gebhart/patrepeval huggingface dataset:
Influence of pH conditions on the viability of Saccharomyces boulardii yeast (2008)

Saccharomyces boulardii is a probiotic with proven health benefits. However its survival is challenged by gastrointestinal transit, and a ratio between 1 and 3% of living yeast is recovered in the feces after oral administration. The aim of the study was to determine to what extent the yeast was sensitive to gastrointestinal pH conditions. Therefore we explored the survival of different concentrations of S. boulardii in conditions mimicking the stomach pH (pH 1.1 0.1 N HCl) and the intestinal pH (pH 6.8 phosphate buffer) in vitro. The probiotic being commercialized as a freeze-dried powder obtained from an aqueous suspension, both forms were evaluated. In phosphate buffer pH 6.8, the viability remained stable for both forms of S. boulardii for 6 h. In HCl pH 1.1, viability of both forms (200 mg L(-1)) significantly decreased from 5 min. Observation under scanning/transmission electron microscopy showed morphological damages and rupture of the yeast wall. Threshold value from which S. boulardii viability was unaltered was pH 4. At the highest concentration of 200 g L(-1), the initial pH value of 1.1 rose to 3.2, exerting a protective effect. In conclusion, although the yeast in aqueous suspension was less sensitive than the freeze-dried yeast to acidic conditions, a gastric protection for improvement of oral bioavailability of viable S. boulardii appears necessary.
Increased expression of matrix metalloproteinases 2 and 9 and tissue inhibitors of metalloproteinases 1 and 2 correlate with poor prognostic variables in renal cell carcinoma. (2001)

Increased expression of MMP2, MMP9, TIMP1, and TIMP2 proteins in RCCs correlate with poor prognostic variables including shortened patient survival. The paradoxical poor prognostic implication of TIMP overexpression complements the recently documented dual function of TIMPs and warrants further investigation.
Efficient Light Harvesting by Sequential Energy Transfer across Aggregates in Polymers of Finite Conjugational Segments with Short Aliphatic Linkages (2001)

Interactions between lumophores have a critical influence on the photophysical properties of conjugated polymers. We synthesized a new series of light-harvesting polymers (poly-DSBs, I-IV) of dialkyloxy- or dialkyl-substituted distyrylbenzene (the substituents being methoxy, 2-ethylhexyloxy, and cyclohexyl) with short aliphatic linkage (methylene or ethylene) and examined the effects of interactions between lumophores and of chemical structures on the absorption, emission, and excitation spectra. The proximity between distyrylbenzene lumophores was shown to be critical to the interactions between lumophores and to the energy-transfer processes. In concentrated solutions and solid films, intermolecular aggregates exist resulting from different extents of interactions between lumophores and are found to involve at least three species: loose, compact, and the most aligned aggregates as observed by photoluminescence and excitation spectroscopies. We also found, for the first time, sequential energy transfer from individual lumophores to the most compact, aligned aggregates via the looser intermolecular aggregates, as observed directly by time-resolved fluorescence spectroscopy. Such a process mimics energy transfer in photosynthesis units and is so efficient such that the fluorescence color can be red-shifted drastically by the presence of comparatively few aggregates and that the light evolved from concentrated solutions and films of poly-DSBs I-IV is entirely or almost the aggregation emission. Although the sequential energy-transfer process in fully conjugated electro-/photoluminescent polymers due to inhomogenity other than distributed conjugation lengths has never been directly observed at room temperature, we suggest that events similar to those observed in poly-DSBs in conjugated polymers could occur but on a much shorter time scale, i.e., a few picoseconds.
Polypeptide hormone degradation and receptor regulation are coupled to ligand internalization. A direct biochemical and morphologic demonstration. (1981)

Binding of a polypeptide hormone such as human growth hormone (hGH) to the cell surface initiates at least three diverse events: generation of a biologic signal, ligand degradation, and regulated receptor loss. Morphologic studies demonstrate that the ligand is internalized by the cell at physiologic temperature and associates intracellularly with lysosomes. Lysosomotropic agents such as NH4Cl and chloroquine inhibit the degradation of cell-associated 125I-hGH and promote irreversible binding of the ligand to the cell in a concentration, time, and temperature fashion. When 0.45 nM hGH is incubated with the cultured human lymphocyte at 37 degrees C, receptor loss occurs in parallel with the internalization of 125I-hGH under the exact same conditions of concentration, time, and temperature. NH4Cl is additive with submaximal concentrations of hGH in inducing receptor down regulation. These studies support the concept that ligand degradation and receptor loss are coupled to initial receptor binding by the internalization process.
Curcumin (Diferuloylmethane) Inhibits Constitutive and IL-6-Inducible STAT3 Phosphorylation in Human Multiple Myeloma Cells (2003)

Numerous reports suggest that IL-6 promotes survival and proliferation of multiple myeloma (MM) cells through the phosphorylation of a cell signaling protein, STAT3. Thus, agents that suppress STAT3 phosphorylation have potential for the treatment of MM. In the present report, we demonstrate that curcumin (diferuloylmethane), a pharmacologically safe agent in humans, inhibited IL-6-induced STAT3 phosphorylation and consequent STAT3 nuclear translocation. Curcumin had no effect on STAT5 phosphorylation, but inhibited the IFN-alpha-induced STAT1 phosphorylation. The constitutive phosphorylation of STAT3 found in certain MM cells was also abrogated by treatment with curcumin. Curcumin-induced inhibition of STAT3 phosphorylation was reversible. Compared with AG490, a well-characterized Janus kinase 2 inhibitor, curcumin was a more rapid (30 min vs 8 h) and more potent (10 micro M vs 100 micro M) inhibitor of STAT3 phosphorylation. In a similar manner, the dose of curcumin completely suppressed proliferation of MM cells; the same dose of AG490 had no effect. In contrast, a cell-permeable STAT3 inhibitor peptide that can inhibit the STAT3 phosphorylation mediated by Src blocked the constitutive phosphorylation of STAT3 and also suppressed the growth of myeloma cells. TNF-alpha and lymphotoxin also induced the proliferation of MM cells, but through a mechanism independent of STAT3 phosphorylation. In addition, dexamethasone-resistant MM cells were found to be sensitive to curcumin. Overall, our results demonstrated that curcumin was a potent inhibitor of STAT3 phosphorylation, and this plays a role in the suppression of MM proliferation.
Complementary use of cross-polarization and standard OCT for differential diagnosis of pathological tissues (2002)

An experimental standard optical coherence tomography (OCT) setup that can be easily modified for cross-polarization OCT (CP OCT) operation has been developed to perform differential diagnosis of pathological tissues. The complementary use of CP OCT, a technique that provides a map of cross-polarization backscattering properties of an object being studied by means of low-coherence interferometry, and standard OCT imaging improves the specificity of diagnostics of pathological changes occurring in tissues. It is shown that healthy, neoplastic and scar tissues of the esophagus have different cross-polarization backscattering properties. A comparative analysis of CP OCT, OCT and histological images from one and the same tissue area has been made. A close correlation between the location of collagen fibers in biological tissue and signal intensity in CP OCT images is found.
The H+para-H2 reaction: Influence of dynamical resonances on H2 (v′=1, j ′=1 and 3) integral cross sections (1991)

We have measured integral rate constants for the reaction H+para-H2→H2(v′=1, j′=1 and 3)+H at 11 center-of-mass collision energies (Erel) between 0.88 and 1.01 eV, a region in which dynamical scattering resonances are present. We have also measured the H2(v′ = 1, j′ = 3)/H2(v′ = 1, j′ = 1) population ratio at two additional values of Erel outside of this range. Tunable uv laser photolysis of HI was used to generate translationally hot H atoms of variable kinetic energy. Quantum-state-specific detection of the H2 reaction product was accomplished via (2+1) resonance-enhanced multiphoton ionization and time-of-flight mass spectrometry. The integral rate constants have a smooth dependence on Erel, in agreement with the recent quantum-mechanical (QM) calculations of Zhang and Miller and contrary to the experimental results of Nieh and Valentini. The QM results are in nearly perfect agreement with the present measurements for the dependence on Erel of both the integral rate constants and the H2(v′ = 1, j′ = 3)/H2(v′= 1, j′ = 1) population ratio. It is concluded that measurements of integral cross sections as a function of collision energy are not highly sensitive to the presence of dynamical resonances in this system.
Polystyrene-Bound Dioxirane: a New Class of Recyclable Oxidising Reagent (1996)

Polystyrene-bound dioxirane containing a five-methylene spacer arm between the polymer matrix and reagent function has been prepared and investigated as a new class of recyclable oxidising reagent for various organic substrates. The new reagent was found to oxidise alkenes to epoxides, pyridines to N-oxides and amines to nitro compounds in near-quantitative yields. The spent reagent could be regenerated to the dioxirane resin by a simple reaction without considerable loss in reactivity.
Mechanism of DNA Transport Through Pores (2007)

The transport of electrically charged macromolecules such as DNA through narrow pores is a fundamental process in life. When polymer molecules are forced to navigate through pores, their transport is controlled by entropic barriers that accompany their conformational changes. During the past decade, exciting results have emerged from single-molecule electrophysiology experiments. Specifically, the passage of single-stranded DNA/RNA through alpha-hemolysin pores and double-stranded DNA through solid-state nanopores has been investigated. By a combination of these results with the entropic barrier theory of polymer transport and macromolecular simulations, an understanding of the mechanism of DNA transport through pores has emerged.
Recent advances, prospects and problems in designing new strategies for oligonucleotide and gene delivery in therapy. (1998)

The field of gene therapy has been in rapid expansion since the first submissions of gene therapy trials in the early 1990s which provided encouraging results. Since then, many gene therapy protocols have been approved for phase I clinical trials for the treatment of inherited genetic diseases and cancer. The possibility of employing gene transfer technology to treat AIDS and neurologic diseases is currently under evaluation. Many gene delivery systems have been developed for in vivo studies and therapy. The efficiency of in vivo gene transfer, however, still needs to be optimized, even though significant advances have recently been achieved in improving gene delivery, gene regulation and avoidance of immune responses. This review provides a general outline focusing on the description of the most common gene delivery systems and on their current applications in therapeutics.
Clinical experience with COP-1 in multiple sclerosis. (1988)

COP-1 is one of a series of polypeptide preparations developed to stimulate myelin basic protein (MBP), a natural component of the myelin sheath. MBP in Freund's complete adjuvant induces experimental allergic encephalomyelitis (EAE), an animal model of multiple sclerosis (MS). In saline, MBP suppresses EAE. This is the rationale for the use of COP-1 in MS.
Oxidation Resistant Germanium Nanowires:  Bulk Synthesis, Long Chain Alkanethiol Functionalization, and Langmuir−Blodgett Assembly (2005)

A simple method is developed to synthesize gram quantities of uniform Ge nanowires (GeNWs) by chemical vapor deposition on preformed, monodispersed seed particles loaded onto a high surface area silica support. Various chemical functionalization schemes are investigated to passivate the GeNW surfaces using alkanethiols and alkyl Grignard reactions. The stability of functionalization against oxidation of germanium for various alkyl chain lengths is elucidated by X-ray photoelectron spectroscopy. Among all schemes tested, long chain alkanethiols (> or = C12) are found to impart the most stable GeNW passivation against oxidation upon extended exposure to ambient air. Further, the chemically functionalized oxidation-resistant nanowires are soluble in organic solvents and can be readily assembled into close-packed Langmuir-Blodgett films potentially useful for future high performance electronic devices.
Transition Metal-Catalyzed Ortho-Functionalization in Organic Synthesis (2005)

Recent progress in the filed of transition-metal mediated C-H bond activation has had a great influence on organic synthesis. Among such transition-metal catalyzed reactions, ortho-functionalization via the chelationassisted strategy has been paid great attentions as one of the powerful methodologies for converting aromatic compounds into ones that are more functionalized at the exclusively ortho-position. In this context, various transition metal-catalyzed ortho-functionalizations such as alkylation, alkenylation, silylation and carbonylation are described briefly and their prospects are suggested.
The Factor H Variant Associated with Age-related Macular Degeneration (His-384) and the Non-disease-associated Form Bind Differentially to C-reactive Protein, Fibromodulin, DNA, and Necrotic Cells (2007)

Recently, a polymorphism in the complement regulator factor H (FH) gene has been associated with age-related macular degeneration. When histidine instead of tyrosine is present at position 384 in the seventh complement control protein (CCP) domain of FH, the risk for age-related macular degeneration is increased. It was recently shown that these allotypic variants of FH, in the context of a recombinant construct corresponding to CCPs 6-8, recognize polyanionic structures differently, which may lead to altered regulation of the alternative pathway of complement. We show now that His-384, corresponding to the risk allele, binds C-reactive protein (CRP) poorly compared with the Tyr-384 form. We also found that C1q and phosphorylcholine do not compete with FH for binding to C-reactive protein. The interaction with extracellular matrix protein fibromodulin, which we now show to be mediated, at least in part, by CCP6-8 of FH, occurs via the polypeptide of fibromodulin and not through its glycosaminoglycan modifications. The Tyr-384 variant of FH bound fibromodulin better than the His-384 form. Furthermore, we find that CCP6-8 is able to interact with DNA and necrotic cells, but in contrast the His-384 allotype binds these ligands more strongly than the Tyr-384 variant. The variations in binding affinity of the two alleles indicate that complement activation and local inflammation in response to different targets will differ between His/His and Tyr/Tyr homozygotes.
Procedures for detection of DNA by matrix‐assisted laser desorption/ionization mass spectrometry using a modified nafion film substrate (1995)

Abstract A Nafion film substrate modified with concentrated ammonia was shown to improve the detection of DNA using matrix‐assisted laser desorption/ionization mass spectrometry (MALDI‐MS), especially for DNA strands greater than 200 base pairs. Experimental procedures relating to the detection of DNA by MALDI‐MS using this modified Nafion substrate are described.
Reactive Oxygen Species Expose Cryptic Epitopes Associated with Autoimmune Goodpasture Syndrome (2000)

Goodpasture syndrome is an autoimmune disease of the kidneys and lungs mediated by antibodies and T-cells directed to cryptic epitopes hidden within basement membrane hexamers rich in alpha3 non-collagenous globular (NC1) domains of type IV collagen. These epitopes are normally invisible to the immune system, but this privilege can be obviated by chemical modification. Endogenous drivers of immune activation consequent to the loss of privilege have long been suspected. We have examined the ability of reactive oxygen species (ROS) to expose Goodpasture epitopes buried within NC1 hexamers obtained from renal glomeruli abundant in alpha3(IV) NC1 domains. For some hexameric epitopes, like the Goodpasture epitopes, exposure to ROS specifically enhanced recognition by Goodpasture antibodies in a sequential and time-dependent fashion; control binding of epitopes to alpha3(IV) alloantibodies from renal transplant recipients with Alport syndrome was decreased, whereas epitope binding to heterologous antibodies recognizing all alpha3 NC1 epitopes remained the same. Inhibitors of hydrogen peroxide and hydroxyl radical scavengers were capable of attenuating the effects of ROS in cells and kidney by 30-50%, respectively, thereby keeping the Goodpasture epitopes largely concealed when compared with a 70% maximum inhibition by iron chelators. Hydrogen peroxide administration to rodents was sufficient to expose Goodpasture epitope in vivo and initiate autoantibody production. Our findings collectively suggest that ROS can alter the hexameric structure of type IV collagen to expose or destroy selectively immunologic epitopes embedded in basement membrane. The reasons for autoimmunity in Goodpasture syndrome may lie in an age-dependent deterioration in inhibitor function modulating oxidative damage to structural molecules. ROS therefore may play an important role in shaping post-translational epitope diversity or neoantigen formation in organ tissues.
Dihydrotestosterone synthesis bypasses testosterone to drive castration-resistant prostate cancer (2011)

In the majority of cases, advanced prostate cancer responds initially to androgen deprivation therapy by depletion of gonadal testosterone. The response is usually transient, and metastatic tumors almost invariably eventually progress as castration-resistant prostate cancer (CRPC). The development of CRPC is dependent upon the intratumoral generation of the potent androgen, dihydrotestosterone (DHT), from adrenal precursor steroids. Progression to CRPC is accompanied by increased expression of steroid-5α-reductase isoenzyme-1 (SRD5A1) over SRD5A2, which is otherwise the dominant isoenzyme expressed in the prostate. DHT synthesis in CRPC is widely assumed to require 5α-reduction of testosterone as the obligate precursor, and the increased expression of SRD5A1 is thought to reflect its role in converting testosterone to DHT. Here, we show that the dominant route of DHT synthesis in CRPC bypasses testosterone, and instead requires 5α-reduction of androstenedione by SRD5A1 to 5α-androstanedione, which is then converted to DHT. This alternative pathway is operational and dominant in both human CRPC cell lines and fresh tissue obtained from human tumor metastases. Moreover, CRPC growth in mouse xenograft models is dependent upon this pathway, as well as expression of SRD5A1. These findings reframe the fundamental metabolic pathway that drives CRPC progression, and shed light on the development of new therapeutic strategies.
Role of Host Cytokine Responses in the Pathogenesis of Avian H5N1 Influenza Viruses in Mice (2006)

Highly pathogenic avian H5N1 influenza viruses are now widespread in poultry in Asia and have recently spread to some African and European countries. Interspecies transmission of these viruses to humans poses a major threat to public health. To better understand the basis of pathogenesis of H5N1 viruses, we have investigated the role of proinflammatory cytokines in transgenic mice deficient in interleukin-6 (IL-6), macrophage inflammatory protein 1 alpha (MIP-1alpha), IL-1 receptor (IL-1R), or tumor necrosis factor receptor 1 (TNFR1) by the use of two avian influenza A viruses isolated from humans, A/Hong Kong/483/97 (HK/483) and A/Hong Kong/486/97 (HK/486), which exhibit high and low lethality in mice, respectively. The course of disease and the extent of virus replication and spread in IL-6- and MIP-1alpha-deficient mice were not different from those observed in wild-type mice during acute infection with 1,000 50% mouse infective doses of either H5N1 virus. However, with HK/486 virus, IL-1R-deficient mice exhibited heightened morbidity and mortality due to infection, whereas no such differences were observed with the more virulent HK/483 virus. Furthermore, TNFR1-deficient mice exhibited significantly reduced morbidity following challenge with either H5N1 virus but no difference in viral replication and spread or ultimate disease outcome compared with wild-type mice. These results suggest that TNF-alpha may contribute to morbidity during H5N1 influenza virus infection, while IL-1 may be important for effective virus clearance in nonlethal H5N1 disease.
An effective method to generate attack graph (2005)

As the traditional method, the result of vulnerability scanning can't directly reflect complex attack routes existing in network, so the attack graph is presented. After analyzing host computer, devices link relation and the characteristic of attack, the model of network security status was built. A forward-search, breadth-first and depth-limited (attack steps limited) algorithm is used to produce attack route, and the tools to generate the attack graph is implemented. The experiment validates the prototype of network attack graph generating tools, and contrasts our method to the other used.
A Role for MOSPD1 in Mesenchymal Stem Cell Proliferation and Differentiation (2015)

Mesenchymal stem cells (MSCs) isolated from many tissues including bone marrow and fat can be expanded in vitro and can differentiate into a range of different cell types such as bone, cartilage, and adipocytes. MSCs can also exhibit immunoregulatory properties when transplanted but, although a number of clinical trials using MSCs are in progress, the molecular mechanisms that control their production, proliferation, and differentiation are poorly understood. We identify MOSPD1 as a new player in this process. We generated MOSPD1-null embryonic stem cells (ESCs) and demonstrate that they are deficient in their ability to differentiate into a number of cell lineages including osteoblasts, adipocytes, and hematopoietic progenitors. The self-renewal capacity of MOSPD1-null ESCs was normal and they exhibited no obvious defects in early germ layer specification nor in epithelial to mesenchymal transition (EMT), indicating that MOSPD1 functions after these key steps in the differentiation process. Mesenchymal stem cell (MSC)-like cells expressing CD73, CD90, and CD105 were generated from MOSPD1-null ESCs but their growth rate was significantly impaired implying that MOSPD1 plays a role in MSC proliferation. Phenotypic deficiencies exhibited by MOSPD1-null ESCs were rescued by exogenous expression of MOSPD1, but not MOSPD3 indicating distinct functional properties of these closely related genes. Our in vitro studies were supported by RNA-sequencing data that confirmed expression of Mospd1 mRNA in cultured, proliferating perivascular pre-MSCs isolated from human tissue. This study adds to the growing body of knowledge about the function of this largely uncharacterized protein family and introduces a new player in the control of MSC proliferation and differentiation.