gebhart/patrepeval huggingface dataset:
An Improved and Scalable Process for the Synthesis of 5-Azacytidine: An Antineoplastic Drug (2013)

An improved, practical, and scalable process for the manufacture of antineoplastic drug, 5-azacytidine (1), is described. A thorough understanding of the reaction parameters and stability of the reaction intermediates led us to the development of a robust process. The challenges in the isolation and systematic approach used to streamline the process into a very robust and practical manufacturing process are described.
Phase III Trial of Gemcitabine Plus Cisplatin Versus Cisplatin Alone in Patients With Locally Advanced or Metastatic Non–Small-Cell Lung Cancer (2000)

For the first-line treatment of NSCLC, the regimen of gemcitabine plus cisplatin is superior to cisplatin alone in terms of response rate, time to disease progression, and overall survival.
Coreceptor/Chemokine Receptor Expression on Human Hematopoietic Cells: Biological Implications for Human Immunodeficiency Virus–Type 1 Infection (1999)

Abstract The recent discovery of chemokine receptors as coreceptors for human immunodeficiency virus–type 1 (HIV-1) entry offers new avenues for investigating the pathogenesis of acquired immunodeficiency syndrome (AIDS)-related cytopenias. To this end, we sought to (1) phenotype human hematopoietic cells for CD4 and the HIV-1 coreceptors CXCR4, CCR5, CCR3, and CCR2b; (2) correlate CD4 and chemokine receptor expression with their susceptibility to HIV-1 infection; and (3) examine any potential interplay between inflammatory cytokines released during HIV-1 infection and regulation of chemokine receptor expression. Fluorescence-activated cell sorting (FACS) analysis of bone marrow mononuclear cells (BMMNC), cells derived from serum-free expanded hematopoietic lineages (colony-forming unit–granulocyte-macrophage [CFU-GM], colony-forming unit-megakaryocyte [CFU-Meg], and burst-forming unit-erythroid [BFU-E]), and CD34+ cells showed differential expression of chemokine receptors and CD4 with some lineage specificity. Significantly, FACS-sorted CXCR4+/CD34+ cells had the same clonogeneic potential as CXCR4−/CD34+ cells. Reverse transcriptase-polymerase chain reaction (RT-PCR) analysis of FACS-sorted human candidate stem cells (HSC; CD34+, c-kit+, Rho123low) showed the presence of CXCR4 mRNA but not CD4 mRNA. Infection studies with HIV-1 Env-pseudotyped luciferase reporter viruses indicated that X4 Env (CXCR4-using) pseudotypes infected megakaryocytic cells, whereas R5 Env (CCR5-using) pseudotypes did not. Similarly, R5 but not X4 Env-pseudotyped viruses infected granulocyte-macrophage cells in a CD4/CCR5-dependent manner. Erythroid cells were resistant to R5 or X4 viral infection. Finally, we found that γ-interferon treatment upregulated CXCR4 expression on primary hematopoietic cells. In summary, the delineation of chemokine receptor expression on primary hematopoietic cells is a first step towards dissecting the chemokine-chemokine receptor axes that may play a role in hematopoietic cell proliferation and homing. Furthermore, susceptibility of hematopoietic cells to HIV-1 infection is likely to be more complicated than the mere physical presence of CD4 and the cognate chemokine receptor. Lastly, our results suggest a potential interplay between γ-interferon secretion and CXCR4 expression.
Roxburghin―A New Stilbene from the Wood of Cassia roxburghii (1987)

Department of Chemistry, Osmania University, Hyderabad-500 007<br> <em>Manuscript received 13 February 1987, accepted 7 August 1987</em> In<strong> </strong>addition to <em>β</em>-sitosterol, chrysophanol and roxburghinol, a new stilbene roxburghin has been isolated from the wood of <em>Cassia roxburghii </em>and characterised as 2,3<em>'</em>,4,5-tetrahydroxy-trans-stilbene on the basis of spectral and chemical evidence.
Multiprocessor Ray Tracing (1986)

Abstract A multiprocessor algorithm for ray tracing is described. The performance of the algorithm is analysed for a cubic and square array of processors with only local communication between near neighbours. Theoretical expressions for the speedup of the system as a function of the number of processors are derived. These analytic results are supported by simulations of ray tracing on a number of simple scenes with polygonal surfaces. It is found that a square network of processors generally performs better than a cubic network. Some comments are made on the construction of such a system using current (1985) microprocessor technology.
Bond Strength between Amalgam and Tooth Hard Tissues with Application of Fluoride, Glass lonomer Cement and Adhesive Resin Cement in Various Combinations (1986)

The bovine enamel and dentin samples ground flat with a series of emery papers were pretreated with fluoride either before or after etching, and several of the dentin samples were lined with glass ionomer cement. Adhesive resin cement, Panavia or Super-Bond, was applied on the enamel and dentin samples, and then amalgam was placed on these samples.The highest bond strength between amalgam and enamel was 90kg/cm2 for Panavia, and 102kg/cm2 for Super-Bond. These values were obtained by the pretreatment with Ag(NH3)2F. The bond strength between amalgam and the dentin treated with fluoride or the etching agent was 13-17kg/cm2 for Panavia, and 23-65kg/cm2 for Super-Bond. The bond strength between amalgam and lined dentin was 41-46kg/cm2 when Panavia was used. The bond strength tended to be increased by the fluoride treatment prior to etching.We suppose that the adhesion technique for amalgam would be clinically valuable.
Locally adaptive dimensionality reduction for indexing large time series databases (2001)

Similarity search in large time series databases has attracted much research interest recently. It is a difficult problem because of the typically high dimensionality of the data.. The most promising solutions involve performing dimensionality reduction on the data, then indexing the reduced data with a multidimensional index structure. Many dimensionality reduction techniques have been proposed, including Singular Value Decomposition (SVD), the Discrete Fourier transform (DFT), and the Discrete Wavelet Transform (DWT). In this work we introduce a new dimensionality reduction technique which we call Adaptive Piecewise Constant Approximation (APCA). While previous techniques (e.g., SVD, DFT and DWT) choose a common representation for all the items in the database that minimizes the global reconstruction error, APCA approximates each time series by a set of constant value segments of varying lengths such that their individual reconstruction errors are minimal. We show how APCA can be indexed using a multidimensional index structure. We propose two distance measures in the indexed space that exploit the high fidelity of APCA for fast searching: a lower bounding Euclidean distance approximation, and a non-lower bounding, but very tight Euclidean distance approximation and show how they can support fast exact searching, and even faster approximate searching on the same index structure. We theoretically and empirically compare APCA to all the other techniques and demonstrate its superiority.
G6b-B Inhibits Constitutive and Agonist-induced Signaling by Glycoprotein VI and CLEC-2 (2008)

Platelets play an essential role in wound healing by forming thrombi that plug holes in the walls of damaged blood vessels. To achieve this, platelets express a diverse array of cell surface receptors and signaling proteins that induce rapid platelet activation. In this study we show that two platelet glycoprotein receptors that signal via an immunoreceptor tyrosine-based activation motif (ITAM) or an ITAM-like domain, namely the collagen receptor complex glycoprotein VI (GPVI)-FcR gamma-chain and the C-type lectin-like receptor 2 (CLEC-2), respectively, support constitutive (i.e. agonist-independent) signaling in a cell line model using a nuclear factor of activated T-cells (NFAT) transcriptional reporter assay that can detect low level activation of phospholipase Cgamma (PLCgamma). Constitutive and agonist signaling by both receptors is dependent on Src and Syk family kinases, and is inhibited by G6b-B, a platelet immunoglobulin receptor that has two immunoreceptor tyrosine-based inhibitory motifs in its cytosolic tail. Mutation of the conserved tyrosines in the two immunoreceptor tyrosine-based inhibitory motifs prevents the inhibitory action of G6b-B. Interestingly, the inhibitory activity of G6b-B is independent of the Src homology 2 (SH2)-domain containing tyrosine phosphatases, SHP1 and SHP2, and the inositol 5'-phosphatase, SHIP. Constitutive signaling via Src and Syk tyrosine kinases is observed in platelets and is associated with tyrosine phosphorylation of GPVI-FcR gamma-chain and CLEC-2. We speculate that inhibition of constitutive signaling through Src and Syk tyrosine kinases by G6b-B may help to prevent unwanted platelet activation.
The Toll-receptor family and control of innate immunity (1999)

Innate immune recognition is mediated by a system of germline-encoded receptors that recognize conserved molecular patterns that are associated with microbial pathogens. These receptors are coupled to signal transduction pathways that control expression of a variety of inducible immune-response genes. Toll receptors and the associated signaling pathways of nuclear factor kappaB may represent the most ancient host defense system found in mammals, insects and plants.
A device architecture for three-dimensional, patterned paper immunoassays (2014)

Diagnostic assays can provide valuable information about the health status of a patient, which include detection of biomarkers that indicate the presence of an infection, the progression or regression of a disease, and the efficacy of a course of treatment. Critical healthcare decisions must often be made at the point-of-care, far from the infrastructure and diagnostic capabilities of centralized laboratories. There exists an obvious need for diagnostic tools that are designed to address the unique challenges encountered by healthcare workers in limited-resource settings. Paper, a readily-available and inexpensive commodity, is an attractive medium with which to develop diagnostic assays for use in limited-resource settings. In this article, we describe a device architecture to perform immunoassays in patterned paper. These paper-based devices use a combination of lateral and vertical flow to control the wicking of fluid in three-dimensions. We provide guidelines to aid in the design of these devices and we illustrate how patterning can be used to tune the duration and performance of the assay. We demonstrate the use of these paper-based devices by developing a sandwich immunoassay for human chorionic gonadotropin (hCG) in urine, a biomarker of pregnancy. We then directly compare the qualitative and quantitative results of these paper-based immunoassays to commercially available lateral flow tests (i.e., the home pregnancy test). Our results suggest paper-based devices may find broad utility in the development of immunoassays for use at the point-of-care.
Auditory Distortions: Origins and Functions (2013)

To enhance weak sounds while compressing the dynamic intensity range, auditory sensory cells amplify sound-induced vibrations in a nonlinear, intensity-dependent manner. In the course of this process, instantaneous waveform distortion is produced, with two conspicuous kinds of interwoven consequences, the introduction of new sound frequencies absent from the original stimuli, which are audible and detectable in the ear canal as otoacoustic emissions, and the possibility for an interfering sound to suppress the response to a probe tone, thereby enhancing contrast among frequency components. We review how the diverse manifestations of auditory nonlinearity originate in the gating principle of their mechanoelectrical transduction channels; how they depend on the coordinated opening of these ion channels ensured by connecting elements; and their links to the dynamic behavior of auditory sensory cells. This paper also reviews how the complex properties of waves traveling through the cochlea shape the manifestations of auditory nonlinearity. Examination methods based on the detection of distortions open noninvasive windows on the modes of activity of mechanosensitive structures in auditory sensory cells and on the distribution of sites of nonlinearity along the cochlear tonotopic axis, helpful for deciphering cochlear molecular physiology in hearing-impaired animal models. Otoacoustic emissions enable fast tests of peripheral sound processing in patients. The study of auditory distortions also contributes to the understanding of the perception of complex sounds.
Homeo Boxes in the Study of Development (1987)

The body plan of Drosophila is determined to a large extent by homeotic genes, which specify the identity and spatial arrangement of the body segments. Homeotic genes share a characteristic DNA segment, the homeo box, which encodes a defined domain of the homeotic proteins. The homeo domain seems to mediate the binding to specific DNA sequences, whereby the homeotic proteins exert a gene regulatory function. By isolating the normal Antennapedia gene, fusing its protein-coding sequences to an inducible promoter, and reintroducing this fusion gene into the germline of flies, it has been possible to transform head structures into thoracic structures and to alter the body plan in a predicted way. Sequence homologies suggest that similar genetic mechanisms may control development in higher organisms.
Clonal analysis of a human antibody response. Quantitation of precursors of antibody-producing cells and generation and characterization of monoclonal IgM, IgG, and IgA to rabies virus. (1990)

We quantitated and characterized the changes in the human B cell repertoire, at the clonal level, before and after immunization with rabies virus. Moreover, we generated 10 monoclonal cell lines producing IgM, IgG, and IgA antibodies to the virus. We found that in healthy subjects, not previously exposed to the virus, nearly 2% of the circulating B lymphocytes were committed to the production of antibodies that bound the virus. These B cells expressed the surface CD5 molecule. The antibodies they produced were polyreactive IgM that displayed a relatively low affinity for the virus components (Kd, 1.0-2.4 x 10(-6) g/microliters). After immunization, different anti-virus (IgG and IgA) antibody-producing cells consistently appeared in the circulation and increased from less than 0.005% to greater than 10% of the total B cells committed to the production of IgG and IgA, respectively. Most of such B cells do not express CD5 and produce monoreactive antibodies of high affinity for rabies virus (Kd, 6.5 x 10(-9) to 1.2 x 10(-10) g/microliters). One of these IgG mAbs efficiently neutralized rabies virus in vitro and in vivo, as detailed elsewhere (Dietzschold, B., P. Casali, Y. Ueki, M. Gore, C. E. Rupprecht, A. L. Notkins, and H. Koprowski, manuscript submitted for publication). Hybridization experiments using probes specific for the different human V gene segment families revealed that cell precursors producing low affinity IgM binding to rabies virus utilized a restricted number of VH gene segments (i.e., only members of the VHIIIb subfamily), whereas cell precursors producing high affinity IgG and IgA to rabies virus utilized an assortment of different VH gene segments (i.e., members of the VHI, VHIII, VHIV, and VHVI families and VHIIIb subfamily). In conclusion, our studies show that EBV transformation in conjunction with limiting dilution technology and somatic cell hybridization techniques are useful methods for quantitating, at the B cell clonal level, the human antibody response to foreign Ags and for generating human mAbs of predetermined specificity and high affinity.
Design considerations for a hard-rock PDC drill bit (1985)

This paper discusses the potential for developing a polycrystalline diamond compact (PDC) drill bit for hard-rock applications such as geothermal drilling. It is concluded that in order to use the inherently efficient drag cutting process in such severe applications, measures must be taken to reduce cutter penetrating forces in order to prevent thermally-accelerated cutter wear and thereby improve bit life. A procedure is developed for determining the conditions under which waterjets can be effectively used for this purpose by directing them at the rock surface ahead of individual cutters. It is concluded that hard rocks with compressive strengths as high as 30 kpsi (200 MPa) may be drillable with a hybrid PDC/waterjet bit using pressures that conventional oil field pumping technology is capable of providing. Extremely hard rocks might be drilled with such a bit using nozzle pressures well below those required to effectively cut the rock with waterjets alone. 13 refs., 6 figs.
Optically detected, single nanoparticle mass spectrometer with pre-filtered electrospray nanoparticle source (2014)

An instrument designed for non-destructive mass analysis of single trapped nanoparticles is described. The heart of the instrument is a 3D quadrupole (Paul) trap constructed to give optical access to the trap center along ten directions, allowing passage of lasers for particle heating and detection, particle injection, collection of scattered or fluorescent photons for particle detection and mass analysis, and collection of particles on TEM grids for analysis, as needed. Nanoparticles are injected using an electrospray ionization (ESI) source, and conditions are described for spraying and trapping polymer particles, bare metal particles, and ligand stabilized particles with masses ranging from 200 kDa to >3 GDa. Conditions appropriate to ESI and injection of different types of particles are described. The instrument is equipped with two ion guides separating the ESI source and nanoparticle trap. The first ion guide is mostly to allow desolvation and differential pumping before the particles enter the trap section of the instrument. The second is a linear quadrupole guide, which can be operated in mass selective or mass band-pass modes to limit transmission to species with mass-to-charge ratios in the range of interest. With a little experience, the design allows injection of single particles into the trap upon demand.
Aspects of North Swedish intonational phonology. (2003)

The present contribution discusses features of North Swedish intonational phonology. One characteristic feature is final element stress in compounds occurring particularly in dialects of North Botnia. The idea proposed here is that the accentual pattern (HL) of a compound has a different alignment in these dialects compared to East Standard Swedish. Another characteristic feature is related to a specific pattern of phrase intonation. This phrasal pattern, also represented as HL, has a distinct difference in timing as well compared to East Swedish. It seems to have a wider geographical distribution among North Swedish dialects than final element stress.
Memory Effects of Standardized Extracts ofPanax ginseng(G115),Ginkgo biloba(GK 501) and their Combination Gincosan® (PHL-00701) (1993)

In experiments on young (aged 3 months) and old (aged 26 months) rats, using some conditioned-reflex methods with punishment or positive reinforcement for active and passive avoidance (shuttle-box, step-down, step-through, and water maze), we studied the effects of the standardized extracts of Panax ginseng (G115), Ginkgo biloba (GK501) and their combination Gincosan (PHL-00701). The extracts were administered orally for 7 days before training at three increasing doses: 17, 50, and 150 mg/kg for G115; 10, 30, and 90 mg/kg for GK501; and 27, 80, and 240 mg/kg for PHL-00701. The two extracts and their combination improved the retention of learned behavior. This effect varied considerably with the extracts, with the dose and with the behavioral method used. The results suggest that the Panax ginseng G115 and the Ginkgo biloba GK501 extracts possess properties similar in every respect to those of nootropic drugs. The favorable effects on learning and memory of the combination of G115 plus GK501 and the other pharmacological activities inherent in the extracts characterize this combination, offered as Gincosan as a particularly promising drug in geriatric practice.
Wound complications after bevacizumab treatment in patients operated on for ovarian cancer. (2010)

We report a high rate of wound complications in ovarian cancer patients receiving bevacizumab after surgery.
The Nonreceptor Tyrosine Kinase ACK2, a Specific Target for Cdc42 and a Negative Regulator of Cell Growth and Focal Adhesion Complexes (2001)

ACK2 (activated Cdc42-associated tyrosine kinase-2) is a nonreceptor tyrosine kinase that is a specific target/effector for the GTP-binding protein Cdc42. Thus far the biological function of this tyrosine kinase has not been determined. Using an inducible eukaryotic expression system in fibroblasts, we demonstrate that ACK2 can strongly influence cell shape and growth as well as focal complex formation. ACK2 was found to associate with the focal adhesion complex components talin and vinculin, but not with the focal adhesion kinase (FAK), in a kinase-independent manner. The tyrosine kinase activity of FAK was also inhibited in cells overexpressing both wild-type and kinase-defective ACK2. This may be due to a competition between ACK2 and FAK for Src, which is an essential cofactor for FAK activation, as we have found that ACK2 specifically binds Src in cells. The ACK2-Src interaction appears to be mediated by the SH3 domain of Src, and the phosphorylation of ACK2 is enhanced in cells overexpressing the hyperactivated Src(Y527F) mutant. Overexpression of both wild-type and kinase-defective ACK2 also results in a severe inhibition of cell growth. In addition, ACK2 dissolves actin stress fibers and disassembles focal complexes but in a kinase-dependent manner. These results, taken together with previous studies demonstrating an association of ACK2 with integrin beta(1) (Yang, W., Lin, Q., Guan, J.-L., Cerione, R. A. (1999) J. Biol. Chem. 274, 8524-8530) and clathrin (Yang, W., Lo, C. G., Dispenza, T., and Cerione, R. A. (2001) J. Biol. Chem. 276, 17468-17473), suggest that the binding and protein tyrosine kinase activities of ACK2 coordinate changes in cell morphology and growth with the disassembly of focal adhesion sites, perhaps to organize new integrin complexes that are required for endocytosis and/or for cellular differentiation.
Lovastatin Biosynthesis by Aspergillus terreus in a Chemically Defined Medium (2001)

Lovastatin is a secondary metabolite produced by Aspergillus terreus. A chemically defined medium was developed in order to investigate the influence of carbon and nitrogen sources on lovastatin biosynthesis. Among several organic and inorganic defined nitrogen sources metabolized by A. terreus, glutamate and histidine gave the highest lovastatin biosynthesis level. For cultures on glucose and glutamate, lovastatin synthesis initiated when glucose consumption levelled off. When A. terreus was grown on lactose, lovastatin production initiated in the presence of residual lactose. Experimental results showed that carbon source starvation is required in addition to relief of glucose repression, while glutamate did not repress biosynthesis. A threefold-higher specific productivity was found with the defined medium on glucose and glutamate, compared to growth on complex medium with glucose, peptonized milk, and yeast extract.
Polymer Light-Emitting Electrochemical Cells (1995)

Electrochemistry provides a convenient means of reversibly doping conjugated polymers n- type (electron carriers) or p -type (hole carriers). When such charge carriers are introduced by electrochemical doping, they are compensated by counter-ions from the electrolyte. At high doping levels, the material becomes metallic, leading to low resistance contacts and easy charge injection (both n -type and p -type, respectively). 1-5