from surfaces which exhibit anisotropy---surfaces with preferred directions. The model allows a new mapping technique, which we call frame mapping . We also discuss the general relationship between geometric models, surface mapping of all types, and lighting models in the context of rendering images with extreme complexity.
Sandwich-type heteroleptic phthalocyaninato and porphyrinato metal complexes (1997)

Over the past decade, a substantial number of sandwich-type metal complexes with mixed phthalocyaninato and/or porphyrinato ligands have been synthesised. Owing to the intriguing π–π interactions associated with these complexes, this family of sandwich compounds displays unique physical, spectroscopic and electrochemical properties which have aroused great interest from researchers in various disciplines. This article seeks to summarise recent developments in this field of reserach and explain the growing interest in this fascinating and important class of complexes.
Synthesis of 2‐aryl‐6‐carbethoxythiazolo[4,5‐c]pyridine and 7‐chloro‐2‐phenylthiazolo[5,4‐c]pyridine (1986)

Abstract Starting from readily available 2‐aryl‐5‐formyl‐4‐mehtylthiazole, 2‐aryl‐6‐carbethoxythiazolo[4,5‐ c ]pyridine was prepared. β‐(2‐Phenylthiazol‐4‐yl)acrylic acid was converted to the corresponding azide (VI). Cyclization of compound VI afforded 2‐phenylthiazolo[5,4‐ c ]pyridin‐7(6 H )one. Reaction of the latter with phosphorous oxychloride gave 7‐chloro‐2‐phenylthiazolo[5,4‐ c ]pyridine.
Estrogens and Progesterone Promote Persistent CCND1 Gene Activation during G 1 by Inducing Transcriptional Derepression via c- Jun /c- Fos /Estrogen Receptor (Progesterone Receptor) Complex Assembly to a Distal Regulatory Element and Recruitment of Cyclin D1 to Its Own Gene Promoter (2004)

Transcriptional activation of the cyclin D1 gene (CCND1) plays a pivotal role in G(1)-phase progression, which is thereby controlled by multiple regulatory factors, including nuclear receptors (NRs). Appropriate CCND1 gene activity is essential for normal development and physiology of the mammary gland, where it is regulated by ovarian steroids through a mechanism(s) that is not fully elucidated. We report here that CCND1 promoter activation by estrogens in human breast cancer cells is mediated by recruitment of a c-Jun/c-Fos/estrogen receptor alpha complex to the tetradecanoyl phorbol acetate-responsive element of the gene, together with Oct-1 to a site immediately adjacent. This process coincides with the release from the same DNA region of a transcriptional repressor complex including Yin-Yang 1 (YY1) and histone deacetylase 1 and is sufficient to induce the assembly of the basal transcription machinery on the promoter and to lead to initial cyclin D1 accumulation in the cell. Later on in estrogen stimulation, the cyclin D1/Cdk4 holoenzyme associates with the CCND1 promoter, where E2F and pRb can also be found, contributing to the long-lasting gene enhancement required to drive G(1)-phase completion. Interestingly, progesterone triggers similar regulatory events through its own NRs, suggesting that the gene regulation cascade described here represents a crossroad for the transcriptional control of G(1)-phase progression by different classes of NRs.