gebhart/patrepeval huggingface dataset:
Modifications in Small Interfering RNA That Separate Immunostimulation from RNA Interference (2008)

Synthetic small interfering RNA (siRNA) can suppress the expression of endogenous mRNA through RNA interference. It has been reported that siRNA can induce type I IFN production from plasmacytoid dendritic cells, leading to off-target effects. To separate immunostimulation from the desired gene-specific inhibitory activity, we designed RNA strands with chemical modifications at strategic positions of the ribose or nucleobase residues. Substitution of uridine residues by 2'-deoxyuridine or thymidine residues was found to decrease type I IFN production upon in vitro stimulation of human PBMC. Thymidine residues in both strands of a siRNA duplex further decreased immunostimulation. Fortunately, the thymidine residues did not affect gene-silencing activity. In contrast, 2'-O-methyl groups at adenosine and uridine residues reduced both IFN-alpha secretion and gene-silencing activity. Oligoribonucleotides with 2'-O-methyladenosine residues actively inhibited IFN-alpha secretion induced by other immunostimulatory RNAs, an effect not observed for strands with 2'-deoxynucleosides. Furthermore, neither 5-methylcytidine nor 7-deazaguanosine residues in the stimulatory strands affected IFN-alpha secretion, suggesting that recognition does not involve sites in the major groove of duplex regions. The activity data, together with structure prediction and exploratory UV-melting analyses, suggest that immunostimulatory sequences adopt folded structures. The results show that immunostimulation can be suppressed by suitable chemical modifications without losing siRNA potency by introducing seemingly minor structural changes.
Blind Multi-Band Signal Reconstruction: Compressed Sensing for Analog Signals (2007)

We address the problem of reconstructing a multi-band signal from its sub-Nyquist point-wise samples. To date, all reconstruction methods proposed for this class of signals assumed knowledge of the band locations. In this paper, we develop a non-linear blind perfect reconstruction scheme for multi-band signals which does not require the band locations. Our approach assumes an existing blind multi-coset sampling method. The sparse structure of multi-band signals in the continuous frequency domain is used to replace the continuous reconstruction with a single finite dimensional problem without the need for discretization. The resulting problem can be formulated within the framework of compressed sensing, and thus can be solved efficiently using known tractable algorithms from this emerging area. We also develop a theoretical lower bound on the average sampling rate required for blind signal reconstruction, which is twice the minimal rate of known-spectrum recovery. Our method ensures perfect reconstruction for a wide class of signals sampled at the minimal rate. Numerical experiments are presented demonstrating blind sampling and reconstruction with minimal sampling rate.
Real Time Spatial Compound Imaging in breast ultrasound: Technology and early clinical experience (2000)

No abstract available.
AUTOMATIC INDEXING USING BIBLIOGRAPHIC CITATIONS (1971)

Bibliographic citations attached to technical documents have been used variously to refer to related items in the literature, to confer importance to a given piece of writing, and to serve as supplementary indications of document content. In the present study, citations are used directly to identify document content, and an attempt is made to evaluate their effectiveness in a retrieval environment. It is shown that the use of bibliographic citations in addition to the normal keyword‐type indicators produces improved retrieval performance, and that in some circumstances, citations are more effective for retrieval purposes than other more conventional terms and concepts.
Anti–α8 integrin immunoliposomes in glomeruli of lupus‐susceptible mice: A novel system for delivery of therapeutic agents to the renal glomerulus in systemic lupus erythematosus (2008)

These findings are the first demonstration of specific delivery of anti-alpha8 integrin immunoliposomes to the mesangium following tail vein injection in mice. Anti-alpha8 integrin immunoliposomes thus offer a novel approach for targeted drug therapy in lupus and other glomerular diseases.
Binding of Heparin to Human Antithrombin III Activates Selective Chemical Modification at Lysine 236 (1989)

A new water-soluble color reagent, 4-N,N-dimethylaminoazobenzene-4'-isothiocyano-2'-sulfonic acid (S-DABITC), was used to identify lysine residues of antithrombin III which participate in the binding of heparin. Antithrombin, modified with S-DABITC in the presence and absence of low molecular weight heparin (Mr 5000) was reduced, carboxymethylated, and digested with trypsin. The digest was analyzed by high-performance liquid chromatography and monitored at 465 nm. In the absence of heparin, four major colored peptides (T1, T2, T3, and T4) were identified. When antithrombin was preincubated with heparin (2-fold by weight), followed by S-DABITC modification, the recovery of peptide T4 remained unchanged, but the recoveries of T1, T2, and T3 were reduced by 93, 86, and 98%, respectively. In addition, a new colored peptide, TA, appeared. Amino acid sequencing of peptides T1, T2, T3, and TA localized S-DABITC modification sites as Lys-136, Lys-125, Lys-107, and Lys-236, respectively. Thus, binding of heparin to human antithrombin diminished S-DABITC modification at Lys-107, Lys-125, and Lys-136, but at the same time enhanced S-DABITC modification at Lys-236. This phenomenon was further characterized by varying the molar ratio of heparin/antithrombin (from 0.04 to 20). The shielding of Lys-125 and Lys-136 was inversely proportional to the activation of Lys-236. At a heparin/antithrombin molar ratio of 1, the extent of shielding of Lys-125 and Lys-136 and the unmasking of Lys-236 were 25-33%. This shielding-unmasking effect correlated with enhanced antithrombin inhibition of thrombin. We conclude that Lys-107, Lys-125, and Lys-136 are situated within the heparin-binding site of human antithrombin and that binding of heparin to antithrombin causes a conformational change of antithrombin that leads to the exposure of Lys-236 for S-DABITC modification.
Protein-protein and lipid-protein interactions in a reconstituted cytochrome P-450 dependent microsomal monooxygenase (1987)

NADPH-cytochrome P-450 reductase and cytochrome P-450, both purified from liver microsomes of phenobarbital-treated rabbits, were incorporated into dimyristoylphosphatidylcholine vesicles. The reduction of cytochrome P-450 by NADPH in the reconstituted vesicles proceeded in a biphasic fashion, and 70-80% of the absorbance change was associated with the fast phase. The Arrhenius plot of the apparent first-order rate constant of the fast-phase reduction showed a marked discontinuity around the phase transition temperature of the synthetic phospholipid; an almost 10-fold change in rate constant was associated with this discontinuity. It was, therefore, suggested that the reduction of cytochrome P-450 by reductase in this system was a diffusion-limited reaction controlled by the viscosity of the phospholipid membrane. The Arrhenius plot of overall drug monooxygenase activity catalyzed by the reconstituted vesicles showed a break but in a different way from that observed for the reduction of cytochrome P-450. This break was accompanied only by a change of the slope of the plot but not by a change in reaction rate. This difference in the two Arrhenius plots was attributed to that in the rate-limiting step of the two reactions. NADPH-cytochrome c reductase activity of the reconstituted vesicles, an activity catalyzed by the reductase alone, and cumene hydroperoxide dependent N-methylaniline demethylation activity catalyzed by cytochrome P-450 alone did not show any break in the Arrhenius plots.
Rapamycin causes down-regulation of CCR5 and accumulation of anti-HIV β-chemokines: An approach to suppress R5 strains of HIV-1 (2003)

Propagation of R5 strains of HIV-1 on CD4 lymphocytes and macrophages requires expression of the CCR5 coreceptor on the cell surface. Individuals lacking CCR5 (CCR5 Delta 32 homozygous genotype) are phenotypically normal and resistant to infection with HIV-1. CCR5 expression on lymphocytes depends on signaling through the IL-2 receptor. By FACS analysis we demonstrate that rapamycin (RAPA), a drug that disrupts IL-2 receptor signaling, reduces CCR5 surface expression on T cells at concentrations as low as 1 nM. In addition, lower concentrations of RAPA (0.01 nM) were sufficient to reduce CCR5 surface expression on maturing monocytes. PCR analysis on peripheral blood mononuclear cells (PBMCs) showed that RAPA interfered with CCR5 expression at the transcriptional level. Reduced expression of CCR5 on PBMCs cultured in the presence of RAPA was associated with increased extracellular levels of macrophage inflammatory protein (MIP)-1 alpha and MIP-1 beta. In infectivity assays, RAPA suppressed the replication of R5 strains of HIV-1 both in PBMC and macrophage cultures. In total PBMC cultures, RAPA-mediated inhibition of CCR5-using strains of HIV-1 occurred at 0.01 nM, a concentration of drug that is approximately 103 times lower than therapeutic through levels of drug in renal transplant recipients. In addition, RAPA enhanced the antiviral activity of the CCR5 antagonist TAK-779. These results suggest that low concentrations of RAPA may have a role in both the treatment and prevention of HIV-1 infection.
Phonetool: integrating telephones and workstations (2003)

The authors argue for computer workstation access to voice telephony functions. They describe several computer-based communication tools developed in their laboratories, and explore one, Phonetool, as a detailed example. They discuss user interface issues for collections of such utilities. Finally, they discuss several architectures for interaction with the PBX and the communication requirements between workstation and switch.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Response to epidermal growth factor receptor inhibitors in non-small cell lung cancer cells: limited antiproliferative effects and absence of apoptosis associated with persistent activity of extracellular signal-regulated kinase or Akt kinase pathways. (2003)

The epidermal growth factor receptor (EGFR) is an important novel target for anticancer therapy. In this study, we examined the molecular mechanisms that underlie the antitumor effects of the anti-EGFR monoclonal antibody C225 (Cetuximab) and the selective EGFR tyrosine kinase inhibitor ZD1839 (Iressa; AstraZeneca) in non-small cell lung cancer (NSCLC) cell lines. Cell growth, assessed by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, was inhibited at low concentrations of ZD1839 and C225 in control A431 cells, whereas the NSCLC cell lines were comparatively more resistant. In A431 cells, but not in the NSCLC cells, ZD1839 treatment resulted in a modest increase in DNA fragmentation, the externalization of phosphatidyl serine, and the activation of caspase-3, known markers of apoptotic cell death. However, poly(ADP-ribose) polymerase cleavage was not detected, and caspase inhibition by carbobenzoxy-Val-Ala-Asp-fluoromethyl ketone partially reduced ZD1839-generated DNA fragmentation. Overexpression of the antiapoptotic protein Bcl-2 in A431 cells suppressed the cytotoxicity upon anti-EGFR treatment. These results thus demonstrate that the toxic effect of ZD1839 in A431 cells is caused by a form of cell death that involves a mitochondrial step and is, at least in part, dependent on caspase activation. EGFR expression levels showed no significant correlation with sensitivity to ZD1839 and C225. Evaluation of the mitogen-activated protein kinase kinase/extracellular signal-regulated kinase and phosphatidylinositol 3'-kinase/Akt pathways showed considerable inhibition of these pathways by ZD1839 and C225 in A431 cells, whereas one or both of these pathways remained active upon anti-EGFR treatment in NSCLC cells. In addition, treatment with specific inhibitors of mitogen-activated protein kinase kinase or phosphatidylinositol 3'-kinase resulted in a smaller effect on proliferation than simultaneous treatment with both inhibitors, whereas induction of apoptosis was observed only when both pathways were blocked. Together, these data suggest that persistent activity of either of these signaling pathways is involved in the lack of sensitivity of NSCLC cell lines to EGFR inhibitors.
The Drosophila nuclear receptors FTZ-F1 alpha and FTZ-F1 beta compete as monomers for binding to a site in the fushi tarazu gene. (1994)

The striped pattern of fushi tarazu (ftz) expression found in the blastoderm of the Drosophila melanogaster embryo is generated largely through complex interactions between multiple transcription factors that bind to the zebra element of the ftz gene. A motif in the zebra element, the FTZ-F1 recognition element (F1RE), has been shown to bind a transcription factor, FTZ-F1 alpha, that is a member of the nuclear receptor family. We recently identified a second, related member of this family, FTZ-F1 beta, that also binds to this motif. To investigate the possibility that FTZ-F1 alpha and FTZ-F1 beta coregulate ftz transcription through the F1RE, we have studied the DNA binding properties of FTZ-F1 alpha and FTZ-F1 beta. We demonstrate that recombinant FTZ-F1 alpha and FTZ-F1 beta proteins produce similar in vitro DNase I footprint patterns on a 14-nucleotide region of the zebra element and bind to this site with similar affinities and sequence specificities. Using wild-type and N-terminally truncated receptors, we have determined that FTZ-F1 alpha and FTZ-F1 beta both bind as monomers to the 9-bp F1RE in the zebra element, as well as to an imperfect inverted F1RE repeat present in the Drosophila alcohol dehydrogenase gene. A polyclonal antibody raised against FTZ-F1 beta identifies a predominant F1RE-binding component in embryonic nuclear extracts. Although FTZ-F1 alpha is also present in these extracts, FTZ-F1 alpha and FTZ-F1 beta do not appear to form heterodimers with each other. Cotransfection assays in mammalian cell culture indicate that both receptors contribute to the net transcriptional activity of a reporter gene through their direct interaction with the F1RE. These data suggest that FTZ-F1 alpha and FTZ-F1 beta likely coregulate common target genes by competition for binding to a 9-bp recognition element.
Quantum-Mechanical Reflection of Electrons at Metal-Semiconductor Barriers: Electron Transport in Semiconductor-Metal-Semiconductor Structures (1966)

Numerical methods have been used to solve the Schrödinger equation for the quantum-mechanical reflection coefficient (QMR) of electrons at metal-semiconductor barriers. The calculations were carried out for a ``MacColl'' type barrier and a ``Thomas-Fermi'' type barrier. It was found that for both barrier models the QMR≳50% for an electron incident on a barrier with energy less than 0.05 eV with respect to the barrier maximum. The QMR decreases slowly with increasing energy. On the basis of these calculations and calculations of the effects of electron-phonon scattering in the collector and emitter semiconductors of semiconductor-metal-semiconductor structures, the predicted net current transfer ratio in such structure is less than 0.5 exclusive of base-transport losses.
The 1.5-Å Resolution Crystal Structure of Bacterial Luciferase in Low Salt Conditions (1996)

Bacterial luciferase is a flavin monooxygenase that catalyzes the oxidation of a long-chain aldehyde and releases energy in the form of visible light. A new crystal form of luciferase cloned from Vibrio harveyi has been grown under low-salt concentrations, which diffract x-rays beyond 1.5-A resolution. The x-ray structure of bacterial luciferase has been refined to a conventional R-factor of 18.2% for all recorded synchrotron data between 30.0 and 1.50-A resolution. Bacterial luciferase is an alpha-beta heterodimer, and the individual subunits fold into a single domain (beta/alpha)8 barrel. The high resolution structure reveals a non-prolyl cis peptide bond that forms between Ala74 and Ala75 in the alpha subunit near the putative active site. This cis peptide bond may have functional significance for creating a cavity at the active site. Bacterial luciferase employs reduced flavin as a substrate rather than a cofactor. The structure presented was determined in the absence of substrates. A comparison of the structural similarities between luciferase and a nonfluorescent flavoprotein, which is expressed in the lux operon of one genus of bioluminescent bacteria, suggests that the two proteins originated from a common ancestor. However, the flavin binding sites of the nonfluorescent protein are likely not representative of the flavin binding site on luciferase. The structure presented here will furnish a detailed molecular model for all bacterial luciferases.
The major components of the paraflagellar rod of Trypanosoma brucei are two similar, but distinct proteins which are encoded by two different gene loci. (1994)

The flagellum of trypanosomatids contains two major structural elements, the microtubular axoneme, which is the mechanochemical motor of the cell, and the paraflagellar rod (PFR), a highly organized, three-dimensional fiber network of unknown function. Its occurrence is limited to a few groups of unicellular eukaryotes, the Euglenoids, Dinoflagellates, and Kinetoplastids. The PFR of trypanosomes consists of two similar proteins of approximate molecular masses of 69 and 73 kDa. This laboratory and others have earlier characterized the genes coding for the 69-kDa PFR species in Trypanosoma brucei and Trypanosoma cruzi. The present study reports the characterization of the genes coding for the 73-kDa PFR protein from T. brucei. Their gene product, PFR-C, is closely related to, but clearly distinct from, the 69 kDa species PFR-A. This finding indicates that the PFR fibers of the flagellum might represent heteropolymers formed by PFR-A and PFR-C, akin to the situation seen in microtubules or intermediate filaments. PFR-A and PFR-C are each coded for by a similarly organized cluster of four closely spaced, tandemly arranged genes. The 5'-untranslated region of the first gene in each cluster is different from those of the following three genes, which are identical among each other. Conversely, the 3'-untranslated regions of the first three genes of each cluster are identical, while the corresponding region of the fourth gene is different. This unusual organization leads to the generation of mRNAs which contain identical coding sequences but different 5'- and 3'-noncoding regions.
Authentication, Authorization, and Accounting Requirements for the Session Initiation Protocol (SIP) (2004)

As Session Initiation Protocol (SIP) services are deployed on the Internet, there is a need for authentication, authorization, and accounting of SIP sessions. This document sets out the basic requirements for this work.
Characterization of particle capture in a sawtooth patterned insulating electrokinetic microfluidic device (2010)

Here we present a scheme to separate particles according to their characteristic physical properties, including size, charge, polarizability, deformability, surface charge mobility, dielectric features, and local capacitance. Separation is accomplished using a microdevice based on direct current insulator gradient dielectrophoresis that can isolate and concentrate multiple analytes simultaneously at different positions. The device is dependent upon dielectrophoretic and electrokinetic forces incorporating a global longitudinal direct current field as well as using shaped insulating features within the channel to induce local gradients. This design allows for the production of strong local field gradients along a global field causing particles to enter, initially transported through the channel by electrophoresis and electroosmosis (electrokinetics), and to be isolated via repulsive dielectrophoretic forces that are proportional to an exponent of the field gradient. Sulfate-capped polystyrene nano and microparticles (20, 200 nm, and 1 μm) were used as probes to demonstrate the influence of channel geometry and applied longitudinal field on separation behavior. These results are consistent with models using similar channel geometry and indicate that specific particulate species can be isolated within a distinct portion of the device, whereas concentrating particles by factors from 10(3) to 10(6).
DAGAN: Deep De-Aliasing Generative Adversarial Networks for Fast Compressed Sensing MRI Reconstruction (2017)

Compressed sensing magnetic resonance imaging (CS-MRI) enables fast acquisition, which is highly desirable for numerous clinical applications. This can not only reduce the scanning cost and ease patient burden, but also potentially reduce motion artefacts and the effect of contrast washout, thus yielding better image quality. Different from parallel imaging-based fast MRI, which utilizes multiple coils to simultaneously receive MR signals, CS-MRI breaks the Nyquist-Shannon sampling barrier to reconstruct MRI images with much less required raw data. This paper provides a deep learning-based strategy for reconstruction of CS-MRI, and bridges a substantial gap between conventional non-learning methods working only on data from a single image, and prior knowledge from large training data sets. In particular, a novel conditional Generative Adversarial Networks-based model (DAGAN)-based model is proposed to reconstruct CS-MRI. In our DAGAN architecture, we have designed a refinement learning method to stabilize our U-Net based generator, which provides an end-to-end network to reduce aliasing artefacts. To better preserve texture and edges in the reconstruction, we have coupled the adversarial loss with an innovative content loss. In addition, we incorporate frequency-domain information to enforce similarity in both the image and frequency domains. We have performed comprehensive comparison studies with both conventional CS-MRI reconstruction methods and newly investigated deep learning approaches. Compared with these methods, our DAGAN method provides superior reconstruction with preserved perceptual image details. Furthermore, each image is reconstructed in about 5 ms, which is suitable for real-time processing.
Comparison of User Mobility Pattern Prediction Algorithms to increase Handover Trigger Accuracy (2006)

The estimation of correct triggers for handover in cellular networks belongs to the critical tasks for accurate network operation. The importance of seamless handover even rises according to the increasing number of available radio access technologies, demanding for a reliable vertical handover. To aid the handover process, mobility prediction technologies gain interest and provide the possibility to prepare for handover in advance. The approaches presented here feature prediction of macro-mobility as an additional measure to aid handover decisions. The prediction is based on statistical data gained from the observation of movement across multiple cells. One of the main features lies in a generic user centric calculation of the most likely next hop during user movement, compared to network specific technological methods