gebhart/patrepeval huggingface dataset:
Resonant noise-canceling current front-end for high-resolution impedance sensing (2018)

The ultimate resolution limit of the current front-end of wideband impedance detection circuits is set by the input total capacitance and input equivalent noise. We present a solution to reduce the noise of more than an order of magnitude when the capacitance cannot be further minimized. By introducing a properly-chosen inductor (and a proper and stable biasing network) it is possible to cancel the capacitive reactance at the resonance frequency (~10 MHz) which becomes the sensing frequency, thus significantly reducing the detection noise, while preserving the accuracy of the transfer function. A detailed analysis of the scheme, and its experimental validation with different inductors are presented. In all cases an improvement larger than 10 is achieved with an input-referred current spectral density of ~1 pA/VHz at the operating frequency of ~20 MHz.
How the anti-(metal chelate) antibody CHA255 is specific for the metal ion of its antigen: X-ray structures for two Fab'/hapten complexes with different metals in the chelate (1993)

Antibodies with bound metal-chelate haptens provide new means for exploiting the diverse properties of metallic elements. The murine monoclonal antibody CHA255 (IgG1 lambda) binds the metal-chelate hapten indium (III)-4-[N'-(2-hydroxyethyl)thioureido]-L-benzyl-EDTA (designated In-EOTUBE) with high affinity (K(a) = 1.1 x 10(10) M-1). Antibody binding is highly specific for the indium chelate; the affinity decreases as much as 10(4) with other metals, even those having ionic radii close to indium. To better understand this selectivity, the crystal structure of the antigen-binding fragment (Fab') of CHA255 complexed with its hapten, In(III)-EOTUBE, was determined by molecular replacement and refined at 2.2-A resolution. The structure of CHA255 Fab' complexed with Fe(III)-EOTUBE was also determined and refined at 2.8-A resolution. In both structures, the hapten's EDTA moiety is half-buried near the center of the complementarity-determining regions (CDR's). Five of the six CDR's on the Fab' interact with the hapten through protein side-chain atoms (but not main-chain atoms). A novel feature of the In-EOTUBE/Fab' complex is coordination of the indium by N epsilon of one histidine from the heavy chain's third CDR (distance = 2.4 A). The histidine coordination is not observed in the Fe-EOTUBE/Fab' complex, due mainly to a slightly different hapten conformation that reduces metal accessibility; this may partially explain the 20-fold lower affinity of CHA255 for iron hapten. An unexpected feature of the Fab' overall is an elbow angle of 193 degrees (the angle between the pseudodyad axes of the Fab's constant and variable domains).
H-Phosphonate Approach for Solid-Phase Synthesis of Oligodeoxyribonucleoside Boranophosphates and Their Characterization (1998)

Substitution of a borano (BH3-) group for nonbridging oxygen in the phosphate backbone of DNA results in a new class of isoelectronic and isoionic DNA analogues. An effective chemical method of synthesis of oligodeoxynucleoside boranophosphates (BH3-−ODNs) on a solid phase has been developed via an H-phosphonate chain elongation approach followed by boronation. The boronation procedure involves the intermediate conversion of an H-phosphonate to a phosphite triester group by silylation and subsequent oxidation by a borane−amine complex. The efficiency of the boronation procedure to form BH3-−ODNs is close to that of iodine oxidation to form phosphodiester ODNs. Oligothymidine boranophosphates of different lengths up to 12-mer have been readily synthesized, purified by HPLC and/or PAGE methods, and characterized by NMR spectroscopy and MS spectrometry. In physiologically relevant buffers the dodecathymidine boranophosphate hybridized with complementary dodecadeoxyadenylate and exhibited a cooperative melting transition (Tm = 14 °C). Studies of substrate properties showed that BH3-−ODNs are readily 5‘-phosphorylated by T4 polynucleotide kinase. Boranophosphate analogues are much more resistant toward nuclease hydrolysis than phosphodiester ODNs, and more resistant to P1 and S1 nucleases and snake venom phosphodiesterase than phosphorothioate ODNs.
Abstraction As a Configuration Design Methodology (1993)

Abstract Configuration design can be thought of as a process of generating artifacts by assembling pre-defined components. This paper introduces a method for reducing the size of configuration problems by abstracting components to higher levels of abstraction. At higher abstraction levels, less important detail is temporarily ignored, and each component represents a family of lower-level components. Configuration is then performed at the highest level, explicitly enumerating all configurations at that level. Any complete configuration at the highest level is recursively instantiated to lower levels. At the same time, any incomplete configuration at the highest level is eliminated, thereby eliminating all possible lower-level instantiations of that configuration. In this manner, all configurations of components at the lowest level of abstraction are implicitly enumerated.
Inhibition of the Influenza Virus M Protein MRNA Translation in vitro with Complementary Oligonucleotides (1991)

Abstract Efficient arrest of the influenza virus M protein mRNA translation is achieved with antisense oligodeoxyribo-nucleotides comlementary to the 5′-terminus of the messenger at the initfation codon and the upstream sequences.
New Trends in Colloidal Liquid Crystals Based on Mineral Moieties (2000)

Lyotropic mineral liquid crystals—materials that are generally electron rich, thermally stable, and often inexpensive—are reviewed. Molecular wires, ribbons, and disks as well as anisotropic crystallites are examined and guidelines useful in the search for new mineral liquid-crystalline suspensions are given. The Figure shows a centimeter-size single domain of nematic clay gel observed between crossed polarizers.
Sepsis Plasma Protein Profiling with Immunodepletion, Three-Dimensional Liquid Chromatography Tandem Mass Spectrometry, and Spectrum Counting (2006)

Sepsis is a systemic, often fatal inflammatory response whose biochemical pathways are not fully understood and with no single biomarker capable of its reliable prediction. Increased interest in protein profiling to reveal fundamental biochemical events as well as disease diagnosis has grown considerably, largely due to advances in mass spectrometry and related front-end technologies. In this study, patients with sepsis and systemic inflammatory response syndrome (SIRS) were examined using plasma protein profiling following immunodepletion treatment to remove the most abundant proteins, serum albumin, transferrin, haptoglobin, anti-trypsin, IgG, and IgA. These proteins cause significant signal suppression, and their removal allows for lower abundance proteins to be examined through improved ion signal. Analyses after immunodepletion were performed using 3-dimensional reverse phase/strong cation exchange/reverse phase liquid chromatography with electrospray ion trap mass spectrometry (3D LC-MS/MS) and spectrum counting for comparative quantitation. The results revealed a major theme in immune system activity, including activation of the complement and coagulation pathways. Additionally, lipid transport may prove to be important in distinguishing sepsis from SIRS. Specifically, significant multi-fold changes were observed in 10 proteins and are now being investigated for the early diagnosis of sepsis.
Human Immunodeficiency Virus Type 1 Spinoculation Enhances Infection through Virus Binding (2000)

The study of early events in the human immunodeficiency virus type 1 (HIV-1) life cycle can be limited by the relatively low numbers of cells that can be infected synchronously in vitro. Although the efficiency of HIV-1 infection can be substantially improved by centrifugal inoculation (spinoculation or shell vial methods), the underlying mechanism of enhancement has not been defined. To understand spinoculation in greater detail, we have used real-time PCR to quantitate viral particles in suspension, virions that associate with cells, and the ability of those virions to give rise to reverse transcripts. We report that centrifugation of HIV-1(IIIB) virions at 1,200 x g for 2 h at 25 degrees C increases the number of particles that bind to CEM-SS T-cell targets by approximately 40-fold relative to inoculation by simple virus-cell mixing. Following subsequent incubation at 37 degrees C for 5 h to allow membrane fusion and uncoating to occur, the number of reverse transcripts per target cell was similarly enhanced. Indeed, by culturing spinoculated samples for 24 h, approximately 100% of the target cells were reproducibly shown to be productively infected, as judged by the expression of p24(gag). Because the modest g forces employed in this procedure were found to be capable of sedimenting viral particles and because CD4-specific antibodies were effective at blocking virus binding, we propose that spinoculation works by depositing virions on the surfaces of target cells and that diffusion is the major rate-limiting step for viral adsorption under routine in vitro pulsing conditions. Thus, techniques that accelerate the binding of viruses to target cells not only promise to facilitate the experimental investigation of postentry steps of HIV-1 infection but should also help to enhance the efficacy of virus-based genetic therapies.
pH-Sensitive Polymer Nanospheres for Use as a Potential Drug Delivery Vehicle (2007)

We report the development and characterization of pH-sensitive poly(2-tetrahydropyranyl methacrylate) [poly(THPMA)] nanospheres and demonstrate their feasibility as an effective drug delivery vehicle. Poly(THPMA) nanospheres were prepared using either the double emulsion or single emulsion method for the encapsulation of, respectively, water soluble (rhodamine B) or organic soluble (paclitaxel) payloads. The resulting nanospheres showed pH-dependent dissolution behavior, resulting in significant morphologic changes and loss of nanoparticle mass under mild acidic conditions (pH 5.1) with a half-life of 3.3 days, as compared to physiologic condition (pH 7.4) with a half-life of 6.2 days. The in vitro drug release profile of the paclitaxel-loaded poly(THPMA) nanospheres revealed that the rate of drug release in pH 5.1 acetate buffer was relatively faster than that in pH 7.4 HEPES buffer. Furthermore, poly(THPMA) nanospheres showed lower cytotoxicity and higher cellular uptake as compared to the FDA-approved PLGA-based nanospheres currently in clinical practice.
alpha-Aminoadipate as a primary nitrogen source for Saccharomyces cerevisiae mutants (1985)

In contrast to wild-type strains of the yeast Saccharomyces cerevisiae, lys2 and lys5 mutants are able to utilize alpha-aminoadipate as a primary source of nitrogen. Chattoo et al. (B. B. Chattoo, F. Sherman, D. A. Azubalis, T. A. Fjellstedt, D. Mehnert, and M. Ogur, Genetics 93:51-65, 1979) relied on this difference in the effective utilization of alpha-aminoadipate to develop a procedure for directly selecting lys2 and lys5 mutants. In this study we used a range of mutant strains and various media to determine why normal strains are unable to utilize alpha-aminoadipate as a nitrogen source. Our results demonstrate that the anabolism of high levels of alpha-aminoadipate through the biosynthetic pathway of lysine results in the accumulation of a toxic intermediate and, furthermore, that lys2 and lys5 mutants contain blocks leading to the formation of this intermediate.
Managing Antibiotic Resistance (2000)

One hundred years ago, the three major causes of death in the United States were tuberculosis, pneumonia, and gastrointestinal infections. Subsequently, the advent of antibiotics resulted in a major decline in the incidence of life-threatening infections in the developed world. By the end of the 20th century, only lower respiratory tract infections still ranked among the top 10 causes of death. As we approach January 2001, however, the unforgiving rise in the frequency of multidrug resistance among leading pathogens should cause great concern and incite a commitment to act responsibly.The pneumococcus is arguably the most important cause of community-acquired . . .
Creating a network for interactivity (1995)

The one most likely system, to serve as the common meeting ground for phone and cable companies, is a hybrid network architecture of optical fibers and coaxial cables. As the industry evolves toward interactive services, three considerations will become paramount. One is the ability to deliver individualized programming to customers, and get responses from them as well. Here, the instantaneous network bandwidth is of less concern than the effective bandwidth per customer. So long as all the programming and services a customer desires are available in a user-friendly way, it is irrelevant how the network delivers them. By its nature, interactivity also implies that the measure of effective bandwidth per customer be extended to bidirectional communication between the customer and the head-end. Several ways of providing that increased effective bandwidth are discussed. A second prime concern is the need for more attention to network reliability in delivering services. Finally, the issues of standards and security must be dealt with.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Regulation of stability and synthesis of EGF-receptor mRNAs encoding for intact and truncated receptor forms. (1990)

The EGF-receptor is a proto-oncogene encoded membrane protein related to the v-erb-B oncogene product of avian erythroblastosis virus. Here we have studied the expression and stability characteristics of two forms of receptor mRNA--a 5.6 kb form that encodes for the intact transmembrane 170 kDa receptor and a 3' deleted 2.6 kb form that encodes for a 100 kDa secreted EGF-receptor. In previous studies we showed that EGF increased the synthesis of its own receptor in human cytotrophoblasts and A431 cells. Now we show that EGF stimulates the transcription of the receptor gene and blocks the degradation of transcripts, and thus elevates the level of receptor mRNA in these cells. To test the role of prior protein synthesis in these phenomena, we examined the effect of cycloheximide, and found that this reagent, either alone or in combination with EGF, leads to an increase in the level of EGF-receptor mRNA. Increases were seen in both size classes of receptor mRNA. Further analysis showed that cycloheximide enhances both synthesis and stability of receptor mRNA. While the intrinsic stability of the 3'-truncated 2.6 kb mRNA is approximately 2-fold higher than that of the 5.6 kb species, it is enhanced by more than 10-fold in the presence of cycloheximide and EGF acting in a synergistic manner. The extent of stabilization was less for the larger mRNA form. The results suggest the involvement of ligand as well as labile proteins in the control of synthesis and stability of EGF-receptor mRNA, and imply the involvement of 3' located structural features in the control of receptor mRNA stability.
Inhaled insulin as adjunctive therapy in subjects with type 2 diabetes failing oral agents: a controlled proof‐of‐concept study (2006)

In subjects with type 2 diabetes inadequately controlled by oral agents, preprandial administration of INH delivered by a MDI provided a comparable metabolic control to bedtime GLA and did not show any safety concerns during a 4-week treatment. These results warrant a more extensive investigation of preprandial treatment with INH in longer term studies.
Hyperbranched polymers—All problems solved after 15 years of research? (2005)

Abstract Fifteen years of research on hyperbranched polymers in the group of Brigitte Voit are described, with a focus first on hyperbranched polyester synthesis and then on the addition and cycloaddition reactions used for the preparation of the hyperbranched structure. The characterization of structural details and bulk, solution, and thin‐film properties is highlighted, and steps toward the elucidation of a general property profile of hyperbranched polymers are discussed. Some effects of hyperbranched polymers in reactive formulations and blends and in thin films are addressed that can lead to applications in coatings, as additives, and in microelectronics or sensorics. The great progress possible in the last years is shown, but open questions and unsolved problems are also pointed out. © 2005 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 43: 2679–2699, 2005
Activation of human endothelial cells from specific vascular beds induces the release of a FVIII storage pool (2010)

Although the liver is known to be the main site of factor VIII (FVIII) production, other organs are probably also important for the regulation of FVIII secretion. However, the study of the regulation of extrahepatic FVIII production has been hampered by the lack of definitive identification of human tissues able to secrete FVIII. Recent studies have shown that lung endothelial cells can synthesize FVIII. We therefore studied the production of FVIII by endothelial cells purified from other vascular beds. Because physiologic stress results in a rapid elevation of FVIII, we also investigated whether endothelial cells can store FVIII and secrete it after treatment with agonists. Microvascular endothelial cells from lung, heart, intestine, and skin as well as endothelial cells from pulmonary artery constitutively secreted FVIII and released it after treatment with phorbol-myristate acetate and epinephrine. By contrast, endothelial cells from the aorta, umbilical artery and umbilical vein did not constitutively secrete FVIII or release it after treatment with agonists, probably because of a lack of FVIII synthesis. Extrahepatic endothelial cells from certain vascular beds therefore appear to be an important FVIII production and storage site with the potential to regulate FVIII secretion in chronic and acute conditions.
Plasmid-encoded AmpC β-lactamases: how far have we gone 10 years after the discovery? (1998)

The dogma that ampC genes are located exclusively on the chromosome was dominant until about 10 years ago. Since 1989 over 15 different plasmid-encoded AmpC beta-lactamases have been reported from several countries. Most of these enzymes evolved in two clusters. The major cluster includes several enzymes with a high similarity to CMY-2, which is the closest related chromosomal AmpC enzyme of Citrobacter freundii. A second cluster centers around CMY-1. It is less homogeneous and not closely related chromosomal AmpC enzymes. Molecular diversification by amino acid substitutions does not usually translate into a change in the resistance phenotype. At this time, CMY-2 appears to be the most prevalent and widely distributed. Further global increase of prevalence and diversity of plasmidic AmpC beta-lactamases have to be anticipated in the next millenium.
Peroxovanadium compounds. A new class of potent phosphotyrosine phosphatase inhibitors which are insulin mimetics. (1994)

Twelve peroxovanadium (pV) compounds, each containing an oxo ligand, one or two peroxo anions, and an ancillary ligand in the inner coordination sphere of V, were synthesized, crystallized, and characterized by 51V NMR as > 95% pure. These compounds activated the insulin receptor kinase (IRK) of cultured hepatoma cells, stimulated lipogenesis in adipocytes, and inhibited the in situ dephosphorylation of autophosphorylated IRs and epidermal growth factor receptors of rat liver endosomes. The phosphotyrosine phosphatase inhibitory and IRK activating potencies of these compounds were linearly correlated (r = 0.74; p < 0.003), decayed in parallel in solution, and varied considerably with the ancillary ligands within these compounds. In vivo administration activated rat liver IRK in parallel with its tyrosine phosphorylation. Co-administration of insulin plus pV was markedly synergistic in both respects. pV administration significantly decreased circulating insulin and plasma glucose concentrations; the latter to levels seen after a dose of insulin yielding > or = 50% occupancy of IRs in vivo. Two compounds (mpV(pic) and mpV(2,6-pdc)) displayed relative specificity as phosphotyrosine phosphatase inhibitors by inhibiting IR dephosphorylation to a significantly greater degree than epidermal growth factor receptor dephosphorylation. Thus, pV compounds are the most potent phosphotyrosine phosphatase inhibitors described to date. Their capacity to activate IRK appears to derive from their phosphotyrosine phosphatase inhibitory activity. Their hypoglycemic action is due to a direct tissue effect.
Role of the ENTH Domain in Phosphatidylinositol-4,5-Bisphosphate Binding and Endocytosis (2001)

Endocytic proteins such as epsin, AP180, and Hip1R (Sla2p) share a conserved modular region termed the epsin NH2-terminal homology (ENTH) domain, which plays a crucial role in clathrin-mediated endocytosis through an unknown target. Here, we demonstrate a strong affinity of the ENTH domain for phosphatidylinositol-4,5-bisphosphate [PtdIns(4,5)P2]. With nuclear magnetic resonance analysis of the epsin ENTH domain, we determined that a cleft formed with positively charged residues contributed to phosphoinositide binding. Overexpression of a mutant, epsin Lys76 --> Ala76, with an ENTH domain defective in phosphoinositide binding, blocked epidermal growth factor internalization in COS-7 cells. Thus, interaction between the ENTH domain and PtdIns(4,5)P2 is essential for endocytosis mediated by clathrin-coated pits.
Coexpression of the interleukin-13 and interleukin-4 genes correlates with their physical linkage in the cytokine gene cluster on human chromosome 5q23-31 (1996)

Interleukin-13 (IL-13) and IL-4 are cytokines produced by T cells that are encoded by the q23-31 region of human chromosome 5. To investigate the regulation of IL-13 gene expression by T cells, we isolated and sequenced the human IL-13 gene, analyzed its 5'-flanking region for potential transcriptional activation elements, and examined its expression in nontransformed T-lineage cell populations. The human IL-13 gene was located 12.5-kb upstream of the IL-4 gene and 2-kb downstream of a CpG island. The IL-13 gene 5' flank region included a segment with sequence homology to P elements of the IL-4 promoter involved in transcriptional activation in T cells. Mutation of the IL-13 P element site significantly reduced IL-13 promoter activity in response to T-cell activation. Oligonucleotides containing the IL-13 or IL-4 P element sites specifically bound the transcriptional activator protein, nuclear factor-activated T cells, preformed (NF-ATp), when incubated with nuclear protein extracts from activated T cells. Similar to IL-4, IL-13 mRNA expression was highest in T-cell populations enriched for cells that had previously been primed in vivo or in vitro, indicating that priming increases the expression of the IL-13 and IL-4 genes in a coordinate manner. Because the primed T cells contain higher levels of nuclear NF-ATp, capable of binding to P elements of the IL-4 and IL-13 promoters, than do freshly-isolated T cells, the NF-AT-binding P elements are attractive candidates to mediate the coordinate expression of these two cytokine genes.