gebhart/patrepeval huggingface dataset:
Serum concentrations of DKK‐1 decrease in patients with multiple myeloma responding to anti‐myeloma treatment (2008)

Lytic bone destruction is a hallmark of multiple myeloma (MM) and is because of an uncoupling of bone remodeling. Secretion of Dickkopf (DKK)-1 by myeloma cells is a major factor which causes inhibition of osteoblast precursors. In this study, the effect of different treatment regimens for MM on serum DKK-1 was evaluated and correlated with the response to treatment in 101 myeloma patients receiving bortezomib, thalidomide, lenalidomide, adriamycin and dexamethasone (AD) or high-dose chemotherapy (HDCT) followed by autologous stem cell transplantation (ASCT). At baseline, myeloma patients had increased serum DKK-1 as compared with patients with MGUS (mean 3786 pg/mL vs. 1993 pg/mL). There was no difference between previously untreated MM patients and patients at relapse. A significant decrease of DKK-1 after therapy was seen in the following groups: Bortezomib (4059 pg/mL vs. 1862 pg/mL, P = 0.016), lenalidomide (11837 pg/mL vs. 4374 pg/mL, P = 0.039), AD (1668 pg/mL vs. 1241 pg/mL, P = 0.016), and AD + HDCT + ASCT (2446 pg/mL vs. 1082 pg/mL, P = 0.001). Thalidomide led to a non-significant decrease in DKK-1 (1705 pg/mL vs. 1269 pg/mL, P = 0.081). Within all groups, a significant decrease of DKK-1 was only seen in responders (i.e. patients achieving complete remission or partial remission), but not in non-responders. We show for the first time that serum DKK-1 levels decrease in myeloma patients responding to treatment, irrespective of the regimen chosen. These data suggest that myeloma cells are the main source of circulating DKK-1 protein and provide a framework for clinical trials on anti-DKK-1 treatment in MM.
Effect of NGM282, an FGF19 analogue, in primary sclerosing cholangitis: A multicenter, randomized, double-blind, placebo-controlled phase II trial (2018)

We present for the first time, the clinical and laboratory effects of a first-in-class, engineered analogue of the endocrine hormone FGF19 in patients with primary sclerosing cholangitis (PSC). By incorporating non-invasive markers of fibrosis, beyond standard liver injury markers, we show that NGM282 impacted on fibrosis turnover and hepatic inflammation without changing alkaline phosphatase. Our findings demonstrate the complexities of using highly potent rational agents in PSC, and furthermore challenge the dogma about what the appropriate endpoints should be for trials in PSC.
The potential of L‐form bacteria in biotechnology (1999)

Abstract L‐form bacteria include both stable and unstable cell wall‐less variants of native walled bacteria. These organisms have been implicated as etiologic agents in both plant and animal diseases. L‐form bacteria may also be used to protect plants or animals against disease‐causing organisms, or to act as a host bacterium for the production and secretion to the growth medium of recombinant proteins. This article summarizes the fundamental biology of these unusual bacteria and discusses their potential uses.
Activity and Inhibition Resistance of a Phospholipase-Resistant Synthetic Surfactant in Rat Lungs (2007)

This study investigates the activity and inhibition resistance in excised rat lungs of a novel synthetic surfactant containing the phospholipase-resistant diether phosphonolipid DEPN-8 plus 1.5% bovine surfactant protein (SP)-B/C compared to calf lung surfactant extract (CLSE). DEPN-8 + 1.5% SP-B/C surpassed CLSE in normalizing surfactant-deficient pressure-volume (P-V) deflation mechanics in lavaged excised lungs in the presence of phospholipase A(2) (PLA(2)) or C18:1 lyso-phosphatidylcholine (LPC). DEPN-8 + 1.5% SP-B/C had activity equal to CLSE in normalizing P-V mechanics in the absence of inhibitors or in the presence of serum albumin. These physiologic activity findings were directly consistent with surface activity measurements on the pulsating bubble surfactometer. In the absence of inhibitors, DEPN-8 + 1.5% SP-B/C and CLSE rapidly reached minimum surface tensions < 1 mN/m (0.5 and 2.5 mg surfactant phospholipid/ml). DEPN-8 + 1.5% SP-B/C maintained its high surface activity in the presence of PLA(2), while the surface activity of CLSE was significantly inhibited by exposure to this enzyme. DEPN-8 + 1.5% SP-B/C also had greater surface activity than CLSE in the presence of LPC, and the two surfactants had equivalent surface activity in the presence of albumin. DEPN-8 + 1.5% SP-B/C also had slightly greater surface activity than CLSE when exposed to peroxynitrite in pulsating bubble studies. These results support the potential of developing highly active and inhibition-resistant synthetic exogenous surfactants containing DEPN-8 + apoprotein/peptide constituents for use in treating direct pulmonary forms of clinical acute lung injury (ALI) and the acute respiratory distress syndrome (ARDS).
Adult BM generates CD5+ B1 cells containing abundant N‐region additions (2009)

The self-renewing capacity of B1 cells infers homeostatic regulation; however, previous work suggests the low level of N-region addition characterizing B1 cells early in life increases with age, which implies that the B1-cell population is not a closed system. To explore this, we evaluated N-region addition in CD5(+) B1 cells generated from adult BM. Adult BM cells were marked with GFP introduced by mouse stem cell virus transduction, and were then adoptively transferred into lethally irradiated recipients. Within 2-3 months, we found GFP-marked CD5(+) B cells in the peritoneal cavities of recipients, which we demonstrate here meet a variety of criteria for B1-cell traits including Mac-1 surface expression; annexin, elfin, and Pax-5 gene expression; mitogenic responsiveness to phorbol ester; and spontaneous immunoglobulin secretion. Notably, we found by single-cell PCR that this population of BM-derived CD5(+) B1 cells expressed immunoglobulin with abundant N-region addition (and little V(H)11/V(H)12 skewing), unlike CD5(+) B1 cells obtained from unmanipulated animals but reminiscent of B2 cells. Further, we confirmed that native CD5(+) B1 cells from older mice contain more N-region additions than native CD5(+) B1 cells from younger mice. These results suggest that adult BM progenitors contribute to the peritoneal CD5(+) B1-cell pool over time.
Application of digital speckle photography to flash x-ray studies of internal deformation fields in impact experiments (1999)

A technique to measure two-dimensional deformation fields of a layer inside materials during dynamic events such as impact experiments is presented. Even optically opaque materials like cement can be evaluated when flash x rays are used. Blocks of polyester and cement were prepared with a layer of x-ray-absorbing lead particles. The specimens were then hit by a 9-mm-diameter steel sphere (ball bearing) fired from a 9-mm-bore gas gun at a velocity of 373.5 +/- 3.0 ms(-1). A 30-ns-long x-ray pulse exposed one radiograph before impact; another radiograph was exposed a short time after the impact on the specimen. The two-dimensional displacement field was obtained when the x-ray radiographs were digitized by a conventional flatbed scanner, and a digital speckle photography algorithm was used to calculate the displacements. The flash x-ray technique allowed examination of the deformation at the layer inside the material during failure, thus giving interesting data about the material flow field around the impactor.
Catecholamine Synthesis is Mediated by Tyrosinase in the Absence of Tyrosine Hydroxylase (1999)

Catecholamine neurotransmitters are synthesized by hydroxylation of tyrosine to L-dihydroxyphenylalanine (L-Dopa) by tyrosine hydroxylase (TH). The elimination of TH in both pigmented and albino mice described here, like pigmented TH-null mice reported previously (Kobayashi et al., 1995; Zhou et al., 1995), demonstrates the unequivocal requirement for catecholamines during embryonic development. Although the lack of TH is fatal, TH-null embryos can be rescued by administration of catecholamine precursors to pregnant dams. Once born, TH-null pups can survive without further treatment until weaning. Given the relatively rapid half-life of catecholamines, we expected to find none in postnatal TH-null pups. Despite the fact that the TH-null pups lack TH and have not been supplemented with catecholamine precursers, catecholamines are readily detected in our pigmented line of TH-null mice by glyoxylic acid-induced histofluorescence at postnatal day 7 (P7) and P15 and quantitatively at P15 in sympathetically innervated peripheral organs, in sympathetic ganglia, in adrenal glands, and in brains. Between 2 and 22% of wild-type catecholamine concentrations are found in these tissues in mutant pigmented mice. To ascertain the source of the catecholamine, we examined postnatal TH-null albino mice that lack tyrosinase, another enzyme that converts tyrosine to L-Dopa but does so during melanin synthesis. In contrast to the pigmented TH-null mice, catecholamine histofluorescence is undetectable in postnatal albino mutants, and the catecholamine content of TH-null pups lacking tyrosinase is 18% or less than that of TH-null mice with tyrosinase. Thus, these extraordinary circumstances reveal that tyrosinase serves as an alternative pathway to supply catecholamines.
Biologic strategies for the therapy of intervertebral disc degeneration (2003)

Recent advances in tissue engineering have led to promising new approaches for the biologic treatment of disc degeneration. At present, there is no effective therapy for disc degeneration, a condition which results in large healthcare and socio-economic costs. This article will examine the current approaches used in biologic therapies for disc degeneration, including cell-based tissue engineering, gene therapy and the application of mesenchymal stem cells, and discuss their therapeutic potential, as demonstrated in animal models and experimental studies to date.
Cell transfection in vitro and in vivo with nontoxic TAT peptide-liposome–DNA complexes (2003)

Liposomes modified with TAT peptide (TATp-liposomes) showed fast and efficient translocation into the cell cytoplasm with subsequent migration into the perinuclear zone. TATp-liposomes containing a small quantity (<or=10 mol %) of a cationic lipid formed firm noncovalent complexes with DNA. Here, we present results demonstrating both in vitro and in vivo transfection with TATp-liposome-DNA complexes. Mouse NIH/3T3 fibroblasts and rat H9C2 cardiomyocytes were transfected with such complexes in vitro. The transfection with the TATp-liposome-associated pEGFP-N1 plasmid encoding for the green fluorescent protein (GFP) was high, whereas the cytotoxicity was lower than that of commonly used cationic lipid-based gene-delivery systems. Intratumoral injection of TATp-liposome-DNA complexes into the Lewis lung carcinoma tumor of mice also resulted in an expression of GFP in tumor cells. This transfection system should be useful for various protocols of cell treatment in vitro or ex vivo as well as for localized in vivo gene therapy.
Adenovirus-mediated overexpression of p15INK4B inhibits human glioma cell growth, induces replicative senescence, and inhibits telomerase activity similarly to p16INK4A. (2000)

The genes encoding the cyclin-dependent kinase inhibitors p16INK4A (CDKN2A) and p15INK4B (CDKN2B) are frequently homozygously deleted in a variety of tumor cell lines and primary tumors, including glioblastomas in which 40-50% of primary tumors display homozygous deletions of these two loci. Although the role of p16 as a tumor suppressor has been well documented, it has remained less well studied whether p15 plays a similar growth-suppressing role. Here, we have used replication-defective recombinant adenoviruses to compare the effects of expressing wild-type p16 and p15 in glioma cell lines. After infection, high levels of p16 and p15 were observed in two human glioma cell lines (U251 MG and U373 MG). Both inhibitors were found in complex with CDK4 and CDK6. Expression of p16 and p15 had indistinguishable effects on U251 MG, which has homozygous deletion of CDKN2A and CDKN2B, but a wild-type retinoblastoma (RB) gene. Cells were growth-arrested, showed no increased apoptosis, and displayed a markedly altered cellular morphology and repression of telomerase activity. Transduced cells became enlarged and flattened and expressed senescence-associated beta-galactosidase, thus fulfilling criteria for replicative senescence. In contrast, the growth and morphology of U373 MG, which expresses p16 and p15 endogenously, but undetectable levels of RB protein, were not affected by exogenous overexpression of either inhibitor. Thus, we conclude that overexpression of p15 has a similar ability to inhibit cell proliferation, to cause replicative senescence, and to inhibit telomerase activity as p16 in glioma cells with an intact RB protein pathway.
The value of volatile resources in electricity markets (2010)

While renewable resources most certainly provide environmental benefits, and also help to meet aggressive renewable energy targets, their deployment has pronounced impacts on system operations. There is an acute need to understand these impacts in order to fully harness the benefits of renewable resource integration. In this paper we focus on the integration of wind energy resources in a multi-settlement electricity market structure. We study the dynamic competitive equilibrium for a stochastic market model, and obtain closed form expressions for the supplier and consumer surpluses. Numerical results based on these formulae show that the value of wind generation to consumers, under the current operational practices, falls dramatically with volatility. In fact, we can establish thresholds for the coefficient of variation beyond which the value of wind is questionable. These findings emphasize the need to investigate operational schemes that address volatility.
Controlled growth of periodic pillars by glancing angle deposition (2002)

It has been shown that glancing angle deposition (GLAD) coupled with a prefabricated seed layer can be used to fabricate periodic microstructures. In this article, we show that the column competition effects inherent within aperiodic GLAD films can be delayed in periodic films due to the tendency of the film to achieve a preferred density at a given flux incidence angle. This technique, coupled with the use of the three-dimensional ballistic simulator, may allow for the design and use of periodic GLAD microstructures in such applications as magnetic pillars and three-dimensional photonic crystals.
Synthesis and biological activity of some new aminoacylcarbazole derivatives. Part I (1982)

Abstract The syntheses of different 9‐( N ‐phthalyl‐ or N ‐tosyl‐ or free aminoacyl)carbazoles and the corresponding derivatives of 3,6‐dinitrocarbazoles and some derivatives of 3,6‐diamino‐9‐( N ‐phthalylaminoacyl)carbazoles (II‐XXXII) are described. Compounds VIII, XIII‐XVII and XXIII‐XXVII were found to be active against a number of microorganisms.
Dissociation of endotoxic activities in a chemically synthesized lipid A precursor after acetylation (1995)

In a previous study, a chemically synthesized disaccharide precursor of lipid A (406; identical to lipid IVA) was shown to have dramatically reduced lethality, B-cell mitogenicity, and tumor necrosis factor induction in macrophages when its hydroxyl groups were replaced with either succinyl or acetyl residues (K. Tanamoto, FEBS Lett. 351:325-329, 1994). Succinylated 406 was found to lose Limulus amoebocyte lysate gelation activity completely as a result of the modification (about 10(5)-fold), too, as expected. However, acetyl 406, surprisingly, exhibited activity comparable to that of the original 406. Both succinylated and acetylated 406 lost pyrogenicity completely. These results indicate that one of the typical endotoxic activities was dissociated from the others and that the ability to induce Limulus amoebocyte lysate gelation is not always representative of endotoxin activity.
Expression cloning of different bacterial phosphataseencoding genes by histochemical screening of genomic libraries onto an indicator medium containing phenolphthalein diphosphate and methyl green (1997)

A system for expression cloning of bacterial phosphatase-encoding genes has been developed, and its potential has been investigated. The system is based on histochemical screening of bacterial genomic libraries, constructed in an Escherichia coli multicopy plasmid vector, for phosphatase-producing clones using an indicator medium (named TPMG) made of Tryptose-Phosphate agar supplemented with the phosphatase substrate phenolphthalein diphosphate and the stain methyl green. To test the performance of this system, three genomic libraries were constructed from bacterial strains of different species which showed different patterns of phosphatase activity, and were screened using the TPMG medium. Following a partial screening, three different phosphatase-encoding genes (respectively encoding a class A non-specific acid phosphatase, an acid-hexose phosphatase and a non-specific alkaline phosphatase) were shotgun-cloned from the above libraries, indicating that the TPMG-based expression cloning system can be useful for rapid isolation of different bacterial phosphatase-encoding genes.
Autoantibody-producing RP105- B cells, from patients with systemic lupus erythematosus, showed more preferential expression of BCMA compared with BAFF-R than normal subjects (2010)

RP105(-) B cells from SLE patients showed more preferential expression of BCMA compared with BAFF-R than normal subjects, and were possibly regulated by BAFF/APRIL. Our results provide a new insight of BCMA and their ligands in B cells from SLE patients.
Single molecules of the bacterial actin MreB undergo directed treadmilling motion in Caulobacter crescentus (2006)

The actin cytoskeleton represents a key regulator of multiple essential cellular functions in both eukaryotes and prokaryotes. In eukaryotes, these functions depend on the orchestrated dynamics of actin filament assembly and disassembly. However, the dynamics of the bacterial actin homolog MreB have yet to be examined in vivo. In this study, we observed the motion of single fluorescent MreB-yellow fluorescent protein fusions in living Caulobacter cells in a background of unlabeled MreB. With time-lapse imaging, polymerized MreB [filamentous MreB (fMreB)] and unpolymerized MreB [globular MreB (gMreB)] monomers could be distinguished: gMreB showed fast motion that was characteristic of Brownian diffusion, whereas the labeled molecules in fMreB displayed slow, directed motion. This directional movement of labeled MreB in the growing polymer provides an indication that, like actin, MreB monomers treadmill through MreB filaments by preferential polymerization at one filament end and depolymerization at the other filament end. From these data, we extract several characteristics of single MreB filaments, including that they are, on average, much shorter than the cell length and that the direction of their polarized assembly seems to be independent of the overall cellular polarity. Thus, MreB, like actin, exhibits treadmilling behavior in vivo, and the long MreB structures that have been visualized in multiple bacterial species seem to represent bundles of short filaments that lack a uniform global polarity.
On a routing problem (1958)

Given a set of <inline-formula content-type="math/mathml"> <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" alttext="upper N"> <mml:semantics> <mml:mi>N</mml:mi> <mml:annotation encoding="application/x-tex">N</mml:annotation> </mml:semantics> </mml:math> </inline-formula> cities, with every two linked by a road, and the times required to traverse these roads, we wish to determine the path from one given city to another given city which minimizes the travel time. The times are not directly proportional to the distances due to varying quality of roads and varying quantities of traffic.
Fe–Cu Bimetallic Catalysts for Selective CO2 Hydrogenation to Olefin-Rich C2+ Hydrocarbons (2018)

This paper reports on Fe–Cu bimetallic catalysts supported on γ-alumina for selective CO2 hydrogenation to olefin-rich C2+ hydrocarbons. A strong synergetic promoting effect on C2+ hydrocarbon synthesis was observed over Fe–Cu bimetallic catalysts when the Cu/(Cu + Fe) atomic ratio was 0.17. Compared to monometallic Fe catalyst, the Fe–Cu bimetallic catalyst significantly enhances C2–C7 hydrocarbon formation and suppresses the formation of undesired CH4. The addition of K into Fe–Cu bimetallic catalysts inhibits the methanation and further enhances the formation of C2+ hydrocarbons in the meantime. The synthesis of olefin-rich C2–C4 hydrocarbons from CO2/H2 was achieved by using K-promoted Fe–Cu/Al2O3 catalysts with higher K/Fe atomic ratios (e.g., K/Fe ≥ 0.5), where the selectivity of C2–C4 olefin contents was even higher than K-promoted Fe–Co catalysts under the same reaction conditions.
Pradefovir: A Prodrug That Targets Adefovir to the Liver for the Treatment of Hepatitis B (2008)

Adefovir dipivoxil, a marketed drug for the treatment of hepatitis B, is dosed at submaximally efficacious doses because of renal toxicity. In an effort to improve the therapeutic index of adefovir, 1-aryl-1,3-propanyl prodrugs were synthesized with the rationale that this selectively liver-activated prodrug class would enhance liver levels of the active metabolite adefovir diphosphate (ADV-DP) and/or decrease kidney exposure. The lead prodrug (14, MB06866, pradefovir), identified from a variety of in vitro and in vivo assays, exhibited good oral bioavailability (F = 42%, mesylate salt, rat) and rate of prodrug conversion to ADV-DP. Tissue distribution studies in the rat using radiolabeled materials showed that cyclic 1-aryl-1,3-propanyl prodrugs enhance the delivery of adefovir and its metabolites to the liver, with pradefovir exhibiting a 12-fold improvement in the liver/kidney ratio over adefovir dipivoxil.
Can recursive bisection alone produce routable placements? (2000)

This work focuses on congestion-driven placement of standard cells into rows in the fixed-die context. We summarize the state-of-the-art after two decades of research in recursive bisection placement and implement a new placer, called Capo, to empirically study the achievable limits of the approach. From among recently proposed improvements to recursive bisection, Capo incorporates a leading-edge multilevel min-cut partitioner [7], techniques for partitioning with small tolerance [8], optimal min-cut partitioners and end-case min-wirelength placers [5], previously unpublished partitioning tolerance computations, and block splitting heuristics. On the other hand, our “good enough” implementation does not use “overlapping” [17], multi-way partitioners [17, 20], analytical placement, or congestion estimation [24, 35]. In order to run on recent industrial placement instances, Capo must take into account fixed macros, power stripes and rows with different allowed cell orientations. Capo reads industry-standard LEF/DEF, as well as formats of the GSRC bookshelf for VLSI CAD algorithms [6], to enable comparisons on available placement instances in the fixed-die regime.
Gene Researchers Hunt Bargains, Fixer-Uppers (2002)

BOSTON, MASSACHUSETTS—Technology buffs, bioinformaticists, and hardcore experimentalists rubbed elbows here 2 to 5 October at TIGR's 14th International Genome Sequencing and Analysis Conference. They met to discuss better ways to gather and use genomic information, a vast array of which is now at their fingertips. Highlights included discussions of chromosome evolution and new low-cost sequencing approaches.
Continuous Intravenous Administration of Live Genetically Modified Salmonella Typhimurium in Patients With Metastatic Melanoma (2003)

Surgery Branch Center for Cancer Research National Cancer Institute National Institutes of Health Bethesda, Maryland, U.S.A. Address correspondence and reprint requests to Steven A. Rosenberg, MD, PhD, Building 10, Room 2B42, 9000 Rockville Pike, Bethesda, MD, U.S.A.; e-mail: [email protected]