gebhart/patrepeval huggingface dataset:
Mitoxantrone in combination with an inhibitor of DNA‐dependent protein kinase: a potential therapy for high risk B‐cell chronic lymphocytic leukaemia (2010)

Defects in the DNA damage response pathway [e.g. del(17p)] are associated with drug-resistant B-cell chronic lymphocytic leukaemia (CLL). We previously demonstrated that over-expression of DNA-dependent protein kinase (DNA-PK) correlates with chemo-resistance and that inhibition of DNA-PK sensitizes CLL cells to chemotherapeutics. Here, we investigated expression of DNA-PK and other proteins that impact on drug resistance, and evaluated the effects of a DNA-PK inhibitor (NU7441) on mitoxantrone-induced cytotoxicity in CLL cells. NU7441 sensitized cells from 42/49 CLL samples to mitoxantrone, with sensitization ranging from 2- to 200-fold Co-culture of CLL cells in conditioned stromal medium increased chemoresistance but did not reduce sensitization by NU7441. Mitoxantrone treatment induced γH2AX foci and NU7441 increased their longevity (24 h). NU7441 prevented mitoxantrone-induced autophosphorylation of the DNA-PK catalytic subunit (DNA-PKcs) at Ser 2056, confirming that DNA-PK participates in repair of mitoxantrone-induced DNA damage. del(17p) cases were more resistant to mitoxantrone than del(13q) cases, but were resensitized (7-16 fold) by co-incubation with NU7441. Expression of DNA-PKcs, Ku80, P-glycoprotein and topoisomerase IIβ were significantly higher in del(17p) cases. PRKDC mRNA levels correlated with DNA-PKcs protein expression, which predicted shorter survival. These data confirm the potential of DNA-PK as a therapeutic target in poor prognosis CLL.
Inhibition of hepatitis C virus infection by anti‐claudin‐1 antibodies is mediated by neutralization of E2–CD81–Claudin‐1 associations† (2009)

These results further define the function of CLDN1 in the HCV entry process and highlight new antiviral strategies targeting E2-CD81-CLDN1 interactions.
Recurrent Hemolytic Uremic Syndrome Secondary to Escherichia coli 0157:H7 Infection (1993)

Recurrence of the hemolytic uremic syndrome (HUS) is unusual; most recurrent cases are atypical,1 that is, not preceded by the customary diarrheal prodrome. We report a case in which results of serologic tests and stool culture provided evidence that both the initial episode and the recurrence followed diarrhea caused by Escherichia coli 0157:H7. This child was previously described because of severe ocular involvement that followed the initial HUS episode.2) CASE REPORT A 16-month-old white boy from rural Idaho was in good health until about 1 week before admission, when a respiratory tract infection complicated by otitis media developed. He was treated with amoxicillin.
Synthesis and Pharmacological Evaluation of 1,2,3,4-Tetrahydro-.BETA.-carboline Derivatives. (1995)

A series of 1,2,3,4-tetrahydro-beta-carbolines has been synthesized and evaluated for cerebral protecting effects against lipid peroxidation and potassium cyanide intoxication in mice. Most of the compounds synthesized had potent effects against lipid peroxidation. Among them, 1-(3,5-dimethoxyphenyl)-2-propyl-1,2,3,4-tetrahydro-beta-carboline (22) was found to have a combination of potent effects against both lipid peroxidation and potassium cyanide intoxication. Structure-activity relationships are discussed.
Evaluation and Management of Bilateral Vocal Cord Immobility (1999)

Bilateral vocal cord immobility can be life threatening for some patients. Others, who have an open glottic chink, may have a breathy dysphonia, intermittent dyspnea, and stridor. These signs and symptoms may also be found in a number of other conditions that cause weakness or paradoxical motion of the vocal cords that mimics paralysis. These other conditions include central nervous system diseases, neuromuscular disorders, laryngospasm, and psychogenic disorders. In addition, patients with cricoarytenoid joint immobility or interarytenoid scar can also have similar symptoms at presentation. It is critical to consider the differential diagnosis of an assumed bilateral vocal cord paralysis and understand the management of paradoxical movement, weakness, joint fixation, interarytenoid scar, laryngospasm, and psychogenic disorders. The treatment for bilateral immobility should proceed only after a thorough evaluation, which might include electromyography and/or examination during general anesthesia under dense anesthetic paralysis. Reconstructive procedures are the treatments of choice, and destructive procedures should be chosen only as a last resort.
Rapid and Tunable Control of Protein Stability in Caenorhabditis elegans Using a Small Molecule (2013)

Destabilizing domains are conditionally unstable protein domains that can be fused to a protein of interest resulting in degradation of the fusion protein in the absence of stabilizing ligand. These engineered protein domains enable rapid, reversible and dose-dependent control of protein expression levels in cultured cells and in vivo. To broaden the scope of this technology, we have engineered new destabilizing domains that perform well at temperatures of 20-25°C. This raises the possibility that our technology could be adapted for use at any temperature. We further show that these new destabilizing domains can be used to regulate protein concentrations in C. elegans. These data reinforce that DD can function in virtually any organism and temperature.
Expression of constitutively activated EGFRvlll in non‐small cell lung cancer (2003)

The epidermal growth factor receptor (EGFR) variant type III (variously called EGFRvIII, de2-7 EGFR or deltaEGFR) has an in-frame deletion of the extracellular domain and is found in numerous types of human tumors. Since EGFRvIII has been reported to be tumor-specific and has oncogenic potential, it is being investigated as a potential therapeutic target. Because the cell-specific expression of EGFRvIII in lung has not been well documented, we examined the expression of EGFRvIII in 76 non-small cell lung cancers (NSCLCs) and 10 non-neoplastic lung tissues by immunohistochemistry using a new monoclonal antibody specific for this variant receptor. We found a higher incidence (30 of 76, 39%) of enhanced EGFRvIII expression in NSCLC than previously described. Interestingly, the presence of EGFRvIII was also observed in several normal tissue components of lung (e.g., normal bronchial epithelium). Given the high prevalence of EGFRvIII in NSCLC, a newly developed phospho-specific (activated) EGFR antibody was employed for immunohistochemical analysis that permitted visualization of activated EGFR and/or EGFRvIII in tumors. This study presents evidence, for the first time, that EGFRvIII expressed in human tumors is phosphorylated and hence activated. Our results suggest that the sustained activation of EGFRvIII is implicated in the pathogenesis of NSCLC and thus EGFRvIII is a potential therapeutic target in this challenging disease.
Variable-Frequency Fluidic Oscillator Driven by a Piezoelectric Bender (2009)

§This paper describes a new actuator for flow control applications ‐ the piezo-fluidic oscillator. The actuator is a fluidic device based on wall-attachment of a fluid jet, and modulated by piezoelectric devices. The piezo-fluidic oscillator successfully decouples the operating frequency from the flow characteristics of the device. The frequency is specified by an input electrical signal that is independent of pressure, making this actuator ideal for closed-loop control applications. The oscillator exhibits high bandwidth (up to 1.2 kHz), modulation rates up to 100%, and a velocity range reaching sonic conditions. Furthermore, the bi-stable actuator may be operated in a steady state, with momentum flux in one of two desired directions. The piezo-fluidic oscillator may be used in flow control applications where synthetic jets cannot provide enough momentum for control authority. The actuator can also be used as an alternative to traditional aircraft control surfaces while operating in the steady bi-directional mode. This paper details the design and characterization of the piezo-fluidic oscillator. The dynamic response characteristics are evaluated with flow visualization and hot film probe measurements on the output. **
Endothelial Progenitor Cells Restore Renal Function in Chronic Experimental Renovascular Disease (2009)

The present study shows that a single intrarenal infusion of autologous EPCs preserved microvascular architecture and function and decreased microvascular remodeling in experimental chronic RAS. It is likely that restoration of the angiogenic cascade by autologous EPCs involved not only generation of new vessels but also acceleration of their maturation and stabilization. This contributed to preserving the blood supply, hemodynamics, and function of the RAS kidney, supporting EPCs as a promising therapeutic intervention for preserving the kidney in renovascular disease.
X‐ray scatter in megavoltage transmission radiography: Physical characteristics and influence on image quality (1994)

The physical characteristics of x rays scattered by the patient and reaching the imaging detector, as well as their effect on verification (portal) image quality, were investigated for megavoltage (0.1-20 MeV) x-ray beams. Monte Carlo calculations and experimental measurements were used to characterize how the scatter and primary fluences at the detector plane were influenced by scattering geometry and the energy spectrum of the incident beam. The calculated scatter fluences were differentiated according to photon energy and scattering process. Scatter fractions were measured on a medical linear accelerator (Clinac 2100c, 6 MV) for a typical imaging geometry using an ionization chamber and a silicon diode. After correction for the energy dependence of the chamber and diode, the scatter fractions generated by the Monte Carlo simulations were found to be in excellent agreement with the measured results. In order to estimate the effect of scatter on image quality, the scatter and primary signals (i.e., energy deposited) produced in five different types of portal imaging detectors (lead plate/film, storage phosphor alone, lead plate/storage phosphor, compton recoil-electron detector, and a copper plate/Gd2O2S phosphor) were calculated. The results show that, for a specified geometry, the scatter fraction can vary by an order of magnitude, depending on the sensitivity of the imaging detector to low-energy (< 1 MeV) scattered radiation. For a common portal imaging detector (copper plate/Gd2O2S phosphor), the scattered radiation (i) reduced contrast by much as 50% for a fixed display-contrast system, and (ii) decreased the differential-signal-to-noise ratio (DSNR) by 10%-20% for a quantum-noise-limited portal imaging system. For currently available TV-camera-based portal imaging systems, which have variable display contrast, the reduction in DSNR depends on the light collection efficiency and the noise characteristics of the TV camera. Overall, these results show that scattered radiation can reduce contrast significantly in portal films while deteriorating image quality only moderately in on-line systems.
Immunotherapeutic elimination of syngeneic tumors in vivo by cytotoxic T lymphocytes generated in vitro from lymphocytes from the draining lymph nodes of tumor‐bearing mice (1991)

The draining lymph nodes (LN) of mice injected with viable syngeneic tumor cells contain populations of lymphoid cells which are capable of generating functional cytotoxic T lymphocytes (CTL) during an in vitro culture period without the need of secondary stimulation with irradiated tumor cells or addition of exogenous cytokines. Intravenous injection of as few as 2.5 x 10(6) tumor-reactive effector cells generated using this protocol effectively eliminated challenges of tumor cells at distal skin sites, whereas injection of cultured control lymphoid cells was ineffective at rejecting tumor challenges. The anti-tumor CTL generated from the draining LN of C57BL10 mice immunized with viable syngeneic tumor cells were found to be specific for the tumor used for immunization both in vitro and in vivo. Phenotypic analysis of the cells responsible for tumor elimination (both in vitro. and in vivo) demonstrated the anti-tumor effector cells to be CD4-CD8+ asialo GM1+NK1.1-. Finally, anti-tumor CTL generated during the short in vitro culture period were able to effectively reject pre-existing tumors in vivo in a systemic fashion. These data indicate that the generation of tumor-reactive CTL from the lymphoid cells contained in the LN draining the site of a tumor may provide a valuable source of effector cells which can be used in the immunotherapeutic treatment of cancer.
Longitudinal determination of total body creatine pool size and skeletal muscle mass in rats by D 3 ‐creatine dilution (2013)

We recently described a new method to determine total body creatine pool size and skeletal muscle mass based on dilution of an oral dose of D 3 ‐creatine in urinary creatinine. Enrichment of D 3 ‐ creatinine was measured by isotope ratio mass spectrometry. Here we adapt the method to LC‐MS/MS, and investigate the potential for repeated application over time. Rats were given an oral tracer dose of D 3 ‐creatine (1.0 mg/kg body weight) at 10 weeks of age. Urine D 3 ‐creatinine enrichment was determined 72 hr after tracer administration and creatine pool size was calculated. Lean body mass (LBM) measured by quantitative magnetic resonance correlated with creatine pool size ( r = 0.92, P = 0.0002). The rate constant for decline in urinary D 3 ‐creatinine enrichment was slow and linear (2.73 ± 0.06 %/day). Subtracting background urinary D 3 ‐creatinine enrichment from the enrichment following a second dose of D 3 ‐creatine at 17 weeks permitted repeat calculations of creatine pool size. As at 10 weeks, 17 week LBM correlated with creatine pool size ( r = 0.98, P &lt; 0.0001). In addition, the change in creatine pool size was correlated with the change in LBM during the 7 weeks of somatic growth between measurements ( r = 0.96, P &lt; 0.0001). Thus, the LC‐MS/MS‐based D 3 ‐creatine dilution method can be applied repeatedly to measure skeletal muscle mass change in longitudinal studies. These studies were funded by GlaxoSmithKline.
Molecular Epidemiology of Adenovirus Type 35 Infections in Immunocompromised Hosts (1987)

Adenovirus type 35 (Ad35) is an uncommon group B adenovirus that has been isolated nearly exclusively from immunosuppressed hosts. In our series of 46 patients with Ad35 isolates, 36 had AIDS or AIDS-related complex (ARC), seven patients were immunocompromised because of other diseases, and three patients were “normal.” Neither patients with AIDS or ARC made specific antibody to Ad35, whereas antibody was present in one immunocompetent host and one renal transplant recipient. All isolates were identified as Ad35 by using genomic analysis with the restriction endonuclease SmaI, but many viruses exhibited other group B hemagglutinins, a property of the fiber protein. Further analysis of DNAs from 40 of these isolates, mapped by using the enzymes BamHI, HpaI, and PstI, revealed a total of 14 genomic variants from the Ad35 prototype. Seven of these genomic types, with either Ad? or Adll hemagglutinin, had corresponding restriction site differences within the fiber gene, a result consistent with recombination events with other group B adenoviruses.
The Effect of Hydrostatic Pressure on Three-Dimensional Chondroinduction of Human Adipose–Derived Stem Cells (2009)

Our results demonstrate chondrogenic differentiation of ASCs in a three-dimensional collagen scaffolds with treatment of a cyclic HP. Cyclic HP was effective in enhancing accumulation of extracellular matrix and expression of genes indicative of chondrogenic differentiation.
A quantitative study of the tissue reaction and its relationship to debris production from a joint implant. (1990)

An attempt has been made to refine the quantitative evaluation of the tissue response to a prosthesis using the goat hip as an experimental model. Total joint replacement was performed in six goats; in three the cup was made of conventional ultrahigh molecular weight polyethylene and in three a new silane cross-linked ultrahigh molecular weight polyethylene was used. The pseudocapsule of the hips was examined histologically at 15, 19 and 24 months following surgery. Small and large polyethylene debris were visualized using semi-crossed polars and were counted. Giant cells were counted after staining with toluidine blue as were macrophages which were identified by dense staining after the acid phosphatase reaction. The amount of small birefringent debris was closely related to the number of macrophages in the pseudocapsule. This method of assessment may be helpful in comparing the tissue reaction of different polymers.
Intraoperative coronary angioscopy: development of practical techniques. (1990)

Techniques and equipment for intraoperative coronary angioscopy were studied in the coronary arteries and cardiac veins of excised and in vivo animal hearts. These studies then allowed development of safe, practical techniques for human clinical use. In coronary artery bypass operations, multichannel angioscopes of 2.3 to 2.8 mm diameter gave the best results for examinations of the bypass vein and anastomosis, whereas smaller optical fibers of 1 mm diameter were required for inspection of the native coronary artery. Abnormalities were detected in 11 of 48 (23%) coronary bypass anastomoses, and significant discrepancy in the degree of coronary artery stenosis as compared with the preoperative angiogram was revealed in 2 patients. The authors concluded that a new design of ultrafine, multichannel angioscope would be more suitable to the different requirements for inspection of both the anastomosis and the recipient artery.
Ibrutinib enhances the antitumor immune response induced by intratumoral injection of a TLR9 ligand in mouse lymphoma (2015)

We have designed a novel therapeutic approach for lymphoma that combines targeted kinase inhibition with in situ vaccination. Intratumoral injection of an unmethylated cytosine guanine dinucleotide (CpG)-enriched oligodeoxynucleotide, an agonist for the toll-like receptor 9 (TLR9), induces the activation of natural killer cells, macrophages, and antigen presenting cells that control tumor growth at the local site. Ibrutinib, an irreversible inhibitor of Bruton's tyrosine kinase, a key enzyme in the signaling pathway downstream of B-cell receptor, is an effective treatment against many types of B-cell lymphomas. The combination of intratumoral injection of CpG with systemic treatment by ibrutinib resulted in eradication of the tumors not only in the injected site, but also at distant sites. Surprisingly, this combinatorial antitumor effect required an intact T-cell immune system since it did not occur in nude, severe combined immunodeficiency, or T-cell depleted mice. Moreover, T cells from animals treated with intratumoral CpG and ibrutinib prevented the outgrowth of newly injected tumors. This result suggests that ibrutinib can induce immunogenic cell death of lymphoma cells and that concomitant stimulation of antigen-presenting cells in the tumor microenvironment by toll-like receptor ligands can lead to a powerful systemic antitumor immune response.
Molecular and genetic analysis of URA5 transformants of Cryptococcus neoformans (1992)

Cryptococcus neoformans var. neoformans ura5 mutants were transformed with linearized or circular plasmids containing the C. neoformans orotidine monophosphate pyrophosphorylase gene. Following electroporation, randomly isolated transformants were analyzed for the mitotic and meiotic stability of uracil prototrophy. All stable transformants tested showed nonspecific ectopic integration. Uracil prototrophy in these transformants was stable through meiosis. Some of the stable transformants showed integration of both URA5 and vector sequences, while others lacked any vector sequences. Unstable transformants exhibited the presence of an autonomously replicating plasmid which had undergone significant sequence rearrangement. The autonomously replicating plasmid in the transformants was observed to be the same size or smaller than the transforming plasmid, was maintained in a linear form, and had acquired a genomic sequence(s) with homology to a sequence(s) on all the chromosomes. The conservation of a 300-bp sequence at the 5' end of the URA5 gene was observed in all the rearranged plasmids. These results suggest mechanisms of plasmid maintenance in C. neoformans that are different from those reported for other yeasts. The ura5 mutant was significantly less virulent than the wild type. The transformants did not recover virulence regardless of prototrophic stability.
Cryopreservation of Hematopoietic Stem Cells: Emerging Science, Technology and Issues (2007)

Cell therapies based on hematopoietic stem cells (HSCs)have become the standard of care for a variety of diseases,and the number of patients and disorders being treated using HSCs continues to grow. Effective methods of preservation are critical for the clinical implementation of HSC-based therapies. Preservation permits the completion of safety and quality control testing, transportation to the site of use and coordination of the therapy with patient care regimes. This review discusses advances in the basic science of preservation that will permit us to improve preservation protocols for HSCs and other cell types. Recent advances in preservation technology can also be used to reduce cell losses during cell processing for preservation and improve the safety of HSCs used therapeutically. Finally, the growth of HSC therapy worldwide has created interest in alternative methods of preservation. This review also includes a discussion of different methods of freezing and storage. Improved methods for preserving HSCs will improve not only therapies based on these cells but can improve and speed development of preservation protocols for other cell types used therapeutically.
Um estudo das dissertações do programa de mestrado em educação da Universidade Estadual de Londrina (1995-2006) (2012)

Este trabalho realiza um estudo das dissertações do Mestrado em Educação da Universidade Estadual de Londrina, entre 1995 e 2006. Seu objetivo é fornecer subsídios a outros pesquisadores que possam se interessar pelo tema e encontrar material disponível para novos estudos, analisar a organização do Programa para detectar seu envolvimento social com a cidade de Londrina e seu entorno regional, especificamente, o norte do Paraná. Seu caráter é censitário-descritivo. O mapeamento dessas produções permite concluir que são significativas suas contribuições ao processo de construção de políticas educacionais no âmbito local, mas principalmente na formação e capacitação de docentes para o ensino superior na região, bem como atender também o professorado das redes municipal e estadual. Proporciona também uma formação crítica de seus discentes para atuar na sociedade e na produção e transmissão do conhecimento como também para a construção coletiva da universidade.