gebhart/patrepeval huggingface dataset:
Deregulating Direct‐to‐Consumer Marketing of Prescription Drugs: Effects on Prescription and Over‐the‐Counter Product Sales (2002)

This paper examines the impact and interrelationships between direct‐to‐consumer (DTC) and physician‐oriented marketing on the sales composition of the prescription (Rx) and over‐the‐counter (OTC) versions of antiulcer and heartburn medications. To understand better the implications for competition of the 1997 Food and Drug Administration’s policies regarding DTC marketing, as well as recent Rx‐to‐OTC switch approvals, we also examine the relationship between order‐of‐entry effects and marketing intensities. We find spillover effects of marketing for Rx drugs on same‐brand OTC versions of the drugs. We also find that the ratio of cumulative marketing intensity (cumulative marketing efforts divided by cumulative sales) in the OTC segment increases monotonically with order of entry. Our regression results show that various marketing demand elasticities depend on order of entry. Our findings document the importance of nonprice competition in the OTC drug market and suggest that the recent deregulation of Rx DTC marketing enhances rivalry and facilitates competition.
Depletion of intracellular Ca 2+ stores, phosphorylation of eIF2α, and sustained inhibition of translation initiation mediate the anticancer effects of clotrimazole (1998)

Regulation of translation initiation plays a critical role in the control of cell growth and division in eukaryotic cells. Translation of many growth regulatory proteins including cyclins depends critically on translation initiation factors because their mRNAs are translated inefficiently. We report that clotrimazole, a potent antiproliferative agent both in vitro and in vivo, inhibits cell growth by interfering with translation initiation. In particular, clotrimazole causes a sustained depletion of intracellular Ca2+ stores, which results in activation of PKR, phosphorylation of eIF2alpha, and thereby in inhibition of protein synthesis at the level of translation initiation. Consequently, clotrimazole preferentially decreases the expression of the growth promoting proteins cyclin A, E and D1, resulting in inhibition of cyclin-dependent kinase activity and blockage of cell cycle in G1.
The combustion behavior of polyacrylate ester/graphite oxide composites (2006)

Abstract There is an increasing interest in polymer layered silicate nanocomposites, due to the enhanced properties of these systems. An additional layered system is the graphite oxide system and this has been studied as polyacrylate ester nanocomposites. These have been characterized using X‐ray diffraction and a variety of fire tests. There is a significant change in the oxygen index for nanocomposites which is absent for microcomposites, unlike the situation for the clay‐based systems. X‐ray photoelectron spectroscopy showed that the surface was covered with a graphite oxide‐like material at high temperatures for the nanocomposites, suggesting that this nano‐dimensional material operates as a barrier, exactly as proposed for polymer‐clay systems. Copyright © 2006 John Wiley &amp; Sons, Ltd.
Genetic Requirements for Growth of Escherichia coli K12 on Methyl-α-D-glucopyranoside and the Five α-D-Glucosyl-D-fructose Isomers of Sucrose (2006)

Strains of Escherichia coli K12, including MG-1655, accumulate methyl-alpha-D-glucopyranoside via the phosphoenolpyruvate-dependent glucose:phosphotransferase system (IICB(Glc)/IIA(Glc)). High concentrations of intracellular methyl-alpha-D-glucopyranoside 6-phosphate are toxic, and cell growth is prevented. However, transformation of E. coli MG-1655 with a plasmid (pAP1) encoding the gene aglB from Klebsiella pneumoniae resulted in excellent growth of the transformant MG-1655 (pAP1) on the glucose analog. AglB is an unusual NAD+/Mn2+-dependent phospho-alpha-glucosidase that promotes growth of MG-1655 (pAP1) by catalyzing the in vivo hydrolysis of methyl-alpha-D-glucopyranoside 6-phosphate to yield glucose 6-phosphate and methanol. When transformed with plasmid pAP2 encoding the K. pneumoniae genes aglB and aglA (an alpha-glucoside-specific transporter AglA (IICB(Agl))), strain MG-1655 (pAP2) metabolized a variety of other alpha-linked glucosides, including maltitol, isomaltose, and the following five isomers of sucrose: trehalulose alpha(1-->1), turanose alpha(1-->3), maltulose alpha(1-->4), leucrose alpha(1-->5), and palatinose alpha(1-->6). Remarkably, MG-1655 (pAP2) failed to metabolize sucrose alpha(1-->2). The E. coli K12 strain ZSC112L (ptsG::cat manXYZ nagE glk lac) can neither grow on glucose nor transport methyl-alpha-D-glucopyranoside. However, when transformed with pTSGH11 (encoding ptsG) or pAP2, this organism provided membranes that contained either the PtsG or AglA transporters, respectively. In vitro complementation of transporter-specific membranes with purified general phosphotransferase components showed that although PtsG and AglA recognized glucose and methyl-alpha-D-glucopyranoside, only AglA accepted other alpha-D-glucosides as substrates. Complementation experiments also revealed that IIA(Glc) was required for functional activity of both PtsG and AglA transporters. We conclude that AglA, AglB, and IIA(Glc) are necessary and sufficient for growth of E. coli K12 on methyl-alpha-D-glucoside and related alpha-D-glucopyranosides.
Identification of specificity‐determining residues in antibodies (1995)

The successful identification of the residues that contact ligand has important implications, especially in view of the increasing use of antibodies in various medical and industrial applications. Analysis of the crystallographically derived, three‐dimensional structures of five antibody‐antigen complexes and of the available amino acid sequence data on antibody variable regions reveals that the residues that contact antigen are in the main also the most variable. It is proposed that a good first guess of the identity of the specificity‐determining residues can be made from an examination of the variability values at sequence positions. New boundaries for the complementarity‐determining regions are proposed.—Padlan, E. A., Abergel, C., Tipper, J. P. Identification of specificity‐determining residues in antibodies. FASEB J. 9, 133‐139 (1995)
Treatment of Chronic Rhinosinusitis With Nasal Polyposis With Oral Steroids Followed by Topical Steroids (2011)

Chief Scientist Office, Scotland; National Health Service Tayside Small Grants Scheme; and an Anonymous Trust grant from University of Dundee.
Targeting Inflammation-Induced Obesity and Metabolic Diseases by Curcumin and Other Nutraceuticals (2010)

Extensive research within the past two decades has revealed that obesity, a major risk factor for type 2 diabetes, atherosclerosis, cancer, and other chronic diseases, is a proinflammatory disease. Several spices have been shown to exhibit activity against obesity through antioxidant and anti-inflammatory mechanisms. Among them, curcumin, a yellow pigment derived from the spice turmeric (an essential component of curry powder), has been investigated most extensively as a treatment for obesity and obesity-related metabolic diseases. Curcumin directly interacts with adipocytes, pancreatic cells, hepatic stellate cells, macrophages, and muscle cells. There, it suppresses the proinflammatory transcription factors nuclear factor-kappa B, signal transducer and activators of transcription-3, and Wnt/beta-catenin, and it activates peroxisome proliferator-activated receptor-gamma and Nrf2 cell-signaling pathways, thus leading to the downregulation of adipokines, including tumor necrosis factor, interleukin-6, resistin, leptin, and monocyte chemotactic protein-1, and the upregulation of adiponectin and other gene products. These curcumin-induced alterations reverse insulin resistance, hyperglycemia, hyperlipidemia, and other symptoms linked to obesity. Other structurally homologous nutraceuticals, derived from red chili, cinnamon, cloves, black pepper, and ginger, also exhibit effects against obesity and insulin resistance.
Personalizing the Treatment of Pediatric Medulloblastoma: Polo-like Kinase 1 as a Molecular Target in High-Risk Children (2013)

Medulloblastoma is the most common malignant brain tumor in children. This disease is heterogeneous and is composed of four subtypes of medulloblastoma [WNT, Sonic Hedgehog (SHH), Group 3, and Group 4]. An immediate goal is to identify novel molecular targets for the most aggressive forms of medulloblastoma. Polo-like kinase 1 (PLK1) is an oncogenic kinase that controls cell cycle and proliferation, making it a strong candidate for medulloblastoma treatment. In this study, pediatric medulloblastomas were subtyped in two patient cohorts (discovery cohort, n = 63 patients; validation cohort, n = 57 patients) using NanoString nCounter analysis and PLK1 mRNA was assessed. We determined that the SHH and Group 3 subtypes were independently associated with poor outcomes in children as was PLK1 using Cox regression analyses. Furthermore, we screened a library of 129 compounds in clinical trials using a model of pediatric medulloblastoma and determined that PLK1 inhibitors were the most promising class of agents against the growth of medulloblastoma. In patient-derived primary medulloblastoma isolates, the PLK1 small-molecule inhibitor BI2536 suppressed the self-renewal of cells with high PLK1 but not low PLK1 expression. PLK1 inhibition prevented medulloblastoma cell proliferation, self-renewal, cell-cycle progression, and induced apoptosis. In contrast, the growth of normal neural stem cells was unaffected by BI2536. Finally, BI2536 extended survival in medulloblastoma-bearing mice with efficacy comparable with Headstart, a standard-of-care chemotherapy regimen. We conclude that patients with medulloblastoma expressing high levels of PLK1 are at elevated risk. These preclinical studies pave the way for improving the treatment of medulloblastoma through PLK1 inhibition.
Biodegradable Thermogels (2011)

All living creatures respond to external stimuli. Similarly, some polymers undergo conformational changes in response to changes in temperature, pH, magnetic field, electrical field, or the wavelength of light. In one type of stimuli-responsive polymer, thermogel polymers, the polymer aqueous solution undergoes sol-to-gel transition as the temperature increases. Drugs or cells can be mixed into the polymer aqueous solution when it is in its lower viscosity solution state. After injection of the solution into a target site, heating prompts the formation of a hydrogel depot in situ, which can then act as a drug releasing system or a cell growing matrix. In this Account, we describe key materials developed in our laboratory for the construction of biodegradable thermogels. We particularly emphasize recently developed polypeptide-based materials where the secondary structure and nanoassembly play an important role in the determining the material properties. This Account will provide insights for controlling parameters, such as the sol-gel transition temperature, gel modulus, critical gel concentration, and degradability of the polymer, when designing a new thermogel system for a specific biomedical application. By varying the stereochemistry of amino acids in polypeptides, the molecular weight of hydrophobic/hydrophilic blocks, the composition of the polypeptides, the hydrophobic end-capping of the polypeptides, and the microsequences of a block copolymer, we have controlled the thermosensitivity and nanoassembly patterns of the polymers. We have investigated a series of thermogel biodegradable polymers. Polymers such as poly(lactic acid-co-glycolic acid), polycaprolactone, poly(trimethylene carbonate), polycyanoacrylate, sebacic ester, polypeptide were used as hydrophobic blocks, and poly(ethylene glycol) and poly(vinyl pyrrolidone) were used as hydrophilic blocks. To prepare a polymer sensitive to pH and temperature, carboxylic acid or amine groups were introduced along the polymer backbone. The sol-gel transition mechanism involves changes in the secondary structures of the hydrophobic polypeptide and in the conformation of the hydrophilic block. The polypeptide copolymers were stable in the phosphate buffered saline, but the presence of proteolytic enzymes such as elastase, cathepsin B, cathepsin C, and matrix metallopreoteinase accelerated their degradation. We also describe several biomedical applications of biogradable thermogel polymers. One subcutaneous injection of the insulin formulation of thermogel polypeptide copolymers in diabetic rats provided hypoglycemic efficacy for more than 16 days. The thermogels also provided a compatible microenvironment for chondrocytes, and these cells produced biomarkers for articular cartilage such as sulfated glucoaminoglycan (sGAG) and type II collagen. The thermogels were also used as a fixing agent for in situ cell imaging, and cellular activities such as endocytosis were observed by live cell microscopy.
Crystal-Structure-Based Design and Synthesis of Novel C-Terminal Inhibitors of HIV Protease (1994)

The X-ray crystal-structure-based design, synthesis, computational evaluation, and activity of a novel class of HIV protease inhibitors are described. The initial lead compounds 2 and 3 were designed by modeling replacement groups for the C-terminal Val-Val-OCH3 of a known hydroxyethylene inhibitor into the active site of the reported crystal structure of HIV protease complexed with MVT-101. The lead compound 2 was found to be a modest inhibitor with a Ki = 1.67 microM. The X-ray crystal structure of compound 2 complexed with HIV protease was solved and used for subsequent design. The lead compound 3 was found to be a more potent inhibitor with Ki = 0.2 microM, and the structure of it complexed with HIV protease was also solved and used for subsequent design. Modification of both the C-terminus and N-terminus of indole 3 resulted in compounds with Ki = 30 nM. Using the crystal structure of compounds 2 and 3 with HIV protease as a starting point, the thermodynamic cycle perturbation molecular dynamics method was applied to a select group of compounds in order to test the accuracy of this type of computation within a series of closely related compounds.
The role of CD5-expressing B cells in health and disease (review). (1999)

The CD5(+) B cell population is prominent in early life and produce low avidity and, thereby, polyreactive antibodies. CD5(+) B cells are receptive to cytokines and interleukin-10 seems to be influential in the regulation of some of these CD5(+) B cells. The question of whether CD5 is a marker of activation or a molecule specific for a B cell lineage remains unresolved because evidence in support or against a separate lineage are still a matter for debate. However, we suggest the possibility of different kind of CD5(+) B cells. Indeed, activated CD5(+) B cells do proliferate, following CD5 engagement, while resting CD5(+) B cells do not. Moreover, three ligands for CD5 have, thus far, been identified but their functional effects are yet unknown. CD5(+) B cells probably play a role in setting up the idiotype network, antigen presentation and tolerance induction. B cells of most of the chronic lymphoid leukemias express CD5 molecules and, surprisingly, these cells may be expanded in non-organ-specific autoimmune diseases, such as rheumatoid arthritis or primary Sjögren's syndrome. CD5(+) B cells seems to be involved in the autoantibody production (this does not necessarily imply that pathogenic autoantibodies are produced by CD5(+) B cells) in autoimmune disease and particularly susceptible to transformation in lymphoproliferative disorders. Thus, this B cell population appears to play a key role at the crossroad of the non-organ-specific autoimmune diseases and B lymphoproliferative disorders.
In Trans T Cell Tolerance Diminishes Autoantibody Responses and Exacerbates Experimental Allergic Encephalomyelitis (2008)

A number of Ag-specific approaches have been developed that ameliorate experimental allergic encephalomyelitis (EAE), an animal model for the human autoimmune disease multiple sclerosis. Translation to humans, however, remains a consideration, justifying the search for more insight into the mechanism underlying restoration of self-tolerance. Ig-proteolipid protein (PLP) 1 and Ig-myelin oligodendrocyte glycoprotein (MOG) are Ig chimeras carrying the encephalitogenic PLP 139-151 and MOG 35-55 amino acid sequence, respectively. Ig-PLP1 ameliorates EAE in SJL/J (H-2(s)) mice while Ig-MOG modulates the disease in C57BL/6 (H-2(b)) animals. In this study, we asked whether the chimeras would suppress EAE in F(1) mice expressing both parental MHC alleles and representing a polymorphism with more relevance to human circumstances. The results show that Ig-MOG modulates both PLP1 and MOG peptide-induced EAE in the F(1) mice, whereas Ig-PLP1 counters PLP1 EAE but exacerbates MOG-induced disease. This in trans aggravation of MOG EAE by Ig-PLP1 operates through induction of PLP1-specific T cells producing IL-5 that sustained inhibition of MOG-specific Abs leading to exacerbation of EAE. Thus, in trans T cell tolerance, which should be operative in polymorphic systems, can aggravate rather than ameliorate autoimmunity. This phenomenon possibly takes place through interference with protective humoral immunity.
Prospective Analysis of The Insulin-Resistance Syndrome (Syndrome X) (1992)

Many studies have shown that hyperinsulinemia and/or insulin resistance are related to various metabolic and physiological disorders including hypertension, dyslipidemia, and non-insulin-dependent diabetes mellitus. This syndrome has been termed Syndrome X. An important limitation of previous studies has been that they all have been cross sectional, and thus the presence of insulin resistance could be a consequence of the underlying metabolic disorders rather than its cause. We examined the relationship of fasting insulin concentration (as an indicator of insulin resistance) to the incidence of multiple metabolic abnormalities in the 8-yr follow-up of the cohort enrolled in the San Antonio Heart Study, a population-based study of diabetes and cardiovascular disease in Mexican Americans and non-Hispanic whites. In univariate analyses, fasting insulin was related to the incidence of the following conditions: hypertension, decreased high-density lipoprotein cholesterol concentration, increased triglyceride concentration, and non-insulin-dependent diabetes mellitus. Hyperinsulinemia was not related to increased low-density lipoprotein or total cholesterol concentration. In multivariate analyses, after adjustment for obesity and body fat distribution, fasting insulin continued to be significantly related to the incidence of decreased high-density lipoprotein cholesterol and increased triglyceride concentrations and to the incidence of non-insulin-dependent diabetes mellitus. Baseline insulin concentrations were higher in subjects who subsequently developed multiple metabolic disorders. These results were not attributable to differences in baseline obesity and were similar in Mexican Americans and non-Hispanic whites. These results support the existence of a metabolic syndrome and the relationship of that syndrome to multiple metabolic disorders by showing that elevations of insulin concentration precede the development of numerous metabolic disorders.
Tobacco use in relation to COPD and asthma: Fig. 1— (2007)

Smoking is the leading cause of preventable death worldwide. Hundreds of millions of individuals still smoke, affecting their health as well as that of their peers, family and offspring. Smoking is a well-established prime risk factor for chronic obstructive pulmonary disease and hampers the response to treatment in asthma and chronic obstructive pulmonary disease. In the present paper, new concepts are discussed with respect to pathology, treatment, smoking cessation and tobacco control. Recommendations for future directions are given.
MILO: personal robot platform (2005)

Recent advances in mobile robotic technology has given rise to new types of robotic applications called personal robotics. The main feature of these applications is that they require low cost robots that involve assisting people in doing their everyday jobs such as providing personal assistance, commercial security, mobile tele-conferencing, tele-presence, home services, entertainment, and elderly care. In this paper we introduce a low cost and general purpose mobile robotic platform called MILO. It offers unique hardware and software features which make MILO suitable for a wide spectrum of personal robotic applications. MILO possesses PC architecture and runs on Windows XP. We have experimentally evaluated MILO's performance. Preliminary results show that MILO can be effectively used to develop personal robotic applications.
Trophic Conversion of an Obligate Photoautotrophic Organism Through Metabolic Engineering (2001)

Most microalgae are obligate photoautotrophs and their growth is strictly dependent on the generation of photosynthetically derived energy. We show that the microalga Phaeodactylum tricornutum can be genetically engineered to thrive on exogenous glucose in the absence of light through the introduction of a gene encoding a glucose transporter (glut1 or hup1). This demonstrates that a fundamental change in the metabolism of an organism can be accomplished through the introduction of a single gene. This also represents progress toward the use of fermentation technology for large-scale commercial exploitation of algae by reducing limitations associated with light-dependent growth.
Improved radioimaging and tumor localization with monoclonal F(ab')2. (1983)

Monoclonal anti-tumor antibodies have great promise for radioimmunodetection and localization of tumors. Fab and F(ab')2 fragments, which lack the Fc fragment of antibody (Ab), are cleared more rapidly from the circulation and may have less nonspecific tissue binding than intact Ab. In radioimaging studies using a murine monoclonal antibody to carcinoembryonic antigen in a human colon carcinoma xenografted into hamsters, F(ab')2 fragments were shown superior to Fab fragments and intact antibody for scintiscanning. In double-label experiments with anti-CEA antibody and control monoclonal IgG, F(ab')2 fragments were found to give better and more rapid specific tumor localization than intact antibody or Fab fragments. F(ab')2 fragments offer significant promise for tumor imaging and possibly therapy.
Sialic acid as a tumor marker. (1994)

The term sialic acid is used to describe derivatives of neuraminic acid, where the amino group of neuraminic acid is substituted by either an acetyl or glycolyl group. The unique structural features of the molecule, which includes a negative charge owing to a carboxyl group, enables it to play a role in cellular functions, such as transport of positively charged compounds, cell-to-cell repulsion, influencing conformation of glycoproteins on cell membranes, and even masking antigenic determinants on receptor molecules. Focus on sialic acid as a tumor marker should be examined from the perspective of aberrant glycosylation in cancer cell membranes owing to activation of new glycosyl transferases that are characteristic of tumor cells, and the role played by sialic acid in tumor cell metastasis including increased capacity to adhere to vascular endothelium, and decreased capacity of cancer cells to be destroyed by host defence mechanisms. The high sensitivity of sialic acid as a tumor marker has been reported in a variety of cancerous conditions. Its specificity, however, is relatively low since there is also an increase in sialic acid-rich glycoproteins in inflammatory diseases. Sialic acid measurements, however, have value in monitoring cancer patients during treatment. A variety of methods are available for the measurement of both total and lipid associated sialic acids in serum or plasma. The newer high performance liquid chromatographic procedures can detect picogram levels of sialic acid and are relatively free of interferences seen with classical procedures.