gebhart/patrepeval huggingface dataset:
Sustained‐Release Naltrexone for Alcoholism Treatment: A Preliminary Study (1998)

This 12‐week study examined the bioavailability, tolerability, and potential efficacy of an injectable sustained‐release preparation (SRP) of naltrexone (NTX). Twenty alcohol‐dependent subjects took NTX 50 mg po daily for 2 weeks, followed by a 2‐week, no‐medication Washout Period, a 4‐week Injection Period, and a 4‐week Follow‐up Period. Fifteen subjects (75%) received a single subcutaneous injection of 206 mg of sustained‐release NTX, and five subjects (25%) received a placebo injection. All subjects also received eight weekly coping skills sessions during the Oral NTX, and the Washout and Injection Periods. Results: After injection, NTX plasma concentrations exceeded a mean of 1 ng/ml for 21 days. Adverse effects produced by the SRP of NTX were comparable with those resulting from oral NTX therapy. Compared with placebo, the SRP of NTX significantly reduced the frequency of heavy drinking days during the Injection and Follow‐up Periods. Conclusions: The results of this preliminary study support the potential clinical utility of the SRP of NTX for treatment of alcohol dependence.
Digital beam forming for sonar systems (1980)

Current generation sonar systems employ high temporal and spatial resolution to achieve acceptable operational performance. This, together with the physical mechanisms of acoustic propagation in the ocean, places a number of constraints on the implementation of beam-forming systems for sonar applications that are in many ways unique; in particular: (a) Low sonar operating frequencies and the use of wide processing and analysis bandwidths necessitate the use of broadband beam-forming techniques, often using true time-delay rather than phase-delay realisation. (b) Large arrays of sensors are required for high spatial resolution and the beam-forming system must be capable of forming and processing from these large numbers of independently steered beams in parallel to achieve useful angular cover, as well as good angular resolution. (c) The sensor arrays themselves are often mounted on mobile platforms, for example on surface ships, and the effects of platform motion on array data must be considered if the intrinsic system resolution is to be maintained. (d) The array geometries employed are often constrained by platform requirements rather than by those of the sonar and consequently sonar beam-forming systems must be able to process data from various diverse array geometries, for example from conformal and cylindrical, as well as planar sensor arrays. This paper outlines the impact of such factors on sonar beam-forming implementations and describes some of the techniques that have been developed, together with their practical realisation using state-of-the-art digital l.s.i. technology.
Making Sandcastles with the Sands of Time (2019)

Rushing through a tutoring session can seem alluringly efficient, but this theorized efficiency is a faulty conception. In a tutoring session, moving through content too quickly can lead to discussion based only on surface level observations. By being fully present and taking the time to explore ideas in depth, a tutor is able to supply a Writing Center visitor with much more helpful and in-depth insights.
Polymer electrolyte membranes based on poly(phenylene ether)s with sulfonic acid via long alkyl side chains (2013)

A series of poly(phenylene ether)s with sulfonic acid groups via long alkyl side chains, SPPEs, were successfully prepared as proton exchange membranes for fuel cells. The new monomer, bis[4-fluoro-3-(p-methoxylbenzoyl)]biphenyl (BFMBP), containing two pendent methoxyphenyl groups was synthesized by the Friedel–Crafts reaction of 5-chloro-2-fluorobenzoyl chloride with anisole, followed by the nickel-mediated homocoupling reaction. Poly(phenylene ether)s (PPEs) were then successfully obtained by the aromatic nucleophilic substitution polycondensation of BFMBP with dihydroxy-monomers in the presence of potassium carbonate. Sulfonated PPEs (SPPEs) (IEC: 1.96–2.45 mequiv. g−1) could be prepared by the reaction of PPEs containing phenol units with 1,4-butanesultone. By the solution casting method, SPPEs produced transparent membranes with good mechanical properties, and showed good oxidative and dimensional stabilities, and high proton conductivities, e.g., 8.60 × 10−3 S cm−1 under 30% relative humidity at 80 °C, which is higher than that of Nafion 117.
2,3,9,10,16,17,24,25-Octakis(octyloxycarbonyl)phthalocyanines. Synthesis, Spectroscopic, and Electrochemical Characteristics (2007)

A series of three novel 2,3,9,10,16,17,24,25-octakis(octyloxycarbonyl)phthalocyanine compounds M[Pc(COOC8H17)8] (M = 2H, Cu, Zn) (1-3) have been synthesized via the cyclic tetramerization of 4,5-di(octyloxycarbonyl)phthalonitrile, which was obtained by a newly developed procedure with o-xylene as starting material, promoted with organic base 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) in the absence and presence of metal salt like M(acac)2.H2O (M = Cu, Zn) in n-octanol at 120 degrees C. In addition to elemental analysis, these novel octakis(octyloxycarbonyl)-substituted phthalocyanine compounds have been characterized by a series of spectroscopic methods. The electrochemistry of these compounds was also studied by cyclic voltammetry (CV) and differential pulse voltammetry (DPV) methods. A significant shift to the positive direction for both the first oxidation and the first reduction of compound 1, relative to H2Pc, reveals the electron-withdrawing nature of octyloxycarbonyl groups attached to the peripheral positions of phthalocyanine. The effect of peripheral octyloxycarbonyl substitution on the electrochemistry of the series of phthalocyanines 1-3 has been reasonably explained by theoretical calculation results using the density functional theory (DFT) method.
Anisotropic etching of diamond by molten Ni particles (2010)

Nanopores in insulating solid state membranes have recently attracted much interest in the field of probing, characterizing, and manipulating single linear polymers such as DNA/RNA and proteins in their native environment. Here a low cost, fast, and effective way to produce nanostructures such as pyramidal shaped nanopores and nanochannels with dimensions down to about 15 nm in diamond membranes without any need for electron-beam lithography is demonstrated. By use of a catalytic process, anisotropic etching of diamond with self-organized Ni nanoparticles in hydrogen atmosphere at 900 °C is achieved and possible etching mechanisms are discussed. It is shown that diamond planes with the crystallographic orientation of [111] are etched slowest with this method.
Two Transport Systems for Tetracycline in Sensitive <i>Escherichia coli</i> : Critical Role for an Initial Rapid Uptake System Insensitive to Energy Inhibitors (1978)

Escherichia coli sensitivity to tetracycline involves transport and accumulation of the antibiotic within the cell by two different uptake systems: an initial rapid uptake, which occurs over the initial 6 min of contact of the cell with tetracycline, and a slower uptake system, which continues indefinitely and whose rate of uptake is 1/10 that of the rapid system. Only the slow uptake system is blocked by inhibitors of energy-driven systems; it appears to be particularly dependent upon energy from oxidative phosphorylation. Although both uptake systems lead to accumulation of intracellular tetracycline and contribute to the cell's sensitivity, the rapid uptake system appears to be the more important. While these studies confirm active transport of tetracycline into the cell, they demonstrate that a critical uptake system which appears insensitive to metabolic inhibitors occurs initially.
Design pattern implementation in Java and aspectJ (2002)

AspectJ implementations of the GoF design patterns show modularity improvements in 17 of 23 cases. These improvements are manifested in terms of better code locality, reusability, composability, and (un)pluggability.The degree of improvement in implementation modularity varies, with the greatest improvement coming when the pattern solution structure involves crosscutting of some form, including one object playing multiple roles, many objects playing one role, or an object playing roles in multiple pattern instances.
Metabolic engineering of<i>Saccharomyces cerevisiae</i>âfor production of carboxylic acids: current status and challenges (2009)

To meet the demands of future generations for chemicals and energy and to reduce the environmental footprint of the chemical industry, alternatives for petrochemistry are required. Microbial conversion of renewable feedstocks has a huge potential for cleaner, sustainable industrial production of fuels and chemicals. Microbial production of organic acids is a promising approach for production of chemical building blocks that can replace their petrochemically derived equivalents. Although Saccharomyces cerevisiae does not naturally produce organic acids in large quantities, its robustness, pH tolerance, simple nutrient requirements and long history as an industrial workhorse make it an excellent candidate biocatalyst for such processes. Genetic engineering, along with evolution and selection, has been successfully used to divert carbon from ethanol, the natural endproduct of S. cerevisiae, to pyruvate. Further engineering, which included expression of heterologous enzymes and transporters, yielded strains capable of producing lactate and malate from pyruvate. Besides these metabolic engineering strategies, this review discusses the impact of transport and energetics as well as the tolerance towards these organic acids. In addition to recent progress in engineering S. cerevisiae for organic acid production, the key limitations and challenges are discussed in the context of sustainable industrial production of organic acids from renewable feedstocks.
Cationic polymerization of diglycidyl ether of Bisphenol A. II. theory (1997)

Network formation in cationic polymerization of polyepoxides was treated using a combination of kinetic theory and the statistical theory of branching processes (TBP). The complex reaction mechanism involved a degradative termination reaction affecting the molecular weight distribution of the primary chains. Moreover, formation of low-molecular-weight products, initiation, two mechanisms of propagation and transfer were taken into account. © 1997 John Wiley & Sons, Inc. J Polym Sci A: Polym Chem 35: 651–663, 1997
미용서비스 조직에서 서비스공정성, 고객몰입 및 고객시민행동 간의 관계 (2010)

본 연구에서는 미용서비스 조직에서 고객들이 종업원들과 마찬가지로 서비스 창출과정에 참여하거나 자발적 행동을 하는 등과 같은 부분적 종업원의 역할들을 수행한다는 관점을 받아들여, 고객이 지각하는 서비스공정성의 하위차원들이 고객몰입과 갖고 있는 각각의 관계 그리고 고객몰입이 고객시민행동의 하위차원인 충성행동, 협력행동 및 참여행동과 갖는 각각의 관계를...
Comparing and Integrating Constraint Programming and Temporal Planning\n for Quantum Circuit Compilation (2018)

Recently, the makespan-minimization problem of compiling a general class of\nquantum algorithms into near-term quantum processors has been introduced to the\nAI community. The research demonstrated that temporal planning is a strong\napproach for a class of quantum circuit compilation (QCC) problems. In this\npaper, we explore the use of constraint programming (CP) as an alternative and\ncomplementary approach to temporal planning. We extend previous work by\nintroducing two new problem variations that incorporate important\ncharacteristics identified by the quantum computing community. We apply\ntemporal planning and CP to the baseline and extended QCC problems as both\nstand-alone and hybrid approaches. Our hybrid methods use solutions found by\ntemporal planning to warm start CP, leveraging the ability of the former to\nfind satisficing solutions to problems with a high degree of task optionality,\nan area that CP typically struggles with. The CP model, benefiting from\ninferred bounds on planning horizon length and task counts provided by the warm\nstart, is then used to find higher quality solutions. Our empirical evaluation\nindicates that while stand-alone CP is only competitive for the smallest\nproblems, CP in our hybridization with temporal planning out-performs\nstand-alone temporal planning in the majority of problem classes.\n
Mechanism of expression and role in transcriptional control of the proto-oncogene NFKB-2/LYT-10. (1994)

The NFKB-2 gene (previously LYT-10, NF-kappa Bp100 or NF-kappa Bp97) codes for a NF-kappa B/rel related protein which is highly homologous to NFKB-1 (previously NF-kappa Bp105) within its rel, poly-glycine and ankyrin domains. The NFKB-2 gene is a candidate proto-oncogene since it is involved in lymphoma-associated chromosomal aberrations. In order to gain insight into the physiological function and role in tumorigenesis of NFKB-2, we have analysed its mechanism of expression and role in transcriptional regulation. We report that, contrary to previous studies, a single 3.2 kb mRNA species and its 100 kD (p100) primary translation product is detectable in all cell types tested. A second NFKB-2 protein, p52, corresponding to the amino-terminal half (rel domain) of NFKB-2 p100, is detectable in the same cell types and derives from the post-translational processing of p100. While p100 is constitutively localized in the cytoplasm, NF-kappa B induction by TPA treatment of Hela cells is associated with cytoplasmic/nuclear translocation of NFKB-2 p52 and its appearance within DNA-binding NF-kappa B complexes. NFKB-2 p52 differs from NFKB-1p50 in its differential affinity for kappa B sequences: by itself it binds H2/HLA-kappa B sites more efficiently than HIV/IgK-kappa B sites, while it can bind both sites efficiently when complexed with Rel-A(p65). Transient co-transfection of expression and reporter plasmids in cells devoid of endogenous NF-kappa B activity showed that p52 has no intrinsic transcriptional activation capabilities: it can stimulate Rel-A(p65)-driven transcription by formation of p65/p52 heterodimers, whereas, overexpressed, it down-regulates p65-dependent transcription by formation of inactive p52/p52 homodimers. These results indicate that the NFKB-2 gene codes for an inducible NF-kappa B transcription factor with the capability of differentially regulating NF-kappa B transcription depending on its abundance in the nucleus.
Discovery of Sodium <i>R</i>-(+)-4-{2-[5-(2-Fluoro-3-methoxyphenyl)-3-(2-fluoro-6-[trifluoromethyl]benzyl)-4-methyl-2,6-dioxo-3,6-dihydro-2<i>H</i>-pyrimidin-1-yl]-1-phenylethylamino}butyrate (Elagolix), a Potent and Orally Available Nonpeptide Antagonist of the Human Gonadotropin-Releasing Hormone Receptor (2008)

The discovery of novel uracil phenylethylamines bearing a butyric acid as potent human gonadotropin-releasing hormone receptor (hGnRH-R) antagonists is described. A major focus of this optimization was to improve the CYP3A4 inhibition liability of these uracils while maintaining their GnRH-R potency. R-4-{2-[5-(2-fluoro-3-methoxyphenyl)-3-(2-fluoro-6-[trifluoromethyl]benzyl)-4-methyl-2,6-dioxo-3,6-dihydro-2H-pyrimidin-1-yl]-1-phenylethylamino}butyric acid sodium salt, 10b (elagolix), was identified as a potent and selective hGnRH-R antagonist. Oral administration of 10b suppressed luteinizing hormone in castrated macaques. These efforts led to the identification of 10b as a clinical compound for the treatment of endometriosis.
HIV inhibits CD4+ T-cell proliferation by inducing indoleamine 2,3-dioxygenase in plasmacytoid dendritic cells (2006)

Infection with the human immunodeficiency virus type-1 (HIV) results in acute and progressive numeric loss of CD4(+) T-helper cells and functional impairment of T-cell responses. The mechanistic basis of the functional impairment of the surviving cells is not clear. Indoleamine 2,3-dioxygenase (IDO) is an immunosuppressive enzyme that inhibits T-cell proliferation by catabolizing the essential amino acid tryptophan (Trp) into the kynurenine (kyn) pathway. Here, we show that IDO mRNA expression is elevated in peripheral blood mononuclear cells (PBMCs) from HIV(+) patients compared with uninfected healthy controls (HCs), and that in vitro inhibition of IDO with the competitive blocker 1-methyl tryptophan (1-mT) results in increased CD4(+) T-cell proliferative response in PBMCs from HIV-infected patients. We developed an in vitro model in which exposure of PBMCs from HCs to either infectious or noninfectious, R5- or X4-tropic HIV induced IDO in plasmacytoid dendritic cells (pDCs). HIV-induced IDO was not inhibited by blocking antibodies against interferon type I or type II, which, however, induced IDO in pDCs when added to PBMC cultures. Blockade of gp120/CD4 interactions with anti-CD4 Ab inhibited HIV-mediated IDO induction. Thus, induction of IDO in pDCs by HIV may contribute to the T-cell functional impairment observed in HIV/AIDS by a non-interferon-dependent mechanism.
Resolution properties of a large-area quasi-monochromatic x-ray source for mammography (1998)

Quasi-monochromatic X-rays with energy in the 16 - 24 keV range have been produced in our laboratory by making use of a conventional W-anode X-ray tube and a monochromator optical system via Bragg diffraction. The optical system is based on an array of mosaic crystals which produces an irradiation field obtained with adjacent reflected beams. The field size is about 10.5 X 12.0 cm<SUP>2</SUP> in the image plane. The introduction of an active optical component such as a mosaic crystal array may modify the imaging performances of the system. In order to investigate how the resolution properties of the quasi-monochromatic source are affected by the use of adjacent beams and the Bragg diffraction phenomenon, images of a hole pattern and a slit camera have been obtained with different magnification factors. The images of the hole pattern show duplication effects due to the partial superposition of adjacent beams. Slit camera images show an unexpected increase of the focal spot blurring along the diffraction plane. This behavior could be explained by considering each crystal monochromator of the array as a secondary source and consequently as a focal spot of the beam coming from it. Along the orthogonal direction the image blurring depends on the focal spot size of the X-ray tube.
Derivatized Cellulose Combined with MALDI-TOF MS:  A New Tool for Serum Protein Profiling (2005)

Providing a rapid and sensitive protein profiling method for biomarker discovery from a variety of biological samples is crucial for the introduction of new markers that improve cancer patient diagnosis at early tumor stages, thus increasing the chances of curative treatment. We report here the development and application of derivatized cellulose particles for selective serum protein profiling. For immobilized metal ion affinity chromatography (IMAC), cellulose was derivatized with glycidyl methacrylate (GMA) and subsequently with iminodiacetic acid (IDA). To investigate the application of this material for generating protein profiles of human serum samples, the serum samples were agitated with the derivatized cellulose particles to a suspension and incubated for 2 h at 30 °C. After washing, 1 μL of the IDA-Cu2+-cellulose suspension was applied directly onto a MALDI-target, mixed with sinapinic acid (SA) and analyzed with MALDI-TOF MS. Consistent serum specific data were obtained from aliquoted samples analyzed several times, indicating the reliability of the method. However, the serum fingerprints obtained proved to be specific for any given serum. The technique presented allows a high enrichment of sample on the developed target leading to a high sensitivity and reproducibility without depletion of albumin and immunoglobulin, and sample elution prior to MS-analysis. The study demonstrates for the first time that derivatized cellulose particles combined with MALDI-TOF MS represent a simple, economical, and rapid approach to generate serum protein profiles for biomarker identification. Keywords: spherical cellulose • protein profiling • direct MALDI-TOF • prostate cancer
Non-V600 BRAF mutations recurrently found in lung cancer predict sensitivity to the combination of Trametinib and Dabrafenib (2016)

Approximately half of BRAF-mutated Non-small cell lung cancers (NSCLCs) harbor a non-V600 BRAF mutation, accounting for ∼40,000 annual deaths worldwide. Recent studies have revealed the benefits of combined targeted therapy with a RAF-inhibitor (Dabrafenib) and a MEK-inhibitor (Trametinib) in treating V600 BRAF mutant cancers, including NSCLC. In contrast, sensitivity of non-V600 BRAF mutations to these inhibitors is not documented. Non-V600 mutations can either increase or impair BRAF kinase activity. However, impaired BRAF kinases can still activate the ERK pathway in a CRAF-dependent manner. Herein, beyond describing a cohort of BRAF mutant NSCLC patients and functionally analyzing 13 tumor-derived BRAF mutations, we demonstrate that both types of non-V600 BRAF mutations can be sensitive to clinically relevant doses of Dabrafenib and Trametinib in HEK293T cells, in lung epithelial cellular model (BEAS-2B) and in human cancer cell lines harboring non-V600 BRAF mutations. ERK activity induced by both types of these mutations is further reduced by combinatorial drug treatment. Moreover, the combination leads to more prolonged ERK inhibition and has anti-proliferative and pro-apoptotic effects in cells harboring both types of non-V600 BRAF mutations. This study provides a basis for the clinical exploration of non-V600 BRAF mutant lung cancers upon treatment with Trametinib and Dabrafenib.
Osmotic effects on the <i>T</i><sub>2</sub> relaxation decay of in vivo muscle (2001)

Saline solutions are commonly employed as a vehicle for drugs administered intramuscularly. In this study, in vivo measurements of spin-spin relaxation (T2) processes by magnetic resonance imaging (MRI) were performed to investigate the distribution of water in rat masseter muscle tissue after intramuscular injection of saline solutions of varying tonicity. Prior to saline injection, image-based T2 relaxation decay of muscle was monoexponential. After injection of saline, the T2 relaxation decay became multiexponential. Non-negative least squares (NNLS) analysis of the decay curves revealed two relaxation components: a fast component (T2 = 20-40 ms) and a slow component (T2 = 150-400 ms), which are assigned to intra- and extracellular water protons, respectively. Injection of hypertonic saline solutions significantly increased the extracellular water component in muscle tissue compared to isotonic saline solutions, an effect which lasted for more than 60 min. These findings suggest that MRI techniques may be useful to investigate the effect of hyper- or hypotonic solutions on muscle tissue in vivo.