gebhart/patrepeval huggingface dataset:
Isolation and characterization of human monoclonal antibodies against hepatitis C virus envelope glycoproteins (1998)

The isolation and characterization of human monoclonal antibodies (humAbs) against the hepatitis C Virus (HCV) glycoproteins E1 and E2 are described. B-cells from blood donors with anti-HCV were transformed with Epstein-Barr virus. The supernatants of the resulting lymphoblastoid clones were screened by ELISA with an extract of cells infected with a recombinant vaccinia virus RMPA95 expressing the envelope proteins E1 and E2 of an HCV genotype 1a virus (H strain). Positive clones were fused to the heteromyeloma cell line K6H6/B5. Fifteen heterohybridoma cell lines have been established. The specificity of the isolated humAbs was determined both by ELISA and Western blot assays. Several recombinant extracts expressing either the E1 or E2 protein or truncated forms were used in an attempt to map the epitopes on the viral glycoproteins. Some of the humAbs were used successfully for immunofluorescence investigation of transfected cells. Seven specific anti-E2 humAbs, which react with the envelope protein 2 of genotype 1a and 1b isolates, were characterized.
Structural Determinants for Activity of Glucagon-like Peptide-2 (2000)

Glucagon-like peptide-2 (GLP-2) is a 33 amino acid gastrointestinal hormone that regulates epithelial growth in the intestine. Dipeptidylpeptidase IV cleaves GLP-2 at the position 2 alanine, resulting in the inactivation of peptide activity. To understand the structural basis for GLP-2 action, we studied receptor binding and activation for 56 GLP-2 analogues with either position 2 substitutions or alanine replacements along the length of the peptide. The majority of position 2 substitutions exhibited normal to enhanced GLP-2 receptor (GLP-2R) binding; in contrast, position 2 substitutions were less well tolerated in studies of receptor activation as only Gly, Ile, Pro, alpha-aminobutyric acid, D-Ala, or nor-Val substitutions exhibited enhanced GLP-2R activation. In contrast, alanine replacement at positions 5,6,17, 20, 22, 23, 25, 26, 30, and 31 led to diminished GLP-2R binding. Position 2 substitutions containing Asp, Leu, Lys, Met, Phe, Trp, and Tyr, and Ala substitutions at positions 12 and 21 exhibited normal to enhanced GLP-2R binding but greater than 75% reduction in receptor activation. D-Ala(2), Pro(2) and Gly(2), Ala(16) exhibited significantly lower EC(50)s for receptor activation than the parent peptide (p < 0.01-0.001). Circular dichroism analysis indicated that the enhanced activity of these GLP-2 analogues was independent of the alpha-helical content of the peptide. These results indicate that single amino acid substitutions within GLP-2 can confer structural changes to the ligand-receptor interface, allowing the identification of residues important for GLP-2R binding and receptor activation.
πBox: a platform for privacy-preserving apps (2013)

We present πBox, a new application platform that addresses an increasingly common problem: the misappropriation of user information by apps resulting in privacy violations. To strike a useful balance between an app’s need to access user data and users ’ desire to protect their private information, πBox shifts much of the responsibility for protecting user privacy from the app and its users to the platform. πBox achieves this by using (1) a sandbox that spans both a user’s device and the cloud, (2) specialized storage and communication channels that enable necessary app functionalities, and (3) a novel adaptation of recent theoretical algorithms for differential privacy under continual observation. We describe a prototype implementation of πBox and show that it enables a wide range of useful apps with minimal performance overhead and without sacrificing user privacy. 1
TGF-β1 Modulates Human Airway Smooth-Muscle Cell Proliferation Induced by Mitogens (1997)

Asthma is a disease of airway inflammation and bronchoconstriction that results in airway smooth-muscle cell hypertrophy and hyperplasia. The underlying mechanisms that induce myocyte proliferation remain unknown. Evidence suggests that cytokines such as transforming growth factor (TGF)-beta 1 may play a role in modulating this process. In this study, we examined the effects of TGF-beta 1 on human airway smooth-muscle (HASM) cell proliferation. We found that treatment of HASM cells with TGF-beta 1 inhibited epidermal growth factor (EGF)- and thrombin-induced DNA synthesis. This inhibition was both dose and time dependent. We then investigated whether these effects are mediated through activation of mitogen-activated protein kinase (MAP kinase), an enzyme that is thought to play a central role in the regulation of cell proliferation. We found that MAP kinase activation induced by EGF was not modulated by TGF-beta 1, despite TGF-beta 1 inhibiting EGF-induced HASM cell growth. These data suggest that TGF-beta 1 inhibits mitogen-induced HASM cell proliferation, but does so downstream from MAP kinase activation, or via a parallel pathway that is independent of MAP kinase activation.
Gene Therapy Tools for Brain Diseases (2019)

Neurological disorders affecting the central nervous system (CNS) are still incompletely understood. Many of these disorders lack a cure and are seeking more specific and effective treatments. In fact, in spite of advancements in knowledge of the CNS function, the treatment of neurological disorders with modern medical and surgical approaches remains difficult for many reasons, such as the complexity of the CNS, the limited regenerative capacity of the tissue, and the difficulty in conveying conventional drugs to the organ due to the blood-brain barrier. Gene therapy, allowing the delivery of genetic materials that encodes potential therapeutic molecules, represents an attractive option. Gene therapy can result in a stable or inducible expression of transgene(s), and can allow a nearly specific expression in target cells. In this review, we will discuss the most commonly used tools for the delivery of genetic material in the CNS, including viral and non-viral vectors; their main applications; their advantages and disadvantages. We will discuss mechanisms of genetic regulation through cell-specific and inducible promoters, which allow to express gene products only in specific cells and to control their transcriptional activation. In addition, we will describe the applications to CNS diseases of post-transcriptional regulation systems (RNA interference); of systems allowing spatial or temporal control of expression [optogenetics and Designer Receptors Exclusively Activated by Designer Drugs (DREADDs)]; and of gene editing technologies (CRISPR/Cas9, Zinc finger proteins). Particular attention will be reserved to viral vectors derived from herpes simplex type 1, a potential tool for the delivery and expression of multiple transgene cassettes simultaneously.
Anti-phospholipid autoantibodies bind to apoptotic, but not viable, thymocytes in a β 2-glycoprotein I-dependent manner (1996)

Anti-phospholipid autoantibodies (aPL) are associated with a clinical syndrome of hypercoagulability, thrombocytopenia, and fetal loss. Several groups have shown that the in vitro target of many aPL is not a pure phospholipid Ag, but is either a complex between anionic phospholipid and the plasma protein beta2-glycoprotein I (beta 2GPI) or the protein beta 2GPI alone. Anionic phospholipids are normally absent from the extracellular surface of cell membranes but redistribute from the inner to the outer leaflet during apoptosis. We show that aPL bind specifically to apoptotic, but not viable, thymocytes, and that binding is dependent upon the presence of beta 2GPI. Moreover, we show that beta 2GPI binds selectively to the surface of apoptotic thymocytes to generate an epitope for antiphospholipid autoantibodies. These findings suggest that apoptotic cells may be the natural immunogen and/or target for aPL. Moreover, we propose that the interaction of circulating beta 2GPI with redistributed anionic phospholipid may itself generate a novel ligand by which apoptotic cells are recognized directly for phagocytic clearance.
Nanoscale Nuclear Magnetic Resonance with a Nitrogen-Vacancy Spin Sensor (2013)

Extension of nuclear magnetic resonance (NMR) to nanoscale samples has been a longstanding challenge because of the insensitivity of conventional detection methods. We demonstrated the use of an individual, near-surface nitrogen-vacancy (NV) center in diamond as a sensor to detect proton NMR in an organic sample located external to the diamond. Using a combination of electron spin echoes and proton spin manipulation, we showed that the NV center senses the nanotesla field fluctuations from the protons, enabling both time-domain and spectroscopic NMR measurements on the nanometer scale.
Olive Leaf Extracts Are a Natural Source of Advanced Glycation End Product Inhibitors (2013)

Advanced glycation end products (AGEs), which are readily formed and accumulated with sustained hyperglycemia, contribute to the development of diabetic complications. As a consequence, inhibition of AGE formation constitutes an attractive therapeutic/preventive target. In the current study, we explored the phytochemical composition and the in vitro effect of two different olive leaf extracts (an aqueous and a methanolic) on AGE formation. The methanolic olive leaf extract inhibited fluorescent AGE formation in a bovine serum albumin (BSA)-ribose system, whereas the aqueous extract had no effect in both BSA-fructose and BSA-ribose systems. The phytochemical profile was investigated with liquid chromatography-ultraviolet-visible (UV-Vis) diode array coupled to electrospray ionization multistage mass spectrometry (LC/DAD/ESI-MS(n)). Quantification of the major phenolic compounds was performed with high performance liquid chromatography with UV-Vis diode array detection and nuclear magnetic resonance spectroscopy. Among the major phenolic components (luteolin, hydroxytyrosol, luteolin-4'-O-β-D-glucopyranoside, luteolin-7-O-β-D-glucopyranoside, and oleuropein), luteolin and luteolin-4'-O-β-D-glucopyranoside were assigned as potent inhibitors of AGE formation. The extraction procedure greatly affects the composition and therefore the anti-glycation potential of olive leaves.
Comparison of activated protein C/protein S-mediated inactivation of human factor VIII and factor V (1996)

The proteolytic cleavage and subsequent inactivation of recombinant human factor VIII (rhFVIII) and human factor VIIIa (rhFVIIIa) by recombinant human activated protein C (rAPC) was analyzed in the presence and absence of human protein S and human factor V (FV). Membrane-bound rhFVIIIa spontaneously looses most of its initial cofactor activity after 15 minutes of incubation at pH 7.4. The remaining activity can be eliminated after incubation with rAPC. Complete inactivation of the membrane-bound rhFVIII and rhFVIIIa by APC correlates with cleavage at Arg336. The inactivation of rhFVIII and human plasma FV by rAPC were also compared. Under similar experimental conditions, complete inactivation of membrane-bound FVIII (60 nmol/L) by rAPC (10 nmol/L) requires 4 hours of incubation, in contrast to 5 minutes for FV (60 nmol/L). The presence of protein S (100 nmol/L) enhances rhFVIII inactivation by rAPC by 6.4-fold and FVa inactivation by twofold, whereas membrane-bound FV showed no protein S dependence during inactivation. The addition of human FV to the APC/protein S inactivation mixture increases by approximately twofold the rate of inactivation of rhFVIII. The effect of FV on the rhFVIII inactivation by APC is protein S-dependent, because FV alone has no effect on the inactivation rate of rhFVIII by APC. Western blotting using a monoclonal antibody that recognizes an epitope between amino acid residues 307 and 506 of human FV showed that FV was completely cleaved by APC at the beginning of the rhFVIII inactivation process. These data suggest that FV fragments derived from the B region of the procofactor after incubation of the membrane-bound procofactor with APC, but not intact single-chain FV, stimulate APC activity in the presence of protein S. rhFVIII, FV, and rhFVIIIa were not inactivated by Glu20-->Ala-substituted rAPC (rAPCgamma20A), and membrane-bound factor Va was only partially inactivated. Our data suggest that (1) FV and FVa are the physiologically significant substrates for APC inactivation and (2) membranes-bound APC-treated FV is a cofactor for the APC inactivation of rhFVIII only in the presence of the intact form of protein S.
The Structure, Chemistry, and Synthesis of Solanone. A New Anomalous Terpenoid Ketone from Tobacco1 (1965)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTThe Structure, Chemistry, and Synthesis of Solanone. A New Anomalous Terpenoid Ketone from Tobacco1Robert R. Johnson and John A. NicholsonCite this: J. Org. Chem. 1965, 30, 9, 2918–2921Publication Date (Print):September 1, 1965Publication History Published online1 May 2002Published inissue 1 September 1965https://pubs.acs.org/doi/10.1021/jo01020a009https://doi.org/10.1021/jo01020a009research-articleACS PublicationsRequest reuse permissionsArticle Views260Altmetric-Citations27LEARN 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
Optimal tracking performance for SIMO systems (2002)

This note studies the optimal tracking problem for linear time-invariant single-input-multiple-output systems responding to a step reference signal. An integral square error criterion is used as the measure for tracking performance. Explicit expressions are developed for the optimal tracking error. These results characterize how nonsquare plants may pose additional difficulties for tracking, other than those resulted from nonminimum phase zeros and unstable poles.
Achieving near-capacity on a multiple-antenna channel (2003)

Recent advancements in iterative processing of channel codes and the development of turbo codes have allowed the communications industry to achieve near-capacity on a single-antenna Gaussian or fading channel with low complexity. We show how these iterative techniques can also be used to achieve near-capacity on a multiple-antenna system where the receiver knows the channel. Combining iterative processing with multiple-antenna channels is particularly challenging because the channel capacities can be a factor of ten or more higher than their single-antenna counterparts. Using a "list" version of the sphere decoder, we provide a simple method to iteratively detect and decode any linear space-time mapping combined with any channel code that can be decoded using so-called "soft" inputs and outputs. We exemplify our technique by directly transmitting symbols that are coded with a channel code; we show that iterative processing with even this simple scheme can achieve near-capacity. We consider both simple convolutional and powerful turbo channel codes and show that excellent performance at very high data rates can be attained with either. We compare our simulation results with Shannon capacity limits for ergodic multiple-antenna channel.
Hepatitis C Virus Core and Nonstructural Protein 3 Proteins Induce Pro- and Anti-inflammatory Cytokines and Inhibit Dendritic Cell Differentiation (2003)

Antiviral immunity requires recognition of viral pathogens and activation of cytotoxic and Th cells by innate immune cells. In this study, we demonstrate that hepatitis C virus (HCV) core and nonstructural protein 3 (NS3), but not envelope 2 proteins (E2), activate monocytes and myeloid dendritic cells (DCs) and partially reproduce abnormalities found in chronic HCV infection. HCV core or NS3 (not E2) triggered inflammatory cytokine mRNA and TNF-alpha production in monocytes. Degradation of I-kappa B alpha suggested involvement of NF-kappa B activation. HCV core and NS3 induced production of the anti-inflammatory cytokine, IL-10. Both monocyte TNF-alpha and IL-10 levels were higher upon HCV core and NS3 protein stimulation in HCV-infected patients than in normals. HCV core and NS3 (not E2) inhibited differentiation and allostimulatory capacity of immature DCs similar to defects in HCV infection. This was associated with elevated IL-10 and decreased IL-2 levels during T cell proliferation. Increased IL-10 was produced by HCV patients' DCs and by core- or NS3-treated normal DCs, while IL-12 was decreased only in HCV DCs. Addition of anti-IL-10 Ab, not IL-12, ameliorated T cell proliferation with HCV core- or NS3-treated DCs. Reduced allostimulatory capacity in HCV core- and NS3-treated immature DCs, but not in DCs of HCV patients, was reversed by LPS maturation, suggesting more complex DC defects in vivo than those mediated by core or NS3 proteins. Our results reveal that HCV core and NS3 proteins activate monocytes and inhibit DC differentiation in the absence of the intact virus and mediate some of the immunoinhibitory effects of HCV via IL-10 induction.
Metabolic and Therapeutic Effects of Insulin-Like Growth Factor I (1994)

The administration of rhIGF-I in appropriate doses leads to a decrease of insulin and growth hormone secretion and to an increase of insulin sensitivity. In type 2 diabetic patients, IGF-I improves glycemic profiles. In normal subjects, IGF-I increases energy expenditure and lipid oxidation and has a protein-sparing effect. Total and VLDL-triglycerides as well as LDL-cholesterol are decreased by IGF-I administration. This metabolic profile of IGF-I allows speculation on its possible usefulness in conditions of relative insulin resistance often associated with increased cardiovascular morbidity and mortality.
Vorticity and Divergence Fields within Tornadic Storms from Dual-Doppler Observations (1976)

Tornadic storms passed between the two NSSL Doppler radars on 20 April and 8 June, 1974. Both radars simultaneously collected Dopplar data throughout these storms. From the derived velocity fields, vorticity and divergence calculations were made. Strongest convergence is noted in the weak echo region and between opposing vorticity centers.
Relationship of chemotherapy on human cancer xenografts in nude mice to clinical response in donor patient (1980)

Responsiveness of experimental chemotherapy on human cancer xenografts in nude mice was directly compared with clinical response to the same chemotherapy in their donor patients. These xenografts were 1 line of rectal cancer (H-26), two lines of gastric cancer (H-08 and H-22), and 1 line of breast cancer (H-62). Experimental chemotherapies studied were single-drug FT-207 to four lines of xenografts and a combination of mitomycin C, 5-FU, and cytosine arabinoside (MFC) to a line of gastric cancer H-08. Single-drug treatment with FT-207 to H-26 resulted in remarkable retardation of the tumor growth. The comparative treatment with FT-207 suppository to the donor patient of H-26 showed appreciable response. All the other chemotherapies to three other lines (H-08, H-22, and H-62) induced no significant response, which was parallel to the corresponding clinical response in each donor patient. The sensitivity to chemotherapeutic drugs was thought to be still preserved in human cancer xenografts in nude mice.
Two patients walk into a clinic...a genomics perspective on the future of schizophrenia (2011)

Progress is being made in schizophrenia genomics, suggesting that this complex brain disorder involves rare, moderate to high-risk mutations and the cumulative impact of small genetic effects, coupled with environmental factors. The genetic heterogeneity underlying schizophrenia and the overlap with other neurodevelopmental disorders suggest that it will not continue to be viewed as a single disease. This has radical implications for clinical practice, as diagnosis and treatment will be guided by molecular etiology rather than clinical diagnostic criteria.
Human High Molecular Weight Melanoma-Associated Antigen Mimicry by Mouse Anti-Idiotypic Monoclonal Antibody MK2-23: Enhancement of Immunogenicity of Anti-Idiotypic Monoclonal Antibody MK2-23 by Fusion with Interleukin 2 (2005)

To overcome unresponsiveness to the self-high molecular weight melanoma-associated antigen (HMW-MAA) in hosts with constitutive HMW-MAA expression, we have used as immunogen the anti-idiotypic monoclonal antibody (mAb) MK2-23, which mimics the antigenic determinant recognized by the anti-HMW-MAA mAb 763.74. In a phase I/II clinical trial, anti-idiotypic mAb MK2-23, conjugated to keyhole limpet hemocyanin (KLH) as a carrier and given with Bacillus Calmette-Guerin (BCG) as an adjuvant, elicited HMW-MAA-specific antibodies in about 60% of the immunized melanoma patients. The immune response was associated with survival prolongation. However, safety and standardization issues associated with the use of KLH and BCG in the clinical setting have prompted us to develop alternative immunization strategies. Conjugation of human interleukin 2 (IL-2) to mAb MK2-23 variable regions covalently linked to human immunoglobulin constant regions enhanced mAb MK2-23 immunogenicity in BALB/c mice to an extent similar to that induced by mAb MK2-23 conjugated to KLH and given with Freund's adjuvant. As determined by the level of serum antibodies and delayed-type hypersensitivity responses to HMW-MAA-bearing melanoma cells, immunization of mice with the MK2-23-IL-2 fusion protein elicited more robust humoral and cellular responses, respectively, than immunization with KLH-conjugated mAb MK2-23 and separate administration of IL-2. The immunogenicity of the fusion protein is dependent on IL-2 conjugation, because immunization of mice with either mAb MK2-23 or chimeric mAb MK2-23, in combination with IL-2, was not as effective in eliciting HMW-MAA-specific immune responses. These results suggest that the MK2-23-IL-2 fusion protein represents a useful immunogen to implement active specific immunotherapy in patients with melanoma, because it bypasses the requirement for KLH conjugation and adjuvant administration.
THE USE OF HUMAN FIBRINOGEN IN RECONSTRUCTIVE SURGERY (1943)

The successful application of the principles involved in the use of human fibrinogen is thought of sufficient and timely interest to report at this time. Work on animals has proved that both bovine and human fibrinogen may be used to good advantage as a bridge for tissue regeneration. The present case report presents the successful use of this substance in the treatment of a human patient. <h3>REPORT OF CASE</h3><h3>History.—</h3> P. B., a man aged 27, was injured by a high explosive fragment on Nov. 19, 1942, sustaining a laceration of the right thigh. He developed a foot drop with paresthesias over the outer aspect of the thigh and foot. A month later he complained of a severe burning pain in the foot. X-ray examination revealed a foreign metallic body in the soft tissues at the middle third of the thigh. On March 23, 1943 a small piece of