gebhart/patrepeval huggingface dataset:
The Unique Antithrombin III Binding Domain of Heparin: A Lead to New Synthetic Antithrombotics (1993)

Abstract Heparin, a sulfated glycosaminoglycan, is well known for its anticoagulant effect mediated by the serine protease inhibitor antithrombin III (AT III). Heparin has been used clinically for more than half a century for the prophylaxis and treatment of venous thrombosis and thromboembolism. Up until the 1980s it was assumed that the biological activity of heparin was mainly caused by its polyanionic character. However, this paradigm was contradicted when it was discovered that part of the heparin polysaccharides contains a well‐defined pentasaccharide domain that specifically binds and activates AT III. The specificity of the interaction between the characteristic pentasaccharide and AT III has become more obvious after the synthesis and biological testing of various heparin analogues. This article reviews the synthesis of the heparin pentasaccharide, some closely related counterparts, and some highly modified analogues. With the aid of molecular modeling and through “tailored” molecular modifications of the pentasaccharide, much knowledge has been gained concerning structure‐activity relationships. On this basis not only have more potent and simplified derivatives been developed, but also the recognition between heparin and AT III can now be understood in greater detail at the molecular level.
The Central Proline of an Internal Viral Fusion Peptide Serves Two Important Roles (2000)

The fusion peptide of the avian sarcoma/leukosis virus (ASLV) envelope protein (Env) is internal, near the N terminus of its transmembrane (TM) subunit. As for most internal viral fusion peptides, there is a proline near the center of this sequence. Robson-Garnier structure predictions of the ASLV fusion peptide and immediate surrounding sequences indicate a region of order (beta-sheet), a tight reverse turn containing the proline, and a second region of order (alpha-helix). Similar motifs (order, turn or loop, order) are predicted for other internal fusion peptides. In this study, we made and analyzed 12 Env proteins with substitutions for the central proline of the fusion peptide. Env proteins were expressed in 293T cells and in murine leukemia virus pseudotyped virions. We found the following. (i) All mutant Envs form trimers, but when the bulky hydrophobic residues phenylalanine or leucine are substituted for proline, trimerization is weakened. (ii) Surprisingly, the proline is required for maximal processing of the Env precursor into its surface and TM subunits; the amount of processing correlates linearly with the propensity of the substituted residue to be found in a reverse turn. (iii) Nonetheless, proteolytically processed forms of all Envs are preferentially incorporated into pseudotyped virions. (iv) All Envs bind receptor with affinity greater than or equal to wild-type affinity. (v) Residues that support high infectivity cluster with proline at intermediate hydrophobicity. Infectivity is not supported by mutant Envs in which charged residues are substituted for proline, nor is it supported by the trimerization-defective phenylalanine and leucine mutants. Our findings suggest that the central proline in the ASLV fusion peptide is important for the formation of the native (metastable) Env structure as well as for membrane interactions that lead to fusion.
Delivery Systems for Biopharmaceuticals. Part I: Nanoparticles and Microparticles (2015)

Pharmaceutical biotechnology has been showing therapeutic success never achieved with conventional drug molecules. Therefore, biopharmaceutical products are currently well-established in clinic and the development of new ones is expected. These products comprise mainly therapeutic proteins, although nucleic acids and cells are also included. However, according to their sensitive molecular structures, the efficient delivery of biopharmaceuticals is challenging. Several delivery systems (e.g. microparticles and nanoparticles) composed of different materials (e.g. polymers and lipids) have been explored and demonstrated excellent outcomes, such as: high cellular transfection efficiency for nucleic acids, cell targeting, increased proteins and peptides bioavailability, improved immune response in vaccination, and viability maintenance of microencapsulated cells. Nonetheless, important issues need to be addressed before they reach clinics. For example, more in vivo studies in animals, accessing the toxicity potential and predicting in vivo failure of these delivery systems are required. This is the Part I of two review articles, which presents the state of the art of delivery systems for biopharmaceuticals. Part I deals with microparticles and polymeric and lipid nanoparticles.
Abstract 649: Emigrant pre-REP tumor infiltrating lymphocytes profoundly differ from remnant T-cells (2017)

Abstract Adoptive T cell therapy with autologous tumor infiltrating lymphocytes (TIL) provides up to 56% objective response rates and a complete response in 24% of patients with metastatic melanoma. The process of generating TIL from resected tumor involves morcellating the tumor into 1-3 mm3 fragments and expanding TIL in the presence of Interleukin 2 (IL-2) in a pre-Rapid Expansion Protocol (pre-REP). During the ‘pre-REP’, tumor-resident immune cells emigrate (eTIL) and proliferate. The length of the pre-REP varies between 11-21 days, depending on cell growth. Residual tumor fragments (remnants) are discarded and the expanded eTIL are subjected to a Rapid Expansion Protocol (REP) with irradiated PBMC feeders, anti-CD3 and IL-2. Viable cells remaining in the tumor remnants (rTIL) following the pre-REP were investigated to assess their function and phenotype. We evaluated and compared the rTIL and eTIL in melanoma, breast, renal, pancreatic, lung and colorectal tumors (n=9). Tumor rTIL are consistently phenotypically distinct from eTIL, as determined by differential expression of various markers (Table 1). The fundamental differences in rTIL were: Increased CD69+ (7 fold MFI in CD4+) (p&amp;lt;.001); diminished LAG3 (2 fold MFI in CD8) (p&amp;lt;.05); TIM3 (3 and 2 fold MFI in CD8 and CD4 respectively) (p&amp;lt;.05/.01); CD154 (3 fold MFI in CD4) (p&amp;lt;.01); and CD56 (5%) (p&amp;lt;.05). Surprisingly, a REP of rTIL and eTIL resulted in comparable expansion. The phenotypic signature of TIL was sustained post-REP with fidelity of the individual expression of LAG3, Tim3, and CD28. These studies have identified significant differences in the biology of cell populations in terms of tissue-resident T cells and the signals associated with emigration and retention. These data provide additional insights on the individual TIL populations that could be utilized for adoptive T-cell therapy in patients and raise important questions about the nature of tissue-resident T cells in sites of chronic inflammation such as tumor. Table 1:Tumor resident remnant T cells are phenotypically distinct from emigrating T cells (N=9)Marker ExpressionLAG3 (CD8/ CD4) MFITim3 (CD8/ CD4) MFIPD-1 (CD8/ CD4) %CD69 (CD8/ CD4) MFICD154 (CD8/ CD4) MFICD28 (CD8/ CD4) MFICD57 (CD8/ CD4) %CD56%eTIL507/ 1442832/ 175636.95/ 471320/ 15431498/ 37511163/ 503618.76/ 19.65.615rTIL209/ 106877/ 74242.8/ 483437/ 223.41034/ 1167458.3/ 27959.16/8.51.027*P-values(CD8/ CD4) 0.05/ 0.210.05/ 0.010.38/ 0.890.11/ 0.0010.55/ 0.010.05/ 0.110.05/ 0.060.05 _______ Citation Format: Michelle R. Simpson-Abelson, Christopher Mosychuk, Maria Fardis, Michael T. Lotze. Emigrant pre-REP tumor infiltrating lymphocytes profoundly differ from remnant T-cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 649. doi:10.1158/1538-7445.AM2017-649
Development and validation of a composite disease activity score for juvenile idiopathic arthritis (2009)

The JADAS was found to be a valid instrument for assessment of disease activity in JIA and is potentially applicable in standard clinical care, observational studies, and clinical trials.
Meta-Analysis: High-Dosage Vitamin E Supplementation May Increase All-Cause Mortality (2005)

High-dosage (> or =400 IU/d) vitamin E supplements may increase all-cause mortality and should be avoided.
Lysophosphatidic Acid, a Multifunctional Phospholipid Messenger (1995)

Research into phospholipid signaling continues to flourish, as more and more bioactive lipids are being identified and their actions characterized. One interesting addition to the growing list of lipid messengers is lysophosphatidic acid (LPA1(1) ; 1-acyl-glycerol-3-phosphate), the simplest of all glycerophospholipids. While LPA has long been known as a precursor of phospholipid biosynthesis in both eukaryotic and prokaryotic cells, only recently has LPA emerged as an intercellular signaling molecule that is rapidly produced and released by activated cells, notably platelets, to influence target cells by acting on a specific cell-surface receptor (1).
Small intestinal permeability (2000)

The noninvasive assessment of small intestinal permeability in humans is now within the capability of any routine biochemistry laboratory. There remain however, many pitfalls for the unwary when performing these tests. Importantly, it has now been shown that normal intestinal permeability relates to geographical location rather than race. Recent studies show that it may be possible to simplify the procedure even further. The main recent focus of interest in measuring intestinal permeability relates to patients with AIDS and inflammatory bowel disease, the effects of nonsteroidal anti-inflammatory drugs on the small bowel, and the use of these tests in the pediatric population and critically ill. Some groups have now started to focus their attention on the possible systemic consequences of increased intestinal permeability, whereas others have shown that increased small bowel permeability results in small intestinal inflammation that may in turn be associated with blood and protein loss.
Homing Peptide-Conjugated Gold Nanorods: The Effect of Amino Acid Sequence Display on Nanorod Uptake and Cellular Proliferation (2014)

Gold nanorods (GNRs) have attracted significant interest in the field of medicine as theranostic agents for both imaging and photothermal ablation of cancerous cells/tissues. Targeting theranostic GNRs specifically to cancer cells is necessary to enhance treatment efficacy and minimize undesired side effects. In this study, targeting functionalized GNR to EphA2 receptors that are overexpressed on prostate cancer cells was investigated as a strategy to achieve enhanced GNR uptake by cancer cells. In addition, the influence of targeting peptide orientation on functionalized GNR uptake by PC-3 cells was explored. GNRs of aspect ratio 4 were functionalized with an EphA2 homing peptide, YSA, using a layer-by-layer polypeptide wrapping approach. In parallel, an analogous population of YSA-modified GNRs, which display a reversed YSA peptide, with the N- and C- termini reversed, was also prepared. GC-MS analysis of the YSA-GNRs indicated that functionalized GNRs displayed approximately 3000 peptides/GNR. The functionalized GNRs remained well-dispersed in biological media for short times (<24 h). An increase in GNRs uptake of the YSA-GNRs by PC-3 cells, compared to the reversed YSA-GNRs, was observed under identical incubation conditions. Lastly, the effect of the YSA-GNRs binding to EphA2 receptors on prostate cancer cell proliferation was also studied. The YSA-functionalized GNRs inhibit PC-3 proliferation at a significantly lower effective dose than free YSA. Overall, the polypeptide LBL deposition technique provides a facile route to target nanoparticles to overexpressed cellular receptors, with the caveat that the specific orientation and display of the targeting moiety plays a critical role in the interaction between the nanoparticle and the cell.
The Rocket Company (2005)

Seven Billionaires and One Big Problem Big Telescopes, Hot Rodders, and Librarians Gateses, Jobses, and the Laureates' Lemma Build Big, Build Many, or Use it Again Small Market, Small Payload, but not a toy Myths, Mistrust, and Trust The Pitch The Business Plan Mazes, Stop Cords, and Skunk Workers Fuel Tanks, Heat Shields, and Fire Walls Balloon Tanks, Fracture Mechanics, and Friction Stir Welding Enthusiasm Bubbles, Ejections, and Expander Cycles Gasoline, Alcohol, Kerosene, or Liquid Methane Design Reviews, Prototypes, and Parawings Guidance, Navigation, and Control Webb Suit, Hard Suit, Space Suit Markets, Philosophy, Techniques, and Approaches Rockets, Jets, and Soft Landings Pilots, Payloads, and Passengers Mooncars, Monks, and Monasteries Aliens, Cheetahs, and Archea Halfway to Everywhere First Stage, First Flight Stop the Production Line! Earth Below Us Money, Manufacturing, and Marketing Always Room for Improvement Epilogue I: Space is Finally a Place Epilogue II: Mars for the Many
Proadrenomedullin NH2-Terminal 20 Peptide Is a Potent Angiogenic Factor, and Its Inhibition Results in Reduction of Tumor Growth (2004)

We have found through ex vivo and in vivo angiogenesis models that the adrenomedullin gene-related peptide, proadrenomedullin NH2-terminal 20 peptide (PAMP), exhibits a potent angiogenic potential at femtomolar concentrations, whereas classic angiogenic factors such as vascular endothelial growth factor and adrenomedullin mediate a comparable effect at nanomolar concentrations. We found that human microvascular endothelial cells express PAMP receptors and respond to exogenous addition of PAMP by increasing migration and cord formation. Exposure of endothelial cells to PAMP increases gene expression of other angiogenic factors such as adrenomedullin, vascular endothelial growth factor, basic fibroblast growth factor, and platelet-derived growth factor C. In addition, the peptide fragment PAMP(12-20) inhibits tumor cell-induced angiogenesis in vivo and reduces tumor growth in xenograft models. Together, our data demonstrate PAMP to be an extremely potent angiogenic factor and implicate this peptide as an attractive molecular target for angiogenesis-based antitumor therapy.
Thermodynamics of ubiquitin unfolding (1994)

The energetics of ubiquitin unfolding have been studied using differential scanning microcalorimetry. For the first time it has been shown directly that the enthalpy of protein unfolding is a nonlinear function of temperature. Thermodynamic parameters of ubiquitin unfolding were correlated with the structure of the protein. The enthalpy of hydrogen bonding in ubiquitin was calculated and compared to that obtained for other proteins. It appears that the energy of hydrogen bonding correlates with the average length of the hydrogen bond in a given protein structure.
Time-based OTP authentication via secure tunnel (TOAST): A mobile TOTP scheme using TLS seed exchange and encrypted offline keystore (2014)

The main objective of this research is to build upon existing cryptographic standards and web protocols to design an alternative multi-factor authentication cryptosystem for the web. It involves seed exchange to a software-based token through a login-protected Transport Layer Security (TLS/SSL) tunnel, encrypted local storage through a password-protected keystore (BC UBER) with a strong key derivation function (PBEWithSHAANDTwofish-CBC), and offline generation of one-time passwords through the TOTP algorithm (IETF RFC 6239). Authentication occurs through the use of a shared secret (the seed) to verify the correctness of the one-time password used to authenticate. With the traditional use of username and password no longer wholly adequate for protecting online accounts, and with regulators worldwide toughening up security requirements (i.e. BSP 808, FFIEC), this research hopes to increase research effort on further development of cryptosystems involving multi-factor authentication.
A remote process creation and execution facility supporting parallel execution on distributed systems (1996)

The parallel execution of processes over a distributed system is an objective, that, if realised, will provide access to a wealth of computational resources currently underutilised in many network environments. What is lacking from current distributed systems is a flexible and user friendly facility for the creation of processes across a network of workstations in a transparent and easily controlled manner. The paper presents an original architecture of a remote process creation and execution facility designed and developed as part of a microkernel and client-server based distributed operating system. The most important feature of this facility is that it coordinates the cooperation of other kernel servers to create (locally or remotely) a process. It was demonstrated that this facility is very fast and, thus can be used efficiently to support parallel execution on a network of workstations.
The Impetus from Sicily (2009)

This chapter concentrates on one of the longest and most influential plague treatises of the sixteenth century, that of the Sicilian physician Giovanni Filippo Ingrassia, written in 1575 and 1576. It broke with previous plague writing that concentrated on preventative measures and cures directed to the individual patient. Instead, it concentrated on the duties of the prince and public health policy—the creation of new plague hospitals, quarantine, street cleaning, plague passports, and sources of contaminated water. Further, it introduced a new rigour to plague chronicling and disease tracking.
Decreased folylpolyglutamate synthetase activity as a mechanism of methotrexate resistance in CCRF-CEM human leukemia sublines. (1991)

Determinants of methotrexate (MTX) resistance in cell lines resistant to short, but not continuous, MTX exposure were investigated since such lines may have relevance to clinical resistance. CCRF-CEM R30dm (R30dm), cloned from CCRF-CEM R30/6 (a MTX-resistant subline of the CCRF-CEM human leukemia cell line), had growth characteristics similar to CCRF-CEM. R30dm was resistant to a 24-h exposure to levels as high as 300 microM MTX but was as sensitive as CCRF-CEM to continuous MTX exposure. MTX resistance of R30dm was stable for greater than 68 weeks in the absence of selective pressure. Initial velocities of MTX transport were comparable for R30dm and CCRF-CEM, as were dihydrofolate reductase specific activity and MTX binding. A 2-fold thymidylate synthase activity decrease for R30dm from that of CCRF-CEM was not a significant factor in R30dm MTX resistance. Decreased MTX poly(gamma-glutamate) synthesis resulted in lower levels of drug accumulation by R30dm. Decreased polyglutamylation was attributable to folylpolyglutamate synthetase (FPGS) activity in R30dm extracts which was 1, 2, and less than or equal to 10% of CCRF-CEM extracts with the substrates MTX, aminopterin, and naturally occurring folates, respectively. Comparison of cell lines with varying levels of resistance to short term MTX exposure indicated that the extent of MTX resistance was proportional to the reduction of FPGS activity. The evidence supported decreased FPGS activity as the mechanism of resistance to short MTX exposure in the cell lines investigated.
Chemically Powered Micro‐ and Nanomotors (2014)

Chemically powered micro- and nanomotors are small devices that are self-propelled by catalytic reactions in fluids. Taking inspiration from biomotors, scientists are aiming to find the best architecture for self-propulsion, understand the mechanisms of motion, and develop accurate control over the motion. Remotely guided nanomotors can transport cargo to desired targets, drill into biomaterials, sense their environment, mix or pump fluids, and clean polluted water. This Review summarizes the major advances in the growing field of catalytic nanomotors, which started ten years ago.
Phosphatidylcholine vesicles. Formation and physical characteristics (1969)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTPhosphatidylcholine vesicles. Formation and physical characteristicsChing-Hsien HuangCite this: Biochemistry 1969, 8, 1, 344–352Publication Date (Print):January 1, 1969Publication History Published online1 May 2002Published inissue 1 January 1969https://pubs.acs.org/doi/10.1021/bi00829a048https://doi.org/10.1021/bi00829a048research-articleACS PublicationsRequest reuse permissionsArticle Views2923Altmetric-Citations1202LEARN 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 Get e-Alerts
Role of sialic acid for platelet life span: exposure of β-galactose results in the rapid clearance of platelets from the circulation by asialoglycoprotein receptor–expressing liver macrophages and hepatocytes (2009)

Although surface sialic acid is considered a key determinant for the survival of circulating blood cells and glycoproteins, its role in platelet circulation lifetime is not fully clarified. We show that thrombocytopenia in mice deficient in the St3gal4 sialyltransferase gene (St3Gal-IV(-/-) mice) is caused by the recognition of terminal galactose residues exposed on the platelet surface in the absence of sialylation. This results in accelerated platelet clearance by asialoglycoprotein receptor-expressing scavenger cells, a mechanism that was recently shown to induce thrombocytopenia during Streptococcus pneumoniae sepsis. We now identify platelet GPIbalpha as a major counterreceptor on ST3Gal-IV(-/-) platelets for asialoglycoprotein receptors. Moreover, we report data that establish the importance of sialylation of the von Willebrand factor in its function.
Computer Analysis of Amino Acid Sequences (1998)

Genome sequences are of minimal use without an adequate interpretation of the sequences of putative protein products, which is only possible on the basis of detailed computer analysis. The approaches to amino acid sequence analysis can be roughly divided into those that explore intrinsic properties of proteins, such as hydropathy, secondary structure, distribution of different types of amino acid sequences, and so on, and those that search for sequence similarity. Both approaches include numerous algorithms and computer programs. In this short chapter, we cannot describe all or even the most widely used and valuable of these methods. Instead, we present a minimal set of procedures that, in our experience, is useful in order to extract a substantial amount of information from an amino acid sequence in a relatively short time. For detailed descriptions of various computer methods for sequence analysis, the reader is referred to the recently published reviews and Methods in Enzymology collections (1–3).