gebhart/patrepeval huggingface dataset:
Effect of Various Oxygenation Conditions and Fluosed-DA on Cytotoxicity and Antitumor Activity of Blemoycin in Mice2 (1988)

In an attempt to improve the antitumor efficacy of bleomycin, the effects of the oxygen-carrying emulsion Fluosol-DA and increased levels of inspired oxygen were tested in the mouse FSaIIC fibrosarcoma system. The dose-dependent cytotoxicity of bleomycin toward the FSaIIC cells in vitro was significantly decreased under hypoxic conditions, but it increased in a 95% O2-5% CO2 (carbogen) atmosphere as compared with the cytotoxicity of bleomycin in normally oxygenated cells. Investigations on the FSaIIC tumor in vivo also demonstrated that growth delays induced by bleomycin (10 mg/kg ip given on days 6, 10, 13, and 16) were significantly increased when one of the following treatments was given with each bleomycin injection: carbogen breathing for 2 hours (4.7 days), carbogen breathing for 6 hours (5.7 days), and breathing 3 atm of hyperbaric oxygen (6.3 days) versus normal air (3.3 days). When Fluosol-DA (12 mL/kg iv) was administered just before each bleomycin injection, the following growth delays were produced: 4.8 days with air breathing, 14.6 days with carbogen breathing for 2 hours, 14.9 days with carbogen breathing for 6 hours, and 19.7 days with breathing 100% O2 at 3 atm for 1 hour. Excision studies on the FSaIIC tumor also demonstrated that the cytotoxicity increased approximately fivefold when Fluosol-DA and carbogen breathing for 2 hours were combined with a single treatment with 10 mg of bleomycin/kg. In contrast, no measurable bone marrow toxicity was evident with this combined regimen. These results suggest that the use of Fluosol-DA plus carbogen breathing could add substantially to the clinical antitumor effects of bleomycin.
Alternative splicing of CD79a ( ) and CD79b ( ) RNA transcripts in human B cells (1995)

The CD79a (Ig-alpha/mb-1) and CD79b (Ig-beta/B29) molecules form a membrane heterodimer that is non-covalently associated with surface membrane immunoglobulin and is the major signaling component of the B cell antigen receptor complex. We have defined variant RNA transcripts for both CD79a (Ig-alpha/mb-1) and CD79b (Ig-beta/B29) which appear to arise by alternative splicing. These splice variants are predicted to encode truncated forms of these molecules that result in the deletion of the entire extracellular Ig-like domain of CD79b and of a major portion of the extracellular domain of CD79a. The presence of these short transcripts in a variety of human B cells and B cell lines was established by an RNAse protection assay. The definition of these variant transcripts provides a basis for a continuing effort to define variant protein products of CD79a and CD79b and examine their role in B cell physiology.
Thermal Emission Spectra from Individual Suspended Carbon Nanotubes (2011)

We study the thermal emission spectra of individual suspended carbon nanotubes induced by electrical heating. Semiconducting and metallic devices exhibit different spectra, based on their distinctive band structures. These spectra are compared with the ideal blackbody emission spectrum. In the visible wavelength range, the thermal emission spectra of semiconducting devices agree well with Planck's law, while the spectra of metallic devices show an additional peak between 1.5 and 1.9 eV. In the near-infrared wavelength range, the semiconducting nanotubes exhibit a peak around 1 eV. These additional peaks are attributed to the E11M and E22SC transitions that are thermally driven under these high applied bias voltages. These peaks show a strong polarization dependence, while the blackbody tail is unpolarized, which provides further evidence for electron-hole recombination in thermal emission. For semiconducting devices, the temperature of the nanotube is fit to Planck's law and compared with the temperatures obtained from the G band and 2D band Raman downshifts, as well as the anti-Stokes/Stokes intensity ratio. For devices showing thermal non-equilibrium, the electron temperature agrees well with G+ downshift but deviates from G_ downshift.
Preparation and characterization of a chimeric CD 19 monoclonal antibody (1991)

FMC63 is an IgG2a mouse monoclonal antibody belonging to the CD19 cluster. CD19 antibodies react with a 95kDa protein expressed by cells of the B lymphocyte lineage, from pre-B cells to mature B lymphocytes. CD19 antibodies have been suggested as candidates for immunological attack on leukaemic and lymphoma cells of the B lineage because the antigen is restricted to the B lineage. With the potential use of FMC63 in immunotherapy in mind, we have produced a mouse-human chimera in which the genes coding for the VDJ region of the heavy chain and the VJ region of the light chain derive from the FMC63 mouse hybridoma, while the C region genes code for human IgG1. The genes have been transfected back into a mouse myeloma line, which secretes low levels of immunoglobulin. (Ig). This Ig was purified and biotinylated in order to determine the specificity of the antibody. The chimeric antibody has a reaction profile concordant with the original FMC63 antibody, but has the properties of a human IgG1, including the ability to fix human complement. However, the antibody is not cytotoxic in vitro in the presence of complement or cells capable of mediating antibody-dependent cellular cytotoxicity. Possible reasons for this and ways of using the antibody are discussed.
Role of a Novel PH-Kinase Domain Interface in PKB/Akt Regulation: Structural Mechanism for Allosteric Inhibition (2009)

Protein kinase B (PKB/Akt) belongs to the AGC superfamily of related serine/threonine protein kinases. It is a key regulator downstream of various growth factors and hormones and is involved in malignant transformation and chemo-resistance. Full-length PKB protein has not been crystallised, thus studying the molecular mechanisms that are involved in its regulation in relation to its structure have not been simple. Recently, the dynamics between the inactive and active conformer at the molecular level have been described. The maintenance of PKB's inactive state via the interaction of the PH and kinase domains prevents its activation loop to be phosphorylated by its upstream activator, phosphoinositide-dependent protein kinase-1 (PDK1). By using a multidisciplinary approach including molecular modelling, classical biochemical assays, and Förster resonance energy transfer (FRET)/two-photon fluorescence lifetime imaging microscopy (FLIM), a detailed model depicting the interaction between the different domains of PKB in its inactive conformation was demonstrated. These findings in turn clarified the molecular mechanism of PKB inhibition by AKT inhibitor VIII (a specific allosteric inhibitor) and illustrated at the molecular level its selectivity towards different PKB isoforms. Furthermore, these findings allude to the possible function of the C-terminus in sustaining the inactive conformer of PKB. This study presents essential insights into the quaternary structure of PKB in its inactive conformation. An understanding of PKB structure in relation to its function is critical for elucidating its mode of activation and discovering how to modulate its activity. The molecular mechanism of inhibition of PKB activation by the specific drug AKT inhibitor VIII has critical implications for determining the mechanism of inhibition of other allosteric inhibitors and for opening up opportunities for the design of new generations of modulator drugs.
Molecular Self-Assembly and Nanochemistry: a Chemical Strategy for the Synthesis of Nanostructures (1991)

Molecular self-assembly is the spontaneous association of molecules under equilibrium conditions into stable, structurally well-defined aggregates joined by noncovalent bonds. Molecular self-assembly is ubiquitous in biological systems and underlies the formation of a wide variety of complex biological structures. Understanding self-assembly and the associated noncovalent interactions that connect complementary interacting molecular surfaces in biological aggregates is a central concern in structural biochemistry. Self-assembly is also emerging as a new strategy in chemical synthesis, with the potential of generating nonbiological structures with dimensions of 1 to 10(2) nanometers (with molecular weights of 10(4) to 10(10) daltons). Structures in the upper part of this range of sizes are presently inaccessible through chemical synthesis, and the ability to prepare them would open a route to structures comparable in size (and perhaps complementary in function) to those that can be prepared by microlithography and other techniques of microfabrication.
Introduction: The University of Nebraska College of Law's Space and Telecommunications Law Program (2007)

The hypercoordinate [SiH<sub>6</sub>]<sup>2-</sup> anion is not stable in solution. Here, we report the room temperature, solution stable molecular [SiH<sub>6</sub>]<sup>2-</sup> complex, [{KCa(NON)(OEt<sub>2</sub>)}<sub>2</sub>][SiH<sub>6</sub>] (NON=4,5-bis(2,6-diisopropylanilido)-2,7-di-tert-butyl-9,9-dimethyl-xanthene)), where the [SiH<sub>6</sub>]<sup>2-</sup> anion is stabilised within a supramolecular assembly that mimics the solid-state environment of the anion in the lattice of K<sub>2</sub>SiH<sub>6</sub>. Solution-state reactivity of the complex towards carbon monoxide, benzaldehyde, azobenzene and acetonitrile is reported, yielding a range of reduction and C-C coupled products.
A tri-hybrid system for the analysis and detection of RNA--protein interactions (1996)

A modification of the two-hybrid system is described for the in vivo reconstruction of specific RNA-protein interactions. In this tri-hybrid system, the DNA binding and transcription activation domains of the yeast transcriptional activator GAL4 are brought together via the interaction of recombinant fusion proteins with a recombinant RNA. The method provides a system for studying RNA-protein interactions with the genetic advantages of the two-hybrid system. It may be used to detect specific RNA-binding proteins or target RNAs from a library of cDNAs, or to analyse the structural specificity of identified RNA-protein interactions.
Adsorption of Follicular Dendritic Cell-secreted Protein (FDC-SP) onto Mineral Deposits (2008)

Follicular dendritic cell-secreted protein (FDC-SP) is a small secretory protein having structural similarities to statherin, a protein in saliva thought to play a role in calcium retention in saliva. In contrast, FDC-SP is thought to play a role in the immune system associated with germinal centers. We report here the very specific expression of FDC-SP in junctional epithelium at the gingival crevice. This region is very important for the host defense against pathogens and for periodontal protection. To be able to better understand the function of FDC-SP, we developed a novel gene expression system that exploited gene trapping and site-specific gene integration to introduce the protein into a mammalian cell culture system. Using this system we were able to express FDC-SP as a fusion protein with green fluorescent protein in an osteogenic progenitor cell line with long term stability, which we then used to find that the fusion protein specifically adsorbs onto mineral deposits and the surface of hydroxyapatite particles exogenously added to the culture. This adsorption was highly dependent on the structural integrity of FDC-SP. These results suggest that FDC-SP may play an important role, adsorbing onto the surface of cementum and alveolar bone adjacent to periodontal ligament and onto tooth surface at the gingival crevice.
The Cerebral Circulation (2009)

This presentation describes structural and functional properties of the cerebral circulation that are unique to the brain, an organ with high metabolic demands, and the need for tight water and ion homeostasis. Autoregulation is pronounced in the brain, with myogenic, metabolic, and neurogenic mechanisms contributing to maintain relatively constant blood flow during both increases and decreases in pressure. In addition, unlike peripheral organs where the majority of vascular resistance resides in small arteries and arterioles, large extracranial and intracranial arteries contribute significantly to vascular resistance in the brain. The prominent role of large arteries in cerebrovascular resistance helps maintain blood flow and protect downstream vessels during changes in perfusion pressure. The cerebral endothelium is also unique in that its barrier properties are in some way more like epithelium than endothelium in the periphery. The cerebral endothelium, known as the blood-brain barrier, has specialized tight junctions that do not allow ions to pass freely and has very low hydraulic conductivity and transcellular transport. This special configuration modifies Starling's forces in the brain such that ions retained in the vascular lumen oppose water movement due to hydrostatic pressure. Tight water regulation is necessary in the brain because it has limited capacity for expansion within the skull. Increased intracranial pressure due to vasogenic edema can cause severe neurologic complications and death. This chapter will review these special features of the cerebral circulation and how they contribute to the physiology of the brain.
The role of tyrosine kinase activity in endocytosis, compartmentation, and down-regulation of the epidermal growth factor receptor (1991)

Occupancy-induced down-regulation of cell surface epidermal growth factor (EGF) receptors attenuates signal transduction. To define mechanisms through which down-regulation of this class of growth factor receptors occurs, we have investigated the relative roles of ligand-induced internalization and recycling in this process. Occupied, kinase-active EGF receptors were internalized through a high affinity, saturable endocytic system at rates up to 10-fold faster than empty receptors. In contrast, full length EGF receptors lacking tyrosine kinase activity underwent internalization at a rate independent of occupancy. This "kinase-independent" internalization rate appeared to reflect constitutive receptor internalization since it was similar to the internalization rate of both receptors lacking a cytoplasmic domain and of antibodies bound to empty receptors. EGF internalized by either kinase-active or kinase-inactive receptors was efficiently recycled and was found within endosomes containing recycling transferrin receptors. However, targeting of internalized receptors to lysosomes did not require receptor kinase activity. All receptors that displayed ligand-induced internalization also underwent down-regulation, indicating that the proximal cause of down-regulation is occupancy-induced endocytosis. Tyrosine kinase activity greatly enhances this process by stabilizing receptor association with the endocytic apparatus.
Antisense Inhibition of Apolipoprotein C-III in Patients with Hypertriglyceridemia (2015)

We found that treatment with ISIS 304801 was associated with significant lowering of triglyceride levels, among patients with a broad range of baseline levels, through selective antisense inhibition of APOC3 synthesis. (Funded by Isis Pharmaceuticals; ClinicalTrials.gov number, NCT01529424.).
Correction of Murine β-Thalassemia by Gene Transfer into the Germ Line (1986)

A murine beta-thalassemia was corrected by the transfer of cloned beta-globin genes into the mouse germ line. The cloned mouse beta maj-globin gene or the cloned human beta-globin gene was introduced into mice deficient in beta-globin synthesis because of a deletion of the beta maj-globin gene. Both introduced genes produced functional beta-globin chains, leading to a reduction in one case, and elimination in another case, of the anemia and associated abnormalities of the red blood cells.
Mutations Designed to Destabilize the Receptor-Bound Conformation Increase MICA-NKG2D Association Rate and Affinity (2007)

MICA is a major histocompatibility complex-like protein that undergoes a structural transition from disorder to order upon binding its immunoreceptor, NKG2D. We redesigned the disordered region of MICA with RosettaDesign to increase NKG2D binding. Mutations that stabilize this region were expected to increase association kinetics without changing dissociation kinetics, increase affinity of interaction, and reduce entropy loss upon binding. MICA mutants were stable in solution, and they were amenable to surface plasmon resonance evaluation of NKG2D binding kinetics and thermodynamics. Several MICA mutants bound NKG2D with enhanced affinity, kinetic changes were primarily observed during association, and thermodynamic changes in entropy were as expected. However, none of the 15 combinations of mutations predicted to stabilize the receptor-bound MICA conformation enhanced NKG2D affinity, whereas all 10 mutants predicted to be destabilized bound NKG2D with increased on-rates. Five of these had affinities enhanced by 0.9-1.8 kcal/mol over wild type by one to three non-contacting substitutions. Therefore, in this case, mutations designed to mildly destabilize a protein enhanced association and affinity.
Sequencing double-stranded DNA by strand displacement (1997)

Duplex probes with five base single-stranded overhangs can capture dsDNA targets from type IIS restriction nuclease digests. Ligation generates a predesigned nick site, where DNA polymerase can generate sequencing ladders by strand displacement or nick translation in the presence of trace amounts of dideoxynucleotides. This allows dsDNA targets to be captured from mixtures and directly sequenced without subcloning, purification or denaturation.
Dimeric/oligomeric DNA methyltransferases: an unfinished story (2009)

DNA methyltransferases (MTases) are enzymes that carry out post-replicative sequence-specific modifications. The initial experimental data on the structure and kinetic characteristics of the EcoRI MTase led to the paradigm that type II systems comprise dimeric endonucleases and monomeric MTases. In retrospect, this was logical because, while the biological substrate of the restriction endonuclease is two-fold symmetrical, the in vivo substrate for the MTase is generally hemi-methylated and, hence, inherently asymmetric. Thus, the paradigm was extended to include all DNA MTases except the more complex bifunctional type I and type III enzymes. Nevertheless, a gradual enlightenment grew over the last decade that has changed the accepted view on the structure of DNA MTases. These results necessitate a more complex view of the structure and function of these important enzymes.
A Series of Related Nucleotide Analogues that Aids Optimization of Fluorescence Signals in Probing the Mechanism of P-Loop ATPases, Such as Actomyosin (2004)

We have synthesized a set of ATP and ADP analogues that have a fluorophore linked to the nucleotide via the 3'-position of the ribose moiety. Combinations of three different coumarins are each attached via different length linkers. A linker based on propylenediamine increases the separation between the nucleotide and fluorophore relative to that of the previously reported ethylenediamine-linked coumarin nucleotides [Webb, M. R., and Corrie, J. E. T. (2001) Biophys. J. 81, 1562-1569]. A synthesis of 3'-amino-3'-deoxyATP is described using a combination of chemical and enzymatic procedures, mostly from published methods for synthesis of this compound but with some modifications that improved the convenience of the experimental procedures. This compound is used as a basis of a series of analogues with effectively a zero-length linker. Fluorescence properties of all these analogues are described, together with the kinetics of their interaction with rabbit skeletal myosin subfragment 1 in the presence and absence of actin. One particular analogue, deac-aminoATP [3'-(7-diethylaminocoumarin-3-carbonylamino)-3'-deoxyadenosine 5'-triphosphate], shows a 17-fold enhancement of fluorescence upon binding to this (skeletal) myosin II. As the diphosphate, it exhibits a large signal change upon dissociation from the actomyosin, with kinetics similar to those of natural ADP. The ability of this set of analogues to produce large signals indicated potential uses when scarce proteins are studied in small amounts.
DNA display for in vitro selection of diverse peptide libraries (2003)

We describe the use of a DNA display system for in vitro selection of peptide ligands from a large library of peptides displayed on their encoding DNAs. The method permits completely in vitro construction of a DNA-tagged peptide library by using a wheat germ in vitro transcription/translation system compartmentalized in water-in-oil emulsions. Starting with a library of 10(9)-10(10) random decapeptides, 21 different peptide ligands were isolated for monoclonal antibody anti-FLAG M2. DNA display selected more diverse peptides with a DYKXXD consensus motif than previously reported phage display systems. Binding and recovery rates of three peptides were significantly higher than those of the original FLAG peptide, implying that these peptides would be superior to the FLAG peptide for purification of tagged proteins. The simplicity of DNA display enables two selection rounds per day to be conducted. Further, DNA display can overcome the limitations of previous display technologies by avoiding the use of bacterial cells and RNA tags. Thus, DNA display is expected to be useful for rapid screening of a wide variety of peptide ligands for corresponding receptors.
Ockelbo Disease in Sweden: Epidemiological, Clinical, and Virological Data from the 1982 Outbreak (1984)

An outbreak of Ockelbo disease, a syndrome with rash, arthralgia and moderate fever reactions, which occurred in Sweden 1982 is described. A virus, designated Edsbyn 5/82, isolated from mosquitoes and closely related to Sindbis virus (Togaviridae: Alphavirus) is the probable etiologic agent. Sixty-five patients with typical clinical manifestations of the disease became ill in August 1982 and exhibited antibody titer rises against both Edsbyn 5/82 and Sindbis viruses by indirect immunofluorescence and the mixed hemadsorption technique. With the latter method, but not by the neutralization tests, antibody titers were significantly higher against Edsbyn 5/82 virus than against Sindbis virus. Most cases occurred in central Sweden between the 60th and 63rd parallels. The frequency of antibody in healthy individuals (blood donors) within the endemic area was 2-3% and in foci with high incidence, antibody positivity reached 8%. Antibody frequencies continuously decreased south and north of this area. Antibody decline was followed in a group of 12 patients who had Ockelbo disease in 1981. Mixed hemadsorption titers were 4-6 times higher against Edsbyn 5/82 than against Sindbis virus. A 2- to 4-fold antibody decline took place from early convalescence to 20 months after onset.
Distributed, scalable routing based on vectors of link states (1995)

We have present a new method for distributed routing in computer networks and internets using link-state information. Link vector algorithms (LVA) are introduced for the distributed maintenance of routing information in large networks and internets.
Are We Ready for Individualized Instruction? (1987)

No abstract available for this article.
Alcoholism and affective disorder: clinical course of depressive symptoms (1995)

Diagnoses of alcohol dependence and affective disorder based on symptom chronology appear to have prognostic significance with respect to remission of depressive symptoms in men with both diagnoses. Depressive symptoms of dysphoric mood, dysfunctional cognitions, vegetative symptoms, and anxiety/agitation showed different rates and levels of remission across the primary diagnostic groups.
Clamped gain travelling wave semiconductor optical amplifier for wavelength division multiplexing applications (2002)

Summary form only given. In this paper, we report a new clamped gain InGaAsP semiconductor optical amplifier (CG SOA) structure with an integrated Bragg grating as a wavelength selective reflector and demonstrate crosstalk suppression in case of WDM application at 2.5 Gbit/s.
Development of an in vitro culture method for heart-shaped embryo in Phaseolus vulgaris (1990)

peer reviewed