gebhart/patrepeval huggingface dataset:
Design, Synthesis, and Structure−Activity Relationships of Alkylcarbamic Acid Aryl Esters, a New Class of Fatty Acid Amide Hydrolase Inhibitors (2003)

Fatty acid amide hydrolase (FAAH), an intracellular serine hydrolase enzyme, participates in the deactivation of fatty acid ethanolamides such as the endogenous cannabinoid anandamide, the intestinal satiety factor oleoylethanolamide, and the peripheral analgesic and anti-inflammatory factor palmitoylethanolamide. In the present study, we report on the design, synthesis, and structure-activity relationships (SAR) of a novel class of potent, selective, and systemically active inhibitors of FAAH activity, which we have recently shown to exert potent anxiolytic-like effects in rats. These compounds are characterized by a carbamic template substituted with alkyl or aryl groups at their O- and N-termini. Most compounds inhibit FAAH, but not several other serine hydrolases, with potencies that depend on the size and shape of the substituents. Initial SAR investigations suggested that the requirements for optimal potency are a lipophilic N-alkyl substituent (such as n-butyl or cyclohexyl) and a bent O-aryl substituent. Furthermore, the carbamic group is essential for activity. A 3D-QSAR analysis on the alkylcarbamic acid aryl esters showed that the size and shape of the O-aryl moiety are correlated with FAAH inhibitory potency. A CoMSIA model was constructed, indicating that whereas the steric occupation of an area corresponding to the meta position of an O-phenyl ring improves potency, a region of low steric tolerance on the enzyme active site exists corresponding to the para position of the same ring. The bent shape of the O-aryl moieties that best fit the enzyme surface closely resembles the folded conformations observed in the complexes of unsaturated fatty acids with different proteins. URB524 (N-cyclohexylcarbamic acid biphenyl-3-yl ester, 9g) is the most potent compound of the series (IC(50) = 63 nM) and was therefore selected for further optimization.
Pore Geometry in High- and Low-Permeability Sandstones, Travis Peak Formation, East Texas (1990)

Summary Petrographic and petrophysical analyses have revealed that tight sandstone possesses distinct petrological properties that differentiate it from conventional sands. Diagenetic alteration changes a wide variety of fluvial, deltaic, and marine sands into similar low-permeability rocks with nearly identical pore structures. In this paper, changes in the pore geometry and petrology as conventional sandstones become tight are examined within a single East Texas sandstone formation.
Enhanced "ULTRA GRIDSEC": Enhancing High Performance Symmetric Key Cryptography Schema Using Pure Peer To Peer Computational Grid Middleware (HIMAN) (2008)

ULTRA GRIDSEC" is a high performance symmetric key cryptography schema used to increase the performance of symmetric key encryption algorithms like DES and TDES by decreasing their execution time and increasing their security by using compression and multithreading techniques and other enhancement points. In this paper we enhancing the performance of a "ULTRA GRIDSEC" by using a pure peer-to-peer computational grid middleware called "HIMAN" that we developed before. "ULTRA GRIDSEC" Performance accelerated by about 254.8% when it was applied as an application for "HIMAN" middleware for file with size 55MB and 1MB block size, and accelerated by 431.2% for file with size 110MB and 10MB block size so every time the size of file is large and choosing the suitable block size and suitable number of threads this can cause a great acceleration for the schema performance regarding to machines capabilities of the running middleware. After that we compared the performance of the enhanced "ULTRA GRIDSEC" with a developed schema called "GRIDCRYPT" developed by Melbourne University in Australia and run over their middleware called Alchemi, so for file with size 55MB and 1MB Block Size and using 4 workers, "ULTRA GRIDSEC" Performance is faster by about 445.37% than the "GRIDCRYPT" Schema, and for file with size 110 MB and 10 MB block size and using 4 workers, "ULTRA GRIDSEC" Performance is faster by about 708.69% than the "GRIDCRYPT" schema. An analysis and results of this schema and comparison of this scheme performance with another existing schema are presented in this paper.
Cross-Coupling Methods for the Large-Scale Preparation of an Imidazole−Thienopyridine:  Synthesis of [2-(3-Methyl-3H-imidazol-4-yl)- thieno[3,2-b]pyridin-7-yl]-(2-methyl-1H-indol-5-yl)-amine (2003)

The multihundred-gram synthesis of [2-(3-methyl-3H-imidazol-4-yl)-thieno[3,2-b]pyridin-7-yl]-(2-methyl-1H-indol-5-yl)-amine (1) is described utilizing a Stille cross-coupling of an iodothienopyridine (3) with 5-(tributylstannyl)-1-methylimidazole (11). Several cross-coupling methods were evaluated for the conversion of thienopyridine 3 to imidazole−thienopyridine 2, but only two were effective: the Stille coupling and a Negishi cross-coupling of the organozinc reagent derived from 2-(tert-butyldimethylsilyl)-1-methylimidazole and iodothienopyridine (3). The latter procedure worked well on laboratory scale (<50 g), but was capricious upon scale-up. The issues with scale-up of an organostannane reagent are discussed, including control and analysis of organotin levels.
FCGR2APolymorphism Is Correlated With Clinical Outcome After Immunotherapy of Neuroblastoma With Anti-GD2 Antibody and Granulocyte Macrophage Colony-Stimulating Factor (2006)

The favorable outcome associated with FCGR2A (R/R) genotype is consistent with the proposed role of FCGR2A and phagocyte-mediated ADCC in 3F8 plus GM-CSF immunotherapy.
Preface (1993)

An abstract is not available for this content so a preview has been provided. Please use the Get access link above for information on how to access this content.
Penta-band one-eighth wavelength PIFA for internal mobile phone antenna (2009)

A planar lambda/8-PIFA with a coupling feed for achieving GSM850/900/1800/ 1900/UMTS operation in the mobile phone has been proposed and studied. With penta-band operation obtained for WWAN communication, the proposed lambda/8-PIFA occupies a small area of 7 times 40 mm <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2</sup> on an inexpensive 1.6-mm thick FR4 substrate. The compact size of the proposed PIFA also makes it promising to be embedded inside the casing of the mobile phone to operate as an internal antenna. In addition, two lambda/8 modes are excited at close frequencies around 900 MHz to form a wide operating band for the antenna's lower band by using a common coupling feed. Further, two higher-order modes (lambda/4 modes) are also successfully excited at close frequencies around 1900 MHz to provide a wide operating band for the antenna's upper band. The obtained wide lower and upper bands allow the proposed PIFA to cover GSM850/900/1800/1900/UMTS penta-band operation for WWAN communication. The proposed planar lambda/8-PIFA is promising for practical application in the mobile phone for WWAN communication.
Quantitative export of FGF‐2 occurs through an alternative, energy‐dependent, non‐ER/Golgi pathway (1995)

Although basic fibroblast growth factor (bFGF/FGF-2) is found outside cells, it lacks a conventional signal peptide sequence; the mechanism underlying its export from cells is therefore unknown. Using a transient COS-1 cell expression system, we have identified a novel membrane-associated transport pathway that mediates export of FGF-2. This export pathway is specific for the 18-kD isoform of FGF-2, is resistant to the anti-Golgi effects of Brefeldin A, and is energy-dependent. In FGF-2-transfected COS-1 cells, this ER/Golgi-independent pathway appears to be constitutively active and functions to quantitatively export metabolically-labeled 18-kD FGF-2. Co-transfection and co-immunoprecipitation experiments, using a vector encoding the cytoplasmic protein neomycin phosphotransferase, further demonstrated the selectivity of this export pathway for FGF-2. When neomycin phosphotransferase was appended to the COOH-terminus of 18-kD FGF-2, the chimera was exported. However, the transmembrane anchor sequence of the integral membrane glycoprotein (G protein) of vesicular stomatitis virus (VSV) blocked export. The chimeric protein localized to the plasma membrane with its FGF-2 domain extracellular and remained cell-associated following alkaline carbonate extraction. Taken together, the data suggest that FGF-2 is "exported" from cells via a unique cellular pathway, which is clearly distinct from classical signal peptide-mediated secretion. This model system provides a basis for the development and testing of therapeutic agents which may block FGF-2 export. Such an intervention may be of considerable use for the treatment of angiogenesis-dependent diseases involving FGF-2.
Crystallography & NMR System: A New Software Suite for Macromolecular Structure Determination (1998)

A new software suite, called Crystallography & NMR System (CNS), has been developed for macromolecular structure determination by X-ray crystallography or solution nuclear magnetic resonance (NMR) spectroscopy. In contrast to existing structure-determination programs, the architecture of CNS is highly flexible, allowing for extension to other structure-determination methods, such as electron microscopy and solid-state NMR spectroscopy. CNS has a hierarchical structure: a high-level hypertext markup language (HTML) user interface, task-oriented user input files, module files, a symbolic structure-determination language (CNS language), and low-level source code. Each layer is accessible to the user. The novice user may just use the HTML interface, while the more advanced user may use any of the other layers. The source code will be distributed, thus source-code modification is possible. The CNS language is sufficiently powerful and flexible that many new algorithms can be easily implemented in the CNS language without changes to the source code. The CNS language allows the user to perform operations on data structures, such as structure factors, electron-density maps, and atomic properties. The power of the CNS language has been demonstrated by the implementation of a comprehensive set of crystallographic procedures for phasing, density modification and refinement. User-friendly task-oriented input files are available for nearly all aspects of macromolecular structure determination by X-ray crystallography and solution NMR.
Parametric images of antibody pharmacokinetics in Bi213-HuM195 therapy of leukemia. (2001)

Rate images make it possible to succinctly display kinetic information about an agent's behavior over the entire acquired image.
Comparison between the different implantation orders in H+and He+coimplantation (2001)

H + and He + were implanted into single crystals in different orders (H + first or He + first). Subsequently, the samples were annealed at different temperatures from 200 C to 450 C for 1 h. Cross sectional transmission electron microscopy, Rutherford backscattering spectrometry and channelling, elastic recoil detection were employed to characterize the defects and the distribution of H and He in the samples. Furthermore, the positron traps introduced by ion implantation and annealing were characterized by slow positron annihilation spectroscopy. Both orders in the coimplantation of H and He have the ability to decreases the total implantation dose after annealing. No bubbles or voids but cracks and platelets, were observed by cross sectional transmission electron microscopy. The different implantation orders affect the density of interstitial atoms and positron traps.
Alveogenesis failure in PDGF-A-deficient mice is coupled to lack of distal spreading of alveolar smooth muscle cell progenitors during lung development (1997)

PDGF-A(-/-) mice lack lung alveolar smooth muscle cells (SMC), exhibit reduced deposition of elastin fibres in the lung parenchyma, and develop lung emphysema due to complete failure of alveogenesis. We have mapped the expression of PDGF-A, PDGF receptor-alpha, tropoelastin, smooth muscle alpha-actin and desmin in developing lungs from wild type and PDGF-A(-/-) mice of pre- and postnatal ages in order to get insight into the mechanisms of PDGF-A-induced alveolar SMC formation and elastin deposition. PDGF-A was expressed by developing lung epithelium. Clusters of PDGF-Ralpha-positive (PDGF-Ralpha+) mesenchymal cells occurred at the distal epithelial branches until embryonic day (E) 15.5. Between E16.5 and E17.5, PDGF-Ralpha+ cells multiplied and spread to acquire positions as solitary cells in the terminal sac walls, where they remained until the onset of alveogenesis. In PDGF-A(-/-) lungs PDGF-Ralpha+ cells failed to multiply and spread and instead remained in prospective bronchiolar walls. Three phases of tropoelastin expression were seen in the developing lung, each phase characterized by a distinct pattern of expression. The third phase, tropoelastin expression by developing alveolar SMC in conjunction with alveogenesis, was specifically and completely absent in PDGF-A(-/-) lungs. We propose that lung PDGF-Ralpha+ cells are progenitors of the tropoelastin-positive alveolar SMC. We also propose that postnatal alveogenesis failure in PDGF-A(-/-) mice is due to a prenatal block in the distal spreading of PDGF-Ralpha+ cells along the tubular lung epithelium during the canalicular stage of lung development.
Toward a neurobiology of temporal cognition: advances and challenges (1997)

A rich tradition of normative psychophysics has identified two ubiquitous properties of interval timing: the scalar property, a strong form of Weber's law, and ratio comparison mechanisms. Finding the neural substrate of these properties is a major challenge for neurobiology. Recently, advances have been made in our understanding of the brain structures important for timing, especially the basal ganglia and the cerebellum. Surgical intervention or diseases of the cerebellum generally result in increased variability in temporal processing, whereas both clock and memory effects are seen for neurotransmitter interventions, lesions and diseases of the basal ganglia. We propose that cerebellar dysfunction may induce deregulation of tonic thalamic tuning, which disrupts gating of the mnemonic temporal information generated in the basal ganglia through striato-thalamo-cortical loops.
Biopolymers: overview of several properties and consequences on their applications (2002)

Recently, interest in composite manufacturing has shifted towards the use of natural fibres as reinforcement because of their environmental benefits. The use of a biodegradable matrix is worth considering since this would result in a completely biodegradable composite. In order to assess the most suitable matrix polymer, one must know the properties of the available polymers. Since data tend to be widely scattered over many sources and are very scarce compared to the conventional polymers, it is the purpose of this article to give an overview of the most relevant properties of a range of biodegradable polymers. An overview such as the one given here may provide a useful guide in establishing the best compromise between conflicting property demands. Data are presented mostly as ranges (in tables) as well as in graphs for quick comparison reasons. One specific application (thermoplastic pultrusion with flax as reinforcement) is also studied.
Microbial Biogeography along an Estuarine Salinity Gradient: Combined Influences of Bacterial Growth and Residence Time (2004)

Shifts in bacterioplankton community composition along the salinity gradient of the Parker River estuary and Plum Island Sound, in northeastern Massachusetts, were related to residence time and bacterial community doubling time in spring, summer, and fall seasons. Bacterial community composition was characterized with denaturing gradient gel electrophoresis (DGGE) of PCR-amplified 16S ribosomal DNA. Average community doubling time was calculated from bacterial production ([(14)C]leucine incorporation) and bacterial abundance (direct counts). Freshwater and marine populations advected into the estuary represented a large fraction of the bacterioplankton community in all seasons. However, a unique estuarine community formed at intermediate salinities in summer and fall, when average doubling time was much shorter than water residence time, but not in spring, when doubling time was similar to residence time. Sequencing of DNA in DGGE bands demonstrated that most bands represented single phylotypes and that matching bands from different samples represented identical phylotypes. Most river and coastal ocean bacterioplankton were members of common freshwater and marine phylogenetic clusters within the phyla Proteobacteria, Bacteroidetes, and ACTINOBACTERIA: Estuarine bacterioplankton also belonged to these phyla but were related to clones and isolates from several different environments, including marine water columns, freshwater sediments, and soil.
Novel Polymeric Nanoparticles for Intracellular Delivery of Peptide Cargos: Antitumor Efficacy of the BCL-2 Conversion Peptide NuBCP-9 (2014)

The preclinical development of peptidyl drugs for cancer treatment is hampered by their poor pharmacologic properties and cell penetrative capabilities in vivo. In this study, we report a nanoparticle-based formulation that overcomes these limitations, illustrating their utility in studies of the anticancer peptide NuBCP-9, which converts BCL-2 from a cell protector to a cell killer. NuBCP-9 was encapsulated in polymeric nanoparticles composed of a polyethylene glycol (PEG)-modified polylactic acid (PLA) diblock copolymer (NuBCP-9/PLA-PEG) or PEG-polypropylene glycol-PEG-modified PLA-tetrablock copolymer (NuBCP-9/PLA-PEG-PPG-PEG). We found that peptide encapsulation was enhanced by increasing the PEG chain length in the block copolymers. NuBCP-9 release from the nanoparticles was controlled by both PEG chain length and the PLA molecular weight, permitting time-release over sustained periods. Treatment of human cancer cells with these nanoparticles in vitro triggered apoptosis by NuBCP-9-mediated mechanism, with a potency similar to NuBCP-9 linked to a cell-penetrating poly-Arg peptide. Strikingly, in vivo administration of NuBCP-9/nanoparticles triggered complete regressions in the Ehrlich syngeneic mouse model of solid tumor. Our results illustrate an effective method for sustained delivery of anticancer peptides, highlighting the superior qualities of the novel PLA-PEG-PPG-PEG tetrablock copolymer formulation as a tool to target intracellular proteins.
Cell types in the mouse cortex and hippocampus revealed by single-cell RNA-seq (2015)

The mammalian cerebral cortex supports cognitive functions such as sensorimotor integration, memory, and social behaviors. Normal brain function relies on a diverse set of differentiated cell types, including neurons, glia, and vasculature. Here, we have used large-scale single-cell RNA sequencing (RNA-seq) to classify cells in the mouse somatosensory cortex and hippocampal CA1 region. We found 47 molecularly distinct subclasses, comprising all known major cell types in the cortex. We identified numerous marker genes, which allowed alignment with known cell types, morphology, and location. We found a layer I interneuron expressing Pax6 and a distinct postmitotic oligodendrocyte subclass marked by Itpr2. Across the diversity of cortical cell types, transcription factors formed a complex, layered regulatory code, suggesting a mechanism for the maintenance of adult cell type identity.
Isolation, characterization and immunolocalization of a novel, modular tomato arabinogalactan‐protein corresponding to the LeAGP‐1 gene (1999)

Arabinogalactan-proteins (AGPs) are a family of hydroxy-proline-rich glycoproteins implicated to function in plant growth and development. This report focuses on a novel, modular AGP found in tomato, LeAGP-1, which was predicted by DNA cloning and herein verified at the protein level as a major AGP component. LeAGP-1 was isolated from tomato suspension-cultured cells and verified to be an AGP by precipitation with (beta-D-galactosyl)3 Yariv phenylglycoside and by amino acid composition analysis. Furthermore, LeAGP-1 was determined to correspond to LeAGP-1 clones based on three criteria: (1) amino acid composition identity, (2) amino acid sequence identity, and (3) specific immunoreactivity of glycosylated and deglycosylated LeAGP-1 with an antibody developed against the highly basic subdomain predicted from LeAGP-1 clones. The antibody was also used to immunolocalize LeAGP-1 in tomato to the cell surface of suspension-cultured cells, maturing metaxylem elements in young internodes and petioles, and stylar transmitting tissue cells. At the subcellular level, LeAGP-1 immunolocalized to the cell walls of these particular cells as well as to intercellular spaces between stylar transmitting tissue cells. LeAGP-1 now emerges as one of the most comprehensively studied AGPs in terms of (1) characterization at the genomic DNA, cDNA and protein levels, (2) known organ-specific and developmentally regulated mRNA expression patterns, (3) development of an antibody against a unique, peptide subdomain which specifically recognizes LeAGP-1 in its glycosylated and deglycosylated states, and (4) immunolocalization of a single, well-defined AGP molecule at the tissue and subcellular levels.
Boosting the free fatty acid synthesis of Escherichia coli by expression of a cytosolic Acinetobacter baylyi thioesterase (2012)

For the first time, an A. baylyi thioesterase was cloned and solubly expressed in the cytosol of E. coli. This leaderless thioesterase ('AcTesA) was found to be capable of enhancing the FFAs production of E. coli. Without detailed optimization of the strain and fermentation, the finally achieved 3.6 g/L FFAs is encouraging. In addition, 'AcTesA exhibited different substrate specificity from other thioesterases previously reported, and can be used to supply the fatty acid-based biofuels with high quality of FFAs. Altogether, this study provides a promising thioesterase for FFAs production, and is of great importance in enriching the library of useful thioesterases.
Risedronate Increases Bone Mass in an Early Postmenopausal Population: Two Years of Treatment Plus One Year of Follow-Up1 (1998)

This double-blind, placebo-controlled study was undertaken to determine 1) the efficacy of oral risedronate for prevention of bone loss in healthy, early postmenopausal patients with normal bone mass, 2) the effect on bone mass when treatment was stopped, and 3) the safety and tolerance of risedronate in this population. A group of 111 patients were randomized to oral placebo, risedronate 5 mg daily, or risedronate 5 mg cyclically, for 2 yr followed by 1 yr off treatment. Measurements included percentage change from baseline in lumbar spine bone mineral density (BMD) at 24 months; percentage change from baseline in BMD of the femoral neck, trochanteric region, and Ward's triangle region of the proximal femur; and changes in biochemical markers of bone turnover. After 2 yr, there was a mean increase in BMD of the lumbar spine of 1.4% from baseline and of 5.7% vs. placebo in the risedronate 5 mg daily group. There were decreases from baseline in BMD of 1.6% and 4.3% in the risedronate 5 mg cyclic and placebo groups, respectively. By the end of 24 months, trochanteric bone mass at the hip increased by 5.4% in the risedronate 5 mg daily group and by 3.3% in the risedronate 5 mg cyclic group vs. placebo. Bone mass was maintained at the femoral neck in the 2 active-treatment groups vs. a 2.4% mean loss with placebo. During the treatment-free follow-up, bone turnover increased toward baseline in both risedronate groups. By the end of that year, lumbar spine bone mass in all 3 groups was lower than at baseline. Oral risedronate was well tolerated. We conclude that risedronate (5 mg daily) increases bone mass and risedronate (5 mg cyclic) appears to prevent bone loss in early postmenopausal women with normal BMD.