gebhart/patrepeval huggingface dataset:
Consecutive use of hormonally defined serum-free media to establish highly differentiated human renal proximal tubule cells in primary culture. (1995)

Highly differentiated human proximal tubule (HPT) cells in primary culture were established from heterogeneous suspension of tubules prepared from the human renal cortex by an original two-step procedure. First, gluconeogenic-competent HPT cells were selected by using a hormonally defined serum-free medium without glucose or insulin; then, the selected HPT cells were grown in a medium containing a low concentration of glucose (1 mM) and insulin (0.5 micrograms/mL) but no antibiotics. HPT cells grown on plastic support formed confluent, cobblestone-like monolayers with numerous mitochondria and pinocytosis vacuoles, solitary cilia, junctional complexes, and a well-developed brush border consisting of densely packed microvilli. Compared with cell monolayers on plastic support, HPT cells grown on porous filter membranes showed better morphologic differentiation. HPT cell monolayers expressed the following differentiated functions of the proximal tubule in situ: a low-affinity, high-capacity Na(+)-dependent glucose transport system inhibited by phlorizin, a high-affinity Na(+)-dependent phosphate transport system, a basolateral organic cation uptake inhibited by mepiperphenidol, parathyroid hormone-sensitive cAMP synthesis, brush-border hydrolase activities, gluconeogenesis-associated enzymes, glutathione-S-transferases and N-acetyl-beta-D-glucosaminidase. The medium containing low glucose and insulin concentrations markedly limited the increase in glycolysis but did not prevent the falls in gluconeogenesis and brush-border hydrolase activity at any time of the culture period. Similar decreases of brush border enzyme activities were obtained for HPT cells grown either on plastic or on porous filter membrane. A thorough characterization study demonstrated that this simple and preparative experimental approach makes it possible to establish highly differentiated HPT cells in primary culture suitable for investigating human renal proximal tubular cell function.
VITAMIN SYNTHESIS IN PLANTS: Tocopherols and Carotenoids (2006)

Carotenoids and tocopherols are the two most abundant groups of lipid-soluble antioxidants in chloroplasts. In addition to their many functional roles in photosynthetic organisms, these compounds are also essential components of animal diets, including humans. During the past decade, a near complete set of genes required for the synthesis of both classes of compounds in photosynthetic tissues has been identified, primarily as a result of molecular genetic and biochemical genomics-based approaches in the model organisms Arabidopsis thaliana and Synechocystis sp. PCC6803. Mutant analysis and transgenic studies in these and other systems have provided important insight into the regulation, activities, integration, and evolution of individual enzymes and are already providing a knowledge base for breeding and transgenic approaches to modify the types and levels of these important compounds in agricultural crops.
AFN-1252, a FabI Inhibitor, Demonstrates a Staphylococcus-Specific Spectrum of Activity (2009)

AFN-1252, a potent inhibitor of enoyl-acyl carrier protein reductase (FabI), inhibited all clinical isolates of Staphylococcus aureus (n = 502) and Staphylococcus epidermidis (n = 51) tested, including methicillin (meticillin)-resistant isolates, at concentrations of <or=0.12 microg/ml. In contrast, AFN-1252 was inactive (MIC(90), >4 microg/ml) against clinical isolates of Streptococcus pneumoniae, beta-hemolytic streptococci, Enterococcus spp., Enterobacteriaceae, nonfermentative gram-negative bacilli, and Moraxella catarrhalis. These data support the continued development of AFN-1252 for the treatment of patients with resistant staphylococcal infections.
Identification of novel loci involved in entry by Legionella pneumophila The GenBank accession numbers for the enh1 and enh2 loci reported in this paper are AF057703 and AF057704, respectively. (2000)

Legionella pneumophila is primarily an intracellular pathogen during infection; thus, the mechanisms of entry into host cells are likely to be important for pathogenesis. Several L. pneumophila mutants that display an enhanced-entry (Enh) phenotype were isolated by selecting for bacteria that enter host cells at a higher frequency than wild-type. In the course of characterizing the genetic basis of one of these mutants, C3, a strategy was developed for the isolation of laboratory-media-repressed virulence determinants from L. pneumophila. Screens for dominant mutations using a genomic DNA library from C3 resulted in the isolation of three cosmids that confer an Enh phenotype to wild-type L. pneumophila. Transposon mutagenesis of these cosmids allowed identification of three loci that affect entry. Analysis of the putative proteins encoded by these loci, designated rtxA and enhC, demonstrated similarity to repeats in the structural toxin protein and the secreted Sel-1 protein from Caenorhabditis elegans, respectively. L. pneumophila rtxA and enhC mutants display significantly reduced entry into host cells, compared to wild-type bacteria. The phenotype that the cosmids containing these loci confer is most likely due to elevated expression resulting from their presence on multicopy vectors. The use of increased gene copy number to overexpress genes that are normally repressed under laboratory growth conditions is generally applicable to the isolation of virulence determinants from L. pneumophila and other bacterial pathogens.
Supply chain 2.0 revisited: a framework for managing volatility-induced risk in the supply chain (2017)

Purpose The purpose of this paper is to provide an update to the Supply Chain Volatility Index (SCVI), and expand on prior work by presenting a conceptual framework illustrating how firms can deal with persistent volatility, the ensuing risk and mitigate the cost implications for their supply chain operations. Design/methodology/approach The authors use long-term time series of secondary data to assemble a “basket” of key indicators that are relevant to the business context within which global supply chains operate. The authors also report on five years of feedback gained from presentations of the SCVI to scholars and practitioners. Findings Volatility has reduced from record levels experienced during the global financial crises, yet remains at levels considerably higher than prior to the crisis, with no sign of a return to the more stable conditions that prevailed when many current supply chain networks were designed. Research limitations/implications The authors reaffirm that new mental models are needed which embrace volatility as a factor in supply chain design, rather than seek to eradicate it in supply chain operations. Traditional static “network optimisation” based on a simple definition of low unit cost seems no longer appropriate under conditions of persistent volatility. Practical implications The authors provide a conceptual link of volatility, risk and cost in the supply chain, and outline how firms can develop a supply chain strategy by managing their exposure to volatility. Originality/value The authors challenge the common assumption that volatility invariably leads to risk and higher cost in the supply chain. Instead the authors argue that the supply chain structure can mitigate the exposure to supply chain risk. The authors introduce the concepts of recovery and resilience cost within a framework designed to help firms manage volatility-induced risk by minimising the adverse cost implications of volatility in their supply chains.
Novel Peptide Ligands for Integrin 6 1 Selected from a Phage Display Library (1996)

Integrin alpha 6 beta 1 is a major adhesion receptor for the basement membrane, specifically binding to laminin-1. To identify the peptide sequences recognized by alpha 6 beta 1, we screened a 15-mer phage display library by panning with alpha 6 beta 1 purified from human placenta. DNA sequencing of 73 randomly picked phage revealed that three clones were dominantly enriched after repeated panning with alpha 6 beta 1. None of the peptide sequences displayed on these phage showed significant homology to laminin-1. A synthetic peptide modeled after the sequence displayed by one of these phage, designated P3, was found to strongly inhibit the binding of laminin-1 to alpha 6 beta 1. This inhibitory effect of the P3 peptide seems to be specific for alpha 6 beta 1, since it did not affect the binding of fibronectin to integrin alpha 5 beta 1. A synthetic peptide with a scrambled P3 amino acid sequence barely inhibited the binding of laminin-1 to alpha 6 beta 1. When coated on a substratum after conjugation with bovine serum albumin, the P3 peptide was capable of promoting cell spreading in an alpha 6 beta 1-dependent manner, although the peptide with the scrambled sequence showed activity similar to that of a control peptide. These results taken together indicate that the P3 peptide is a novel ligand for integrin alpha 6 beta 1 with potent cell spreading activity.
Targeting Tumor Endothelial Marker 8 in the Tumor Vasculature of Colorectal Carcinomas in Mice (2009)

Tumor endothelial marker 8 (TEM8) is a recently described protein that is preferentially expressed within tumor endothelium. We have developed a fusion protein that targets TEM8 and disrupts tumor vasculature by promoting localized thrombosis. Fusion protein specificity and function were evaluated using Western blot analysis, ELISA, and enzymatic assays. A xenograft model of colorectal carcinoma was used to test the efficacy of targeted and control fusion proteins. Mice treated with the gene encoding anti-TEM8/truncated tissue factor exhibited a 53% reduction in tumor volume when compared with the untreated animals (P < 0.0001; n = 10) and achieved a 49% increase in tumor growth delay by Kaplan-Meier analysis (P = 0.0367; n = 6). Immunohistochemistry confirmed tumor endothelial expression of TEM8, fusion protein homing to tumor vasculature, decrease in vessel density, and localized areas of thrombosis. These data support the hypothesis that targeting TEM8 can be an effective approach to influence tumor development by disrupting tumor vasculature.
Cloning and expression of cDNA for human endonexin II, a Ca2+ and phospholipid binding protein. (1988)

Endonexin II is a member of the family of Ca2+-dependent phospholipid binding proteins known as annexins. We cloned human endonexin II cDNA and expressed it in Escherichia coli. The apparent size and Ca2+-dependent phospholipid binding properties of purified recombinant endonexin II were indistinguishable from those of the placental protein. A single mRNA of approximately 1.6 kilobase pairs was found to be expressed in human cell lines and placenta and was in close agreement with the length of the cDNA clone (1.59 kilobase pairs). The cDNA predicted a 320-amino acid protein with a sequence that was in agreement with the previously determined partial amino acid sequence of endonexin II isolated from placenta. Endonexin II contained 58, 46, and 43% sequence identity to protein II, calpactin I (p36, protein I), and lipocortin I (p35), respectively. The partial sequence of bovine endonexin I was aligned with the sequence of endonexin II to give 63% sequence identity. Like these other proteins, endonexin II had a 4-fold internal repeat of approximately 70 residues preceded by an amino-terminal domain lacking similarity to the repeated region. It also had significant sequence identity with 67-kDa calelectrin (p68), a protein with an 8-fold internal repeat. Comparing the amino-terminal domains of these four proteins of known sequence revealed that, in general, only endonexin II and protein II had significant sequence identity (29%). Endonexin II was not phosphorylated by Ca2+/phospholipid-dependent enzyme (protein kinase C) even though it contained a threonine at a position analogous to the protein kinase C phosphorylation sites of lipocortin I, calpactin I, and protein II.
Sex Differences in Carotid Bifurcation Anatomy and the Distribution of Atherosclerotic Plaque (2001)

Sex differences in carotid bifurcation anatomy are not limited to absolute vessel size. In addition, the outflow to inflow area ratio is bigger in women, and relative to the CCA and ECA, women have larger ICAs than men. Irrespective of whether these differences are congenital or acquired, they may partly explain the sex differences that we found in the distribution of plaque and the sex differences in the prevalence of carotid atheroma in the general population.
Identification and Characterization of Two Contiguous Operons Required for Aerobactin Transport and Biosynthesis in Vibrio mimicus (2004)

In response to iron deprivation, Vibrio mimicus produces aerobactin as a major siderophore. Application of the Fur titration assay to a V. mimicus genomic DNA library followed by further cloning of the surrounding regions led to the identification of two adjacent, iron-regulated operons. One contains three genes encoding homologs of the Escherichia coli FhuCDB and the other, five genes encoding homologs of the E. coli IucABCD IutA. Construction of the V. mimicus polar disruptants in the respective operons allowed us to confirm their functions. The genetic arrangement of the aerobactin-mediated iron acquisition system in V. mimicus is unique in that the aerobactin operon (iucABCD iutA ) is contiguous to the operon (matCDB ) encoding components of an ATP-binding cassette transport system for ferric aerobactin. This is the first report demonstrating that aerobactin transport and biosynthesis genes are present in a species outside the family Enterobacteriaceae.
Guidelines for the selection of highly effective siRNA sequences for mammalian and chick RNA interference (2004)

In the present study, the relationship between short interfering RNA (siRNA) sequence and RNA interference (RNAi) effect was extensively analyzed using 62 targets of four exogenous and two endogenous genes and three mammalian and Drosophila cells. We present the rules that may govern siRNA sequence preference and in accordance with which highly effective siRNAs essential for systematic mammalian functional genomics can be readily designed. These rules indicate that siRNAs which simultaneously satisfy all four of the following sequence conditions are capable of inducing highly effective gene silencing in mammalian cells: (i) A/U at the 5' end of the antisense strand; (ii) G/C at the 5' end of the sense strand; (iii) at least five A/U residues in the 5' terminal one-third of the antisense strand; and (iv) the absence of any GC stretch of more than 9 nt in length. siRNAs opposite in features with respect to the first three conditions give rise to little or no gene silencing in mammalian cells. Essentially the same rules for siRNA sequence preference were found applicable to DNA-based RNAi in mammalian cells and in ovo RNAi using chick embryos. In contrast to mammalian and chick cells, little siRNA sequence preference could be detected in Drosophila in vivo RNAi.
p53-dependent chemokine production by senescent tumor cells supports NKG2D-dependent tumor elimination by natural killer cells (2013)

The induction of cellular senescence is an important mechanism by which p53 suppresses tumorigenesis. Using a mouse model of liver carcinoma, where cellular senescence is triggered in vivo by inducible p53 expression, we demonstrated that NK cells participate in the elimination of senescent tumors. The elimination of senescent tumor cells is dependent on NKG2D. Interestingly, p53 restoration neither increases ligand expression nor increases the sensitivity to lysis by NK cells. Instead, p53 restoration caused tumor cells to secrete various chemokines with the potential to recruit NK cells. Antibody-mediated neutralization of CCL2, but not CCL3, CCL4 or CCL5, prevented NK cell recruitment to the senescent tumors and reduced their elimination. Our findings suggest that elimination of senescent tumors by NK cells occurs as a result of the cooperation of signals associated with p53 expression or senescence, which regulate NK cell recruitment, and other signals that induce NKG2D ligand expression on tumor cells.
The Design, Fabrication and Characterization of Capacitive Micromachined Ultrasonic Transducers for Imaging Applications (2010)

Capacitive micromachined ultrasonic transducers (CMUTs) have proven themselves to be excellent candidates for medical ultrasonic imaging applications. The use of semiconductor fabrication techniques facilitates the fabrication of high quality arrays of uniform cells and elements, broad acoustic bandwidth, the potential to integrate the transducers with the necessary electronics, and the opportunity to exploit the benefits of batch fabrication. &#13;\nIn this thesis, the design, fabrication and testing of one- and two-dimensional CMUT arrays using a novel wafer bonding process whereby the membrane and the insulation layer are both silicon nitride is reported. A user-grown insulating membrane layer avoids the need for expensive SOI wafers, permits optimization of the electrode size, and allows more freedom in selecting the membrane thickness, while also enjoying the benefits of wafer bonding fabrication. Using a row-column addressing scheme for an NxN two-dimensional array permits three-dimensional imaging with a large reduction in the complexity of the array when compared to a conventional 2D array with connections to all N2 elements. Only 2N connections are required and the image acquisition rate has the potential to be greatly increased. A simplification of the device at the imaging end will facilitate the integration of a three-dimensional imaging CMUT array into either an endoscope or catheter which is the ultimate purpose of this research project. &#13;\nTo date, many sizes of transducers which operate at different frequencies have been successfully fabricated. Initial characterization in terms of resonant frequency and, transmission and reception in immersion has been performed on most of the device types. Extensive characterization has been performed with a linear 32 element array transducer and a 32x32 element row-column transducer. Two- and three-dimensional phased array imaging has been demonstrated.
Subwavelength hyperspectral THz studies of articular cartilage (2018)

Terahertz-spectroscopy probes dynamics and spectral response of collective vibrational modes in condensed phase, which can yield insight into composition and topology. However, due to the long wavelengths employed (λ = 300 μm at 1THz), diffraction limited imaging is typically restricted to spatial resolutions around a millimeter. Here, we demonstrate a new form of subwavelength hyperspectral, polarization-resolved THz imaging which employs an optical pattern projected onto a 6 μm-thin silicon wafer to achieve near-field modulation of a co-incident THz pulse. By placing near-field scatterers, one can measure the interaction of object with the evanescent THz fields. Further, by measuring the temporal evolution of the THz field a sample's permittivity can be extracted with 65 μm spatial resolution due to the presence of evanescent fields. Here, we present the first application of this new approach to articular cartilage. We show that the THz permittivity in this material varies progressively from the superficial zone to the deep layer, and that this correlates with a change in orientation of the collagen fibrils that compose the extracellular matrix (ECM) of the tissue. Our approach enables direct interrogation of the sample's biophysical properties, in this case concerning the structure and permittivity of collagen fibrils and their anisotropic organisation in connective tissue.
SecondNet (2010)

In this paper, we propose virtual data center (VDC) as the unit of resource allocation for multiple tenants in the cloud. VDCs are more desirable than physical data centers because the resources allocated to VDCs can be rapidly adjusted as tenants' needs change. To enable the VDC abstraction, we design a data center network virtualization architecture called SecondNet. SecondNet achieves scalability by distributing all the virtual-to-physical mapping, routing, and bandwidth reservation state in server hypervisors. Its port-switching based source routing (PSSR) further makes SecondNet applicable to arbitrary network topologies using commodity servers and switches. SecondNet introduces a centralized VDC allocation algorithm for bandwidth guaranteed virtual to physical mapping. Simulations demonstrate that our VDC allocation achieves high network utilization and low time complexity. Our implementation and experiments show that we can build SecondNet on top of various network topologies, and SecondNet provides bandwidth guarantee and elasticity, as designed.
Autofluorescence and diffuse reflectance spectroscopy of oral epithelial tissue using a depth-sensitive fiber-optic probe (2008)

Optical spectroscopy can provide useful diagnostic information about the morphological and biochemical changes related to the progression of precancer in epithelial tissue. As precancerous lesions develop, the optical properties of both the superficial epithelium and underlying stroma are altered; measuring spectral data as a function of depth has the potential to improve diagnostic performance. We describe a clinical spectroscopy system with a depth-sensitive, ball lens coupled fiber-optic probe for noninvasive in vivo measurement of oral autofluorescence and diffuse reflectance spectra. We report results of spectroscopic measurements from oral sites in normal volunteers and in patients with neoplastic lesions of the oral mucosa; results indicate that the addition of depth selectivity can enhance the detection of optical changes associated with precancer.
Newer Purine Analogues for the Treatment of Hairy-Cell Leukemia (1994)

Hairy-cell Leukemia, or leukemic reticuloendotheliosis, is an uncommon chronic lymphoproliferative disorder first described by Bouroncle et al. in 19581. Its defining features are mononuclear cells with prominent cytoplasmic projections (Figure 1) that retain acid phosphatase stain when treated with tartrate, and a typical pattern of cellular infiltration in the bone marrow and spleen1,2. In the marrow the hairy cells contain abundant pale cytoplasm, giving rise to a “fried egg” appearance, and in the spleen the disruption of normal sinus architecture results in the formation of blood-filled spaces. Immunophenotypic analysis of the circulating hairy cells reveals them to . . .
Identification and Molecular Characterization of the Mg 2+ Stimulon of Escherichia coli (2003)

Transcription profile microarray analysis in Escherichia coli was performed to identify the member genes of the Mg(2+) stimulon that respond to the availability of external Mg(2+) in a PhoP/PhoQ two-component system-dependent manner. The mRNA levels of W3110 in the presence of 30 mM MgCl(2), WP3022 (phoP defective), and WQ3007 (phoQ defective) were compared with those of W3110 in the absence of MgCl(2). The expression ratios of a total of 232 genes were <0.75 in all three strains (the supplemental data are shown at http://www.nara.kindai.ac.jp/nogei/seiken/array.html), suggesting that the PhoP/PhoQ system is involved directly or indirectly in the transcription of these genes. Of those, 26 contained the PhoP box-like sequences with the direct repeats of (T/G)GTTTA within 500 bp upstream of the initiation codon. Furthermore, S1 nuclease assays of 26 promoters were performed to verify six new Mg(2+) stimulon genes, hemL, nagA, rstAB, slyB, vboR, and yrbL, in addition to the phoPQ, mgrB, and mgtA genes reported previously. In gel shift and DNase I footprinting assays, all of these genes were found to be regulated directly by PhoP. Thus, we concluded that the phoPQ, mgrB, mgtA, hemL, nagA, rstAB, slyB, vboR, and yrbL genes make up the Mg(2+) stimulon in E. coli.