gebhart/patrepeval huggingface dataset:
Reversal of Established Lupus Nephritis and Prolonged Survival of New Zealand Black × New Zealand White Mice Treated with the Topoisomerase I Inhibitor Irinotecan (2010)

Systemic lupus erythematosus is a chronic autoimmune disorder that predominantly affects women of childbearing age. Lupus-associated glomerulonephritis is a major cause of mortality in these patients. Current treatment protocols for systemic lupus erythematosus include cyclophosphamide, prednisolone, azathioprine, and mycophenolate mofetil. However, in mice none of these agents alone or in combination were shown to reverse established proteinuria. Using New Zealand Black x New Zealand White F1 mice, we report that administration of the topoisomerase I inhibitor irinotecan from week 13 completely prevented the onset of proteinuria and prolonged survival up to at least 90 wk without detectable side effects. Furthermore, application of irinotecan to mice with established lupus nephritis, as indicated by grade 3+ (> or =300 mg/dl) and grade 4+ (> or =2000 mg/dl) proteinuria and, according to a median age of 35 wk, resulted in remission rates of 75% and 55%, respectively. Survival was significantly prolonged with 73 wk (grade 3+ and 4+ combined) versus 40 wk for control animals. Although total IgG and anti-dsDNA Abs in the serum and mesangial IgG deposits in the kidneys were not reduced in irinotecan-treated mice, subendothelial immune deposits were considerably diminished, suggesting a prevention of glomerular basement membrane disruption. This effect was accompanied by increased rates of ssDNA breaks and inhibition of renal cell apoptosis being different to what is known about irinotecan in anticancer therapy. In conclusion, our data provide evidence that irinotecan might represent an entirely new strategy for the treatment of systemic lupus erythematosus.
Vasoactive parathyroid hormone in the treatment of acute ischemic left ventricular failure and the prevention of cardiogenic shock. (1985)

Molecular fragment 1-34 of synthetic bovine parathyroid hormone (bPTH[1-34]) has been found to be a potent coronary vasodilator, a moderate systemic vasodilator, and a positive inotropic agent for the myocardium. On that basis, the hypothesis was tested that "vasoactive" PTH might be effective in the treatment of acute ischemic left ventricular failure (LVF) and the prevention of cardiogenic shock. Dogs whose sympathetic nerve activity was blocked by a combination of reserpine, propranolol, and chlorpromazine were anesthetized and subjected to open-chest occlusion of the left anterior descending coronary artery (LAD) plus sequential ligation of three diagonal branches. In ten untreated animals (control group), acute myocardial ischemia led to LVF and, within 4 hours, to cardiogenic shock (50% or greater reduction in cardiac output; 30% or greater reduction in mean aortic pressure; elevation of left atrial pressure above 20 mm Hg; and significant elevation of arterial blood lactate concentration). At the end of 4 hours, myocardial infarction measured by the incubation of transverse slices of the left ventricle in TTC solution represented 96 +/- 3% of the myocardium "at risk." In ten treated animals (experimental group), PTH(1-34) was administered intravenously, 1 U/kg/min, starting 30 minutes after coronary occlusion. Treatment improved left coronary blood flow from 55 +/- 5 to 120 +/- 11 ml/100 g LV/min, increased cardiac index from 72.5 +/- 7 to 117.5 +/- 12 ml/kg/min, reduced left atrial pressure from 27.5 +/- 2.5 to 15 +/- 2.5 mm Hg (all changes, P less than 0.005), sustained aortic pressure, and prevented the elevation of arterial blood lactate. At the end of 4 hours, myocardial infarction represented 30 +/- 1.2% of the myocardium at risk (difference between the two groups significant, P less than 0.005). Thus, PTH(1-34) exerted a tissue-sparing effect on the myocardium, restored LV function, and prevented the development of shock.
Reversal of multidrug resistance by non-antitumor anthracycline analogs. (1984)

It was found that three synthetic anthracycline analogs lacking not only antitumor activity but also calcium-antagonizing action possessed an activity to potentiate vincristine cytotoxicity against vincristine-resistant P388 leukemia. ID-8279, one of these analogs, significantly reversed resistance to vincristine and daunorubicin by increasing their intracellular accumulation.
Characteristics of load resonant converters operated in a high power factor mode (2002)

The performance of the parallel resonant converter and the combination series/parallel resonant converter (LCC converter) when operated above resonance in a high power factor mode are determined and compared for single-phase applications. When the DC voltage applied to the input of these converters is obtained from a single-phase rectifier with a small DC link capacitor, a relatively high power factor inherently results, even with no active control of the input line current. This behaviour is due to the pulsating nature of the DC link and the inherent capability of the converters to boost voltage during the valleys of the input AC wave. With no active control of the input line current, the power factor depends on the ratio of operating frequency to tank resonant frequency. With active control of the input line current, near unity power factor and low input harmonic currents can be obtained.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Analysis of alpha-fetoprotein gene expression in hepatocellular carcinoma and liver cirrhosis by in situ hybridization (1988)

The expression of the alpha-fetoprotein (AFP) gene in hepatocellular carcinoma (HCC) and liver cirrhosis by in situ hybridization analysis of AFP mRNA in cryostat and paraffin-embedded tissue sections was studied. In HCC sections the majority of tumor cells showed positive hybridization with a 3H-labeled AFP complementary DNA probe. The number of radioactive hybrid grains detected in HCC sections generally paralleled the level of serum AFP in the patient. In liver cirrhosis sections a small number of cells showed positive hybridization. These cells were dispersed in the tissue and morphologically indistinguishable from surrounding hepatocytes. Each of these cells contained a high level of hybridization signals to permit easy identification. In situ hybridization analysis of AFP mRNA may be of use in detecting preneoplastic cells in liver cirrhosis that cannot be defined on the morphologic and immunohistochemical basis.
Mass Spectrometry for Characterization of Microorganisms (1993)

The advantages and disadvantages of mass spectrometry for the characterization of microorganisms are summarized. Different families of chemotaxonomic markers are reviewed, especially with respect to mass spectrometric analysis. An overview is provided to the chapters in the book.
Identification of Neoantigen-Reactive Tumor-Infiltrating Lymphocytes in Primary Bladder Cancer (2019)

Immune checkpoint inhibitors are effective in treating a variety of malignancies, including metastatic bladder cancer. A generally accepted hypothesis suggests that immune checkpoint inhibitors induce tumor regressions by reactivating a population of endogenous tumor-infiltrating lymphocytes (TILs) that recognize cancer neoantigens. Although previous studies have identified neoantigen-reactive TILs from several types of cancer, no study to date has shown whether neoantigen-reactive TILs can be found in bladder tumors. To address this, we generated TIL cultures from patients with primary bladder cancer and tested their ability to recognize tumor-specific mutations. We found that CD4<sup>+</sup> TILs from one patient recognized mutated C-terminal binding protein 1 in an MHC class II-restricted manner. This finding suggests that neoantigen-reactive TILs reside in bladder cancer, which may help explain the effectiveness of immune checkpoint blockade in this disease and also provides a rationale for the future use of adoptive T cell therapy targeting neoantigens in bladder cancer.
Antiapoptotic Drugs: A Therapautic Strategy for the Prevention of Neurodegenerative Diseases (2011)

The purpose of this review is to discuss potential pathways involved in the pathogenesis of neurodegenerative diseases, highlighting current pharmacological drug targets in neuronal apoptosis prevention. The incidence of these disorders is expected to rise in the coming years and so finding effective treatments represents a significant challenge for medicine. Alzheimer's disease and Parkinson's disease were both described almost a century ago and are the most important neurodegenerative disorders in the developed world. However, the molecular mechanisms that lead to the development of the neuronal pathology in both diseases are unclear. For this reason, despite substantial research in the area, an effective treatment for these diseases does not yet exist. In the present study we discuss in depth the pathways involved in apoptosis and neuronal death in neurodegenerative diseases. We also examine drugs that may have a neuroprotective effect. Inhibition of apoptosis mediated by oxidative stress generation and mitochondrial alteration or by the blockade of NMDA receptors could constitute a suitable therapeutic strategy for Alzheimer's disease. A multiple therapy with antioxidants, cell cycle inhibitors, GSK3β inhibitors, and STATINS could, in the future, represent a suitable strategy for delaying the progression of neurodegenerative diseases. This research contributes to the development of new methods in the field of apoptosis inhibitors that could provide the future tools for the treatment of Alzheimer's and Parkinson's disease, as well as other neurodegenerative diseases.
Nuclear transport in vitro (1989)

In this paper, progress towards the goal of understanding communication between the nucleus and cytoplasm using an in vitro system is reviewed. To probe the mechanism of nuclear targeting, we developed an in vitro transport system and have begun to dissect the highly selective process of nuclear transport. The basic parameters of transport were defined using an easily isolated nuclear protein, nucleoplasmin. To study the interaction of nuclear targeting signals with the pore, an artificial nuclear transport substrate was constructed, which consists of human serum albumin coupled to the signal sequence of the SV40 T-antigen. A similar peptide-protein conjugate was made using a mutant signal sequence. These conjugates were fluorescently labeled and/or tagged with gold and tested for transport in the in vitro system. High levels of nuclear transport of the wild-type signal sequence-containing protein were observed, while no transport of the mutant signal sequence-containing protein was seen. Thus, the in vitro system correctly recognizes the single amino acid change between the wild-type and mutant signal sequences. We found that the observed nuclear transport was completely dependent on the presence of ATP. Using the in vitro system we identified a specific inhibitor of nuclear transport, the lectin wheat germ agglutinin (WGA), which we find binds directly to the nuclear pore. Probing blots of nuclear proteins with 125I-WGA identified a family of nuclear pore glycoproteins, including one major glycoprotein of 62K (K = 10(3)Mr) molecular weight. With the inhibitor and the in vitro assay, it has been possible to experimentally separate nuclear transport into two steps: (1) a step in which the signal sequence-bearing protein binds to the pore, followed by (2) a step in which the protein translocates through the pore. It is this second step which is the ATP-dependent step of transport, since pore binding but not translocation was seen to occur in the absence of ATP.
The Nature Relatedness Scale (2008)

Disconnection from the natural world may be contributing to our planet's destruction. The authors propose a new construct, Nature Relatedness (NR), and a scale that assesses the affective, cognitive, and experiential aspects of individuals' connection to nature. In Study 1, the authors explored the internal structure of the NR item responses in a sample of 831 participants using factor analysis. They tested the construct validity of NR with respect to an assortment of environmental and personality measures. In Study 2, they employed experience sampling methodology examining if NR people spend more time outdoors, in nature. Across studies, NR correlated with environmental scales, behavior, and frequency of time in nature, supporting the reliability and validity of NR, as well as the contribution of NR (over and above other measures) to environmental concern and behavior. The potential of NR as a useful method for investigating human-nature relationships and the processes underlying environmental concern and behaviors are discussed.
Fluorous-Based Carbohydrate Microarrays (2005)

The success of microarrays, such as DNA chips, for biosample screening with minimal sample usage has led to a variety of technologies for assays on glass slides. Unfortunately, for small molecules, such as carbohydrates, these methods usually rely on covalent bond formation, which requires unique functional handles and multiple chemical steps. A new simpler concept in microarray formation is based on noncovalent fluorous-based interactions. A fluorous tail is designed not only to aid in saccharide purification but also to allow direct formation of carbohydrate microarrays on fluorous-derivatized glass slides for biological screening with lectins, such as concanavalin A. The noncovalent interactions in the fluorous-based array are even strong enough to withstand the detergents used in assays with the Erythrina crystagalli lectin. Additionally, the utility of benzyl carbonate protecting groups on fucose building blocks for the formation of alpha-linkages is demonstrated.
Thiol−Ene Modification of 1,2-Polybutadiene Using UV Light or Sunlight (2008)

ADVERTISEMENT RETURN TO ISSUEPREVNoteNEXTThiol−Ene Modification of 1,2-Polybutadiene Using UV Light or SunlightNiels ten Brummelhuis, Christina Diehl, and Helmut Schlaad*View Author Information Max Planck Institute of Colloids and Interfaces, Colloid Chemistry, Research Campus Golm, 14424 Potsdam, Germany* Corresponding author: fax +49 331 567 9502; e-mail [email protected]Cite this: Macromolecules 2008, 41, 24, 9946–9947Publication Date (Web):November 7, 2008Publication History Received8 September 2008Revised13 October 2008Published online7 November 2008Published inissue 23 December 2008https://pubs.acs.org/doi/10.1021/ma802047whttps://doi.org/10.1021/ma802047wbrief-reportACS PublicationsCopyright © 2008 American Chemical SocietyRequest reuse permissionsArticle Views6046Altmetric-Citations222LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-AlertscloseSupporting Info (1)»Supporting Information Supporting Information SUBJECTS:Cyclization,Functionalization,Mixtures,Modification,Thiols Get e-Alerts
Pentosan Polysulfate as an Inhibitor of Extracellular HIV-1 Tat (2001)

HIV-1 Tat protein, released from HIV-infected cells, may act as a pleiotropic heparin-binding growth factor. From this observation, extracellular Tat has been implicated in the pathogenesis of AIDS and of AIDS-associated pathologies. Here we demonstrate that the heparin analog pentosan polysulfate (PPS) inhibits the interaction of glutathione S-transferase (GST)-Tat protein with heparin immobilized to a BIAcore sensor chip. Competition experiments showed that Tat-PPS interaction occurs with high affinity (K(d) = 9.0 nm). Also, GST.Tat prevents the binding of [(3)H]heparin to GST.Tat immobilized to glutathione-agarose beads. In vitro, PPS inhibits GST.Tat internalization and, consequently, HIV-1 long terminal repeat transactivation in HL3T1 cells. Also, PPS inhibits cell surface interaction and mitogenic activity of GST.Tat in murine adenocarcinoma T53 Tat-less cells. In all assays, PPS exerts its Tat antagonist activity with an ID(50) equal to approximately 1.0 nm. In vivo, PPS inhibits the neovascularization induced by GST.Tat or by Tat-overexpressing T53 cells in the chick embryo chorioallantoic membrane. In conclusion, PPS binds Tat protein and inhibits its cell surface interaction, internalization, and biological activity in vitro and in vivo. PPS may represent a prototypic molecule for the development of novel Tat antagonists with therapeutic implications in AIDS and AIDS-associated pathologies, including Kaposi's sarcoma.
Crystal‐state structural analysis of two γ‐lactam‐restricted analogs of Pro‐Leu‐Gly‐NH2 (1989)

The crystal structures of two analogs of Pro-Leu-Gly-NH2 (1), containing a gamma-lactam conformational constraint in place of the -Leu-Gly- sequences, are described. The highly biologically active (S,R)-diastereomer 2a is semi-extended at the C-terminus, with the N-terminal Pro residue in the unusual "C5" conformation [psi 1 = -0.8(15) degrees] stabilized by a (peptide)N-H...N(amino) intramolecular H-bond [the N(3)...N(4) separation is 2.687(11)A]. Conversely, the N,N'-isopropylidene aminal trihydrate of the (S,S)-diastereomer 2b, compound 3, adopts a beta-bend conformation at the C-terminus, as already reported for 1. However, the backbone torsion angles [phi 2 = 57.4(4), psi 2 = -129.9(3) degrees; psi 3 = -92.3(4), phi 3 = 6.4(5) degrees] lie close to the values expected for the corner residues of an ideal type-II' beta-bend. A weak intramolecular 4----1 H-bond is seen between the Gly carboxyamide anti-NH and Pro C = O groups. In the newly formed 2,2,3,4-tetraalkyl-5-oxo-imidazolidin-1-yl moiety the psi 1 torsion angle is 12.9(4) degrees and the intramolecular N(3)...N(4) separation is 2.321(4)A.
Analysis of Tumor Specimens at the Time of Acquired Resistance to EGFR-TKI Therapy in 155 Patients with EGFR -Mutant Lung Cancers (2013)

This is the largest series reporting mechanisms of acquired resistance to EGFR-TKI therapy. We identified EGFR T790M as the most common mechanism of acquired resistance, whereas MET amplification, HER2 amplification, and small cell histologic transformation occur less frequently. More comprehensive methods to characterize molecular alterations in this setting are needed to improve our understanding of acquired resistance to EGFR-TKIs.
A new rate control scheme using quadratic rate distortion model (2002)

A new rate control scheme is used to calculate the target bit rate for each frame based on a quadratic formulation of the rate distortion function. The distortion measure are assumed to be either the average quantization scale of a frame or mean square error. The rate distortion function is modeled as a second order function of the inverse of the distortion measure. We presented a closed form solution for the target bit allocation which applies to both the digital storage media (DSM) applications (e.g., MPEG-2) and very low bit rate (VLBR) applications (e.g., MPEG-4). We perform experiments on a wavelet-based coder to demonstrate the versatility of our scheme. Model parameters are estimated using statistical linear regression analysis. Since the estimation uses the past encoded frames of the same picture prediction type (I, P and B pictures), the proposed approach is a single pass rate control technique. For the MPEG-2 coder the fluctuations of the bit counts are significantly reduced by 20 percent to 65 percent in the standard deviation of the bit count while the picture quality remains the same. For the MPEG-4 VM coder, the PSNR is improved by almost one dB as compared to the best MPEG-4 VM rate control using exhaustive combinations of quantization scale parameters.
Direct detection of multiple point mutations in mitochondrial DNA (1997)

Mitochondrial defects can be caused by mutations in nuclear or mitochondrial DNA. Large deletion/duplication and point mutations are the two major types of mitochondrial DNA (mtDNA) mutations. Comprehensive molecular diagnosis requires the analysis of multiple point mutations. We developed an effective multiplex PCR/allele-specific oligonucleotide (ASO) method to simultaneously screen multiple point mutations in mtDNA. The system involved three pairs of primers to amplify mutation "hot spots" at tRNA(leu(UUR)), tRNA(lys)/ATPase, and ND4 regions, followed by detection of point mutations with ASO probes. Over 2000 specimens were analyzed and the results were compared with those from previous studies with the PCR/restriction fragment length polymorphism method. Our data demonstrate that the multiplex PCR/ASO method is much more sensitive in the detection of low mutant heteroplasmy. It is simple and cost effective, especially if a large number of samples are to be screened for multiple point mutations.
Angiotensin II Receptor Blockers and Nephropathy Trials (2001)

This is the first of a series of reports on the American Diabetes Association (ADA) 61st Scientific Sessions held in Philadelphia in June 2001. It covers topics related to angiotensin II receptor blockers (ARBs) and nephropathy.

At a symposium at the 61st Scientific Sessions of the ADA in June 2001, the results of three recent diabetic nephropathy trials with angiotensin II subtype 1 receptor antagonists were presented. Hans-Henrik Parving, Gentofte, Denmark, pointed out that kidney disease develops in 40% of patients with type 2 diabetes, with 25% of patients in Europe and 46% in the U.S. with end-stage renal disease (ESRD) having diabetes. In the latter population, the proportion increases annually by 1.5%. In type 2 diabetes, microalbuminuria is associated with a 5–10% lifetime risk of progression to overt nephropathy, while patients with normoalbuminuria have a 10- to 20-fold lower risk. In the Irbesartan for Micro-Albuminuria in Type 2 Diabetes (IRMA) study, 590 patients with 20–200 μg/min albuminuria with normal serum creatinine and with blood pressure (BP) >135/85 mm Hg were randomized to placebo or 150 or 300 mg irbesartan daily for 2 years. The mean age was 58 years; 70% were male; all were Caucasian; baseline BP was 153/90 mm Hg; baseline albuminuria was 55 μg/min; baseline glomerular filtration rate (GFR) was 110 ml/min; and baseline HbA1c was 7.2%. Patients treated with aspirin in a dose exceeding 325 mg daily were excluded because of the effect on proteinuria and renal function. The mean trough BP (measured 24 h after the last dose of medication) during the study was 145/84, 143/84, and 142/84 mm Hg with placebo and 150 and 300 mg irbesartan daily, respectively. Progression to macroalbuminuria occurred in 15, 10, and 5%, respectively, of the three groups at 2 years, with adjusted risk reduction of 68% with 300 mg and …