gebhart/patrepeval huggingface dataset:
A comparison of different lysis buffers to assess allele dropout from single cells for preimplantation genetic diagnosis (2001)

Single cell polymerase chain reaction (PCR) for preimplantation genetic diagnosis (PGD) requires high efficiency and accuracy. Allele dropout (ADO), the random amplification failure of one of the two parental alleles, remains the most significant problem in PCR-based PGD testing since it can result in serious misdiagnosis for compound heterozygous or autosomal dominant conditions. A number of different strategies (including the use of lysis buffers to break down the cell and make the DNA accessible) have been employed to combat ADO with varying degrees of success, yet there is still no consensus among PGD centres over which lysis buffer should be used (ESHRE PGD Consortium, 1999). To address this issue, PCR amplification of three genes (CFTR, LAMA3 and PKP1) at different chromosomal loci was investigated. Single lymphocytes from individuals heterozygous for mutations within each of the three genes were collected and lysed in either alkaline lysis buffer (ALB) or proteinase K/SDS lysis buffer (PK). PCR amplification efficiencies were comparable between alkaline lysis and proteinase K lysis for PCR products spanning each of the three mutated loci (DeltaF508 in CFTR 90% vs 88%; R650X in LAMA3 82% vs 78%; and Y71X in PKP1 91% vs 87%). While there was no appreciable difference between ADO rates between the two lysis buffers for the LAMA3 PCR product (25% vs 26%), there were significant differences in ADO rates between ALB and PK for the CFTR PCR product (0% vs 23%) and the PKP1 PCR product (8% vs 56%). Based on these results, we are currently using ALB in preference to PK/SDS buffer for the lysis of cells in clinical PGD.
Syntheses of 3-Substituted 1-Methyl-6-phenylpyrimido(5,4-e)-1,2,4-triazine-5,7(1H,6H)-diones (6-Phenyl Analogs of Toxoflavin) and Their 4-Oxides, and Evaluation of Antimicrobial Activity of Toxoflavins and Their Analogs. (1993)

6-Phenyl analogs of toxoflavin (1-methyl-6-phenylpyrimido[5,4-e]-1,2,4-triazine-5,7(1H,6H)-diones ) (7a--f) and their 4-oxides (8a-f) were synthesized by nitrosative or nitrative cyclization of the aldehyde hydrazones (6a-f) of 6-(1-methylhydrazino)-3-phenyluracil (5). Both sets of compounds, 7a-f and 8a-f, gave the corresponding 1-demethyl derivatives (10a-f) upon treatment with nucleophiles such as dimethylformamide (DMF) and acetic acid under heating. The activities of toxoflavins (1a-e), toxoflavin 4-oxides (3a-e) and their 6-phenyl analogs (7a-f and 8a-f) against a variety of bacterial and fungal strains were examined. Most of the compounds showed strong inhibitory activities against gram-positive bacteria. Among the compounds, 1c, 1d, 1e, and 3c exhibited the strongest inhibitions of Micrococcus lutea (0.5 micrograms/ml minimal growth-inhibitory concentration) and Staphylococcus aureus 4R (1 microgram/ml), as well as Bacillus subtilis and Staphylococcus aureus (1-2 micrograms/ml). Most of the compounds had strong antifungal activity (2-100 micrograms/ml minimal growth-inhibitory concentration) against Candida albicans and Saccharomyces cerevisiae.
Novel Langmuir-Blodgett films of conducting polymers. 1. Polyion complexes and their multilayer heterostructures (1992)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTNovel Langmuir-Blodgett films of conducting polymers. 1. Polyion complexes and their multilayer heterostructuresA. T. Royappa and M. F. RubnerCite this: Langmuir 1992, 8, 12, 3168–3177Publication Date (Print):December 1, 1992Publication History Published online1 May 2002Published inissue 1 December 1992https://doi.org/10.1021/la00048a052Request reuse permissionsArticle Views228Altmetric-Citations41LEARN 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 InReddit PDF (2 MB) Get e-Alertsclose Get e-Alerts
Estimation of individual-specific progression to impending cardiovascular instability using arterial waveforms (2013)

Trauma patients with "compensated" internal hemorrhage may not be identified with standard medical monitors until signs of shock appear, at which point it may be difficult or too late to pursue life-saving interventions. We tested the hypothesis that a novel machine-learning model called the compensatory reserve index (CRI) could differentiate tolerance to acute volume loss of individuals well in advance of changes in stroke volume (SV) or standard vital signs. Two hundred one healthy humans underwent progressive lower body negative pressure (LBNP) until the onset of hemodynamic instability (decompensation). Continuously measured photoplethysmogram signals were used to estimate SV and develop a model for estimating CRI. Validation of the CRI was tested on 101 subjects who were classified into two groups: low tolerance (LT; n = 33) and high tolerance (HT; n = 68) to LBNP (mean LBNP time: LT = 16.23 min vs. HT = 25.86 min). On an arbitrary scale of 1 to 0, the LT group CRI reached 0.6 at an average time of 5.27 ± 1.18 (95% confidence interval) min followed by 0.3 at 11.39 ± 1.14 min. In comparison, the HT group reached CRI of 0.6 at 7.62 ± 0.94 min followed by 0.3 at 15.35 ± 1.03 min. Changes in heart rate, blood pressure, and SV did not differentiate HT from LT groups. Machine modeling of the photoplethysmogram response to reduced central blood volume can accurately trend individual-specific progression to hemodynamic decompensation. These findings foretell early identification of blood loss, anticipating hemodynamic instability, and timely application of life-saving interventions.
Structural determinants of Trk receptor specificities using BNDF‐based neurotrophin chimeras (1996)

Neurotrophins play very important roles in the development and maintenance of the vertebrate nervous system. In mammals, there are four members of the family: NGF, BDNF, NT-3, and NT-4/5. Members of the neurotrophin family activate different receptors that belong to a class of receptor tyrosine kinases known as “Trks.” For example, NGF is the specific ligand of TrkA, while BDNF activates TrkB. To elucidate which regions of the two neurotrophins determine the receptor specificities, chimeric neurotrophins were constructed using BDNF as the backbone, with various regions being substituted by the corresponding regions of NGF. The activity of the chimeras on the Trk receptors was assayed in transfected fibroblasts ectopically expressing the Trk receptors. Our findings revealed that, although BDNF is absolutely conserved in mammals, substitution of several small variable regions from NGF into the BDNF backbone did not lead to significant loss in TrkB activity or gain in TrkA activity. Moreover, important determinants of TrkB activation might be located in the carboxy-terminal half of BDNF. On the other hand, critical elements for TrkA activation might be located within the amino-terminal half of the mature NGF molecule. © 1996 Wiley-Liss, Inc.
Overexpression of HMGB1 A-box reduced lipopolysaccharide-induced intestinal inflammationviaHMGB1/TLR4 signalingin vitro (2015)

HMGB1 A-box, not only EP, can reduce LPS-induced intestinal inflammation through inhibition of the HMGB1/TLR4 signaling pathways.
Serum and Cerebrospinal Fluid Prolactin levels in Male and Female Patients with Clinically‐Isolated Syndrome or Relapsing‐Remitting Multiple Sclerosis (2010)

There is considerable evidence that prolactin (PRL) exerts immunomodulatory actions, thus being involved in the processes of autoimmune diseases. Animal studies suggest that elevated serum PRL levels may be related to neuroprotection or participate in remyelination after brain injury. To address this question, we estimated PRL levels in both serum and cerebrospinal fluid (CSF) in drug-free male and female patients with clinically-isolated syndrome (CIS) suggestive of MS (i.e. after the first episode) as well as in patients with relapsing-remitting (RR) MS after two or more relapses, and related them to clinical, paraclinical and laboratory data. Seventy two patients with RR MS and 80 patients with CIS in the age range 17-61 years were studied. PRL levels of patients were compared with 74 control subjects, separately for males and females. Significantly higher PRL levels in serum and CSF were found in female RRMS patients but not in males. Patients with CIS had normal PRL levels. No associations were found with disease activity, duration of illness, presence of active lesions or the presence of oligoclonal bands in CSF. The elevated PRL levels observed in female but not in male RRMS patients, or in patients with CIS, could be suggestive of a sexually dimorphic response to central nervous system injury as a result of an increased proneness of females to synthesise and release PRL, which is possibly linked to the relatively more favourable prognosis of MS in women.
Potent and Highly Selective Hypoxia-Activated Achiral Phosphoramidate Mustards as Anticancer Drugs (2008)

A series of achiral hypoxia-activated prodrugs were synthesized on the basis of the DNA cross-linking toxin of the prodrug, ifosfamide. The hypoxia-selective cytotoxicity of several of the compounds was improved over previously reported racemic mixtures of chiral bioreductive phosphoramidate prodrugs. Prodrugs activated by 2-nitroimidazole reduction demonstrated up to 400-fold enhanced cytotoxicity toward H460 cells in culture under hypoxia versus their potency under aerobic conditions. Compounds were further assessed for their stability to cytochrome P450 metabolism using a liver microsome assay. The 2-nitroimidazole containing lead compound 3b (TH-302) was selectively potent under hypoxia and stable to liver microsomes. It was active in an in vivo MIA PaCa-2 pancreatic cancer orthotopic xenograft model as a monotherapy and demonstrated dramatic efficacy when used in combination with gemcitabine, extending survival with one of eight animals tumor free at day-44. Compound 3b has emerged as a promising antitumor agent that shows excellent in vivo efficacy and is currently being evaluated in the clinic.
A history of optogenetics: the development of tools for controlling brain circuits with light (2011)

Understanding how different kinds of neuron in the brain work together to implement sensations, feelings, thoughts, and movements, and how deficits in specific kinds of neuron result in brain diseases, has long been a priority in basic and clinical neuroscience. "Optogenetic" tools are genetically encoded molecules that, when targeted to specific neurons in the brain, enable their activity to be driven or silenced by light. These molecules are microbial opsins, seven-transmembrane proteins adapted from organisms found throughout the world, which react to light by transporting ions across the lipid membranes of cells in which they are genetically expressed. These tools are enabling the causal assessment of the roles that different sets of neurons play within neural circuits, and are accordingly being used to reveal how different sets of neurons contribute to the emergent computational and behavioral functions of the brain. These tools are also being explored as components of prototype neural control prosthetics capable of correcting neural circuit computations that have gone awry in brain disorders. This review gives an account of the birth of optogenetics and discusses the technology and its applications.
The First Potent Subtype‐Selective Retinoid X Receptor (RXR) Agonist Possessing a 3‐Isopropoxy‐4‐isopropylphenylamino Moiety, NEt‐3IP (RXRα/β‐dual agonist) (2008)

Retinoid X receptor (RXR) agonists (rexinoids) are attracting much attention for their use in treatment of cancers, including tamoxifen-resistant breast cancer and taxol-resistant lung cancer, and metabolic disease. However, known RXR agonists have a highly lipophilic character. In addition, no subtype-selective RXR agonists have been found. We previously reported an RXRalpha-preferential agonist 4-[N-methanesulfonyl-N-(5,5,8,8-tetramethyl-5,6,7,8-tetrahydro-2-naphthyl)amino]benzoic acid (6 a). The RXR agonistic activity is much less than that of well-known RXR agonists. To develop potent, less-lipophilic, and subtype-selective RXR agonists, we created new RXR agonists possessing alkoxy and isopropyl groups as a lipophilic domain of the common structure of well-known RXR agonists. As a result, compounds possessing branched alkoxy groups, 6-[N-ethyl-N-(3-isopropoxy-4-isopropylphenyl)amino]nicotinic acid (NEt-3IP: 7 a) and 6-[N-ethyl-N-(3-isobutoxy-4-isopropylphenyl)amino]nicotinic acid (NEt-3IB: 7 c), showed RXR agonistic activity as potent as, or more potent than, the activities of representative RXR agonists. Moreover, NEt-3IP (7 a) was found to be the first RXRalpha/beta-selective (or RXRalpha/beta-dual) agonist. Being potent, less lipophilic, and having RXR subtype-selective activity, NEt-3IP (7 a) is expected to become a new drug candidate and to be a useful biological tool for clarifying each RXR subtype function.
Ligation reaction specificities of an NAD+-dependent DNA ligase from the hyperthermophile Aquifex aeolicus (2000)

An NAD(+)-dependent DNA ligase from the hyperthermophilic bacterium Aquifex aeolicus was cloned, expressed in Escherichia coli and purified to homogeneity. The enzyme is most active in slightly alkaline pH conditions with either Mg(2+)or Mn(2+)as the metal cofactor. Ca(2+)and Ni(2+)mainly support formation of DNA-adenylate intermediates. The catalytic cycle is characterized by a low k (cat)value of 2 min(-1)with concomitant accumulation of the DNA - adenylate intermediate when Mg(2+)is used as the metal cofactor. The ligation rates of matched substrates vary by up to 4-fold, but exhibit a general trend of T/A < or = G/C < C/G < A/T on both the 3'- and 5'-side of the nick. Consistent with previous studies on Thermus ligases, this Aquifex ligase exhibits greater discrimination against a mismatched base pair on the 3'-side of the nick junction. The requirement of 3' complementarity for a ligation reaction is reaffirmed by results from 1 nt insertions on either the 3'- or 5'-side of the nick. Furthermore, most of the unligatable 3' mismatched base pairs prohibit formation of the DNA-adenylate intermediate, indicating that the substrate adenylation step is also a control point for ligation fidelity. Unlike previously studied ATP ligases, gapped substrates cannot be ligated and intermediate accumulation is minimal, suggesting that complete elimination of base pair complementarity on one side of the nick affects substrate adenylation on the 5'-side of the nick junction. Relationships among metal cofactors, ligation products and intermediate, and ligation fidelity are discussed.
Detection of Rhythmic Bioluminescence From Luciferase Reporters in Cyanobacteria (2007)

The unicellular cyanobacterium Synechococcus elongatus PCC 7942 is the model organism for studying prokaryotic circadian rhythms. Although S. elongatus does not display an easily measurable overt circadian behavior, its gene expression is under circadian control; hence, a "behavior" is created by linking a cyanobacterial promoter to either the bacterial luxAB or firefly luc luciferase genes to create reporter fusions whose activity can be easily monitored by bioluminescence. Numerous vectors have been created in our lab for introducing luciferase reporter genes into the S. elongatus chromosome. A choice of methods and equipment to detect light production from the luciferase fusions provides a means for high-throughput, automated mutant screens as well as testing rhythms from two promoter fusions within the same cell culture.
Inhibition of Ultraviolet B-induced Activator Protein-1 (AP-1) Activity by Aspirin in AP-1-Luciferase Transgenic Mice (1997)

Aspirin is under consideration as a promising chemopreventative agent for human cancers. To study the usefulness of aspirin as a chemopreventative agent for UV-induced human skin cancer, we investigated the effect of aspirin on UVB-induced activator protein-1 (AP-1) activity. In the JB6 cell culture system, aspirin or sodium salicylate (SA) inhibited UVB-induced AP-1 activity in a dose-dependent manner; this inhibitory effect occurred only in cells pretreated with aspirin or SA before UVB irradiation but not cells treated with aspirin or SA after UVB irradiation. Furthermore, these inhibitory effects on UVB-induced AP-1 activity appeared to be mediated through blocking of activation of MAP kinase family members, including extracellular signal-regulated protein kinases, c-Jun N-terminal kinases, and p38. It was not due to absorption of UVB light by aspirin. In the skin of AP-1-luciferase transgenic mice, UVB irradiation induced a rapid increase in AP-1 activity, which reached the peak at 48 h post-UVB irradiation. The topical pretreatment of mouse skin with aspirin markedly blocked the UVB-induced AP-1 transactivation in vivo. These data provide the first evidence that aspirin and SA are inhibitors of UV-induced signal transduction and thus could be used as a chemopreventative agent for skin cancer.
Emerging 'A' therapies in hemoglobinopathies: agonists, antagonists, antioxidants, and arginine. (2012)

Sickle cell disease and thalassemia have distinctly different mutations, but both share common complications from a chronic vasculopathy. In the past, fetal hemoglobin-modulating drugs have been the main focus of new therapy, but the increased understanding of the complex pathophysiology of these diseases has led to the development of novel agents targeting multiple pathways that cause vascular injury. This review explores the pathophysiology of hemoglobinopathies and novel drugs that have reached phase 1 and 2 clinical trials. Therapies that alter cellular adhesion to endothelium, inflammation, nitric oxide dysregulation, oxidative injury, altered iron metabolism, and hematopoiesis will be highlighted. To evaluate these therapies optimally, recommendations for improving clinical trial design in hemoglobinopathies are discussed.
2003 Claude S. Hudson Award Address in Carbohydrate Chemistry. Heparin:  Structure and Activity (2003)

ADVERTISEMENT RETURN TO ISSUEPerspectiveNEXT2003 Claude S. Hudson Award Address in Carbohydrate Chemistry. Heparin: Structure and ActivityRobert J. LinhardtView Author Information Departments of Chemistry, Medicinal and Natural Products Chemistry, and Chemical and Biochemical Engineering, University of Iowa, Iowa City, Iowa 52242 Cite this: J. Med. Chem. 2003, 46, 13, 2551–2564Publication Date (Web):May 20, 2003Publication History Received15 April 2003Published online20 May 2003Published inissue 1 June 2003https://pubs.acs.org/doi/10.1021/jm030176mhttps://doi.org/10.1021/jm030176mreview-articleACS PublicationsCopyright © 2003 American Chemical SocietyRequest reuse permissionsArticle Views2907Altmetric-Citations436LEARN 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-Alertsclose SUBJECTS:Anatomy,Anions,Heparin,Peptides and proteins,Screening assays Get e-Alerts
The VLA protein family. Characterization of five distinct cell surface heterodimers each with a common 130,000 molecular weight beta subunit. (1987)

The family of human cell surface heterodimers which includes VLA-1 and VLA-2 is now shown to include three additional heterodimers, here called VLA-3, VLA-4, and VLA-5. Each of these separate VLA structures is composed of a distinct alpha subunit (Mr 110,000-200,000 nonreduced) noncovalently associated with a common beta subunit (Mr 110,000 nonreduced). Chemical cross-linking experiments provided evidence that each VLA complex exists predominantly as a 1:1 alpha beta heterodimer. The VLA proteins are widely distributed, with one or more of the heterodimers present on nearly all cell types tested. Evidence for five distinct VLA alpha subunits was obtained from differences observed in antibody recognition, cell distribution patterns, two-dimensional gel analyses, and V8 protease cleavage patterns. On the other hand, the beta subunit present in each heterodimer was immunochemically and electrophoretically indistinguishable, and yielded identical V8 cleavage fragments. Immunoblotting experiments revealed that besides the Mr 110,000 beta normally seen, another beta protein was present that is smaller in size (Mr 90,000 nonreduced), altered or deficient in glycosylation, and not available for cell surface radiolabeling.
The role of the natriuretic peptides in the cardiovascular system (2001)

The discovery of the natriuretic peptide family was a breakthrough in modern cardiovascular physiology as it provided a direct link between the heart and the kidneys in the regulation of natriuresis. Along with vasopressin and the renin-angiotensin-aldosterone system, the natriuretic peptides comprise the key peptides on which our present understanding of neuroendocrine regulation of the cardiovascular system is based. Three natriuretic peptides have been identified; the A-type, B-type and C-type natriuretic peptides. The former two, the A- and B-type natriuretic peptides, function mainly in the cardiovascular system and comprise the cardiac natriuretic peptides. Together with our increased understanding of the neurohormonal regulation of the cardiovascular system in recent years, the discovery of the natriuretic peptide family was important in the establishment of the new field of cardiovascular endocrinology.
Synthesis of novel 1‐phenyl‐1H‐indole‐2‐carboxylic Acids. I. Utilization of ullmann and dieckmann reactions for the preparation of 3‐hydroxy, 3‐alkoxy, and 3‐alkyl derivatives (1987)

Abstract Methods for the synthesis of novel 3‐hydroxy, 3‐alkoxy, and 3‐alkyl indole‐2‐carboxylic acids and esters are described. Dieckmann cyclization of various 2‐[(carboxymethyl)amino]benzoic acid diesters yielded 1‐unsubstituted‐, 1‐methyl‐, and 1‐phenyl‐3‐hydroxy‐1 H ‐indole‐2‐carboxylic acid esters. An Ullmann reaction with bromobenzene converted 1 H ‐indoles to 1‐phenylindoles.