gebhart/patrepeval huggingface dataset:
Enhanced detection of circulating tumor DNA by fragment size analysis (2018)

Existing methods to improve detection of circulating tumor DNA (ctDNA) have focused on genomic alterations but have rarely considered the biological properties of plasma cell-free DNA (cfDNA). We hypothesized that differences in fragment lengths of circulating DNA could be exploited to enhance sensitivity for detecting the presence of ctDNA and for noninvasive genomic analysis of cancer. We surveyed ctDNA fragment sizes in 344 plasma samples from 200 patients with cancer using low-pass whole-genome sequencing (0.4×). To establish the size distribution of mutant ctDNA, tumor-guided personalized deep sequencing was performed in 19 patients. We detected enrichment of ctDNA in fragment sizes between 90 and 150 bp and developed methods for in vitro and in silico size selection of these fragments. Selecting fragments between 90 and 150 bp improved detection of tumor DNA, with more than twofold median enrichment in >95% of cases and more than fourfold enrichment in >10% of cases. Analysis of size-selected cfDNA identified clinically actionable mutations and copy number alterations that were otherwise not detected. Identification of plasma samples from patients with advanced cancer was improved by predictive models integrating fragment length and copy number analysis of cfDNA, with area under the curve (AUC) >0.99 compared to AUC <0.80 without fragmentation features. Increased identification of cfDNA from patients with glioma, renal, and pancreatic cancer was achieved with AUC > 0.91 compared to AUC < 0.5 without fragmentation features. Fragment size analysis and selective sequencing of specific fragment sizes can boost ctDNA detection and could complement or provide an alternative to deeper sequencing of cfDNA.
Induction of intrachromosomal homologous recombination in whole plants (1995)

Summary The influence of different factors on frequencies of intrachromosomal homologous recombination in whole Arabidopsis thaliana and tobacco plants was analyzed using a disrupted β‐glucuronidase marker gene. Recombination frequencies were enhanced severalfold by DNA damaging agents like UV‐light or MMS (methyl methanesulfonate). Applying 3‐methoxybenzamide (3‐MB), an inhibitor of poly(ADP)ribose polymerase (PARP), an enzyme that is postulated to be involved in DNA repair, enhanced homologous recombination frequencies strongly. These findings indicate that homologous recombination is involved in DNA repair and can (at least partially) compensate for other DNA repair pathways. Indications that recombination in plants can be induced by environmental stress factors that are not likely to be involved in DNA metabolism were also found; Arabidopsis plants growing in a medium containing 0.1 M NaCl exhibited elevated recombination frequencies. The possible general effects of ‘environmental’ challenges on genome flexibility are discussed.
A human hybrid myeloma for production of human monoclonal antibodies. (1984)

We produced somatic cell hybrids between human myeloma cells and a lymphoblastoid cell line that is hypoxanthine phosphoribosyl transferase-deficient and ouabain-resistant. These hybrids were phenotypically similar to the human myeloma parental cells and grew as well as the human lymphoblastoid parental cells. After counterselection in 6-thioguanine, mutants that were 6-thioguanine-and ouabain-resistant were obtained, one of which was used as a fusion partner with lymphoblastoid B cells that produce anti-tetanus toxoid (TT) antibodies. These hybrids secreted human anti-TT monoclonal antibodies in much larger amounts than the parental lymphoblastoid cells, and were stable for a period of over 10 mo until the present time. Thus, by hybridizing plasmacytomas with lymphoblastoid cells, we constructed a fusion partner that secretes large amounts of immunoglobulin (Ig), grows at a fast rate, has a high fusion frequency, and supports the production of monoclonal antibodies over long periods of time. Moreover, anti-TT antibody-producing hybrids have been grown as solid tumors in irradiated BALB/c nude mice and then adopted to ascites growth, producing 1 to 8 mg of human immunoglobulin per 1 ml of ascites fluid.
Pregnenolone synthesis from cholesterol and hydroxycholesterols by mitochondria from ovaries following the stimulation of immature rats with pregnant mare's serum gonadotropin and human choriogonadotropin (1989)

The rate of pregnenolone synthesis by cytochrome P-450scc was measured in mitochondria isolated from ovaries of immature rats treated with pregnant mare's serum gonadotropin and human choriogonadotropin. Using cholesterol, 25-hydroxycholesterol, 20 alpha-hydroxycholesterol, (22R)-22-hydroxycholesterol and (22R)-20 alpha,22-dihydroxycholesterol as substrates, we have determined that the first hydroxylation of cholesterol, in the 22R position, is rate limiting in pregnenolone synthesis. It proceeds at only 22% of the rate of either of the subsequent two hydroxylations. 25-Hydroxycholesterol proved to be a suitable substrate for determining the maximum rate of pregnenolone synthesis by cytochrome P-450scc in isolated mitochondria. The maximum rate was 13 mol steroid.min-1.mol cytochrome P-450scc-1 and did not change after the follicles in the immature ovary had been stimulated to mature and luteinize with gonadotropin. Using endogenous cholesterol in isolated mitochondria as substrate, the time course of pregnenolone synthesis was the same during the follicular phase as in the luteal stage of gonadotropin-induced development. We conclude that during the artificial induced development of follicles in the immature ovary, the major cause of the increase in the rate of pregnenolone synthesis is the increase in the cytochrome P-450scc content of the mitochondria, rather than changes in the catalytic activity of cytochrome P-450scc or the cholesterol availability to the cytochrome.
Treatment of Refractory Partial Seizures: Preliminary Results of a Controlled Study (1992)

Vagus nerve stimulation for the treatment of epilepsy has been studied in medically refractory patients with partial seizures in a randomized, blinded, parallel study. After a 3-month baseline period, the patients were implanted with the Neurocybernetic Prosthesis (NCP) system consisting of the NCP Generator and the Bipolar Vagal Stimulation Lead. Two stimulation paradigms were used, HIGH, which delivers what is considered to be optimal stimulation parameters and LOW, which is considered to be less or noneffective. The system and vagus nerve stimulation were well tolerated and few adverse events have been attributed to either. One patient experienced a period of direct current to the nerve due to a generator malfunction. This results in paralysis of the left vocal cord. Efficacy analysis on the first 37 patients to complete the controlled portion of the study has shown that the patients in the HIGH group experienced a mean reduction in seizure frequency of 33.3% and patients in the LOW group experienced a mean reduction in seizure frequency of 8.4%. The difference between the groups is statistically significant with a P value of 0.025. Analysis of seizure duration and intensity does not show any significant change. Ratings of the patient's overall condition by the patient, investigator, and companion as a measurement of "quality of life" also show improvement in the HIGH group. The results of this interim study demonstrate that vagus nerve stimulation is a safe and effective method of treating partial epileptic seizures.
Construction of Adenoviral Vectors (2003)

Human adenovirus is a double-stranded DNA virus with a 36-kb linear genome that contains four early transcription units (E1–E4), active at early (3–12 h) times after infection and five late transcription units (L1–L5) active thereafter and producing the structural genes of the virus. For further details on human adenovirus and its life cycle, the reader is referred to ref. , which provides a description of the genome structure, and types of these viruses.
Microchip Separations of Neutral Species via Micellar Electrokinetic Capillary Chromatography (1995)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTMicrochip Separations of Neutral Species via Micellar Electrokinetic Capillary ChromatographyAlvin W. Moore, Stephen C. Jacobson, and J. Michael. RamseyCite this: Anal. Chem. 1995, 67, 22, 4184–4189Publication Date (Print):November 15, 1995Publication History Published online1 May 2002Published inissue 15 November 1995https://pubs.acs.org/doi/10.1021/ac00118a023https://doi.org/10.1021/ac00118a023research-articleACS PublicationsRequest reuse permissionsArticle Views303Altmetric-Citations104LEARN 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 Get e-Alerts
A viewpoint determination system for stenosis diagnosis and quantification in coronary angiographic image acquisition (1998)

This paper describes the usefulness of computer assistance in the acquisition of "good" images for stenosis diagnosis and quantification in coronary angiography. The system recommends the optimal viewpoints from which stenotic lesions can be observed clearly based on images obtained from initial viewpoints. First, the viewpoint dependency of the apparent severity of a stenotic lesion is experimentally analyzed using software phantoms in order to show the seriousness of the problem. The implementation of the viewpoint determination system is then described. The system provides good user-interactive tools for the semiautomated estimation of the orientation and diameter of stenotic segments and the three-dimensional (3-D) reconstruction of vessel structures. Using these tools, viewpoints that will not give rise to foreshortening and vessel overlap can be efficiently determined. Experiments using real coronary angiograms show the system to be capable of the reliable diagnosis and quantification of stenosis.
Obesity Is an Independent Risk Factor of Mortality in Severely Injured Blunt Trauma Patients (2004)

Critically injured obese trauma patients have similar demographics and injury patterns as nonobese patients. Obesity is an independent predictor of mortality following severe blunt trauma.
Degradation of o-nitrophenol and m-nitrophenol by a Pseudomonas putida (1984)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTDegradation of o-nitrophenol and m-nitrophenol by a Pseudomonas putidaJosef Zeyer and Philip C. KearneyCite this: J. Agric. Food Chem. 1984, 32, 2, 238–242Publication Date (Print):March 1, 1984Publication History Published online1 May 2002Published inissue 1 March 1984https://pubs.acs.org/doi/10.1021/jf00122a015https://doi.org/10.1021/jf00122a015research-articleACS PublicationsRequest reuse permissionsArticle Views788Altmetric-Citations114LEARN 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 Get e-Alerts
New developments in the use of gene therapy to treat Duchenne muscular dystrophy (2013)

The applicability of exon skipping as a therapy to DMD is restricted and the development of alternative strategies that are more encompassing is needed. The rapid pre-clinical advances that are being made in the field of adeno-associated virus (AAV)-based delivery of micro-dystrophin would address this. The obstacles to be faced with gene replacement strategies would include the need for high viral titres, efficient muscle targeting and avoidance of immune response to vector and transgene. The new emerging field of gene editing could potentially provide permanent correction of the DMD gene and the feasibility of such an approach to DMD is discussed.
Proteome Analysis of Human Vitreous Proteins (2003)

A map of protein expression was made in human vitreous from eyes with MH and PDR. In the PDR eyes, the increased protein expression observed was due to barrier dysfunction and/or production in the eye. Proteome analysis was useful in systematic screening of various protein expression in human vitreous samples.
Thin Film Deposition of Organic−Inorganic Hybrid Materials Using a Single Source Thermal Ablation Technique (1999)

A versatile single source thermal ablation (SSTA) technique is demonstrated, enabling the deposition of high-quality films of organic−inorganic hybrid materials. The SSTA process involves rapidly heating the organic−inorganic compound using a resistively heated sheet. The organic and inorganic components ablate from the heater at effectively the same time, without decomposition, and the components reassemble on a substrate to form crystalline films of the original hybrid.
Antiretroviral Preexposure Prophylaxis for Heterosexual HIV Transmission in Botswana (2012)

Daily TDF-FTC prophylaxis prevented HIV infection in sexually active heterosexual adults. The long-term safety of daily TDF-FTC prophylaxis, including the effect on bone mineral density, remains unknown. (Funded by the Centers for Disease Control and Prevention and the National Institutes of Health; TDF2 ClinicalTrials.gov number, NCT00448669.).
A comparison of dynamic branch predictors that use two levels of branch history (1993)

Recent attention to speculative execution as a mechanism for increasing performance of single instruction streams has demanded substantially better branch prediction than what has been previously available. We [1,2] and Pan, So, and Rahmen [4] have both proposed variations of the same aggressive dynamic branch predictor for handling those needs. We call the basic model Two-Level Adaptive Branch Prediction; Pan, So, and Rahmeh call it Correlation Branch Prediction. In this paper, we adopt the terminology of [2] and show that there are really nine variations of the same basic model. We compare the nine variations with respect to the amount of history information kept. We study the effects of different branch history lengths and pattern history table configurations. Finally, we evaluate the cost effectiveness of the nine variations.
AN EFFICIENT SYNTHESIS OF 3,4-DIHYDRO-1H-2,3-BENZOTHIAZINE 2,2-DIOXIDES USING AMBERLYST 15 AND AMBERLYST XN 1010 (2002)

ABSTRACT Resins Amberlyst 15 and Amberlyst XN 1010 are used in the synthesis of 3,4-dihydro-1H-2,3-benzothiazines 2,2-dioxide. Advantages of this new procedure are simple work-up, high yield and selectivity, easy recovery of the catalyst and no waste problems. ACKNOWLEDGMENTS The authors thank CONICET and CICBA for financial support and Dr. A. Lieberknecht for valuable discussions.
Kinetic and Molecular Analysis of 5-Epiaristolochene 1,3-Dihydroxylase, a Cytochrome P450 Enzyme Catalyzing Successive Hydroxylations of Sesquiterpenes (2004)

The final step of capsidiol biosynthesis is catalyzed by 5-epiaristolochene dihydroxylase (EAH), a cytochrome P450 enzyme that catalyzes the regio- and stereospecific insertion of two hydroxyl moieties into the bicyclic sesquiterpene 5-epiaristolochene (EA). Detailed kinetic studies using EA and the two possible monohydroxylated intermediates demonstrated the release of 1beta-hydroxy-EA ((OH)EA) at high EA concentrations and a 10-fold catalytic preference for 1beta(OH)EA versus 3alpha(OH)EA, indicative of a preferred reaction order of hydroxylation at C-1, followed by that at C-3. Sequence alignments and homology modeling identified active-site residues tested for their contribution to substrate specificity and overall enzymatic activity. Mutants EAH-S368C and EAH-S368V exhibited wild-type catalytic efficiencies for 1beta(OH)EA biosynthesis, but were devoid of the successive hydroxylation activity for capsidiol biosynthesis. In contrast to EAH-S368C, EAH-S368V catalyzed the relative equal biosynthesis of 1beta(OH)EA, 2beta(OH)EA, and 3beta(OH)EA from EA with wild-type efficiency. Moreover, EAH-S368V converted approximately 1.5% of these monohydroxylated products to their respective ketone forms. Alanine and threonine mutations at position 368 were significantly compromised in their conversion rates of EA to capsidiol and correlated with 3.6- and 5.7-fold increases in their Km values for the 1beta(OH)EA intermediate, respectively. A role for Ile486 in the successive hydroxylations of EA was also suggested by the EAH-I468A mutant, which produced significant amounts 1beta(OH)EA, but negligible amounts of capsidiol from EA. The altered product profile of the EAH-I486A mutant correlated with a 3.6-fold higher Km for EA and a 4.4-fold slower turnover rate (kcat) for 1beta(OH)EA. These kinetic and mutational studies were correlated with substrate docking predictions to suggest how Ser368 and Ile486 might contribute to active-site topology, substrate binding, and substrate presentation to the oxo-Fe-heme reaction center.
A walk around the A3-coupling (2012)

In recent years, the transition-metal catalyzed three-component coupling of an aldehyde, an alkyne and an amine, commonly called A(3)-coupling, has been established as a convenient and general approach towards propargylamines. Furthermore, the A(3)-coupling has found a broad application as a key step in the construction of various nitrogen-containing heterocycles, biologically active compounds and natural products. Several interesting modifications of the A(3)-coupling as well as different tandem reactions involving A(3)-coupling have been developed. This tutorial review aims to highlight the current achievements in the field of A(3)-couplings and related transformations.
Biochemical Assay of Alzheimer's Disease—Associated Protein(s) in Human Brain Tissue (1990)

The concentration of Alzheimer's disease-associated protein (ADAP) was measured in postmortem brain tissue samples of temporal or frontal cortex from 111 human brains using a sandwich immunoassay. Alzheimer's disease-associated protein has three major ALZ-50-reactive subunits, including A-68. This assay utilizes ALZ-50 and a rabbit antibody raised against a highly ADAP-enriched brain protein fraction. The frequently observed cross-reactivity of ALZ-50 with normal brain components in direct immunoassays is minimized by this configuration. There were 27 normal controls, 28 neurologic disease controls, and 56 Alzheimer's disease cases. The normal control and neurologic disease control cases had essentially no detectable level of ADAP, while ADAP was clearly detected in 85.7% of the Alzheimer's disease cases. Clinical dementia, neuritic plaques, and old age per se are not correlated with increased ADAP levels. This biochemical assay of ADAP may prove to be helpful as an adjunct in the clinicopathologic diagnosis of Alzheimer's disease.
Zonal distribution of immunoglobulin‐synthesizing cells within the germinal centre: An in situ hybridization and immunohistochemical study (1990)

Immunohistologic studies have shown that synthesis of cytoplasmic immunoglobulin (cIg) is a normal function of some follicle centre cells (FCCs). The mechanisms regulating this synthesis of immunoglobulin and its function within the germinal centre are still poorly understood. In this study we applied a recently developed in situ hybridization method for the detection of kappa and lambda light chain mRNA to reactive lymph nodes and tonsils in order to investigate further the immunoglobulin-synthesizing cells of the germinal centre. FCCs containing detectable levels of light chain mRNA corresponded closely to cells containing cIg. The detection of light chain mRNA rather than its immunoglobulin product was found to be an advantage in that problems associated with the detection of extracellular immunoglobulin were eliminated. This was most apparent in germinal centres where the absence of 'network' immunoglobulin led to the observations that immunoglobulin-synthesizing FCCs are predominantly small centrocytes and that in a proportion of germinal centres they localize in that part of the light zone closest to the dark zone. This zonal distribution of immunoglobulin-synthesizing FCCs raises the possibility of further functional and micro-environmental subcompartments within the light zone.
Biomimetic Triblock Copolymer Membrane Arrays: A Stable Template for Functional Membrane Proteins (2009)

It is demonstrated that biomimetic stable triblock copolymer membrane arrays can be prepared using a scaffold containing 64 apertures of 300 microm diameter each. The membranes were made from a stock solution of block copolymers with decane as a solvent using a new deposition method. By using decane, we avoid low molecular weight solvents such as chloroform and toluene, which are strong protein denaturants. The membranes show a low ionic conductance and a long lifetime at room temperature. Contrast phase microscopy shows the presence of a polymer region delimited by a Plateau-Gibbs border similar to what is observed in black lipid membranes. The ion-channel gramicidin A was successfully incorporated into the membrane in a functional form.