gebhart/patrepeval huggingface dataset:
Mitogenic effects of growth hormone in cultured human fibroblasts. Evidence for action via local insulin-like growth factor I production. (1988)

We examined human growth hormone's (hGH) effect on mitogenesis in cultured human fibroblasts, and the role of local insulin-like growth factor I (IGF-I). With 0.5% human hypopituitary serum (HPS), hGH increased thymidine incorporation (TI) over serum-free medium dose responsively, with half-maximal effect at 10 ng/ml (0.5 nM) (hGH 127 +/- 8.8%; IGF-I 107 +/- 1.7% [SEM]) (n = 10). Similarly, with 0.5% HPS, hGH and IGF-I increased cell replication by 172 +/- 8.2% and 169 +/- 25%, respectively (n = 4). Specific IGF-I monoclonal antibody (Sm1.2) dose dependently blunted TI stimulated by 10 ng/ml hGH or IGF-I (at 1:1000, 38 +/- 6.5% and 30 +/- 14% reduction, respectively). Sm1.2 also reduced cell replication by both 10 ng/ml hGH and IGF-I, respectively, to 32% and 42% of stimulated values. Dexamethasone (0.1 microM) synergistically enhanced TI by both IGF-I and hGH. A 28-h time course for TI showed that hGH stimulated a similar peak to IGF-I, lagging in its effect by 4-10 h. We have provided further evidence that hGH stimulates growth of cultured human fibroblasts via local IGF-I production, consistent with IGF-I's paracrine-autocrine role.
Sequential generations of hematopoietic colonies derived from single nonlineage-committed CD34+CD38- progenitor cells (1991)

Multiparameter flow cytometry was applied on normal human bone marrow (BM) cells to study the lineage commitment of progenitor cells ie, CD34+ cells. Lineage commitment of the CD34+ cells into the erythroid lineage was assessed by the coexpression of high levels of the CD71 antigen, the myeloid lineage by coexpression of the CD33 antigen and the B-lymphoid lineage by the CD10 antigen. Three color immunofluorescence experiments showed that all CD34+ BM cells that expressed the CD71, CD33, and CD10 antigens, concurrently stained brightly with anti-CD38 monoclonal antibodies (MoAbs). In addition, the CD38 antigen was brightly expressed on early T lymphocytes in human thymus, characterized by CD34, CD5, and CD7 expression. Only 1% of the CD34+ cells, 0.01% of nucleated cells in normal BM, did not express the CD38 antigen. The CD34+, CD38- cell population lacked differentiation markers and were homogeneous primitive blast cells by morphology. In contrast the CD34+, CD38 bright cell populations were heterogeneous in morphology and contained myeloblasts and erythroblasts, as well as lymphoblasts. These features are in agreement with properties expected from putative pluripotent hematopoietic stem cells; indeed, the CD34 antigen density decreased concurrently with increasing CD38 antigen density suggesting an upregulation of the CD38 antigen on differentiation of the CD34+ cells. Further evidence for a strong enrichment of early hematopoietic precursors in the CD34+, CD38- cell fraction was obtained from culture experiments in which CD34+ cell fractions with increasing density of the CD38 antigen were sorted singularly and assayed for blast colony formation. On day 14 of incubation, interleukin-3 (IL-3), IL-6, and GM-CSF, G-CSF, and erythropoietin (Epo) were added in each well. Twenty-five percent of the single sorted cells that expressed CD34 but lacked CD38 antigen gave rise to primitive colonies 28 to 34 days after cell sorting. The ability to form primitive colonies decreased rapidly with increasing density of the CD38 antigen. During 120 days of culture, up to five sequential generations of colonies were obtained after replating of the first-generation primitive colonies. This study provides direct evidence for the existence of a single class of progenitors with extensive proliferative capacity in human BM and provides an experimental approach for their purification, manipulation, and further characterization.
Surgical Progress (1978)

FUCHS, JAMES C. A. M.D.; MITCHENER, JAMES S. III M.S.; HAGEN, PER-OTTO PH.D. Author Information
Small-molecule inhibition of 6-phosphofructo-2-kinase activity suppresses glycolytic flux and tumor growth (2008)

Abstract 6-Phosphofructo-1-kinase, a rate-limiting enzyme of glycolysis, is activated in neoplastic cells by fructose-2,6-bisphosphate (Fru-2,6-BP), a product of four 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase isozymes (PFKFB1-4). The inducible PFKFB3 isozyme is constitutively expressed by neoplastic cells and required for the high glycolytic rate and anchorage-independent growth of ras-transformed cells. We report herein the computational identification of a small-molecule inhibitor of PFKFB3, 3-(3-pyridinyl)-1-(4-pyridinyl)-2-propen-1-one (3PO), which suppresses glycolytic flux and is cytostatic to neoplastic cells. 3PO inhibits recombinant PFKFB3 activity, suppresses glucose uptake, and decreases the intracellular concentration of Fru-2,6-BP, lactate, ATP, NAD+, and NADH. 3PO markedly attenuates the proliferation of several human malignant hematopoietic and adenocarcinoma cell lines (IC50, 1.4-24 μmol/L) and is selectively cytostatic to ras-transformed human bronchial epithelial cells relative to normal human bronchial epithelial cells. The PFKFB3 enzyme is an essential molecular target of 3PO because transformed cells are rendered resistant to 3PO by ectopic expression of PFKFB3 and sensitive to 3PO by heterozygotic genomic deletion of PFKFB3. Importantly, i.p. administration of 3PO (0.07 mg/g) to tumor-bearing mice markedly reduces the intracellular concentration of Fru-2,6-BP, glucose uptake, and growth of established tumors in vivo. Taken together, these data support the clinical development of 3PO and other PFKFB3 inhibitors as chemotherapeutic agents. [Mol Cancer Ther 2008;7(1):110–20]
A single amino acid determines the subunit-specific spider toxin block of alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate/kainate receptor channels. (1993)

Joro spider toxin (JSTX) is one of the most potent antagonists of glutamatergic AMPA/KA (alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate/kainate) receptor channels in invertebrates and vertebrates. A differential blocking effect on certain types of glutamatergic synapses--e.g., parallel and climbing fiber synaptic inputs to rat cerebellar Purkinje neurons--has been shown by using a synthetic analog of the spider toxin. By investigating the molecular basis of the JSTX action on the recombinant AMPA/KA receptors GluR1-GluR4 and GluR6 expressed in Xenopus oocytes, we found that submicromolar concentrations of JSTX exert a subunit-specific block. Thus, receptor subunits forming a receptor channel with a linear current-voltage (I-V) relationship (GluR1/2, GluR2/3, and GluR6) were not affected, while receptor subunits with rectifying I-V relationships (GluR1, GluR3, GluR4, and GluR1/3) were reversibly blocked by JSTX. By using receptor-subunit mutants obtained by site-directed mutagenesis, we have identified a single amino acid position (glutamine in the proposed second transmembrane domain) that is critical for the JSTX block. Since this site has previously been shown to control the I-V relationship of the AMPA/KA receptor channel and to participate in the regulation of the channel's permeability for calcium ions, our findings suggest that JSTX binds close to the central pore region of the channel.
Eicosanoids: mediators and therapeutic targets in fibrotic lung disease (2005)

Fibrosis is a common end-stage sequella of a number of acute and chronic lung diseases. Current concepts of pathogenesis implicate dysregulated interactions between epithelial cells and mesenchymal cells. Although investigative efforts have documented important roles for cytokines and growth factors in the pathogenesis of fibrotic lung diseases, these observations have not as yet been translated into efficacious therapies, and there is a pressing need for new pathogenetic insights and therapeutic approaches for these devastating disorders. Eicosanoids are lipid mediators derived from arachidonic acid, the most studied of which are the prostaglandins and leukotrienes. Although they are primarily known for their roles in asthma, pain, fever and vascular responses, present evidence indicates that eicosanoids exert relevant effects on immune/inflammatory, as well as structural, cells pertinent to fibrogenesis. In general, leukotrienes promote, whereas prostaglandin E(2) opposes, fibrogenic responses. An imbalance of eicosanoids also exists in pulmonary fibrosis, which favours the production of leukotrienes over prostaglandin E(2). This review highlights the role of this imbalance in the evolution of fibrotic lung disease, discusses the mechanisms by which it may arise and considers approaches for therapeutic targeting of eicosanoids in these conditions.
A Study of Traffic Noise Characteristics on the National Highways (2013)

PURPOSES : This study presents the noise level and frequency characteristics investigated in the national highways with the consideration of various measuring conditions and/or methods. METHODS : The noise levels on the asphalt concrete pavement(ACP) and the jointed plain concrete pavement(JPCP) of the national highway were measured and analysed with respect to three variables, i.e., pavement type, surface condition, and measurement distance. The PASS-By method is utilized for the noise measurement and then using CPB spectrum analysis method with 1/3 octave bandwidth, the noise levels and frequency characteristics were calculated for two-second periods before and after the peak noise. RESULTS : Depending on the pavement type, the noise level was changed as the average noise levels are 73.3dB(A) and 78.3dB(A) for ACP and JPCP, respectively. With respect to the effect of surface condition, the average noise levels for crack H(high), M(medium), and L (low) sections are 77.4dB(A), 77.4dB(A), and 78.1dB(A), respectively. Regarding the measurement distance, 1.2meter difference in measuring location reduces 1.6dB(A) of noise level; the average noise levels at 5.3m and 7.5m from the centerline of outer lane are 72.8dB(A) and 71.2dB(A), respectively. It should be noted that the noise levels are slightly different as a function of vehicle speed and type. However, the overall trends for each case was similar. It was found that the domain frequency bands for ACP and JPCP were 400Hz~2000Hz and 500Hz~2000Hz, respectively. CONCLUSIONS : Based on the analysis with the measured noise date from national highway, it was concluded that the noise level and frequency band vary depending on the various conditions. It was also found that some variables significantly affect the noise level while others do not. With further systematic investigation, the comprehensive noise characteristics on the national highway can be achieved. Using such database, it is possible to develop the fundamental noise reduction technology.
Efficient Java RMI for parallel programming (2001)

Java offers interesting opportunities for parallel computing. In particular, Java Remote Method Invocation (RMI) provides a flexible kind of remote procedure call (RPC) that supports polymorphism. Sun's RMI implementation achieves this kind of flexibility at the cost of a major runtime overhead. The goal of this article is to show that RMI can be implemented efficiently, while still supporting polymorphism and allowing interoperability with Java Virtual Machines (JVMs). We study a new approach for implementing RMI, using a compiler-based Java system called Manta. Manta uses a native (static) compiler instead of a just-in-time compiler. To implement RMI efficiently, Manta exploits compile-time type information for generating specialized serializers. Also, it uses an efficient RMI protocol and fast low-level communication protocols.A difficult problem with this approach is how to support polymorphism and interoperability. One of the consequences of polymorphism is that an RMI implementation must be able to download remote classes into an application during runtime. Manta solves this problem by using a dynamic bytecode compiler, which is capable of compiling and linking bytecode into a running application. To allow interoperability with JVMs, Manta also implements the Sun RMI protocol (i.e., the standard RMI protocol), in addition to its own protocol.We evaluate the performance of Manta using benchmarks and applications that run on a 32-node Myrinet cluster. The time for a null-RMI (without parameters or a return value) of Manta is 35 times lower than for the Sun JDK 1.2, and only slightly higher than for a C-based RPC protocol. This high performance is accomplished by pushing almost all of the runtime overhead of RMI to compile time. We study the performance differences between the Manta and the Sun RMI protocols in detail. The poor performance of the Sun RMI protocol is in part due to an inefficient implementation of the protocol. To allow a fair comparison, we compiled the applications and the Sun RMI protocol with the native Manta compiler. The results show that Manta's null-RMI latency is still eight times lower than for the compiled Sun RMI protocol and that Manta's efficient RMI protocol results in 1.8 to 3.4 times higher speedups for four out of six applications.
Cancer of the Ovary (2004)

Patients with ovarian cancer usually present with advanced disease, and the disease is generally managed with surgical resection followed by platinum-based chemotherapy. Recent chemotherapeutic advances have led to improved survival, and a better understanding of genetic risk factors has permitted a tailored approach to preventive strategies, such as bilateral salpingo-oophorectomy in selected women. This review describes the clinical features of ovarian cancer and recent advances in postoperative management.
Redundant Proteolytic Mechanisms Process Seed Storage Proteins in the Absence of Seed-Type Members of the Vacuolar Processing Enzyme Family of Cysteine Proteases (2002)

Seed-type vacuolar processing enzyme (VPE) activity is predicted to be essential for post-translational proteolysis of seed storage proteins in the protein storage vacuole of developing seeds. To test this hypothesis, we examined the protein profiles of developing and germinating seeds from Arabidopsis plants containing transposon-insertional knockout mutations in the genes that encode the two seed-type VPEs in Arabidopsis, betaVPE, which was identified previously, and deltaVPE, which is described here. The effects of these mutations were studied individually in single mutants and together in a double mutant. Surprisingly, we found that most of the seed protein still was processed proteolytically in seed-type VPE mutants. The minor differences observed in polypeptide accumulation between wild-type and betaVPE mutant seeds were characterized using a two-dimensional gel/mass spectrometric analysis approach. The results showed increased amounts of propolypeptide forms of legumin-type globulins accumulating in mutant seeds. However, the majority of protein (>80%) still was processed to mature alpha- and beta-chains, as observed in wild-type seeds. Furthermore, we identified several legumin-type globulin polypeptides, not corresponding to pro or mature forms, that increased in accumulation in betaVPE mutant seeds compared with wild-type seeds. Together, these results indicate the existence of both redundant and alternative processing activities in seeds. The latter was substantiated by N-terminal sequencing of a napin-type albumin protein, indicating cleavage consistent with previous in vitro studies using purified aspartic protease. Analysis of genome-wide transcript profiling data sets identified six protease genes (including an aspartic protease gene and betaVPE) that shared spatial and temporal expression patterns with seed storage proteins. From these results, we conclude that seed-type VPEs constitute merely one pathway for processing seed storage protein and that other proteolytic enzymes also can process storage proteins into chains capable of stable accumulation in mature seeds.
Receptor editing in self-reactive bone marrow B cells. (1993)

A central paradigm of immunology is clonal selection: lymphocytes displaying clonally distributed antigen receptors are generated and subsequently selected by antigen for growth or elimination. Here we show that in mice transgenic for anti-H-2Kk,b antibody genes, in which a homogeneous clone of developing B cells can be analyzed for the outcome of autoantigen encounter, surface immunoglobulin M+/idiotype+ immature B cells binding to self-antigens in the bone marrow are induced to alter the specificity of their antigen receptors. Transgenic bone marrow B cells encountering membrane-bound Kb or Kk proteins modify their receptors by expressing the V(D)J recombinase activator genes and assembling endogenously encoded immunoglobulin light chain variable genes. This (auto)antigen-directed change in the specificity of newly generated lymphocytes is termed receptor editing.
Planar Microwave Engineering (2004)

Scientists and engineers working in the fields of radio and microwaves have always been hard-working authors as well. Since the days of the Second World War -and even before ­ we have entire libraries of high quality books in many languages describing the vari ous design methods, applications, physical backgrounds, and later, also computer simulations of RF circuits, devices, and equipment. However, as many of our readers are well aware, the vast majority of written material is inherently of narrow scope. entire WOO-page giant can be full of electromagnetic theory, and its author possibly still calls it An Introduction. We have seen some attempts of broader approach, but typically such books have been crun ched to unreasonably low page numbers and they have tumed more to entry-level illustrative collections of practical engineering. Cambridge Univers ity Press mailed to me some months ago an interestin g set of their recent titles that they though might be of interest to Systems readers. I picked Planar Microwave Engineering, authored by Professor Thomas Lee, for a closer look, because alread y its Preface suggested that this time we may have the o pportunity to get a real multi-purpose RF engineering book - something that is typically of more use to system engineers and scientists in the laboratory. In its 23 separate chapters, the book covers some basic microwave circuit concepts and theory, the Smith chart with its appli cations, conne cto rs and cables, passives, microstrip and stripline design, diodes, mixers, transistors, amplifiers (both hig h power and low noise), oscillators, synthesizers, antennas, filters and measurement methods, and devices such as spectrum analyzers,
Vertical emitting aperture nanoantennas (2012)

Herein we propose, theoretically investigate, and numerically demonstrate a compact design for a vertical emitter at a wavelength of 1.5 μm based on nanophotonic aperture antennas coupled to a dielectric waveguide. The structure utilizes a plasmonic antenna placed above a Si3N4 waveguide with a ground plane for breaking the up-down symmetry and increasing the emission efficiency. Three-dimensional (3-D) finite-difference time-domain (FDTD) simulations reveal that up to 60% vertical emission efficiency is possible in a structure only four wavelengths long with a 3 dB bandwidth of over 300 nm.
Azidothymidine Inhibition of Thymidine Kinase and Synergistic Cytotoxicity with Methotrexate and 5-Fluorouracil in Rat Hepatoma and Human Colon Cancer Cells (1990)

Azidothymidine (AZT, 3'-azido-3'-deoxythymidine, zidovudine) competitively inhibited the activity of thymidine kinase (EC 2.7.1.21) in extracts of rat hepatoma and sarcoma cells; Dixon plots yielded a Ki = 1-2 microM. Azidothymidine (100 microM) exerted synergistic cytotoxicity with methotrexate (0.05 microM) in hepatoma cells in culture in clonogenic assay. Thymidine (50 microM) counteracted the effect of azidothymidine and prevented synergistic action. Azidothymidine (10 microM) was synergistically cytotoxic with 5-fluorouracil (0.3 and 0.5 microM) in HT-29 human colon carcinoma cells. Thymidine (10 microM) abolished synergism. These studies suggest a new role for azidothymidine which, as an inhibitor of thymidine salvage, should enhance synergistically the clinical anticancer impact of blockers of de novo biosynthesis of thymidylates (methotrexate, 5-fluorouracil).
Fluorescent styryl dyes FM1‐43 and FM2‐10 are muscarinic receptor antagonists: intravital visualization of receptor occupancy (2006)

The fluorescent styryl dyes FM1-43 and FM2-10 have been used to visualize the endocytic and exocytic processes involved in neurotransmission in a variety of central and peripheral nerve preparations. Their utility is limited to some extent by a poorly understood vesicular-independent labelling of cells and tissues. We show here that one likely cause of this troublesome background labelling is that FM1-43 and FM2-10 are selective and competitive antagonists at both cloned and endogenously expressed muscarinic acetylcholine receptors. In radioligand binding studies, FM1-43 and FM2-10 bound with moderate affinity (23-220 nM) to membranes of Chinese hamster ovary (CHO) cells expressing cloned human muscarinic receptors (M1-M5). In functional studies in vitro, FM1-43 and FM2-10 inhibited electrical field stimulation (EFS) and acetylcholine-induced cholinergic contractions of guinea-pig tracheal strips (IC50: FM1-43, 0.4 +/- 0.1; FM2-10, 1.6 +/- 0.1 microM; concentration of antagonist producing a 2-fold leftward shift in the acetylcholine concentration-response curve (Kb): FM1-43, 0.3 +/- 0.1; FM2-10, 15.8 +/- 10.1 microM). Neither compound inhibited EFS-evoked, non-adrenergic non-cholinergic nerve-mediated relaxations or contractions of the airways, or contractions mediated by histamine H1 receptor or tachykinin NK2 receptor activation. Incubating freshly excised tracheal whole-mount preparations with 5 microM FM1-43 resulted in intense fluorescence labelling of the smooth muscle that was reduced by up to 90% in the presence of selective M2 and M3 receptor antagonists. The potency of the FM dyes as muscarinic receptor antagonists is within the concentration range used to study vesicular cycling at nerve terminals. Given that muscarinic receptors play a key role in the regulation of neurotransmitter release from a variety of neurones, the anticholinergic properties of FM dyes may have important implications when studying vesicular events in the nervous system. In addition, these dyes may provide a novel tool for visualizing muscarinic receptor occupancy in living tissue or cell preparations.