gebhart/patrepeval huggingface dataset:
Mutational and crystallographic analyses of the active site residues of the bacillus circulans xylanase (1994)

Using site-directed mutagenesis we have investigated the catalytic residues in a xylanase from Bacillus circulans. Analysis of the mutants E78D and E172D indicated that mutations in these conserved residues do not grossly alter the structure of the enzyme and that these residues participate in the catalytic mechanism. We have now determined the crystal structure of an enzyme-substrate complex to 108 A resolution using a catalytically incompetent mutant (E172C). In addition to the catalytic residues, Glu 78 and Glu 172, we have identified 2 tyrosine residues, Tyr 69 and Tyr 80, which likely function in substrate binding, and an arginine residue, Arg 112, which plays an important role in the active site of this enzyme. On the basis of our work we would propose that Glu 78 is the nucleophile and that Glu 172 is the acid-base catalyst in the reaction.
Influence of ovarian steroids on relaxin-induced uterine growth in ovariectomized gilts (1992)

This study examined the influence of ovarian steroids on the uterotropic actions of relaxin (RLX) in ovariectomized prepubertal gilts. Ovariectomized gilts received (im) corn oil (CO), estradiol benzoate (EB), or EB and progesterone (P) for 0-16 days. Steroid administration was patterned to approximate the plasma concentrations of endogenous ovarian steroids observed during 1) the follicular phase (EB), 2) luteal phase (EB+P), and 3) early pregnancy (EB+P+EB). Half of each group also received PBS or 0.5 mg RLX every 6 h for 54 h, coinciding with the final 2 days of the experimental period. After hysterectomy, uterine tissues were analyzed for water, dry matter, protein, DNA, glycosaminoglycans (GAGs), and collagen contents. Administration of EB or P increased uterine weight 5- to 6-fold, but no differences were observed between EB+P- and EB+P+EB-treated gilts. Cotreatment with RLX enhanced steroid-induced uterine growth 40-70%, and RLX stimulated growth in CO- and EB+CO control gilts 2- to 3-fold. The water content of uterine tissues was greater in EB-, EB+P-, and EB+P+EB-treated gilts than in their respective controls, and this response was augmented by RLX in all treatment groups. Administration of steroids stimulated a 4- to 5-fold increase in uterine dry weight compared to that in controls, with responses not differing between EB+P- and EB+P+EB-treated gilts. In all groups, RLX increased uterine dry weight. Protein and DNA contents of uterine tissue increased with steroid treatment, but neither variable differed between EB+P- and EB+P+EB-treated gilts. Administration of RLX, alone or in combination with steroids, increased protein and DNA contents of uterine tissues. The tissue content of GAGs increased in response to steroids, and coadministration of RLX did not alter this response. Although the uterine tissue concentration of collagen was reduced in steroid- and RLX-treated gilts, the collagen content of the uterus was not affected by the various treatments. The results of this study indicate that RLX is a potent stimulator of uterine growth under a variety of steroidal environments. RLX- or steroid-induced uterine growth was manifest by increased water, dry matter, protein, and DNA and GAG contents, but the uterine content of collagen was not affected. The overall growth-promoting effects of EB and the stimulation of DNA accretion by RLX were not observed when gilts were cotreated with P.(ABSTRACT TRUNCATED AT 400 WORDS)
Stereocontrolled and Versatile Total Synthesis of Bispyrrolidinoindoline Diketopiperazine Alkaloids: Structural Revision of the Fungal Isolate (+)‐Asperdimin (2009)

Homo- and heterodimeric bispyrrolidinoindoline diketopiperazine alkaloids have been synthesized following a concise, versatile, and stereoselective route. Highlights of the sequence are a diastereoselective construction of the C3a-bromo-hexahydropyrrolo[2,3-b]indole nucleus, its Co(I)-induced C3a-C3a' dimerization, and the twofold or sequential amide-bond formation before cyclization to the diketopiperazine of the homo- or heterodimeric alkaloids, respectively. Stereochemical diversity is achieved through the choice of the appropriate amino acids combined with the base-induced epimerization of the C2-acyl-hexahydropyrrolo[2,3-b]indole at C2. According to this strategy, the natural products (+)-WIN 64821 1, (+)-WIN 64745 2 and (+)-asperdimin 6 as well as analogues (5, 22, 32, 44) with different relative and absolute configuration have been efficiently synthesized. The flexibility of this synthetic methodology has facilitated the structural revision of the natural product (+)-asperdimin, whose structure has been corrected to diastereomer 6.
Organic Thin-Film Transistors Based on Carbonyl-Functionalized Quaterthiophenes:  High Mobility N-Channel Semiconductors and Ambipolar Transport (2005)

New carbonyl-functionalized quaterthiophenes, 5, 5' ''-diheptanoyl-2,2':5',2' ':5' ',2' ''-quaterthiophene (DHCO-4T), 5, 5' ''-diperfluorohexylcarbonyl-2,2':5',2' ':5' ',2' ''-quaterthiophene (DFHCO-4T), and 2,7-[bis-(5-perfluorohexylcarbonylthien-2-yl)]-4H-cyclopenta[2,1-b:3,4-b']-dithiophen-4-one (DFHCO-4TCO) have been synthesized and characterized. Field-effect transistors fabricated with these materials exhibit high electron mobilities both in a vacuum (up to 0.6 cm2 V-1 s-1) and in air (up to 0.02 cm2 V-1 s-1) and very high Ion:Ioff currents ratios (>107). DHCO-4T is the first organic material exhibiting excellent ambipolar transport (mue/muh up to 0.1/0.01 cm2 V-1 s-1, (Ion:Ioff)e/(Ion:Ioff)h up to 107/108 for the same device) over a broad range of deposition temperatures. These materials are therefore promising for organic complementary circuits.
Degeneration in vivo of rat hippocampal neurons by wild-type Alzheimer amyloid precursor protein overexpressed by adenovirus-mediated gene transfer. (1998)

In an attempt to elucidate the pathological implications of intracellular accumulation of the amyloid precursor protein (APP) in postmitotic neurons in vivo, we transferred APP695 cDNA into rat hippocampal neurons by using a replication-defective adenovirus vector. We first improved the efficiency of adenovirus-mediated gene transfer into neurons in vivo by using hypertonic mannitol. When a beta-galactosidase-expressing recombinant adenovirus suspended in 1 M mannitol was injected into a dorsal hippocampal region, a number of neurons in remote areas were positively stained, presumably owing to increased retrograde transport of the virus. When an APP695-expressing adenovirus was injected into the same site, part of the infected neurons in the hippocampal formation underwent severe degeneration in a few days, whereas astrocytes near the injection site showed no apparent degeneration. These degenerating neurons accumulated different epitopes of APP, and beta/A4 protein (Abeta)-immunoreactive materials were undetected in the extracellular space. A small number of degenerating neurons showed nuclear DNA fragmentation. Electron microscopic examinations demonstrated that degenerating neurons had shrunken perikarya along with synaptic abnormalities. Microglial cells/macrophages were often found in close proximity to degenerating neurons, and in some cases they phagocytosed these neurons. These results suggest that intracellular accumulation of wild-type APP695 causes a specific type of neuronal degeneration in vivo in the absence of extracellular Abeta deposition.
Associations of gut-flora-dependent metabolite trimethylamine-N-oxide, betaine and choline with non-alcoholic fatty liver disease in adults (2016)

Many studies suggest that trimethylamine-N-oxide (TMAO), a gut-flora-dependent metabolite of choline, contributes to the risk of cardiovascular diseases, but little is known for non-alcoholic fatty liver disease (NAFLD). We examined the association of circulating TMAO, choline and betaine with the presence and severity of NAFLD in Chinese adults. We performed a hospital-based case-control study (CCS) and a cross-sectional study (CSS). In the CCS, we recruited 60 biopsy-proven NAFLD cases and 35 controls (18-60 years) and determined serum concentrations of TMAO, choline and betaine by HPLC-MS/MS. For the CSS, 1,628 community-based adults (40-75 years) completed the blood tests and ultrasonographic NAFLD evaluation. In the CCS, analyses of covariance showed adverse associations of ln-transformed serum levels of TMAO, choline and betaine/choline ratio with the scores of steatosis and total NAFLD activity (NAS) (all P-trend <0.05). The CSS revealed that a greater severity of NAFLD was independently correlated with higher TMAO but lower betaine and betaine/choline ratio (all P-trend <0.05). No significant choline-NAFLD association was observed. Our findings showed adverse associations between the circulating TMAO level and the presence and severity of NAFLD in hospital- and community-based Chinese adults, and a favorable betaine-NAFLD relationship in the community-based participants.
The relative rate of aequorin regeneration from apoaequorin and coelenterazine analogues (1993)

The regeneration of an active semi-synthetic aequorin, from apoaequorin produced in cells and a coelenterazine analogue, is a key step in measuring Ca2+ in the cells. The relative rates of the regeneration of semi-synthetic aequorins from apoaequorin and 28 synthetic coelenterazine analogues were compared. The results indicated that the rate is strongly influenced by the analogues used. The regeneration of ordinary aequorin with normal coelenterazine was relatively fast (50% regeneration in 22 min), whereas the rates of regenerating semi-synthetic aequorins with coelenterazine analogues varied widely, and all were slower than that of regenerating ordinary aequorin, except for e-type coelenterazines (containing an extra ethano group). The regeneration with e-type coelenterazines was significantly faster, indicating the possible superiority of e-type analogues in the intracellular regeneration of aequorin, especially when an increased sensitivity to Ca2+ is needed.
Purification and Properties of Glycerol Kinase from Escherichia coli (1967)

1,6-diphosphate, and ATP were obtained
Maximum power supply noise estimation in VLSI circuits using multimodal genetic algorithms (2002)

This paper presents a genetic algorithm (GA) based method for finding the maximum voltage drop in the power bus of digital VLSI circuits. The worst-case voltage drop at a specified node in the power bus is defined as the fitness value for different input-vector pairs. A gate-level simulator and a sparse linear solver are applied to compute the fitness value. A sharing technique is applied to find the global optima accurately and rapidly. Comparisons with input-independent simulations for circuits extracted from layouts are used to validate our approach.
Insulin Stimulates Increased Catalytic Activity of Phosphoinositide-Dependent Kinase-1 by a Phosphorylation-Dependent Mechanism (2001)

Phosphoinositide-dependent kinase-1 (PDK-1) is a serine-threonine kinase downstream from PI 3-kinase that phosphorylates and activates other important kinases such as Akt that are essential for cell survival and metabolism. Previous reports have suggested that PDK-1 has constitutive catalytic activity that is not regulated by stimulation of cells with growth factors. We now show that insulin stimulation of NIH-3T3(IR) cells or rat adipose cells may significantly increase the intrinsic catalytic activity of PDK-1. Insulin treatment of NIH-3T3(IR) fibroblasts overexpressing PDK-1 increased both phosphorylation of recombinant PDK-1 in intact cells and PDK-1 kinase activity in an immune-complex kinase assay. Insulin stimulation of rat adipose cells also increased catalytic activity of endogenous PDK-1 immunoprecipitated from the cells. Both insulin-stimulated phosphorylation and activity of PDK-1 were inhibited by wortmannin and reversed by treatment with the phosphatase PP-2A. A mutant PDK-1 with a disrupted PH domain (W538L) did not undergo phosphorylation or demonstrate increased kinase activity in response to insulin stimulation. Similarly, a PDK-1 phosphorylation site point mutant (S244A) had no increase in kinase activity in response to insulin stimulation. Thus, the insulin-stimulated increase in PDK-1 catalytic activity may involve PI 3-kinase- and phosphorylation-dependent mechanisms. We conclude that the basal constitutive catalytic activity of PDK-1 in NIH-3T3(IR) cells and rat adipose cells can be significantly increased upon insulin stimulation.
Interaction of Rhus laccase with dioxygen and its reduction intermediates. (1980)

Reduction-oxidation of native Rhus vernicifem laccase produces specific long-lived spectral changes in the near UV and visible region.These can be attained 1) in aerobic reduction experiments, 2) from partially and fully reduced laccase molecules reacting with 0 2 , 3) by reacting peroxylaccase with 2 reduction eq, and
A nickel complex with a biscarbene pincer-type ligand shows high electrocatalytic reduction of CO2over H2O (2015)

We report a planar nickel complex coordinated with a pincer-type carbene–pyridine–carbene ligand which exhibits high selectivity for electrocatalytic CO<sub>2</sub>reduction in the presence of H<sub>2</sub>O.
Identification of Actin as a 15-Deoxy-Δ12,14-prostaglandin J2Target in Neuroblastoma Cells:  Mass Spectrometric, Computational, and Functional Approaches To Investigate the Effect on Cytoskeletal Derangement (2007)

A proteomic approach was used to identify 15-deoxy-Delta12,14-prostaglandin J2 (15d-PGJ2) protein targets in human neuroblastoma SH-SY5Y cells. By using biotinylated 15d-PGJ2, beta-actin was found as the major adducted protein; at least 12 proteins were also identified as minor biotin-positive spots, falling in different functional classes, including glycolytic enzymes (enolase and lactate dehydrogenase), redox enzymes (biliverdin reductase), and a eukaryotic regulatory protein (14-3-3gamma). 15d-PGJ2 induced marked morphological changes in the actin filament network and in particular promoted F-actin depolymerization as confirmed by Western blot analysis. By using a mass spectrometric approach, we found that 15d-PGJ2 reacts with isolated G-actin in a 1:1 stoichiometric ratio and selectively binds the Cys374 site through a Michael adduction mechanism. Computational studies showed that the covalent binding of 15d-PGJ2 induces a significant unfolding of actin structure and in particular that 15d-PGJ2 distorts the actin subdomains 2 and 4, which define the nucleotide binding sites impeding the nucleotide exchange. The functional effect of 15d-PGJ2 on G-actin was studied by polymerization measurement: in the presence of 15d-PGJ2, a lower amount of F-actin forms, as followed by the increase in pyrenyl-actin fluorescence intensity, as the major effect of increasing 15d-PGJ2 concentrations occurs on the maximum extent of actin polymerization, whereas it is negligible on the initial rate of reaction. In summary, the results here reported give an insight into the role of 15d-PGJ2 as a cytotoxic compound in neuronal cell dysfunction. Actin is the main protein cellular target of 15d-PGJ2, which specifically binds through a Michael adduction to Cys374, leading to a protein conformational change that can explain the disruption of the actin cytoskeleton, F-actin depolymerization, and impairment of G-actin polymerization.
PD‐L2:PD‐1 involvement in T cell proliferation, cytokine production, and integrin‐mediated adhesion (2005)

The B7 family member programmed death ligand 2 (PD-L2) has been implicated in both positive and negative regulation of T cell activity. In this study, we demonstrate that on human T cells, PD-L2 acts only as a negative regulator of T cell activity, inhibiting proliferation, IL-2 production, and IFN-gamma production via its interaction with programmed death-1 (PD-1). This study also shows a novel role for PD-1 in inhibiting beta1 and beta2 integrin-mediated adhesion. PD-L2 inhibition of T cell function involves modulation of the phosphoinositide 3-OH kinase (PI 3-K)/AKT and extracellular signal-related kinase (ERK)/mitogen-activated protein kinase (MAPK) pathways, with PD-L2 inhibiting anti-CD3-induced AKT phosphorylation within minutes and ERK phosphorylation after hours. Analysis of phosphatase activity of Src homology 2 domain-containing tyrosine phosphatase (SHP)-1 and SHP-2 in response to anti-CD3 mAb or anti-CD3 mAb + PD-L2 stimulation revealed that while SHP-1 phosphatase activity is not affected by stimulation, SHP-2 phosphatase activity is significantly increased by anti-CD3 mAb + PD-L2 stimulation. Anti-CD3 mAb + PD-L2 stimulation also increased the level of SHP-2 associated with the PD-1 receptor. These results suggest that catalytically active SHP-2 associated with the PD-1 receptor is involved in modulating T cell function.
Naturally Combined Photoacoustic Microscopy and Optical Coherence Tomography for Simultaneous Multimodal Imaging (2010)

A combined photoacoustic microscopy and spectral-domain optical coherence tomography is developed for simultaneous multimodal volumetric microscopic imaging of both optical absorption and scattering contrasts in biological tissues.
Stacked Patch Antenna With Dual-Polarization and Low Mutual Coupling for Massive MIMO (2016)

Massive multiple input and multiple output (MIMO) has attracted significant interests in both academia and industry. It has been considered as one of most promising technologies for 5G wireless systems. The large-scale antenna array for base stations naturally becomes the key to deploy the Massive MIMO technologies. In this communication, we present a dual-polarized antenna array with 144 ports for Massive MIMO operating at 3.7 GHz. The proposed array consists of 18 low profile subarrays. Each subarray consists of four single units. Each single antenna unit consists of one vertically polarized port and one horizontally polarized port connected to power splitters, which serve as a feeding network. A stacked patch design is used to construct the single unit with the feeding network, which gives higher gain and lower mutual coupling within the size of a conversional dual-port patch antenna. Simulation results of the proposed single antenna unit, sub-array, and Massive MIMO array are verified by measurement.
Fluorescence enhancement from Langmuir-Blodgett monolayers on silver island films (1988)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTFluorescence enhancement from Langmuir-Blodgett monolayers on silver island filmsR. Aroca, Gregory J. Kovacs, C. A. Jennings, R. O. Loutfy, and P. S. VincettCite this: Langmuir 1988, 4, 3, 518–521Publication Date (Print):May 1, 1988Publication History Published online1 May 2002Published inissue 1 May 1988https://pubs.acs.org/doi/10.1021/la00081a004https://doi.org/10.1021/la00081a004research-articleACS PublicationsRequest reuse permissionsArticle Views378Altmetric-Citations77LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-Alertsclose Get e-Alerts
Metabolism. Lysosomal amino acid transporter SLC38A9 signals arginine sufficiency to mTORC1. (2015)

The mechanistic target of rapamycin complex 1 (mTORC1) protein kinase is a master growth regulator that responds to multiple environmental cues. Amino acids stimulate, in a Rag-, Ragulator-, and vacuolar adenosine triphosphatase-dependent fashion, the translocation of mTORC1 to the lysosomal surface, where it interacts with its activator Rheb. Here, we identify SLC38A9, an uncharacterized protein with sequence similarity to amino acid transporters, as a lysosomal transmembrane protein that interacts with the Rag guanosine triphosphatases (GTPases) and Ragulator in an amino acid-sensitive fashion. SLC38A9 transports arginine with a high Michaelis constant, and loss of SLC38A9 represses mTORC1 activation by amino acids, particularly arginine. Overexpression of SLC38A9 or just its Ragulator-binding domain makes mTORC1 signaling insensitive to amino acid starvation but not to Rag activity. Thus, SLC38A9 functions upstream of the Rag GTPases and is an excellent candidate for being an arginine sensor for the mTORC1 pathway.
Conversion of metaplastic Barrett’s epithelium into post-mitotic goblet cells by γ-secretase inhibition (2010)

Barrett's esophagus (BE) affects approximately 2% of the Western population and progresses to esophageal adenocarcinoma (EAC) in 0.5% of these patients each year. In BE, the stratified epithelium is replaced by an intestinal-type epithelium owing to chronic gastroduodenal reflux. Since self-renewal of intestinal crypts is driven by Notch signaling, we investigated whether this pathway was active in the proliferative crypts of BE. Immunohistochemistry confirmed the presence of an intact and activated Notch signaling pathway in metaplastic BE epithelium, but not in the normal human esophagus. Similar observations were made in two well-known human Barrett's-derived EAC cell lines, OE33 and SKGT-5. We then sought to investigate the effects of Notch inhibition by systemic treatment with a gamma-secretase inhibitor in a well-validated rodent model for BE. As we have shown previously in normal intestinal epithelium, Notch inhibition converted the proliferative Barrett's epithelial cells into terminally differentiated goblet cells, whereas the squamous epithelium remained intact. These data imply that local application of gamma-secretase inhibitors may present a simple therapeutic strategy for this increasingly common pre-malignant condition.
Three-dimensional reconstruction of monoclonal antibody uptake in tumor and calculation of beta dose-rate nonuniformity (1994)

The several orders of magnitude improvement in calculational speed provided by the fast Fourier transform technique allowed an investigation of the effects of the calculational parameters. This investigation enabled tuning of both data acquisition and dose computation. These studies can lead to further enhancements in the calculational efficiency of three-dimensional dose-rate distributions. These improvements will allow the study of summing techniques to yield average total dose distributions.
Orchestrating serine resolvases (2010)

A remarkable feature of the serine resolvases is their regulation: the wild-type enzymes will catalyse intra- but not inter-molecular recombination, can sense the relative orientation of their sites and can exchange strands directionally, despite the fact that there is no net release of chemical bond energy. The key to this regulation is that they are only active within a large intertwined complex called the 'synaptosome'. Because substrate topology greatly facilitates (or, in other cases, inhibits) formation of the synaptosome, it acts as a 'topological filter'. Within the defined topology of the synaptosome, strand exchange releases supercoiling tension, providing an energy source to bias the reaction direction. The regulatory portion of this complex contains additional copies of the recombinase and sometimes other DNA-bending proteins. We are using a combination of X-ray crystallography, biochemistry and genetics to model the full synaptic complex and to understand how the regulatory portion activates the crossover-site-bound recombinases.