gebhart/patrepeval huggingface dataset:
Dpc4 transcriptional activation and dysfunction in cancer cells. (1998)

Dpc4 (Smad4) is implicated in mediation of signals from transforming growth factor (TGF) beta and related ligands, and wild-type Dpc4 mediates TGF-beta-stimulated gene transcription at specific DNA sequences bound by Dpc4 [Smad binding element (SBE)]. We characterized panels of DPC4 tumor mutations and cancer cell lines. Amino acid substitutions within the NH2-terminal third of Dpc4 weakened or ablated SBE-mediated gene regulation by a disruption of DNA binding. An interaction of the COOH-terminal end with the DNA-binding domain of Dpc4 was evident but was not required to explain the functional impairment produced by NH2-terminal DPC4 mutations. Both substitution and truncation mutations of the COOH-terminal half of DPC4 lacked the ability to regulate transcription while retaining the sequence-specific DNA-binding function, but through differing mechanisms. A modular domain to redistribute Dpc4 to the nuclear compartment allowed SBE-mediated transcriptional activation in a cell line having a TGF-1 receptor defect and was sufficient to restore SBE-mediated transactivation ability to COOH-terminal DPC4 missense mutants. Cells harboring DPC4 alterations had a universal impairment of the TGF-beta-stimulated SBE transcriptional response. These studies identify the loss of SBE-mediated gene regulation as a uniform outcome of the selection for DPC4 alterations during tumorigenesis. They raise the possibility of restoration of some Dpc4-associated transcriptional events in cancer cells through the targeted redistribution of wild-type and some missense mutant forms of Dpc4 to the nucleus.
Phosphorylation of Human Cytomegalovirus Glycoprotein B (gB) at the Acidic Cluster Casein Kinase 2 Site (Ser <sub>900</sub> ) Is Required for Localization of gB to the <i>trans-</i> Golgi Network and Efficient Virus Replication (2003)

ABSTRACT Human cytomegalovirus (HCMV) glycoprotein B (gB), encoded by the UL55 open reading frame, is an essential envelope glycoprotein involved in cell attachment and entry. Previously, we identified residue serine 900 (Ser 900 ) as a unique site of reversible casein kinase 2 phosphorylation in the cytoplasmic domain of HCMV gB. We have also recently shown that gB is localized to the trans -Golgi network (TGN) in HCMV-permissive cells, thereby identifying the TGN as a possible site of virus envelopment. The aim of the current study was to determine the role of Ser 900 phosphorylation in transport of gB to the TGN and in HCMV biogenesis. Recombinant HCMV strains were constructed that expressed gB molecules containing either an aspartic acid (gBAsp 900 ) or alanine residue (gBAla 900 ) substitution at Ser 900 to mimic the phosphorylated or nonphosphorylated form, respectively. Immunofluorescence analysis of the trafficking of gB mutant molecules in fibroblasts infected with the HCMV recombinants revealed that gBAsp 900 was localized to the TGN. In contrast, gBAla 900 was partially mislocalized from the TGN, indicating that phosphorylation of gB at Ser 900 was necessary for TGN localization. The increased TGN localization of gBAsp 900 was due to a decreased transport of the molecule to post-TGN compartments. Remarkably, the substitution of an aspartic acid residue for Ser 900 also resulted in an increase in levels of progeny virus production during HCMV infection of fibroblasts. Together, these results demonstrate that phosphorylation of gB at Ser 900 is necessary for gB localization to the TGN, as well as for efficient viral replication, and further support the TGN as a site of HCMV envelopment.
Transition density: a new measure of activity in digital circuits (1993)

Noting that a common element in most causes of runtime failure is the extent of circuit activity, i.e. the rate at which its nodes are switching, the author proposes a measure of activity, called the transition density, which may be defined as the average switching rate at a circuit node. An algorithm is also presented to propagate density values from the primary inputs to internal and output nodes. To illustrate the practical significance of this work, it is shown how the density values at internal nodes can be used to study circuit reliability by estimating the average power and ground currents; the average power dissipation; the susceptibility to electromigration failures; and the extent of hot-electron degradation. The density propagation algorithm has been implemented in a prototype density simulator which is used to assess the validity and feasibility of the approach experimentally. The results show that the approach is very efficient, and makes possible the analysis of VLSI circuits.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">></ETX>
Makyoh Topography for the Study of Large-Area Extended Defects in Semiconductors (1999)

A quantitative approach to the Makyoh-topography image formation mechanism is presented. General relations are given on the optical settings; geometrical optical simulations of a sinusoidal surface and a hillock (or depression) are presented. Optimum working conditions are established, and general features of the imaging are pointed out. The experimental images taken for Si wafers are compared to the results of the model.
Freeze–thawing method: a bleeding method from lepidopteran larvae utilizing a spontaneous insect body contraction after a freezing‐thawing treatment (1999)

Insect haemolymph contains growth promotor(s) for cultured insect cells and is frequently used as an additive to the culture media. Insect haemolymph serves as a pool of a protein product produced by a virus vector–insect host system. Haemolymph collection is an essential step in the above process, which should limit the scale and cost of their performance. In the present study, a simple procedure for bleeding from lepidopteran larvae, Bombyx mori , has been developed which utilized a spontaneous contraction of the insect body after a freezing–thawing treatment. In the case of fifth‐instar B. mori , 60 to 80% of the total haemolymph was collected by this method. The authors applied the method to a haemolymph collection from frozen larvae stored at −80°C for longer than 1 month. Preservability of the frozen larvae enabled the development of a system dealing with a huge bulk of insects. The bleeding method was effective under cooled condition at 0°C or 4°C, which was desired for protein handling. Development of a large system would result in a cost reduction for the insect haemolymph products such as insect cell‐culture additive. Furthermore, the above bleeding method was applied to the nuclear polyhedrosis virus‐infected B. mori larvae and up to 80% of the total haemolymph was collected from the virus‐infected larvae. It suggests the bleeding method as an effective means of haemolymph collection in the protein productive system using a virus vector and its insect host.
Anti-TNF-induced lupus (2009)

The use of protein-based anti-TNF-alpha therapies such as antibodies and soluble TNF-alpha receptors is commonly associated with the induction of autoantibodies, whereas anti-TNF-induced lupus (ATIL) is rare. ATIL can occur with any of the available TNF inhibitors, but the frequency and clinical characteristics of ATIL vary between different drugs. Cutaneous, renal and cerebral involvement as well as dsDNA antibodies are more common in ATIL compared to classical drug-induced lupus (DIL), suggesting different pathogenic mechanisms of ATIL and DIL. True ATIL must be clinically differentiated from mixed CTD, SLE or overlap syndromes unmasked, but not induced, by anti-TNF-alpha treatment of unclassified polyarthritis. The pathogenesis of ATIL is still unknown. Concomitant immunosuppression can reduce autoantibody formation in ATIL, and withdrawal of anti-TNF-alpha therapy usually leads to resolution of symptoms. Steroids and/or immunosuppressive therapy may be required in severe cases.
In vitro and in vivo inhibition of human papillomavirus type 16 E6 and E7 genes. (1995)

Human cervical cancers are often associated with human papillomavirus (HPV). In HPV-positive cervical cancers, the oncoproteins E6 and E7 are consistently expressed. In this study, the effects of antisense inhibition of both proteins were examined. Phosphorothioate oligonucleotides (ODNs) AE6 and AE7 complementary to regions flanking the start codons of HPV16 E6 and E7 genes, respectively, were synthesized. These anti-HPV ODNs inhibited the growth of cervical cell lines CaSki and SiHa, which harbor HPV16 but had little effect on cells that do not. Both ODNs also affected the ability of CaSki cells to form colonies in soft agar. In nude mice, treatment with either AE6, AE7, or a mixture of both led to substantially smaller tumors. AE7 was observed to inhibit E7 synthesis. The AE6 ODN probably exerts its effect by suppressing the expression of E6 as well as E7. Cell cultures and tumors treated with AE6 showed a decrease in E7 expression. In addition, an antisense ODN targeted at the retinoblastoma gene was able to reverse some of the inhibitory effect of AE6 on CaSki cells, indicating that AE6 inhibited E7 synthesis. This study further demonstrates that anti-HPV ODNs may be useful therapeutically.
STUDIES ON ANTIGEN-ANTIBODY COMPLEXES (1971)

Solid phase immunoadsorbents were prepared by coupling antigens to agarose. With this technique specific antibodies were easily isolated in large amounts. The gammaG-globulin class of antibodies isolated in this manner were not denatured as judged by their normal biological half-life in rabbits. Soluble immune complexes at fivefold antigen excess were prepared from isolated specific antibodies and HSA, human lambda-chains, human lambdaG-globulins, and a Waldenström's macroglobulin as antigens. In all these preparations a characteristic immune complex was encountered that represented the smallest stable antigen-antibody union. In the HSA-anti-HSA system they were found to be AgAb(2) complexes, and Ag(2)Ab complexes in the gammaG-anti-gammaG system. These stable complexes fixed complement ineffectively. Also, a spectrum of larger complexes was present in each system, and these complexes fixed complement effectively. With intact antibodies the disappearance curves of immune complexes from the circulation were composed of three exponential components. The immune complexes larger than AgAb(2) were quickly removed from the circulation with half-lives of 0.09-0.37 hr. Their clearance was not dependent on complement components, in that depletion of complement by cobra venom factor and aggregated gammaG-globulin did not alter the pattern of their removal from the circulation. However, when the interchain disulfide bonds of antibodies were reduced and alkylated, the removal of the lambda-anti-lambda, HSA-anti-HSA, and gammaG-anti-gammaG complexes was altered. In these experiments the disappearance curves were composed of two exponential components and the rapid removal of the greater than AgAb(2) complexes did not occur. The immune complexes prepared from reduced and alkylated antibodies fixed complement ineffectively. The presented data indicate that the rapid removal of circulating immune complexes, containing gammaG-globulin molecules as antibodies, depends primarily on the number of antibodies involved. Furthermore, complement fixation is not involved in the rapid removal of such complexes. Nevertheless, the rapid removal of immune complexes and their ability to fix complement have similarities for optimal function in that both processes require intact interchain disulfide bonds of antibodies and complexes that exceed the AgAb(2) combination.
Cis-platinum: a new anticancer agent. (1979)

The introduction of the platinum group of anticancer agents is a classic story of serendipity. In 1975, while investigating the effect of an electrical field on bacterial growth, Rosenberg et al1 found that the replication of Escherichia coli was inhibited by an electrical current passed between platinum electrodes. They later found that this growth inhibition was not caused by the electrical current, but by several platinum compounds formed in the medium. Subsequent investigation of these compounds led to the identification of platinum diamminodichloride (as-platinum ; DDP) as the most active antitumour agent in animal systems. Since 1972 DDP has been available as a research drug from the National Cancer Institute in the USA, and it is now commercially available in Britain (Neoplatin; Mead Johnson). This review aims at providing clinicians with infor mation on the optimal methods of use, the toxicity, and the antitumour effects of the drug.
Cytosolic calcium oscillators (1988)

Many cells display oscillations in intracellular calcium resulting from the periodic release of calcium from intracellular reservoirs. Frequencies are varied, but most oscillations have periods ranging from 5 to 60 s. For any given cell, frequency can vary depending on external conditions, particularly the concentration of natural stimuli or calcium. This cytosolic calcium oscillator is particularly sensitive to those stimuli (neurotransmitters, hormones, growth factors) that hydrolyze phosphoinositides to give diacylglycerol and inositol 1,4,5-trisphosphate (Ins1,4,5P3). The ability of Ins1,4,5P3 to mobilize intracellular calcium is a significant feature of many of the proposed models that are used to explain oscillatory activity. Receptor-controlled oscillator models propose that there are complex feedback mechanisms that generate oscillations in the level of Ins1,4,5P3. Second messenger-controlled oscillator models demonstrate that the oscillator is a component of the calcium reservoir, which is induced to release calcium by a constant input of either Ins1,4,5P3 or calcium itself. In the latter case, the process of calcium-induced calcium release might be the basis of oscillatory activity in many cell types. The function of calcium oscillations is still unknown. Because oscillator frequency can vary with agonist concentration, calcium transients might be part of a frequency-encoded signaling system. When an external stimulus arrives at the cell surface the information is translated into a train of calcium spikes, i.e., the signal is digitized. Certain cells may then convey information by varying the frequency of this digital signal.
Electron mobility in an AlGaN/GaN two-dimensional electron gas I-carrier concentration dependent mobility (2003)

The transport properties of two-dimensional electron gas (2-DEG) at the AlGaN/GaN interface were studied by characterizing the 2-DEG mobility dependence on carrier concentration, n/sub s/, and temperature. High-quality AlGaN/GaN heterostructures were grown, and heterostructure field effect transistors (HFETs) using a Fat FET geometry were fabricated. Measurements of 2-DEG mobility were performed by magnetoresistance and capacitance-conductance. In order to understand the dominant transport factors, the mobility was modeled using different scattering mechanisms and compared to our results. It is found that mobility dependence on n/sub s/ shows a bell-shape behavior over the whole temperature range. For low n/sub s/ the mobility is dominated by Coulomb interaction from interface charge, and at high n/sub s/ the mobility is dominated by interface roughness. Using previously reported experimental values of interface charge and interface roughness in our modeling, we show good agreement with mobility measurement results. Scattering from interface states in AlGaN/GaN heterostructures, seems to be related to the high polarization field in the heterointerface. At temperatures higher than 200K polar optical phonon scattering dominates the transport, yet both interface charge and roughness affect the mobility at the low and high n/sub s/, respectively.
Use of solid-phase PCR for enhanced detection of airborne microorganisms (1994)

The solid-phase PCR (SP-PCR) was compared with a culture-based technique for the detection of aerosolized Escherichia coli DH1. Results with SP-PCR showed an increase in detection sensitivity over that of culture methods. Therefore, SP-PCR may be useful for the detection of airborne microorganisms which may be nonculturable because of aerosolization or sampling stress.
Estimated Risks for Developing Obesity in the Framingham Heart Study (2005)

The long-term risks for overweight or more or obesity exceeded 50% and 25%, respectively, indicating a large public health burden. These estimates suggest that the future burden of obesity-associated diseases may be substantial.
Vascular endothelial growth factor is produced by peritoneal fluid macrophages in endometriosis and is regulated by ovarian steroids. (1996)

Angiogenesis is important in the pathophysiology of endometriosis, a condition characterized by implantation of ectopic endometrium in the peritoneal cavity. Vascular endothelial growth factor (VEGF) is a potent angiogenic factor involved in physiological and pathological angiogenesis, and elevated levels of VEGF are found in peritoneal fluid of patients with endometriosis. Our aim was to investigate the site of expression and regulation of VEGF in endometriosis. VEGF immunoreactivity was found in tissue macrophages present in ectopic endometrium and in activated peritoneal fluid macrophages. Macrophage activation was highest in women with endometriosis, and media conditioned by peritoneal fluid macrophages from these women caused a VEGF-dependent increase in endothelial cell proliferation above that seen from normal women. Peritoneal fluid macrophages secreted VEGF in response to ovarian steroids, and this secretion was enhanced after activation with lipopolysaccharide. Peritoneal fluid macrophages expressed receptors for steroid hormones. VEGF receptors flt and KDR (kinase domain receptor) were also detected, suggesting autocrine regulation. During the menstrual cycle, expression of flt was constant but that of KDR was increased in the luteal phase, at which time the cells migrated in response to VEGF. KDR expression and the migratory response were significantly higher in patients with endometriosis. This study demonstrates that activated macrophages are a major source of VEGF in endometriosis and that this expression is regulated directly by ovarian steroids.
Production and characterization of monoclonal antibodies to Mycobacterium tuberculosis, M. bovis (BCG) and M. leprae. (1984)

Thirty-two monoclonal antibodies (MoAb) to Mycobacterium tuberculosis H37Rv, M. bovis BCG and M. leprae were produced. The spleen cells of BALB/c mice immunized with sonicated or intact bacilli were fused with Sp2/0-Ag-14 myeloma cells. Many more antibody producing hybridomas were found when M. tuberculosis, rather than M. leprae, was used as the immunogen. The MoAb were characterized by an enzyme immunoassay and immunofluorescence on 16 mycobacterial species. The sodium dodecylsulphate polyacrylamide gel electrophoresis immunoperoxidase assay was used to determine the molecular weight of the antigens detected by the MoAb. Antigens of high, low and intermediate molecular weight were found. Some of the antigens were proteinaceous, others of a glycolipid nature. The immunofluorescence assay proved to be essential for the selection of MoAb since some MoAb reacted only in this assay and not in the enzyme immunoassay. The most specific clones were found in the fusions with spleen cells of mice immunized with intact rather than sonicated bacteria. One MoAb (F29-29) reacted only with M. tuberculosis H37Rv; one (F41-3) only with M. leprae and another (F29-45) reacted with M. tuberculosis and M. gastrii. Several MoAb only reacted with three mycobacterial species: M. tuberculosis, M. kansasii and M. gastrii. Others showed unique patterns of reactivity by enzyme immuno- and immunofluorescence assay. The potential use of the MoAb for the identification of mycobacteria and mycobacterial antigens is discussed.
A Speech Biometrics System With Multi-Grained Speaker Modeling (2000)

The paper describes a system for voice-based personal authentication in a conceptual framework of conversational speech biometrics relying on two sources of authentication - the acoustic voice-print and the user knowledge. Several technologies are closely integrated: speaker recognition and speech recognition as well as natural language understanding and dialog management. The first part of this paper details on the algorithms for the acoustic voice-print modeling and recognition and presents experimental results on two databases with telephony speech. The second part describes the integration of acoustic voice-print recognition and speech recognition in a prototype that allows for natural language input and dynamic authentication scenaria in the telephony environment, together with an experimental evaluation carried out on a speech-biometrics database.
De Novo Synthesis of Tamiflu via a Catalytic Asymmetric Ring-Opening of <i>meso</i>-Aziridines with TMSN<sub>3</sub> (2006)

An asymmetric ring-opening reaction of meso-aziridines with TMSN3 was developed using a catalyst prepared from Y(OiPr)3 and chiral ligand 2 in a 1:2 ratio. Excellent enantioselectivity was realized from a wide range of substrates with a practical catalyst loading. The products were efficiently converted to enantiomerically enriched 1,2-diamines, which are versatile chiral building blocks for pharmaceuticals and chiral ligands. This reaction was applied to a catalytic asymmetric synthesis of Tamiflu, a very important anti-influenza drug containing a chiral 1,2-diamino functionality.
Ionic liquids as refolding additives: N′‐alkyl and N′‐(ω‐hydroxyalkyl) N‐methylimidazolium chlorides (2005)

The purpose of this work was to investigate the influence of a series of N'-alkyl and N'-(omega-hydroxy-alkyl)-N-methylimidazolium chlorides on the renaturation of two model proteins, namely hen egg white lysozyme and the single-chain antibody fragment ScFvOx. All tested ionic liquids acted as refolding enhancers, with varying efficacies and efficiencies. The results of the refolding screening could be interpreted by taking into account the effect of the studied ionic liquids on protein aggregation, together with the systematic variations of their influence on the stability of native proteins in solution. More hydrophobic imidazolium cations carrying longer alkyl chains were increasingly destabilizing, while terminal hydroxylation of the alkyl chain made the salts more compatible with protein stability. The studied ionic liquids can be classified as preferentially bound, slightly to moderately chaotropic cosolvents for proteins.
Characterization of <i>Star</i> and its interactions with <i>sevenless</i> and <i>EGF receptor</i> during photoreceptor cell development in <i>Drosophila</i> (1994)

Loss-of-function mutations in Star impart a dominant rough eye phenotype and, when homozygous, are embryonic lethal with ventrolateral cuticular defects. We have cloned the Star gene and show that it encodes a novel protein with a putative transmembrane domain. Star transcript is expressed in a dynamic pattern in the embryo including in cells of the ventral midline. In the larval eye disc, Star is expressed first at the morphogenetic furrow, then in the developing R2, R5, and R8 cells as well as in the posterior clusters of the disc in additional R cells. Star interacts with Drosophila EGF receptor in the eye and mosaic analysis of Star in the larval eye disc reveals that homozygous Star patches contain no developing R cells. Taken together with the expression pattern at the morphogenetic furrow, these results demonstrate an early role for Star in photoreceptor development. Additionally, loss-of-function mutations in Star act as suppressors of R7 development in a sensitized genetic background involving the Son of sevenless (Sos) locus, and overexpression of Star enhances R7 development in this genetic background. Based on the genetic interactions with Sos, we suggest that Star also has a later role in photoreceptor development including the recruitment of the R7 cell through the sevenless pathway.