gebhart/patrepeval huggingface dataset:
The Human CD38 Monoclonal Antibody Daratumumab Shows Antitumor Activity and Hampers Leukemia–Microenvironment Interactions in Chronic Lymphocytic Leukemia (2016)

<b>Purpose:</b> To establish a proof-of-concept for the efficacy of the anti-CD38 antibody daratumumab in the poor prognosis CD38<sup>+</sup> chronic lymphocytic leukemia (CLL) subtype.<b>Experimental Design:</b> The mechanism of action of daratumumab was assessed in CLL primary cells and cell lines using peripheral blood mononuclear cells to analyze antibody-dependent cell cytotoxicity (ADCC), murine and human macrophages to study antibody-dependent cell phagocytosis (ADCP), or human serum to analyze complement-dependent cytotoxicity (CDC). The effect of daratumumab on CLL cell migration and adhesion to extracellular matrix was characterized. Daratumumab activity was validated in two <i>in vivo</i> models.<b>Results:</b> Daratumumab demonstrated efficient lysis of patient-derived CLL cells and cell lines by ADCC <i>in vitro</i> and ADCP both <i>in vitro</i> and <i>in vivo</i> whereas exhibited negligible CDC in these cells. To demonstrate the therapeutic effect of daratumumab in CLL, we generated a disseminated CLL mouse model with the CD38<sup>+</sup> MEC2 cell line and CLL patient-derived xenografts (CLL-PDX). Daratumumab significantly prolonged overall survival of MEC2 mice, completely eliminated cells from the infiltrated organs, and significantly reduced disease burden in the spleen of CLL-PDX. The effect of daratumumab on patient-derived CLL cell dissemination was demonstrated <i>in vitro</i> by its effect on CXCL12-induced migration and <i>in vivo</i> by interfering with CLL cell homing to spleen in NSG mice. Daratumumab also reduced adhesion of CLL cells to VCAM-1, accompanied by downregulation of the matrix metalloproteinase MMP9.<b>Conclusions:</b> These unique and substantial effects of daratumumab on CLL viability and dissemination support the investigation of its use in a clinical setting of CLL. <i>Clin Cancer Res; 23(6); 1493-505. ©2016 AACR</i>.
Orthogonal nonnegative matrix t-factorizations for clustering (2006)

Currently, most research on nonnegative matrix factorization (NMF)focus on 2-factor $X=FG^T$ factorization. We provide a systematicanalysis of 3-factor $X=FSG^T$ NMF. While it unconstrained 3-factor NMF is equivalent to it unconstrained 2-factor NMF, itconstrained 3-factor NMF brings new features to it constrained 2-factor NMF. We study the orthogonality constraint because it leadsto rigorous clustering interpretation. We provide new rules for updating $F,S, G$ and prove the convergenceof these algorithms. Experiments on 5 datasets and a real world casestudy are performed to show the capability of bi-orthogonal 3-factorNMF on simultaneously clustering rows and columns of the input datamatrix. We provide a new approach of evaluating the quality ofclustering on words using class aggregate distribution andmulti-peak distribution. We also provide an overview of various NMF extensions andexamine their relationships.
Structure of [NiFe] Hydrogenase Maturation Protein HypE from Escherichia coli and Its Interaction with HypF (2007)

Hydrogenases are enzymes involved in hydrogen metabolism, utilizing H2 as an electron source. [NiFe] hydrogenases are heterodimeric Fe-S proteins, with a large subunit containing the reaction center involving Fe and Ni metal ions and a small subunit containing one or more Fe-S clusters. Maturation of the [NiFe] hydrogenase involves assembly of nonproteinaceous ligands on the large subunit by accessory proteins encoded by the hyp operon. HypE is an essential accessory protein and participates in the synthesis of two cyano groups found in the large subunit. We report the crystal structure of Escherichia coli HypE at 2.0-A resolution. HypE exhibits a fold similar to that of PurM and ThiL and forms dimers. The C-terminal catalytically essential Cys336 is internalized at the dimer interface between the N- and C-terminal domains. A mechanism for dehydration of the thiocarbamate to the thiocyanate is proposed, involving Asp83 and Glu272. The interactions of HypE and HypF were characterized in detail by surface plasmon resonance and isothermal titration calorimetry, revealing a Kd (dissociation constant) of approximately 400 nM. The stoichiometry and molecular weights of the complex were verified by size exclusion chromatography and gel scanning densitometry. These experiments reveal that HypE and HypF associate to form a stoichiometric, hetero-oligomeric complex predominantly consisting of a [EF]2 heterotetramer which exists in a dynamic equilibrium with the EF heterodimer. The surface plasmon resonance results indicate that a conformational change occurs upon heterodimerization which facilitates formation of a productive complex as part of the carbamate transfer reaction.
Strategy in Oligosaccharide Synthesis:  An Application to a Concise Total Synthesis of the KH-1(adenocarcinoma) Antigen (1998)

A concise and potentially practical synthesis of the title compound has been achieved. The route features a high degree of convergence and economy of synthetic operations. A key step is the concurrent introductory addition of three α-l-fucosyl residues at required hydroxyl acceptor sites (see 37 → 39). Conjugation to carrier protein was achieved, and a route to include truncated structures for investigations for antibody specificity was accomplished.
iPhoto '08: The Missing Manual (2002)

With better ways to get your photos online and new options for creating printed projects, iPhoto '11 makes it easier than ever to transfer photos from a digital camera, organize them, and publish, print, or share them in maps-but there's still no printed manual for the program. Fortunately, David Pogue and Lesa Snider team up in this witty, authoritative book that should have been in the box. Organize your collection. Discover all of the options for grouping your pictures-by events, in albums, or based on who's in the photo or where it was taken.Sharpen your editing skills. Learn how to use
Morocco - Jorf Lasfar Power Project : environmental impact assessment (1996)

The Jorf Lasfar Power Plant Project in Morocco (JLPP), while providing much-needed cost-effective new power supplies, will be expanded in a manner protective of the environment. This impact assessment covers the negative effects and mitigations needed during the construction and operation of the two additional coal-fired units constituting this project. Impacts during construction include: increased dust emissions, soil erosion, stormwater runoff and sediment loading, groundwater, noise generation, and increased wastewater and solid waste generation. Measures to mitigate dust are : using dust suppression control methods, such as spraying water on roads or dirt areas or using crushed rock on roadways; covering or seeding stockpiles of fill material to prevent wind erosion; using dust collectors for batch plant operations; spraying or covering trucks carrying fine material; and restricting the traffic on the project site to construction-related vehicles and reducing vehicle speed. Erosion control measures include: silt curtains, hay bales, mulching and seeding to prevent stormwater runoff from carrying sediment and/or surface water contamination to drainage areas and the Atlantic Ocean. Site retention areas or sediment retention ponds will be built to handle diverted and treated storm water runoff. Spill prevention and clean up practices will prevent contamination of stormwater runoff and groundwater from accidental spills or leaks from construction equipment. Groundwater will be monitored and dewatering methods will be applied to remove surface water and shallow groundwater from pooling in excavation areas and to prevent possible contamination or sediment loading from construction activities. Mitigations of operations-related emissions of sulfur dioxide, oxides of nitrogen, and particulate emissions include: monitoring coal sulfur content to control sulfur dioxide emissions; properly operating and maintaining coal burners and registers to control nitrogen oxides; properly operating and maintaining ESPs; regularly spraying the coal pile with water to reduce dust emissions; and good housekeeping to minimize volatile organic compound emissions from paints, solvents, cleaning fluids, and fuel oil. The following mitigative measures involving surface water, ash disposal, wastewater, and noise levels will be take to ensure that JLPP fully complies with project guideline standards of operation: setting basins for coal stormwater runoff used to intercept the suspended matter; land disposal/ash reuse will replace ash disposal at sea; treatment of sanitary wastewater will prevent contamination; and the quarry used for ash disposal may be eventually converted to industrial or agricultural land use.
Group B Streptococcal Vaccines (1985)

In recent years group B Streptococcus (GBS) has been recognized as a major perinatal pathogen. As with other encapsulated bacteria, protective immunity appears to correlate with serum antibody specific for the homologous capsular polysaccharide antigen of each serotype. Since susceptibility of the young infant to disseminated GBS infection relates to type-specific antibody deficiency in maternal serum, immunization of women with purified GBS type-specific polysaccharides has been proposed as a method for the prevention of infant disease through placental transport of protective antibodies. Candidate native polysaccharides from GBS have been purified, immunochemically and structurally characterized, and employed as immunogen in healthy adult volunteers. Native type Ia, II, and III polysaccharides have been shown to be nontoxic, safe, and immunogenic in approximately 65%, 95%, and 70%, respectively, of nonimmune adults. Antibody response to immunization approaches 100% in previously immune volunteers. Vaccine-induced type-specific antibodies to these candidate polysaccharide vaccines promote in vitro opsonophagocytosis, protect animals given a lethal challenge of homologous organisms, and are predominantly of the IgG isotype. Once similar results can be documented in women immunized during the last half of pregnancy, efficacy of these candidate GBS polysaccharide vaccines in the prevention of neonatal and young infant GBS disease should be evaluated.
Digital predistortion of amplitude varying phased array utilising over-the-air combining (2017)

In this paper, we propose a simple polynomial linearisation technique for nonlinear phased arrays including amplitude control. Due to the large number of antennas and thus power amplifiers in the array, it is inefficient to linearise each power amplifier individually. Therefore, it is demonstrated that the array can be linearised over-the-air using single polynomial. The simulations show that the linearisation is achieved by first linearising the higher driven PAs at the precompression region and then cancelling the compression by the heavily expanding lower driven PAs. The proposed approach offers an alternative way of re-thinking the concept of array linearisation over multiple PAs.
Interactions of acid sphingomyelinase and lipid bilayers in the presence of the tricyclic antidepressant desipramine (2004)

The tricyclic antidepressant desipramine causes a decrease in cellular acid sphingomyelinase (A-SMase, EC 3.1.4.12) activity when added to culture medium of human fibroblasts. This effect can be prevented by incubation of the cells with the protease inhibitor leupeptin, which suggests that desipramine induces proteolytic degradation of the lysosomal enzyme. By using surface plasmon resonance (SPR, Biacore) we were able to monitor the interactions of A-SMase and substrate-containing lipid bilayers immobilized on the surface of a Pioneer trade mark L1 sensor chip. SPR binding curves show that the enzyme hardly dissociates from the lipid surface at acidic pH values. On the other hand, a drop in binding signals (resonance units, RU) of approximately 50% occurred after injection of 20 mM desipramine. Our findings indicate that desipramine interferes with the binding of A-SMase to the lipid bilayers and thereby displaces the enzyme from its membrane-bound substrate. The application of control substances suggests a key role for the cationic moiety of desipramine. We hypothesize that the displacement of the glycoprotein A-SMase from the inner membranes of late endosomes and lysosomes by desipramine renders it susceptible to proteolytic cleavage by lysosomal proteases.
Assigning Significance to Peptides Identified by Tandem Mass Spectrometry Using Decoy Databases (2007)

Automated methods for assigning peptides to observed tandem mass spectra typically return a list of peptide-spectrum matches, ranked according to an arbitrary score. In this article, we describe methods for converting these arbitrary scores into more useful statistical significance measures. These methods employ a decoy sequence database as a model of the null hypothesis, and use false discovery rate (FDR) analysis to correct for multiple testing. We first describe a simple FDR inference method and then describe how estimating and taking into account the percentage of incorrectly identified spectra in the entire data set can lead to increased statistical power.
Measurement of immunotargeted plasmonic nanoparticles’ cellular binding: a key factor in optimizing diagnostic efficacy (2008)

In this study, we use polarized light scattering to study immunotargeted plasmonic nanoparticles which bind to live SK-BR-3 human breast carcinoma cells. Gold nanoparticles can be conjugated to various biomolecules in order to target specific molecular signatures of disease. This specific targeting provides enhanced contrast in scattering-based optical imaging techniques. While there are papers which report the number of antibodies that bind per nanoparticle, there are almost no reports of the key factor which influences diagnostic or therapeutic efficacy using nanoparticles: the number of targeted nanoparticles that bind per cell. To achieve this goal, we have developed a 'negative' method of determining the binding concentration of those antibody/nanoparticle bioconjugates which are targeted specifically to breast cancer cells. Unlike previously reported methods, we collected unbound nanoparticle bioconjugates and measured the light scattering from dilute solutions of these particles so that quantitative binding information can be obtained. By following this process, the interaction effects of adjacent bound nanoparticles on the cell membrane can be avoided simply by measuring the light scattering from the unbound nanoparticles. Specifically, using nanoshells of two different sizes, we compared the binding concentrations of anti-HER2/nanoshell and anti-IgG/nanoshell bioconjugates targeted to HER2-positive SK-BR-3 breast cancer cells. The results indicate that, for anti-HER2/nanoshell bioconjugates, there are approximately 800-1600 nanoshells bound per cell; for anti-IgG/nanoshell bioconjugates, the binding concentration is significantly lower at nearly 100 nanoshells bound per cell. These results are also supported by dark-field microscopy images of the cells labeled with anti-HER2/nanoshell and anti-IgG/nanoshell bioconjugates.
Speeding the Pollard and elliptic curve methods of factorization (1987)

Since 1974, several algorithms have been developed that attempt to factor a large number <italic>N</italic> by doing extensive computations modulo <italic>N</italic> and occasionally taking GCDs with <italic>N</italic>. These began with Pollard’s <inline-formula content-type="math/mathml"> <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" alttext="p minus 1"> <mml:semantics> <mml:mrow> <mml:mi>p</mml:mi> <mml:mo>−</mml:mo> <mml:mn>1</mml:mn> </mml:mrow> <mml:annotation encoding="application/x-tex">p - 1</mml:annotation> </mml:semantics> </mml:math> </inline-formula> and Monte Carlo methods. More recently, Williams published a <inline-formula content-type="math/mathml"> <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" alttext="p plus 1"> <mml:semantics> <mml:mrow> <mml:mi>p</mml:mi> <mml:mo>+</mml:mo> <mml:mn>1</mml:mn> </mml:mrow> <mml:annotation encoding="application/x-tex">p + 1</mml:annotation> </mml:semantics> </mml:math> </inline-formula> method, and Lenstra discovered an elliptic curve method (ECM). We present ways to speed all of these. One improvement uses two tables during the second phases of <inline-formula content-type="math/mathml"> <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" alttext="p plus-or-minus 1"> <mml:semantics> <mml:mrow> <mml:mi>p</mml:mi> <mml:mo>±</mml:mo> <mml:mn>1</mml:mn> </mml:mrow> <mml:annotation encoding="application/x-tex">p \pm 1</mml:annotation> </mml:semantics> </mml:math> </inline-formula> and ECM, looking for a match. Polynomial preconditioning lets us search a fixed table of size <italic>n</italic> with <inline-formula content-type="math/mathml"> <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" alttext="n slash 2 plus o left-parenthesis n right-parenthesis"> <mml:semantics> <mml:mrow> <mml:mi>n</mml:mi> <mml:mrow class="MJX-TeXAtom-ORD"> <mml:mo>/</mml:mo> </mml:mrow> <mml:mn>2</mml:mn> <mml:mo>+</mml:mo> <mml:mi>o</mml:mi> <mml:mo stretchy="false">(</mml:mo> <mml:mi>n</mml:mi> <mml:mo stretchy="false">)</mml:mo> </mml:mrow> <mml:annotation encoding="application/x-tex">n/2 + o(n)</mml:annotation> </mml:semantics> </mml:math> </inline-formula> multiplications. A parametrization of elliptic curves lets Step 1 of ECM compute the <italic>x</italic>-coordinate of <italic>nP</italic> from that of <italic>P</italic> in about 9.3 <inline-formula content-type="math/mathml"> <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" alttext="log Subscript 2"> <mml:semantics> <mml:mrow class="MJX-TeXAtom-ORD"> <mml:msub> <mml:mi>log</mml:mi> <mml:mn>2</mml:mn> </mml:msub> </mml:mrow> <mml:annotation encoding="application/x-tex">{\log _2}</mml:annotation> </mml:semantics> </mml:math> </inline-formula> <italic>n</italic> multiplications for arbitrary <italic>P</italic>.
Inhibition of the visual cycle in vivo by 13 -cis retinoic acid protects from light damage and provides a mechanism for night blindness in isotretinoin therapy (2001)

Isotretinoin (13-cis retinoic acid) is frequently prescribed for severe acne [Peck, G. L., Olsen, T. G., Yoder, F. W., Strauss, J. S., Downing, D. T., Pandya, M., Butkus, D. & Arnaud-Battandier, J. (1979) N. Engl. J. Med. 300, 329-333] but can impair night vision [Fraunfelder, F. T., LaBraico, J. M. & Meyer, S. M. (1985) Am. J. Ophthalmol. 100, 534-537] shortly after the beginning of therapy [Shulman, S. R. (1989) Am. J. Public Health 79, 1565-1568]. As rod photoreceptors are responsible for night vision, we administered isotretinoin to rats to learn whether night blindness resulted from rod cell death or from rod functional impairment. High-dose isotretinoin was given daily for 2 months and produced systemic toxicity, but this caused no histological loss of rod photoreceptors, and rod-driven electroretinogram amplitudes were normal after prolonged dark adaptation. Additional studies showed, however, that even a single dose of isotretinoin slowed the recovery of rod signaling after exposure to an intense bleaching light, and that rhodopsin regeneration was markedly slowed. When only a single dose was given, rod function recovered to normal within several days. Rods and cones both showed slow recovery from bleach after isotretinoin in rats and in mice. HPLC analysis of ocular retinoids after isotretinoin and an intense bleach showed decreased levels of rhodopsin chromophore, 11-cis retinal, and the accumulation of the biosynthetic intermediates, 11-cis and all-trans retinyl esters. Isotretinoin was also found to protect rat photoreceptors from light-induced damage, suggesting that strategies of altering retinoid cycling may have therapeutic implications for some forms of retinal and macular degeneration.
Molecular studies of identification of genes for osteoporosis: the 2002 update (2003)

We aim to give a comprehensive review, updated to 2002, of the most important and representative molecular genetic studies, performed mainly within the past decade, that aimed to identify the gene(s) involved in osteoporosis. Early reviews were largely confined to association studies in humans, but we review here, separately, the results of both association and linkage studies in humans, and quantitative trait locus (QTL) mapping in animal models. The main results of all the studies are tabulated for comparison and ease of reference, and to provide a comprehensive retrospective view of molecular genetics studies of osteoporosis. The most striking findings and the most representative studies are singled out for comment regarding the immediacy of their influence on present understanding of the genetics of osteoporosis and on the current status of genetic research in osteoporosis. This is particularly relevant for studies on the association of the vitamin D receptor (VDR) gene, for which there has been a large body of studies and reviews published. The format adopted by this review should be ideal for accommodating future new advances and studies in a fairly young field that is still developing rapidly.
Charge carrier transport and electroluminescence in atomic layer deposited poly-GaN/c-Si heterojunction diodes (2018)

In this work, we study the charge carrier transport and electroluminescence (EL) in thin-film polycrystalline (poly-) GaN/c-Si heterojunction diodes realized using a plasma enhanced atomic layer deposition process. The fabricated poly-GaN/p-Si diode with a native oxide at the interface showed a rectifying behavior (Ion/Ioff ratio ∼ 103 at ±3 V) with current-voltage characteristics reaching an ideality factor n of ∼5.17. The areal (Ja) and peripheral (Jp) components of the current density were extracted, and their temperature dependencies were studied. The space charge limited current (SCLC) in the presence of traps is identified as the dominant carrier transport mechanism for Ja in forward bias. An effective trap density of 4.6 × 1017/cm3 at a trap energy level of 0.13 eV below the GaN conduction band minimum was estimated by analyzing Ja. Other basic electrical properties of the material such as the free carrier concentration, effective density of states in the conduction band, electron mobility, and dielectric relaxation time were also determined from the current-voltage analysis in the SCLC regime. Further, infrared EL corresponding to the Si bandgap was observed from the fabricated diodes. The observed EL intensity from the GaN/p-Si heterojunction diode is ∼3 orders of magnitude higher as compared to the conventional Si only counterpart. The enhanced infrared light emission is attributed to the improved injector efficiency of the GaN/Si diode because of the wide bandgap of the poly-GaN layer and the resulting band discontinuity at the GaN/Si interface.
Unconditional Security From Noisy Quantum Storage (2012)

We consider the implementation of two-party cryptographic primitives based on the sole assumption that no large-scale reliable quantum storage is available to the cheating party. We construct novel protocols for oblivious transfer and bit commitment, and prove that realistic noise levels provide security even against the most general attack. Such unconditional results were previously only known in the so-called bounded-storage model which is a special case of our setting. Our protocols can be implemented with present-day hardware used for quantum key distribution. In particular, no quantum storage is required for the honest parties.