gebhart/patrepeval huggingface dataset:
Thyroid hormone analogues: their role in treatment of (2014)

Thyroid hormones are central regulators of lipid metabolism and energy homeostasis, which primarily act through Thyroid Hormone Receptors (TRs). Selective Thyroid Hormone Receptor Modulators (STRMs) are chemical analogues of thyroid hormone, designed to preferentially induce beneficial actions of thyroid hormone through specificity for TR β (isoform specificity) and specific accumulation in liver (tissue selectivity). Although initial results from studies of TH analogs that combine TRβ and tissue selectivity were promising, producing Impressive to Dramatic reductions of serum LDLC and triglycerides in animal models and human patients, none of these compounds has progressed beyond the early clinical stage so far. While recent human trials of STRMs have consistently produced impressive improvements in serum lipid parameters, they have also revealed unexpected side effects. Although STRMs have the potential to serve as treatments for hyperlipidemia, these developments make their widespread use in the future highly uncertain.
Investigation of spore surface antigens in the genus Bacillus by the use of polyclonal antibodies in immunofluorescence tests (1988)

Fluorescein-conjugated rabbit antibodies to formalized spores of Bacillus anthracis were tested against strains of B. anthracis and other Bacillus species in a subjective immunofluorescence test. The lack of reaction of B. anthracis Vollum spores with conjugated antibody raised against B. anthracis Sterne spores indicated that spores of the Vollum strain lacked a major surface antigen present in most of the other anthrax strains tested, including the non-encapsulated strains Sterne and the Soviet ST1, variants cured of the pX01 plasmid that codes for the toxin, and several virulent strains. Four other antibody preparations, raised against B. anthracis Vollum, New Hampshire, Ames and Strain 15, reacted to an approximately similar degree with spores of all four strains and of Sterne, indicating that Vollum has at least one spore antigen in common with these other strains. The anti-Sterne and anti-Vollum conjugates both displayed cross-reactions with spores of strains of B. cereus, B. coagulans, B. subtilis, B. megaterium, B. polymyxa, B. pumilus and B. thuringiensis. Absorption of the anti-anthrax conjugates with B. cereus NCTC 8035 and NCTC 10320 removed all these cross-reactions, demonstrating the existence of spore antigens specific for anthrax.
Convenient synthesis of bifunctional tetraaza macrocycles (1992)

A convenient synthesis of 4-nitrobenzyl-substituted macrocyclic tetraamines and their conversion to bifunctional poly(amino carboxylate) chelating agents is described. Cyclization of (4-nitrobenzyl)-ethylenediamine with appropriate BOC-protected amino disuccinimido esters in dioxane at 90 degrees C resulted in the formation of 12- and 14-membered ring diamides in 40% and 44% yield, respectively. A 12-membered macrocyclic triamide was also prepared in 44% yield by cyclization of N-(2-aminoethyl)-4-nitrophenylalaninamide with disuccinimidyl N-(tert-butoxycarbonyl)iminodiacetate. Deprotection (HCl/dioxane) and reduction with borane gave the substituted macrocyclic amines which were then alkylated with either bromoacetic acid or tert-butyl bromoacetate. Preparation of the isothiocyanate derivatives and 14C labeled chelating agents are described. Attempts to prepare a 9-membered macrocyclic diamide using this cyclization technique resulted instead in a 20% yield of a 10:1 mixture of isomeric fused 5,6 ring acylamidines. Deprotection (HCl/dioxane) and reduction with borane gave a substituted piperazine derivative in 55% yield.
The Challenges of RSV Vaccines. Where do we Stand? (2010)

The most realistic way to control RSV infection would be the development of an effective and safe vaccine. A formalin-inactivated RSV vaccine was evaluated in infants and children in the 1960's which disappointingly was linked with aggravation of RSV disease following the natural infection. Two candidate vaccines with purified protein F, have been tested, in humans and have been considered safe and somewhat immunogenic in seropositive persons providing different levels of protection against RSV re-infection. Live attenuated RSV vaccines induce local and systemic immunity without producing enhanced disease upon exposure of the vaccinee to the wild virus. Plasmid DNA vaccines were also evaluated in mice and elicited balanced systemic and pulmonary Th1/Th2 response without inducing an atypical pulmonary inflammatory reaction following the RSV challenge in cotton rats. Gene gun vaccination, a method to overcome the problem of DNA quantity, has been associated with a Th-2 biased response. Recent patents, such as plant vaccines, combined vaccines, attempted to invent new techniques for the generation of safe and effective vaccines. The new RSV vaccines should overcome many obstacles before being established as effective vaccines for the control of RSV infections especially for the young infants who are more susceptible to the virus.
Sex hormone‐binding globulin, androgen‐binding protein, and vitamin K‐dependent protein S are homologous to laminin A, merosin, and Drosophila crumbs protein (1992)

Androgen-binding protein (ABP) and sex hormone-binding globulin (SHBG) are extracellular steroid-binding proteins that are homologous to the COOH-terminal domain of vitamin K-dependent protein S, a protein important in blood clotting. We find that the sequences of ABP, SHBG, and protein S are also similar to two basement membrane proteins, laminin and merosin, and to an integral membrane protein, Drosophila crumbs protein. These latter three proteins have important roles in regulating differentiation and development. The sequence similarity corresponds to the G domain of laminin A chain, which binds heparin and type IV collagen. Analysis of a multiple alignment of these proteins reveals one well-conserved segment corresponding to the part of SHBG that binds to its membrane receptor and another corresponding to the part of protein S that binds to C4b-binding protein. The similarities suggest that ABP, SHBG, and protein S may also have functions related to that of laminin and merosin.
Beckwith-Wiedemann Syndrome-associated Hepatoblastoma: Wnt Signal Activation Occurs Later in Tumorigenesis in Patients with 11p15.5 Uniparental Disomy (2003)

Beckwith-Wiedemann syndrome (BWS) patients with chromosome 11p15.5 uniparental isodisomy (UPD) have an increased risk for developing embryonal tumors. UPD in these patients involves maternal loss of heterozygosity (LOH) and paternal duplication, which leads to tissue overgrowth and tumor development. Although 11p15.5 UPD predisposes to tumorigenesis, the events leading to tumorigenesis in UPD patients remains unknown. We have examined two hepatoblastomas in the BWS patients with UPD to determine the sequence of genetic events. Constitutional 11p15.5 LOH was detected in the blood or nonneoplastic liver of the BWS patients with hepatoblastoma. Mutation of beta-catenin gene (CTNNB1) was found in one hepatoblastoma. Although mutations in CTNNB1 were not found in the second hepatoblastoma, nuclear accumulation of beta-catenin was detected. However, mutation of CTNNB1 or nuclear accumulation of beta-catenin was not detected in the tissue with hepatomegaly which contains UPD cells. These data indicate that Wnt signal activation can be involved as a later event in BWS-associated hepatoblastoma involving 11p15.5 UPD.
High Capacity, Temperature-Stable Lithium Aluminum Manganese Oxide Cathodes for Rechargeable Batteries (1999)

Manganese oxides are of great interest as low cost and environmentally sound intercalation cathodes for rechargeable lithium batteries, but have suffered from limited capacity and instability upon cycling at the moderately high temperatures encountered in many applications. Here, we show that of both the monoclinic and orthorhombic ordered rock salt structures exhibit stable cycling and high discharge capacities at elevated temperatures, after an initial transient associated with a spinel like phase transformation. In cells utilizing anodes tested at , rechargeable capacities of for the orthorhombic and for the mono‐ clinic phase and energy densities were achieved over more than 100 cycles . At low current densities, charge capacities approached the theoretical limit. The temperature stability and excellent electrochemical performance, combined with nontoxicity and low raw materials cost, make these compounds attractive cathodes for advanced lithium batteries. ©1999 The Electrochemical Society
Implantable Electrocatalytic Glucose Sensor (1994)

An electrocatalytic glucose sensor for in vivo application has been developed to determine the glucose level in blood and further to control the insulin dosage in a closed loop system for diabetes therapy. The principle of the electrocatalytic glucose sensor is based on the direct electrochemical oxidation of glucose at a membrane-covered platinum electrode. For a possible clinical application the sensor was built as a catheter. A set of implantations in the vena cava of sheep demonstrated the potential feasibility of the sensor. The sensor values were simultaneously checked by the enzymatic analysis of glucose in blood samples drawn separately from a femoral vein. It was possible to determine the glucose concentration in sheep for more than 130 days with tolerable deviations from glucose reference measurements. The mean error was 2.5 mmol/l. One of the catheters was explanted after 211 days and the histological examination revealed a good biocompatibility of all materials used. In additional experiments, the differences of the glucose concentration in vena cava as well as in the anterior and posterior femoral veins of a sheep were examined during glucose tolerance tests. These experiments verified our method of in vivo calibration of the long-term implantable glucose sensor.
Preparation of single-stranded PCR products for electrospray ionization mass spectrometry using the DNA repair enzyme lambda exonuclease (2000)

Electrospray ionization mass spectrometry (ESI-MS) has been utilized to obtain accurate mass measurements of intact PCR products; however, single-stranded PCR products are necessary to detect sequence modifications such as base substitutions, additions or deletions. The locations of these modifications can subsequently be determined using additional stages of mass spectrometry. The recombinant enzyme lambda exonuclease selectively digests one strand of a DNA duplex from a 5' phosphorylated end leaving the complementary strand intact. Using this rapid enzymatic step, we were able to produce single-stranded PCR products by digestion of an intact PCR product derived from the Human Tyrosine Hydroxylase (HUMTHO1) gene, which contains a tetrameric repeating motif. The non-template directed 3' adenylation common when using Taq polymerase resulted in three distinct species (blunt-ended, mono-adenylated and di-adenylated), which added complexity to the spectrum of the double-stranded product. The data from the single-stranded products shows that one strand is preferentially adenylated over the other, which cannot be determined from the mass spectrum of the double-stranded PCR product alone. The ESI-FTICR (Fourier transform ion cyclotron resonance) mass spectra of the lambda exonuclease treated PCR products exhibited less than expected signal-to-noise (S/N) ratios. This is attributed to inaccurate concentration calculations due to remaining double-stranded PCR product amplified with unphosphorylated primers, and to matrix effects contributed by the lambda exonuclease reaction buffer. To further test this hypothesis, we investigated and determined the limit of detection to be 0.27 microM using standard curve statistics for single acquisitions of a synthetic 75-mer. The concentrations of the noncoding and coding strands produced by lambda exonuclease digestion were calculated to be 0.29 and 0.37 microM, respectively, taking into account the presence of double-stranded product. The products were electrosprayed from concentrations at the limit of detection requiring the averaging of 5-10 acquisitions to produce a sufficient S/N ratio, indicating that product concentration, base composition and matrix effects play a combined, significant role in detection of lambda exonuclease treated PCR products. Although additional work will be required to further exploit this strategy, lambda exonuclease clearly provides mass spectrometrists with a method to generate single-stranded PCR products.
Genes encoding actin in higher plants: intron positions are highly conserved but the coding sequences are not. (1983)

We have isolated actin genes from genomic libraries of two highly diverged plants, maize and soybean. The complete nucleotide sequences of a maize actin gene, MAc1, and a soybean actin gene, SAc1, were determined. The nucleotide sequences of these two actin genes and of a previously sequenced soybean actin gene were compared with the actin gene sequences from a wide spectrum of evolutionarily diverged eukaryotes. Some striking features pertinent to the evolution and function of the plant actin gene families have emerged. The deduced amino acid sequence of the plant actins resembles both cytoplasmic- and muscle-specific actins. DNA sequence analysis as well as genomic blotting experiments using cloned actin sequences as probes show that large sequence heterogeneity exists among members of the plant actin multigene families and between genes from two highly diverged plant species. The sequences of the first nine amino acids at the amino terminal end of the plant actins are far more conserved between distant plant actins than the corresponding sequences in distantly related animal actin genes, suggesting a unique and conserved function for the NH2 terminal sequence in higher plants. The soybean and maize actin genes examined each contain three introns in precisely the same positions, quite contrary to the divergent placement of introns observed in animal, protozoan, and fungal actins. The position of the first intron in soybean and maize actin genes corresponds precisely to the position of an intron found in a nematode actin gene. The position of the second intron coincides with one found in rat and chicken skeletal actin genes. These data suggest that the numerous introns found in all actins are of ancient origin. The degree of silent substitution and replacement substitution was compared among plant actin genes and to those of animal, protozoan, and yeast actin genes. It is clear that the silent substitution sites are saturated among all the genes compared, whereas the replacement sites have diverged in only 5-17% of their possible positions. By these criteria the most distant animal actins are only 6% diverged. The three plant actin genes examined are 8-10% diverged in replacement sites from each other and approximately 14% diverged in replacement sites from any of the animal actins examined. The data in this manuscript suggest that the families of soybean and maize actin genes may have diverged from a single common ancestral actin gene long before the divergence of monocots and dicots.
The Role of CD4+ T Cell Help and CD40 Ligand in the In Vitro Expansion of HIV-1-Specific Memory Cytotoxic CD8+ T Cell Responses (2000)

CD4(+) T cells have been shown to play a critical role in the maintenance of an effective anti-viral CD8(+) CTL response in murine models. Recent studies have demonstrated that CD4(+) T cells provide help to CTLs through ligation of the CD40 receptor on dendritic cells. The role of CD4(+) T cell help in the expansion of virus-specific CD8(+) memory T cell responses was examined in normal volunteers recently vaccinated to influenza and in HIV-1 infected individuals. In recently vaccinated normal volunteers, CD4(+) T cell help was required for optimal in vitro expansion of influenza-specific CTL responses. Also, CD40 ligand trimer (CD40LT) enhanced CTL responses and was able to completely substitute for CD4(+) T cell help in PBMCs from normal volunteers. In HIV-1 infection, CD4(+) T cell help was required for optimal expansion of HIV-1-specific memory CTL in vitro in 9 of 10 patients. CD40LT could enhance CTL in the absence of CD4(+) T cell help in the majority of patients; however, the degree of enhancement of CTL responses was variable such that, in some patients, CD40LT could not completely substitute for CD4(+) T cell help. In those HIV-1-infected patients who demonstrated poor responses to CD40LT, a dysfunction in circulating CD8(+) memory T cells was demonstrated, which was reversed by the addition of cytokines including IL-2. Finally, it was demonstrated that IL-15 produced by CD40LT-stimulated dendritic cells may be an additional mechanism by which CD40LT induces the expansion of memory CTL in CD4(+) T cell-depleted conditions, where IL-2 is lacking.
Fast track assembly of multigene constructs using Golden Gate cloning and the MoClo system (2012)

Recent progress in the field of synthetic biology has led to the creation of cells containing synthetic genomes. Although these first synthetic organisms contained copies of natural genomes, future work will be directed toward engineering of organisms with modified genomes and novel phenotypes. Much work, however, remains to be done to be able to routinely engineer novel biological functions. As a tool that will be useful for such purpose, we have recently developed a modular cloning system (MoClo) that allows high throughput assembly of multiple genetic elements. We present here new features of this cloning system that allow to increase the speed of assembly of multigene constructs. As an example, 68 DNA fragments encoding basic genetic elements were assembled using three one-pot cloning steps, resulting in a 50 kb construct containing 17 eukaryotic transcription units. This cloning system should be useful for generating the multiple construct variants that will be required for developing gene networks encoding novel functions, and fine-tuning the expression levels of the various genes involved.
Phosphorylation-dependent Inhibition of Protein Phosphatase-1 by G-substrate (1999)

G-substrate, a specific substrate of the cGMP-dependent protein kinase, has previously been localized to the Purkinje cells of the cerebellum. We report here the isolation from mouse brain of a cDNA encoding G-substrate. This cDNA was used to localize G-substrate mRNA expression, as well as to produce recombinant protein for the characterization of G-substrate phosphatase inhibitory activity. Brain and eye were the only tissues in which a G-substrate transcript was detected. Within the brain, G-substrate transcripts were restricted almost entirely to the Purkinje cells of the cerebellum, although transcripts were also detected at low levels in the paraventricular region of the hypothalamus and the pons/medulla. Like the native protein, the recombinant protein was preferentially phosphorylated by cGMP-dependent protein kinase (Km = 0.2 microM) over cAMP-dependent protein kinase (Km = 2.0 microM). Phospho-G-substrate inhibited the catalytic subunit of native protein phosphatase-1 with an IC50 of 131 +/- 27 nM. Dephospho-G-substrate was not found to be inhibitory. Both dephospho- and phospho-G-substrate were weak inhibitors of native protein phosphatase-2A1, which dephosphorylated G-substrate 20 times faster than the catalytic subunit of protein phosphatase-1. G-substrate potentiated the action of cAMP-dependent protein kinase on a cAMP-regulated luciferase reporter construct, consistent with an inhibition of cellular phosphatases in vivo. These results provide the first demonstration that G-substrate inhibits protein phosphatase-1 and suggest a novel mechanism by which cGMP-dependent protein kinase I can regulate the activity of the type 1 protein phosphatases.
Photodissociation and vibrational relaxation of I2− in ethanol (1993)

The dissociation, internal conversion, and vibrational relaxation of photoexcited I2− in ethanol have been examined using ultrafast transient-absorption spectroscopy. I2− was photoexcited at 770 nm (1.6 eV) and probed on the subpicosecond time scale at 15 wavelengths between 580 and 950 nm, permitting a determination of the temporal evolution of the absorption spectrum. The data reveal that internal conversion and vibrational relaxation at the top of the well are extremely rapid (≤0.3 ps), with loss of the final 0.3 eV of energy (v≤20) occurring on a time scale of ∼4 ps. Simple kinetic and spectral models are able to qualitatively account for the observed behavior of the transient-absorption signals.
Determination of cobalt, copper, mercury, and nickel as bis(2-hydroxyethyl)dithiocarbamate complexes by high-performance liquid chromatography (1987)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTDetermination of cobalt, copper, mercury, and nickel as bis(2-hydroxyethyl)dithiocarbamate complexes by high-performance liquid chromatographyJeffrey N. King and James S. FritzCite this: Anal. Chem. 1987, 59, 5, 703–708Publication Date (Print):March 1, 1987Publication History Published online1 May 2002Published inissue 1 March 1987https://pubs.acs.org/doi/10.1021/ac00132a005https://doi.org/10.1021/ac00132a005research-articleACS PublicationsRequest reuse permissionsArticle Views322Altmetric-Citations51LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-Alertsclose Get e-Alerts
A design tradeoff study with monolithic 3D integration (2012)

This paper studies various design tradeoffs existing in the monolithic 3D integration technology. Different design styles in monolithic 3D ICs are studied, including transistor-level monolithic integration (MI-TR) and gate-level integration (MI-G). GDSII-level layout of monolithic 3D designs are constructed and analyzed. Compared with its 2D counterparts, MI-TR designs have advantages in footprint area, wire-length, timing, and power, because of the smaller footprint. MI-G design style also demonstrate advantages in area, timing and power over TSV-based designs, because of the smaller size and parasitics of inter-tier vias compared with TSVs. To further take the advantage of monolithic 3D technology, several technology improvement options are also explored. Besides, some possible design challenges with monolithic 3D are also studied, including global variation and signal integrity issues.
Software process modeling and evolution in EPOS (2003)

Software process models are meant to describe software engineering activities around evolving software products. Process models need modifications due to gained experience, changed policies or project-specific requirements, and a set of versions of the original models must be maintained. Thus, software process models are evolving products and should be under the control of a configuration management (CM) system. EPOS models software processes in an object-oriented data model. Both process models and running instances are stored in a versioned database. EPOS software process models may be evolved and reused by the same CM techniques as used for software systems.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>