gebhart/patrepeval huggingface dataset:
Granulosa Cell Aromatase Bioassay for Follicle-Stimulating Hormone: Validation and Application of the Method* (1986)

Stimulation of rat granulosa cell aromatase activity by FSH has recently been used as a sensitive biological end point to develop an in vitro FSH bioassay. The present report provides a detailed validation and application of this assay. In the presence of androstenedione and diethylstilbestrol, FSH stimulated estrogen production in a dose-dependent manner. Although addition of high doses of a phosphodiesterase inhibitor [1-methyl-3-isobutyl xanthine (MIX)] decreased maximal estrogen production, treatment with 0.125 mM MIX increased the sensitivity of granulosa cells to FSH, presumably by minimizing endogenous cAMP breakdown. Addition of insulin and human CG (hCG) further synergistically enhanced granulosa cell sensitivity to FSH. Although inclusion of gonadotropin-free serum obtained from hypophysectomized male rats decreased the assay sensitivity, pretreatment of serum with polyethylene glycol [(PEG) 10-14%] resulted in a dose-dependent decrease in the serum-interfering effect. Studies using exogenous [125I]iodo-rat FSH or RIA measurement indicated recovery of 94-98% FSH after pretreatment of serum with 12% PEG. In the presence of the PEG-pretreated gonadotropin-free serum (4%), ovine, rat, and human FSH preparations induced parallel dose-response curves for estrogen production with minimal detectable doses of 0.12 ng, 0.12 ng, and 0.12 mIU/culture, respectively. In contrast, treatment with GH, PRL, TSH, and ACTH did not affect estrogen production. The apparent stimulatory effect of high doses (greater than 60 ng/culture) of LH and hCG could be attributed to FSH contamination or intrinsic FSH activity in these preparations. Changes in serum bioactive FSH levels were studied in adult male rats after GnRH administration. GnRH (5 micrograms/rat) treatment significantly elevated FSH levels within 30 min after injection. Maximal increases (approximately 2.8-fold) in serum bioactive FSH were observed between 60-120 min. At 8 h after treatment, FSH levels decreased to control levels. Comparison between granulosa cell aromatase bioassay and RIA results indicated no apparent changes in the bio- to immuno- ratio of FSH after GnRH treatment. In conclusion, extreme sensitivity of the bioassay allows the measurement of circulating levels of bioactive FSH. Since rat granulosa cells respond to FSH preparations from different species, the in vitro assay should also provide valuable information on FSH levels in many animal species including those lacking a specific RIA. Measurement of serum levels of bioactive FSH should provide insight regarding the role of FSH in various physiological and pathological conditions.
Synthesis of 2,4‐diamino‐9H‐indeno[2,1‐d]pyrimidines (1969)

Abstract As part of a search for new antifolic, antimalarial, and antitumor agents, a series of 2,4‐diamino‐9 H ‐indeno[2,1‐ d ]pyrimidines was prepared by condensation of guanidine with substituted 2‐alkoxy‐3‐cyano‐1 H ‐indenes. Base‐catalyzed cyclization of 1,2‐bis(cyanomethyl)benzenes afforded 2‐amino‐3‐cyano‐1 H ‐indenes, which were converted into 3‐cyano‐2‐methoxy‐1 H ‐indenes by acid hydrolysis and treatment of the resultant 1‐cyano‐2‐indanones with diazomethane. Alternatively, 2‐amino‐3‐cyano‐1 H ‐indenes could be transformed directly into 2‐ethoxy‐3‐eyano‐1 H ‐indenes by reaction with ethanol and sulfuric acid. The 2,4‐diamino‐9 H ‐indeno[2,1‐d]‐pyrimidines represent a new type of planar, tricyclic pyrimethamine analog, in which free rotation of the phenyl and pyrimidine rings is prevented by means of a methylene bridge.
Sequence Selective Hydrolysis of Linear DNA Using Conjugates of Zr(IV) Complexes and Peptide Nucleic Acids (2003)

A series of conjugates of peptide nucleic acids (PNA) and Zr(IV) complexes was prepared. Their ability to hydrolyze DNA was tested using MALDI-TOF mass spectrometry and HPLC. The most efficient artificial restriction enzyme found, PNA conjugate with Zr(IV) complex of tris(hydroxymethyl)-aminomethane, cleaves DNA targets sequence selectively in close proximity to the Zr(IV) complex. It was demonstrated that cleavage products are substrates of terminal transferase.
Attenuation regulation of amino acid biosynthetic operons in proteobacteria: comparative genomics analysis (2004)

Candidate attenuators were identified that regulate operons responsible for biosynthesis of branched amino acids, histidine, threonine, tryptophan, and phenylalanine in gamma- and alpha-proteobacteria, and in some cases in low-GC Gram-positive bacteria, Thermotogales and Bacteroidetes/Chlorobi. This allowed us not only to describe the evolutionary dynamics of regulation by attenuation of transcription, but also to annotate a number of hypothetical genes. In particular, orthologs of ygeA of Escherichia coli were assigned the branched chain amino acid racemase function. Three new families of histidine transporters were predicted, orthologs of yuiF and yvsH of Bacillus subtilis, and lysQ of Lactococcus lactis. In Pasteurellales, the single bifunctional aspartate kinase/homoserine dehydrogenase gene thrA was predicted to be regulated not only by threonine and isoleucine, as in E. coli, but also by methionine. In alpha-proteobacteria, the single acetolactate synthase operon ilvIH was predicted to be regulated by branched amino acids-dependent attenuators. Histidine biosynthetic operons his were predicted to be regulated by histidine-dependent attenuators in Bacillus cereus and Clostridium difficile, and by histidine T-boxes in L. lactis and Streptococcus mutans.
Prolonged Maturation and Enhanced Transduction of Dendritic Cells Migrated from Human Skin Explants After In Situ Delivery of CD40-Targeted Adenoviral Vectors (2002)

Therapeutic tumor vaccination with viral vectors or naked DNA, carrying the genetic code for tumor-associated Ags, critically depends on the in vivo transduction of dendritic cells (DC). Transfection of predominantly nonprofessional APC and only small numbers of DC may hamper proper T cell activation. Aim of this study was, therefore, the targeted, selective, and enhanced in situ transduction of DC. A human skin explant model was used to explore targeted transduction of cutaneous DC after intradermal injection of a bispecific Ab conjugate to link adenoviral (Ad) vectors directly to CD40 on the DC surface. A significantly enhanced transduction efficiency and selectivity, and an increased activation state of migrating DC were thus achieved. Moreover, DC transduced by CD40-targeted Ad maintained their Ag-specific CTL-stimulatory ability for up to 1 wk after the start of migration, in contrast to DC transduced by untargeted Ad, which had lost this capacity by that time. Because DC targeting in vivo might obviate the need for the in vitro culture of autologous DC for adoptive transfer, CD40-targeted Ad vectors constitute a promising new vaccine modality for tumor immunotherapy.
Linear diversity combining techniques (2003)

This paper provides analyses of three types of diversity combining systems in practical use. These are: selection diversity, maximal-ratio diversity, and equal-gain diversity systems. Quantitative measures of the relative performance (under realistic conditions) of the three systems are provided. The effects of various departures from ideal conditions, such as non-Rayleigh fading and partially coherent signal or noise voltages, are considered. Some discussion is also included of the relative merits of predetection and postdetection combining and of the problems in determining and using long-term distributions. The principal results are given in graphs and tables, useful in system design. It is seen that the simplest possible combiner, the equal-gain system, will generally yield performance essentially equivalent to the maximum obtainable from any quasilinear system. The principal application of the results is to diversity communication systems and the discussion is set in that context, but many of the results are also applicable to certain radar and navigation systems.
Diode Laser Arrays (1994)

This book provides a comprehensive overview of the fundamental principles and applications of semiconductor diode laser arrays. All of the major types of arrays are discussed in detail, including coherent, incoherent, edge- and surface-emitting, horizontal- and vertical-cavity, individually addressed, lattice-matched and strained-layer systems. The initial chapters cover such topics as lasers, amplifiers, external-cavity control, theoretical modelling, and operational dynamics. Spatially incoherent arrays are then described in detail, and the uses of vertical-cavity surface emitter and edge-emitting arrays in parallel optical-signal processing and multi-channel optical recording are discussed. Engineers, established researchers and graduate students studying the properties and applications of such arrays will find this book invaluable.
Single‐channel activations and concentration jumps: comparison of recombinant NR1a/NR2A and NR1a/NR2D NMDA receptors (1998)

1. We have expressed recombinant NR1a/NR2A and NR1a/NR2D N-methyl-D-aspartate (NMDA) receptor channels in Xenopus oocytes and made recordings of single-channel and macroscopic currents in outside-out membrane patches. For each receptor type we measured (a) the individual single-channel activations evoked by low glutamate concentrations in steady-state recordings, and (b) the macroscopic responses elicited by brief concentration jumps with high agonist concentrations, and we explore the relationship between these two sorts of observation. 2. Low concentration (5-100 nM) steady-state recordings of NR1a/NR2A and NR1a/NR2D single-channel activity generated shut-time distributions that were best fitted with a mixture of five and six exponential components, respectively. Individual activations of either receptor type were resolved as bursts of openings, which we refer to as 'super-clusters'. 3. During a single activation, NR1a/NR2A receptors were open for 36 % of the time, but NR1a/NR2D receptors were open for only 4 % of the time. For both, distributions of super-cluster durations were best fitted with a mixture of six exponential components. Their overall mean durations were 35.8 and 1602 ms, respectively. 4. Steady-state super-clusters were aligned on their first openings and averaged. The average was well fitted by a sum of exponentials with time constants taken from fits to super-cluster length distributions. It is shown that this is what would be expected for a channel that shows simple Markovian behaviour. 5. The current through NR1a/NR2A channels following a concentration jump from zero to 1 mM glutamate for 1 ms was well fitted by three exponential components with time constants of 13 ms (rising phase), 70 ms and 350 ms (decaying phase). Similar concentration jumps on NR1a/NR2D channels were well fitted by two exponentials with means of 45 ms (rising phase) and 4408 ms (decaying phase) components. During prolonged exposure to glutamate, NR1a/NR2A channels desensitized with a time constant of 649 ms, while NR1a/NR2D channels exhibited no apparent desensitization. 6. We show that under certain conditions, the time constants for the macroscopic jump response should be the same as those for the distribution of super-cluster lengths, though the resolution of the latter is so much greater that it cannot be expected that all the components will be resolvable in a macroscopic current. Good agreement was found for jumps on NR1a/NR2D receptors, and for some jump experiments on NR1a/NR2A. However, the latter were rather variable and some were slower than predicted. Slow decays were associated with patches that had large currents.
Large Models for Virtual Environments: A Review of Work by the Architectural Walkthrough Project at UNC (1996)

Oth law of model dynamics: In a finite (and usually very short) amount of time, users of a graphics system will generate a model that shall bring said system to its knees. The purpose of this paper is to discuss our experiences with the impact of megamodels on interactive virtual environments. We consider a megamodel to be any model that causes the Oth law of model dynamics to come into effect. We will demonstrate how working with megamodels quickly reveals the limitations of the graphics hardware and software being used to support the virtual environment. We will give examples, based upon our experiences on the Architectural Walkthrough Project here at the University of North Carolina at Chapel Hill (UNC), of the kinds of extra effort required to overcome these limitations.
HIV-1 subtype C viruses rapidly develop K65R resistance to tenofovir in cell culture (2006)

Tenofovir -based regimens will need to be carefully monitored in subtype C infections for the possible selection of K65R.
Mannose-Binding Lectin Binds to a Range of Clinically Relevant Microorganisms and Promotes Complement Deposition (2000)

Mannose-binding lectin (MBL) is a collagenous serum lectin believed to be of importance in innate immunity. Genetically determined low levels of the protein are known to predispose to infections. In this study the binding of purified MBL to pathogens isolated from immunocompromised children was investigated by flow cytometry. Diverse Candida species, Aspergillus fumigatus, Staphylococcus aureus, and beta-hemolytic group A streptococci exhibited strong binding of MBL, whereas Escherichia coli, Klebsiella species, and Haemophilus influenzae type b were characterized by heterogeneous binding patterns. In contrast, beta-hemolytic group B streptococci, Streptococcus pneumoniae, and Staphylococcus epidermidis showed low levels of binding. Bound MBL was able to promote C4 deposition in a concentration-dependent manner. We conclude that MBL may be of importance in first-line immune defense against several important pathogens.
Independent Component Analysis of Event-Related Potentials (2008)

Independent component analysis (ICA) is a potentially powerful tool for analyzing eventrelated potentials (ERPs), one of the most popular measures of brain function in cognitive neuroscience. Based on the statistics of the electroencephalogram (EEG), from which ERPs are derived, ICA may be able to extract multiple, functionally distinct sources of an ERP generated by disparate regions of cerebral cortex. Extracting such sources greatly increases the informativeness of ERPs by providing a cleaner, less ambiguous measure of source activity and by facilitating the identification of this activity across different experimental paradigms. The main purpose of this review article is to explain the logic of ICA, to illustrate how ICA could in principle extract spatiotemporally overlapping ERP sources, and to review evidence that ICA is a well motivated methodology that can extract latent ERP sources in practice. In addition, we close the article by noting potential problems with ICA and by comparing it to three alternative methods for extracting ERP sources/components: spatial principal component analysis, source localization, and temporal principal component analysis.
Improvement of Cardiac Functions by Chronic Metformin Treatment Is Associated With Enhanced Cardiac Autophagy in Diabetic OVE26 Mice (2011)

Decreased AMPK activity and subsequent reduction in cardiac autophagy are important events in the development of diabetic cardiomyopathy. Chronic AMPK activation by metformin prevents cardiomyopathy by upregulating autophagy activity in diabetic OVE26 mice. Thus, stimulation of AMPK may represent a novel approach to treat diabetic cardiomyopathy.
Parallel evolution of transcriptome architecture during genome reorganization (2011)

Assembly of genes into operons is generally viewed as an important process during the continual adaptation of microbes to changing environmental challenges. However, the genome reorganization events that drive this process are also the roots of instability for existing operons. We have determined that there exists a statistically significant trend that correlates the proportion of genes encoded in operons in archaea to their phylogenetic lineage. We have further characterized how microbes deal with operon instability by mapping and comparing transcriptome architectures of four phylogenetically diverse extremophiles that span the range of operon stabilities observed across archaeal lineages: a photoheterotrophic halophile (Halobacterium salinarum NRC-1), a hydrogenotrophic methanogen (Methanococcus maripaludis S2), an acidophilic and aerobic thermophile (Sulfolobus solfataricus P2), and an anaerobic hyperthermophile (Pyrococcus furiosus DSM 3638). We demonstrate how the evolution of transcriptional elements (promoters and terminators) generates new operons, restores the coordinated regulation of translocated, inverted, and newly acquired genes, and introduces completely novel regulation for even some of the most conserved operonic genes such as those encoding subunits of the ribosome. The inverse correlation (r=-0.92) between the proportion of operons with such internally located transcriptional elements and the fraction of conserved operons in each of the four archaea reveals an unprecedented view into varying stages of operon evolution. Importantly, our integrated analysis has revealed that organisms adapted to higher growth temperatures have lower tolerance for genome reorganization events that disrupt operon structures.
Production of human c-myc protein in insect cells infected with a baculovirus expression vector. (1985)

A cDNA fragment coding for human c-myc was inserted into the genome of the baculovirus Autographa californica nuclear polyhedrosis virus adjacent to the strong polyhedrin promoter. Insect cells infected with the recombinant virus produced significant amounts of c-myc protein, which constituted the major phosphoprotein component in these cells. By immunoprecipitation and immunoblot analysis, two proteins of 61 and 64 kilodaltons were detected with c-myc-specific antisera. The insect-derived proteins were compared with recombinant human c-myc-encoded proteins synthesized in Escherichia coli and Saccharomyces cerevisiae cells. The c-myc gene product was found predominantly in the nucleus by subcellular fractionation of infected insect cells.
Single-shot measurement of the amplitude and phase of ultrashort laser pulses in the violet (1995)

Using single-shot, self-diffraction, frequency-resolved optical gating, we measure the complete electric field amplitude and phase of 405-nm second-harmonic pulses from an amplified Ti:sapphire system. The single-shot frequency-resolved optical gating device gives both qualitative and quantitative information, which is useful for analyzing and optimizing the grating compressor in the chirped-pulse amplification system.
Factors Affecting B-Cell Growth and Differentiation (1985)

Since the discovery of T-B interactions in the antibody response, the mechanism of the regulatory functions of T cells in the B-cell response has been studied extensively in immunology. The possibility that helper functions of T cells may be mediated by soluble products released from T cells was originally proposed by Dutton and his colleagues in 1971 (1). In their experiment with murine splenic B cells, they showed that anti-SRBC (sheep red blood cell) response in T cell-depleted splenic lymphocytes could be reconstituted by culture supernatants of mixed lymphocyte reactions. This was confirmed by Schimpl & Wecker (2) and several other investi­ gators (3-5) who showed the active soluble factor(s) in culture supernatants of mitogens or antigen-stimulated T cells. Schimpl & Wecker demonstrated that cell-free supernatants from alloantigen-stimulated or concanavalin A (Con A}-stimulated T cells could fully substitute for T cells in the response in vitro to unrelated antigens such as SRBC. They postulated that T cells stimulated by their specific antigen released a substance, T cell-replacing factor (TRF), which was able to stimulate B cells to proliferate and/or differentiate only when B cells carried antigens on their receptors. Essentially the same result was reported by Kishimoto & Ishizaka with rabbit B cells (3). They demonstrated that anti-DNP (dinitrophenyl) antibody response could be induced in DNP-primed B cells by the stimulation with DNP-heterologous carrier conjugate and a cell-free supernatant from carrier-primed T cells stimulated with the primed carrier antigen. In a series of experiments, they also demonstrated that the factor(s)
Synergic antistaphylococcal properties of lactoferrin and lysozyme (1998)

Staphylococcus epidermidis colonises a wide range of implanted prosthetic devices, but rarely contact lenses -- despite a similarity in material composition. A conceivable explanation for this anomaly is the action of the tear defences, including the constitutive proteins lactoferrin and lysozyme. Therefore this study investigated the effect of lactoferrin, lysozyme and serum on the growth of S. epidermidis isolates in artificial tear fluid. Whether supplemented with serum alone or serum with either apolactoferrin or lysozyme, this medium induced a similar, strain-variable effect. However, simultaneous addition of these proteins induced a greater bactericidal or bacteristatic effect. Of those strains killed by the concerted action of apolactoferrin and lysozyme, the absence of serum led to a further increase in the bactericidal effect, whereas strains displaying bacteriostasis were unaffected by serum. Iron saturation of lactoferrin reversed the antimicrobial synergy of apolactoferrin and lysozyme. These results show synergy between lactoferrin and lysozyme which is dependent on the iron limitation of lactoferrin. As a bactericidal mechanism, this synergy is augmented by serum, but bacteriostasis remains unaffected by serum supplemention. Thus, the combination of lysozyme and lactoferrin may partly explain the low level of contact lens colonisation by S. epidermidis in vivo.
Regiochemically Flexible Substitutions of Di-, Tri-, and Tetrahalopyridines:  The Trialkylsilyl Trick (2005)

[reactions: see text] 2,4-Difluoropyridine, 2,4-dichloropyridine, 2,4,6-trifluoropyridine, 2,4,6-trichloropyridine and 2,3,4,6-tetrafluoropyridine react with standard nucleophiles exclusively at the 4-position under halogen displacement. However, the regioselectivity can be completely reversed if a trialkylsilyl group is introduced in the 5-position of the 2,4-dihalopyridines or in the 3-position of the 2,4,6-trihalopyridines or 2,3,4,6-tetrahalopyridine. Then only the halogen most remote from the bulky silyl unit (at the 2-position in the case of the 2,4-halopyridines, at the 6-position with the other substrates) gets involved in the exchange process. After removal of the silyl protective group the nucleophile is invariably found to occupy the nitrogen-neighboring position.