gebhart/patrepeval huggingface dataset:
Differential effect of nucleoside analog triphosphates on ribonucleotide reductases from uninfected and herpes simplex virus-infected HeLa cells. (2020)

Effects of the triphosphates of eight pyrimidine nucleoside analogs (5-substituted, 2'-fluoroara-, and acyclonucleosides) and acycloguanosine were examined on the ribonucleotide reductases prepared from uninfected and herpes simplex virus (types 1 and 2)-infected HeLa cells. Of the analogs tested, E-5-propenyl- and E-5-(2-bromovinyl)-dUTP were more potent inhibitors than dTTP of the enzymes from virus-infected cells, whereas only the former compound showed this effect on the uninfected HeLa enzyme.
Heterogeneity of proteinases from the hyperthermophilic archaeobacterium Pyrococcus furiosus (1991)

Intracellular and extracellular samples from the extremely thermophilic archaeobacterium Pyrococcus furiosus showed the presence of multiple active proteinases. Using gelatin-containing SDS-PAGE, up to 13 activity bands were visualized with apparent molecular masses of between 66 and 135 kDa. Characterization studies revealed these bands to be due to discrete polypeptides, and not artefacts. Results from gel permeation chromatography, sucrose density gradient centrifugation and non-denaturing PAGE suggested that some of these proteohtic polypeptides may exist as active aggregates either in vivo or in vitro before being dissociated by SDS to active monomers.
Anaplastic variant of diffuse large B‐cell lymphoma with hallmark cell appearance: Two cases highlighting a broad diversity in the diagnostics (2018)

The anaplastic variant of diffuse large B-cell lymphoma (A-DLBCL) is morphologically defined but remains an enigmatic disease in its clinicopathologic distinctiveness. Here, we report two cases involving Japanese women aged 59 years, both with A-DLBCL with the hallmark cell appearance and both indistinguishable from common and giant cell-rich patterns, respectively, of anaplastic lymphoma kinase (ALK)-positive anaplastic large cell lymphoma. Case 1 was immunohistochemically positive for CD20, CD79a and OCT-2 but not for the other pan-B-cell markers, CD30 and ALK. Case 2 showed CD20 and CD30 positivity for 50% and 20% of tumor cells in addition to strong expression of p53 and MYC. Both were positive for fascin without Epstein-Barr virus association. Our cases provide additional support for the earlier reports that A-DLBCL exhibits clinicopathologic features distinct from ordinal diffuse large B-cell lymphoma (DLBCL), and documented its broader morphologic diversity than previously recognized. They also shed light on the unique feature of absent expression of pan-B-cell markers except for CD20 and CD79a, suggesting that A-DLBCL may biologically mimic a gray zone or intermediate lymphoma between DLBCL and classic Hodgkin lymphoma.
Room-temperature optical bistability in InGaAsP/InP amplifiers and implications for passive devices (1985)

Optical bistability has been observed for the first time in a room-temperature InGaAsP/InP amplifier. Switching occurred at an optical input power of about 3 μW, corresponding to a change in the refractive index of 5×10−4. The results are discussed in terms of a light-induced change in carrier concentration. Implications for bistability in passive devices are also discussed.
Statin Use and Risk of Sepsis After Percutaneous Nephrolithotomy (2015)

Statin use is not associated with reductions in postoperative sepsis, nonfebrile UTIs, ICU utilization, or hospital LOS after PCNL. To increase the safety of PCNL, urologists will have to consider other processes of care (e.g., clinical care pathways).
Discovery and Development of Montelukast (Singulair®) (2012)

This chapter contains sections titled: Introduction Drug Development Strategies LTD4 Antagonist Program The Discovery of Montelukast (Singulair®) Synthesis of Montelukast ADME Studies with MK-0476 (Montelukast) Safety Assessment of Montelukast Clinical Development of Montelukast Summary Personal Impact References
Spectral energy cascade in nonlinear acoustic and thermoacoustic waves (2018)

Gupta, Lodato, and Scalo (JFM, 2017) have demonstrated the existence of an equilibrium spectral energy cascade in shock waves formed as a result of continued modal thermoacoustic amplification consistent with Kolmogorov’s theory for high-Reynolds-number hydrodynamic turbulence. In this work, we develop a rigorous theory of spectral energy cascade in an ensemble of nonlinear acoustic waves, which fully develop into randomly distributed shock waves resulting in acoustic wave turbulence. In analogy to hydrodynamic turbulence, the dynamics are shown very similar to the homogeneous isotropic turbulence in a box. To elucidate the energy dynamics, we derive mathematically exact energy corollary for second order nonlinear acoustics thus identifying the second-order energy norm for acoustics. For randomly initialized nonlinear waves, the mean energy in the domain decays with a −2/3 law in time due to coalescence of shock waves. In the spectral space, the energy corollary yields analytical expressions of spectral energy, spectral energy flux, and spectral energy dissipation. We derive the spectral energy scaling laws based on the Kolmogorov length scale which corresponds to the shock thickness in acoustic wave turbulence.
1,5-Anhydro-2-Deoxy-D-Altritol Oligonucleotides as Conformationally Restricted Analogues of Rna (1998)

Abstract As part of a project concerning the investigation of new hexitol nucleic acids (HNA), the 1,5-anhydro-2-deoxy-D-altritol nucleoside building blocks with a uracil, cytosine, adenine and guanine base moiety were synthesized. The uracil analogue was used for the automated synthesis of corresponding oligonucleotides. Hybridization capabilities of these altritol nucleic acids (ANA) are illustrated by the Tm values obtained for the (a hU)13/(dA)13 duplex.
The plasma concentration‐time profile of beta‐alanine using a controlled‐release formulation (Carnosyn ® ) (2008)

Carnosine (β‐Alanylhistidine) synthesis in muscle cells is limited by the availability of β‐Alanine, but can be increased 80% or more when the diet is supplemented with β‐Ala. This is of interest to athletes since increased levels of muscle Carnosine have been shown to improve exercise performance. Above 10mg/kg bwt, however, β‐Ala in solution or rapidly‐dissolving capsules causes symptoms of paraesthesia, despite the amount being less than that available from normal‐size portions of meat. PURPOSE To investigate β‐Ala absorption using a controlled‐release formulation. METHOD Three males and 3 females were given 1600mg β‐Ala dissolved in water (C), 2 × 800mg β‐Ala controlled release tablets (T2) and 4 tablets (T4), on separate occasions. Controlled release tablets were Carnosyn™ supplied by Collegiate Sports Nutrition. Plasma from 100μl capillary blood samples was collected over 6h, initially every 0.25h, and analysed for β‐Ala by HPLC. RESULTS Subjects reported significant paraesthesia with C, no symptoms with T2 and zero/trace symptoms with T4. Peak β‐Ala (P) with C was 219±78μM with return to ~10uM at 3h. Increases in P were greatly attenuated with T2 (126±36μM) and T4 (177±123μM) but greatly extended (&gt;50μM at 3h). Areas under the plasma concentration curve were C: 286±48; T2: 309±154; T4: 518±220 μM.h. with C or T2 vs T4: P&lt;0.05; C vs T2: P&gt;0.05. CONCLUSION : T2 was bioequivalent to C but did not cause paraesthesia.
Clinical dose-response curves of human malignant epithelial tumours (1973)

Optimally, the total radiation dose, over-all treatment time, and fractionation should be individualized for every tumour on the basis of histology, the number of malignant cells, the percentage of anoxic cells, and the kinetics of that particular tumour. The histological variety within the epithelial tumours does not affect radiosensitivity. Dose-response curves obtained clinically are shown for subclinical disease in the lymphatic areas. Correlation is attempted between the volume of cancer and the doses necessary to obtain a high percentage of controls. It is shown that, depending upon the anatomical site and the clinical variety of the cancer, the doses and treatment times may be different. Reoxygenation during treatment has been considered necessary to explain the control of human cancers by irradiation. The percentage of controls of very large, poorly vascularized tumour masses irradiated with long treatment times compared with shorter treatment times suggests that reoxygenation may be a factor. Some reflections are made on the repopulation potential of malignant cells by comparing results obtained with the split-course technique versus 850 rads weekly dosage rate.
Is Hepatitis C Virus Involved in Hepatitis-Associated Aplastic Anemia? (1990)

Hepatitis C virus is not a frequent cause of non-A, non-B hepatitis-associated aplastic anemia. Either a non-A, non-B, non-C hepatitis virus is involved in non-A, non-B hepatitis-related aplasia or hepatitis C virus prevalence is underestimated in patients with hepatitis-related aplasia, possibly as a result of immunologic defects.
Quality assessment pathway for respiratory oscillometry (2022)

<b>A flow-chart-driven procedure is presented to facilitate respiratory oscillometry operator competency and measurement quality. A novel feature is a quality grading system, in line with other standards of lung function.</b> https://bit.ly/3G4r0X1.
Figure S8 from Cathepsin B Is Dispensable for Cellular Processing of Cathepsin B-Cleavable Antibody–Drug Conjugates (2023)

&lt;p&gt;Supplementary Figure 8: Dose-titration curves for KPL-4 cells exposed to anti-HER2-VC(S)-MMAE (IC50 = 0.0060 ÃŽÂ¼g/mL), anti-HER2-VC(R)-MMAE (IC50 = 0.022 ÃŽÂ¼g/mL), and anti-HER2-MC-MMAE (IC50 = 0.070 ÃŽÂ¼g/mL).&lt;/p&gt;
Leptin restores the insulinotropic effect of exenatide in a mouse model of type 2 diabetes with increased adiposity induced by streptozotocin and high-fat diet (2014)

Leptin may reduce pancreatic lipid deposition, which increases with progression of obesity and can impair β-cell function. The insulinotropic effect of glucagon-like peptide-1 (GLP-1) and the efficacy of GLP-1 receptor agonist are reduced associated with impaired β-cell function. In this study, we examined whether leptin could restore the efficacy of exenatide, a GLP-1 receptor agonist, in type 2 diabetes with increased adiposity. We chronically administered leptin (500 μg·kg⁻¹·day⁻¹) and/or exenatide (20 μg·kg⁻¹·day⁻¹) for 2 wk in a mouse model of type 2 diabetes with increased adiposity induced by streptozotocin and high-fat diet (STZ/HFD mice). The STZ/HFD mice exhibited hyperglycemia, overweight, increased pancreatic triglyceride level, and reduced glucose-stimulated insulin secretion (GSIS); moreover, the insulinotropic effect of exenatide was reduced. However, leptin significantly reduced pancreatic triglyceride level, and adding leptin to exenatide (LEP/EX) remarkably enhanced GSIS. These results suggested that the leptin treatment restored the insulinotropic effect of exenatide in the mice. In addition, LEP/EX reduced food intake, body weight, and triglyceride levels in the skeletal muscle and liver, and corrected hyperglycemia to a greater extent than either monotherapy. The pair-feeding experiment indicated that the marked reduction of pancreatic triglyceride level and enhancement of GSIS by LEP/EX occurred via mechanisms other than calorie restriction. These results suggest that leptin treatment may restore the insulinotropic effect of exenatide associated with the reduction of pancreatic lipid deposition in type 2 diabetes with increased adiposity. Combination therapy with leptin and exenatide could be an effective treatment for patients with type 2 diabetes with increased adiposity.
Season variation of wastewater treatment characterictic and eukaryotic community structure of down-flow hanging sponge (DHS) reactor applied for post-treatment of UASB reactor treating municipal sewage (2013)

本研究では下水処理UASB後段のDHSリアクターにおける排水処理特性と保持汚泥の真核生物群集構造に与える季節変動の影響を調査した. その結果, 運転季節によって真核生物群集構造は異なっており, 流入水温による影響を受けていたと考えられた. また, CODCr濃度やNH4+濃度が高濃度の環境(DHS上部)では繊虫門のParamecium属やColpidium属, 低濃度の環境(DHS下部)では肉質虫亜門のArcella属やCentropyxis属が優占するなど, 水質に応じて優占する生物種が異なっていた. また汚泥中で優占する真核生物を単離し, 18S rRNA遺伝子の塩基配列による同定を試みた結果, 種レベルでの同定が可能であった. そのため汚泥から1個体ずつ単離することで真核生物の形態と種を正確に評価できる可能性が示唆された.
CDMA multiuser detection: a nonlinear programming approach (2002)

The optimum receiver to detect the bits of multiple code-division multiple access (CDMA) users has an exponential complexity in the number of active users in the system. Consequently, many suboptimum receivers have been developed to achieve good performance with less complexity. We take the approach of approximating the solution of the optimum multiuser detection problem (OMUD) using nonlinear programming relaxations. First, we observe that some popular suboptimum receivers indeed correspond to relaxations of the optimal detection problem. In particular, one proposed approximation method yields to iterative solutions which correspond to previously proposed heuristic nonlinear detectors. Using a nonlinear programming approach, we identify the convergence properties of these iterative detectors. Secondly, we propose a relaxation that yields a receiver which we call the generalized minimum mean squared error detector. We give a simple iterative implementation of the detector. Its performance is evaluated and comparisons to other suboptimum detection schemes are given.
Normal Tissue Responses to Radiation Therapy (1975)

AFTER the introduction of supervoltage equipment into clinical practice some 25 years ago, radiation therapy assumed an increasingly prominent role in the management of patients with cancer. Current estimates are that 50 per cent of patients with cancer will receive radiation therapy at some time during the course of their disease, and a large percentage of these patients will be treated with curative intent. Survival rates approximating 90 per cent are reported by many centers treating early seminoma of the testis, Hodgkin's disease, and cancers of the larynx and cervix. Impressive results have recently been reported in prostatic cancer1 and . . .
Abstract 2583: LA480, a bivalent humanized c-Met monoclonal antibody, inhibits tumor growth without eliciting significant agonist activity (2010)

Abstract The receptor tyrosine kinase c-Met and its ligand HGF elicit multiple cellular activities including cell proliferation, motility, invasion, tubulogenesis, angiogenesis and anti-apoptosis. Dysregulation of this pathway has emerged as a crucial feature for many human tumors. However, past efforts in developing c-Met therapeutic antibodies that inhibit both ligand-dependent and ligand-independent c-Met activation have been largely unsuccessful due to agonist properties of the antibodies. In fact, c-Met antibodies exhibiting medium to strong agonist activity stimulate proliferation of both normal and tumor cells. We report here that LA480, a bivalent humanized monoclonal c-Met antibody, blocks HGF binding to c-Met and also induces c-Met internalization. Moreover, LA480 inhibits growth of xenograft tumors mediated by HGF-dependent and HGF-independent c-Met pathway activation. In order to evaluate whether LA480 has agonist activity, we tested LA480 in the following HGF-responsive biological assays: proliferation of primary human hepatocytes and tumor cell lines, scattering of DU145 cells, stimulation of HepG2 invasion and tubulogenesis, tube formation in endothelial and stromal cell co-cultures, and protection from apoptosis induced by staurospor in Caki-1 cells. A bivalent c-Met agonist antibody and HGF were included in the assays as positive controls, in addition to antibody isotype negative controls. Our results demonstrate that LA480 does not significantly stimulate cell proliferation, scattering, invasion, tubulogenesis, angiogenesis or apoptosis protection in the above assay systems. Under the same conditions, the agonist positive control c-Met antibody and HGF both significantly induced these biological effects. These unique properties of LA480 suggest that it may be a promising therapeutic reagent for treatment of cancers driven by ligand-dependent and ligand-independent c-Met activation. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 2583.
Interleukin-2 receptor alpha-subunit deficiency and spontaneous perforation secondary to cytomegalovirus (CMV) colitis (2006)

The authors present the difficulties of diagnosis and treatment of a 9-year-old girl with IL-2 receptor alpha-subunit (IL-2Rα) deficiency -a rare type of severe combined immunodeficiency (ID)- causing severe complications.
Rad52-Rad51 association is essential to protect Rad51 filaments against Srs2, but facultative for filament formation (2018)

Homology search and strand exchange mediated by Rad51 nucleoprotein filaments are key steps of the homologous recombination process. In budding yeast, Rad52 is the main mediator of Rad51 filament formation, thereby playing an essential role. The current model assumes that Rad51 filament formation requires the interaction between Rad52 and Rad51. However, we report here that Rad52 mutations that disrupt this interaction do not affect γ-ray- or HO endonuclease-induced gene conversion frequencies. In vivo and in vitro studies confirmed that Rad51 filaments formation is not affected by these mutations. Instead, we found that Rad52-Rad51 association makes Rad51 filaments toxic in Srs2-deficient cells after exposure to DNA damaging agents, independently of Rad52 role in Rad51 filament assembly. Importantly, we also demonstrated that Rad52 is essential for protecting Rad51 filaments against dissociation by the Srs2 DNA translocase. Our findings open new perspectives in the understanding of the role of Rad52 in eukaryotes.
Octapeptin C4 Induces Less Resistance and Novel Mutations in an Epidemic Carbapenemase-producing Klebsiella pneumoniae ST258 Clinical Isolate Compared to Polymyxins (2018)

ABSTRACT Polymyxin B and E (colistin) have been pivotal in the treatment of extensively drug-resistant (XDR) Gram-negative bacterial infections, with increasing use over the past decade. Unfortunately, resistance to these antibiotics is rapidly emerging. The structurally-related octapeptin C4 (OctC4) has shown significant potency against XDR bacteria, including against polymyxin-resistant (Pmx-R) strains, but its mode of action remains undefined. We sought to compare and contrast the acquisition of XDR Klebsiella pneumoniae (ST258) resistance in vitro with all three lipopeptides to help elucidate the mode of action of the drugs and potential mechanisms of resistance evolution. Strikingly, 20 days of exposure to the polymyxins resulted in a dramatic (1000-fold) increase in the minimum inhibitory concentration (MIC) for the polymyxins, reflecting the evolution of resistance seen in clinical isolates, whereas for OctC4 only a 4-fold increase was witnessed. There was no cross-resistance observed between the polymyxin - and octapeptin-induced resistant strains. Sequencing revealed previously known gene alterations for polymyxin resistance, including crrB , mgrB , pmrB , phoPQ and yciM , and novel mutations in qseC . In contrast, mutations in mlaDF and pqiB , 1genes related to phospholipid transport, were found in octapeptin-resistant isolates. Mutation effects were validated via complementation assays. These genetic variations were reflected in phenotypic changes to lipid A. Pmx-R isolates increased 4-amino-4-deoxy-arabinose fortification to phosphate groups of lipid A, whereas OctC4 induced strains harbored a higher abundance of hydroxymyristate and palmitoylate. The results reveal a differing mode of action compared to polymyxins which provides hope for future therapeutics to combat the increasingly threat of XDR bacteria.
The Potential Role of Perfluorochemicals (PFCS) in Diagnostic Imaging (1994)

Although perfluorochemicals (PFCs) are known for their ability to carry oxygen, they are the most versatile and only universal contrast agents with important applications using x-ray, ultrasound, or magnetic resonance (MR). The characteristics that make them unique diagnostic agents are lack of hydrogen atoms, immiscibility with water, low surface tension, compressibility, and long intravascular persistence when emulsified and given i.v. When made radiopaque, they are visible with x-ray computed tomography (CT) and standard radiography. Because the neat liquid is inert it can be ingested, instilled in the lung, or introduced into any hollow organ to image the lumen without untoward effects. The long intravascular persistence allows the imaging of blood vessels and vascularized tissues. Small or deep vessels become visible on Color Doppler Imaging and angiographic images of any vascular tree including the coronaries can be rendered from the serial CT images. As PFCs accumulate within RE cells, specific liver and spleen enhancement is achieved allowing the detection of small tumors within these organs. When injected interstitially, the particles find their way to the draining lymphnodes providing detail of the internal architecture to detect the presence or absence of tumor involvement on both CT and sonography. Using 19F MR, tissue perfusion and tissue pO2 measurements can be achieved. As can be seen, the applications of PFC in diagnosis are vast, unique, and important. These new capabilities will carry radiological tools to new horizons.
Isolierstoffe (1978)

Als Rückblick auf die Leiter und Halbleiter und als Vorausschau auf die Isolierstoffe ist in Tabelle 17.1 der Gesamtbereich aller bekannten spezifischen Widerstände von den Supraleitern über die Metalle und Halbleiter bis zu den Isolatoren dargestellt. Dabei sind z.B. die Metalle bei Raumtemperatur eingegrenzt zwischen ihrem bestleitenden Vertreter, dem Silber, mit ρ ~ 10-8 Ωm und den Widerstandslegierungen mit ρ ~ 10-6 Ωm. Den letzteren Wert hat auch ungefähr das reine Wolfram bei 2000 °C. Die Größe des Sprunges zwischen den tiefgekühlten Normalleitern bis hinab zu den Supraleitern ist evident. Nach der anderen Seite klafft zum Graphit hin eine Lücke zwischen 10-6 und 10-5, die bei tiefen Temperaturen noch größer würde, indem die Metalle dann nach unten, Graphit etc. nach oben rutschen, ebenso wie die Halbleiter. Bei diesen lassen sich die Grenzen von 10-4 bis 10+7 nicht bestimmten technisch interessanten Werkstoffen zuordnen, da die spezifischen Widerstände hier ja bei ein- und derselben Grundsubstanz durch Reinheitsgrad und Dotierung um Zehnerpotenzen verändert werden können. Der Bereich der Halbleiter überlappt sich bei Raumtemperatur und erst recht in der Kälte mit dem der Isolatoren.