gebhart/patrepeval huggingface dataset:
A cytochrome P450-like gene possibly involved in oleandomycin biosynthesis byStreptomyces antibioticus (1995)

A cosmid clone from an oleandomycin producer, Streptomyces antibioticus, contains a large open reading frame encoding a type I polyketide synthase subunit and an oleandomycin resistance gene (oleB). Sequencing of a 1.4-kb DNA fragment adjacent to oleB revealed the existence of an open reading frame (oleP) encoding a protein similar to several cytochrome P450 monooxygenases from different sources, including the products of the eryF and eryK genes from Saccharopolyspora erythraea that participate in erythromycin biosynthesis. The oleP gene was expressed in Escherichia coli as a fusion protein to a maltose-binding protein. Using polyclonal antibodies against this fusion protein it was observed that the synthesis of the cytochrome P450 was in parallel to that of oleandomycin. The cytochrome P450 encoded by the oleP gene could be responsible for the epoxidation of carbon 8 of the oleandomycin lactone ring.
Solving Elliptic Finite Element Systems in Near-Linear Time with Support Preconditioners (2004)

We consider linear systems arising from the use of the finite element method for solving scalar linear elliptic problems. Our main result is that these linear systems, which are symmetric and positive semidefinite, are well approximated by symmetric diagonally dominant matrices. Our framework for defining matrix approximation is support theory. Significant graph theoretic work has already been developed in the support framework for preconditioners in the diagonally dominant case, and in particular it is known that such systems can be solved with iterative methods in nearly linear time. Thus, our approximation result implies that these graph theoretic techniques can also solve a class of finite element problems in nearly linear time. We show that the support number bounds, which control the number of iterations in the preconditioned iterative solver, depend on mesh quality measures but not on the problem size or shape of the domain.
Ras-induced ROS upregulation affecting cell proliferation is connected with cell type-specific alterations of HSF1/SESN3/p21Cip1/WAF1pathways (2013)

Oncogenes of the RAS family regulate many of the cell's activities, including proliferation, survival and differentiation. Activating mutations in these genes are common events for many types of cancer. One of the contradictory points concerning the biological significance of Ras activation is its dual effect (pro- or anti-proliferative) on cell reproduction. One of mechanisms by which Ras proteins influence cell growth is a regulation of intracellular level of reactive oxygen species (ROS), second messengers affecting variety of cellular processes including cell proliferation. Recently it was shown that repression of SESN1 and SESN3 genes, whose protein products control regeneration of peroxiredoxins, can play a critical role in Ras-induced ROS upregulation. In the present study we have found that Ras-induced repression of SESN3 expression and ROS upregulation is mediated via the modifications of transcriptional activity of HSF1. Interestingly, mutant Ras overexpression altered the activity of HSF1 in opposite directions in different cell contexts, in particular in human normal fibroblasts and HaCaT immortalized keratinocytes, but these opposite changes caused similar repression of SESN3 expression followed by elevation of ROS content and inhibition of cell proliferation in corresponding cell types. The inhibitory effect on cell proliferation was mediated by upregulation of p21(Cip1/WAF1). Thus, HSF1/SESN3/ROS/p21(Cip1/WAF1)-mediated deceleration of cell growth may contribute to cell defense systems protecting the organism from excessive proliferation of cells that overexpress activated Ras oncoproteins.
Yeast Aldehyde Dehydrogenase (1968)

Abstract Homogeneous preparations of the potassium-requiring yeast aldehyde dehydrogenase are active with either DPN or TPN in the oxidation of a wide variety of aldehydes. Exogenous mercaptan is not a requirement for catalytic activity. The enzyme is denatured in 6 m guanidine hydrochloride to form a protein species with a molecular weight somewhat greater than 21,000. The denatured protein may be reassociated to yield functional enzyme of higher molecular weight.
Expression of matrix metalloprotease-9 in vascular pericytes in human breast cancer. (1997)

Matrix metalloprotease-9 (MMP-9; 92-kd type IV collagenase, gelatinase B) is regarded as important for degradation of the basement membrane and extracellular matrix during cancer invasion and other tissue-remodeling events. Expression of MMP-9 was analyzed in 22 cases of human ductal breast cancer by immunohistochemistry and in 8 of these cases also by in situ hybridization. For immunohistochemistry we used affinity-purified polyclonal antibodies as well as a MMP-9-specific monoclonal antibody (clone 6-6B). Three different stromal cell types with a positive MMP-9 immunoreaction were identified morphologically: neutrophils and macrophage-like cells in all cases and vascular cells in 16 of 22 cases. Double immunofluorescence with antibodies to CD68 conclusively demonstrated MMP-9 expression in macrophages. To identify the positive vascular cells, we employed antibodies to von Willebrand factor and PAL-E for identification of endothelial cells, high molecular weight melanoma-associated antigen for pericytes, and alpha-smooth muscle actin for vascular smooth muscle cells. Using conventional and confocal double immunofluorescence microscopy, colocalization of MMP-9 was seen with high molecular weight melanoma-associated antigen, the pericyte marker, whereas little or no coexpression was seen with alpha-smooth muscle actin. Virtually no coexpression was seen with the endothelial cell markers PAL-E and von Willebrand factor. In situ hybridization showed that MMP-9 mRNA colocalized with MMP-9 immunoreactivity in macrophages and vascular structures, whereas no MMP-9 mRNA was detected in neutrophils. No MMP-9 immunostaining or in situ hybridization signal was detected in cancer cells in any of the cases. Based on these results, it is concluded that MMP-9 in human breast cancer is located in tumor-infiltrating stromal cells, including neutrophils, macrophages, and vascular pericytes, and that the latter two cell types also produce this metalloprotease. We suggest that the MMP-9 produced in pericytes may play a role in extracellular matrix degradation during tumor angiogenesis.
Functional interpretation of non‐coding sequence variation: Concepts and challenges (2013)

Understanding the functional mechanisms underlying genetic signals associated with complex traits and common diseases, such as cancer, diabetes and Alzheimer's disease, is a formidable challenge. Many genetic signals discovered through genome-wide association studies map to non-protein coding sequences, where their molecular consequences are difficult to evaluate. This article summarizes concepts for the systematic interpretation of non-coding genetic signals using genome annotation data sets in different cellular systems. We outline strategies for the global analysis of multiple association intervals and the in-depth molecular investigation of individual intervals. We highlight experimental techniques to validate candidate (potential causal) regulatory variants, with a focus on novel genome-editing techniques including CRISPR/Cas9. These approaches are also applicable to low-frequency and rare variants, which have become increasingly important in genomic studies of complex traits and diseases. There is a pressing need to translate genetic signals into biological mechanisms, leading to prognostic, diagnostic and therapeutic advances.
New Ideas for Old Dams: Developing Solutions for a Shrinking Colorado River (2008)

The objective of this article is to discuss the need for a comprehensive and public review of alternative management options for the Colorado River system in the future. Due to the institutional and physical complexity of the basin, this analysis should be accomplished through the use of the National Environmental Policy Act of 1969 (“NEPA”) and incorporating the requirements of the Endangered Species Act of 1973 (“ESA”). We believe this review is necessary due to requirements of the ESA, impacts to the Colorado River delta, and increasing concerns related to the changing climate.
Cloning and characterization of a cDNA for murine macrophage inflammatory protein (MIP), a novel monokine with inflammatory and chemokinetic properties. (1988)

In the course of studies on cachectin/TNF being conducted in our laboratory, a novel macrophage product has been detected and characterized. Termed macrophage inflammatory protein or MIP, this protein appears to be an endogenous mediator of the inflammatory events induced by endotoxin. A cDNA cloned probe for this protein has been isolated from a lambda gt10 phage library prepared from poly(A)+ RNA obtained of endotoxin-induced RAW264.7 cells. The sequence codes for a 92 amino acid-long polypeptide, of which 69 amino acids correspond to the mature product. The sequence predicts a molecular weight of 7,889 and structural analysis of the protein indicates a characteristic signal sequence alpha-helix and a hydrophobic core. Sequence data also confirm no sequence similarity to any other protein listed in the Dayhoff data base.
Brief Communication: Immunotherapy of Cancer: Tumor Suppression and Regression by Cell Walls of Mycobacterium phlei Attached to Oil Droplets2 (1975)

Components of mycobacterial cell wall(s) (CW) attached to oil droplets were evaluated for their ability 1) to inhibit the growth of line-10 tumor transplants in the skin of syngeneic guinea pigs when inoculated together with 10(6) tumor cells (suppression experiments) and 2) to regress established 7-day-old intradermal tumors and eradicate microscopic lymph node metastases upon injection into the tumors (regression experiments). CW and cell-wall skeleton (CWS) preparations from Mycobacterium phlei, a fast-growing saprophyte of group IV of the atypical mycobacteria, suppressed tumor growth in essentially all animals when 37.5-mug doses were administered; at a dose of 300 mug, they cured 50-60% of the animals in regression tests. The addition of 300 mug of a purified trehalose mycolate, isolated from M. tuberculosis strain Aoyama B, to 300 mug M. phlei CW or CWS preparations significantly increased their tumor regressive potency to provide cure rates to about 90%. Because M. phlei can be propagated more readily, it can be used advantageously in place of BCG to prepare stable, non-living immunologic adjuvants of defined composition and consistently high potency to meet the need for standards with minimal residual malignant disease.
Comparison of three different PCR methods for detection ofBrucellaspp. in human blood samples (2002)

In the diagnosis of human brucellosis, PCR could be a more sensitive technique than blood cultures and more specific than conventional serological tests. We compared three different PCR methods for the detection of Brucella spp. and we studied whether human genomic DNA affect the sensitivity of three primer pairs for the detection of Brucella DNA in a peripheral-blood PCR assay. These three pairs of primers amplified three different fragments included in: (i). a gene encoding a 31-kDa Brucella abortus antigen (primers B4/B5), (ii). a sequence 16S rRNA of B. abortus (primers F4/R2), and (iii). a gene encoding an outer membrane protein (omp-2) (primers JPF/JPR). The three primers assayed showed a difference in sensitivity for detecting purified Brucella DNA, ranging between 8 fg and 20 pg. However, the sensitivity of the primers F4/R2 and B4/B5 was affected by the presence of human DNA while the primers JPF/JPR were not. Therefore, although the sensitivity of PCR using primers F4/R2 is affected by human DNA, they are still the most sensitive and they could provide a useful tool for the diagnosis of human brucellosis.
Pathology of Pulmonary Parasitic Migration: Morphological and Bronchoalveolar Cellular Responses Following Nippostrongylus brasiliensis Infection in Rats (1991)

Nippostrongylus brasiliensis has an obligatory migratory phase through the lungs during its development in rats. This migration is associated with marked tissue damage and pronounced cellular reaction. Given that cells from the lower respiratory tract, especially alveolar macrophages, can adhere to and kill larvae of N. brasiliensis in vitro, we studied the time course of morphological changes associated with parasitic migration. Compared to a primary infection, a secondary infection resulted in significant changes in the pulmonary tissue characterized by an early acute inflammation leading to granulomatous reaction in the parenchyma and a leucocytosis in the bronchoalveolar lavage fluids with an anamnestic increase in absolute numbers of neutrophils, alveolar macrophages, eosinophils, and lymphocytes. Scanning electron microscopy showed that inflammatory cells, especially alveolar macrophages, granulocytes, lymphocytes, erythrocytes, and platelets, adhered to the larvae following secondary infection and this adhesion was associated with disruption of cuticular surface in some larvae. Secondary infection also resulted in retention of larvae in granulomatous lesions in the lungs even up to 21 days postinfection. There was mast cell and type II pneumocyte hyperplasia and these cells appeared to be activated. Thus, the histopathological changes in lungs correlated with the bronchoalveolar cellular responses and further document the inflammatory and immunological reactions during the migration of N. brasiliensis larvae.
A Study on the Strain Analysis of Plane by Electronic Speckle Pattern Interferometry(ESPI) (1994)

Electronic speckle pattern interferometry(ESPI) using a CW laser, a video system and an image processor were applied to the in-plane displacement measurements. Unlike traditional strain gauges or Moire method, ESPI method requires no special surface preparation or attachments and it can be measured in-plane displacement without any contact and real time. In this experiment, specimen was loaded in paralled with a loa cell. The specimen was plance to which strain gauges was attached. The study provides an example of how ESPI have been used to measure displacement and strain distribution in this specimen. The results measured by ESPI were compared with the data which were measured by strain gauge method in tensile testing.
DNA microarray analyses of genes regulated during the differentiation of embryonic stem cells (2000)

Embryonic stem (ES) cells are derived from the inner cell mass of blastocysts, and in response to retinoic acid (RA) are induced to differentiate to form some of the first distinguishable cell types of early mammalian development. This makes ES cells an attractive model system for studying the initial developmental decisions that occur during embryogenesis and the molecular genetics and associated mechanisms underlying these decisions. Additionally, ES cells are of significant interest to those characterizing various gene functions utilizing transgenic and gene-targeting techniques. With the advent of DNA microarray technology, which allows for the study of expression patterns of a large number of genes simultaneously within a cell type, there is an efficient means of gaining critical insights to the expression, regulation, and function of genes involved in mammalian development for which information is not currently available. To this end, we have utilized Clontech's Atlas Mouse cDNA Expression Arrays to examine the expression of 588 known regulatory genes in D3 ES cells and their RA-induced differentiated progeny. We report that nearly 50% of the regulatory genes are expressed in D3 and/or D3-differentiated cells. Of these genes, the steady-state levels of 18 are down-regulated and 61 are up-regulated by a factor of 2.5-fold or greater. These changes in gene expression are highly reproducible and represent changes in the expression of a variety of molecular markers, including: transcription factors, growth factors and their receptors, cytoskeletal and extracellular matrix proteins, cell surface antigens, and intracellular signal transduction modulators and effectors.
International definition of Devonian System boundaries (2015)

Since 1960 three committees of the International Union of Geological Sciences have been considering international definition of the base, top and subdivisions of the Devonian System. Agreement on these has either been achieved or is imminent. The committees have travelled to many countries and met a fascinating range of problems relating to international correlation and many personal, national and scientific considerations have been discussed. Extraordinary evidence of the diverse use of so-called standard subdivisions of the Devonian have been uncovered as a result of refined global correlation. A review is given of the new definitions and how these will apply to the rocks of south-west England, on the basis of which the Devonian System was founded in 1839.
Some mismatch repair activities in Escherichia coli. (1988)

Heterozygous bacteriophage lambda DNA molecules, whose replication requires mismatch correction of a mutant nucleotide in the transcribed strand, provide an assay for localized mismatch repair in Escherichia coli. We describe two systems: one removes the A in C.A or G.A mismatches and the other removes one or the other C in a C.C mismatch. Mutations disabling the first system result in a mutator phenotype that may be identical to mutY.
DC-SIGN ligation on dendritic cells results in ERK and PI3K activation and modulates cytokine production (2006)

The generation of pathogen-specific immune responses is dependent on the signaling capabilities of pathogen-recognition receptors. DC-SIGN is a C-type lectin that mediates capture and internalization of viral, bacterial, and fungal pathogens by myeloid dendritic cells. DC-SIGN-interacting pathogens are thought to modulate dendritic cell maturation by interfering with intracellular signaling from Toll-like receptor molecules. We report that engagement of DC-SIGN by specific antibodies does not promote dendritic cell maturation but induces ERK1/2 and Akt phosphorylation without concomitant p38MAPK activation. DC-SIGN ligation also triggers PLCgamma phosphorylation and transient increases in intracellular calcium in dendritic cells. In agreement with its signaling capabilities, a fraction of DC-SIGN molecules partitions within lipid raft-enriched membrane fractions both in DC-SIGN-transfected and dendritic cells. Moreover, DC-SIGN in dendritic cells coprecipitates with the tyrosine kinases Lyn and Syk. The relevance of the DC-SIGN-initiated signals was demonstrated in monocyte-derived dendritic cells, as DC-SIGN cross-linking synergizes with TNF-alpha for IL-10 release and enhances the production of LPS-induced IL-10. These results demonstrate that DC-SIGN-triggered intracellular signals modulate dendritic cell maturation. Since pathogens stimulate Th2 responses via preferential activation of ERK1/2, these results provide a molecular explanation for the ability of DC-SIGN-interacting pathogens to preferentially evoke Th2-type immune responses.
Polyethylene glycol-mediated bacterial colony transformation. (1995)

A moderately efficient and quick method of bacterial colony transformation is described. Plasmid DNA was added to bacteria suspended in a solution of polyethylene glycol/calcium chloride (PEG/CaCl2). After a brief incubation and heat shock, the cells were directly plated. Transformation efficiencies up to 8.6 +/- 1.28 x 10(6) transformants per microgram of pUC18 were obtained. We have found that the reverse of the transformation process could also take place. Suspending a bacterial pellet harboring the plasmid of interest in PEG/CaCl2 results in the release of the plasmid DNA, and thus indirectly lends support to the transformation process.
Structural Studies of Lithium Intercalation in a Nanocrystalline α-Fe2O3 Compound (2005)

A nanocrystalline Fe2O3, synthesized via a low-temperature aqueous synthesis route, is reported as a cathode material for rechargeable lithium batteries. This compound possesses a structure similar to that of hematite or α-Fe2O3 with crystallites ca. 5 nm in size. The electrochemical properties of this compound are seen to be dramatically superior to those of microcrystalline α-Fe2O3, with specific capacities of 200−250 mA·h/g and energy densities of 425−500 mW·h/g at different current rates. The compound also shows excellent reversibility upon discharge/charge cycling, much improved over that reported for most microcrystalline iron oxides. Detailed structural analysis of the compound and its lithium intercalation process has been conducted via X-ray diffraction and X-ray absorption fine structure spectroscopy (XAFS), and unique features associated with the nanocrystalline compound have been observed. First, owing to the very small crystallite size and the associated structural disorder, deviations in the local structure of the nanocrystalline compound in comparison to microcrystalline α-Fe2O3 are seen. Second, the nanocrystalline compound is observed to yield much higher single-phase capacity than that of the microcrystalline α-Fe2O3. The nanocrystalline compound allows accommodation of up to 0.47 Li per Fe2O3 whereas the microcrystalline compound is known to yield single-phase capacity up to only 0.03 Li per Fe2O3. Finally, upon further discharge the nanocrystalline compound shows transformation to a substantially disordered structure that can be indexed to a cubic lattice. Isosbestic points in the XAFS data clearly show the occurrence of this phase transformation and emerge as a strong tool for determining phase transformations incipient at the local scale. This study reveals the surprising electrochemical performance of the nanocrystalline iron oxide and the underlying novel structural and mechanistic characteristics and highlights the striking contrast between nanocrystalline intercalation compounds and their microcrystalline counterparts.
Oxygen vacancies in ZnO (2005)

The electronic properties of ZnO have traditionally been explained by invoking intrinsic defects. In particular, the frequently observed unintentional n-type conductivity has often been attributed to oxygen vacancies. We report first-principles calculations showing that the oxygen vacancy VO is not a shallow donor, but has a deep ε(2+∕0) level at ∼1.0eV below the conduction band. The negative-U behavior that causes the 1+charge state to be unstable is associated with large local lattice relaxations. We present a detailed configuration coordinate diagram, which allows us to provide a detailed interpretation of recently reported ODEPR (optically detected electron paramagnetic resonance) measurements [L. S. Vlasenko and G. D. Watkins, Phys. Rev. B 71, 125210 (2005)].
Active data mining (1995)

We introduce an active data mining paradigm that combines the recent work in data mining with the rich literature on active database systems. In this paradigm, data is continuously mined at a desired frequency. As rules are discovered, they are added to a rulebase, and if they already exist, the history of the statistical parameters associated with the rules is updated. When the history starts exhibiting certain trends, specified as shape queries in the user-specified triggers, the triggers are fired and appropriate actions are initiated.

To be able to specify shape queries, we describe the constructs for defining shapes, and discuss how the shape predicates are used in a query construct to retrieve rules whose histories exhibit the desired trends. We describe how this query capability is integrated into a trigger system to realize an active mining system. The system presented here has been validated using two sets of customer data.