gebhart/patrepeval huggingface dataset:
the role of α4β1 integrin in cell motility and fibronectin matrix assembly (1995)

The alpha 4 beta 1 integrin has been suggested to play important roles in embryogenesis and pathogenesis of many diseases which involve both cell adhesion and cell migration. Previous studies using anti-alpha 4 beta 1 antibodies and fibronectin (Fn) fragments have suggested that alpha 4 beta 1 integrins may be involved in cell motility on Fn and vascular cell adhesion molecule-1 (VCAM-1). However, the cells used in these studies also express other Fn integrin receptors including alpha 5 beta 1 integrin, which is known to function in cell motility on Fn. To test whether alpha 4 beta 1 integrins mediate cell motility on Fn and VCAM-1 in the absence of alpha 5 beta 1 integrin, we expressed human alpha 4 integrin in a Chinese hamster ovary (CHO) cell line that is deficient in alpha 5 beta 1 integrin (CHO B2). The parental alpha 5 deficient CHO B2 cells were unable to adhere, spread or migrate on Fn, nor could they assemble a fibrillar Fn matrix. Expression of alpha 4 beta 1 integrin in the CHO B2 cells enabled the cells to adhere, spread and migrate on Fn and on VCAM-1 but not to assemble a fibrillar Fn matrix. The cellular processes mediated by the interaction of alpha 4 beta 1 with Fn or VCAM-1 were inhibited by the CS1 peptide derived from the major alpha 4 beta 1 binding site on Fn. These findings demonstrate that alpha 4 beta 1 integrins not only function as cell adhesion receptors but also as cell motility receptors for Fn and VCAM-1 independent of alpha 5 beta 1. Moreover, they reveal important functional differences between Fn binding integrins. The alpha 4-positive, alpha 5-negative CHO cells described in this report will be useful tools in studying the mechanism of molecular signalling during integrin mediated cellular processes.
Subdomain Chimeras of Hepatic Lipase and Lipoprotein Lipase (1998)

To specify and localize carboxyl-terminal domain functions of human hepatic lipase (HL) and human lipoprotein lipase (LPL), two subdomain chimeras were created in which portions of the carboxyl-terminal domain were exchanged between the two lipases. The first chimera (HL-LPLC1) was composed of residues 1-344 of human HL, residues 331-388 of human LPL, and residues 415-476 of human HL. The second chimera (HL-LPLC2) consisted of just two segments, residues 1-414 of human HL and residues 389-448 of human LPL. These chimeric constructs effectively divided the HL C-terminal domain into halves, with corresponding LPL sequences either in the first or second portion of that domain. Both chimeras were lipolytically active and hydrolyzed triolein emulsions to a similar extent compared with native HL and LPL. Heparin-Sepharose chromatography demonstrated that HL-LPLC1 and HL-LPLC2 eluted at 0.80 and 1.3 M NaCl, respectively, elution positions that corresponded to native HL and LPL. Hence, substitution of LPL sequences into the HL carboxyl-terminal domain resulted in the production of functional lipases, but with distinct heparin binding properties. In addition, HL-LPLC2 trioleinase activity was responsive to apoC-II activation, although the -fold stimulation was less than that observed with native LPL. Moreover, an apoC-II fragment (residues 44-79) was specifically cross-linked to LPL and HL-LPLC2, but not to HL or HL-LPLC1. Finally, both chimeras hydrolyzed phospholipid with a specific activity similar to that of HL, which was unaffected by the presence of apoC-II. These findings indicated that in addition to a region found within the amino-terminal domain of LPL, apoC-II also interacted with the last half of the carboxyl-terminal domain (residues 389-448) to achieve maximal lipolytic activation. In addition, the relative heparin affinity of HL and LPL was determined by the final 60 carboxyl-terminal residues of each enzyme.
Molecular Recognition in Lamellar Solids and Thin Films (1998)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTMolecular Recognition in Lamellar Solids and Thin FilmsThomas E. Mallouk and Julia A. GavinView Author Information Department of Chemistry, The Pennsylvania State University, University Park, Pennsylvania 16802 Cite this: Acc. Chem. Res. 1998, 31, 5, 209–217Publication Date (Web):April 1, 1998Publication History Received12 June 1997Published online1 April 1998Published inissue 1 May 1998https://pubs.acs.org/doi/10.1021/ar970038phttps://doi.org/10.1021/ar970038presearch-articleACS PublicationsCopyright © 1998 American Chemical SocietyRequest reuse permissionsArticle Views964Altmetric-Citations247LEARN 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-Alertsclose SUBJECTS:Intercalation,Metals,Organophosphorus compounds,Supramolecular chemistry,Thin films Get e-Alerts
Decision-Making in a Fuzzy Environment (1970)

By decision-making in a fuzzy environment is meant a decision process in which the goals and/or the constraints, but not necessarily the system under control, are fuzzy in nature. This means that the goals and/or the constraints constitute classes of alternatives whose boundaries are not sharply defined. An example of a fuzzy constraint is: “The cost of A should not be substantially higher than α,” where α is a specified constant. Similarly, an example of a fuzzy goal is: “x should be in the vicinity of x 0 ,” where x 0 is a constant. The italicized words are the sources of fuzziness in these examples. Fuzzy goals and fuzzy constraints can be defined precisely as fuzzy sets in the space of alternatives. A fuzzy decision, then, may be viewed as an intersection of the given goals and constraints. A maximizing decision is defined as a point in the space of alternatives at which the membership function of a fuzzy decision attains its maximum value. The use of these concepts is illustrated by examples involving multistage decision processes in which the system under control is either deterministic or stochastic. By using dynamic programming, the determination of a maximizing decision is reduced to the solution of a system of functional equations. A reverse-flow technique is described for the solution of a functional equation arising in connection with a decision process in which the termination time is defined implicitly by the condition that the process stops when the system under control enters a specified set of states in its state space.
CD28z CARs and Armored CARs (2014)

CD19-targeted chimeric antigen receptor (CAR) T cells are currently being tested in the clinic with very promising outcomes. However, limitations to CAR T cell therapy exist. These include lack of efficacy against some tumors, specific targeting of tumor cells without affecting normal tissue and retaining activity within the suppressive tumor microenvironment. Whereas promising clinical trials are in progress, preclinical development is focused on optimizing CAR design, to generate "armored CAR T cells," which are protected from the inhibitory tumor microenvironment. Studies investigating the expression of cytokine transgenes, combination therapy with small molecule inhibitors, or monoclonal antibodies, are aimed at improving the antitumor efficacy of CAR T cell therapy. Other strategies aimed at improving CAR T cell therapy include using dual CARs and chemokine receptors to more specifically target tumor cells. This review will describe the current clinical data and some novel armored CAR T cell approaches for improving antitumor efficacy therapy.
Rectal absorption enhancement of gentamicin in rabbits from hollow type suppositories by sodium salicylate or sodium caprylate. (1989)

The absorption of gentamicin (GM) from the rectum of rabbits after coadministration of GM (60 mg) and sodium salicylate (SA) or sodium caprylate (CA) as absorption-enhancing agents was investigated. Two types of hollow type suppositories were used--a conventional type (Type I) and a release-restricted type (Type II). Without SA or CA, GM was not absorbed. However, GM absorption was marked when 90 mg of solid SA or CA was added (the bioavailability of GM was 58% with SA, and 59% with CA). The enhancing effect of SA or CA (30 mg) in solid or aqueous solution form on GM absorption was evaluated using the Type I suppository. In the case of SA, the highest plasma GM level (Cmax 15.3 +/- 1.7 micrograms/ml, AUC0-4 27.3 +/- 3.9 h.micrograms/ml) was obtained following coadministration of powdered GM and SA; the plasma GM level (Cmax 1.5 +/- 0.6 micrograms/ml, AUC0-4 3.0 +/- 1.3 h.micrograms/ml) following the administration of a solution of GM and SA was significantly decreased as compared with the results using the powdered form. In the case of CA, the plasma GM level (Cmax 14.8 +/- 4.5 micrograms/ml, AUC0-4 25.4 +/- 8.7 h.micrograms/ml) following administration of the solution form was not significantly decreased in comparison with the results obtained using the powdered form. A marked increase in the enhancing effect of SA on the rectal GM absorption was found following use of Type II suppositories when GM and SA were coadministered in solution form. However, the GM absorption after coadministration of GM and CA using Type II suppositories was not significantly different from the absorption resulting from use of Type I suppositories. Our results suggest that the form and concentration of drug should not be ignored in evaluating the enhancing effects of SA or CA on the rectal absorption of poorly absorbed drugs such as GM.
89. Sapogenins. Part II. Sarsasapogenin and smilagenin (1937)

S. N. Farmer and G. A. R. Kon, J. Chem. Soc., 1937, 414 DOI: 10.1039/JR9370000414
Molecular cloning and nucleotide sequence of the colonization factor antigen I gene of Escherichia coli (1989)

The colonization factor antigen I (CFA/I) gene has been isolated and sequenced. The amino acid sequence of CFA/I deduced from the nucleotide sequence is composed of 170 amino acids. The first 23 amino acids are considered to be the signal peptide of the CFA/I protein since they are not present in the protein sequence. Among the remaining amino acids, only two are different from the protein sequence: amino acid position 76 is an aspartic acid instead of an asparagine, and position 97 is a serine instead of an alanine. The CFA/I gene has a typical Shine-Dalgarno sequence located 10 base pairs (bp) upstream from the initiation codon. The sequence TACAAT located 48 bp upstream from the initiation codon was tentatively designated the -10 sequence of the CFA/I gene promoter. No sequences homologous to the consensus -35 promoter sequence was found. A pair of inverted repeat sequences followed by a stretch of eight A's are located 45 bp downstream from the termination codon of the CFA/I gene; this region may be a rho-independent transcriptional terminator.
Gene Therapy Using Neural Stem Cells (2003)

Cell replacement and gene transfer approaches for the diseased or injured CNS have provided the basis for the development of potentially powerful new therapeutic strategies for a broad spectrum of brain diseases. Transplantation of cells engineered to produce growth factors or molecules with antitumor effects shows the potential of grafted cells as vectors for protein delivery. However, for any possible clinical application, evidence that the gene transfer is completely innocuous and safe for the recipient must be obtained. To this regard, special cautions must be taken not to interfere with other brain functions apart from the one to be targeted. The grafted cells must integrate without inducing further damage to the recipient brain, with no apparent systemic or local side effects, such as uncontrolled growth, production/release of harmful compounds, or inflammatory response.
Solution Structures of Human LL-37 Fragments and NMR-Based Identification of a Minimal Membrane-Targeting Antimicrobial and Anticancer Region (2006)

To understand the structure and activity relationship of human LL-37, a series of peptide fragments was designed. The N-terminal fragment, LL-37(1-12), was not active, while the C-terminal fragment, LL-37(13-37), killed Escherichia coli, as well as drug-sensitive and drug-resistant cancer cells. A 13-residue core antibacterial and anticancer peptide, corresponding to residues 17-29 of LL-37, was identified based on total correlated spectroscopy by trimming nonessential regions (TOCSY-trim). Because LL-37 acts on bacterial membranes, three-dimensional structures of its fragments were determined in micelles by NMR, including structural refinement by natural abundance 15N and 13C chemical shifts. Aromatic-aromatic interactions in the N-terminal fragment were proposed to be essential for LL-37 aggregation. The LL-37 core peptide adopts a similar structure in the micelles of SDS or dioctanoyl phosphatidylglycerol. This structure is retained in the C-terminal fragment LL-37(13-37) and very likely in intact LL-37 based on peptide-aided signal assignments. The higher antibacterial activity of the LL-37 core peptide than aurein 1.2 was attributed to additional cationic residues. To achieve selective membrane targeting, D-amino acids were incorporated into LL-37(17-32). While the D-peptide showed similar antibacterial activity to the L-diastereomer, it lost toxicity to human cells. Structural analysis revealed hydrophobic defects in the new amphipathic structure of the D-peptide, leading to a much shorter retention time on a reversed-phase HPLC column. It is proposed that hydrophobic defects as a result of incoherent hydrophobic packing provide a structural basis for the improvement in cell selectivity of the LL-37 fragment.
POU5F1 (OCT3/4) identifies cells with pluripotent potential in human germ cell tumors. (2003)

Human germ cell tumors (GCTs) may have variable histology and clinical behavior, depending on factors such as sex of the patient, age at clinical diagnosis, and anatomical site of the tumor. Some types of GCT, i.e., the seminomas/germinomas/dysgerminomas and embryonal carcinomas (the stem cell component of nonseminomas), have pluripotent potential, which is demonstrated by their capacity to differentiate into somatic and/or extraembryonic elements. Although embryonal carcinoma cells are intrinsically pluripotent, seminoma/germinoma/dysgerminoma cells, as well as their precursor carcinoma in situ/gonadoblastoma cells, have the phenotype of early germ cells that can be activated to pluripotency. The other types of GCT (teratomas and yolk sac tumors of infants and newborn, dermoid cyst of the ovary, and spermatocytic seminoma of elderly) are composed of (fully) differentiated tissues and lack the appearance of undifferentiated and pluripotent stem cells. OCT3/4, a transcription factor also known as OTF3 and POU5F1, is involved in regulation of pluripotency during normal development and is detectable in embryonic stem and germ cells. We analyzed the presence of POU5F1 in GCT and other tumor types using immunohistochemistry. The protein was consistently detected in carcinoma in situ/gonadoblastoma, seminomas/germinoma/dysgerminoma, and embryonal carcinoma but not in the various types of differentiated nonseminomas. Multitumor tissue microarray analysis covering >100 different tumor categories and 3600 individual cancers verified that POU5F1 expression is specific for particular subtypes of GCT of adults. No protein was observed in GCT of newborn and infants, spermatocytic seminomas, and the various tumors of nongerm cell origin. In addition, no difference in staining pattern was found in chemosensitive and chemoresistant GCT of adults. These results indicate preservation of the link between POU5F1 and pluripotency, as reported during normal development, after malignant transformation. Therefore, POU5F1 immunohistochemistry is an informative diagnostic tool for pluripotent GCT and offers new insights into the histological heterogeneity of this cancer.
DETAILED WEATHER PREDICTION SYSTEM FOR SNOW AND ICE CONTROL (1993)

A computerized weather prediction system for snowstorms and blizzards was designed and tested extensively during the 1991-1992 winter in Colorado, and installed operationally in January 1993. The system contains several technological innovations. It uses the raw radiosonde and surface observations disseminated via satellite communication links by the National Weather Service. From these data a numerical prediction model generates forecasts at 3-min intervals over a 24-hr period, covering an area the size of the United States, but zooming in over a statewide area (e.g., Colorado) with much greater prediction details. The system runs on a 486 PC and relies on a detailed geographic data base with topographic elevations available in 1- x 1-km horizontal resolution. This data base is used to (a) compute the effects of terrain on weather development and (b) generate graphic displays of terrain and weather. A road network data base is also available for display. Terrain and predicted weather can be shown in several resolution steps, specified by the user, throughout the state, maintenance district, or county. The user can compare predicted weather (precipitation, temperature, winds, humidity) with actual data from sensors or human observers as they become available. If major discrepancies develop, the user can change forecasts locally or regionally by simple point-and-click operations on the computer screen, calling on embedded expert systems.
Hypertriglyceridemia: its etiology, effects and treatment (2007)

Elevated plasma triglyceride concentration is a common biochemical finding, but the evidence for the benefit of treating this lipid disturbance remains less robust than that for treating elevated low-density lipoprotein-cholesterol. Part of the difficulty in the provision of specific recommendations has been the frequent coexistence of elevated triglycerides with other conditions that affect cardiovascular disease risk, such as depressed high-density lipoprotein-cholesterol, obesity, metabolic syndrome, proinflammatory and prothrombotic biomarkers, and type 2 diabetes. Recent investigations of outcomes of cardiovascular disease when medications are used to reduce triglyceride levels suggest that, although a net benefit probably exists, both relative and absolute risk reductions seem underwhelming when compared with the benefit of reducing low-density lipoprotein-cholesterol levels with treatment. However, the totality of evidence suggests that elevated triglyceride levels likely contribute independently to increased risk of cardiovascular disease, although there is no consensus about appropriate target levels. Furthermore, severe hypertriglyceridemia is associated with an increased risk of acute pancreatitis, irrespective of its effect on risk of cardiovascular disease. We review the causes and classification of elevated triglyceride levels, the clinical manifestations of primary hypertriglyceridemia and the management of patients with elevated triglyceride levels.
Short-Term Synaptic Plasticity (1989)

The brain's default mode network consists of discrete, bilateral and symmetrical cortical areas, in the medial and lateral parietal, medial prefrontal, and medial and lateral temporal cortices of the human, nonhuman primate, cat, and rodent brains. Its ...Read More
Carbohydrate triazoles and isoxazoles as inhibitors of galectins-1 and -3 (2006)

Galactosides and lactosides bearing triazoles or isoxazoles, regiospecifically prepared by [1,3]-dipolar cycloadditions between alkynes, azides or nitrile oxides, provided specific galectin-1 and -3 inhibitors with potencies as low as 20 microM.
C60 Pyrrolidine Bis-carboxylic Acid Derivative as a Versatile Precursor for Biocompatible Fullerenes (2014)

A C60 Prato derivative with bis-(t)Bu ester was prepared as a stable and convenient scaffold for the development of fullerene derivatives such as water-soluble C60-PEG conjugates, fulleropeptides via solid phase synthesis, and bis-functionalized C60.
A Modulatory Subunit of Acid Sensing Ion Channels in Brain and Dorsal Root Ganglion Cells (1997)

MDEG1 is a cation channel expressed in brain that belongs to the degenerin/epithelial Na+ channel superfamily. It is activated by the same mutations which cause neurodegeneration in Caenorhabditis elegans if present in the degenerins DEG-1, MEC-4, and MEC-10. MDEG1 shares 67% sequence identity with the recently cloned proton-gated cation channel ASIC (acid sensing ion channel), a new member of the family which is present in brain and in sensory neurons. We have now identified MDEG1 as a proton-gated channel with properties different from those of ASIC. MDEG1 requires more acidic pH values for activation and has slower inactivation kinetics. In addition, we have cloned from mouse and rat brain a splice variant form of the MDEG1 channel which differs in the first 236 amino acids, including the first transmembrane region. This new membrane protein, which has been called MDEG2, is expressed in both brain and sensory neurons. MDEG2 is activated neither by mutations that bring neurodegeneration once introduced in C. elegans degenerins nor by low pH. However, it can associate both with MDEG1 and another recently cloned H+-activated channel DRASIC to form heteropolymers which display different kinetics, pH dependences, and ion selectivities. Of particular interest is the subunit combination specific for sensory neurons, MDEG2/DRASIC. In response to a drop in pH, it gives rise to a biphasic current with a sustained current which discriminates poorly between Na+ and K+, like the native H+-gated current recorded in dorsal root ganglion cells. This sustained current is thought to be required for the tonic sensation of pain caused by acids.