gebhart/patrepeval huggingface dataset:
Tumor Radiosensitization by Monomethyl Auristatin E: Mechanism of Action and Targeted Delivery (2015)

Intrinsic tumor resistance to radiotherapy limits the efficacy of ionizing radiation (IR). Sensitizing cancer cells specifically to IR would improve tumor control and decrease normal tissue toxicity. The development of tumor-targeting technologies allows for developing potent radiosensitizing drugs. We hypothesized that the anti-tubulin agent monomethyl auristatin E (MMAE), a component of a clinically approved antibody-directed conjugate, could function as a potent radiosensitizer and be selectively delivered to tumors using an activatable cell-penetrating peptide targeting matrix metalloproteinases and RGD-binding integrins (ACPP-cRGD-MMAE). We evaluated the ability of MMAE to radiosensitize both established cancer cells and a low-passage cultured human pancreatic tumor cell line using clonogenic and DNA damage assays. MMAE sensitized colorectal and pancreatic cancer cells to IR in a schedule- and dose-dependent manner, correlating with mitotic arrest. Radiosensitization was evidenced by decreased clonogenic survival and increased DNA double-strand breaks in irradiated cells treated with MMAE. MMAE in combination with IR resulted in increased DNA damage signaling and activation of CHK1. To test a therapeutic strategy of MMAE and IR, PANC-1 or HCT-116 murine tumor xenografts were treated with nontargeted free MMAE or tumor-targeted MMAE (ACPP-cRGD-MMAE). While free MMAE in combination with IR resulted in tumor growth delay, tumor-targeted ACPP-cRGD-MMAE with IR produced a more robust and significantly prolonged tumor regression in xenograft models. Our studies identify MMAE as a potent radiosensitizer. Importantly, MMAE radiosensitization can be localized to tumors by targeted activatable cell-penetrating peptides.
Pressure‐Assisted Capillary Force Lithography (2004)

Pressure‐assisted capillary force lithography is introduced using a permeable fluoropolymer material as a mold. Slight pressing (∼ 2–3 bar), when combined with a newly developed experimental set‐up, ensures conformal contact between the stiff fluoropolymer mold and the substrate. The stiff nature of the mold material makes it possible to pattern sub‐100 nm features (see Figure and cover).
The Insulin-Like Growth Factor-I Receptor (1994)

The nonclassical binding kinetics of IGF-I and insulin to their respective receptors, suggestive of negative cooperativity, can be readily explained by our recently proposed novel binding mechanism whereby the bivalent ligand bridges the two receptor alpha-subunits alternatively at opposite sites in a symmetrical receptor structure. The bivalent binding mechanism also explains bell-shaped bioactivity curves. The possible role of different binding modes versus differences in downstream signaling by insulin and IGF-I in producing specific mitogenic or metabolic responses is discussed.
Insights into Molecular Classifications of Triple-Negative Breast Cancer: Improving Patient Selection for Treatment (2019)

Triple-negative breast cancer (TNBC) remains the most challenging breast cancer subtype to treat. To date, therapies directed to specific molecular targets have rarely achieved clinically meaningful improvements in outcomes of patients with TNBC, and chemotherapy remains the standard of care. Here, we seek to review the most recent efforts to classify TNBC based on the comprehensive profiling of tumors for cellular composition and molecular features. Technologic advances allow for tumor characterization at ever-increasing depth, generating data that, if integrated with clinical-pathologic features, may help improve risk stratification of patients, guide treatment decisions and surveillance, and help identify new targets for drug development. SIGNIFICANCE: TNBC is characterized by higher rates of relapse, greater metastatic potential, and shorter overall survival compared with other major breast cancer subtypes. The identification of biomarkers that can help guide treatment decisions in TNBC remains a clinically unmet need. Understanding the mechanisms that drive resistance is key to the design of novel therapeutic strategies to help prevent the development of metastatic disease and, ultimately, to improve survival in this patient population.
Protein D, a putative immunoglobulin D-binding protein produced by Haemophilus influenzae, is glycerophosphodiester phosphodiesterase (1993)

Protein D of Haemophilus influenzae is 67% identical to the periplasmic glycerophosphodiester phosphodiesterase of Escherichia coli. Extracts prepared from E. coli expressing recombinant protein D had an 8- to 22-fold-higher specific activity of glycerophosphodiester phosphodiesterase compared with extracts of E. coli not expressing protein D.
Weight Loss Reduces the Risk for Symptomatic Knee Osteoarthritis in Women (1992)

Objective: To evaluate the effect of weight loss in preventing symptomatic knee osteoarthritis in women. Design: Cohort analytic study. Setting: The Framingham Study, based on a sample of a defined population. Patients: Women who participated in the Framingham Knee Osteoarthritis Study (1983 to 1985): Sixty-four out of 796 women studied had recent-onset symptomatic knee osteoarthritis (knee symptoms plus radiographically confirmed osteoarthritis) were compared with women without disease. Measurements: Recalled date of symptom onset was used as the incident date of disease. Historical weight was defined as baseline body mass index up to 12 years before symptom onset. Change in body mass index was assessed at several intervals before the current examination. Odds ratios assessing the association between weight change and knee osteoarthritis were adjusted for age, baseline body mass index, history of previous knee injury, habitual physical activity level, occupational physical labor, smoking status, and attained education. Results: Weight change significantly affected the risk for the development of knee osteoarthritis. For example, a decrease in body mass index of 2 units or more (weight loss, approximately 5.1 kg) over the 10 years before the current examination decreased the odds for developing osteoarthritis by over 50% (odds ratio, 0.46; 95% Cl, 0.24 to 0.86; P = 0.02). Among those women with a high risk for osteoarthritis due to elevated baseline body mass index (> 25), weight loss also decreased the risk (for 2 units of body mass index, odds ratio, 0.41 ; P = 0.02). Weight gain was associated with a slightly increased risk for osteoarthritis, which was not statistically significant. Conclusion: Weight loss reduces the risk for symptomatic knee osteoarthritis in women.
Differential nociceptive responses in mice lacking the α1B subunit of N-type Ca2+ channels (2001)

The role of N-type Ca(2+) channels in nociceptive transmission was examined in genetically engineered mice lacking the alpha(1B) subunit of N-type channels and in their heterozygote and wild-type littermates. In alpha(1B)-deficient mice, N-type channel activities in dorsal root ganglion neurons and spinal synaptoneurosomes were eliminated without compensation by other types of voltage-dependent Ca(2+) channels. The alpha(1B)-deficient mice showed a diminution in the phase 2 nociceptive responses more extensively than in the phase 1 nociceptive responses of the formalin test. The alpha(1B)-deficient mice exhibited significantly increased thermal nociceptive thresholds in the hot plate test, but failed to increase mechanical nociceptive thresholds in the tail pinch test. These results suggest a crucial role of N-type channels in nociceptive transmission, especially for persistent pain like phase 2 of the formalin test and for nociception induced by thermal stimuli.
Nonequilibrium Capillary Electrophoresis of Equilibrium Mixtures: A Universal Tool for Development of Aptamers (2005)

Aptamers are DNA (or RNA) ligands selected from large libraries of random DNA sequences and capable of binding different classes of targets with high affinity and selectivity. Both the chances for the aptamer to be selected and the quality of the selected aptamer are largely dependent on the method of selection. Here we introduce selection of aptamers by nonequilibrium capillary electrophoresis of equilibrium mixtures (NECEEM). The new method has a number of advantages over conventional approaches. First, NECEEM-based selection has exceptionally high efficiency, which allows aptamer development with fewer rounds of selection. Second, NECEEM can be equally used for selecting aptamers and finding their binding parameters. Finally, due to its comprehensive kinetic capabilities, the new method can potentially facilitate selection of aptamers with predefined K(d), k(off), and k(on) of the aptamer-target interaction. In this proof-of-principle work, we describe the theoretical bases of the method and demonstrate its application to a one-step selection of DNA aptamers with nanomolar affinity for protein farnesyltransferase.
Versatile ultrathin nanoporous silicon nitride membranes (2009)

Single- and multiple-nanopore membranes are both highly interesting for biosensing and separation processes, as well as their ability to mimic biological membranes. The density of pores, their shape, and their surface chemistry are the key factors that determine membrane transport and separation capabilities. Here, we report silicon nitride (SiN) membranes with fully controlled porosity, pore geometry, and pore surface chemistry. An ultrathin freestanding SiN platform is described with conical or double-conical nanopores of diameters as small as several nanometers, prepared by the track-etching technique. This technique allows the membrane porosity to be tuned from one to billions of pores per square centimeter. We demonstrate the separation capabilities of these membranes by discrimination of dye and protein molecules based on their charge and size. This separation process is based on an electrostatic mechanism and operates in physiological electrolyte conditions. As we have also shown, the separation capabilities can be tuned by chemically modifying the pore walls. Compared with typical membranes with cylindrical pores, the conical and double-conical pores reported here allow for higher fluxes, a critical advantage in separation applications. In addition, the conical pore shape results in a shorter effective length, which gives advantages for single biomolecule detection applications such as nanopore-based DNA analysis.
Handbook Of Media for Clinical Microbiology (2006)

While evolving molecular diagnostic methods are being heralded for the role they will play in improving our ability to cultivate and identify bacteria, fungi, and viruses, the reality is that those new methods are still beyond the technical and financial reach of most clinical laboratories. Most clinical microbiology laboratories still rely upon cu
Human Adrenomedullin Up-regulates Interleukin-13 Receptor α2 Chain in Prostate Cancer In vitro and In vivo : A Novel Approach to Sensitize Prostate Cancer to Anticancer Therapy (2008)

Interleukin-13 (IL-13) receptor alpha2 (IL-13Ralpha2), a high-affinity IL-13 binding subunit and a tumor antigen, is amplified in a variety of human tumor cell lines and tumors in vivo. By cDNA microarray, we have shown that gene transfer of human and rat adrenomedullin (AM) up-regulates IL-13Ralpha2 in a human prostate tumor cell line. Here, we show that IL-13Ralpha2 mRNA and protein are also up-regulated in PC-3 prostate tumor cells by recombinant AM (rAM) and human synthetic AM peptide in a dose-dependent manner in vitro and in vivo in mouse prostate tumor model. The 8- to 10-fold up-regulation of IL-13Ralpha2 by rAM or AM peptide in prostate tumor cells in vitro and in vivo increased their sensitivity to IL-13PE cytotoxin consisting of IL-13 and a truncated form of Pseudomonas exotoxin. Immunodeficient mice with established prostate tumors transfected with AM or treated with AM peptide showed reduction in tumor size by intratumoral administration of IL-13PE in a dose-dependent manner. At the highest dose (three 100 mug/kg/d every alternate day), >70% reduction of tumor size was observed compared with controls (P <or= 0.01). These results indicate that two completely unrelated hormones (AM and IL-13) are closely related to each other and that we have identified a novel role of AM in sensitizing certain types of prostate tumors to IL-13R-directed therapeutic agent.
Many-objective reconfiguration of operational satellite constellations with the Large-Cluster Epsilon Non-dominated Sorting Genetic Algorithm-II (2009)

A general framework for the reconfiguration of satellite constellations is developed for the operational scenario when a loss of capacity has occurred and the future configuration must be constructed from the remaining assets. A multi-objective evolutionary algorithm, epsiv-NSGA-2, adapted for use on large heterogeneous clusters, facilitated the exploration of a six-dimensional fitness landscape for several loss scenarios involving the Global Positioning System Constellation. An a posteriori decision support process was used to characterize and evaluate non-traditional but innovative constellation designs identified. The framework has enhanced design discovery and innovation for extremely complex space domain problems that have traditionally been considered computationally intractable.
Diet, nutrition, and cancer: The role of fiber (1986)

The mechanisms by which dietary fiber could inhibit development of colon cancer include effects on fecal weight and transit time, adsorption of bile acids, dilution of colonic contents, production of short chain fatty acids (products of fiber fermentation), inhibition of dehydroxylation of bile acids, and regulation of energy intake. Review of the literature suggests that effects on fecal weight and transit time and adsorption of bile acids are not likely mechanisms. Since concentration of bile acids is lower in feces of less susceptible populations, dilution of colonic contents may contribute to fiber effects. High colonic pH is associated with promotion of cancer and production of short chain fatty acids would counteract this effect. Animals maintained on calorie-restricted diets exhibit fewer spontaneous or experimentally induced tumors. Regulation of energy intake by fiber may contribute towards reduction of colon cancer incidence in man especially when caloric content is low from infancy.
Comparative recombination distances among Zea mays L. inbreds, wide crosses and interspecific hybrids. (1995)

Recombination distances and linkage heterogeneity were compared among a wide range of maize inbreds, wide crosses and maize x teosinte hybrids. Twelve maize and four teosinte races were backcrossed to stocks fixed for rare marker alleles on chromosome arm 1L. Recombination fraction estimates were higher for exotic germplasm than for either U.S. maize or maize x teosinte crosses. Serrano, Tuxpeño and a US-adapted inbred line of tropical origin, NC300, exhibited enhanced recombination. Three of the four maize x teosinte hybrids had little or no recombination between two loci. The observed recombination "shrinkage" resulted from an apparent inversion in the vicinity of the Amp1 locus. Average recombination distances among common marker loci for composite maps were highly variable, even when map construction was restricted to maize germplasm of similar origins.
Clinical significance of epithelial mesenchymal transition (EMT) in chronic obstructive pulmonary disease (COPD): potential target for prevention of airway fibrosis and lung cancer (2014)

Unfortunately, the research effort directed into chronic obstructive pulmonary disease (COPD) has been disproportionately weak compared to its social importance, and indeed it is the least researched of all common chronic conditions. Tobacco smoking is the major etiological factor. Only 25% of smokers will develop "classic" COPD; in these vulnerable individuals the progression of airways disease to symptomatic COPD occurs over two or more decades. We know surprisingly little about the pathobiology of COPD airway disease, though small airway fibrosis and obliteration are likely to be the main contributors to physiological airway dysfunction and these features occur earlier than any subsequent development of emphysema. One potential mechanism contributing to small airway fibrosis/obliteration and change in extracellular matrix (ECM) is epithelial mesenchymal transition (EMT), so called Type-II EMT. When associated with angiogenesis (Type-III EMT) it may well also be a link with the development of lung (airway) cancer which is closely associated with COPD. Active EMT in COPD may help to explain why lung cancer is so common in smokers and also the core pathophysiology of small airway fibrosis. Better understanding may lead to new markers for incipient neoplasia, and better preventive management of patients. There is serious need to understand key components of airway EMT in smokers and COPD, and to demarcate novel drug targets for the prevention of lung cancer and airway fibrosis, as well as better secondary management of COPD. Since over 90% of human cancer arises in epithelia and the involvement of EMT in all of these may be a central paradigm, insights gained in COPD may have important generalizable value.
Complete regression of MX-1 human breast carcinoma xenografts after targeted chemotherapy with a cytotoxic analog of luteinizing hormone-releasing hormone, AN-207 (1999)

The results of this study indicate that powerful, targeted cytotoxic LH-RH analogs such as AN-207 could be considered for the treatment of human breast carcinomas that possesses receptors for LH-RH.
Signal transduction pathways involved in T cell receptor-induced regulation of CD2 avidity for CD58 (1993)

Through physiologic interactions with its ligands CD58 (lymphocyte function-associated Ag-3, LFA-3) and CD59, the T cell glycoprotein CD2 plays a role in T cell signaling and promotes lymphocyte adhesion. We have recently demonstrated that the interaction of CD2 with CD58 is dynamic: TCR stimulation or treatment with the phorbol ester PMA rapidly up-regulates CD2 ligand avidity, and this regulation requires the carboxyl-terminal asparagine residue of the CD2 cytoplasmic domain. Here we have analyzed the regulation of CD2 avidity for CD58, as assessed by the binding of CD2+ cells to purified CD58 and by the formation of rosettes between CD2+ cells and SRBC. In murine T cell hybridomas transfected with human CD2, we show that, unlike CD2-mediated IL-2 production, cell surface expression of the TCR-CD3 structure is not required for up-regulation of CD2 ligand avidity. TCR-initiated up-regulation of CD2 avidity requires the activity of both protein tyrosine kinases and protein kinase C. Agents which elevate intracellular levels of cAMP also up-regulate CD2 ligand avidity and act either distal to or independently of protein kinase C and protein tyrosine kinases. Cell lines expressing single amino acid substitutions of the carboxyl-terminal asparagine of CD2 are incapable of avidity regulation by TCR signaling, PMA treatment, or elevation of intracellular cAMP levels, demonstrating that each of these stimuli utilizes a common structural element for regulating CD2 avidity. The response to both cAMP and phorbol ester treatment distinguishes the regulation of CD2 avidity from that of a second major adhesion pathway, LFA-1 (CD11a/CD18)/ICAM-1 (CD54) and from that of the TCR coreceptor CD8. These observations identify the signaling events involved in the regulation of CD2 avidity and help to define the signal transduction processes that participate in "inside-out" signaling.
Synthesis and hybridization properties of oligonucleotides containing 2'-O-modified ribonucleotides (1993)

A versatile, general way is described for the introduction of different functional groups into oligonucleotides by means of a simple linker at the 2'-position of the sugar. Nucleotide building blocks carrying lipophilic, intercalating or tertiary amino groups can be placed deliberately at any desired position of oligonucleotides by standard automated oligonucleotide synthesis. Thermal denaturation studies with these oligonucleotides reveal the following general trends: i) Modification with lipophilic n-octyl groups has little if any effect on duplex stability; a destabilizing (lipophilic) substituent is better tolerated at or near the ends than in the middle of the oligo. ii) An intercalating substituent (2-aminoanthraquinone) substantially increases duplex stability. iii) N,N-Dimethyl amino residues also increase duplex stability though to a smaller extent than intercalating residues. iv) Modifications at the 5'-end have a more pronounced influence on the TM than the corresponding 3'-modifications. v) Oligonucleotides modified in such a way show little or no loss in sequence specificity.
Lupus Erythematosus and Brain Scanning (1975)

Comments and Correction1 November 1975Lupus Erythematosus and Brain ScanningGRAEME STEWART, M.B., M.R.A.C.P., ANTONY BASTEN, M.B., M.R.C.P.GRAEME STEWART, M.B., M.R.A.C.P.Search for more papers by this author, ANTONY BASTEN, M.B., M.R.C.P.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-83-5-733 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptTo the editor: We were concerned to read the paper in the December 1974 issue on the interpretation of a positive brain scan in patients with systemic lupus erythematosus and localising neurologic signs (1). While not disputing that the patients described may have had cerebral vasculitis, we believe that opportunistic infection of the central nervous system is an equally likely cause of this clinical feature when such patients are receiving immunosuppressive therapy. This is exemplified by three cases, (two with cerebral toxoplasmosis, one with brain abscesses due to nocardial infection) described below and shown in Figure 1. We believe that...References1. BENNAHUM D, MESSNER R, and SHOOP J: Brain scan findings in central nervous system involvement by lupus erythematosus. Ann Intern Med 81:763-765, 1974 LinkGoogle Scholar2. KRAAG G, RICHARDS A, and GORDON D: Brain scanning in lupus erythematosus. Ann Intern Med 82:594, 1975 LinkGoogle Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAuthors: GRAEME STEWART, M.B., M.R.A.C.P.; ANTONY BASTEN, M.B., M.R.C.P.Affiliations: Department of Clinical Immunology Royal Prince Alfred Hospital Camperdonn, N.S.W. 2050 Australia PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited byTreatment of Nocardial Brain Abscess in a Patient With Systemic Lupus Erythematosus and Idiopathic Thrombocytopenic Purpura: Case Report and a Review of the LiteratureNocardiosis in systemic lupus erythematosusCerebral ArteritisPsychiatric Manifestations of Systemic Lupus Erythematosus in Children and AdolescentsNeurological complications of connective tissue and other “collagen-vascular” diseases 1 November 1975Volume 83, Issue 5 Page: 733-734 Keywords Abscesses Brain Central nervous system Immunosuppressives Lupus erythematosus Opportunistic infections Toxoplasmosis Vasculitis ePublished: 1 December 2008 Issue Published: 1 November 1975 PDF downloadLoading ...