gebhart/patrepeval huggingface dataset:
High-throughput screening for compounds toxic to human leukemic cells derived from lineage-depleted cord blood cells (2007)

A98 Over the past 10 years, research has conclusively shown the existence of a rare population of cancer cells, termed cancer stem cells, in leukemia, brain, colon, and breast cancers. These cells are biologically distinct from bulk cells and are the only cells able to initiate and sustain the disease. Recent experiments indicate that standard chemotherapy for leukemia is less effective against leukemia stem cells (LSC) than bulk leukemia cells and typically does not spare normal hematopoietic stem cells (HSC) and progenitor cells leading to myelosuppression, indicating that a new paradigm is needed to develop cancer therapeutics that effectively eradicate the disease by targeting the LSC. Here, we sought to identify compounds that selectively target LSC but not normal HSC. The novelty of this proposal is to use populations enriched for LSC and HSC, instead of cancer cell lines, in high-throughput screening of small chemical libraries. Recently, we generated human leukemia cell lines by direct transformation of normal human primitive hematopoietic cells (Lin(-) CB cells) with leukemogenic fusion oncogenes, TLS-ERG and MLL-ENL1. These cells exhibit features of LSC, such as hierarchical organization, engraftment of NOD/SCID mice, and a differentiation block, and have been stably maintained in culture for over a year. As a proof of principle, we screened two of the leukemia cell lines, TEX and M9-ENL1, using a simple cell-growth inhibition assay. We used three libraries of small chemicals comprising over 4000 unique known bioactive, off-patent, and natural compounds. 200 compounds (5%) were scored as positive against either TEX or M9-ENL1 cells. For further IC50 studies, we concentrated on the top 80 compounds that inhibited cell growth to 25% of controls. Numerous anti-cancer therapeutics (paclitaxel, etoposide, and vincristine), general cytotoxic agents (brefeldin), and the digitalis family of ion pump inhibitors (digoxin, ouabain) were identified. At this point, we removed 25 redundant compounds and screened 55 compounds on Lin(-) CB cells to identify compounds more specific for leukemia cells than normal cells. Half of the compounds were toxic to Lin(-) CB cells; Lin(-) CB cells were more sensitive than the leukemias for a third of the compounds; and 10 compounds had more activity on both leukemias than Lin(-) CB cells. Currently, we are testing these top 10 compounds using in vitro progenitor assays and will validate the compounds using the NOD/SCID xenotransplantation model. These approaches will rapidly identify potential agents for the development of therapies directly targeting LSC.
A novel bifunctional chimeric complement inhibitor that regulates C3 convertase and formation of the membrane attack complex. (1995)

Human cells express cell surface complement regulatory molecules that inhibit the activity of the C3/C5 convertases (DAF, MCP, CR1) or inhibit the membrane attack complex (CD59). A single molecule that inhibits both the convertase activity and formation of the membrane attack complex has never been characterized. To this end, we have developed two reciprocal chimeric complement inhibitors (CD, NH2-CD59-DAF-GPI; and DC, NH2-DAF-CD59-GPI) that contain the functional domains of decay accelerating factor (DAF; CD55) and CD59. Cell surface expression of the CD and DC chimeric proteins was detected with DAF- and CD59-specific antisera. Cell surface C3d deposition was inhibited on cells expressing the chimeric molecules, thereby indicating that the DAF moiety was functional in both molecules. Conversely, Ab-blocking experiments demonstrated that only the DC molecule retained CD59 function. Therefore, the DC molecule represents a novel potent chimeric bifunctional complement inhibitor that retains the functional domains of two distinct complement regulatory molecules.
NEW CHEMICAL CONVERSIONS OF 5-HYDROXYMETHYLFURFURAL AND THE ELECTROCHEMICAL OXIDATION OF ITS DERIVATIVES (1993)

(1993). NEW CHEMICAL CONVERSIONS OF 5-HYDROXYMETHYLFURFURAL AND THE ELECTROCHEMICAL OXIDATION OF ITS DERIVATIVES. Organic Preparations and Procedures International: Vol. 25, No. 3, pp. 353-355.
Novel Drug Delivery Systems (1991)

Concepts and System Design for the Rate-Controlled Drug Delivery Fundamentals of Rate-Controlled Drug Delivery Oral Drug Delivery and Delivery Systems Mucosal Drug Delivery: Potential Routes for Noninvasive Systemic Administration Nasal Drug Delivery and Delivery Systems Ocular Drug Delivery and Delivery Systems Transdermal Drug Delivery and Delivery Systems Parenteral Drug Delivery and Delivery Systems Vaginal Drug Delivery and Delivery Systems Intrauterine Drug Delivery and Delivery Systems Systemic Delivery of Peptide-Based Pharmaceuticals Regulatory Considerations in Controlled Drug Delivery
Photoperiodic Control of Gibberellin Metabolism in Spinach (1982)

[(3)H]GA(20) applied to spinach plants (Spinacia oleracea L.) was metabolized to several products. Two of these were identified by combined gasliquid chromatography-radio counting as [(3)H]GA(29) and [(3)H]3-epi-GA(1). Inasmuch as both GA(20) and GA(29) are endogenous gibberellins in spinach (Metzger, Zeevaart 1980 Plant Physiol 65: 623-626), it was concluded that the conversion of GA(20) to GA(29) is a natural process. However, 3-epi-GA(1) was not detected in extracts of spinach shoots analyzed by combined gas chromatography-mass spectrometry. This indicates that the conversion of exogenous [(3)H]GA(20) to [(3)H]3-epi-GA(1) may be an artifact.Long-day pretreatment of spinach shoots caused a 2-fold increase in the rate of [(3)H]GA(20) metabolism over the rate of metabolism in plants maintained under short-day conditions. Furthermore, [(3)H]GA(29) accumulated more rapidly under long than under short days, whereas photoperiodic treatment had no effect on the accumulation of [(3)H]3-epi-GA(1). Thus, the long-day-induced increase in the level of endogenous GA(29) in spinach shoots (Metzger, Zeevaart 1980 Plant Physiol 66: 844-846) appears to be the result of an increased capability to convert GA(20) to GA(29).
Dataset of the binding kinetic rate constants of anti-PCSK9 antibodies obtained using the Biacore T100, ProteOn XPR36, Octet RED384, and IBIS MX96 biosensor platforms (2016)

Here we provide data from a head-to-head comparison study using four biosensor platforms: GE Healthcare׳s Biacore T100, Bio-Rad׳s ProteOn XPR36, ForteBio׳s Octet RED384, and Wasatch Microfluidics׳s IBIS MX96. We used these instruments to analyze the binding interactions of a panel of ten high-affinity monoclonal antibodies with their antigen, human proprotein convertase subtilisin kexin type 9 (PCSK9). For each instrument, binding curves obtained at multiple densities of surface antibodies were fit to the 1:1 Langmuir kinetic model, and the association and dissociation rate constants and corresponding affinity constants were calculated. The data supplied in this article accompany the research article entitled, "Comparison of biosensor platforms in the evaluation of high affinity antibody-antigen binding kinetics" (Yang et al., 2016) [1], which further discusses the strengths and weaknesses of each biosensor platform with an emphasis on data consistency, comparability, and operational efficiency.
Polyhydroxylated chiral building block by enzymic desymmetrization of meso 1,3 syn diols (1993)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTPolyhydroxylated chiral building block by enzymic desymmetrization of meso 1,3 syn diolsCarlo Bonini, Rocco Racioppi, Giuliana Righi, and Licia ViggianiCite this: J. Org. Chem. 1993, 58, 4, 802–803Publication Date (Print):February 1, 1993Publication History Published online1 May 2002Published inissue 1 February 1993https://pubs.acs.org/doi/10.1021/jo00056a002https://doi.org/10.1021/jo00056a002research-articleACS PublicationsRequest reuse permissionsArticle Views209Altmetric-Citations30LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-AlertscloseSupporting Info (1)»Supporting Information Supporting Information Get e-Alerts
The Soluble Acyl-Acyl Carrier Protein Synthetase of Vibrio harveyi B392 Is a Member of the Medium Chain Acyl-CoA Synthetase Family (2006)

The gene encoding the unique soluble acyl-acyl carrier protein synthetase (AasS) of the bioluminescent Vibrio harveyi strain B392 has been isolated by expression cloning in Escherichia coli. This enzyme catalyzes the ATP-dependent acylation of the thiol of acyl carrier protein (ACP) with fatty acids with chain lengths from C4 to C18. The gene (called aasS) encodes a protein of 60 kDa, a hexahistidine-tagged version of which was readily expressed in E. coli and purified in large quantities. Surprisingly, the sequence of the encoded protein was significantly more similar to that of an acyl-CoA synthetase of the distantly related bacterium, Thermus thermophilus, than to that of the membrane-bound acyl-acyl carrier protein synthetase of E. coli, an enzyme that catalyzes the same reaction from a more closely related organism. Indeed, the AasS sequence can readily be modeled on the known crystal structures of the T. thermophilus acyl-CoA synthetase with remarkably high levels of conservation of the catalytic site residues. To test the possible role of AasS in the fatty aldehyde-dependent bioluminescence pathway of V. harveyi, the chromosomal aasS gene of the organism was disrupted by insertion of a kanamycin cassette by homologous recombination. The resulting aasS::kan strains retained low levels of acyl-acyl carrier protein synthetase consistent with prior indications of a second such activity in this bacterium. The mutant strains grew normally and had normal levels of bioluminescence but were deficient in the incorporation of exogenous octanoic acid into the cellular phospholipids of V. harveyi, particularly at low octanoate concentrations. These data indicate that AasS is responsible for a high-affinity and high-capacity uptake system that efficiently converts exogenous fatty acids into acyl-ACP species competent to enter the fatty acid biosynthetic cycle.
Locked nucleic acid (LNA) mediated improvements in siRNA stability and functionality (2005)

Therapeutic application of the recently discovered small interfering RNA (siRNA) gene silencing phenomenon will be dependent on improvements in molecule bio-stability, specificity and delivery. To address these issues, we have systematically modified siRNA with the synthetic RNA-like high affinity nucleotide analogue, Locked Nucleic Acid (LNA). Here, we show that incorporation of LNA substantially enhances serum half-life of siRNA's, which is a key requirement for therapeutic use. Moreover, we provide evidence that LNA is compatible with the intracellular siRNA machinery and can be used to reduce undesired, sequence-related off-target effects. LNA-modified siRNAs targeting the emerging disease SARS, show improved efficiency over unmodified siRNA on certain RNA motifs. The results from this study emphasize LNA's promise in converting siRNA from a functional genomics technology to a therapeutic platform.
Characterization of mitral valve anterior leaflet perfusion patterns. (2009)

The ovine AML is perfused by vessels that run through the SC and annulus simultaneously, and then create a communicating arcade in the leaflet. These vessels originate from the mid- and distal portions of the LCx. A loss of perfusion as a result of microvascular disease could have adverse implications. Derangements in the extensive vascular component of the mitral valve could be an important contributing factor to valve disease.
Naive T Cells Transiently Acquire a Memory-like Phenotype during Homeostasis-Driven Proliferation (2000)

In a depleted lymphoid compartment, naive T cells begin a slow proliferation that is independent of cognate antigen yet requires recognition of major histocompatibility complex-bound self-peptides. We have followed the phenotypic and functional changes that occur when naive CD8(+) T cells undergo this type of expansion in a lymphopenic environment. Naive T cells undergoing homeostasis-driven proliferation convert to a phenotypic and functional state similar to that of memory T cells, yet distinct from antigen-activated effector T cells. Naive T cells dividing in a lymphopenic host upregulate CD44, CD122 (interleukin 2 receptor beta) and Ly6C expression, acquire the ability to rapidly secrete interferon gamma, and become cytotoxic effectors when stimulated with cognate antigen. The conversion of naive T cells to cells masquerading as memory cells in response to a homeostatic signal does not represent an irreversible differentiation. Once the cellularity of the lymphoid compartment is restored and the T cells cease their division, they regain the functional and phenotypic characteristics of naive T cells. Thus, homeostasis-driven proliferation provides a thymus-independent mechanism for restoration of the naive compartment after a loss of T cells.
An Enhanced and Simplified Optical Feedback Pixel Circuit for AMOLED Displays (2006)

Active-matrix organic light emitting diode (AMOLED) displays have been considered a potential candidate for the next generation of flat panel displays due to the ability of AMOLED in providing wider viewing angle, larger color gamut, and lower fabrication cost. In this paper we present a new optical feedback pixel circuit that preserves the advantages of active matrix structure while demanding simple off-panels driver and four active components at each pixel but compensates for the luminance degradation of the AMOLED display
Synchronized Biventricular Heart Pacing in a Closed-chest Porcine Model based on Wirelessly Powered Leadless Pacemakers (2020)

About 30% of patients with impaired cardiac function have ventricular dyssynchrony and seek cardiac resynchronization therapy (CRT). In this study, we demonstrate synchronized biventricular (BiV) pacing in a leadless fashion by implementing miniaturized and wirelessly powered pacemakers. With their flexible form factors, two pacemakers were implanted epicardially on the right and left ventricles of a porcine model and were inductively powered at 13.56 MHz and 40.68 MHz industrial, scientific, and medical (ISM) bands, respectively. The power consumption of these pacemakers is reduced to µW-level by a novel integrated circuit design, which considerably extends the maximum operating distance. Leadless BiV pacing is demonstrated for the first time in both open-chest and closed-chest porcine settings. The clinical outcomes associated with different interventricular delays are verified through electrophysiologic and hemodynamic responses. The closed-chest pacing only requires the external source power of 0.3 W and 0.8 W at 13.56 MHz and 40.68 MHz, respectively, which leads to specific absorption rates (SARs) 2-3 orders of magnitude lower than the safety regulation limit. This work serves as a basis for future wirelessly powered leadless pacemakers that address various cardiac resynchronization challenges.
Influence of Time of Day of Blood Pressure–Lowering Treatment on Cardiovascular Risk in Hypertensive Patients With Type 2 Diabetes (2011)

Among patients with diabetes, treatment with ≥1 hypertension medications at bedtime, compared with all medications upon waking, resulted in improved ambulatory blood pressure control and significantly reduced cardiovascular morbidity and mortality.
Insoluble Collagen Matrices for Prolonged Delivery of Proteins (1996)

The purpose of this investigation was to evaluate the application of high molecular weight, insoluble collagen as a carrier material for proteins. Matrices were formulated and their behavior in buffer solution was investigated with focus on swelling and inner structure. Cross-linking with glutaraldehyde was introduced prior to the formation of the devices and its influence characterized. In addition, the enzymatic degradation process was studied and release experiments with systems loaded with fluorescent-labeled bovine serum albumin were carried out. Insoluble collagen matrices were characterized by intensive swelling in buffer resulting in development of a coarse porous character. Cross-linking strongly reduced the water penetration, leading to denser structures of the swollen devices. The continuous enzymatic degradation of the disk-shaped matrices by collagenase followed the kinetics of an heterogeneous enzymatic process with hindrance of proteolysis by the addition of glutaraldehyde. Release studies demonstrated that large amounts of model protein were held in the matrices with increased cross-linking degree. In presence of collagenase a prolonged release of the trapped protein over several days by matrix cleavage could be achieved. Insoluble collagen can be effective as a carrier material for proteins with an in vitro release characteristic by both diffusion-controlled and enzymatic degradation mechanisms. Cross-linking at the stage of preparing the aqueous dispersion offers an alternative to subsequent cross-linking processes.
Are Large-Scale 3D Models Really Necessary for Accurate Visual Localization? (2017)

Accurate visual localization is a key technology for autonomous navigation. 3D structure-based methods employ 3D models of the scene to estimate the full 6DOF pose of a camera very accurately. However, constructing (and extending) large-scale 3D models is still a significant challenge. In contrast, 2D image retrieval-based methods only require a database of geo-tagged images, which is trivial to construct and to maintain. They are often considered inaccurate since they only approximate the positions of the cameras. Yet, the exact camera pose can theoretically be recovered when enough relevant database images are retrieved. In this paper, we demonstrate experimentally that large-scale 3D models are not strictly necessary for accurate visual localization. We create reference poses for a large and challenging urban dataset. Using these poses, we show that combining image-based methods with local reconstructions results in a pose accuracy similar to the state-of-the-art structure-based methods. Our results suggest that we might want to reconsider the current approach for accurate large-scale localization.
Arrayed-waveguide grating for wavelength division multi/demultiplexer with nanometre resolution (1990)

A novel diffraction grating based on arrayed channel waveguides has been proposed for nanometre-spaced wavelength division multiplexing. A grating with a diffraction order of 20 has been fabricated using a composite glass waveguide. A wavelength resolution of 0.63 nm has been achieved in the 1.3 μm wavelength band.
Apoptosis and fibrosis in non-alcoholic fatty liver disease. (2005)

Nonalcoholic fatty liver disease is becoming an increasingly common medical problem in the developed countries which, unfortunately, still is associated with the lack of any effective treatment. However, recent data favor a model in which a pathologically increased rate of hepatocytic apoptosis and the subsequent induction and upregulation of inflammation and fibrosis in the liver provide both a rationale for the pathogenesis of nonalcoholic fatty liver disease, as well as a clue for designing first effective therapeutic strategies. In order to illuminate this context, this article focuses on the pathogenesis and possible new therapeutic options in nonalcoholic fatty liver disease.
A robust rate-adaptive hybrid ARQ scheme for frequency-hopped spread-spectrum multiple-access communication systems (1994)

This paper considers the application of rate-adaptive coding (RAC) to a spread spectrum multiple access (SSMA) communication system. Specifically, RAC using a variable rate Reed-Solomon (RS) code with a single decoder is applied to frequency-hopped SSMA. We show that this combination can accommodate a larger number of users compared to that with conventional fixed-rate coding. This increase is a result of a reduction in the channel interference from other users. The penalty for this improvement in most cases is a slight increase in the delay (composed of propagation and decoding delay). The throughput and the undetected error probability for a M-ary symmetric channel are analyzed, and performance results are presented.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Crystal Structure of theHomo sapiensKynureninase-3-Hydroxyhippuric Acid Inhibitor Complex: Insights into the Molecular Basis Of Kynureninase Substrate Specificity (2008)

Homo sapiens kynureninase is a pyridoxal-5'-phosphate dependent enzyme that catalyzes the hydrolytic cleavage of 3-hydroxykynurenine to yield 3-hydroxyanthranilate and L-alanine as part of the tryptophan catabolic pathway leading to the de novo biosynthesis of NAD(+). This pathway results in quinolinate, an excitotoxin that is an NMDA receptor agonist. High levels of quinolinate have been correlated with the etiology of neurodegenerative disorders such as AIDS-related dementia and Alzheimer's disease. We have synthesized a novel kynureninase inhibitor, 3-hydroxyhippurate, cocrystallized it with human kynureninase, and solved the atomic structure. On the basis of an analysis of the complex, we designed a series of His-102, Ser-332, and Asn-333 mutants. The H102W/N333T and H102W/S332G/N333T mutants showed complete reversal of substrate specificity between 3-hydroxykynurenine and L-kynurenine, thus defining the primary residues contributing to substrate specificity in kynureninases.
Identification of a Peptide Recognized by Five Melanoma-Specific Human Cytotoxic T Cell Lines (1994)

Of several thousand peptides presented by the major histocompatibility molecule HLA-A2.1, at least nine are recognized by melanoma-specific cytotoxic T lymphocytes (CTLs). Tandem mass spectrometry was used to identify and to sequence one of these peptide epitopes. Melanoma-specific CTLs had an exceptionally high affinity for this nine-residue peptide, which reconstituted an epitope for CTL lines from each of five different melanoma patients tested. Recognition by multiple CTL lines suggests that this may be a promising candidate for use in peptide-based melanoma vaccines.