gebhart/patrepeval huggingface dataset:
Structure elucidation of the glycopeptide antibiotic complex A40926 (1987)

The structure of the two factors of the novel glycopeptide antibiotic A40926 have been determined using a combination of FAB-MS, GC-MS and 1H n.m.r. studies. A40926 Is a member of the vancomycin family of antibiotics and is structurally related to teicoplanin, A35512B and aridicin.
DNA Topoisomerase II in Therapy-Related Acute Promyelocytic Leukemia (2005)

Drug-induced cleavage of DNA by topoisomerase II mediates the formation of chromosomal translocation breakpoints in mitoxantrone-related APL and in APL that occurs after therapy with other topoisomerase II poisons.
“Should we sell human organs?” Correction of a faulty analysis (2005)

Purpose The purpose of this research is to correct the flawed analysis contained in a recent paper by Kolnsberg that appeared in this journal. Design/methodology/approach In her paper, Kolnsberg raises the extremely important question of whether we should allow the sale of human organs for transplantation. She concludes, mistakenly, that we should not allow such sales. The error that leads her to this incorrect conclusion is the application of a nonsensical criterion for determination of whether sales of a good should be allowed. Specifically, she argues that, if the suppliers of living donor organs will be unable to earn substantial economic profits in the long run, then such sales should be banned. This arbitrary (and erroneous) criterion ignores: the social welfare gains achievable through organ sales; the much greater promise offered by cadaveric donor payments; and the very real and tragic consequences of the current ban on such payments – over 6,000 lives lost unnecessarily each year in the US alone. Findings The principal finding of the corrected analysis is that, contrary to the conclusion reached by Kolnsberg, paying cadaveric organ donors would save both money and lives. Research limitations/implications Given the compelling case for cadaveric donor payments, trials need to be conducted to reveal both the magnitude of compensation required to resolve the shortage and the most efficient payment mechanisms. Originality/value Given the historical failure of the current altruistic organ procurement policy, asserts that a revised system that incorporates organ donor payments is essential to a successful resolution of this shortage.
Phenotyping of Transgenic Cloned Piglets (2002)

Numerous reports list the abnormalities obtained from cloning sheep and cattle. To date, few reports provide detailed information regarding the overall health status and performance data of cloned animals. This report follows three litters totaling 10 transgenic cloned piglets from birth through puberty. Significant findings from physical examinations and response to treatments are included, as well as necropsy data from five of the piglets that died during the study. The birth weights, placental weights, and growth rates for this group of piglets were not different from that of control animals raised in the same environment. Hematology and serum chemistry data were collected at 2 days of age, and at 2, 4, 8, 12, 16, 20, and 24 weeks of age. Results indicated a mild anemia and hypoproteinemia in the cloned piglets from birth through 4 weeks of age, but both conditions were corrected by 8 weeks of age. Echocardiography was performed on seven of the piglets. No anatomical defects were detected, but three of the piglets had decreased cardiac output values. However, both animals are growing and show no evidence of clinical disease. The immune system was evaluated by quantification of serum IgM and IgG levels and by determining the population of B-cells, macrophages, helper T-cells (CD4), cytotoxic T-cell (CD8), and double positive T-cells (CD4/CD8). With the exception of one animal, no abnormalities were detected with the immune system of the examined piglets. During the course of this study, five of the 10 piglets were euthanized or died, indicating there is a high mortality rate among cloned piglets, but the remaining five cloned piglets are free from detectable defects.
Deep proteome and transcriptome mapping of a human cancer cell line (2011)

While the number and identity of proteins expressed in a single human cell type is currently unknown, this fundamental question can be addressed by advanced mass spectrometry (MS)-based proteomics. Online liquid chromatography coupled to high-resolution MS and MS/MS yielded 166 420 peptides with unique amino-acid sequence from HeLa cells. These peptides identified 10 255 different human proteins encoded by 9207 human genes, providing a lower limit on the proteome in this cancer cell line. Deep transcriptome sequencing revealed transcripts for nearly all detected proteins. We calculate copy numbers for the expressed proteins and show that the abundances of > 90% of them are within a factor 60 of the median protein expression level. Comparisons of the proteome and the transcriptome, and analysis of protein complex databases and GO categories, suggest that we achieved deep coverage of the functional transcriptome and the proteome of a single cell type.
Design and synthesis of a morphine‐6‐succinyl‐bovine serum albumin hapten for vaccine development (1999)

A morphine-6-succinyl-BSA (M-6-S-BSA) hapten was designed in an effort to obtain a potent, long-lasting anti-morphine immune response for the treatment of morphine abuse. The analogue incorporated a succinic anhydride linker moiety in place of hydroxy group at C-6 of the morphine framework. Then morphine 6-hemisuccinate was conjugated to BSA in aqueous solution in the presence of water-soluble carbodi-imide. M-6-S-BSA was synthesized in three chemical steps starting from morphine sulphate, and the extent of conjugation was determined by base hydrolysis of the conjugate, extraction and measurement of free morphine. An average of 6.5 molecules of morphine were conjugated to each molecule of protein. Six male mice, Swiss White strain, immunized with various doses of the conjugate, were found to be producing antibody 8 weeks later, as determined by a modification of the (NH(4))(2)SO(4) method, which measures primary binding of antigen by antibody.
EWS/FLI Alters 5′-Splice Site Selection (2001)

The chimeric gene EWS/FLI is present in at least 85% of Ewing's sarcomas as a result of chromosomal translocations. The resulting fusion protein contains the N terminus of the RNA-binding protein EWS and the ETS DNA-binding domain of the transcription factor FLI-1. Although EWS/FLI binds DNA and activates transcription, both EWS and EWS/FLI also interact with SF1 and U1C, essential components of the splicing machinery. Therefore, we tested the ability of EWS and EWS/FLI to alter 5'-splice site selection using an E1A gene in vivo splicing assay. We found that EWS/FLI, but not EWS, interfered with heterogeneous nuclear ribonucleoprotein A1-dependent splice site selection of E1A. Mutational analysis of EWS/FLI revealed that the ability to affect pre-mRNA splicing coincided with transforming activity. Therefore, EWS/FLI has the ability to influence splicing as well as transcription.
A Prospective Double-Blind Clinically Controlled Multicenter Trial of Sodium Pentosanpolysulfate in the Treatment of Interstitial Cystitis and Related Painful Bladder Disease (1987)

Painful bladder disease, sensory bladder disease, chronic abacterial cystitis and interstitial cystitis are ill-defined conditions of unknown etiology and pathogenesis, and, therefore, they are without any rational therapy. Pathogenetic theories concerning defects in the epithelium and/or mucous surface coat (including glycosaminoglycans) of the bladder, and theories concerning immunological disturbances predominate. Sodium pentosanpolysulfate (Elmiron) acts by substituting a defective glycosaminoglycan layer and inhibits complement reactions in inflammatory processes. We compared sodium pentosanpolysulfate versus placebo in a prospective double-blind, clinically controlled multicenter trial of 115 patients with painful bladder disease. Two protocols were used. Protocol A included 43 patients with clinically and pathologically anatomically verified interstitial cystitis (28 or more mast cells per mm.2), and protocol B included 72 patients with a painful bladder and unspecific histological findings. The patients were randomized to receive either sodium pentosanpolysulfate (200 mg. twice daily) or placebo capsules for 4 months. Before and after the trial the patients were evaluated with symptom grading, urodynamics and cystoscopy with distension and deep bladder biopsies. The results showed no difference between the pre-trial and post-trial values in the sodium pentosanpolysulfate and placebo groups in both protocols in regard to symptoms, urodynamic parameters, cystoscopic appearance and mast cell counts. A significant increase in the cystoscopically determined bladder capacity in the sodium pentosanpolysulfate group in protocol A was found. We conclude that no statistically or clinically significant effect of sodium pentosanpolysulfate was found compared to placebo in patients with painful bladder disease.
Excitotoxic cell death (1992)

Excitotoxicity refers to the ability of glutamate or related excitatory amino acids to mediate the death of central neurons under certain conditions, for example, after intense exposure. Such excitotoxic neuronal death may contribute to the pathogenesis of brain or spinal cord injury associated with several human disease states. Excitotoxicity has substantial cellular specificity and, in most cases, is mediated by glutamate receptors. On average, NMDA receptors activation may be able to trigger lethal injury more rapidly than AMPA or kainate receptor activation, perhaps reflecting a greater ability to induce calcium influx and subsequent cellular calcium overload. It is possible that excitotoxic death may share some mechanisms with other forms of neuronal death.
Mechanical Entrapment Is Insufficient and Intercellular Adhesion Is Essential for Metastatic Cell Arrest in Distant Organs (2005)

In this report, we challenge a common perception that tumor embolism is a size-limited event of mechanical arrest, occurring in the first capillary bed encountered by blood-borne metastatic cells. We tested the hypothesis that mechanical entrapment alone, in the absence of tumor cell adhesion to blood vessel walls, is not sufficient for metastatic cell arrest in target organ microvasculature. The in vivo metastatic deposit formation assay was used to assess the number and location of fluorescently labeled tumor cells lodged in selected organs and tissues following intravenous inoculation. We report that a significant fraction of breast and prostate cancer cells escapes arrest in a lung capillary bed and lodges successfully in other organs and tissues. Monoclonal antibodies and carbohydrate-based compounds (anti-Thomsen-Friedenreich antigen antibody, anti-galectin-3 antibody, modified citrus pectin, and lactulosyl-l-leucine), targeting specifically beta-galactoside-mediated tumor-endothelial cell adhesive interactions, inhibited by >90% the in vivo formation of breast and prostate carcinoma metastatic deposits in mouse lung and bones. Our results indicate that metastatic cell arrest in target organ microvessels is not a consequence of mechanical trapping, but is supported predominantly by intercellular adhesive interactions mediated by cancer-associated Thomsen-Friedenreich glycoantigen and beta-galactoside-binding lectin galectin-3. Efficient blocking of beta-galactoside-mediated adhesion precludes malignant cell lodging in target organs.
Topological templates as tool in molecular recognition and peptide mimicry: Synthesis of a TASK library (1995)

Topological templates disposing orthogonally protected reactive sites in defined spatial positions of a variable degree of flexibility can serve as a pool for the selective functionalization by groups thought to interact with an acceptor molecule. This strategy is exemplified by the chemo-selective ligation of amino-acid residues to a cyclic peptide as a structural motif (template-assembled side chains; TASK) applying the concept of combinatorial libraries. Binding assays to a monoclonal antibody allow for the delineation of a lead compound mimicking the structural features of a discontinuous epitope. The conceptually novel approach may serve as a tool in molecular recognition studies and in drug development.
The Dysfunctional Elimination Syndrome in Children—Is Sacral Neuromodulation Worth the Trouble? (2012)

No AccessJournal of UrologyEditorial1 Oct 2012The Dysfunctional Elimination Syndrome in Children—Is Sacral Neuromodulation Worth the Trouble? Moira E. Dwyer and Yuri E. Reinberg Moira E. DwyerMoira E. Dwyer More articles by this author and Yuri E. ReinbergYuri E. Reinberg More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2012.07.059AboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail "The Dysfunctional Elimination Syndrome in Children—Is Sacral Neuromodulation Worth the Trouble?." The Journal of Urology, 188(4), pp. 1076–1077 References 1 : Effectiveness of biofeedback for dysfunctional elimination syndrome in pediatrics: a systematic review. J Pediatr Urol2011; 7: 342. Google Scholar 2 : Dysfunctional elimination syndrome in children without obvious spinal cord diseases. Pediatr Clin North Am2001; 48: 1489. Google Scholar 3 : Animated biofeedback: an ideal treatment for children with dysfunctional elimination syndrome. J Urol2011; 186: 2379. Google Scholar 4 : New strategies for medical management of overactive bladder in children. Curr Opin Urol2010; 20: 313. Google Scholar 5 : Trospium chloride for the treatment of detrusor instability in children. J Urol2003; 170: 1978. Google Scholar 6 : Primary bladder neck dysfunction in children and adolescents Ill: results of long-term alpha blocker therapy. J Urol2010; 183: 724. Link, Google Scholar 7 : The use of botulinum toxin A injection for the management of external sphincter dyssynergia in neurologically normal children. J Urol2007; 178: 1775. Link, Google Scholar 8 : The outcome of voiding dysfunction managed with clean intermittent catheterization in neurologically and anatomically normal children. BJU Int2002; 89: 923. Google Scholar 9 : Sacral neuromodulation for neurogenic bladder dysfunction in children. J Urol2004; 172: 1673. Link, Google Scholar 10 : Preliminary results of sacral neuromodulation in 23 children. J Urol2006; 176: 2227. Link, Google Scholar 11 : Sacral neuromodulation with an implantable pulse generator in children with lower urinary tract symptoms: 15-year experience. J Urol2012; 188: 1313. Link, Google Scholar Mayo Clinic, Rochester, MinnesotaPediatric Surgical Associates, Minneapolis, Minnesota© 2012 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetailsCited byStephany H, Juliano T, Clayton D, Tanaka S, Thomas J, Adams M, Brock J and Pope J (2013) Prospective Evaluation of Sacral Nerve Modulation in Children with Validated QuestionnairesJournal of Urology, VOL. 190, NO. 4S, (1516-1522), Online publication date: 1-Oct-2013. Volume 188Issue 4October 2012Page: 1076-1077 Advertisement Copyright & Permissions© 2012 by American Urological Association Education and Research, Inc.MetricsAuthor Information Moira E. Dwyer More articles by this author Yuri E. Reinberg More articles by this author Expand All Advertisement PDF downloadLoading ...
Protein structure prediction and analysis using the Robetta server (2004)

The Robetta server (http://robetta.bakerlab.org) provides automated tools for protein structure prediction and analysis. For structure prediction, sequences submitted to the server are parsed into putative domains and structural models are generated using either comparative modeling or de novo structure prediction methods. If a confident match to a protein of known structure is found using BLAST, PSI-BLAST, FFAS03 or 3D-Jury, it is used as a template for comparative modeling. If no match is found, structure predictions are made using the de novo Rosetta fragment insertion method. Experimental nuclear magnetic resonance (NMR) constraints data can also be submitted with a query sequence for RosettaNMR de novo structure determination. Other current capabilities include the prediction of the effects of mutations on protein-protein interactions using computational interface alanine scanning. The Rosetta protein design and protein-protein docking methodologies will soon be available through the server as well.
SEPARATION OF TRANSIENT INFORMATION IN MUSICAL AUDIO USING MULTIRESOLUTION ANALYSIS TECHNIQUES (2001)

Whilst musical transients are generally acknowledged as holding much of the perceptual information within musical tones, most research in sound analysis and synthesis tends to focus on the steady state components of signals. A method is presented which separates the noisy transient information from the slowly time varying steady state components of musical audio. Improvements of using adaptive thresholding, and multiresolution analysis methods are then illustrated. It is shown that by analyzing the resulting transient information only, current onset detection algorithms can be improved considerably, especially for those instruments with noisy attack information, such as plucked or struck strings. The idea is then applied to audio processing techniques to enhance or decrease the strength of note attack information. Finally, the transient extraction
Summarizing visual data using bidirectional similarity (2008)

We propose a principled approach to summarization of visual data (images or video) based on optimization of a well-defined similarity measure. The problem we consider is re-targeting (or summarization) of image/video data into smaller sizes. A good ldquovisual summaryrdquo should satisfy two properties: (1) it should contain as much as possible visual information from the input data; (2) it should introduce as few as possible new visual artifacts that were not in the input data (i.e., preserve visual coherence). We propose a bi-directional similarity measure which quantitatively captures these two requirements: Two signals S and T are considered visually similar if all patches of S (at multiple scales) are contained in T, and vice versa. The problem of summarization/re-targeting is posed as an optimization problem of this bi-directional similarity measure. We show summarization results for image and video data. We further show that the same approach can be used to address a variety of other problems, including automatic cropping, completion and synthesis of visual data, image collage, object removal, photo reshuffling and more.
Cutting Edge: DNA Sensing via the STING Adaptor in Myeloid Dendritic Cells Induces Potent Tolerogenic Responses (2013)

Cytosolic DNA sensing via the stimulator of IFN genes (STING) adaptor incites autoimmunity by inducing type I IFN (IFN-αβ). In this study, we show that DNA is also sensed via STING to suppress immunity by inducing IDO. STING gene ablation abolished IFN-αβ and IDO induction by dendritic cells (DCs) after DNA nanoparticle (DNP) treatment. Marginal zone macrophages, some DCs, and myeloid cells ingested DNPs, but CD11b(+) DCs were the only cells to express IFN-β, whereas CD11b(+) non-DCs were major IL-1β producers. STING ablation also abolished DNP-induced regulatory responses by DCs and regulatory T cells, and hallmark regulatory responses to apoptotic cells were also abrogated. Moreover, systemic cyclic diguanylate monophosphate treatment to activate STING induced selective IFN-β expression by CD11b(+) DCs and suppressed Th1 responses to immunization. Thus, previously unrecognized functional diversity among physiologic innate immune cells regarding DNA sensing via STING is pivotal in driving immune responses to DNA.
Female Reproductive Tissues Are the Primary Target ofAgrobacterium-Mediated Transformation by the Arabidopsis Floral-Dip Method (2000)

The floral-dip method for Agrobacterium-mediated transformation of Arabidopsis allows efficient plant transformation without need for tissue culture. To facilitate use with other plant species, we investigated the mechanisms that underlie this method. In manual outcrossing experiments, application of Agrobacterium tumefaciens to pollen donor plants did not produce any transformed progeny, whereas application of Agrobacterium to pollen recipient plants yielded transformants at a rate of 0.48%. Agrobacterium strains with T-DNA carrying gusA (encoding beta-glucuronidase [GUS]) under the control of 35S, LAT52, or ACT11 promoters revealed delivery of GUS activity to developing ovules, whereas no GUS staining of pollen or pollen tubes was observed. Transformants derived from the same seed pod contained independent T-DNA integration events. In Arabidopsis flowers, the gynoecium develops as an open, vase-like structure that fuses to form closed locules roughly 3 d prior to anthesis. In correlation with this fact, we found that the timing of Agrobacterium infection was critical. Transformants were obtained and GUS staining of ovules and embryo sacs was observed only if the Agrobacterium were applied 5 d or more prior to anthesis. A 6-fold higher rate of transformation was obtained with a CRABS-CLAW mutant that maintains an open gynoecium. Our results suggest that ovules are the site of productive transformation in the floral-dip method, and further suggest that Agrobacterium must be delivered to the interior of the developing gynoecium prior to locule closure if efficient transformation is to be achieved.
THE INFLUENCE OF DIETARY NUCLEOTIDES ON CELL-MEDIATED IMMUNITY (1983)

VAN BUREN, CHARLES T.; KULKARNI, ANIL D.; SCHANDLE, VICKY B.; RUDOLPH, FREDERICK B. Author Information
Phase I and clinical pharmacological study of mercaptopurine administered as a prolonged intravenous infusion. (1985)

The bioavailability of oral mercaptopurine (MP) is poor, and plasma levels following p.o. dosing are highly variable. In an attempt to circumvent these problems, we conducted a Phase I trial and clinical pharmacological study of MP administered as a prolonged i.v. infusion. An infusion rate of 50 mg/sq m/h, which was designed to achieve therapeutic drug levels in plasma, was used in all patients. The infusion duration was escalated in 12-h increments. Thirty-eight patients were evaluated. The dose-limiting toxicity was mucositis. Other reversible toxicities were myelosuppression and hepatotoxicity. An infusion duration of 48 h was found to be safe, unassociated with dose-limiting toxicity. Objective responses were seen in five patients. The mean plasma steady-state MP concentration achieved was 6.9 microM with little interpatient variability seen. Allopurinol coadministration had no effect on the plasma pharmacokinetics of i.v. MP. However, allopurinol did alter the urinary metabolite pattern, decreasing thiouric acid and increasing MP and thioxanthine levels. The steady-state cerebrospinal fluid:plasma ratio for MP was 0.27, suggesting that this approach may be of value in the treatment of central nervous system cancer. MP can be safely administered as a 48-h i.v. infusion at a dose rate which reliably achieves MP levels associated with optimal antileukemic activity in vitro.