gebhart/patrepeval huggingface dataset:
Its Biology, Clinical Aspects, and Possibilities (1992)

Thrombopoietin or thrombocytopoiesis-stimulating factor (TSF) is known to be the natural stimulator of megakaryocytopoiesis and, thus, stimulates thrombocytopoiesis. In the past 15 years, new assay technology and sources of the hormone have made possible partial characterization of the molecule and clarification of the biologic role of thrombopoietin. Experiments describing the biology and characterization of TSF are reviewed. In addition, a brief history of the molecule, its biology, and the effects of thrombopoietin on both thrombocytopoiesis and megakaryocytopoiesis are discussed, including the effects of thrombopoietin on platelet counts, platelet sizes, and incorporation of isotopes. In the discussion of thrombopoietin's control of megakaryocytopoiesis there is specific information showing that thrombopoietin stimulates an increase in megakaryocyte size and number, DNA content, endomitosis, and maturation. Thrombopoietin also increases the number of early precursor cells of the megakaryocytic series, that is, small acetyl-cholinesterase-positive cells. New information is given on the chemistry of thrombopoietin, along with present assays and the relationship of thrombopoietin to interleukin-6. The clinical aspects of thrombopoietin, with detailed descriptions of several disease states in which decreases and excesses of the hormone have been found, are presented. The potential uses of thrombopoietin in clinical medicine are reviewed. In the near future, it appears that successful gene cloning of the hormone will be achieved, which will allow production of large amounts of recombinant thrombopoietin. The pure material will be helpful in clarifying the hormone's mode of action. Thrombopoietin will no doubt prove to be useful in treating patients with various hematologic disorders, such as patients undergoing bone marrow transplantation, chemotherapy, or radiotherapy, and other patients with various types of marrow hypoplasia.
Selection of Normal Human Hematopoietic Stem Cells for Bone Marrow Transplantation Using Immunomagnetic Microspheres and CD34 Antibody (1991)

Complete yet nontoxic removal of tumor cells from autologous marrow grafts has proved difficult. New methods for separating normal stem cells from tumor cells are needed. The CD34+ cells in bone marrow, 1-2% of the low-density leukocytes, include precursors of all lymphohematopoietic lineages and probably also the primitive cells responsible for engraftment. A nontoxic, inexpensive, reproducible, and clinically applicable method for positive selection of CD34+ cells was developed. Paramagnetic microspheres coated with goat anti-mouse IgG1 are used to partition the cells; brief incubation with chymopapain is used to release them from the beads. Chymopapain exposure does not injury colony-forming cells or delay engraftment in rodents. Clinical volumes of bone marrow can be processed rapidly. In pilot experiments, the resulting grafts have a purity of 85-99% CD34+ cells and 40% median recovery of the assayable colony-forming cells. These studies form the background for a Phase I trial of autologous BMT using CD34+ stem cells.
The Selenocysteine-Inserting tRNA Species: Structure and Function (2014)

The occurrence of the amino acid selenocysteine in proteins was first demonstrated for protein A of glycine reductase from Clostridium sticklandii in 1976, and questions were immediately raised on its mechanism of incorporation. At that time, the universality of the 20 proteinogenic amino acids was taken for granted, as was the fact that the 64 codons of the “universal” genetic code are assigned either to code for one of these 20 amino acids or to serve as termination signals. Thus, it seemed unlikely that selenocysteine would be considered as a classical amino acid. In principle, the definition of such a 21st amino acid would require (i) that its incorporation proceeds via a cotranslational mechanism, (ii) that it is directed by a specific codon, and (iii) that a specific tRNA mediates its transport to the ribosome. This chapter illustrates that selenocysteine fulfills these criteria. It first describes the unusual structural properties of tRNASec, and then discusses the unique pathway of selenocysteine insertion that has been worked out for Escherichia coli, which has finally led to the proposal of a model for the co-translational incorporation process at the ribosome. The chapter further compares the pathway established in E. coli with the current knowledge on the mammalian system. Finally, it addresses the interesting question of the evolution of the pathway for the incorporation of selenocysteine that differs from that of the 20 standard amino acids in many respects
BIACORE J: a new platform for routine biomolecular interaction analysis† (2001)

SPR biosensor technology continues to evolve. The recently released platform from Biacore AB (Uppsala, Sweden), BIACORE J, is designed for the routine analysis of biomolecular interactions. Using an antibody-protein A and a ligand-receptor system, we demonstrate the utility of BIACORE J in determining active concentration and binding affinities. The results from these studies illustrate the high sensitivity of the instrument and its ability to generate reproducible binding responses. The BIACORE J is easy to operate and useful in diverse applications, making SPR technology widely accessible as a research tool.
O-184 (2012)

Ross, Mary A.; Stanek, Lindsay Wichers; Long, Thomas C.; Luben, Thomas J.; Johns, Douglas O.; Kirrane, Ellen; Buckley, Barbara; Brown, James S.; Vandenberg, John J.; Cote, Ila Author Information
An Underground Mapping System Using Impulse Radar (2005)

The system is designed to produce a map of underground objects such as pipes, cables, vaults, building foundations and some natural features. A radar impulse is transmitted into the ground from a broadband dipole antenna. A similar antenna receives the reflected signals which are digitized and stored on a magnetic disc. The radar system is mounted on a handcart, the wheels of which are coupled to a shaft encoder. The output of this encoder is also saved. After an area has been scanned, a minicomputer processes the stored data and prints a map.
Lightweight Directory Access Protocol (1995)

This document specifies an Internet standards track protocol for the Internet community, and requests discussion and suggestions for improvements. Please refer to the current edition of the "Internet Official Protocol Standards" (STD 1) for the standardization state and status of this protocol. Distribution of this memo is unlimited.
Two Interrelated Strategies for Cephalotaxine Synthesis (1996)

Studies of two interrelated strategies for the synthesis of members of the cephalotaxus alkaloid family have culminated in a concise route for the preparation of the parent member cephalotaxine (1). As part of efforts exploring the use of an SET-promoted photocyclization reaction of aryl-substituted silylallyliminium salts to generate the spirocyclic DE unit of the target, we noted that attempts to generate the pentacyclic amino ketone 23 by deacylation of the enol ester 20 led to production of a mixture of 23 and the macrocyclic amino enone 24. A rapid equilibrium was shown to exist between 23 and 24, favoring the latter ring-opened form. This contrasts with the behavior of desmethylcephalotaxinone (22), a key late intermediate in several earlier cephalotaxine syntheses, which is known to exist in a ring-closed form. These observations led to the design of a second generation strategy which relies on transannular cyclization of the macrocyclic amino enedione 28. In practice, the sequence following this design transforms the known iodopiperonylethanol derivative 4 to 22 in 13 steps and a 12% overall yield and, thus, corresponds to an efficient formal synthesis of cepahalotaxine.
Design and Synthesis of Novel Dimeric Morphinan Ligands for κ and μ Opioid Receptors (2003)

A novel series of morphinans were synthesized, and their binding affinity at and functional selectivity for micro, delta, and kappa opioid receptors were evaluated. These dimeric ligands can be viewed as dimeric morphinans, which were formed by coupling two identical morphinan pharmacophores (cyclorphan (1) or MCL 101 (2)) with varying connecting spacers. Ligands 6 and 7 with alkyl spacers on the nitrogen position and ligands 8 and 9 in which the two morphinan pharmacophores were coupled by ether moieties at the 3-hydroxyl positions showed significant decrease in affinity at all three opioid receptors. An improvement in the affinity was achieved by introducing an ester moiety as the spacer in the dimeric morphinans. It was observed that the affinity of these ligands was sensitive to the character and length of the spacer. Compound 13 (MCL-139) with a 4-carbon ester spacer, compound 17 (MCL-144) containing a 10-carbon spacer, and compound 19 (MCL-145) with the conformationally constrained fumaryl spacer were the most potent ligands in this series, displaying excellent affinities at micro and kappa receptors (K(i) = 0.09-0.2 nM at micro and K(i) = 0.078-0.049 nM at kappa), which were comparable to the parent compound 2. Ligand 12, a compound containing only one morphinan pharmacophore and a long-chain ester group, had affinity at both micro and kappa receptors almost identical to that of the parent ligand 2. In the [(35)S]GTPgammaS binding assay, ligands 13, 17, and 19 and their parent morphinans 1 and 2 stimulated [(35)S]GTPgammaS binding mediated by the micro and kappa receptors. Compounds 13 and 17 were full kappa agonists and partial micro agonists, while compound 19 was a partial agonist at both micro and kappa receptors. These novel ligands, as well as their interesting pharmacological properties, will serve as the basis for our continuing investigation of the dimeric ligands as potential probes for the pharmacotherapy of cocaine abuse and may also open new avenues for the characterization of opioid receptors.
Isolation and cDNA Cloning of Ksp-cadherin, a Novel Kidney-specific Member of the Cadherin Multigene Family (1995)

Cadherins are recognized as the principal mediators of homotypic cellular recognition and play a demonstrated role in the morphogenic direction of tissue development. We report here the identification of a structurally unique, kidney-specific member of the cadherin multigene family (Ksp-cadherin). cDNA cloning and molecular analysis of the 130-kDa protein confirmed that it was novel and indicated that it most closely resembled members of the LI-cadherin/HPT-1 cadherin subgroup. The predicted protein possesses the definitive cadherin-specific sequence motifs LDRE, DXND, and DXD in well conserved sequential arrangement, and the characteristic cysteine residues found in the last ectodomains of almost all known cadherins. Like LI-cadherin and HPT-1, Ksp-cadherin lacks the prosequence and HAV adhesion recognition sequence typical of most classical cadherins, and possesses a truncated cytoplasmic domain (18-22 amino acids). When expressed in a transient Vaccinia/T7 expression system, Ksp-cadherin displayed the classic calcium sensitivity to trypsin proteolysis that is observed in all cadherins. Immunolocalization studies and Northern analysis indicated that expression of Ksp-cadherin was kidney-specific and limited to the basolateral membranes of renal tubular epithelial cells. In summary, we have identified and cloned a novel, kidney-specific member of the cadherin multigene family that we propose be designated Ksp-cadherin.
Test for Trend Change in NBUE-ness Using Randomly Censored Data (1995)

Let F be a life distribution with finite mean Then F is said to be in new better then worse than used in expectation (NBWUE(p)) class if for and for $t_0 is the scaled total-time-on-test transform and . We propose a testing procedure for : F is exponential against : NBWUE(p), and is not expontial, (or : F is NWBUE (p), and is not exponential) using randomly censored data. Our procedure assumes kmowledge of the proportion p of the population that fail at or before the change-point . Know ledge of itself is not assumed. The asymptotic normality of the test statistic is established and a Monte Carlo experiment is performed to investigate the speed of convergence of the test statistic to normality. The power of our test is also studied.
Flavopiridol inducesBCL-2expression and represses oncogenic transcription factors in leukemic blasts from adults with refractory acute myeloid leukemia (2011)

Flavopiridol is a cyclin-dependent kinase inhibitor that induces cell cycle arrest, apoptosis, and clinical responses in selected patients with acute myeloid leukemia (AML). A better understanding of the molecular pathways targeted by flavopiridol is needed to design optimal combinatorial therapy. Here, we report that in vivo administration of flavopiridol induced expression of the BCL-2 anti-apoptotic gene in leukemic blasts from adult patients with refractory AML. Moreover, flavopiridol repressed the expression of genes encoding oncogenic transcription factors (HMGA1, STAT3, E2F1) and the major subunit of RNA Polymerase II. Our results provide mechanistic insight into the cellular pathways targeted by flavopiridol. Although further studies are needed, our findings also suggest that blocking anti-apoptotic pathways could enhance cytotoxicity with flavopiridol.
Fusiform Gyrus Dysfunction is Associated with Perceptual Processing Efficiency to Emotional Faces in Adolescent Depression: A Model-Based Approach (2016)

While the extant literature has focused on major depressive disorder (MDD) as being characterized by abnormalities in processing affective stimuli (e.g., facial expressions), little is known regarding which specific aspects of cognition influence the evaluation of affective stimuli, and what are the underlying neural correlates. To investigate these issues, we assessed 26 adolescents diagnosed with MDD and 37 well-matched healthy controls (HCL) who completed an emotion identification task of dynamically morphing faces during functional magnetic resonance imaging (fMRI). We analyzed the behavioral data using a sequential sampling model of response time (RT) commonly used to elucidate aspects of cognition in binary perceptual decision making tasks: the Linear Ballistic Accumulator (LBA) model. Using a hierarchical Bayesian estimation method, we obtained group-level and individual-level estimates of LBA parameters on the facial emotion identification task. While the MDD and HCL groups did not differ in mean RT, accuracy, or group-level estimates of perceptual processing efficiency (i.e., drift rate parameter of the LBA), the MDD group showed significantly reduced responses in left fusiform gyrus compared to the HCL group during the facial emotion identification task. Furthermore, within the MDD group, fMRI signal in the left fusiform gyrus during affective face processing was significantly associated with greater individual-level estimates of perceptual processing efficiency. Our results therefore suggest that affective processing biases in adolescents with MDD are characterized by greater perceptual processing efficiency of affective visual information in sensory brain regions responsible for the early processing of visual information. The theoretical, methodological, and clinical implications of our results are discussed.
Crystal structure of subtilisin BPN′ variants containing disulfide bonds and cavities: Concerted structural rearrangements induced by mutagenesis (1990)

The X-ray structures of four genetically engineered disulfide variants of subtilisin have been analyzed to determine the energetic and structural constraints involved in inserting disulfide bonds into proteins. Each of the engineered disulfides exhibited atypical sets of dihedral angles compared with known structures of natural disulfide bridges in proteins and affected its local structural environment to a different extent. The disulfides located in buried regions, Cys26-Cys232 and Cys29-Cys119, induced larger changes than did Cys24-Cys87 and Cys22-Cys87, which are located on the surface of the molecule. An analysis of the concerted changes in secondary structure units such as alpha-helices and beta-sheets indicated systematic long-range effects. The observed changes in the mutants were largely distributed asymmetrically around the inserted disulfides, reflecting different degrees of inherent flexibility of neighboring secondary structure types. The disulfide substitution in each variant molecule created some invaginations or cavities, causing a reorganization of the surrounding water structure. These changes are described, as well as the changes in side chain positions of groups that border the cavities.
Phase I Dose-Finding Study of Weekly Docetaxel Followed by Flavopiridol for Patients with Advanced Solid Tumors (2007)

Treatment with weekly, sequential docetaxel followed by flavopiridol is an effective and safe regimen at all flavopiridol dose levels. The pharmacokinetic data indicate that concentrations of flavopiridol that enhance the effects of docetaxel both in vitro and in vivo can be achieved. Clinical activity is encouraging, even in patients who have received a prior taxane and in patients with gemcitabine-refractory metastatic pancreatic cancer.
DB2 advisor: an optimizer smart enough to recommend its own indexes (2002)

This paper introduces the concept of letting an RDBMS optimizer optimize its own environment. In our project, we have used the DB2 optimizer to tackle the index selection problem, a variation of the knapsack problem. This paper discusses our implementation of index recommendation, the user interface, and provide measurements on the quality of the recommended indexes.
Green chemistry for organic solar cells (2013)

Essentially all methods of energy production—e.g., fracking, damming, drilling, nuclear fission, and excavation of rare elements for photovoltaics—are associated with some degree of environmental degradation. Organic solar cells (OSCs) are regarded as low-cost and potentially environmentally benign sources of power. π-Conjugated (semiconducting) polymers—the components of OSCs responsible for absorbing light and transporting charge—are not typically synthesized in laboratories in ways that are amenable to manufacturing with low environmental impact. This article discusses strategies for producing conjugated polymers using green chemistry. That is, reaction methodology with low energy intensity, with minimal production of toxic waste, and at low cost. This article briefly reviews the major findings in the literature on the energy intensity and carbon emissions associated with fabricating OSCs on the laboratory scale, and identifies several strategies and materials invented by the community to lower the cost and environmental impact of the components of the devices. The principles of green chemistry, applied to the synthesis of conjugated polymers, are identified as important guidelines for the multi-tonne manufacturing of these materials. A general theme in both green chemistry and process research is that low cost can be correlated to environmental benignity when the costs of disposing wastes are high. This Perspective then highlights five synthetic strategies that satisfy several of the criteria of green chemistry: (1) polymerization using metal-mediated cross-coupling reactions that reduce or eliminate stoichiometric organotin waste; (2) the use of heterogeneously catalyzed polymerizations; (3) polymerization involving activation of C–H bonds; (4) use of biofeedstock-derived starting materials; and (5) polycondensation reactions that evolve water as a byproduct.
Anisotropy and growth-sequence dependence of atomic-scale interface structure in InAs/Ga1−xInxSb superlattices (1997)

We have used cross-sectional scanning tunneling microscopy to study the atomic-scale interface structure of InAs/Ga1−xInxSb superlattices grown by molecular beam epitaxy. Detailed, quantitative analysis of interface profiles obtained from constant-current images of both (110) and (11̄0) cross-sectional planes of the superlattice indicate that interfaces in the (11̄0) plane exhibit a higher degree of interface roughness than those in the (110) plane, and that the Ga1−xInxSb-on-InAs interfaces are rougher than the InAs-on-Ga1−xInxSb interfaces. The roughness data are consistent with anisotropy in interface structure arising from anisotropic island formation during growth, and in addition a growth-sequence-dependent interface asymmetry resulting from differences in interfacial bond structure between the superlattice layers.
A Methodology for Conceptual Design of Mechanisms by Parsing Design Specifications (2005)

In this paper, design specifications for the conceptual design of mechanisms are parsed into three coherent categories: functional requirements, structural requirements, and design constraints. Based on functional requirements, the functioning kinematic chain of a mechanism can be constructed by connecting the functioning links accordingly. From structural requirements, admissible kinematic structures are searched from the existing atlases of kinematic structures. Those admissible kinematic structures, which comprise at least one segment with the same characteristics of the functioning kinematic chain, are identified as compatible kinematic structures. Thus, feasible mechanisms that fulfill design specifications can be yielded by labeling joints in the compatible kinematic structures subject to design constraints. With this methodology, classified design specifications are used to guide designer through various stages of the conceptual design process in a systematic manner. The creation of the variable-stroke engine mechanism [Freudenstein, F., Maki, E. R., 1983, “Development of an Optimum Variable-Stroke Internal-Combustion Engine Mechanism From the Viewpoint of Kinematic Structure,” ASME J. Mech., Trans., Automat., Des., Vol. 105, pp. 259–267] is used as an illustrative example.
Effect of hexafluoro-1,25-dihydroxyvitamin D3 and sodium butyrate combination on differentiation and proliferation of HL-60 leukemia cells. (1993)

We have investigated the combined effects of 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3] and its fluoroanalog 26,26,26,27,27,27-hexafluoro-1,25-(OH)2D3 [F6-1,25-(OH)2D3] with sodium butyrate (NaB) on growth and differentiation of HL-60 human promyelocytic leukemia cells. F6-1,25-(OH)2D3 was 10-fold more active than 1,25-(OH)2D3 for induction of cell differentiation in HL-60 cells. Exposure to suboptimal concentration of F6-1,25-(OH)2D3 and NaB had synergistic effects compared to that of F6-1,25-(OH)2D3 or NaB alone and in the presence of 0.1-0.3 mM NaB, the dosage of F6-1,25-(OH)2D3 required to inhibit cell growth and colony formation and to induce cell differentiation was significantly reduced. The mechanism for the synergistic effect is probably that NaB increases cytoplasm content and nuclear binding of 1,25-(OH)2D3.
Robust visible light photoswitching with ortho-thiol substituted azobenzenes (2013)

Introduction of S-ethyl groups in all four ortho positions of azobenzene prevents reduction of the azo group by intracellular glutathione, while enhancing the absorptivity to ~10,000 M(-1) cm(-1) in the blue and green regions of the visible spectrum. cis-to-trans isomerization occurs thermally on the minutes timescale. Further, this substitution pattern permits switching with red light, a color that is more penetrating through biological tissues than other parts of the visible spectrum.