gebhart/patrepeval huggingface dataset:
The epidermal growth factor receptor: from mutant oncogene in nonhuman cancers to therapeutic target in human neoplasia. (2001)

Approximately two decades ago, the epidermal growth factor receptor (EGFR) was discovered to be the proto-oncogene of the mutant, constitutively active oncogenic v-erbB tyrosine kinase, which induces avian erythroblastosis. Unlike the mutant oncogene, the EGFR requires activation by binding of ligand to its extracellular (EC) domain, whereas its cellular effects depend on activation of its cytoplasmic tyrosine kinase. The overexpression of EGFR and its ligands in several human carcinomas and their association with accelerated tumor progression provided a rationale for targeting this network with tumor-selective strategies. Two of those antireceptor approaches, both solidly based on the known structure and function of the EGFR, are discussed. The first strategy involves the development of humanized monoclonal antibodies against the nonconserved receptor's EC domain. These antibodies block ligand binding and can induce receptor endocytosis and downregulation. The second approach is the generation of ATP mimetics that compete with ATP for binding to the receptor's kinase pocket, thus disabling signal transduction. Preclinical and early clinical studies already suggest that both of these approaches, either alone or in combination with standard anticancer therapies, will be able to alter the natural history of EGFR-expressing cancers with little to no toxicity to the tumor-bearing host.
Effects of antioxidants on oxidant-induced sister chromatid exchange formation. (1985)

Stimulated human phagocytes produce sister chromatid exchanges in cultured mammalian cells by a mechanism involving oxygen metabolites. Experiments were designed to determine whether antioxidants inhibit this process. Superoxide dismutase, catalase, and hydroxyl radical scavengers (benzoate, mannitol) protected target Chinese hamster ovary cells from phagocyte-induced sister chromatid exchanges, implicating the involvement of hydroxyl radicals in this chromosomal damage. N-acetylcysteine and beta-carotene were also protective. alpha-Tocopherol (greater than 5 microM) protected target cells exposed to phagocytes but not to enzymatically generated oxidants when the vitamin was added just before the source of oxygen radicals, suggesting, as reported by others, that the principal action of tocopherol in this setting was to inhibit the release of oxidants from phagocytes. On the other hand, cultivation of target cells with supplemental tocopherol protected them from the toxic effects of the enzymatic oxidant-producing system, indicating a role for membrane-associated free radicals in the mechanism of sister chromatid exchange induction. Low concentrations of sodium selenite (0.1-1.0 microM) protected the target cells. However, higher concentrations (10 microM) of selenite had no effect on oxidant-induced sister chromatid exchange formation, and 0.1 mM selenite increased the number of exchanges. Sodium selenite concentrations of 0.1 mM also decreased the intracellular glutathione concentration of target cells during an oxidant stress, and reducing target cell glutathione concentrations with buthionine sulfoximine increased their sensitivity to oxygen-related chromosomal damage. Therefore, the potentiation of oxygen radical-induced chromosomal damage observed with high concentrations of selenite may result from a decrease in the thiol antioxidant defense systems within the cell. The findings suggest that the hydroxyl radical has an important role in the production of phagocyte-induced cytogenetic injury, membrane-derived intermediates may be involved, depletion of intracellular glutathione renders cells more susceptible to this injury, and supplementation of target cells with antioxidants can protect them from oxygen radical-generated chromosomal injury.
Advances in recombinant antibody manufacturing (2016)

Since the first use of Chinese hamster ovary (CHO) cells for recombinant protein expression, production processes have steadily improved through numerous advances. In this review, we have highlighted several key milestones that have contributed to the success of CHO cells from the beginning of their use for monoclonal antibody (mAb) expression until today. The main factors influencing the yield of a production process are the time to accumulate a desired amount of biomass, the process duration, and the specific productivity. By comparing maximum cell densities and specific growth rates of various expression systems, we have emphasized the limiting parameters of different cellular systems and comprehensively described scientific approaches and techniques to improve host cell lines. Besides the quantitative evaluation of current systems, the quality-determining properties of a host cell line, namely post-translational modifications, were analyzed and compared to naturally occurring polyclonal immunoglobulin fractions from human plasma. In summary, numerous different expression systems for mAbs are available and also under scientific investigation. However, CHO cells are the most frequently investigated cell lines and remain the workhorse for mAb production until today.
Mobility Prediction Based Resource Reservation for Handoff in Multimedia Wireless Cellular Networks. (2008)

Abstract: In this paper, a mobility predictive based resource (bandwidth) reservation is proposed to provide flexible usage of limited resource in wireless cellular networks. Currently, multimedia communications is urgently expected in wireless networks. That as there is more and more high speed applications that emerge for wireless networks. One of the most important and complicated issues is the Quality of Service (QoS) in next wireless networks. In other words, the problem to maintain the playing continuity of multimedia streams during handoff is hard for solution. Hence, in this paper, the scheme is proposed to provide high accurate prediction of next crossing cell that Mobile Terminal is going to, in order to avoid too early or over reservation resulting in a waste of resources. The amount of bandwidth to be reserved is dynamically adjusted according to the current position and extrapolated direction of Mobile Terminal. An admission control scheme is also considered to further guarantee the QoS of real time traffic. The performance of system is evaluated through discrete event simulation of realistic wireless cellular environment. Simulation results show that the proposed scheme as compared to the existing schemes is efficient to reduce the New Call Blocking Probability and the Handoff Call Dropping Probability of real time traffic. In addition, it is efficient to reduce the number of terminated ongoing calls of non-real time traffic and the cancels reservation that increase the system bandwidth utilization.
To Give or Not to Give? Lessons from the Arginine Paradox (2011)

Arginine is one of the 20 amino acids (AA) found in proteins and synthesized by human cells. However, arginine is also the substrate for a series of reactions leading to the synthesis of other AA and is an obligatory substrate for two enzymes with diverging actions, arginases and nitric oxide synthases (NOS), giving origin to urea and NO, respectively. NO is a very potent vasodilator when produced by endothelial NOS (eNOS). The 'arginine paradox' is the fact that, despite intracellular physiological concentration of arginine being several hundred micromoles per liter, far exceeding the ∼5 μM K(M) of eNOS, the acute provision of exogenous arginine still increases NO production. Clinically, an additional paradox is that the largest controlled study on chronic oral arginine supplementation in patients after myocardial infarction had to be interrupted for excess mortality in treated patients. Expression and activity of arginases, which produce urea and divert arginine from NOS, are positively related to exogenous arginine supplementation. Therefore, the more arginine is introduced, the more it is destroyed, eventually leading to impaired NO production. In this review, conditions influencing the low arginine concentrations found in plasma will be reviewed, revising the paradigm that simple replenishment of what is lacking will always produce beneficial consequences.
Differential diagnosis of adult hemoglobin A, F, and S conditions. A case of G gamma-beta(+)-hereditary persistence of fetal hemoglobin. (1991)

Hemoglobin (Hb) S/beta(+)-thalassemia is a hemoglobinopathy of variable but potentially severe clinical course. The condition is usually confirmed by the presence of a microcytic anemia and elevated levels of Hbs S, F, and A2 by electrophoresis. However, other less common disorders of Hb structure and synthesis may exhibit laboratory findings that mimic Hb S/beta(+)-thalassemia but have a more favorable prognosis. We present a case occurring in a man with clinical and laboratory features that were suggestive of Hb S/beta(+)-thalassemia but with normocythemia. Although nonmicrocytic variants of beta(+)-thalassemia, including concomitant nutritional deficiencies, were considered, high-pressure liquid chromatography revealed nearly all of the patient's fetal Hb to contain only G gamma chains. This pattern is most consistent with the rate but clinically benign condition of Hb S/G gamma-beta(+)-hereditary persistence of fetal Hb, a nondeletional type of hereditary persistence of fetal Hb. We discuss a diagnostic approach to adult Hb A, F, and S conditions, including thalassemias and thalassemia-like syndromes.
Sulfation of Thyroid Hormone and Dopamine during Human Development: Ontogeny of Phenol Sulfotransferases and Arylsulfatase in Liver, Lung, and Brain (2001)

Sulfation is an important mechanism for regulating the biological activity of numerous hormones and neurotransmitters in man. Here we have investigated the ontogeny of sulfotransferases (SULT) and sulfatase (ARS) involved in the metabolism of thyroid hormone and dopamine. SULT1A1 enzyme activity was lower in postnatal liver and lung than in fetal tissues. Hepatic SULT1A3 (dopamine) was expressed at high levels early in development, but decreased substantially in late fetal/early neonatal liver and was essentially absent from the adult liver. In lung, significant SULT1A3 activity was observed in the fetus, but neonatal levels were considerably lower. In brain, the highest activity was observed in the choroid plexus for SULT1A1, with low and widespread activity for both SULT1A1 and SULT1A3 in other brain regions. SULT activity with 3,3´-diiodothyronine (3,3´-T2) as substrate was measured in all tissues and correlated significantly with SULT1A1 activity (4-nitrophenol), suggesting that SULT1A1 is primarily responsible for the sulfation of this iodothyronine. The developmental expression of SULT1A3 and SULT1A1 in liver and brain was confirmed by immunoblot, and immunohistochemistry of developing liver showed substantial expression of these proteins in hemopoietic cells in fetal liver. We also detected low activity for the hydrolysis of 3,3´- T2sulfate by ARS, although there was less distinction between fetal and neonatal samples than with SULT activities. We have therefore shown that the developing fetus has substantial sulfation capacity. Sulfation may therefore play a major role in the homeostasis of hormones and other endogenous compounds as well as in detoxification in the fetus, particularly as other conjugating enzyme systems, such as the UDP-glucuronosyltransferases, are not expressed at significant levels until the neonatal period.
Expeditious Synthesis of Aza sugars by the Double Reductive Amination of Dicarbonyl Sugars (1994)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTExpeditious Synthesis of Aza sugars by the Double Reductive Amination of Dicarbonyl SugarsEllen W. Baxter and Allen B. ReitzCite this: J. Org. Chem. 1994, 59, 11, 3175–3185Publication Date (Print):June 1, 1994Publication History Published online1 May 2002Published inissue 1 June 1994https://pubs.acs.org/doi/10.1021/jo00090a040https://doi.org/10.1021/jo00090a040research-articleACS PublicationsRequest reuse permissionsArticle Views1959Altmetric-Citations154LEARN 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 Get e-Alerts
Certificate of non-coverage for the project of NOCECO with 10 MVA 69/13/2 kb at Brgy, Lalagsan, La Castellana, and Negros Occidental (2007)

The objective of the Additional Financing for Rural Power Project for Philippines is to render better and effective to its consumer members, establishes the 10 MVA power sub-station to primarily solve the problem of power shortage. Negative measures include: loss of vegetation due to land clearing and backfilling, disturbance of wildlife within the influence area due to noise and other construction activities, generation of soil waste, air pollution, increase in the incidence of crime and accidents, erosion from exposed cuts and landslides due to earthmoving and excavation activities, and pollution of nearby water body due to improper disposal of construction wastes. Mitigation measures include: (a) set-up temporary disposal mechanism within the construction area and properly dispose the generated solid wastes; (b) limit land clearing as much as possible; (c) provide temporary fencing to vegetation that will be retained; (d) re-establish or stimulate the habitat of affected wildlife in another suitable area; (e) segregation of recyclable materials; and (f) schedule noise construction activities during day time.
Immunohistochemical detection of HER‐2/neu expression in spontaneous feline mammary tumours (2005)

Mammary gland tumours (MGT) are the third most common tumours in the cat. At least 85% are malignant and metastasis is common. The HER-2/neu protooncogene encodes a 185-kDa transmembrane tyrosine receptor kinase protein. Approximately 25-30% of human MGT demonstrate HER-2/neu protein overexpression in the malignant cells, and overexpression has been associated with an increased metastatic propensity and a decreased prognosis. No reports have been published, to date, investigating the expression of Her-2/neu in cats or cats with spontaneous mammary tumours. Based on the increased percentage of malignant mammary cancers in cats, compared to that in dogs, and the correlation of an increased malignancy and a decreased prognosis with Her-2 overexpression in human mammary cancer, we hypothesized that cats with spontaneous malignant mammary adenocarcinoma overexpress Her-2/neu in the neoplastic mammary epithelial cells. Thirty cats with MGT were assayed for Her-2/neu immunohistochemical expression. The median percentage of cells from feline MGT expressing Her-2/neu by utilizing the Dako polyclonal and CB11 monoclonal antibodies was 85 and 92.5, respectively. Her-2/neu expression intensity grades 2 and 3 consistent with the overexpression by utilizing the Dako polyclonal and CB11 monoclonal antibodies were observed in 90 and 76.7% of cats with MGT, respectively. The level of overexpression concordance across the two antibodies was 70%. The results from this study suggest that Her-2/neu overexpression is common in cats with spontaneous MGT, and therefore appears to represent an excellent model for Her-2/neu-overexpressing human breast cancer.
Electronic properties of InN nanowires (2005)

Indium nitride nanowires (NWs) grown by a catalyst-free, vapor-solid method are shown to be high-purity, single-crystal hexagonal wurtzite and intrinsic n type with uniform diameters that range from 70to150nm and lengths that vary between 3 and 30μm. Single NWs were fabricated into field-effect transistors and the electronic material parameters of the wires were extracted and are found to be identical to comparable bulk InN.
The effects of tea extracts on proinflammatory signaling (2006)

Tea extracts are an efficient, broadly available treatment option for patients suffering from acute radiation-induced skin toxicity. The molecular mechanisms underlying the beneficial effects are complex, and most likely not exclusively dependent on effects of tea polyphenols such as epigallocatechin-gallate.
Reprogramming of CTLs into natural killer–like cells in celiac disease (2006)

Celiac disease is an intestinal inflammatory disorder induced by dietary gluten in genetically susceptible individuals. The mechanisms underlying the massive expansion of interferon gamma-producing intraepithelial cytotoxic T lymphocytes (CTLs) and the destruction of the epithelial cells lining the small intestine of celiac patients have remained elusive. We report massive oligoclonal expansions of intraepithelial CTLs that exhibit a profound genetic reprogramming of natural killer (NK) functions. These CTLs aberrantly expressed cytolytic NK lineage receptors, such as NKG2C, NKp44, and NKp46, which associate with adaptor molecules bearing immunoreceptor tyrosine-based activation motifs and induce ZAP-70 phosphorylation, cytokine secretion, and proliferation independently of T cell receptor signaling. This NK transformation of CTLs may underlie both the self-perpetuating, gluten-independent tissue damage and the uncontrolled CTL expansion leading to malignant lymphomas in severe forms of celiac disease. Because similar changes were detected in a subset of CTLs from cytomegalovirus-seropositive patients, we suggest that a stepwise transformation of CTLs into NK-like cells may underlie immunopathology in various chronic infectious and inflammatory diseases.
Synthesis and structure-activity studies of corticosteroid 17-heterocyclic aromatic esters. 1. 9.alpha.,11.beta.-Dichloro series (1987)

The preparation and topical antiinflammatory potencies of a series of 9 alpha, 11 beta-dichloro-16-methyl corticosteroid 17-heteroaryl carboxylates are described. The 17-acyl group was introduced to the 9 alpha, 11 beta-dichloro 21-acetate by direct acylation with the appropriate heteroaryl carbonyl chloride in the presence of 4-(dimethylamino)pyridine. Alternatively, the 21-functionalized 17-hydroxy delta 9(11) compound was acylated at 17, followed by C-ring chlorination. The most extensively studied heterocyclic acyl functionality was the 2-furoyl, but the 3-furoyl, and 2- and 3-thenoyl derivatives were also investigated. Antiinflammatory potencies were measured in mice by a 5-day modification of the Tonelli croton oil ear assay. The most potent topical antiinflammatory compounds were 17-heteroaryl esters in the 16 alpha-methyl series where the 21-substituent was chloro or fluoro. Thus 2p [21-chloro 17-(2'-furoate)] was 8 times as potent as betamethasone valerate, while 2s [21-fluoro 17-(2'-furoate)], 2r [21-chloro 17-(2'-theonate)], and 2v [6 alpha-fluoro 21-chloro 17-(2'-furoate)] were 3 times as potent as betamethasone valerate.
The nucleation of microcellular thermoplastic foam with additives: Part II: Experimental results and discussion (1987)

Abstract Experiments were performed to validate the model for the nucleation of microcellular foams in amorphous thermoplastic polymers. The polystyrene‐zinc stearate system was chosen as the model system. Other additives such as stearic acid and carbon black were also investigated. Molecular weight and orientation effects were studied. Nitrogen and carbon dioxide were used to produce the microcellular bubbles. Results show that amounts of soluble additives at levels just below their solubility limit and high gas saturation pressures yield the most acceptable foams—ones with a large number of uniform small bubbles. In this region, the bubble number is sensitive to both the gas saturation pressure and the concentration of solutes. Increasing the concentration of soluble additives above the solubility limit has little effect on bubble number and almost eliminates the dependence on saturation pressure. Molecular weight and orientation had no effect on the number of bubbles produced. Similarly, carbon black, which is insoluble in and which bonds well to polystyrene, produced no effect on bubble numbers. The agreement between theoretical predictions and experimental results is reasonably good.
Human interferon omega (omega) binds to the alpha/beta receptor. (1991)

It was proposed that human interferon omega (omega) binds to the interferon alpha/beta receptor but not to the interferon gamma receptor. However, since no studies were performed to provide direct evidence for this hypothesis, we carried out cross-linking experiments and saturation binding assays between a 32P-labeled human interferon-alpha (Hu-IFN-alpha) and unlabeled Hu-IFN-alpha A, -beta, -gamma, and -omega. These assays demonstrated that Hu-IFN-alpha A, -beta, and -omega, but not Hu-IFN-gamma, were able to block binding of 32P-labeled Hu-IFN-alpha A to human cells. These results indicate that Hu-IFN-omega binds to the alpha/beta receptor.
Triggering of Inflammasome by Aggregated α–Synuclein, an Inflammatory Response in Synucleinopathies (2013)

Parkinson's disease (PD) is one of the most common neurodegenerative diseases. It is characterized by the loss of dopaminergic neurons in the substantia nigra pars compacta of the brain. Another feature is represented by the formation in these cells of inclusions called Lewy bodies (LB), principally constituted by fibrillar α-synuclein (αSyn). This protein is considered a key element in the aetiology of a group of neurodegenerative disorders termed synucleinopathies, which include PD, but the cellular and molecular mechanisms involved are not completely clear. It is established that the inflammatory process plays a crucial role in the pathogenesis and/or progression of PD; moreover, it is known that aggregated αSyn, released by neurons, activates microglia cells to produce pro-inflammatory mediators, such as IL-1β. IL-1β is one of the strongest pro-inflammatory cytokines; it is produced as an inactive mediator, and its maturation and activation requires inflammasome activation. In particular, the NLRP3 inflammasome is activated by a wide variety of stimuli, among which are crystallized and particulate material. In this work, we investigated the possibility that IL-1β production, induced by fibrillar αSyn, is involved the inflammasome activation. We demonstrated the competence of monomeric and fibrillar αSyn to induce synthesis of IL-1β, through TLR2 interaction; we found that the secretion of the mature cytokine was a peculiarity of the fibrillated protein. Moreover, we observed that the secretion of IL-1β involves NLRP3 inflammasome activation. The latter relies on the phagocytosis of fibrillar αSyn, followed by increased ROS production and cathepsin B release into the cytosol. Taken together, our data support the notion that fibrillar αSyn, likely released by neuronal degeneration, acts as an endogenous trigger inducing a strong inflammatory response in PD.