gebhart/patrepeval huggingface dataset:
Are continuous cell lines safe as substrates for human drugs and biologics? A case study with human growth hormone. (1989)

The development of a genetically engineered human growth hormone (hGH) preparation is described. The cell line used to produce hGH is a C127 mouse cell transformed with a bovine papilloma virus (BPV) vector. Master, Extended Production, and Working Cell Banks were established. Product is produced by culturing in growth medium, and purified using a series of chromatography and ultrafiltration steps. Extensive testing of cell banks, and bulk and finished product reveals that the cells used to produce hGH are phenotypically and genotypically stable and are free from contamination with adventitious agents. Levels of residual host cell DNA are well below accepted guidelines. Clinical data gathered in multicenter trials confirm the efficacy and safety of the product in the treatment of classic growth hormone deficiency. The regulatory history of human growth hormone in the U.S. is reviewed.
Autoimmune priming, tissue attack and chronic inflammation — The three stages of rheumatoid arthritis (2014)

Extensive genome-wide association studies have recently shed some light on the causes of chronic autoimmune diseases and have confirmed a central role of the adaptive immune system. Moreover, better diagnostics using disease-associated autoantibodies have been developed, and treatment has improved through the development of biologicals with precise molecular targets. Here, we use rheumatoid arthritis (RA) as a prototype for chronic autoimmune disease to propose that the pathogenesis of autoimmune diseases could be divided into three discrete stages. First, yet unknown environmental challenges seem to activate innate immunity thereby providing an adjuvant signal for the induction of adaptive immune responses that lead to the production of autoantibodies and determine the subsequent disease development. Second, a joint-specific inflammatory reaction occurs. This inflammatory reaction might be clinically diagnosed as the earliest signs of the disease. Third, inflammation is converted to a chronic process leading to tissue destruction and remodeling. In this review, we discuss the stages involved in RA pathogenesis and the experimental approaches, mainly involving animal models that can be used to investigate each disease stage. Although we focus on RA, it is possible that a similar stepwise development of disease also occurs in other chronic autoimmune settings such as multiple sclerosis (MS), type 1 diabetes, and systemic lupus erythematosus.
Wirth: Key to slowing population growth -- education of girls. (1998)

The president of the UN Foundation, Tim Wirth, cites education programs for girls as a key to slowing the pace of population growth. Wirth suggests stabilizing the world's population in order to be sure, particularly in the poorest countries, that people have opportunities. The security of the nation and the world hinges upon a sustainable, equitable balance between human numbers and the planet's capacity to support life. Disregarding the issue of population and consumption will destroy the habitat of the world and destroy the very systems that allow life to exist on Earth. The education of girls is a critical area for stabilizing population. Hence, inadequate education is a powerful determinant of high fertility and ensures that individuals do not live up to their potential. The Program of Action adopted at the 1994 ICPD held in Cairo showed that when women have control over their lives, they are better able to contribute to a society that presents them with choices. Conversely, the lack of decision-making power negatively affects a woman's productive role in the family. Wirth also emphasizes the importance of family planning as part of a comprehensive approach to slow population growth. Wirth believes that the Cairo Plus Five Conference to be held in the Hague on February 8-12, 1999, will be very important in making the Program of Action more visible and effective.
Management of neurotrauma by surgeons and orthopedists in a military operational setting (2010)

There is a considerable discrepancy between the potential demand for neurosurgeons and the actual availability of such specialists not only in civilian settings but even more so in military operational environments. For this reason, the Department of Neurosurgery at the German Armed Forces Hospital in Ulm conducts courses for surgeons and orthopedists on the management of patients with neurotrauma. Twelve such courses have already taken place. Each course lasts 1 week. Participants can expect to gain the theoretical knowledge and practical skills they need to provide initial surgical care for patients with traumatic brain injuries and/or spinal trauma. Surgical techniques are practiced above all in pig and human cadavers. At the end of the course, participants with previous surgical knowledge should be able to independently perform a craniotomy, from the planning of the procedure to the closure of the wound. Former course participants have successfully used their neurosurgical knowledge in countries of deployment where they managed patients during teleconsultation sessions and helped repatriate, or even provided surgical treatment to, patients with traumatic brain injuries. In these situations, it was particularly helpful when the physician deployed abroad and the neurosurgeon in Germany knew each other personally. In the future, efforts will be made to combine telemedicine and neuronavigation in an attempt to further improve direct support for physicians under military deployment conditions.
Unrevealing the real pigment composition of green tattoo inks (2019)

Since losing their maverick image, tattoos are no longer fringe groups markings, but a widespread&#13;\npractice with estimated 120 million people tattooed worldwide in 20161. This poses problems of&#13;\nsafety of the materials injected under the skin. In spite of a foreseeable concern, no uniform regulation&#13;\nhas been put in place to monitor the inks composition, determine the potential risks for human health&#13;\nand consequently restrict, whether necessary, the use of specific inks. There are indications on this&#13;\nissue by the ResAP(2008)12, dealing with cosmetics, and safety of the tattooing procedure, which&#13;\nwere accepted in few countries in Europe, and largely neglected by the others. Meantime, new&#13;\nindications are being proposed by the Committee for Risk Assessment (RAC- Nov.2018)3 and the&#13;\nCommittee for Socio-Economic Analysis (SEAC- also Nov.2018)3. In this overall scenario, aiming&#13;\nat tackling tattoo inks safety, the first issue to address is their actual composition. Inks can be&#13;\nconsidered as roughly being composed of a pigment, imparting the colour, and a vehicle, ensuring&#13;\nthe ink fluidity and asepticity. We selected green inks and performed multiple-techniques&#13;\ninvestigations to determine the actual pigment composition. In all of them, PG36, a hexabrominedecachlorine Cu-phthalocyanine was indicated as pigment both on the bottle labels and on the safety&#13;\nsheets, and PG7, a hexadecachlorine Cu-phthalocyanine was found, instead, which is restricted in&#13;\ncountries where legislation on tattoo inks is enforced4. More false declarations on ink compositions&#13;\nwere found, also for additional pigments in the inks, even if none of them is restricted4. Whitening&#13;\nagents such as TiO2 nanoparticles may be present, but in this case, additional dispersing agent, with&#13;\nnon-negligible Al and Si content were not declared. Issues on TiO2 nanoparticles size are also to be&#13;\nconsidered for their potential cytotoxic aspect4.&#13;\n___________&#13;\n[1] S. Everts, Chemical and Engineering News, American Chemical Society, &#13;\n[2] Council of Europe Resolution ResAp(2008)1 on requirements and criteria for the safety of tattoos and permanent&#13;\nmake-up Feb. 20th 2008.&#13;\n[3] Compiled RAC and SEAC Opinion on an Annex XV dossier proposing restrictions on substances used in tattoo&#13;\ninks and permanent make-up ECHA/RAC/RES-O-0000001412-86-240/F, ECHA/SEAC/ ECHA/SEAC/RES-O0000001412-86-265/F, https://echa.europa.eu/it/registry-of-restriction-intentions/-/dislist/details/0b0236e180dff62a&#13;\n[4] E.M. Bauer, T. De Caro, P. Tagliatesta, M. Carbone, Dyes and Pigments 2019, 167, 225-235.
A Tooth Finishing Method with A New Tool of a Vitrified CBN Wheel for Involute Internal Spline. (1999)

In high accurate and high efficient tooth finishing, a vitrified CBN (cubic boron nitride) wheel or a electro-deposited CBN wheel shows superior performance. And honing by a involute spline tooth meshing is profitable due to the generating motion. However, a lack of wheel rigidity and an inadequate feeding motion of the wheel trend to reduce finishing performance. As a result, it is difficult to keep the tooth surface smooth. In this study, the finishing with a vitrified CBN wheel is carried out using a new honing tool. The finishing performance is compared with that obtained using a electro-deposited wheel. And the finishing by braking a internal spline axis is carried out. The influence of different feeding methods is investigated on the finished tooth surface roughness. The finishing by using a vitrified CBN wheel and braking a internal spline axis shows superior performance.
Effects of the conditions of the microemulsion preparation on the properties of Fe3O4 nanoparticles (2008)

Fe 3O4 nanoparticles have been prepared by the microemulsion technique with water as the aqueous phase, n-hexane as the oil phase and Span 80 as the surfactant. The reaction occurred under air, N 2 or high temperature and high pressure atmosphere. Particle size can be controlled by the concentration of the reactants dissolved in water, the ratio of water/surfactant and the atmospheric conditions. The particle size is of 6 - 20 nm. They are superparamagnetic with the saturation magnetization of 50 emu/g. Functionalization of the particle surface has been carried out by using a single layer of oleic acid for hydrophilic surface and double layer of oleic acid and sodium dodecyl sulfate for hydrophilic surface to disperse them in non-aqueous and aqueous solvents, respectively. Changing the conditions of the preparation affected to the properties of the product. This technique showed advantages such as simple, small size particles, monodisperse over the coprecipitation methods.
Increased Remnant Lipoproteins in Apo E Deficient Mice Induce Coronary Atherosclerosis following Transverse Aortic Constriction and Aggravate the Development of Pressure Overload-Induced Cardiac Hypertrophy and Heart Failure (2022)

Murine coronary arteries are very resistant to the development of atherosclerosis, which may be related to their intramyocardial course. Blood pressure promotes atherosclerotic plaque formation by acting as a physical force that potentiates the migration of pro-atherogenic lipoproteins across the endothelium. C57BL/6N apolipoprotein (apo) E deficient mice have increased remnant lipoproteins that are a risk factor for coronary atherosclerosis. In this study, our aim was to quantify coronary atherosclerosis and artery remodeling following transverse aortic constriction (TAC) in C57BL/6N apo E<sup>-/-</sup> mice and to evaluate the impact of increased remnant lipoproteins on the development of pressure overload-induced cardiac hypertrophy and heart failure. Advanced atherosclerotic lesions were observed in the left coronary artery of C57BL/6N apo E<sup>-/-</sup> TAC mice but not in C57BL/6N TAC mice. Pressure overload resulted in markedly increased cardiac hypertrophy and more pronounced heart failure in C57BL/6N apo E<sup>-/-</sup> TAC mice in comparison to C57BL/6N TAC mice. Pathological hypertrophy, as evidenced by increased myocardial fibrosis and capillary rarefaction, was more prominent in C57BL/6N TAC apo E<sup>-/-</sup> than in C57BL/6N TAC mice and led to more marked cardiac dysfunction. In conclusion, TAC in apo E deficient mice induces coronary atherosclerosis and aggravates the development of pathological cardiac hypertrophy and heart failure.
Efficient approach to superior vena cava baffle stenosis following the Mustard procedure: Expanding the role of a mechanical rotating dilator sheath for lead extraction (2020)

Use of the mechanical rotating dilator sheath is an evolving treatment strategy in adult congenital heart disease to minimize the risk of bleeding, trauma to surrounding structures, and death. Its ability to fully alleviate baffle stenosis even when full lead extraction is not feasible or is associated with significant procedural risk, further demonstrates its expanded role in this patient population. A multidisciplinary approach and great diligence must be employed to avoid potential complications.
Hybrid Fibers for Dispersion Management at 1 μm (2019)

Hybrid fibers with high (60–400 ps/(nm·km)) anomalous dispersion at 1.06 μm were developed. Utilization of such fibers allowed us to fabricate femtosecond all-fiber master oscillator and nonlinear chirped pulses compressor (p p eak 3 kW). © 2019 The Author(s)
Characteristics and outcomes of patients with EGFR-mutation positive non-small-cell lung cancer receiving gefitinib beyond radiological progression (2018)

Some patients may benefit from continuation of gefitinib beyond PD.
Corrosion Testing, Lifetime Prediction, and Corrosion Sensor Development for Coated Aircraft Systems - Emphasis on Environmentally Compliant Practices (2001)

Abstract : The work in this report summarizes a four year, multi-disciplinary effort at North Dakota State University funded as a University Research Initiative grant that was part of a major funding program at AFOSR to address these needs. This study, entitled Testing, Lifetime Prediction, and Corrosion Sensor Development for Coated Aircraft Systems - Emphasis on Environmentally Compliant Practices, had as its goals the following: Improved Testing of Corrosion Protection of Coatings by ENM (electrochemical noise methods) and ElS (electrochemical impedance spectroscopy) Improved Lifetime Prediction of Coated Metal Systems Electrochemistry and SPM Microstructure Measurements at Metal/Polymer Interfaces, Development of New Data Analysis Methods, In-Situ Sensor Development Studies, and Improved Film Transport Property Characterization.
Evidence for interatomic Coulombic decay in XeK-shell-vacancy decay of XeF2 (2012)

Charge production, charge redistribution, and ion fragmentation are explored in the decay of a Xe $K$-shell vacancy in XeF${}_{2}$. Coincidence measurements of all ionic fragments in XeF${}_{2}$ provide evidence that an interatomic-Coulombic-decay-like (ICD-like) process plays a role in the cascade decay. The signature of the ICD-like process is an enhancement of the total number of electrons ejected as compared to the case of atomic Xe. The results indicate that the F atoms participate in the decay cascade within the first few femtoseconds after core-hole formation and that fragmentation begins during the decay process.
Neuropeptide Y (NPY) Y4Receptor Selective Agonists Based on NPY(32−36):  Development of an Anorectic Y4Receptor Selective Agonist with Picomolar Affinity (2006)

We have previously shown [Cys-Trp-Arg-Nva-Arg-Tyr-NH(2)](2), 1, to be a moderately selective neuropeptide Y (NPY) Y(4) receptor agonist. Toward improving the selectivity and potency for Y(4) receptors, we studied the effects of dimerizing H-Trp-Arg-Nva-Arg-Tyr-NH(2) using various diamino-dicarboxylic acids containing either di-, tri-, or tetramethylene spacers. These parallel dimers, 2A, 2B, 3, 4A, and 4B, and the corresponding linear tandem dimer and trimer analogues, 5 and 6, had enhanced selectivity and affinity for Y(4) receptors compared to 1 (Table 1). Substitution of Trp and Nva with Tyr and Leu, respectively, as in 2,7-d/l-diaminosuberic acid derivatized dimer, 7, resulted in a superior Y(4) selective agonist with picomolar affinity. Intraperitoneal (ip) injection of 7 potently inhibited food intake in fasted mice. Moreover, 7 (ip) inhibited the food intake in wild-type mice and not in Y(4)(-/-) knock-out mice, confirming that the actions of 7 on food intake are not due to global effects, but specifically mediated Y(4) receptors.
An Initial Multicenter, Randomized Controlled Trial on the Safety and Efficacy of Acadesine in Patients Undergoing Coronary Artery Bypass Graft Surgery (1994)

Acadesine (5-amino-4-imidazole carboxamide riboside) is a purine nucleoside analog that has been shown in animals to reduce myocardial ischemic injury by selectively increasing the availability of adenosine in ischemic tissues. Because patients undergoing coronary artery bypass graft (CABG) surgery are especially vulnerable to developing myocardial ischemia, we investigated whether perioperative use of this adenosine-regulating drug with potential anti-ischemic properties could modify the incidence and severity of perioperative myocardial ischemia. The goals of this study were to evaluate safety and the effects of acadesine on myocardial ischemia, left ventricular function, and, secondarily, on adverse clinical outcomes (myocardial infarction, heart failure, life-threatening dysrhythmias, and death) in patients undergoing CABG surgery. One hundred sixteen patients were randomized to receive one of three continuous intravenous dosing regimens (placebo [control] or one of two doses of acadesine [high- and low-dose infusion]) in double-blind fashion intraoperatively and in the early postoperative period (total infusion time was 7 h). Multidose cold crystalloid cardioplegia (each containing either acadesine or placebo) was used for myocardial protection. All were monitored for potentially drug-related adverse events and the presence of myocardial ischemia was assessed by continuous Holter electrocardiography (ECG) and transesophageal echocardiography (TEE). All patients received standardized anesthetic, surgical, and hemodynamic management during the intraoperative period. All research data (ECG, TEE, outcome data) were evaluated at the coordinating center (San Francisco) in blinded fashion to ensure that uniform data analysis criteria were employed. The administration of acadesine was safe: mild increases in plasma uric acid (a metabolite of acadesine) occurred only in patients receiving high doses (mean increase 1.6 +/- 0.2 mg/dL) and were without clinical sequelae. Before drug administration in the preoperative period (baseline), the incidence and severity of ECG ischemia did not differ among the three groups (placebo = 18%; low-dose = 14%; high-dose = 14%). During prebypass, the incidence of ECG ischemia was similar in all three groups (0%, 3%, 3%, respectively). The incidence of TEE ischemia was numerically lower in the two acadesine groups (high-dose = 6%, low-dose = 15%) than in the control group (19%), but this was not statistically significant (P = 0.22). During postbypass, the incidence of ECG ischemia was 11% in the high-dose group, 22% in the low-dose group, and 18% in the control group (P = 0.42), and TEE ischemia was similar in incidence in all groups (placebo = 29%; low dose = 27%; high-dose = 24%) (P = 0.86).(ABSTRACT TRUNCATED AT 400 WORDS)
Primer on Detectors and Electronics for Particle Physics Experiments (2019)

This primer is a brief introduction to the technologies used in particle detectors designed for high-energy particle physics experiments. The intended readers are students, especially undergraduates, starting laboratory work.
AlphaHGA; A New Antiviral Substance Against HIV Affecting Capsid Assembly (2005)

Background We have previously shown that the tripeptide glycyl-prolyl-glycine-amide (GPG-amide) inhibits HIV-1 replication in vitro by affecting proper capsid assembly of HIV-1. However, GPG-amide failed in a phase II clinical trial on HIV-infected individuals. In the search for what went wrong we have now found that the tripeptide in itself does not exert the antiviral activity but is metabolised in two steps into the active compound by serum enzymes. The first step is cleavage of GPG-amide into GP and glycineamide (G-amide) by the soluble di-peptidyl peptidase CD26. In the present study we show that G-amide is further metabolised to the actve antiviral substance by an enzyme present in foetel bovine serum but not in human serum.
Negative regulation of Candida glabrata Pdr1 by the deubiquitinase subunit Bre5 occurs in a ubiquitin independent manner (2018)

The primary route for development of azole resistance in the fungal pathogen Candida glabrata is acquisition of a point mutation in the PDR1 gene. This locus encodes a transcription factor that upon mutation drives high level expression of a range of genes including the ATP-binding cassette transporter-encoding gene CDR1. Pdr1 activity is also elevated in cells that lack the mitochondrial genome (ρ<sup>°</sup> cells), with associated high expression of CDR1 driving azole resistance. To gain insight into the mechanisms controlling activity of Pdr1, we expressed a tandem affinity purification (TAP)-tagged form of Pdr1 in both wild-type (ρ<sup>+</sup> ) and ρ<sup>°</sup> cells. Purified proteins were analyzed by multidimensional protein identification technology mass spectrometry identifying a protein called Bre5 as a factor that co-purified with TAP-Pdr1. In Saccharomyces cerevisiae, Bre5 is part of a deubiquitinase complex formed by association with the ubiquitin-specific protease Ubp3. Genetic analyses in C. glabrata revealed that loss of BRE5, but not UBP3, led to an increase in expression of PDR1 and CDR1 at the transcriptional level. These studies support the view that Bre5 acts as a negative regulator of Pdr1 transcriptional activity and behaves as a C. glabrata-specific modulator of azole resistance.
Acceleration of hematopoietic reconstitution with a synthetic cytokine (SC-55494) after radiation-induced bone marrow aplasia (1996)

The synthetic cytokine (Synthokine) SC-55494 is a high-affinity interleukin-3 (IL-3) receptor ligand that stimulates greater in vitro multilineage hematopoietic activity than native IL-3, while inducing no significant increase in inflammatory activity relative to native IL-3. The aim of this study was to investigate the in vivo hematopoietic response of rhesus monkeys receiving Synthokine after radiation-induced marrow aplasia. Administration schedule and dose of Synthokine were evaluated. All animals were total-body irradiated (TBI) with 700 cGy 60Co gamma radiation on day 0. Beginning on day 1, cohorts of animals (n = 5) received Synthokine subcutaneously (SC) twice daily with 25 micrograms/kg/d or 100 micrograms/kg/d for 23 days or 100 micrograms/kg/d for 14 days. Control animals (n = 9) received human serum albumin SC once daily at 15 micrograms/kg/d for 23 days. Complete blood counts were monitored for 60 days postirradiation and the durations of neutropenia (NEUT; absolute neutrophil count [ANC] < 500/microL) and thrombocytopenia (THROM; platelet count < 20,000/microL) were assessed. Synthokine significantly (P < .05) reduced the duration of THROM versus the HSA-treated animals regardless of dose or protocol length. The most striking reduction was obtained in the animals receiving 100 micrograms/kg/d for 23 days (THROM = 3.5 v 12.5 days in HSA control animals). Although the duration of NEUT was not significantly altered, the depth of the nadir was significantly lessened in all animal cohorts treated with Synthokine regardless of dose versus schedule length. Bone marrow progenitor cell cultures indicated a beneficial effect of Synthokine on the recovery of granulocyte-macrophage colony-forming units that was significantly higher at day 24 post-TBI in both cohorts treated at 25 and 100 micrograms/kg/d for 23 days relative to the control animals. Plasma pharmacokinetic parameters were evaluated in both normal and irradiated animals. Pharmacokinetic analysis performed in irradiated animals after 1 week of treatment suggests an effect of repetitive Synthokine schedule and/or TBI on distribution and/or elimination of Synthokine. These data show that the Synthokine, SC55 94, administered therapeutically post-TBI, significantly enhanced platelet recovery and modulated neutrophil nadir and may be clinically useful in the treatment of the myeloablated host.