gebhart/patrepeval huggingface dataset:
Role of current and emerging antithrombotics in thrombosis andcancer (2006)

In the nearly 130 years since Trousseau first described migratory thrombophlebitis in cancer patients, thromboembolism has become a well-established presenting sign and complication of cancer. The coagulation system is activated in cancer and is further amplified by treatment with chemotherapy, radiation or surgery. Hypercoagulation is documented in virtually all cancer types, albeit at different rates, and is the second leading cause of death in cancer patients. The relationship between clotting activation and carcinogenesis supports the view of cancer as a hypercoagulable state and holds implications for the development of thrombosis, enhancement of tumor growth and risk of poor clinical outcomes. Although it is well recognized that cancer can activate the coagulation cascade, it is less well known that activation of the coagulation system may also support tumor progression. Additionally, platelet activation in cancer patients and its impact on tumor progression and metastasis further expand the role of the hemostatic system in malignancy. The problem of thrombosis in patients with metastatic diseases is a serious concern for clinicians. This review explores the mechanisms and clinical implications of coagulation and platelet activation in cancer. The prevention and treatment of venous thromboembolism in cancer will also be discussed by reviewing data from key clinical investigations. Finally, the emerging role of low-molecular-weight heparin as an antineoplastic agent will be explored. Warfarin and unfractionated heparin have been in clinical use for more than 50 years. Both are effective anticoagulants, but their use is associated with a number of impediments, including the need for intensive coagulation monitoring, wide variation in dose-response relationships, multiple drug interactions (in the case of warfarin), and serious immune-mediated thrombocytopenia (in the case of heparin). The introduction of low-molecular weight heparin advanced anticoagulation therapy by enhancing efficacy and eliminating the need for intensive coagulation monitoring. Fondaparinux, the first selective factor Xa inhibitor, represents yet another improvement in anticoagulation therapy. By binding rapidly and strongly to antithrombin, its sole physiologic target in plasma, fondaparinux catalyzes specifically the inhibition of factor Xa, which results in effective and linear dose-dependent inhibition of thrombin generation. Additionally, efficient inhibition of factor Xa activity impairs the activation of tissue factor/factor VIIa complex leading to downregulation of procoagulant state, pro-angiogenesis, and proinflammatory factors induced by tissue factor/factor VIIa. Furthermore, a number of orally active direct antithrombin and anti-factor Xa are in advanced clinical development for various thromboembolic disorders.
Orbitofrontal cortex involvement in chronic analgesic-overuse headache evolving from episodic migraine (2005)

The way in which medication overuse transforms episodic migraine into chronic daily headache is unknown. To search for candidate brain areas involved in this process, we measured glucose metabolism with 18-FDG PET in 16 chronic migraineurs with analgesic overuse before and 3 weeks after medication withdrawal and compared the data with those of a control population (n = 68). Before withdrawal, the bilateral thalamus, orbitofrontal cortex (OFC), anterior cingulate gyrus, insula/ventral striatum and right inferior parietal lobule were hypometabolic, while the cerebellar vermis was hypermetabolic. All dysmetabolic areas recovered to almost normal glucose uptake after withdrawal of analgesics, except the OFC where a further metabolic decrease was found. A subanalysis showed that most of the orbitofrontal hypometabolism was due to eight patients overusing combination analgesics and/or an ergotamine-caffeine preparation. Medication overuse headache is thus associated with reversible metabolic changes in pain processing structures like other chronic pain disorders, but also with persistent orbitofrontal hypofunction. The latter is known to occur in drug dependence and could predispose subgroups of migraineurs to recurrent analgesic overuse.
ChemInform Abstract: Novel Powder‐Processing Methods for Advanced Ceramics (2000)

Abstract ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
Voltage-gated potassium channels regulate calcium-dependent pathways involved in human T lymphocyte activation. (1993)

The role that potassium channels play in human T lymphocyte activation has been investigated by using specific potassium channel probes. Charybdotoxin (ChTX), a blocker of small conductance Ca(2+)-activated potassium channels (PK,Ca) and voltage-gated potassium channels (PK,V) that are present in human T cells, inhibits the activation of these cells. ChTX blocks T cell activation induced by signals (e.g., anti-CD2, anti-CD3, ionomycin) that elicit a rise in intracellular calcium ([Ca2+]i) by preventing the elevation of [Ca2+]i in a dose-dependent manner. However, ChTX has no effect on the activation pathways (e.g., anti-CD28, interleukin 2 [IL-2]) that are independent of a rise in [Ca2+]i. In the former case, both proliferative response and lymphokine production (IL-2 and interferon gamma) are inhibited by ChTX. The inhibitory effect of ChTX can be demonstrated when added simultaneously, or up to 4 h after the addition of the stimulants. Since ChTX inhibits both PK,Ca and PK,V, we investigated which channel is responsible for these immunosuppressive effects with the use of two other peptides, noxiustoxin (NxTX) and margatoxin (MgTX), which are specific for PK,V. These studies demonstrate that, similar to ChTX, both NxTX and MgTX inhibit lymphokine production and the rise in [Ca2+]i. Taken together, these data provide evidence that blockade of PK,V affects the Ca(2+)-dependent pathways involved in T lymphocyte proliferation and lymphokine production by diminishing the rise in [Ca2+]i that occurs upon T cell activation.
Resistance to gefitinib and cross‐resistance to irreversible EGFR‐TKIs mediated by disruption of the Keap1‐Nrf2 pathway in human lung cancer cells (2018)

The development of resistance to epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) occurs by various mechanisms and appears to be almost inevitable, even in patients with lung cancer who initially respond well to EGFR-TKIs. Consequently, considerable efforts have been made to develop more effective EGFR-TKIs. Therefore, an understanding of the mechanisms behind TKI resistance is essential for improving EGFR-TKI therapeutic efficacy in non-small cell lung cancer (NSCLC) patients. In this study, we discovered that overexpression of antioxidant-responsive element (ARE)-containing Nrf2 target genes by increased transactivation of Nrf2 occurred because of an acquired Keap1 mutation in the gefitinib-resistant (GR) NSCLC cell line we established. These GR cells also acquired cross-resistance to the irreversible EGFR-TKIs, afatinib and osimertinib, and showed increased viability, invasiveness, proliferation, and tumorigenicity both in vitro and in vivo. These results were confirmed by the fact that inhibition of Nrf2 activity, either by treatment with brusatol or by inducing expression of exogenously introduced wild-type Keap1, suppressed tumor cell proliferation and tumorigenicity in vitro and in vivo. Our data suggest that disruption of the Keap1-Nrf2 pathway is one of the mechanisms by which EGFR-TKI resistance occurs, a fact that must be considered when treating patients with EGFR-TKI.-Park, S.-H., Kim, J. H., Ko, E., Kim, J.-Y., Park, M.-J., Kim, M. J., Seo, H., Li, S., Lee, J.-Y. Resistance to gefitinib and cross-resistance to irreversible EGFR-TKIs mediated by disruption of the Keap1-Nrf2 pathway in human lung cancer cells.
Dose‐response of acetylcholine receptor channels opened by a flash‐activated agonist in voltage‐clamped rat myoballs. (1986)

Whole-cell or single-channel currents through acetylcholine (ACh) receptor channels were studied in voltage-clamped rat myoballs or in excised membrane patches from myoballs. The recording pipette contained CsCl to suppress outward currents, and tetrodotoxin was used to help suppress Na+ currents. To minimize problems associated with bath applied agonists, myoballs were bathed in a solution containing the inactive (cis) isomer of the photo-isomerizable azobenzene derivative, Bis-Q. Calibrated light flashes of varying intensity were presented to produce concentration jumps of agonist, trans-Bis-Q. The resulting whole-cell current relaxations through ACh channels approach a steady state along an exponential time course, then decline as the newly created agonist diffuses away over the next few seconds. The dose-response relationship was inferred from Hill (double-log) plots for myoballs bathed in 500 nM-cis-Bis-Q at three membrane potentials. At low agonist concentrations (less than 300 nM-trans-Bis-Q), the slope of the Hill plot averaged 1.62 at -150 mV, 1.89 at -100 mV, and 2.05 at +80 mV. These results are consistent with an apparent agonist affinity constant that decreases with membrane depolarization and shifts the responses further down on the dose-response curve. When the myoballs were bathed in higher concentrations of cis-Bis-Q (1.5-20 microM), the slope of the Hill plot was reduced at all membrane potentials, although it was still closer to two at positive potentials. This is expected from the known sigmoid shape of the dose-response relation. The shallow dependence of the Hill slope on agonist concentration suggests the presence of negative cooperativity in the over-all binding of agonist molecules. Following treatment of the membrane with dithiothreitol to reduce disulphide groups, the Hill slope for the reversibly bound agonist, trans-Bis-Q, remained near two. The kinetics of currents at hyperpolarized membrane potentials became complicated at higher agonist concentrations in a manner that was consistent with open-channel block by trans-Bis-Q; the currents showed a slow secondary increase in conductance. Averaged single-channel recordings at higher agonist concentrations resemble macroscopic relaxations under comparable conditions. Furthermore, those recordings also suggested that open channels are blocked by trans-Bis-Q at concentrations greater than 2 microM; the block depends strongly on membrane potential and increases with hyperpolarization. Currents at positive membrane potentials showed no evidence of open-channel block.(ABSTRACT TRUNCATED AT 400 WORDS)
785. Polysaccharides of baker's yeast. Part II. Yeast glucan (1958)

S. Peat, W. J. Whelan and T. E. Edwards, J. Chem. Soc., 1958, 3862 DOI: 10.1039/JR9580003862
Interlaminar fracture behaviour of re-formed bamboo/aluminium sheet laminates (2001)

Sandwich laminates containing re-formed bamboo core and aluminium face sheets were produced using two different types of adhesive: an epoxy and a modified polyethylene. The interlaminar fracture behaviour of the laminates was characterized based on peel and lap-shear tests. It was shown that the laminates bonded with polyethylene had much higher peel and shear strengths than those bonded with epoxy. For the polyethylene-bonded laminates, the major failure mechanisms were a combination of cohesive and interfacial failure, whereas for the epoxy-bonded laminates, the fracture occurred almost exclusively along the aluminium/epoxy interface. There was a significant dependence of the failure mechanism and interlaminar strength on the loading direction relative to the bamboo fibre axis and on whether the aluminium sheets were bonded to the inner or outer bamboo surface.
Role of regulatory T cell in the pathogenesis of inflammatory bowel disease (2016)

Regulatory T (Treg) cells play key roles in various immune responses. For example, Treg cells contribute to the complex pathogenesis of inflammatory bowel disease (IBD), which includes Crohn's disease and ulcerative colitis during onset or development of that disease. Many animal models of IBD have been used to investigate factors such as pathogenic cytokines, pathogenic bacteria, and T-cell functions, including those of Treg cells. In addition, analyses of patients with IBD facilitate our understanding of the precise mechanism of IBD. This review article focuses on the role of Treg cells and outlines the pathogenesis and therapeutic strategies of IBD based on previous reports.
On the mechanism of reductive cleavage of aryl phosphates (1977)

Evidence is presented which strongly indicates that cleavage of aryl phosphates with electron donors may occur either by a one-electron or two-electron pathway. Thus, high concentrations and greater reducing power of the electron donor favor production of arene (C-0 cleavage product) while low concentrations and/or lower reducing power of the electron donor favor production of phenol (P-0 cleavage product) from aryl phosphates. A rationale based on the intermediacy of a trigonal bipyramidal phosphate ester anion radical which either undergoes P-0 (a) scission or is reduced further and undergoes C - 0 (0) scission, is presented. Comparison is also made with the electron transfer chemistry of sulfonate esters.
Decorsin. A potent glycoprotein IIb-IIIa antagonist and platelet aggregation inhibitor from the leech Macrobdella decora. (1990)

The discovery, purification, and characterization of decorsin, a protein isolated from the North American leech Macrobdella decora, are described. Decorsin acts as an antagonist of platelet glycoprotein IIb-IIIa (GPIIb-IIIa), and is a potent inhibitor of platelet aggregation. The protein was purified to apparent homogeneity from crude whole leech extracts by treatment with trifluoroacetic acid followed by GPIIb-IIIa affinity chromatography and C18 reverse-phase high performance liquid chromatography. Decorsin was also isolated from a solution of leech ingestate by treatment with trifluoroacetic acid followed by C18 reverse-phase high performance liquid chromatography. The primary sequence of decorsin indicates that the protein is 39 amino acids long and contains 6 cysteine and 6 proline residues, as well as the sequence Arg-Gly-Asp, (RGD), a proposed recognition site of many adhesion proteins. A molecular mass of 4379 was obtained by fast atom bombardment mass spectrometry and is consistent with the mass calculated from the observed sequence. Evidence for an N-3 isoform, lacking the first 3 amino-terminal residues is also presented. Both decorsin and the N-3 isoform inhibit GP IIb-IIIa binding to immobilized fibrinogen with an IC50 of approximately 1.5 nM. Human platelet aggregation induced by ADP is inhibited by decorsin with an IC50 of approximately 500 nM; complete inhibition was observed at less than or equal to 1 microM. Based on overall sequence homology, decorsin does not belong to the family of GPIIb-IIIa protein antagonists that is found in snake venoms (Dennis, M. S., Henzel, W. J., Pitti, R. M., Lipari, M. T., Napier, M. A., Deisher, T. A., Bunting, S., and Lazarus, R. A. (1990) Proc. Natl. Acad. Sci. U.S.A. 87, 2471-2475); however the carboxyl-terminal RGD-containing region from residues 27 to 38 of decorsin is approximately 60% homologous with the corresponding region of the snake venom proteins, suggesting that high affinity binding of these proteins to GPIIb-IIIa is defined by this epitope.
The Alzheimer's Aβ-peptide is deposited at sites of complement activation in pathologic deposits associated with aging and age-related macular degeneration (2002)

Age-related macular degeneration (AMD) is a leading cause of irreversible vision loss in older individuals worldwide. The disease is characterized by abnormal extracellular deposits, known as drusen, that accumulate along the basal surface of the retinal pigmented epithelium. Although drusen deposition is common in older individuals, large numbers of drusen and/or extensive areas of confluent drusen represent a significant risk factor for AMD. Widespread drusen deposition is associated with retinal pigmented epithelial cell dysfunction and degeneration of the photoreceptor cells of the neural retina. Recent studies have shown that drusen contain a variety of immunomodulatory molecules, suggesting that the process of drusen formation involves local inflammatory events, including activation of the complement cascade. Similar observations in Alzheimer's disease (AD) have lead to the hypothesis that chronic localized inflammation is an important element of AD pathogenesis, with significant neurodegenerative consequences. Accordingly, the amyloid beta (A beta) peptide, a major constituent of neuritic plaques in AD, has been implicated as a primary activator of complement in AD. Here we show that A beta is associated with a substructural vesicular component within drusen. A beta colocalizes with activated complement components in these "amyloid vesicles," thereby identifying them as potential primary sites of complement activation. Thus, A beta deposition could be an important component of the local inflammatory events that contribute to atrophy of the retinal pigmented epithelium, drusen biogenesis, and the pathogenesis of AMD.
Heparan sulfate proteoglycans in experimental models of diabetes: a role for perlecan in diabetes complications (2001)

Proteoglycans are ubiquitous extracellular proteins that serve a variety of functions throughout the organism. Unlike other glycoproteins, proteoglycans are classified based on the structure of the glycosaminoglycan carbohydrate chains, not the core proteins. Perlecan, a member of the heparan sulfate proteoglycan (HSPG) family, has been implicated in many complications of diabetes. Decreased levels of perlecan have been observed in the kidney and in other organs, both in patients with diabetes and in animal models. Perlecan has an important role in the maintenance of the glomerular filtration barrier. Decreased perlecan in the glomerular basement membrane has a central role in the development of diabetic albuminuria. The involvement of this proteoglycan in diabetic complications and the possible mechanisms underlying such a role have been addressed using a variety of models. Due to the importance of nephropathy among diabetic patients most of the studies conducted so far relate to diabetes effects on perlecan in different types of kidney cells. The various diabetic models used have provided information on some of the mechanisms underlying perlecan's role in diabetes as well as on possible factors affecting its regulation. However, many other aspects of perlecan metabolism still await full elucidation. The present review provides a description of the models that have been used to study HSPG and in particular perlecan metabolism in diabetes and some of the factors that have been found to be important in the regulation of perlecan.
Gastric secretion (2014)

Our understanding of the regulation of gastric acid secretion continues to advance. Such knowledge is crucial for the management of acid-peptic disorders and the development of novel medications, such as cholecystokinin-2 receptor antagonists.
Phase II Placebo-Controlled Randomized Discontinuation Trial of Sorafenib in Patients With Metastatic Renal Cell Carcinoma (2006)

Sorafenib has significant disease-stabilizing activity in metastatic renal cell carcinoma and is tolerable with chronic daily therapy.
Kinetics of Viremia and NS1 Antigenemia Are Shaped by Immune Status and Virus Serotype in Adults with Dengue (2011)

Background: Dengue is a major public health problem in tropical and subtropical countries. Exploring the relationships between virological features of infection with patient immune status and outcome may help to identify predictors of disease severity and enable rational therapeutic strategies.
Role of the Seeding Promoter in MoS2 Growth by Chemical Vapor Deposition (2014)

The thinnest semiconductor, molybdenum disulfide (MoS2) monolayer, exhibits promising prospects in the applications of optoelectronics and valleytronics. A uniform and highly crystalline MoS2 monolayer in a large area is highly desirable for both fundamental studies and substantial applications. Here, utilizing various aromatic molecules as seeding promoters, a large-area, highly crystalline, and uniform MoS2 monolayer was achieved with chemical vapor deposition (CVD) at a relatively low growth temperature (650 °C). The dependence of the growth results on the seed concentration and on the use of different seeding promoters is further investigated. It is also found that an optimized concentration of seed molecules is helpful for the nucleation of the MoS2. The newly identified seed molecules can be easily deposited on various substrates and allows the direct growth of monolayer MoS2 on Au, hexagonal boron nitride (h-BN), and graphene to achieve various hybrid structures.
Occupational Therapy Intervention for Residents in a Skilled Nursing Facility: A Focus on Atypical Patients (1997)

The 1990 implementation of the Omnibus Budget Reconciliation Act (OBRA) has expanded opportunities for occupational therapists to treat individuals with non-traditional illnesses. Therapists working in skilled nursing and long term care can benefit from gaining an understanding of the OBRA guidelines and patient's rights, especially regarding restraint reduction. Occupational therapists possess the necessary skills to assess and treat these individuals to help maximize their functioning as well as improve their quality of life (Moon-Sperling & Pinson, 1991). The premise of this article is to inform therapists about various types of ethical and legal intervention with atypical patients in skilled nursing facilities and to introduce therapists to the laws supporting provision of these services. [Article copies available for a fee from The Haworth Document Delivery Service: 1-800-342-9678. E-mail address: getinfo@haworth.com].
An Optically Pumped Magnetometer Working in the Light-Shift Dispersed Mz Mode (2017)

We present an optically pumped magnetometer working in a new operational mode-the light-shift dispersed Mz (LSD-Mz) mode. It is realized combining various features; (1) high power off-resonant optical pumping; (2) Mz configuration, where pumping light and magnetic field of interest are oriented parallel to each other; (3) use of small alkali metal vapor cells of identical properties in integrated array structures, where two such cells are pumped by circularly polarized light of opposite helicity; and (4) subtraction of the Mz signals of these two cells. The LSD-Mz magnetometer's performance depends on the inherent and very complex interplay of input parameters. In order to find the configuration of optimal magnetometer resolution, a sensitivity analysis of the input parameters by means of Latin Hypercube Sampling was carried out. The resulting datasets of the multi-dimensional parameter space exploration were assessed by a subsequent physically reasonable interpretation. Finally, the best shot-noise limited magnetic field resolution was determined within that parameter space. As the result, using two 50 mm3 integrated vapor cells a magnetic ﬁeld resolution below 10 fT/√Hz at Earth's magnetic ﬁeld strength is possible.