gebhart/patrepeval huggingface dataset:
Dietary Fat Modulates the Testosterone Pharmacokinetics of a New Self‐Emulsifying Formulation of Oral Testosterone Undecanoate in Hypogonadal Men (2012)

This study investigates the effect of dietary fat on the testosterone (T) pharmacokinetics in hypogonadal men following administration of a self-emulsifying capsule formulation of oral T undecanoate (TU). In an open-label, 2-center, 5-way crossover study, a single oral dose of TU containing 300-mg equivalents of T (maximum anticipated human dose per administration) was administered to 16 hypogonadal men with a washout period of at least 5 days between doses. All participants were randomized to receive the TU capsules fasting or 30 minutes after an approximately 800-calorie meal containing 10%, 20%, 30%, or 50% fat. Serial blood samples were collected from 2 hours predose to 25 hours postdose to determine serum T and dihydrotestosterone (DHT) by liquid chromatography tandem mass spectrometry. Administering TU with a meal increased serum T concentrations, with the magnitude of the increase being directly dependent on the amount of fat in the meal. Average and peak serum T concentrations and area under the curve increased as the fat content of the meal was increased. Neither the high-fat meal (50% fat) nor the lower-fat meal (20% fat) showed a significant food effect relative to the normal-fat (Western diet) meal (30% fat). However, administering TU while fasting resulted in 50% or less of the cumulative exposure obtained when administered with 20%- to 50%-fat meals (albeit still substantial). A very-low-fat meal (10% fat) showed a significant food effect relative to the normal meal, but still exceeded the fasting condition by approximately 50%. Serum DHT concentrations showed corresponding increases to the serum T. As expected with the maximum anticipated clinical dose of TU (300 mg T), oral administration of this new formulation with food containing 20% to 50% dietary fat produced T levels at or above the upper range of adult men, and T levels trended higher as dietary fat content increased. Only with a very-low-fat diet (10%) or in a fasted state did a clinically significant food effect occur, but even then sufficient TU was absorbed with the self-emulsifying TU formulation to produce average serum T concentration predicted to be in the normal reference range (10 to 35 nmol/L).
InGaN-based violet laser diodes (1999)

High-efficiency light-emitting diodes emitting amber, green, blue and ultraviolet light have been obtained through the use of InGaN active layers instead of GaN active layers. The localized energy states caused by In composition fluctuation in the InGaN active layer seem to be related to the high efficiency of the InGaN-based emitting devices. Long-lifetime violet InGaN multi-quantum-well/GaN/AlGaN separate-confinement heterostructure laser diodes (LDs) were successfully fabricated using epitaxially laterally overgrown GaN by reducing a large number of threading dislocations originating from the interface between GaN and sapphire substrate. The threading dislocations shorten the lifetime of the LDs through an increase of the threshold current density. The LDs with cleaved mirror facets showed an output power as high as 30 mW under room-temperature continuous-wave (CW) operation with a stable fundamental transverse mode. The lifetime of the LDs at a constant output power of 5 mW was estimated to be approximately 3000 h under CW operation at an ambient temperature of 50 °C. These results indicate that these LDs already can be used for many real applications, such as digital versatile disks, laser printers, sensors and exciting light sources as a commercial product with a high output power and a high reliability.
Silicon nanocrystal-based photosensor on low-temperature polycrystalline-silicon panels (2007)

A photodetector, comprising a layer of silicon nanocrystals that is sandwiched between two electrodes, is proposed and demonstrated in a photosensing application on low-temperature polysilicon panels. Laser annealing of silicon-rich oxide films can form nanocrystals that respond optimally to a certain absorption spectrum of a light source. These silicon nanocrystals are smaller than 10nm in diameter, which size determines the effectiveness of their quantum confinement, and promote electron-hole pair generation in the photosensing region because of their direct band gap. Besides obtaining a photosensitivity that is comparable to that of a p-i-n diode, which is currently used in low-temperature polysilicon technology, the sensor maximizes the photosensing area of a pixel by its stacked structure.
Interleukin-4: a prototypic immunoregulatory lymphokine (1991)

THE IMMUNE RESPONSE involves the participation of a large number of distinct cell types whose functions must be coordinated to insure a response that is appropriate in quality and in magnitude to the eliciting antigenic stimulus. This coordination of function is generally believed to be regulated by the action of T lymphocytes, whose receptors are specific for peptides derived from the eliciting antigen, bound to a groove in a class I or a class II major histocompatibility complex (MHC) molecule. Much of the regulatory function of such T cells is mediated by the secretion of a set of potent polypeptides often designated as lymphokines or interleukins (ILs). 1 Those that appear to be principally secreted by immunocompetent cells in response to the interaction of antigen with a specific receptor are listed in Table 1. I will refer to these molecules as “immune recognition-induced lymphokines.”
Periventricular leucomalacia and intraventricular haemorrhage in the preterm neonate. (1986)

Two hundred very low birthweight infants were prospectively scanned to ascertain the incidence of periventricular leucomalacia (PVL) and haemorrhage. Before collection of data, clear definitions of ultrasound abnormalities believed to represent PVL and intraventricular haemorrhage were described. These referred to small and moderate intraventricular haemorrhage, paenchymal haemorrhage, and PVL, including prolonged flare (echoes in the periventricular region lasting for two weeks or more and not becoming cystic). Sixty nine infants (34%) had no abnormality on ultrasound scans. Intraventricular haemorrhage occurred in 107 babies (37 grade I and 62 grade II), and only eight infants were thought to have true parenchymal haemorrhage. Ultrasound appearances of PVL were seen in 27 infants, 19 of whom developed cysts and eight died in the precystic stage. Prolonged flare occurred in another 25 babies. Unilateral parenchymal haemorrhage occurred in four infants who subsequently developed cystic PVL in the contralateral hemisphere. Twenty one infants developed ventricular dilatation, 12 of whom had associated parenchymal lesions. Haemorrhage, PVL, and flare occurred commonly in infants of 30 weeks' gestation and below and became markedly less common in more mature infants. We believe prolonged flare represents a form of PVL, and in this study a total of 52 (26%) infants had an ultrasound appearance of periventricular leucomalacia, an incidence considerably higher than previously reported.
Anti-hypervariable region antibody induced by a defined peptide: an approach for studying the structural correlates of idiotypes. (1984)

The structural correlates of idiotypes have been sought in several antibody systems. However, the precise molecular basis of idiotypes are exceedingly difficult to define. Antibodies of predetermined specificity can be induced by immunization with synthetic peptides. In the present experiments, a synthetic peptide corresponding to a hypervariable region on a monoclonal human IgM rheumatoid factor (Sie) has been used to induce specific anti-hypervariable region antibodies. The antibodies bound to the intact Ig molecule and to its isolated heavy chains but not to other IgM paraproteins nor to pooled human IgG. The binding of the antibody to the intact IgM was inhibited specifically by the free peptide, and the antibody activity was removed by a peptide-coupled affinity column. These results clearly demonstrate that specific anti-idiotypic antibody of predefined specificity can be induced by a hypervariable region peptide. Antibodies of this class may provide a new tool for defining the structural correlates of idiotypes.
Delivery and evaluation of recombinant adeno‐associated viral vectors in the equine distal extremity for the treatment of laminitis (2015)

The current experiments demonstrate that transgenes can be successfully delivered to the equine distal extremity using rAAV vectors and that serotypes 2/8, 2/9 and 2/1 can successfully transduce tissues of the equine foot. When the vector was diluted with surfactant-containing saline, the level of transduction increased dramatically. The increased level of transduction due to the addition of surfactant also improved the distribution pattern of transduction.
Immunospecific Reduction of Antioligonucleotide Antibody-Forming Cells with a Tetrakis-oligonucleotide Conjugate (LJP 394), a Therapeutic Candidate for the Treatment of Lupus Nephritis (1995)

A discrete tetravalent conjugate, 7a (LJP 394), consisting of four oligonucleotides attached to a common carrier or platform was prepared. Single-stranded oligonucleotide 20-mers consisting of alternating deoxycytidine-deoxyadenosine nucleotides, (CA)10, were attached to a tetrabromoacetylated platform by displacement with sulfhydryl-terminated linkers. The tetrabromoacetylated platform 3a was synthesized in three steps using triethylene glycol bis-(chloroformate). The single-stranded conjugate was characterized by polyacrylamide gel electrophoresis, DNA sequencing, phosphate analysis, carbon and nitrogen combustion analysis, and correlation of stoichiometry to conversion in the conjugation process. HPLC and capillary electrophoretic methods were developed to evaluate purity. The tetrakis, single-stranded conjugate was annealed with a stoichiometric amount of a complementary single-stranded oligonucleotide 20-mer consisting of alternating thymidine-deoxyguanosine nucleotides, (TG)10. The double-stranded conjugate LJP 394 was characterized by melt temperature and hyperchromicity, phosphate analysis, and carbon and nitrogen combustion analysis. LJP 394 inhibits binding of DNA to anti-double-stranded oligonucleotide antibodies and reduces anti-oligonucleotide-specific plaque (antibody)-forming cells in an immunized mouse model by a proposed mechanism involving cross-linking B cell surface immunoglobins.
Crystallization of progesterone polymorphs using polymer-induced heteronucleation (PIHn) method (2014)

Progesterone is a natural hormone steroid used in humans for several treatments and in livestock for artificial insemination, which exhibits two polymorphic forms at ambient conditions: form 1 and form 2. Form 2 is metastable and more soluble than form 1; however, it is not suitable to use as powder raw material because it transforms into form 1 by the effects of grinding. A polymorphic screening of progesterone based on polymer-induced heteronucleation method was performed as an alternative to prepare the metastable form. Polyvinyl alcohol, hydroxypropyl methylcellulose (HPMC), dextran, gelatin, polyisoprene (PI) and acrylonitrile-butadiene (NBR) copolymer were used. Crystals were prepared from 0.5, 10 and 40 mg/mL solutions in acetone at room temperature by solvent evaporation. The samples were characterized by X-ray powder diffraction, differential scanning calorimetry (DSC), scanning electron microcopy and attenuated total reflectance infrared Fourier transform spectroscopy. Form 1 was nucleated from 40 mg/mL solutions on the six polymers and from 10 mg/mL solutions on PI and NBR. The mixture of form 1 and form 2 was obtained from 10 mg/mL solution on HPMC, dextran and gelatin and from 0.5 mg/mL solution crystallizations. Therefore, the polymeric devices, which crystallized the metastable and more soluble polymorph (2) of progesterone, would be a promissory alternative for the pharmaceutical applications.
Mechanism of direct side-chain acylamination and aminoarylation of 2- and 4-picoline 1-oxides (1981)

The isolation of radical coupling products and the observation of appropriate C.I.N.D.P. signals suggest that most of the title reactions proceed by homolysis of the anhydro-bases (4) or (9) followed by radical recombinations; a diaza-oxy-Cope rearrangement may still account for the formation of α-acylamination products.
Molecular-weight-dependent effects of nonanticoagulant heparins on allergic airway responses (1999)

We have hypothesized that antiallergic activity of inhaled heparin is molecular weight dependent and mediated by "nonanticoagulant fractions" (NAF-heparin). Therefore, we studied comparative effects of high-, medium-, and ultralow-molecular-weight (HMW, MMW, and ULMW, respectively) NAF-heparins on acute bronchoconstrictor response (ABR) and airway hyperresponsiveness (AHR) in allergic sheep. Specific lung resistance was measured in 23 allergic sheep, before and immediately after challenge with Ascaris suum antigen, without and after pretreatment with inhaled NAF-heparins. Airway responsiveness was estimated before and 2 h postantigen as the cumulative provocating dose of carbachol in breath units, which increased specific lung resistance by 400%. NAF-heparins attenuated ABR and AHR in a molecular-weight-dependent fashion. HMW NAF-heparin (n = 8) was the least effective agent: it attenuated ABR [inhibitory dose causing 50% protection (ID50) = 4 mg/kg] but had no effect on AHR. MMW NAF-heparin (n = 8) showed intermediate efficacy (ABR ID50 = 0.8 mg/kg, AHR ID50 = 1.4 mg/kg), whereas ULMW NAF-heparin (n = 7) was the most effective agent (ABR ID50 = 0.4 mg/kg, AHR ID50 = 0.2 mg/kg). ULMW NAF-heparin was 3.5 times more potent in attenuating antigen-induced AHR when administered "after" antigen challenge and failed to inhibit the bronchoconstrictor response to carbachol and histamine. In 15 additional sheep, segmental antigen challenge caused a marked increase in histamine in bronchoalveolar lavage fluid that was not prevented by any of the inhaled NAF-heparins. These data indicate that antiallergic activity of inhaled heparin is independent of its anticoagulant action and resides in the <2,500 ULMW chains. The antiallergic activity of NAF-heparins is mediated by an unknown biological action and may have therapeutic potential.
A conserved amino acid residue critical for product and substrate specificity in plant triterpene synthases (2016)

Triterpenes are structurally complex plant natural products with numerous medicinal applications. They are synthesized through an origami-like process that involves cyclization of the linear 30 carbon precursor 2,3-oxidosqualene into different triterpene scaffolds. Here, through a forward genetic screen in planta, we identify a conserved amino acid residue that determines product specificity in triterpene synthases from diverse plant species. Mutation of this residue results in a major change in triterpene cyclization, with production of tetracyclic rather than pentacyclic products. The mutated enzymes also use the more highly oxygenated substrate dioxidosqualene in preference to 2,3-oxidosqualene when expressed in yeast. Our discoveries provide new insights into triterpene cyclization, revealing hidden functional diversity within triterpene synthases. They further open up opportunities to engineer novel oxygenated triterpene scaffolds by manipulating the precursor supply.
Moisture Swing Sorbent for Carbon Dioxide Capture from Ambient Air (2011)

An amine-based anion exchange resin dispersed in a flat sheet of polypropylene was prepared in alkaline forms so that it would capture carbon dioxide from air. The resin, with quaternary ammonium cations attached to the polymer structure and hydroxide or carbonate groups as mobile counterions, absorbs carbon dioxide when dry and releases it when wet. In ambient air, the moist resin dries spontaneously and subsequently absorbs carbon dioxide. This constitutes a moisture induced cycle, which stands in contrast to thermal pressure swing based cycles. This paper aims to determine the isothermal performance of the sorbent during such a moisture swing. Equilibrium experiments show that the absorption and desorption process can be described well by a Langmuir isothermal model. The equilibrium partial pressure of carbon dioxide over the resin at a given loading state can be increased by 2 orders of magnitude by wetting the resin.
Probing the Specificity of Aminoglycoside−Ribosomal RNA Interactions with Designed Synthetic Analogs (1998)

The binding of neomycin B and related aminoglycoside antibiotics to the prokaryotic ribosomal RNA decoding region has been investigated using a recently developed surface plasmon resonance assay. A number of naturally occurring aminoglycosides containing a neamine or neamine-like substructure bind specifically to a model of the site of the ribosomal decoding region RNA. This recognition event is the basis of the antibacterial activity of this class of compounds. A series of analogs was designed and synthesized to probe the role of neomycin ring IV (2,6-dideoxy-2,6-diamino-β-l-idopyranose). The binding results indicate that the positive charge presented on the idose ring is necessary for specific binding in vitro and cannot be replaced by amines attached via flexible linkers. However, the antibiotic activity (minimum inhibitory concentration) of the analog where ring IV is replaced with a diamine tail is the same as neomycin B in a liquid culture assay against Escherichia coli.
Flow Visualization and Characteristics of a Coaxial Jet with a Tabbed Annular Nozzle (2006)

Flow visualization and measurements of mean and fluctuating velocities were performed on a coaxial jet with a velocity ratio of 0.6 at a Reynolds number of 3000 in an open water tank using hot-film anemometry, particle image velocimetry (2D and stereoscopic PIV) and laser-induced fluorescence (LIF). Axisymmetric and streamwise vortical structures were revealed in the near-field of the coaxial jet. The annular nozzle has six vortex generators in order to enhance the streamwise vortices generated in the mixing layer. Furthermore, the annular jet was excited by a shaker in order to enhance the axisymmetric vortices. For the tabbed coaxial jet, jet spreading downstream was greater than for the jet without tabs. The cause of the entrainment increment is the development of axisymmetric and streamwise vortex structures. In the case of excited jets, significant axisymmetric and streamwise vortical structures develop, and the jet width expands from the exit nozzle. Consequently, the flow rate of the excited jet with tabs is larger than that of the unexcited jet without tabs.
Deposition and electrical properties of N–In codoped p-type ZnO films by ultrasonic spray pyrolysis (2004)

The N–In codoped p-type ZnO films have been prepared by ultrasonic spray pyrolysis. X-ray photoelectron spectroscopy analysis confirmed the presence of nitrogen and indium in the codoped films, and the incorporation of indium causes the change in the chemical state of nitrogen, which promotes the formation of p-type conduction. Low resistivity of 1.7×10−2 Ω cm, high carrier concentration of 2.44×1018 cm−3 and Hall mobility of 155 cm2 V−1 s−1 at room temperature for the codoped films were obtained. A conversion from p-type conduction to n type in a range of temperature has been identified by the measurement of Seebeck and Hall effect.
Plant Regeneration in Callus Cultures Derived from Young Inflorescences of Little Bluestem1 (1986)

Little Bluestem [ Schizachyrium scoparium (Michx.) Nash], a warm‐season perennial grass, is valuable for range and conservation plantings in the Great Plains. The objectives of this study were to develop rapid vegetative propagation techniques to facilitate selection of superior genotypes and to elucidate differentiation patterns in tissue culture. Embryogenic call! were induced from 5‐ to 10‐mm segments of unemerged young inflorescences and maintained on Linsmaier and Skoog's RM medium supplemented with 5 mg 2,4‐Dichlorophenoxy acetic acid (2,4‐D)/L in the dark at 25°C. The explants were furnished from three genotypes selected from a breeding nursery. Plants regenerated through somatic embryogenesis from callus were grown on RM medium containing no hormones and with the same physical conditions as for callus initiation. Embryogenesis tended to be suppressed by 2,4‐D concentrations of 1 mg/L or higher, but was promoted by the addition of 1 to 5 mg kinetin/L. Regenerated plants grew to maturity in 24 weeks after being transplanted into pots in the greenhouse and were phenotypically similar to their source plants.
The role of JAGGED in shaping lateral organs (2004)

Position-dependent regulation of growth is important for shaping organs in multicellular organisms. We have characterized the role of JAGGED, a gene that encodes a protein with a single C(2)H(2) zinc-finger domain, in controlling the morphogenesis of lateral organs in Arabidopsis thaliana. Loss of JAGGED function causes organs to have serrated margins. In leaves, the blade region is most severely affected. In sepals, petals and stamens, the strongest defects are seen in the distal regions. By monitoring cell-cycle activity in developing petals with the expression of HISTONE 4, we show that JAGGED suppresses the premature differentiation of tissues, which is necessary for the formation of the distal region. The localization of defects overlaps with the expression domain of JAGGED, which is restricted to the growing regions of lateral organs. JAGGED expression is notably absent from the cryptic bract, the remnant of a leaf-like organ that subtends the flower in many species but does not normally develop in wild-type Arabidopsis. If misexpressed, JAGGED can induce the formation of bracts, suggesting that the exclusion of JAGGED from the cryptic bract is a cause of bractless flowers in Arabidopsis.
The evolution of amidine-based brain penetrant BACE1 inhibitors (2014)

Beta site amyloid precursor protein cleaving enzyme 1 (BACE1) inhibitors hold great potential as disease modifying anti-Alzheimer's drugs. This digest provides an overview of the amidine containing class of BACE1 inhibitors, of which multiple examples are now progressing through clinical trials. The various structural modifications highlight the struggle to combine potency with the optimal properties for a brain penetrant BACE1 inhibitor, and illustrate the crowded competitive landscape. This overview concludes with a summary of potential issues including substrate and target selectivity and a synopsis of the status of the current and past clinical assets.
Multi-Label Learning with Weak Label (2010)

Multi-label learning deals with data associated with multiple labels simultaneously. Previous work on multi-label learning assumes that for each instance, the “full” label set associated with each training instance is given by users. In many applications, however, to get the full label set for each instance is difficult and only a “partial” set of labels is available. In such cases, the appearance of a label means that the instance is associated with this label, while the absence of a label does not imply that this label is not proper for the instance. We call this kind of problem “weak label” problem. In this paper, we propose the WELL (WEak Label Learning) method to solve the weak label problem. We consider that the classification boundary for each label should go across low density regions, and that each label generally has much smaller number of positive examples than negative examples. The objective is formulated as a convex optimization problem which can be solved efficiently. Moreover, we exploit the correlation between labels by assuming that there is a group of low-rank base similarities, and the appropriate similarities between instances for different labels can be derived from these base similarities. Experiments validate the performance of WELL.