gebhart/patrepeval huggingface dataset:
Soluble tumor necrosis factor (TNF) receptors are effective therapeutic agents in lethal endotoxemia and function simultaneously as both TNF carriers and TNF antagonists. (1993)

Two forms (monomeric or dimeric) of the extracellular, ligand-binding portion of the human p80 cell-surface receptor for TNF were used to antagonize TNF activity in vitro and in vivo. The dimeric sTNFR:Fc molecule was a more potent inhibitor of TNF than the monomeric sTNFR (50 to 1000x), as assessed in vitro by inhibition of TNF binding or bioactivity and in vivo by protection of mice from an otherwise lethal injection of LPS. Surprisingly, the dimeric sTNFR:Fc construct demonstrated a beneficial effect even when administered 3 h after a lethal LPS injection (i.e., after serum TNF levels had peaked and receded). To study the mechanism by which the soluble TNFR functions in vivo, serum TNF levels were examined in mice given LPS in the presence or absence of soluble receptor. Administration of a mortality-reducing dose of sTNFR:Fc ablated the rise in serum TNF bioactivity that normally occurs in response to LPS. However, TNF bioactivity was revealed in these "TNF-negative" serum samples when the L929 bioassay was modified by inclusion of a mAb that blocks the binding of murine TNF to the human soluble TNFReceptor. These results indicate that the absence of direct cytolytic activity in the L929 assay was caused by neutralization of TNF, rather than to an absence of TNF in the serum. Moreover, administration of either monomeric sTNFR or low doses of dimeric sTNFR:Fc actually resulted in increased serum TNF levels compared to mice given LPS but no soluble receptor. However, these "agonistic" doses of soluble receptor did not lead to increased mortality when an LD60 dose of LPS was given. Thus, dimeric sTNFR are effective inhibitors of TNF and under some circumstances function simultaneously as both TNF "carriers" and antagonists of TNF biologic activity.
Amplification and overexpression of the ID4 gene at 6p22.3 in bladder cancer (2005)

Extending previous reports, our data indicate that the 6p22.3 amplicon in TCC is highly heterogeneous and targets several genes in a variable fashion. Among these, expression of E2F3 and DEK appear to be generally increased in TCC, with additional increases caused by amplifications. In contrast, over-expression of ID4, which is normally predominantly expressed in testes and brain, appears to depend more strictly on gene amplification. Accordingly, the effect of amplifications at 6p22.3 in bladder cancer is expected to be non-uniform, thereby contributing to the highly variable biological and clinical behavior of advanced stage tumors. ID4 is a potential oncogene in a small subset of bladder cancers.
Antitumor Activity and Immune Responses Induced by a Recombinant Carcinoembryonic Antigen-Vaccinia Virus Vaccine (1992)

These studies demonstrate that antitumor activity can be induced with the use of a recombinant CEA-vaccinia virus construct derived from an attenuated vaccinia strain, and they reveal the range of cell-mediated and humoral responses induced by this recombinant vaccine.
Feasibility and review of anomalous X-ray diffraction at long wavelengths in materials research and protein crystallography (2000)

The feasibility and a review of progress in the long-wavelengths anomalous dispersion technique is given in the context of the development of beamline ID1 of the ESRF for such studies. First experiments on this beamline and their analyses are described. The first study reports on the use of uranium which exhibits an unusually strong anomalous dispersion at its M(V) absorption edge (lambda(M(V)) = 3.5 A). The anomalous scattering amplitude of uranium with 110 anomalous electrons exceeds the resonance scattering of other strong anomalous scatterers like that of the rare earth ions by a factor of four. The resulting exceptional phasing power of uranium is most attractive in protein crystallography using the MAD method. The anomalous dispersion of a uranium derivative of asparaginyl-tRNA synthetase (hexagonal, a = 124.4 A, c = 123.4 A) has been measured at three wavelengths near the M(V) edge using beamline ID1 of the ESRF. The present set-up allowed the measurement of 10% of the possible reflections at a resolution of 8 A. This is mainly due to the low sensitivity of the CCD camera. The second study, involving DAFS experiments at wavelengths near the K-absorption edge of chlorine (lambda(K) = 4.4 A), reports the use of salt crystals which give rise to much stronger intensities of diffraction peaks than those of protein crystals. In the case of a crystal of pentamethylammonium undecachlorodibismuthate (PMACB, orthorhombic, a = 13.00 A, b = 14.038 A, c = 15.45 A), all reflections within the resolution range from 6.4 A to 3.5 A and the total scan width of 24 degrees were collected. The crystalline structure of PMACB implies two chemically distinct states of the Cl atom. Consequently, different dispersions near the K-edge of chlorine are expected. The dispersion of the intensity of five Bragg peaks of the PMACB crystal has been measured at 30 wavelengths. The relative success of these preliminary experiments with X-rays of long wavelength shows that the measurement of anomalous X-ray diffraction at wavelengths beyond 3 A is feasible. Starting from the experience gained in these experiments, an increased efficiency of the instrument ID1 by two to three orders of magnitude will be achieved in this wavelength range. A comparison with different techniques of anomalous diffraction which rely on the use of argon/ethane-filled multiwire chambers and image plates as detectors for wavelengths near the K-edge of sulfur and phosphorus is also given.
Targeting Vector Construction Through Recombineering (2010)

Gene targeting in mouse embryonic stem cells is an essential, yet still very expensive and highly time-consuming, tool and method to study gene function at the organismal level or to create mouse models of human diseases. Conventional cloning-based methods have been largely used for generating targeting vectors, but are hampered by a number of limiting factors, including the variety and location of restriction enzymes in the gene locus of interest, the specific PCR amplification of repetitive DNA sequences, and cloning of large DNA fragments. Recombineering is a technique that exploits the highly efficient homologous recombination function encoded by λ phage in Escherichia coli. Bacteriophage-based recombination can recombine homologous sequences as short as 30-50 bases, allowing manipulations such as insertion, deletion, or mutation of virtually any genomic region. The large availability of mouse genomic bacterial artificial chromosome (BAC) libraries covering most of the genome facilitates the retrieval of genomic DNA sequences from the bacterial chromosomes through recombineering. This chapter describes a successfully applied protocol and aims to be a detailed guide through the steps of generation of targeting vectors through recombineering.
Synthetic peptide ligands of the antigen binding receptor induce programmed cell death in a human B-cell lymphoma. (1994)

Peptide ligands for the antigen binding site of the surface immunoglobulin receptor of a human B-cell lymphoma cell line were identified with the use of filamentous phage libraries displaying random 8- and 12-amino acid peptides. Corresponding synthetic peptides bound specifically to the antigen binding site of this immunoglobulin receptor and blocked the binding of an anti-idiotype antibody. The ligands, when conjugated to form dimers or tetramers, induced cell death by apoptosis in vitro with an IC50 between 40 and 200 nM. This effect was associated with specific stimulation of intracellular protein tyrosine phosphorylation.
Synthesis tools for mixed-signal ICs (1996)

Article Free Access Share on Synthesis tools for mixed-signal ICs: progress on frontend and backend strategies Authors: L. Richard Carley Electrical and Computer Engineering, Carnegie Mellon University, Pittsburgh, PA Electrical and Computer Engineering, Carnegie Mellon University, Pittsburgh, PAView Profile , Georges G. E. Gielen Electrical Engineering, Katholieke Universiteit Leuven, Leuven, Belgium Electrical Engineering, Katholieke Universiteit Leuven, Leuven, BelgiumView Profile , Rob A. Rutenbar Electrical and Computer Engineering, Carnegie Mellon University, Pittsburgh, PA Electrical and Computer Engineering, Carnegie Mellon University, Pittsburgh, PAView Profile , Willy M. C. Sansen Electrical Engineering, Katholieke Universiteit Leuven, Leuven, Belgium Electrical Engineering, Katholieke Universiteit Leuven, Leuven, BelgiumView Profile Authors Info & Claims DAC '96: Proceedings of the 33rd annual Design Automation ConferenceJune 1996 Pages 298–303https://doi.org/10.1145/240518.240573Online:01 June 1996Publication History 36citation523DownloadsMetricsTotal Citations36Total Downloads523Last 12 Months21Last 6 weeks5 Get Citation AlertsNew Citation Alert added!This alert has been successfully added and will be sent to:You will be notified whenever a record that you have chosen has been cited.To manage your alert preferences, click on the button below.Manage my AlertsNew Citation Alert!Please log in to your account Save to BinderSave to BinderCreate a New BinderNameCancelCreateExport CitationPublisher SiteeReaderPDF
Design of 200 GHz SiGe HBT's (2002)

In this paper the high-frequency capability of SiGe HBT's is examined by using 1-dimensional device simulations in MEDIC. SiGe HBT's with f/sub T/=200 GHz for BV/sub CE0/=1.7 V and R/sub B/=2 k/spl Omega//sq are demonstrated in simulations that include non-local avalanche multiplication in the collector and an optimization strategy for the E-B-C profile.
The effect of BIMT 17, a new potential antidepressant, in the forced swimming test in mice (1995)

BIMT 17 inhibits cortical electrical activity through the activation of cortical 5-HT(1A) receptors combined with the antagonism of 5-HT(2) receptors. The aim of this study was to evaluate the potential antidepressant activity of BIMT 17 and its mechanism of action by using the forced swimming test in mice. BIMT 17, when administered i.p. (16mg/kg), s.c. (8mg/kg) and orally (32mg/kg), increased the struggling time in mice forced to swim. With i.p. administration, BIMT 17 did not alter locomotor activity. The effect of BIMT 17 seems to be mediated by 5-HT(1A) receptors since it was antagonised by WAY 100135 (10mg/kg i.p.), a selective 5-HT(1A) antagonist. The 5-HT(2) component does not seem to modulate BIMT 17 activity since the administration of DOI (1mg/kg i.p.), a 5-HT(2A/2C) agonist, did not modify the BIMT 17 effect. Antagonism of BIMT 17 was also produced by buspirone (30mg/kg p.o.), alpha-methyl-p-tyrosine (250mg/kg i.p.) and sulpiride (50mg/kg i.p.) but not by pindolol (20mg/kg i.p.). Neither the reduction of 5-HT synthesis brought about by p-chlorophenylalanine nor the selective destruction of 5-HT containing neurons by 5,7-dihydroxytryptamine reduced the BIMT 17 effect, suggesting that BIMT 17 acts postsynaptically in increasing struggling behaviour.
Rab7 Regulates Late Endocytic Trafficking Downstream of Multivesicular Body Biogenesis and Cargo Sequestration (2009)

The small molecular weight G-protein RAB7 is localized to both early and late endosomes and has been shown to be critical for trafficking through the endocytic pathway. The role of RAB7 in the endocytic pathway has been controversial, with some groups reporting that it regulates trafficking from early to late endosomes and others ascribing its role to trafficking between late endosomes and lysosomes. In this study, we use RNA interference to identify the exact step RAB7 regulates in the movement of the epidermal growth factor receptor (EGFR) from the cell surface to the lysosome. In the absence of RAB7, trafficking of the EGF.EGFR complex through the early endosome to the late endosome/multivesicular body (LE/MVB) does not change, but exiting from the LE/MVB is blocked. Ultrastructural analysis reveals that RAB7 is not required for formation of intraluminal vesicles of the LE/MVB, since RAB7-deficient cells have an increased number of enlarged LE/MVBs densely packed with intraluminal vesicles. Biochemical data indicate that the EGFR complex is sequestered in these intraluminal vesicles. Together, these data provide evidence that RAB7 is required for the transfer of cargo from the LE/MVB to the lysosome and for endocytic organelle maintenance.
Review Roles of B cells in rheumatoid arthritis (2003)

B lymphocytes play several critical roles in the pathogenesis of rheumatoid arthritis. They are the source of the rheumatoid factors and anticitrullinated protein antibodies, which contribute to immune complex formation and complement activation in the joints. B cells are also very efficient antigenpresenting cells, and can contribute to T cell activation through expression of costimulatory molecules. B cells both respond to and produce the chemokines and cytokines that promote leukocyte infiltration into the joints, formation of ectopic lymphoid structures, angiogenesis, and synovial hyperplasia. The success of B cell depletion therapy in rheumatoid arthritis may depend on disruption of all these diverse functions.
Isolation of Transcriptionally Regulated Root-Specific Genes from Tobacco (1990)

Four root-specific cDNA clones and their corresponding genomic clones have been isolated from tobacco (Nicotiana tabacum) by a novel differential hybridization procedure. The genes are expressed at high levels in roots and are not detectable in leaves. The cDNAs are encoded by small gene families of two to four members. Transcription experiments with isolated nuclei demonstrate that the genes are, at least in part, transcriptionally regulated. Constructions in which 1.4 kilobase pairs of 5' flanking region of one of the root-specific genes was fused to a reporter gene (beta-glucuronidase) were transformed into tobacco. beta-Glucuronidase activity in transgenic plants was localized in the roots, demonstrating the cis-acting sequences regulating root-specific expression are present on the 5' flanking region.
Synthesis and Dimerization of Chloro[10]cycloparaphenylene: A Directly Connected Cycloparaphenylene Dimer (2014)

The first synthesis and dimerization of monochlorinated [10]cycloparaphenylene (chloro[10]CPP) are described. By assembling a chlorinated 1,4-diborylbenzene unit with brominated and borylated cis-1,4-diphenylcyclohexane units by Suzuki-Miyaura coupling, a triangle-shaped chloro-containing macrocycle was synthesized. The acid-mediated "cyclohexane-to-benzene" aromatization afforded chloro[10]CPP without losing the chloro group. By the action of Ni(0) complex, chloro[10]CPP was converted to a directly connected [10]CPP dimer, which would be an ideal precursor for the "carbon nanobelt".
Results of Long-term Rice Bran Treatment on Stone Recurrence in Hypercalciuric Patients (1991)

A series of 182 calcium stone formers with idiopathic hypercalciuria underwent treatment with rice bran for 1 to 94 months. Urinary calcium excretion was considerably reduced, but there was some increase in urinary phosphate and oxalate. Urinary excretion of magnesium and uric acid, serum calcium, magnesium, phosphate, uric acid, parathyroid hormone (PTH) and ALP was unaffected. There were no obvious changes in serum iron, zinc and copper even when patients were treated for long periods. Rice bran was well tolerated in almost all cases and there were no serious side effects; 49 patients have undergone treatment for more than 3 years (average duration of administration 5.09 years). The frequency of new stone formation was drastically reduced (individual stone formation rate (no./year) from 0.720 +/- 0.533 to 0.125 +/- 0.204; group stone formation rate (no./patient-year) from 0.721 to 0.120) compared with the 3-year period before treatment. During treatment, 61.2% of patients remained in remission. Although rice bran therapy should be effective in correcting absorptive hypercalciuria, there may be limits to the overall ability of rice bran monotherapy to prevent recurrence.
Enzyme Systems Involved in the Formation of Reactive Metabolites in the Renal Medulla: Cooxidation via Prostaglandin H Synthase (1984)

Enzyme Systems Involved in the Formation of Reactive Metabolites in the Renal Medulla; Cooxidation via Prostaglandin H Synthase. ZENSER, T. V., AND DAVIS, B. B. (1984). Fundam. Appl. Toxicol. 4, 922–929. Metabolism of drugs and xenobiotics by renal mixed-function oxidases and prostaglandin H synthase was examined. Significant mixed-function oxidase activity was observed in the cortex and outer medulla. However, mixed-function oxidase activity was not detected in the inner medulla. In contrast, prostaglandin H synthase is quite active in the inner and outer medulla with no detectable activity in the cortex. Prostaglandin H synthase was shown to activate a variety of protoxins and procarcinogens by way of its hydroperoxidase activity. Peroxidatic activation of acetaminophen and benzidine appears to involve the formation of a free radical intermediate which binds nudeophilic sites on macromolecules. The latter is proposed to initiate pathogenic effects. Prostaglandin H synthase is a potential alternative to mixed-function oxidase activation of chemicals which exert pathologic effects on the renal inner medulla.
Identification of functional VEGF receptors on human platelets (2002)

Platelets secrete platelet-derived growth factor (PDGF) and vascular endothelial growth factor (VEGF) upon stimulation. We have demonstrated that platelets have functionally active PDGF alpha-receptors, a transmembrane tyrosine kinase involved in negative feedback regulation. Here we demonstrate the presence of the related VEGF receptors fms-like tyrosine kinase-1 and kinase-insert domain region on human platelets. VEGF itself did not cause platelet aggregation. However, addition of exogenous VEGF to SFRLLN or thrombin-stimulated platelets potentiated platelet aggregation. Moreover, thrombin-induced phosphoinositide 3-kinase and mitogen-activated protein kinase activity were enhanced in the presence of VEGF.
Craniosynostosis (2013)

Craniosynostosis is a premature pathologic fusion of one or more cranial vault sutures that leads to abnormal shape of the skull. The fused sutures lead to restricted growth in some areas and compensatory bossing in other areas. The head may assume different shapes depending upon the site and timing of the abnormally fused suture. The exact cause of this suture pathology is still unknown, but the local dura, cranial base and the fibroblast growth factors seem to influence this. The diagnosis rests on clinical examination and confirmation is generally on the computed tomography scan. The need for surgery is both for cosmetic and functional reasons. Many cases may be associated with raised intracranial pressure with its attendant deleterious effects on vision and brain. The aim of treatment is to increase the cranial volume and reshape the skull. The surgery can be safely undertaken around 9-12 months in most of the cases. The conventional management is through an open surgical approach; although, some centres have claimed impressive results with limited endoscopic techniques in selected cases. The review article deals with the aetiopathogenesis, clinical presentations and management of the common varieties of craniosynostoses seen in the Indian scenario.
Perivascular T Cells Express the Pro‐Inflammatory Chemokine RANTES mRNA in Multiple Sclerosis Lesions (1997)

Multiple sclerosis (MS) is an inflammatory demyelinating disease of the central nervous system (CNS), characterized by accumulation of mononuclear cells. The pathogenesis of MS is complex and probably involves soluble immune mediators, particularly cytokines, and activated memory T cells, that are thought to migrate into the CNS. During lesion formation in MS, cytokines regulate cell functions, such as cell recruitment and migration. Because the chemokine RANTES play a role in both activating and recruiting leucocytes, particularly memory T cells into inflammatory sites, the authors have assessed RANTES mRNA levels at the site of lesions. Expression levels were analysed in brain samples and compared with neurological, infectious and other controls. RANTES was expressed by activated perivascular memory T cells, predominantly located at the edge of active plaques. While RANTES mRNA was detected in all 17 MS brains analysed, it was only found in six of the 14 control patients and generally at a lower expression level. In view of the regulatory and chemotactic properties of RANTES, these results imply that RANTES in MS lesions may play an important role in the activation and/or selective accumulation of memory T cells and, thereby, in the pathogenic events associated with MS.
An Improved Spectrogram Using the Multiangle Centered Discrete Fractional Fourier Transform (2006)

The spectrogram is a useful tool for the time-frequency analysis of non stationary signals. This tool, however, is based upon a multicomponent sinusoidal model over a signal analysis frame and is not suitable when, for example, the frequency content over the frame is chirping. Recently, the centered version of the discrete fractional Fourier transform was shown to possess the capability to concentrate a linear chirp signal in a few transform coefficients. We present a modified version of the spectrogram which incorporates the centered discrete fractional Fourier transform and its multiangle version and which instead decomposes the signal over the analysis frame into multiple chirp signals. We present simulation results that study the efficiency of this improved spectrogram and its application to the analysis of harmonically related chirps and bat echolocation signals.
Annexin II regulates fibrin homeostasis and neoangiogenesis in vivo (2004)

A central tenet of fibrinolysis is that tissue plasminogen activator-dependent (t-PA- dependent) conversion of plasminogen to active plasmin requires the presence of the cofactor/substrate fibrin. However, previous in vitro studies have suggested that the endothelial cell surface protein annexin II can stimulate t-PA-mediated plasminogen activation in the complete absence of fibrin. Here, homozygous annexin II-null mice displayed deposition of fibrin in the microvasculature and incomplete clearance of injury-induced arterial thrombi. While these animals demonstrated normal lysis of a fibrin-containing plasma clot, t-PA-dependent plasmin generation at the endothelial cell surface was markedly deficient. Directed migration of annexin II-null endothelial cells through fibrin and collagen lattices in vitro was also reduced, and an annexin II peptide mimicking sequences necessary for t-PA binding blocked endothelial cell invasion of Matrigel implants in wild-type mice. In addition, annexin II-deficient mice displayed markedly diminished neovascularization of fibroblast growth factor-stimulated cornea and of oxygen-primed neonatal retina. Capillary sprouting from annexin II-deficient aortic ring explants was markedly reduced in association with severe impairment of activation of metalloproteinase-9 and -13. These data establish annexin II as a regulator of cell surface plasmin generation and reveal that impaired endothelial cell fibrinolytic activity constitutes a barrier to effective neoangiogenesis.