gebhart/patrepeval huggingface dataset:
Quantitation of Plasma Human Immunodeficiency Virus Type 1 RNA by Competitive Polymerase Chain Reaction (1992)

Clinical measures of human immunodeficiency virus (HIV) type 1 activity in vivo are limited and hinder the assessment of antiretroviral therapies. Reported here is a method for quantitating HIV-1 RNA in human plasma using the polymerase chain reaction (PCR). This method uses an internal cRNA standard generated from a cloned 113-bp deletion mutation of a highly conserved HIV-1 gag region sequence. The mutant cRNA (K4) was shown to amplify with efficiency equivalent to that of wild-type HIV-1. Known quantities of K4 cRNA added to wild-type HIV-1 in a competitive PCR strategy using a radiolabeled primer permitted quantitation of wild-type HIV-1 RNA over four orders of magnitude (10(3)-10(6) RNA copies). RNA isolated from plasma from AIDS patients yielded 10(3) to 8 x 10(4) HIV-1 RNA copies/ml of plasma with an average intrasample coefficient of variation of .26. This method offers a sensitive assay with a broad dynamic range for monitoring HIV-1 activity in the plasma of AIDS patients. It may provide a useful tool for assessing the effects of antiretroviral therapy.
The global burden of low back pain: estimates from the Global Burden of Disease 2010 study (2014)

LBP causes more global disability than any other condition. With the ageing population, there is an urgent need for further research to better understand LBP across different settings.
The Rearrangement of 10-Bromo-10,11-dihydrodibenzo[b,f]thiepin-11-one and Related Compounds in an Alkaline Solution (1975)

Abstract The reaction of 10-bromo-10,11-dihydrodibenzo[b,f]thiepin-11-one (1) with sodium methoxide in methanol has been shown to lead to thioxanthone (4) and 10-hydroxy-10,11-dihydrodibenzo[b,f]thiepin-11-one (5). If the reaction of 1 in an aqueous sodium hydroxide solution is carried out, six products, 4, 5, 9-hydroxy-thioxanthene-9-carboxylic acid (6), thioxanthene-9-carboxylic acid (7), thioxanthene (8), and 10,11-dihydrodibenzo [b,f]thiepin-10-one (9), are formed. The structures of the products were established by elementary analysis, by an examination of the spectral data, by gas chromatography, and by an independent synthesis. The results were discussed in terms of the mechanism proposed.
Chemical-free inactivated whole influenza virus vaccine prepared by ultrashort pulsed laser treatment (2014)

There is an urgent need for rapid methods to develop vaccines in response to emerging viral pathogens. Whole inactivated virus (WIV) vaccines represent an ideal strategy for this purpose; however, a universal method for producing safe and immunogenic inactivated vaccines is lacking. Conventional pathogen inactivation methods such as formalin, heat, ultraviolet light, and gamma rays cause structural alterations in vaccines that lead to reduced neutralizing antibody specificity, and in some cases, disastrous T helper type 2-mediated immune pathology. We have evaluated the potential of a visible ultrashort pulsed (USP) laser method to generate safe and immunogenic WIV vaccines without adjuvants. Specifically, we demonstrate that vaccination of mice with laser-inactivated H1N1 influenza virus at about a 10-fold lower dose than that required using conventional formalin-inactivated influenza vaccines results in protection against lethal H1N1 challenge in mice. The virus, inactivated by the USP laser irradiation, has been shown to retain its surface protein structure through hemagglutination assay. Unlike conventional inactivation methods, laser treatment did not generate carbonyl groups in protein, thereby reducing the risk of adverse vaccine-elicited T helper type 2 responses. Therefore, USP laser treatment is an attractive potential strategy to generate WIV vaccines with greater potency and safety than vaccines produced by current inactivation techniques.
Effect of inspiratory muscle unloading on arousal responses to CO2 and hypoxia in sleeping dogs (1993)

Chemical respiratory stimuli can induce arousal from sleep, but the specific mechanisms involved have not been established. Therefore, we tested the hypothesis that mechanoreceptor stimuli arising in the ventilatory apparatus have a role in the arousal responses to progressive hypercapnia and hypoxia by comparing arousal responses during spontaneous ventilation with those obtained when the inspiratory muscles were unloaded by mechanical ventilatory assistance. Studies were performed in three trained dogs in which the adequacy of inspiratory muscle unloading was verified by diaphragmatic electromyographic (EMG) recordings. In rapid-eye-movement (REM) sleep the arousal threshold during progressive hypercapnia increased from 68.4 +/- 0.5 (SE) mmHg during spontaneous runs to 72.3 +/- 0.8 mmHg during mechanically assisted runs (P < 0.01). In contrast there were no changes in arousal responses to hypercapnia during non-REM (NREM) sleep or to hypoxia in either NREM or REM sleep. However, during the assisted hypoxic runs, EMG activity of the transversus abdominis muscle was increased compared with the unassisted runs; therefore, the effects on arousal threshold of unloading the inspiratory muscles may have been offset by increased loading of the expiratory muscles. The findings indicate that even in the absence of added mechanical loads, mechanoreceptor stimuli probably arising in the respiratory muscles contribute to the arousal response to hypercapnia during REM sleep.
Expression of prelamin A but not mature lamin A confers sensitivity of DNA biosynthesis to lovastatin on F9 teratocarcinoma cells (1994)

The role of inhibition of prelamin A processing in the inhibition of DNA synthesis by lovastatin was examined by expressing prelamin A in F9 teratocarcinoma cells. These cells, normally lacking expression of the A/C lamins, were transfected with constructs expressing either prelamin A or mature lamin A and the effect of lovastatin on DNA biosynthesis was assessed. It was found that expression of prelamin A specifically conferred sensitivity to inhibition of DNA biosynthesis by lovastatin on F9 cells.
A new look into an old problem: keratins as tools to investigate determination, morphogenesis, and differentiation in skin. (1989)

We have investigated keratin and keratin mRNA expression during (1) differentiation of stem cells into epidermis and hair follicles and (2) morphogenesis of follicles. Our results indicate that a type I keratin K14 is expressed early in embryonal basal cells. Subsequently, its expression is elevated in the basal layer of developing epidermis but suppressed in developing matrix cells. This difference represents an early and major biochemical distinction between the two diverging cell types. Moreover, because expression of this keratin is not readily influenced by extracellular regulators or cell culture, it suggests a well-defined and narrow window of development during which an irreversible divergence in basal and matrix cells may take place. In contrast to K14, which is expressed very early in development and coincident with basal epidermal differentiation, a hair-specific type I keratin and its mRNA is expressed late in hair matrix development and well after follicle morphogenesis. Besides providing an additional developmental difference between epidermal and hair matrix cells, the hair-specific keratins provide the first demonstration that keratin expression may be a consequence rather than a cause of cell organization and differentiation.
Randomized trial of fenretinide in superficial bladder cancer using DNA flow cytometry as an intermediate end point. (2000)

Retinoids have shown a potential activity in preventing tumor recurrence in superficial bladder cancer. We assessed the activity of the synthetic retinoid fenretinide in superficial bladder cancer using DNA flow cytometry and conventional cytology as surrogate biomarkers. A total of 99 subjects with resected superficial bladder cancer (pTa, pT1) were randomized to either fenretinide (200 mg day p.o. for 24 months) or no intervention. Cystoscopy and bladder washing for DNA flow cytometry end points (proportion of DNA aneuploid histograms, hyperdiploid fraction, and percentage of apoptotic cells) and proportion of abnormal cytological examinations were repeated every 4 months for up to 36 months. The primary study end point was the proportion of DNA aneuploid histograms after 12 months. This figure was 48.9% in the fenretinide arm and 41.9% in the control arm (odds ratio, 1.16; 95% confidence interval, 0.44-3.07). There was no difference in any other response biomarker between the two groups up to 36 months, nor was any biomarker able to predict recurrence risk. Recurrence-free survival was comparable between the arms (27 events in the fenretinide arm versus 21 in the control arm; P = 0.36). Twelve subjects in the fenretinide arm complained of diminished dark adaptability, and nine subjects in the fenretinide arm versus one control subject had mild dermatological alterations. We conclude that fenretinide showed a lack of effect on the DNA content distribution and the morphology of urothelial cells obtained in serial bladder washings. Recurrence-free survival was comparable between groups. Because our data are hampered by the lack of predictivity of the selected biomarkers, additional studies are necessary to assess the activity of fenretinide in preventing bladder cancer.
Aflatoxin B1-induced DNA adduct formation and p53 mutations in CYP450- expressing human liver cell lines (1997)

Epidemiological evidence has been supporting a relationship between dietary aflatoxin B1 (AFB1) exposure, development of human primary hepatocellular carcinoma (HCC) and mutations in the p53 tumor suppressor gene. However, the correlation between the observed p53 mutations, the AFB1 DNA adducts and their activation pathways has not been elucidated. Development of relevant cellular in vitro models, taking into account species and tissue specificity, could significantly contribute to the knowledge of cytotoxicity and genotoxicity mechanisms of chemical procarcinogens, such as AFB1, in humans. For this purpose a non-tumorigenic SV40-immortalized human liver epithelial cell line (THLE cells) which retained most of the phase II enzymes, but had markedly reduced phase I activities was used for stable expression of the human CYP1A2, CYP2A6, CYP2B6 and CYP3A4 cDNA. The four genetically engineered cell lines (T5-1A2, T5-2A6, T5-2B6 and T5-3A4) produced high levels of the specific CYP450 proteins and showed comparable or higher catalytic activities related to the CYP450 expression when compared to human hepatocytes. The T5-1A2, T5-2A6, T5-2B6 and T5-3A4 cell lines exhibited a very high sensitivity to the cytotoxic effects of AFB1 and were approximately 125-, 2-, 2- and 15-fold, respectively, more sensitive than the control T5-neo cells, transfected with an expressing vector which does not contain CYP450 cDNA. In the CYP450-expressing cells, nanomolar doses of AFB1-induced DNA adduct formation including AFB1-N7-guanine, -pyrimidyl and -diol adducts. In addition, the T5-1A2 cells showed AFM1-DNA adducts. At similar levels of total DNA adducts, both the T5-1A2 and T5-3A4 cells showed, at codon 249 of the p53 gene, AGG to AGT transversions at a relative frequency of 15x10(-6). In contrast, only the T5-3A4 cells showed CCC to ACC transversion at codon 250 at a high frequency, whereas the second most frequent mutations found in the T5-1A2 cells were C to T transitions at the first and second position of the codon 250. No significant AFB1-induced p53 mutations could be detected in the T5-2A6 cells. Therefore, the differential expression of specific CYP450 genes in human hepatocytes can modulate the cytotoxicity, DNA adduct levels and frequency of p53 mutations produced by AFB1.
Augmented Cardiac Cardiotrophin-1 in Experimental Congestive Heart Failure (2000)

The present study demonstrates that both atrium and ventricle synthesize CT-1 and that cardiac production of CT-1 is augmented in a canine model of experimental CHF. This study also demonstrates that ventricular CT-1 mRNA correlates with left ventricular hypertrophy, suggesting that CT-1 plays an important role in the structural remodeling that characterizes CHF.
Antitumor Constituents from Bulbs ofCrocosmia crocosmiiflora (1988)

The water extract from the bulbs of Crocosmia crocosmiiflora (Nicholson) N. E. Br. (Iridaceae) and its pass-through fraction obtained by gel-filtration chromtography showed strong antitumor activity against Ehrlich carcinoma ascites and solid in Jcl-ICR mice when administered intraperitoneally. Some chemical studies revealed that the active principles in this plant were saponins consisting of medicagenic acid and polygalacic acid as the major sapogenins, and glucose, xylose, arabinose, rhamnose, and fucose as the sugar moieties.
The stacked‐X DNA Holliday junction and protein recognition (2006)

The crystal structure of the four-stranded DNA Holliday junction has now been determined in the presence and absence of junction binding proteins, with the extended open-X form of the junction seen in all protein complexes, but the more compact stacked-X structure observed in free DNA. The structures of the stacked-X junction were crystallized because of an unexpected sequence dependence on the stability of this structure. Inverted repeat sequences that contain the general motif NCC or ANC favor formation of stacked-X junctions, with the junction cross-over occurring between the first two positions of the trinucleotides. This review focuses on the sequence dependent structure of the stacked-X junction and how it may play a role in structural recognition by a class of dimeric junction resolving enzymes that themselves show no direct sequence recognition.
High-power DBR laser diodes grown in a single epitaxial step (2008)

Spectral and output power data of distributed Bragg reflector lasers emitting in the technologically important wavelength range from 780 nm to 1083 nm are presented. These devices are fabricated in a single molecular beam epitaxy growth step, and the gratings are defined by holographic interferometry. Spectral dependencies on the grating and gain section lengths are systematically investigated. Experimental data for the side-mode suppression ratio, mode spacing, and thermal wavelength shift are given for devices emitting in the near infrared wavelength range between 780 nm and 1083 nm.
Partial characterization of α‐mannosidase from Yarrowia lipolytica (1988)

Abstract An exo‐α‐mannosidase (E.C. 3.2.1.24) was characterized in the yeast form of Yarrowia lipolytica. The enzyme located in a crude particulate fraction of the cell extract is under catabolite repression, has an optimum pH of 6.0, a K m of 0.27 mM with p ‐nitrophenyl‐α‐D‐mannopyranoside and is partially inhibited by D‐mannose. The enzyme is not affected by ethylenediaminotetraacetic acid, several cations (only Zn ++ increased its activity in a 25%) or sulphydryl reagents and can be partially solubilized by treatment with digitonine.
Essential features of the P-glycoprotein pharmacophore as defined by a series of reserpine analogs that modulate multidrug resistance. (1989)

We have shown previously that reserpine is an effective "modulator" of P-glycoprotein-associated multidrug resistance (MDR). In addition to enhancing drug cytotoxicity in our multidrug-resistant human leukemia cell line, CEM/VLB100, reserpine strongly competes with a photoactivatible analog of vinblastine, N-(p-azido-3-[125I]iodosalicyl)-N'-(beta-aminoethyl)vindesine, for binding to P-glycoprotein. We also demonstrated previously that there are three substructural domains present in many compounds that modulate P-glycoprotein-associated MDR: a basic nitrogen atom and two planar aromatic rings. In the present study, we wished to test more rigorously the hypothesis that not only are these domains necessary for modulators of MDR but also they must exist in an appropriate conformation. Reserpine is a modulator of MDR in which these domains are present in a well-defined conformation. Accordingly, we prepared eight compounds that vary the spatial orientation of these domains, using either naturally occurring reserpine or yohimbine as chemical templates. When tested for their ability to enhance the cytotoxic activity of natural product antitumor drugs in CEM/VLB100 cells, five compounds that retained the pendant benzoyl function in an appropriate spatial orientation all modulated MDR. By contrast, compounds lacking this moiety failed to do so. These active modulators competed strongly with the 125I-labeled vinblastine analog for binding to P-glycoprotein in plasma membrane vesicles prepared from these cells. Conformational analysis using molecular mechanics revealed the structural similarities of the active modulators. Our results support the hypothesis that the relative disposition of aromatic rings and basic nitrogen atom is important for modulators of P-glycoprotein-associated MDR, and they suggest a ligand-receptor relationship for these agents. These results also provide direction for the definition of an MDR "pharmacophore."
Evolution of apolipoprotein E: mouse sequence and evidence for an 11-nucleotide ancestral unit. (1985)

Apolipoprotein E (apo E) is responsible for the binding of very low density lipoprotein and chylomicron remnants to cellular receptors thereby removing them from circulation. We have isolated and determined the sequence of a cDNA encoding 285 amino acids and the entire 3' untranslated region of 112 nucleotides of mouse apo E. The remaining coding sequence was determined by sequencing mouse liver mRNA. Comparisons with rat and human apo E sequences showed a high degree of conservation although there were regions in each species that were characterized by unique insertions and deletions. Analysis of the sequence homologies within apo E revealed that the entire sequence is made up of repetitive units. The most primitive unit appeared to be an 11-nucleotide repeat within higher order repeats of 22 or 33 nucleotides. The 11-nucleotide unit -TCGGACGAGGC- is read in all three reading frames, and when tandemly repeated, it encodes the highly conserved amino acid sequence Xaa-(Glu/Asp)-(Glu/Asp)-Xaa-Arg-Xaa-Arg-Leu-Gly-Xaa-Xaa. We postulate that apo E and those other apolipoproteins related to it have arisen by duplications and subsequent modifications of this or a closely related 11-nucleotide ancestral sequence.
Transforming Growth Factor α: Mutation of Aspartic Acid 47 and Leucine 48 Results in Different Biological Activities (1988)

To study the relationship between the primary structure of transforming growth factor alpha (TGF-alpha) and some of its functional properties (competition with epidermal growth factor (EGF) for binding to the EGF receptor and induction of anchorage-independent growth), we introduced single amino acid mutations into the sequence for the fully processed, 50-amino-acid human TGF-alpha. The wild-type and mutant proteins were expressed in a vector by using a yeast alpha mating pheromone promoter. Mutations of two amino acids that are conserved in the family of the EGF-like peptides and are located in the carboxy-terminal part of TGF-alpha resulted in different biological effects. When aspartic acid 47 was mutated to alanine or asparagine, biological activity was retained; in contrast, substitutions of this residue with serine or glutamic acid generated mutants with reduced binding and colony-forming capacities. When leucine 48 was mutated to alanine, a complete loss of binding and colony-forming abilities resulted; mutation of leucine 48 to isoleucine or methionine resulted in very low activities. Our data suggest that these two adjacent conserved amino acids in positions 47 and 48 play different roles in defining the structure and/or biological activity of TGF-alpha and that the carboxy terminus of TGF-alpha is involved in interactions with cellular TGF-alpha receptors. The side chain of leucine 48 appears to be crucial either indirectly in determining the biologically active conformation of TGF-alpha or directly in the molecular recognition of TGF-alpha by its receptor.
Denosumab (2009)

Denosumab is an anti-receptor activator of nuclear factor (NF)-kappaB (RANK) ligand human monoclonal antibody studied as a treatment for postmenopausal osteoporosis (PMO) and bone destruction due to rheumatoid arthritis (RA) or metastatic cancers. As of February 2009, the candidate was undergoing US Food and Drug Administration review, and might be approved by October 2009. Late phase clinical trials demonstrated that denosumab possesses a similar safety profile to bisphosphonates and that it can be either equally or more effective than bisphosphonates at preventing bone loss due to PMO, RA or cancer treatment and metastases.
ANDROGEN RECEPTOR DOWN-REGULATION IN PROSTATE CANCER WITH PHOSPHORODIAMIDATE MORPHOLINO ANTISENSE OLIGOMERS (2004)

An AR antisense PMO with unique chemical properties administered once daily can decrease AR protein levels and PSA in vivo. The reduction of AR protein with an antisense PMO may be an effective method of interfering with AR mediated growth in advanced human PCa.
Genetic and genomic approaches to characterize crop varieties (2017)

Memoria de Tesis Doctoral presentada por Leticia Ayllon Egea, Licenciada en Biologia, para optar al grado de Doctor por la Universidad de Cordoba con la mencion de Doctorado Internacional.
Gremlin Plays a Key Role in the Pathogenesis of Pulmonary Hypertension (2012)

These findings demonstrate a central role for increased gremlin in hypoxia-induced pulmonary vascular remodeling and the increased pulmonary vascular resistance in hypoxic pulmonary hypertension. High levels of basal gremlin expression in the lung may account for the unique vulnerability of the pulmonary circulation to heterozygous mutations of BMP type 2 receptor in pulmonary arterial hypertension.
Double‐Network Hydrogels with Extremely High Mechanical Strength (2003)

Very strong hydrogels (with a fracture strength of some tens of MPa) , as required for both industrial and biomedical applications, have been generated by inducing a double‐network (DN) structure for various combinations of hydrophilic polymers. The Figure shows a hydrogel before, during, and after application of a fracture stress of 17.2 MPa.
Rv3133c/dosR is a transcription factor that mediates the hypoxic response of Mycobacterium tuberculosis (2003)

Unlike many pathogens that are overtly harmful to their hosts, Mycobacterium tuberculosis can persist for years within humans in a clinically latent state. Latency is often linked to hypoxic conditions within the host. Among M. tuberculosis genes induced by hypoxia is a putative transcription factor, Rv3133c/DosR. We performed targeted disruption of this locus followed by transcriptome analysis of wild-type and mutant bacilli. Nearly all the genes powerfully regulated by hypoxia require Rv3133c/DosR for their induction. Computer analysis identified a consensus motif, a variant of which is located upstream of nearly all M. tuberculosis genes rapidly induced by hypoxia. Further, Rv3133c/DosR binds to the two copies of this motif upstream of the hypoxic response gene alpha-crystallin. Mutations within the binding sites abolish both Rv3133c/DosR binding as well as hypoxic induction of a downstream reporter gene. Also, mutation experiments with Rv3133c/DosR confirmed sequence-based predictions that the C-terminus is responsible for DNA binding and that the aspartate at position 54 is essential for function. Together, these results demonstrate that Rv3133c/DosR is a transcription factor of the two-component response regulator class, and that it is the primary mediator of a hypoxic signal within M. tuberculosis.