gebhart/patrepeval huggingface dataset:
Phosphorylation-dependent interaction of osteopontin with its receptors regulates macrophage migration and activation (2002)

Neutrophil-independent macrophage responses are a prominent part of delayed-type immune and healing processes and depend on T cell-secreted cytokines. An important mediator in this setting is the phosphoprotein osteopontin, whose secretion by activated T cells confers resistance to infection by several intracellular pathogens through recruitment and activation of macrophages. Here, we analyze the structural basis of this activity following cleavage of the phosphoprotein by thrombin into two fragments. An interaction between the C-terminal domain of osteopontin and the receptor CD44 induces macrophage chemotaxis, and engagement of beta(3)-integrin receptors by a nonoverlapping N-terminal osteopontin domain induces cell spreading and subsequent activation. Serine phosphorylation of the osteopontin molecule on specific sites is required for functional interaction with integrin but not CD44 receptors. Thus, in addition to regulation of intracellular enzymes and substrates, phosphorylation also regulates the biological activity of secreted cytokines. These data, taken as a whole, indicate that the activities of distinct osteopontin domains are required to coordinate macrophage migration and activation and may bear on incompletely understood mechanisms of delayed-type hypersensitivity, wound healing, and granulomatous disease.
Control concrete sewer corrosion via the crown spray process (1996)

The crown spray process involves the spray application of a high‐pH mixture to the crown area of the sewer. The aim is to deactivate the sulfur‐ or sulfide‐oxidizing bacteria (SOB) and neutralize the acid at the sewer crown; to render the sewer crown environment unfavorable for regrowth and recolonization of SOB; to leave a residual alkalinity on the sewer crown to neutralize the acid produced as the SOB recolonize the sewer, and, consequently, control the crown corrosion process. A number of different chemicals, both hazardous and nonhazardous, were investigated for use with the process. The use of biocides as additives to enhance the deactivation potentials of the various treatment mixtures was also evaluated. To gauge the effectiveness of the treatment, surface pH of the sewer crown is measured before and after treatment. Immediately after spraying the surface, pH of the crown generally increases from less than 2 to greater than 9 and then gradually decreases with time to background levels. The mechanism of deactivation and regrowth of the organisms is discussed. Magnesium hydroxide slurry, a nonhazardous chemical, is the most effective treatment chemical tested to date. Application of a 50% slurry to the crown of a highly corroded active sewer has maintained the surface pH at or greater than 9 for approximately 9 months. Microbiological assays indicate a reduction in population of SOB from 10 7 to 10 2 cells/g of corrosion product (below detectable levels). Approximately 9 months after treatment, the number of SOB are still 1 to 2 orders of magnitude below the background population level. The operational aspects, economics, and the mechanism of the crown spray process are discussed. The data indicate the crown spray process is the most economical corrosion control technology of eight other methods previously evaluated by the districts.
γ-Secretase, Evidence for Multiple Proteolytic Activities and Influence of Membrane Positioning of Substrate on Generation of Amyloid β Peptides of Varying Length (1999)

gamma-Secretase activity is the final cleavage event that releases the amyloid beta peptide (Abeta) from the beta-secretase cleaved carboxyl-terminal fragment of the amyloid beta protein precursor (APP). No protease responsible for this highly unusual, purportedly intramembranous, cleavage has been definitively identified. We examined the substrate specificity of gamma-secretase by mutating various residues within or adjacent to the transmembrane domain of the APP and then analyzing Abeta production from cells transfected with these mutant APPs by enzyme-linked immunosorbent assay and mass spectrometry. Abeta production was also analyzed from a subset of transmembrane domain APP mutants that showed dramatic shifts in gamma-secretase cleavage in the presence or absence of pepstatin, an inhibitor of gamma-secretase activity. These studies demonstrate that gamma-secretase's cleavage specificity is primarily determined by location of the gamma-secretase cleavage site of APP with respect to the membrane, and that gamma-secretase activity is due to the action of multiple proteases exhibiting both a pepstatin- sensitive activity and a pepstatin-insensitive activity. Given that gamma-secretase is a major therapeutic target in Alzheimer's disease these studies provide important information with respect to the mechanism of Abeta production that will direct efforts to isolate the gamma-secretases and potentially to develop effective therapeutic inhibitors of pathologically relevant gamma-secretase activities.
Discrete smooth interpolation (1989)

Interpolation of a function ƒ (.) known at some data points of R P is a common problem. Many computer applications (e.g., automatic contouring) need to perform interpolation only at the nodes of a given grid. Whereas most classical methods solve the problem by finding a function defined everywhere, the proposed method avoids explicitly computing such a function and instead produces values only at the grid points. For two-dimensional regular grids, a special case of this method is identical to the Briggs method (see “Machine Contouring Using Minimum Curvature,” Geophysics 17 , 1 (1974)), while another special case is equivalent to a discrete version of thin plate splines (see J. Duchon, Fonctions Splines du type Plaque Mince en Dimention 2 , Séminaire d'analyse numérique, n 231, U.S.M.G., Grenoble, 1975; and J. Enriquez, J. Thomann, and M. Goupillot, Application of bidimensional spline functions to geophysics, Geophysics 48 , 9 (1983)).
Targeting Photoreceptors via Intravitreal Delivery Using Novel, Capsid-Mutated AAV Vectors (2013)

Development of viral vectors capable of transducing photoreceptors by less invasive methods than subretinal injection would provide a major advancement in retinal gene therapy. We sought to develop novel AAV vectors optimized for photoreceptor transduction following intravitreal delivery and to develop methodology for quantifying this transduction in vivo. Surface exposed tyrosine (Y) and threonine (T) residues on the capsids of AAV2, AAV5 and AAV8 were changed to phenylalanine (F) and valine (V), respectively. Transduction efficiencies of self-complimentary, capsid-mutant and unmodified AAV vectors containing the smCBA promoter and mCherry cDNA were initially scored in vitro using a cone photoreceptor cell line. Capsid mutants exhibiting the highest transduction efficiencies relative to unmodified vectors were then injected intravitreally into transgenic mice constitutively expressing a Rhodopsin-GFP fusion protein in rod photoreceptors (Rho-GFP mice). Photoreceptor transduction was quantified by fluorescent activated cell sorting (FACS) by counting cells positive for both GFP and mCherry. To explore the utility of the capsid mutants, standard, (non-self-complementary) AAV vectors containing the human rhodopsin kinase promoter (hGRK1) were made. Vectors were intravitreally injected in wildtype mice to assess whether efficient expression exclusive to photoreceptors was achievable. To restrict off-target expression in cells of the inner and middle retina, subsequent vectors incorporated multiple target sequences for miR181, an miRNA endogenously expressed in the inner and middle retina. Results showed that AAV2 containing four Y to F mutations combined with a single T to V mutation (quadY-F+T-V) transduced photoreceptors most efficiently. Robust photoreceptor expression was mediated by AAV2(quadY-F+T-V) -hGRK1-GFP. Observed off-target expression was reduced by incorporating target sequence for a miRNA highly expressed in inner/middle retina, miR181c. Thus we have identified a novel AAV vector capable of transducing photoreceptors following intravitreal delivery to mouse. Furthermore, we describe a robust methodology for quantifying photoreceptor transduction from intravitreally delivered AAV vectors.
Novel optical circuit suitable for wavelength division bidirectional optical amplification (1993)

A novel optical circuit is presented which is suitable for bidirectional amplification based on the wavelength division multiplexing method using an Er3+doped fibre amplifier and commercially available optical components. The optical gain characteristics for simultaneous bidirectional transmission have been experimentally clarified.
Flow cytometric immunophenotyping for hematologic neoplasms (2008)

Flow cytometric immunophenotyping remains an indispensable tool for the diagnosis, classification, staging, and monitoring of hematologic neoplasms. The last 10 years have seen advances in flow cytometry instrumentation and availability of an expanded range of antibodies and fluorochromes that have improved our ability to identify different normal cell populations and recognize phenotypic aberrancies, even when present in a small proportion of the cells analyzed. Phenotypically abnormal populations have been documented in many hematologic neoplasms, including lymphoma, chronic lymphoid leukemias, plasma cell neoplasms, acute leukemia, paroxysmal nocturnal hemoglobinuria, mast cell disease, myelodysplastic syndromes, and myeloproliferative disorders. The past decade has also seen refinement of the criteria used to identify distinct disease entities with widespread adoption of the 2001 World Health Organization (WHO) classification. This classification endorses a multiparametric approach to diagnosis and outlines the morphologic, immunophenotypic, and genotypic features characteristic of each disease entity. When should flow cytometric immunophenotyping be applied? The recent Bethesda International Consensus Conference on flow cytometric immunophenotypic analysis of hematolymphoid neoplasms made recommendations on the medical indications for flow cytometric testing. This review discusses how flow cytometric testing is currently applied in these clinical situations and how the information obtained can be used to direct other testing.
Stability and Intrinsic Fluctuations of Dissipative Cavity Solitons in Kerr Frequency Microcombs (2015)

The generation of dissipative cavity solitons is one of the most intriguing features of microresonator-based Kerr frequency combs, enabling effective mode locking of comb modes and synthesis of ultrafast pulses. With the Lugiato-Lefever model, here, we conduct detailed theoretical investigations on the transient dynamics of dissipative cavity solitons and describe how several intrinsic effects of the Kerr comb disturb the stability of cavity solitons, including soliton breathing, higher order dispersion, dispersive wave emission, and cavity mode coupling. Our results and analysis agree well with recent measurements and provide insight into some as yet unexplained observations.
In Vitro and In Vivo Mechanisms of Action of the Antiproliferative and Immunosuppressive Agent, Brequinar Sodium (1998)

Intracellular pyrimidine nucleotides (PyN) can be synthesized de novo from glutamine, CO2, and ATP, or they can be salvaged from preformed pyrimidine nucleosides. The antiproliferative and immunosuppressive activities of brequinar sodium (BQR) are thought to be due to the inhibition of the activity of dihydroorotate dehydrogenase, which results in a suppression of de novo pyrimidine synthesis. Here we describe the effects of the pyrimidine nucleoSide, uridine, on the antiproliferative and immunosuppressive activities of BQR. In vitro reduction of PyN levels in Con A-stimulated T cells and inhibition of cell proliferation by low concentrations of BQR (< or =65 microM) are reversed by uridine. However, uridine is unable to reverse the effects of high concentrations of BQR (> or =65 microM). The ability of BQR to induce anemia in BALB/c mice is prevented by the coadministration of uridine. In contrast, the immunosuppressive activity of BQR is unaffected by similar doses of uridine. PyN levels in the bone marrow, but not in the spleen, are depressed in mice treated with BQR. These observations suggest that the induction of anemia by BQR is due to depletion of intracellular PyN in hemopoietic stem cells located in the bone marrow. They also suggest that the mechanism of immunosuppression by BQR may be only marginally dependent on depletion of intracellular PyN in lymphocytes located in the periphery. We report a novel activity of BQR: inhibition of tyrosine phosphorylation, and hypothesize that the immunosuppressive activity may be due, in part, to this unsuspected ability of BQR to inhibit tyrosine phosphorylation in lymphocytes.
Role of the YadA protein in prevention of opsonization of Yersinia enterocolitica by C3b molecules (1993)

When mixed with normal human serum, wild-type pathogenic Yersinia enterocolitica, previously incubated at 37 degrees C, fixed less C3b than its variant cured of the virulence plasmid pYV. Mutants unable to secrete the Yop proteins were still protected against C3b deposition. By contrast, mutants deficient in the production of outer membrane protein YadA fixed more C3b than their YadA+ parent. Gene yadA, cloned as a minimal polymerase chain reaction fragment and introduced in trans, complemented the mutations. Production of YadA by recombinant Escherichia coli LK111 also resulted in a reduction of the amount of C3b deposited on the bacterial surface. The reduction of C3b at the surface of Y. enterocolitica YadA+ compared with YadA- cells correlated with an increase of the amount of factor H fixed at the bacterial surface. The YadA monomer separated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and transferred to a nitrocellulose membrane was able to bind factor H. We conclude that factor H bound to YadA reduces the C3b deposition on the bacterial surface, probably by a rapid inactivation of C3b.
Silica-Supported TEMPO Catalysts:  Synthesis and Application in the Anelli Oxidation of Alcohols (2001)

The application of silica-supported TEMPO as a recyclable catalyst in the Anelli oxidation of alcohols is reported. The catalyst is easily obtained in a one-step reductive amination procedure starting from a commercially available aminopropyl-functionalized silica. Details of the synthesis of the supported catalyst and its analysis by MAS NMR are presented. Various alcohol oxidations according to the Anelli protocol have been carried out and the stability of the applied silica-supported TEMPO has been studied.
Comparative Analysis of Noncoding Regions of 77 Orthologous Mouse and Human Gene Pairs (1999)

A data set of 77 genomic mouse/human gene pairs has been compiled from the EMBL nucleotide database, and their corresponding features determined. This set was used to analyze the degree of conservation of noncoding sequences between mouse and human. A new alignment algorithm was developed to cope with the fact that large parts of noncoding sequences are not alignable in a meaningful way because of genetic drift. This new algorithm, DNA Block Aligner (DBA), finds colinear-conserved blocks that are flanked by nonconserved sequences of varying lengths. The noncoding regions of the data set were aligned with DBA. The proportion of the noncoding regions covered by blocks >60% identical was 36% for upstream regions, 50% for 5' UTRs, 23% for introns, and 56% for 3' UTRs. These blocks of high identity were more or less evenly distributed across the length of the features, except for upstream regions in which the first 100 bp upstream of the transcription start site was covered in up to 70% of the gene pairs. This data set complements earlier sets on the basis of cDNA sequences and will be useful for further comparative studies. [This paper contains supplementary data that can be found at http://www.genome.org [corrected]].
Cultivation of hepatitis C virus in primary hepatocyte culture from patients with chronic hepatitis C results in release of high titre infectious virus (1996)

To investigate the viral replication cycle and genomic heterogeneity of hepatitis C virus (HCV), we established an HCV cultivation system by using a primary hepatocyte culture from patients with chronic hepatitis C. Liver tissue was obtained by needle biopsy or surgery, then hepatocytes were isolated by collagenase digestion. After several weeks, we determined the HCV RNA titre of the cultured cells and supernatant by a competitive polymerase chain reaction (PCR) method. A significant amount of HCV RNA was observed in the cells and supernatant during cultivation. Negative-strand RNA, regarded as a marker of viral replication, could be detected by a strand-specific reverse transcription PCR method and the HCV core protein could be detected by immunofluorescence microscopy. Many HCV particles released into the supernatant were infectious. In addition, we compared the nucleotide sequences in the E2/NS1 region of pre- and post-cultivation hepatocytes for 8 weeks. At the beginning of the culture period, three major HCV types containing two subtypes were isolated. Following cultivation, the same types were isolated from the cultured hepatocytes in the same ratio as prior to cultivation. We could detect the same clones in this patient's serum, but in vivo we observed genetic variability over a 6 month interval. One clone detected throughout the 6 month period mutated extensively in the hypervariable region. These results indicated that HCV can replicate in cultured hepatocytes, and that infectious virions are released into the supernatant. This cultivation system should facilitate the study of HCV genomic heterogeneity, infection and replication.
Reactions of co-ordinated ligands. Part 10. Rhodium-catalysed cyclisation of 3-(2-fluorophenyl)propanols to chromans (1984)

The cyclisation of several 3-(2-fluorophenyl)-propanols to the corresponding chroman occurs in nitromethane–acetone solution at 80 °C when either the hexafluorophosphate (3) or tetrafluoroborate salt (4) of the (η5-ethyltetramethylcyclopentadienyl)(η6-benzene)rhodium(III) cation is used as a catalyst; the former salt is the more effective catalyst. The cyclisation is believed to involve the activation of the aryl fluoride (towards intramolecular nucleophilic substitution by the hydrpxy group) by the formation of a metal complex in which the aryl fluoride is π-bonded with the metal cation. It is suggested that the arene-exchange reaction which gives this π-bonded complex proceeds faster with the salt (3) than with the salt (4), and that this is the main factor for the greater efficiency of the former salt as a cyclisation catalyst.
A Use of Double Integration in Sigma Delta Modulation (1985)

Sigma delta modulation is viewed as a technique that employs integration and feedback to move quantization noise out of baseband. This technique may be iterated by placing feedback loop around feedback loop, but when three or more loops are used the circuit can latch into undesirable overloading modes. In the desired mode, a simple linear theory gives a good description of the modulation even when the quantization has only two levels. A modulator that employs double integration and two-level quantization is easy to implement and is tolerant of parameter variation. At sampling rates of 1 MHz it provides resolution equivalent to 16 bit PCM for voiceband signals. Digital filters that are suitable for converting the modulation to PCM are also described.
NONSEGMENTED NEGATIVE-STRAND RNA VIRUSES: Genetics and Manipulation of Viral Genomes (1998)

Protocols to recover negative-stand RNA viruses entirely from cDNA have been established in recent years, opening up this virus group to the detailed analysis of molecular genetics and virus biology. The unique gene-expression strategy of nonsegmented negative-strand RNA viruses, which involves replication of ribonucleoprotein complexes and sequential synthesis of free mRNAs, has also allowed the use of these viruses to express heterologous sequences. There are advantages in terms of easy manipulation of constructs, high capacity for foreign sequences, genetically stable expression, and the possibility of adjusting expression levels. Fascinating prospects for biomedical applications and transient gene therapy are offered by chimeric virus vectors carrying novel envelope protein genes and targeted to defined host cells.
Relationship between metamorphism and ore formation at the Sukhoi Log gold deposit hosted in black slates from the data of U-Th-Pb isotopic SHRIMP-dating of accessory minerals (2011)

The formation conditions and age of the Sukhoi Log gold deposit are considered on the basis of new isotopic-geochemical data. The U-Pb isotopic study of zircon and monazite from high-grade ore and host black slates at the Sukhoi Log deposit was carried out with SIMS technique using a SHRIMP II instrument. Two generations of monazite are distinguished on the basis of optical and scanning electron microscopy, cathodoluminescence, and micro X-ray spectroscopy. Monazite I is characterized by black opaque porphyroblasts with microinclusions of minerals pertaining to metamorphic slates and structural attributes of pre- and synkinematic formation. Monazite II occurs only within the ore zone as transparent crystals practically free of inclusions and as rims around monazite I. The REE contents are widely variable in both generations. Porphyroblastic monazite I differs in low U and Th (0.01–0.7 wt % ThO2) contents, whereas transparent monazite II contains up to 4 wt % ThO2. The average weighted U-Pb isotopic age of monazite I is 650 ± 8.1 Ma (MSWD = 1.6; n = 9) and marks the time of metamorphism or catagenesis. The U-Pb age estimates of synore monazite II cover the interval of 486 ± 18 to 439 ± 17 Ma. Zircons of several populations from 0.5 to 2.6 Ga in age are contained in the ore. Most detrital zircon grains have porous outer rims composed of zircon and less frequent xenotime with numerous inclusions of minerals derived from slates. The peaks of 206Pb/238U ages in the most abundant zircon populations fall on 570 and 630 Ma and correspond to the age of newly formed metamorphic mineral phases. The discordant isotopic ages indicate that the U-ThPb isotopic system of ancient detrital zircons was disturbed 470–440 Ma ago in agreement with isotopic age of monazite II and the Rb-Sr whole -rock isochron age of black slates (447 ± 6 Ma). The new data confirm the superimposed character of the gold-quartz-sulfide mineralization at the deposit. Black shales of the Khomolkho Formation of the Bodaibo Synclinorium were affected by metamorphism over a long period; the peaks of metamorphism and catagenesis are dated at 570 and 650–630 Ma. The high-temperature ore formation was probably related to a hidden granitic pluton emplaced 450–440 Ma ago, that is, 200 Ma later than the events of greenschist metamorphism. Hercynian granitoid magmatism (320–270 Ma) did not exert a substantial effect on the U-Th-Pb isotopic system in accessory minerals from the ore and could not have been a major source of ore-forming fluids.