gebhart/patrepeval huggingface dataset:
Autocrine signaling by IL-10 mediates altered responsiveness of atopic sensitized airway smooth muscle (2001)

To elucidate the role and mechanism of action of interleukin (IL)-10 in regulating airway smooth muscle (ASM) responsiveness in the atopic asthmatic state, isolated rabbit tracheal ASM segments were passively sensitized with serum from atopic asthmatic patients or nonatopic nonasthmatic (control) subjects in both the absence and presence of an anti-IL-10 receptor blocking antibody (Ab). Relative to control ASM, atopic asthmatic serum-sensitized tissues exhibited enhanced isometric constrictor responses to administered acetylcholine and attenuated the relaxation responses to isoproterenol. These proasthmatic effects were prevented in atopic asthmatic serum-sensitized ASM that was pretreated with anti-IL-10 receptor Ab. In complementary experiments, exposure of cultured human ASM cells to atopic asthmatic serum induced upregulated expression of IL-10 mRNA. Moreover, extended studies demonstrated that 1) exogenous IL-10 administration to naive ASM elicited augmented contractility to acetylcholine and impaired relaxation to isoproterenol, 2) these effects of IL-10 were prevented by pretreating the tissues with an IL-5 receptor Ab, and 3) IL-10 administration induced upregulated mRNA expression and release of IL-5 protein from cultured ASM cells. Collectively, these findings provide new evidence demonstrating that the altered responsiveness of atopic asthmatic serum-sensitized ASM is largely attributed to activation of an intrinsic T helper type 2-type autocrine mechanism involving IL-10-mediated release and the action of IL-5 in the sensitized ASM itself.
Remarkably Mild and Simple Preparations of Sulfinates, Sulfonyl Chlorides and Sulfonamides from Thioanisoles (1997)

New and highly yielding procedures to convert thioanisoles into versatile sulfonyl chloride derivatives were developed by strategically taking advantage of the Pummerer reaction.
A General and Expeditious One-Pot Synthesis of Sulfoxides in High Optical Purity from Norephedrine-Derived Sulfamidites (2002)

A general and simple procedure for preparing any kind of enantiomerically enriched sulfoxide starting from norephedrine-derived N-benzyloxycarbonylsulfamidite 3a is reported. After one-pot reaction of 3a with RMgX, HBF(4), and R'MgX, a variety of sulfoxides 6 are obtained in ee usually higher than 93% and isolated yields ranging between 50 and 78%. The obtained configuration is tunable by simply electing the order of the addition of the reagents. [reaction--see text]
Tumor immunity and autoimmunity induced by immunization with homologous DNA. (1998)

The immune system can recognize self antigens expressed by cancer cells. Differentiation antigens are prototypes of these self antigens, being expressed by cancer cells and their normal cell counterparts. The tyrosinase family proteins are well characterized differentiation antigens recognized by antibodies and T cells of patients with melanoma. However, immune tolerance may prevent immunity directed against these antigens. Immunity to the brown locus protein, gp75/ tyrosinase-related protein-1, was investigated in a syngeneic mouse model. C57BL/6 mice, which are tolerant to gp75, generated autoantibodies against gp75 after immunization with DNA encoding human gp75 but not syngeneic mouse gp75. Priming with human gp75 DNA broke tolerance to mouse gp75. Immunity against mouse gp75 provided significant tumor protection. Manifestations of autoimmunity were observed, characterized by coat depigmentation. Rejection of tumor challenge required CD4(+) and NK1.1(+) cells and Fc receptor gamma-chain, but depigmentation did not require these components. Thus, immunization with homologous DNA broke tolerance against mouse gp75, possibly by providing help from CD4(+) T cells. Mechanisms required for tumor protection were not necessary for autoimmunity, demonstrating that tumor immunity can be uncoupled from autoimmune manifestations.
Reaction coupling of chelation and antigen binding in the calcium ion-dependent antibody binding of cyclic AMP. (1991)

Polyclonal antibodies, raised against cyclic AMP (cAMP) by the immunization of animals with a 2'-O-succinyl cAMP/bovine albumin conjugate, have been reported to be dependent upon the presence of calcium ion (Ca2+) for antigen binding. They also exhibit a major "bridge" effect whereby 2'-O-succinyl and 2'-O-acetyl derivatives are bound more avidly than the parent nucleotide. Since cAMP and these derivatives bind Ca2+ very weakly, they do not present substantially in the chelated form over the range of Ca2+ concentrations used. Thus direct antigen modification is excluded as an explanation for the observed ion dependence of the reaction. Instead, we propose a mechanism based on reaction coupling. The actual antigens are the Ca2+ chelates of these nucleotides, whose formation in the absence of antibody is rapid but not favored (as indicated by their weak association constants). When antibody is added, the chelates act as transient intermediates whose concentration remains low but which is replenished as they are consumed by antibody. The coupled reaction is driven by the antibody-antigen step which occurs more slowly but with a substantial gain in free energy. The reaction is limited by the availability of Ca2+. It also appears that the rabbit antibody-forming cell responds preferentially to the Ca(2+)-bound form of the 2'-O-succinyl cAMP/bovine albumin conjugate which may appear to be more "foreign" than the unbound form of the hapten containing the ubiquitous nucleotide cAMP.
Silylated Initiators for the Efficient Preparation of Borane-End-Functionalized Polymers via ATRP (2007)

Borane-end-functionalized polymers have been prepared through (i) atom transfer radical polymerization (ATRP) of styrene using a silylated initiator, 1-bromo-1-(4-trimethylsilylphenyl)ethane (PEB-SiMe3), (ii) exchange of the SiMe3 end groups with BBr3, and (iii) modification of the Lewis acidic boron centers with nucleophiles. Ditelechelic α,ω-borane-functionalized polymers were obtained through atom transfer radical coupling (ATRC) of the silane-end-functionalized polymers followed by exchange with BBr3 and subsequent reaction with nucleophiles. Self-assembly of the borane-functionalized mono- and ditelechelic polymers into supramolecular structures by means of reversible noncovalent and covalent interactions including Lewis acid−base complexation and boroxine formation has been explored.
A Note on the X-Ray Absorption Method of Determining Fluid Saturation in Cores (1952)

Lipson has recently presented a technical note wherein theoreticalconsiderations were used to demonstrate "… that the adsorption vssaturation relation for a linear absorption method is not necessarily a singlevalued function of saturation." It was concluded that the absorption vssaturation relationship is subject to the same hysteretic effect as is the flowbehavior between the drainage and imbibition systems. It is the purpose of thisnote to show, by experimental results, that for the manner in which fluids aredistributed in porous materials during fluid flow, the relative X-rayabsorption vs saturation relationship is single-valued regardless of thesaturation history. The design of the apparatus used to measure relative X-ray absorption ofcores undergoing fluid flow tests is similar to that described by Morgan, McDowell and Doty. A few modifications have been incorporated in the design toincrease sensitivity and simplicity of measurement. The sensitivity is suchthat for usual types of cores a recording pen movement of approximately 12linear in. is occasioned between the recording of the core dry and when it iscompletely full of an absorbing liquid, a solution of approximately five percent by volume of iodobenzene in a close-cut hydrocarbon fraction, or asolution of 50,000 ppm sodium iodide in water. Two types of experiments were conducted, one in which the liquid was insidethe core, and the other with the liquid outside the core. Tests with the liquidinside the core were run to cover the saturation range encountered in both thedrainage (gas drive) and imbibition (liquid flood) flow systems. It is pointedout that the same core was used, but the tests were conducted at differenttimes with the recording mechanism balanced at a different position. Therefore, the absolute values of relative X-ray intensity at any saturation are not thesame in each test. In the second type of test the same core was used, but this time its porespace contained only gas, and various thicknesses of oil contained in plasticcells were placed in front of the dry core. T.N. 110
Is Toso/IgM Fc receptor (FcμR) expressed by innate immune cells? (2013)

Proceedings of the National Academy of Sciences (PNAS), a peer reviewed journal of the National Academy of Sciences (NAS) - an authoritative source of high-impact, original research that broadly spans the biological, physical, and social sciences.
Acción antrópica y erosión del suelo en la Comunidad Valenciana (1987)

espanolEn el presente trabajo se analiza la accion del hombre en el proceso erosivo, asi como la situacion actual del problema de la erosion del suelo en la Comunidad Valenciana. A esos efectos, la aplicacion de la Educacion Universal de Perdida de Suelo nos permite predecir una situacion alarmante en tierras de la Comunidad; situacion a la que el hombre contribuye como elemento catalizador de los procesos erosivos, mediante el abandono de parcelas marginales, los incendios forestales, las practicas agricolas deficientes, etc. Todo ello determina unas perdidas de suelo superiores a las admisibles que exigen una toma de conciencia por parte de la sociedad. EnglishThe object of this study is to analyse the action of man in the erosive process, as well as the actual situation of the problem of the ground erosion in the Comunidad Valenciana. For this purpose, the aplication of the “Educacion Universal de Perdida de Suelo” allows us the foretell an alarming situation in this area; situation in which man contributes as an element that catalyses the erosive process, by abandoning the marginal plots, causing forest fires, or by practicing agricultural task deficienctly, etc… All this leads to a great loss of ground which calls for a touch of coscience from society.
Nonseismic methods can provide many views of a drillsite (1996)

In a world of low oil and gas prices it is well to keep in mind other advanced exploration techniques that have the ability to quickly focus on promising targets that can then be defined in detail by the ever improving but more expensive seismic method. This article looks at the predictive accuracy of various nonseismic methods to suggest the positive effect their use can have on discovery rates, development programs, finding costs, and reducing the number of dry holes.
One-Year Outcomes After Transcatheter Insertion of an Interatrial Shunt Device for the Management of Heart Failure With Preserved Ejection Fraction (2016)

Background— Heart failure with preserved ejection fraction has a complex pathophysiology and remains a therapeutic challenge. Elevated left atrial pressure, particularly during exercise, is a key contributor to morbidity and mortality. Preliminary analyses have demonstrated that a novel interatrial septal shunt device that allows shunting to reduce the left atrial pressure provides clinical and hemodynamic benefit at 6 months. Given the chronicity of heart failure with preserved ejection fraction, evidence of longer-term benefit is required. Methods and Results— Patients (n=64) with left ventricular ejection fraction ≥40%, New York Heart Association class II–IV, elevated pulmonary capillary wedge pressure (≥15 mm Hg at rest or ≥25 mm Hg during supine bicycle exercise) participated in the open-label study of the interatrial septal shunt device. One year after interatrial septal shunt device implantation, there were sustained improvements in New York Heart Association class ( P &lt;0.001), quality of life (Minnesota Living with Heart Failure score, P &lt;0.001), and 6-minute walk distance ( P &lt;0.01). Echocardiography showed a small, stable reduction in left ventricular end-diastolic volume index ( P &lt;0.001), with a concomitant small stable increase in the right ventricular end-diastolic volume index ( P &lt;0.001). Invasive hemodynamic studies performed in a subset of patients demonstrated a sustained reduction in the workload corrected exercise pulmonary capillary wedge pressure ( P &lt;0.01). Survival at 1 year was 95%, and there was no evidence of device-related complications. Conclusions— These results provide evidence of safety and sustained clinical benefit in heart failure with preserved ejection fraction patients 1 year after interatrial septal shunt device implantation. Randomized, blinded studies are underway to confirm these observations. Clinical Trial Registration— URL: https://www.clinicaltrials.gov . Unique identifier: NCT01913613.
Recent Progress in Herpes Simplex Virus Immunobiology and Vaccine Research (2003)

Herpes simplex virus types 1 and 2 (HSV-1 and HSV-2) cause prevalent, chronic infections that have serious outcomes in some individuals. Neonatal herpes may occur when the infant traverses the cervix during maternal genital herpes. Genital herpes is a major risk factor for human immunodeficiency virus type 1 transmission. Considerable efforts have been made to design and test vaccines for HSV, focusing on genital infection with HSV-2. Several protein subunit vaccines based on HSV-2 envelope glycoproteins have reached advanced-phase clinical trials. These antigens were chosen because they are the targets of neutralizing-antibody responses and because they elicit cellular immunity. Encouraging results have been reported in studies of treatment of HSV-seronegative women with a vaccine consisting of truncated glycoprotein D of HSV-2 and a novel adjuvant. Because most sexual HSV transmission occurs during asymptomatic shedding, it is important to evaluate the impact of vaccination on HSV-2 infection, clinically apparent genital herpes, and HSV shedding among vaccine recipients who acquire infection. There are several other attractive formats, including subunit vaccines that target cellular immune responses, live attenuated virus strains, and mutant strains that undergo incomplete lytic replication. HSV vaccines have also been evaluated for the immunotherapy of established HSV infection.
Essential Roles of Her2/erbB2 in Cardiac Development and Function (2004)

The tyrosine kinase receptor erbB2, also known in humans as Her2, is a member of the epidermal growth factor receptor (EGFR or erbB1) family, which also includes erbB3 and erbB4. The erbBs were discovered in an avian erythroblastosis tumor virus and exhibited similarities to human EGFR (Yarden and Sliwkowski, 2001). Her2/erbB2 is highly expressed in many cancer types. Its overexpression is correlated with a poor prognosis for breast and ovarian cancer patients. ErbB receptors bind to a family of growth factors, termed neuregulins/heregulin (NRG/HRG), which comprise NRG-1, -2, -3, and -4 and include multiple isoforms. ErbB2/Her2 is an orphan receptor that does not bind ligand alone but heterodimerizes with the other erbB receptors for NRG signaling. ErbB2 is expressed in multiple neuronal and non-neuronal tissues in embryos and adult animals, including the heart. Genetic data demonstrated that erbB2 is required for normal embryonic development of neural crest-derived cranial sensory neurons. ErbB2/Her2-null mutant embryos of a trabeculation defect die before embryonic day (E) 11. To study its role at later stages of development, we generated a transgenic mouse line that specifically expresses the rat erbB2 cDNA in the heart under the control of the cardiac-specific alpha-myosin heavy chain promoter. When crossed into the null background, the expression of the rat erbB2 cDNA rescued the cardiac phenotype in the erbB2-null mutant mice that survive until birth but display an absence of Schwann cells and a severe loss of both motor and spinal sensory neurons. To study the role of erbB2 in the adult heart, we generated conditional mutant mice carrying a cardiac-restricted deletion of erbB2. These erbB2 conditional mutants exhibited multiple independent parameters of dilated cardiomyopathy, including chamber dilation, wall thinning, and decreased contractility. Interestingly, treatment of breast cancers overexpressing erbB2 with Herceptin (Trastuzumab), a humanized monoclonal antibody specific to the extracellular domain of erbB2, results in some patients developing cardiac dysfunction. The adverse effect is increased significantly in those patients who also receive the chemotherapeutical agent anthracycline. We found that erbB2-deficient cardiac myocytes are more susceptible to anthracycline-induced cytotoxicity. These results suggest that erbB2 signaling in the heart is essential for the prevention of dilated cardiomyopathy. These lines of mice provide models with which to elucidate the molecular and cellular mechanisms by which erbB2 signaling regulates cardiac functions. These mice also will provide important information for devising strategies to mitigate the cardiotoxic effects of Herceptin treatment, allowing for the potential expanded use of this drug to treat all cancers overexpressing erbB2.
Potential antitumor agents. Synthesis, reactivity, and cytotoxicity of .alpha.-methylene carbonyl compounds (1978)

The alpha-methylene lactones 9, 12, 21, and 24 were prepared by a mild, convenient alpha-methylenation process using the alpha-ethyloxalyl derivatives in nonoptimized yields ranging from 23 to 90%. The rates of reaction of these and several other lactones with cysteine at pH 7.4 and their KB toxicities were measured. These studies showed that neither the strained trans-fused alpha-methylene lactone 12 nor the hydroxy-alpha-methylene lactones 5 and 6 reacted with cysteine with rates comparable to elephantopin. Based on these limited studies, the rate of cysteine addition appears to be relatively insensitive to changes in strain energy and neighboring groups. In addition, the rate constant for reaction with cysteine did not correlate with cytotoxicity.
Imaging of primaries and multiples using a dual‐sensor towed streamer (2010)

Multiple reflections are commonly treated as noise in oneway imaging methods. High effort is put into research and data processing worldwide in an effort to suppress this source of noise. In a new perspective multiples are treated as valuable imaging information. Based on dual‐sensor towed streamer measurement, we decompose the wavefield and apply up/down imaging of primary and multiple reflections. This approach is tested using shallow water synthetic data and finally applied on dual‐sensor field data.
Fluorescence resonance energy transfer (FRET) microscopy imaging of live cell protein localizations (2003)

The current advances in fluorescence microscopy, coupled with the development of new fluorescent probes, make fluorescence resonance energy transfer (FRET) a powerful technique for studying molecular interactions inside living cells with improved spatial (angstrom) and temporal (nanosecond) resolution, distance range, and sensitivity and a broader range of biological applications.
In Situ Anionic Shielding for Regioselective Metalation: Directed peri and Iterative Metalation Routes to Polyfunctionalized 7‐Azaindoles (2012)

Strolling the ring: a general regioselective directed peri(C4)-metalation route to 1 through an in situ N-anionic protection of C2 is reported. The azaindoles may be elaborated by directed ortho metalation (DoM) and Suzuki coupling to more complex heterocyclic systems. An iterative ring-walk DoM sequence furnishes the exhaustively substituted 2. DMG=directed metalation group, TMEDA=N,N,N',N'-tetramethylethylenediamine, TMS=trimethylsilyl.
Downregulation of mTOR by lentivirus inhibits prostate cancer cell growth. (2014)

Prostate cancer, one of the most lethal forms of urinary system cancer, remains resistant to currently available treatments. Therefore, novel mechanism and target-based approaches are needed for the management of this neoplasm. PI3K/AKT signaling pathway activation correlates with human prostate cancer progression and metastasis. However, the role of mTOR in prostate cancer is not well-established. Here, we demonstrate that mTOR is over-expressed in both clinical tissue specimens and cultured human prostate cancer cells when compared to normal prostate tissues, respectively. Further, mTOR gene knockdown via lentivirus mediated mTOR specific shRNA resulted in a significant decrease in the viability and growth of prostate cancer cells without affecting normal human prostate cells. In addition, mTOR inhibition resulted in a significant i) decrease in 4EBP1, S6K, PI3K and AKT protein, ii) increase in PARP protein of prostate cancer cells. Most importantly, mTOR inhibition triggered apoptosis and suppressed pancreatic carcinoma growth in vivo in a mouse xenograft model. We suggest that targeting of mTOR may be a viable approach for the treatment of prostate cancer.
Fibroblast Growth Factor-2 Determines Severity of Joint Disease in Adjuvant-Induced Arthritis in Rats (2002)

Rheumatoid arthritis (RA), a systemic inflammatory disease of unknown etiology, mainly affects synovial joints. Although angiogenic growth factors, including fibroblast growth factor-2 (FGF-2) and vascular endothelial growth factor (VEGF), may play a critical role in the development and progression of RA joint disease, little information is now available regarding their exact role in initiation and/or progression of RA. In this study, we show that both polypeptides were up-regulated in the rat joint synovial tissue of an adjuvant-induced model of arthritis (AIA), as well as human subjects with RA. FGF-2 overexpression via Sendai virus-mediated gene transfer significantly worsened clinical symptoms and signs of rat AIA, including hind paw swelling and radiological bone destruction, as well as histological findings based on inflammatory reaction, synovial angiogenesis, pannus formation, and osteocartilaginous destruction, associated with up-regulation of endogenous VEGF. FGF-2 gene transfer to non-AIA joints was without effect. These findings suggested that FGF-2 modulated disease progression, but did not affect initiation. Reverse experiments using anti-FGF-2-neutralizing rabbit IgG attenuated clinical symptoms and histopathological abnormalities of AIA joints. To our knowledge, this is the first report indicating direct in vivo evidence of disease-modulatory effects of FGF-2 in AIA, as probably associated with endogenous VEGF function. FGF-2 may prove to be a possible therapeutic target to treat subjects with RA.
Azatides:  Solution and Liquid Phase Syntheses of a New Peptidomimetic (1996)

An efficient method has been developed for the solution and liquid phase syntheses of a biopolymer mimetic consisting of "α-aza-amino acids" linked in a repetitive manner to form what we term an azatide oligomer. To construct this biopolymer mimetic, three stages of research were pursued as follows: (1) development of general synthetic procedures that allowed the synthesis of a wide variety of Boc-protected aza-amino acid monomers, (2) optimization of solution phase procedures for the coupling of aza-amino acids in a repetitive manner, and (3) design and synthesis of a linker that would support azatide synthesis using a liquid phase synthetic format. The successful completion of these three phases of research demonstrates that oligoazatides can now be rapidly assembled on a homogeneous polymeric support. The long term prospectus of this new biopolymer is the exploration of peptide structure as well as a potential source of new peptidomimetic libraries.