gebhart/patrepeval huggingface dataset:
RagA is a functional homologue of S. cerevisiae Gtr1p involved in the Ran/Gsp1-GTPase pathway (1998)

Human RagA and RagB is reported to be 52% identical to a putative GTPase of Saccharomyces cerevisiae, Gtr1p. According to the reported nucleotide sequence, we amplified human RagA and RagBs cDNAs from the human B cell cDNA library with PCR. Both cDNAs rescued a cold sensitivity of S. cerevisiae, gtr1-11. Furthermore, we introduced into the cloned human RagA cDNA, the mutation 'T21L' corresponding to the gtr1-11 mutation which has been reported to suppress not only all of rcc1-, temperature-sensitive mutants of Ran/Gsp1p GTPase GDP/GTP-exchanging factor, but also rna1-1, a temperature-sensitive mutant of Ran/Gsp1p GTPase-activating protein. The resulting RagAgtr1-11 cDNA partially, but significantly, suppressed both rcc1- and rna1-1 mutations. These results indicated that RagA and RagBs are functional homologues of S. cervisiae Gtr1p. Interestingly, while wild-type human RagA and RagBs were localized within the cytoplasm, similar to S. cerevisiae Gtr1p, the mutated human RagAgtr1-11 corresponding to a dominant negative form of RagA was distributed in discrete speckles in the nucleus, being localized side by side with SC-35, a non-snRNP of the splicing complex. In contrast, a dominant positive form of RagA, Q66L was localized in the cytoplasm. Thus, RagA was suggested to shuttle between the cytoplasm and the nucleus, depending on the bound nucleotide state.
Automated discovery of dependencies between logical components in document image understanding (2002)

Document image understanding denotes the recognition of semantically relevant components in the layout extracted from a document image. This recognition process is based on some visual models, whose manual specification can be a highly demanding task. In order to automatically acquire these models, we propose the application of machine learning techniques. Problems raised by possible dependencies between concepts to be learned are illustrated and solved with a computational strategy based on the separate-and-parallel-conquer search. The approach is tested on a set of real multi-page documents processed by the system WISDOM++. New results confirm the validity of the proposed strategy and show some limits of the learning system used in this work.
Studies on Toxinogenesis in Vibrio cholerae. I. Isolation of Mutants with Altered Toxinogenicity (1974)

Journal Article Studies on Toxinogenesis in Vibrio cholerae. I. Isolation of Mutants with Altered Toxinogenicity Get access Richard A. Finkelstein, Richard A. Finkelstein From the Departments of Microbiology and Internal Medicine, University of Texas Southwestern Medical School, Dallas, Texas Search for other works by this author on: Oxford Academic PubMed Google Scholar Michael L. Vasil, Michael L. Vasil From the Departments of Microbiology and Internal Medicine, University of Texas Southwestern Medical School, Dallas, Texas Search for other works by this author on: Oxford Academic PubMed Google Scholar Randall K. Holmes Randall K. Holmes From the Departments of Microbiology and Internal Medicine, University of Texas Southwestern Medical School, Dallas, Texas Search for other works by this author on: Oxford Academic PubMed Google Scholar The Journal of Infectious Diseases, Volume 129, Issue 2, February 1974, Pages 117–123, https://doi.org/10.1093/infdis/129.2.117 Published: 01 February 1974 Article history Received: 02 April 1973 Published: 01 February 1974
Effect of Flavonol Derivatives on the Carrageenin-Induced Paw Edema in the Rat and Inhibition of Cyclooxygenase-1 and 5-Lipoxygenase in Vitro (2000)

Alkoxyflavonols were synthesized by the Algar-Flynn-Oyamada (AFO) cyclization of chalcones. Hydroxyflavonols were prepared by dealkylation of methoxyflavonols by refluxing in hydroiodic acid. The alkoxyflavonols 3-hydroxy-2-(2,3,4-trimethoxy-phenyl)- 4H-chromen-4-one (6), 2-(4-ethoxyphenyl)-3-hydroxy-4H- chromen-4-one (7), 2-(4-butoxyphenyl)-3-hydroxy-4H- chromen-4-one (10), and 2-(3-n-butoxyphenyl)-3-hydroxy-4H- chromen-4-one (11) as well as the trihydroxy derivative 3-hydroxy- 2-(3,4,5-trihydroxyphenyl)-4H-chromen-4-one (18) displayed high anti-inflammatory activity in carrageenin-induced rat paw edema. Additionally, the inhibition of enzymes of the arachidonic acid cascade by the derivatives was investigated in vitro. In contrast to the natural compound quercetin, the com-pounds were more potent inhibiting cyclooxygenase-1 than 5-lipoxygenase except for 3-hydroxy-7-methoxy-2-(4-methoxyphenyl)- 4H-chromen-4-one (5). No correlation between the antiinflammatory activity in the rat paw edema test and the inhibition of 5-lipoxygenase or cyclooxygenase-1 could be observed. In conclusion, the present results suggest that other effects than inhibition of these enzymes of the arachidonic acid cascade are important for the anti-inflammatory activity of the investigated alkoxyflavonols.
CMOS design near the limit of scaling (2002)

Beginning with a brief review of CMOS scaling trends from 1 µm to 0.1 µm, this paper examines the fundamental factors that will ultimately limit CMOS scaling and considers the design issues near the limit of scaling. The fundamental limiting factors are electron thermal energy, tunneling leakage through gate oxide, and 2D electrostatic scale length. Both the standby power and the active power of a processor chip will increase precipitously below the 0.1-µm or 100-nm technology generation. To extend CMOS scaling to the shortest channel length possible while still gaining significant performance benefit, an optimized, vertically and laterally nonuniform doping design (superhalo) is presented. It is projected that room-temperature CMOS will be scaled to 20-nm channel length with the superhalo profile. Low-temperature CMOS allows additional design space to further extend CMOS scaling to near 10 nm.
Safinamide as an Add-On Therapy to a Stable Dose of a Single Dopamine Agonist: Results from a Randomized, Placebo-Controlled, 24-Week Multicenter Trial in Early Idiopathic Parkinson Disease (PD) Patients (MOTION Study) (P01.061) (2013)

OBJECTIVE: To evaluate the efficacy and safety of two fixed doses of safinamide (50 and 100mg/day), compared to placebo, as add-on treatment to early PD patients receiving a stable dose of a single DA-agonist.
Dirhodium(II) Tetrakis[3(S)-phthalimido-2-piperidinonate]: A Novel Dirhodium(II) Carboxamidate Catalyst for Asymmetric Cyclopropanation (1996)

Dirhodium(I1) tetrakis[3(S)-phthalimido-2-piperidinonate] catalyzes cyclopropanation of a-methylstyrene with d-menthyl diazoacetate to give dmenthyl (lS,2S)-2-methyl-2-phenylcyclopropan~ of 90% de.The design and development of asymmetric catalysts to induce a high level of enantioselection in carboncarbon bond forming reactions have been the subject of intensive investigations in organic synthesis.'Our efforts in this area have led to the development of dirhodium(I1) tetrakis[N-phthaloyl-(S)phenylalaninate], Rhz[(S)-PTPA14, for intramolecular C-H insertion reactions of a-diazocarbonyl compounds,2 the efficacy of which has been demonstrated by the construction of optically active cyclopentanone, Zindanone, and 2-azetidinone derivatives with up to 95% ee, and also rationalized by evaluating an asymmetric environment at the rhodium(I1) carbene center featured by the two protruding phthalimido walls.As a logical extension of our efforts directed toward the development of dirhodium(I1)-catalyzed enantioselective carbene transformation^,^ our interest was centered on asymmetric cyclopropanation reactions.
Time-Sampled Linear Optical Phase Demodulation (2008)

Time-sampled optical phase demodulation is proposed, based on heterodyne detection of a phase modulated signal, digital frequency division and measurement of the timing of zero-crossings using an XOR-gate. 30dB improvement in intermodulation terms is measured.
The General Anesthetic Propofol Enhances the Function of γ‐Aminobutyric Acid‐Coupled Chloride Channel in the Rat Cerebral Cortex (1990)

The effect of the general anesthetic propofol on t-[35S]butylbicyclophosphorothionate ([35S]TBPS) binding to unwashed membrane preparations from rat cerebral cortex was studied and compared to that of other general anesthetics (pentobarbital, alphaxalone) which are known to enhance GABAergic transmission. Propofol produced a concentration-dependent complete inhibition of [35S]TBPS binding, an effect similar to that induced by pentobarbital and alphaxalone, although these agents differ markedly in potency (alphaxalone greater than propofol greater than pentobarbital). The concomitant addition of propofol either with alphaxalone or pentobarbital produced an additive inhibition of [35S]TBPS binding, suggesting separate sites of action or different mechanisms of these drugs. Moreover, although bicuculline (0.1 microM) completely antagonized the propofol-induced inhibition of [35S]TBPS binding, the effect of this anesthetic was not due to a direct interaction with the gamma-aminobutyric acidA (GABAA) recognition site. In fact, propofol, like alphaxalone and pentobarbital, markedly enhanced [3H]GABA binding in the rat cerebral cortex. Finally, propofol was able to enhance [3H]GABA binding in membranes previously incubated with the specific chloride channel blocker picrotoxin. Taken together these data strongly suggest that propofol, like other anesthetics and positive modulators of GABAergic transmission, might exert its pharmacological effects by enhancing the function of the GABA-activated chloride channel.
Wavelength-Scanned Surface-Enhanced Raman Excitation Spectroscopy (2005)

A detailed wavelength-scanned surface-enhanced Raman excitation spectroscopy (WS SERES) study of benzenethiol adsorbed on Ag nanoparticle arrays, fabricated by nanosphere lithography (NSL), is presented. These NSL-derived Ag nanoparticle array surfaces are both structurally well-characterized and extremely uniform in size. The WS SERES spectra are correlated, both spatially and spectrally, with the corresponding localized surface plasmon resonance (LSPR) spectra of the nanoparticle arrays. The surface-enhanced Raman scattering (SERS) spectra were measured in two excitation wavelength ranges: (1) 425-505 nm, and (2) 610-800 nm, as well as with the 532-nm line from a solid-state diode-pumped laser. The WS SERES spectra have line shapes similar to those of the LSPR spectra. The maximum SERS enhancement factor is shown to occur for excitation wavelengths that are blue-shifted with respect to the LSPR lambda(max) of adsorbate-covered nanoparticle arrays. Three vibrational modes of benzenethiol (1575, 1081, and 1009 cm(-1)) are studied simultaneously on one substrate, and it is demonstrated that the smaller Raman shifted peak shows a maximum enhancement closer to the LSPR lambda(max) than that of a larger Raman shifted peak. This is in agreement with the predictions of the electromagnetic (EM) enhancement mechanism of SERS. Enhancement factors of up to approximately 10(8) are achieved, which is also in good agreement with our previous SERES studies.
Successful scale-up of human embryonic stem cell production in a stirred microcarrier culture system (2009)

Future clinical applications of human embryonic stem (hES) cells will require high-yield culture protocols. Currently, hES cells are mainly cultured in static tissue plates, which offer a limited surface and require repeated sub-culturing. Here we describe a stirred system with commercial dextran-based microcarriers coated with denatured collagen to scale-up hES cell production. Maintenance of pluripotency in the microcarrier-based stirred system was shown by immunocytochemical and flow cytometry analyses for pluripotency-associated markers. The formation of cavitated embryoid bodies expressing markers of endoderm, ectoderm and mesoderm was further evidence of maintenance of differentiation capability. Cell yield per volume of medium spent was more than 2-fold higher than in static plates, resulting in a significant decrease in cultivation costs. A total of 10(8) karyotypically stable hES cells were obtained from a unitary small vessel that needed virtually no manipulation during cell proliferation, decreasing risks of contamination. Spinner flasks are available up to working volumes in the range of several liters. If desired, samples from the homogenous suspension can be withdrawn to allow process validation needed in the last expansion steps prior to transplantation. Especially when thinking about clinical trials involving from dozens to hundreds of patients, the use of a small number of larger spinners instead of hundreds of plates or flasks will be beneficial. To our knowledge, this is the first description of successful scale-up of feeder- and Matrigel-free production of undifferentiated hES cells under continuous agitation, which makes this system a promising alternative for both therapy and research needs.
Performance and structure of single-mode bosonic codes (2018)

The early Gottesman, Kitaev, and Preskill (GKP) proposal for encoding a qubit in an oscillator has recently been followed by cat- and binomial-code proposals. Numerically optimized codes have also been proposed, and we introduce codes of this type here. These codes have yet to be compared using the same error model; we provide such a comparison by determining the entanglement fidelity of all codes with respect to the bosonic pure-loss channel (i.e., photon loss) after the optimal recovery operation. We then compare achievable communication rates of the combined encoding-error-recovery channel by calculating the channel's hashing bound for each code. Cat and binomial codes perform similarly, with binomial codes outperforming cat codes at small loss rates. Despite not being designed to protect against the pure-loss channel, GKP codes significantly outperform all other codes for most values of the loss rate. We show that the performance of GKP and some binomial codes increases monotonically with increasing average photon number of the codes. In order to corroborate our numerical evidence of the cat-binomial-GKP order of performance occurring at small loss rates, we analytically evaluate the quantum error-correction conditions of those codes. For GKP codes, we find an essential singularity in the entanglement fidelity in the limit of vanishing loss rate. In addition to comparing the codes, we draw parallels between binomial codes and discrete-variable systems. First, we characterize one- and two-mode binomial as well as multiqubit permutation-invariant codes in terms of spin-coherent states. Such a characterization allows us to introduce check operators and error-correction procedures for binomial codes. Second, we introduce a generalization of spin-coherent states, extending our characterization to qudit binomial codes and yielding a multiqudit code.
Recent Progress in the Understanding of Pulsars (1986)

My life has been an interesting voyage. I became an astronomer because I could not imagine living on Earth and not trying to understand how the Universe works. My scientific career has revolved around observing the motions of stars within galaxies and the ...Read More
A Mechanistic Perspective of Monoclonal Antibodies in Cancer Therapy Beyond Target-Related Effects (2007)

Several monoclonal antibodies are now in clinical use for cancer therapy, and many others are currently undergoing clinical evaluation. These agents offer unique specificity against key molecular targets on tumor cells or in the tumor microenvironment. The clinical efficacy of monoclonal antibodies is generally attributed to target-specific mechanisms resulting from neutralizing or inhibiting a growth factor or receptor that drives cell proliferation and tumor growth. Several targets, including CD20, human epidermal growth factor receptor 2, vascular endothelial growth factor, and epidermal growth factor receptor, have been validated in specific malignancies on the basis of monoclonal antibody efficacy. However, monoclonal antibodies also have the potential to activate immune-mediated effector functions, including antibody-dependent cell-mediated cytotoxicity and complement-dependent cytotoxicity. These functions result from interactions involving the Fc domain of the antibody, and, consequently, may vary by antibody, isotype, and Fc modification, such as changes in glycosylation. Accordingly, all monoclonal antibodies directed against a given target should not be considered equivalent in their ability to stimulate immune-mediated effector functions.
Droplet Microfluidics for Producing Functional Microparticles (2013)

Isotropic microparticles prepared from a suspension that undergoes polymerization have long been used for a variety of applications. Bulk emulsification procedures produce polydisperse emulsion droplets that are transformed into spherical microparticles through chemical or physical consolidation. Recent advances in droplet microfluidics have enabled the production of monodisperse emulsions that yield highly uniform microparticles, albeit only on a drop-by-drop basis. In addition, microfluidic devices have provided a variety of means for particle functionalization through shaping, compartmentalizing, and microstructuring. These functionalized particles have significant potential for practical applications as a new class of colloidal materials. This feature article describes the current state of the art in the microfluidic-based synthesis of monodisperse functional microparticles. The three main sections of this feature article discuss the formation of isotropic microparticles, engineered microparticles, and hybrid microparticles. The complexities of the shape, compartment, and microstructure of these microparticles increase systematically from the isotropic to the hybrid types. Each section discusses the key idea underlying the design of the particles, their functionalities, and their applications. Finally, we outline the current limitations and future perspectives on microfluidic techniques used to produce microparticles.
Ubiquitin fusion augments the yield of cloned gene products in Escherichia coli. (1989)

Despite the availability of efficient transcription and translation signals, some heterologous gene products are not adequately expressed when introduced into prokaryotes and eukaryotes. An expression system has been established in Escherichia coli to increase the yield of cloned gene products, where the C terminus of ubiquitin was fused to the N terminus of unstable or poorly expressed proteins. Fusion of ubiquitin to yeast metallothionein or to the alpha subunit of the adenylate cyclase-stimulatory GTP-binding protein increased the yield from undetectable to 20% of the total cellular protein. A ubiquitin-N alpha-protein hydrolase has been partially purified from rabbit reticulocytes; this enzyme faithfully cleaves the junction peptide bound between the C-terminal Gly-76 of ubiquitin and the fusion protein. The increased yield of cloned gene products is very likely due to increased stability and/or more efficient translation of the fusion proteins. Possible mechanisms for the augmentation of ubiquitin fusion-protein expression in prokaryotes and eukaryotes are discussed.
Identification of Hepatitis C Virus NS5A Inhibitors (2009)

Using a cell-based replicon screen, we identified a class of compounds with a thiazolidinone core structure as inhibitors of hepatitis C virus (HCV) replication. The concentration of one such compound, BMS-824, that resulted in a 50% inhibition of HCV replicon replication was approximately 5 nM, with a therapeutic index of >10,000. The compound showed good specificity for HCV, as it was not active against several other RNA and DNA viruses. Replicon cells resistant to BMS-824 were isolated, and mutations were identified. A combination of amino acid substitutions of leucine to valine at residue 31 (L31V) and glutamine to leucine at residue 54 (Q54L) in NS5A conferred resistance to this chemotype, as did a single substitution of tyrosine to histidine at amino acid 93 (Y93H) in NS5A. To further explore the region(s) of NS5A involved in inhibitor sensitivity, genotype-specific NS5A inhibitors were used to evaluate a series of genotype 1a/1b hybrid replicons. Our results showed that, consistent with resistance mapping, the inhibitor sensitivity domain also mapped to the N terminus of NS5A, but it could be distinguished from the key resistance sites. In addition, we demonstrated that NS5A inhibitors, as well as an active-site inhibitor that specifically binds NS3 protease, could block the hyperphosphorylation of NS5A, which is believed to play an essential role in the viral life cycle. Clinical proof of concept has recently been achieved with derivatives of these NS5A inhibitors, indicating that small molecules targeting a nontraditional viral protein like NS5A, without any known enzymatic activity, can also have profound antiviral effects on HCV-infected subjects.
Splice junctions in adenovirus 2 early region 4 mRNAs: multiple splice sites produce 18 to 24 RNAs (1984)

We localized the splice junctions in adenovirus 2 early region 4 (E4) mRNAs. Processing of the E4 precursor RNA positioned the donor splice site of the 5' leader sequence adjacent to acceptor sites near the 5' ends of five of the six open reading regions in the E4 transcription unit. Of particular interest among the E4 mRNAs is an extensively spliced class which includes multiple species with sizes ranging from 1.1 to 0.75 kilobases (kb). Purified 1.1- to 0.75-kb mRNAs specified at least 10 polypeptides in vitro. We detected eight acceptor and two donor splice sites utilized in the deletion of the intron from the 3' portion of these mRNAs. E4 RNAs were isolated from the cytoplasm of infected cells at 5, 9, 12, and 18 h after infection. The E4 mRNAs were present throughout infection, but different members of the 1.1- to 0.7-kb class were predominant at each time assayed. Alternate splicing of the 3.0-kb E4 precursor RNA can generate as many as 25 mRNAs that encode at least 16 polypeptides.
Building Trust Online (2000)

Abstract A fundamental obstacle to the growth of E-commerce is the lack of trust which consumers are voicing over doing business online. Three main factors cause apprehension amongst online consumers.
Up71 and Up140, two novel transcripts of utrophin that are homologues of short forms of dystrophin (1999)

Utrophin is a large protein which accumulates at the neuromuscular synapse and myotendinous junctions in adult skeletal muscle, and is widely expressed in several non-skeletal muscle tissues. Evidence from a variety of sources suggests that a successful strategy for treatment of Duchenne muscular dystrophy patients will be to increase expression of utrophin in muscle. There is still much to be learnt about utrophin gene regulation, in particular regarding alternative isoforms, their promoters and role in muscle and non-muscle tissues. Using 5"-RACE we have identified two novel transcripts of utrophin, Up71 and Up140, with unique first exons and promoters located in intron 62 and intron 44, respectively. These transcripts appear to be structural homologues of the short dystrophin transcripts, Dp140 and Dp71, emphasizing the high degree of structural conservation between the utrophin and dystrophin genes. RT-PCR shows that Up71 and Up140 are widely expressed in both human and mouse tissues, including skeletal muscle. We present evidence for transcript-specific differential mRNA splicing of exon 71, in both Up71 and Up140, similar to that described for dystrophin. No evidence for splicing of exon 78 of utrophin was found. This is in contrast to dystrophin and may reflect a subtle functional difference in patterns of phosphorylation between the two proteins.