gebhart/patrepeval huggingface dataset:
The Rod Photoreceptor-Specific Nuclear Receptor Nr2e3 Represses Transcription of Multiple Cone-Specific Genes (2005)

This study addresses one genetic regulatory mechanism that establishes the distinct identities of rod and cone photoreceptors. Previous work has shown that mutations in either humans or mice in the gene coding for photoreceptor-specific nuclear receptor Nr2e3 cause a progressive retinal degeneration characterized by increased numbers of short-wave cones. In the present work, we have examined the cellular and developmental pattern of Nr2e3 protein localization in mammals and fish, identified an optimal Nr2e3 DNA-binding site using cycles of binding to recombinant Nr2e3, characterized the transcriptional activity of wild type and one of the disease-associated point mutations in Nr2e3 in transfected cells, and characterized the transcriptional defects in the naturally occurring Nr2e3 mutant (rd7) mouse. These experiments indicate that in the mature vertebrate retina Nr2e3 is expressed exclusively in rods, that expression of Nr2e3 is one of the earliest events in the pathway of rod-specific photoreceptor development, and that Nr2e3 functions, either directly or indirectly, as a repressor of cone-specific genes in rod photoreceptor cells.
Tissue Engineering Using Magnetite Nanoparticles and Magnetic Force: Heterotypic Layers of Cocultured Hepatocytes and Endothelial Cells (2004)

Novel technologies to establish three-dimensional, in vivo-like tissue consisting of various types of cells are required for tissue engineering. We applied magnetic force to construct a heterotypic, layered coculture system of rat hepatocytes and human aortic endothelial cells (HAECs) that was not limited by cell type. Magnetite cationic liposomes carrying a positive surface charge to improve adsorption accumulated in HAECs at a concentration of 38 pg of magnetite per cell. Magnetically labeled HAECs specifically accumulated onto hepatocyte monolayers at sites where a magnet (4000 G) was positioned, and then adhered to form a heterotypic, layered construct with tight and close contact. This cocultured construct significantly (p < 0.05) enhanced albumin secretion by hepatocytes compared with that in homotypic cultures of hepatocytes or heterotypic cocultures of hepatocytes and HAECs without magnets. These results suggest that this novel use of magnetite nanoparticles and magnetic force, which we refer to as "magnetic force-based tissue engineering" (Mag-TE), offers a major advancement in tissue engineering.
Optical sensors for automotive applications (1992)

The authors describe the development of two automotive sensors by a co-operation between First Inertia Switch Ltd. and Sira R&D. The sensors in question were an automatic headlamp dipswitch, and a steering wheel rotation sensor. In both cases FISL provided the impetus and marketing strengths to maintain focus on the requirements, and Sira provided a design and development resource to meet the technical challenge. The automatic headlamp dipswitch is a device that changes the headlights from main beam to dipped beam when a bright source (e.g. oncoming car headlamps) are in the field of view. It consists of a lens, aperture plate, photocell and processing circuitry. The steering wheel rotation sensor consists of a launcher, light collectors, and electronic processing. It uses IR LED technology. The authors briefly describe how each sensor works.<
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Studies on Phenyl Glycosides as Inhibitors of D-G1ucose Uptake by Rhesus Monkey Kidney Cells (1980)

Some analogs of phenyl 6-halogeno-6-deoxy-beta-D-glucopyranosides have been found to be inhibitors of glucose uptake by Rhesus monkey kidney cells (LLCMK2 cells). The structures of the glycone and aglycone parts were both found to contribute to the inhibitory activity. Introduction of alkyl groups into the phenyl residue caused appreciable enhancement of the inhibition. p-(sec-Butyl)phenyl-6-chloro-6-deoxy-beta-D-glucopyranoside, which is the most potent inhibitor in this series, showed competitive and reversible inhibition. As a result of this study, we prepared p-azidophenyl-6-chloro-6-deoxy-beta-D-glucopyranoside as a possible compound for photoaffinity labeling of the glucose uptake site in animal cells.
Recognition by viral and cellular DNA polymerases of nucleosides bearing bases with nonstandard hydrogen bonding patterns. (1995)

The ability of DNA polymerases (pols) to catalyze the template-directed synthesis of duplex oligonucleotides containing a nonstandard Watson-Crick base pair between a nucleotide bearing a 5-(2,4-diaminopyrimidine) heterocycle (d kappa) and a nucleotide bearing either deoxyxanthosine (dX) or N1-methyloxoformycin B (pi) has been investigated. The kappa-X and kappa-pi base pairs are jointed by a hydrogen bonding pattern different from and exclusive of those joining the AT and GC base pairs. Reverse transcriptase from human immunodeficiency virus type 1 (HIV-1) incorporates dXTP into an oligonucleotide opposite d kappa in a template with good fidelity. With lower efficiency and fidelity, HIV-1 reverse transcriptase also incorporates d kappa TP opposite dX in the template. With d pi in the template, no incorporation of d kappa TP was observed with HIV reverse transcriptase. The Klenow fragment of DNA pol I from Escherichia coli does not incorporate d kappa TP opposite dX in a template but does incorporate dXTP opposite d kappa. Bovine DNA pols alpha, beta, and epsilon accept neither dXTP opposite d kappa nor d kappa TP opposite d pi. DNA pols alpha and epsilon (but not beta) incorporate d kappa TP opposite dX in a template but discontinue elongation after incorporating a single additional base. These results are discussed in light of the crystal structure for pol beta and general considerations of how polymerases must interact with an incoming base pair to faithfully copy genetic information.
Sub-Nyquist Sampling of Short Pulses: Theory (2011)

We develop sub-Nyquist sampling systems for analog signals comprised of several, possibly overlapping, finite duration pulses with unknown shapes and time positions. Efficient sampling schemes when either the pulse shape or the locations of the pulses are known have been previously developed. To the best of our knowledge, stable and low-rate sampling strategies for continuous signals that are superpositions of unknown pulses without knowledge of the pulse locations have not been derived. The goal in this paper is to fill this gap. We propose a multichannel scheme based on Gabor frames that exploits the sparsity of signals in time and enables sampling multipulse signals at subNyquist rates. Our approach is based on modulating the input signal in each channel with a properly chosen waveform, followed by an integrator. We show that, with proper preprocessing, the Gabor coefficients necessary for almost perfect reconstruct of the input signal, can be recovered from the samples using standard methods of compressed sensing. In addition, we provide error estimates on the reconstruction and analyze the proposed architecture in the presence of noise. The resulting scheme is flexible and exhibits good noise robustness.
Crystal Structure of the Extracellular Segment of Integrin αVβ3 in Complex with an Arg-Gly-Asp Ligand (2002)

The structural basis for the divalent cation-dependent binding of heterodimeric alphabeta integrins to their ligands, which contain the prototypical Arg-Gly-Asp sequence, is unknown. Interaction with ligands triggers tertiary and quaternary structural rearrangements in integrins that are needed for cell signaling. Here we report the crystal structure of the extracellular segment of integrin alphaVbeta3 in complex with a cyclic peptide presenting the Arg-Gly-Asp sequence. The ligand binds at the major interface between the alphaV and beta3 subunits and makes extensive contacts with both. Both tertiary and quaternary changes are observed in the presence of ligand. The tertiary rearrangements take place in betaA, the ligand-binding domain of beta3; in the complex, betaA acquires two cations, one of which contacts the ligand Asp directly and the other stabilizes the ligand-binding surface. Ligand binding induces small changes in the orientation of alphaV relative to beta3.
Smads bind directly to the Jun family of AP-1 transcription factors (1999)

Smad3 and Smad4 are sequence-specific DNA-binding factors that bind to their consensus DNA-binding sites in response to transforming growth factor beta (TGFbeta) and activate transcription. Recent evidence implicates Smad3 and Smad4 in the transcriptional activation of consensus AP-1 DNA-binding sites that do not interact with Smads directly. Here, we report that Smad3 and Smad4 can physically interact with AP-1 family members. In vitro binding studies demonstrate that both Smad3 and Smad4 bind all three Jun family members: JunB, cJun, and JunD. The Smad interacting region of JunB maps to a C-terminal 20-amino acid sequence that is partially conserved in cJun and JunD. We show that Smad3 and Smad4 also associate with an endogenous form of cJun that is rapidly phosphorylated in response to TGFbeta. Providing evidence for the importance of this interaction between Smad and Jun proteins, we demonstrate that Smad3 is required for the activation of concatamerized AP-1 sites in a reporter construct that has previously been characterized as unable to bind Smad proteins directly. Together, these data suggest that TGFbeta-mediated transcriptional activation through AP-1 sites may involve a regulated interaction between Smads and AP-1 transcription factors.
Phylogenetic Analysis of 16S Ribosomal RNA Gene Sequences from Human Fecal Microbiota and Improved Utility of Terminal Restriction Fragment Length Polymorphism Profiling (2006)

We have developed a terminal restriction fragment length polymorphism (T-RFLP) method for determining the structure and dynamics of the microbial gut community. In this paper, the improved T-RFLP method in combination with an analysis of the fecal 16S rDNA (ribosomal RNA gene) clone libraries from six individuals is described. A total of 418 different partial sequences of 16S rDNA were determined and subjected to a phylogenetic analysis and homology examination. We found that the sequences were roughly divided into six phylogenetic groups containing seven subgroups and were related to 71 known species with over 90% similarity. With the exception of a few cases, we found that in silico BslI-digestion of the sequences belonging to the same bacterial group or subgroup generated terminal restriction fragments of similar lengths. We concluded that human intestinal microbiota predominantly consists of the members of approximately ten phylogenetic bacterial groups and that these bacterial groups are effectively distinguished by our T-RFLP system.
HOXB9, a gene overexpressed in breast cancer, promotes tumorigenicity and lung metastasis (2009)

The mechanisms underlying tumoral secretion of signaling molecules into the microenvironment, which modulates tumor cell fate, angiogenesis, invasion, and metastasis, are not well understood. Aberrant expression of transcription factors, which has been implicated in the tumorigenesis of several types of cancers, may provide a mechanism that induces the expression of growth and angiogenic factors in tumors, leading to their local increase in the tumor microenvironment, favoring tumor progression. In this report, we demonstrate that the transcription factor HOXB9 is overexpressed in breast carcinoma, where elevated expression correlates with high tumor grade. HOXB9 induces the expression of several angiogenic factors (VEGF, bFGF, IL-8, and ANGPTL-2), as well as ErbB (amphiregulin, epiregulin, and neuregulins) and TGF-ss, which activate their respective pathways, leading to increased cell motility and acquisition of mesenchymal phenotypes. In vivo, HOXB9 promotes the formation of large, well-vascularized tumors that metastasize to the lung. Thus, deregulated expression of HOXB9 contributes to breast cancer progression and lung metastasis by inducing several growth factors that alter tumor-specific cell fates and the tumor stromal microenvironment.
ZD1839 induces p15INK4b and causes G1 arrest by inhibiting the mitogen-activated protein kinase/extracellular signal–regulated kinase pathway (2007)

Inactivation of the retinoblastoma protein pathway is the most common abnormality in malignant tumors. We therefore tried to detect agents that induce the cyclin-dependent kinase inhibitor p15(INK4b) and found that ZD1839 (gefitinib, Iressa) could up-regulate p15(INK4b) expression. ZD1839 has been shown to inhibit cell cycle progression through inhibition of signaling pathways such as phosphatidylinositol 3'-kinase-Akt and mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase (ERK) cascades. However, the mechanism responsible for the differential sensitivity of the signaling pathways to ZD1839 remains unclear. We here showed that ZD1839 up-regulated p15(INK4b), resulting in retinoblastoma hypophosphorylation and G(1) arrest in human immortalized keratinocyte HaCaT cells. p15(INK4b) induction was caused by MAPK/ERK kinase inhibitor (PD98059), but not by Akt inhibitor (SH-6, Akt-III). Moreover, mouse embryo fibroblasts lacking p15(INK4b) were resistant to the growth inhibitory effects of ZD1839 compared with wild-type mouse embryo fibroblasts. Additionally, the status of ERK phosphorylation was related to the antiproliferative activity of ZD1839 in human colon cancer HT-29 and Colo320DM cell lines. Our results suggest that induction of p15(INK4b) by inhibition of the MAPK/ERK pathway is associated with the antiproliferative effects of ZD1839.
In Situ Study of the Growth Kinetics of Individual Island Electrodeposition of Copper (2006)

The growth kinetics for individual islands during electrodeposition of copper have been studied using in situ transmission electron microscopy. We show that for sufficiently large overpotentials, the growth kinetics approach the rate laws expected for diffusion-limited growth of hemispherical islands, characterized by two distinct regimes. At short times, the island growth exponent is 0.5 as expected for diffusion-limited growth of uncoupled hemispherical islands, while at longer times, the growth exponent approaches 1/6 as expected for planar diffusion to the growing islands. These results provide the first direct measurements of the growth of individual islands during electrochemical deposition. However, quantitative comparison with rate laws shows that the island radii are smaller than predicted and the island densities are much larger than predicted, and we suggest that this is related to adatom formation and surface diffusion, processes which are not included in conventional growth models.
An immunoprotective molecule, the major secretory protein of Legionella pneumophila, is not a virulence factor in a guinea pig model of Legionnaires' disease. (1990)

We have examined whether a molecule that is capable of inducing immune protection, the major secretory protein (MSP) of Legionella pneumophila, is required for virulence in a guinea pig model of Legionnaires' disease. To do so, we have compared the virulence in guinea pigs of an isogenic pair of L. pneumophila, Philadelphia 1 strain, one of which produces MSP (MSP+) and one of which does not (MSP-). Both the MSP- strain and the MSP+ strain of L. pneumophila are highly virulent for guinea pigs, inducing similar signs and progression of illness. Both strains are lethal and have comparable LD50s and LD100s. Both strains multiply in the lungs of guinea pigs at a similar rate, and both strains produce indistinguishable pathological lesions in the lungs. Both strains maintain a stable phenotype with guinea pig passage, i.e., the MSP- strain does not regain the capacity to secrete MSP and the MSP+ strain retains its capacity to secrete MSP after lung passage. Although vaccination with MSP induces strong protective immunity in the guinea pig against lethal aerosol challenge with L. pneumophila, this protective immunogen is not required in its intact proteolytically active form for the expression of virulence by the intracellular pathogen L. pneumophila. This demonstrates that a protective immune response need not necessarily be directed against a virulence determinant and suggests that any molecule that allows the host immune system to detect and act against an intracellularly sequestered pathogen may potentially serve as a protective immunogen against such a pathogen.
An efficient route to the production of an IgG-like bispecific antibody (2000)

Production of IgG-form bispecific antibody (BsAb-IgG) by co-expressing two antibodies in transfected cells is often inefficient owing to the unwanted pairing between the component heavy and light chains. We have developed an efficient method for the production of a novel IgG-like BsAb by using the natural dimerization mechanism between IgG heavy and light chains. Two single-chain Fv (scFv) of different specificity are fused to the constant domain of human kappa chain (C(L)) and the first constant domain of human heavy chain (C(H1)), to form two polypeptides, (scFv)(1)-C(L) and (scFv)(2)-C(H1)-C(H2)-C(H3), respectively. Co-expression of the two polypeptides in mammalian cells results in the formation of a covalently linked IgG-like hetero-tetramer, Bs(scFv)(4)-IgG, with dual specificity. Our approach yields a homogeneous bispecific IgG-like antibody product with each molecule containing four antigen binding sites, two for each of its target antigens. A Bs(scFv)(4)-IgG was prepared using two scFv antibodies each directed against a different epitope of a vascular endothelial growth factor receptor, the kinase insert domain-containing receptor (KDR). The Bs(scFv)(4)-IgG is capable of simultaneously binding to the two epitopes on the receptor. Further, the Bs(scFv)(4)-IgG also retains the antigen-binding efficacy and biological activity of its component antibodies.
A low-voltage, low-power microwave SOI MOSFET (2002)

Summary form only given. Recently, it has been demonstrated that the use of high-resistivity SOI (SIMOX) substrates (5,000 and 10,000 /spl Omega/.cm) yields MOSFETs which offer interesting microwave performances. Indeed unity-gain frequencies (f/sub T/) of 14 and 23.6 GHz and maximum oscillation frequencies (f/sub max/) of 21 and 32 GHz have been reported for effective gate lengths of 0.36 and 0.25 /spl mu/m, respectively, and using supply voltages ranging from 3 to 5 volts. Such devices can be integrated with planar lines to implement MMIC circuits. These transistors were fabricated using a dedicated MOS process, called MICROX/sup TM/, which uses non-standard CMOS features, such as a metal (gold) gate and air-bridge metallisation. In this work, the high-frequency performances of microwave transistors fabricated using a standard fully-depleted SOI CMOS process are described. These devices are, therefore, compatible with analog and digital circuits fabricated using the same low-cost process.
Highly Efficient ReversibleZ−EPhotoisomerization of a Bridged Azobenzene with Visible Light through Resolved S1(nπ*) Absorption Bands (2009)

The reversible Z-E photoswitching properties of the (Z) and (E) isomers of the severely constrained bridged azobenzene derivative 5,6-dihydrodibenzo[c,g][1,2]diazocine (1) were investigated quantitatively by UV/vis absorption spectroscopy in solution in n-hexane. In contrast to normal azobenzene (AB), 1 has well separated S(1)(n pi*) absorption bands, peaking at lambda(Z) = 404 nm and lambda(E) = 490 nm. Using light at lambda = 385 nm, it was found that 1Z can be switched to 1E with very high efficiency, Gamma = 92 +/- 3%. Conversely, 1E can be switched back to 1Z using light at lambda = 520 nm with approximately 100% yield. The measured quantum yields are Phi(Z-->E) = 72 +/- 4% and Phi(E-->Z) = 50 +/- 10%. The thermal lifetime of the (E) isomer is 4.5 +/- 0.1 h at 28.5 degrees C. The observed photochromic and photoswitching properties of 1 are much more favorable than those for normal AB, making our title compound a promising candidate for interesting applications as a molecular photoswitch especially at low temperatures. The severe constraints by the ethylenic bridge apparently do not hinder but favor the Z-E photoisomerization reactions.
Efficient distributed backup with delta compression (1997)

Inexpensive storage and more powerful processors have resulted in a proliferation of data that needs to be reliably backed up. Network resource limitations make it increasingly difficult to backup a distributed file system on a nightly or even weekly basis. By using delta compression algorithms, which minimally encode a version of a file using only the bytes that have changed, a backup system can compress the data sent to a server. With the delta backup technique, we can achieve significant savings in network transmission time over previous techniques.
Disulfide linkages in the in vitro refolded intermediates of recombinant human macrophage-colony-stimulating factor: analysis of the sulfhydryl alkylation of free cysteine residues by fast-atom bombardment mass spectrometry. (1994)

Fast-atom bombardment mass spectrometry was used to follow the time course of disulfide bond formation during in vitro refolding of recombinant human macrophage-colony-stimulating factor. The content of iodoacetamide-alkylated half-cystines in proteolytic peptides of trapped refolding intermediates collected at 0, 6, 17, 24, and 72 hr was determined under reducing conditions. Size-exclusion high-performance liquid chromatography analyses of the collected alkylated samples indicate that aggregated monomer proceeded through a nonaggregated monomer to an intermediate dimer and finally to the fully folded and active dimer. Underalkylation was first detected by fast-atom bombardment mass spectrometry in 17-hr samples at Cys157 and Cys159 and this corresponded to the first sample containing dimer. Analyses of intermediates from subsequent time points indicated a decrease in alkylated sulfhydryls, and at 72 hr no alkylated peptide was detected. Early samples containing only monomer showed no evidence of disulfide bonds, and the occurrence of disulfide shuffling at the monomer stage could be ruled out under the highly reducing conditions used for refolding. Biological activity was not detectable in early samples but increased to 3.6% after 24 hr of refolding and to 86% of maximum at the 72-hr time point.
Induction by TNF-αof IL-6 and IL-8 in Cystic Fibrosis Bronchial IB3-1 Epithelial Cells Encapsulated in Alginate Microbeads (2010)

We have developed a microencapsulation procedure for the entrapment and manipulation of IB3-1 cystic fibrosis cells. The applied method is based on generation of monodisperse droplets by a vibrational nozzle. Different experimental parameters were analyzed, including frequency and amplitude of vibration, polymer pumping rate and distance between the nozzle and the gelling bath. We have found that the microencapsulation procedure does not alter the viability of the encapsulated IB3-1 cells. The encapsulated IB3-1 cells were characterized in term of secretomic profile, analyzing the culture medium by Bio-Plex strategy. The experiments demonstrated that most of the analyzed proteins, were secreted both by the free and encapsulated cells, even if in a different extent. In order to determine the biotechnological applications of this procedure, we determined whether encapsulated IB3-1 cells could be induced to pro-inflammatory responses, after treatment with TNF-α. In this experimental set-up, encapsulated and free IB3-1 cells were treated with TNF-α, thereafter the culture media from both cell populations were collected. As expected, TNF-α induced a sharp increase in the secretion of interleukins, chemokines and growth factors. Of great interest was the evidence that induction of interleukin-6 and interleukin-8 occurs also by encapsulated IB3-1 cells.