gebhart/patrepeval huggingface dataset:
Specific inhibition of hepatitis C viral gene expression by antisense phosphorothioate oligodeoxynucleotides (1995)

The inhibitory effect of antisense phosphorothioate oligodeoxynucleotides (S-ODN) on hepatitis C viral gene expression and analyzed in an in vitro test system and in cell culture. S-ODN were directed against different stem loop structures in the 5'noncoding region (NCR) of the hepatitis C virus, (HCV) RNA and against a nucleotide stretch, including the start codon of the polyprotein precursor. The inhibitory effect of these S-ODN was quantified employing a viral RNA consisting of the first 407 nucleotides of a HCV type 1b genome fused to the coding sequence of the firefly luciferase gene. For in vitro assays this RNA was generated by in vitro transcription and used as a template in a rabbit reticulocyte lysate in vitro translation system. The production of active luciferase in the absence or presence of S-ODN was monitored using an enzymatic assay. The best results were obtained with S-ODN 4 directed against nucleotides 326 to 348, comprising the start AUG of the polyprotein coding sequence. With this oligonucleotide, a specific and dose-dependent effect was observed with a maximal inhibition of 96 +/- 1% at a S-ODN concentration of 4.14 mumol/L. For cell culture experiments, the hepatoblastoma cell line HepG2 was transfected with a plasmid expressing the HCV-luciferase fusion RNA. In this assay system S-ODN 2, complementary to nucleotides 264 to 282 of the HCV RNA, and S-ODN 4 were most efficient and reduced the viral translation by 96 +/- 0.4% and 94 +/- 0.7%, respectively, at a concentration of 0.3 mumol/L. The inhibition was specific (1) because the expression of the HCV-luciferase fusion RNA was not significantly impaired by the control S-ODN and (2) because the expression of an unrelated messenger RNA was not or only slightly downregulated. These data suggest that HCV gene expression can be inhibited effectively by antisense S-ODN. Therefore, this approach represents a promising perspective for the treatment of hepatitis C.
The Synergistic Effects of DNA-Targeted Chemotherapeutics and Histone Deacetylase Inhibitors As Therapeutic Strategies for Cancer Treatment (2012)

Histone deacetylase (HDAC) inhibitors are a group of anticancer drugs which cause growth arrest and apoptosis of several tumor cells. HDAC inhibitors have been also found to increase the anticancer efficacy of several treatment modalities i.e. chemotherapy or radiotherapy. Here, we review the literature on combinations of HDAC inhibitors both with ionizing radiation and with other drugs, highlighting DNA-damaging compounds. The results of numerous studies with several types of cancer cells discussed in this review demonstrate that HDAC inhibitors enhance the effect of DNA damaging agents, such as inhibitors of topoisomerases, inhibitors of DNA synthesis, DNA-intercalators and agents covalently modifying DNA (i.e. doxorubicin, etoposid, 5-fluorouracil, cisplatin, melphalan, temozolomide and ellipticine) or of irradiation. Hence, the use of HDAC inhibitors combined with these antitumor drugs or ionizing radiation is a promising tool which may make treatment of patients suffering from many types of cancer more efficient. Several molecular mechanisms are responsible for the observed higher sensitivity of tumor cells towards therapeutic agents elicited by HDAC inhibitors. These mechanisms are discussed also in this review.
Mechanisms of inhibition of adenine phosphoribosyltransferase by adenine nucleosides and nucleotides (1970)

Kinetic studies of the inhibition of adenine phosphoribosyltransferase by adenine 6′-deoxyallofuranoside and 2′-deoxyadenylate indicate that both compounds bind to free enzyme and to the enzyme–phosphoribosylpyrophosphate complex, although they bind with different relative affinities to each enzyme form. The sites to which these inhibitors bind appear to be different from those to which substrates and products bind. Kinetic and physical studies show that adenosine diphosphate and adenosine triphosphate also bind to several enzyme forms, and that their mechanisms of inhibition of this enzyme are complex.
Amplitude Reduction and Phase Shifts of Melatonin, Cortisol and Other Circadian Rhythms after a Gradual Advance of Sleep and Light Exposure in Humans (2012)

Alterations in the timing of the sleep-wake cycle and associated bright or moderate light exposure can lead to changes in phase and reduction of circadian amplitude which are consistent across multiple variables but differ between individuals. These data have implications for our understanding of circadian organization and the negative health outcomes associated with shift-work, jet-lag and exposure to artificial light.
Optomechanical eye model with imaging capabilities for objective evaluation of intraocular lenses (2006)

The optomechanical eye model provided objective grading of IOLs through the evaluation of simulated visual acuity, which can be scaled usefully to human vision. The eye model also allowed the qualitative visualization of IOL imaging properties, making it potentially useful in characterizing and distinguishing different IOL types.
Spinal Cord Stimulation Electrode Design: Prospective, Randomized, Controlled Trial Comparing Percutaneous and Laminectomy Electrodes???Part I: Technical Outcomes (2002)

OBJECTIVE The clinical use of spinal cord stimulation for treatment of chronic intractable pain has been increasingly successful because of recent technical improvements, particularly the development of multiple-contact electrodes supported by programmable implanted pulse generators. Contemporary electrodes can be placed percutaneously in some cases and require a limited laminectomy in other cases. METHODS We performed a prospective, randomized, controlled trial comparing two prototypical electrode designs, using a computerized system that allows direct patient interaction and quantitative measurements. A series of 24 patients with chronic lumbosacral pain syndromes first underwent testing with percutaneous four-contact electrodes and then underwent implantation, at the same spinal level, of one of two different electrode configurations; 12 patients received a new percutaneous four-contact electrode of the same design and 12 received an insulated four-contact array, which was implanted via laminectomy. RESULTS The insulated array performed significantly (P = 0.0005–0.0047) better than the temporary percutaneous electrode for the same patients, according to all three measures tested (ratings of paresthesia coverage of pain, coverage calculated from patient drawings, and amplitudes), at the “usage” amplitude for the three standard bipoles examined. The insulated array also performed significantly (P = 0.0000–0.026) better than the permanent percutaneous electrode in terms of coverage ratings and amplitude requirements. Low back coverage ratings were significantly better for the insulated array than for the temporary percutaneous electrode, and scaled amplitudes necessary for low back coverage were significantly better for the permanent percutaneous electrode than for the temporary electrode. In comparison with the percutaneous temporary electrode, at subjectively identical stimulation intensities, the permanent insulated array required significantly lower amplitude. CONCLUSION We can immediately infer from these technical data that the use of an insulated array, in comparison with a percutaneous electrode, would double battery life. Extended follow-up monitoring will be required to assess the extent to which the technical advantages we observed for the insulated array might be associated with improved clinical outcomes.
Dynamic wavelength selective add/drop node comprisingtunable gratings (1997)

The authors propose an add/drop node, consisting of pairs of tunable and static gratings for the realisation of dynamic wavelength selection. Wavelength switching with small wavelength tuning and maximum wavelength channel density for a given grating bandwidth are attained.
Asymmetric synthesis of chiral amines with omega-transaminase. (1999)

The asymmetric synthesis of chiral amines using prochiral ketones was carried out with (S)-specific omega-transaminase (omega-TA) from Vibrio fluvialis JS17. This reaction is inhibited severely by both products, (S)-amine and deaminated ketone. In addition, thermodynamic equilibrium strongly favored the reverse reaction. L-Alanine proved to be the best amino donor based on easy removal of the products. Optimal pH of the reactions with both whole cells and cell-free extract was 7. Amino acceptor reactivities of ketone substrates and reaction profiles of the asymmetric synthesis showed that the initial rate as well as the reaction yield were lower when the resulting (S)-amine from a prochiral ketone substrate was a more reactive amino donor. The yield could be increased dramatically by removing pyruvate, which is a more inhibitory product than (S)-alpha-methylbenzylamine [(S)-alpha-MBA] when acetophenone and L-alanine are used as an amino acceptor and donor, respectively. The removal of pyruvate was carried out by incorporating lactate dehydrogenase (LDH) in cell-free extract or by using whole cells. The whole cell reaction yielded a much better result. When 25 mM benzylacetone and 30 mM acetophenone were used as an amino acceptor with 300 mM L-alanine, 90.2% and 92.1% of the reaction yields after 1 day were obtained with whole cells, respectively. Enantiomeric excesses of both (S)-alpha-MBA and (S)-1-methyl-3-phenylpropylamine [(S)-MPPA] were all above 99%.
Charge equilibration for molecular dynamics simulations (1991)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTCharge equilibration for molecular dynamics simulationsAnthony K. Rappe and William A. Goddard IIICite this: J. Phys. Chem. 1991, 95, 8, 3358–3363Publication Date (Print):April 1, 1991Publication History Published online1 May 2002Published inissue 1 April 1991https://doi.org/10.1021/j100161a070RIGHTS & PERMISSIONSArticle Views11733Altmetric-Citations2479LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InReddit PDF (1 MB) Get e-Alerts
CMOL FPGA: a reconfigurable architecture for hybrid digital circuits with two-terminal nanodevices (2005)

This paper describes a digital logic architecture for 'CMOL' hybrid circuits which combine a semiconductor–transistor (CMOS) stack and two levels of parallel nanowires, with molecular-scale nanodevices formed between the nanowires at every crosspoint. This cell-based, field-programmable gate array (FPGA)-like architecture is based on a uniform, reconfigurable CMOL fabric, with four-transistor CMOS cells and two-terminal nanodevices ('latching switches'). The switches play two roles: they provide diode-like I–V curves for logic circuit operation, and allow circuit mapping on CMOL fabric and its reconfiguration around defective nanodevices. Monte Carlo simulations of two simple circuits (a 32-bit integer adder and a 64-bit full crossbar switch) have shown that the reconfiguration allows one to increase the circuit yield above 99% at the fraction of bad nanodevices above 20%. Estimates have shown that at the same time the circuits may have extremely high density (approximately 500 times higher than that of the usual CMOS FPGAs with the same design rules), while operating at higher speed at acceptable power consumption.
A functional comparison of CD34 + CD38- cells in cord blood and bone marrow (1995)

We present cell cycling and functional evidence that the CD34+CD38- immunophenotype can be used to define a rare and primitive subpopulation of progenitor cells in umbilical cord blood. CD34+CD38- cells comprise 0.05% +/- 0.08% of the mononuclear cells present in cord blood. Cell cycle analysis with the fluorescent DNA stain 7-aminoactinomycin D showed that the percentage of CD34+ cells in cycle directly correlated with increasing CD38 expression. CD34+CD38- cord blood cells were enriched for long-term culture-initiating cells (LTCIC; cells able to generate colony-forming unit-cells [CFU-C] after 35 to 60 days of coculture with bone marrow stroma) relative to CD34+CD38- cells. In an extended LTCIC assay, CD34+CD38- cells were able to generate CFU-C between days 60 and 100, clearly distinguishing them from CD34+CD38+ cells that did not generate CFU-C beyond day 40. When plated as single cells, onset of clonal proliferation was markedly delayed in a subpopulation of CD34+CD38- cells; clones (defined as > 100 cells) appeared after 60 days of culture in 2.9% of CD34+CD38- cells. In contrast, 100% of CD34+CD38+ cells formed clones by day 21. Although the CD34+CD38- immunophenotype defines highly primitive populations in both bone marrow and cord blood, important functional differences exist between the two sources. CD34+CD38- cord blood cells have a higher cloning efficiency, proliferate more rapidly in response to cytokine stimulation, and generate approximately sevenfold more progeny than do their counterparts in bone marrow.
Selective Guest Binding by Tailored Channels in a 3-D Porous Zinc(II)−Benzenetricarboxylate Network (1997)

Diffusion of triethylamine into an ethanol solution containing 1,3,5-benzenetricarboxylic acid (H3BTC) and zinc(II) nitrate hexahydrate yields crystalline Zn2(BTC)(NO3)·(H2O)(C2H5OH)5, which was formulated by elemental microanalysis, solid-state NMR, and single-crystal X-ray diffraction [cubic, P213, a = 14.728(2) Å, V = 3195(2) Å3, Z = 4]. This compound possesses a 3-D structure with nearly 44% of the framework represented by an extended channel system having a 14 Å cross-section, where highly mobile ethanol and water guest molecules reside. The multidentate functionality of BTC imparts rigidity to the structure, consequently allowing the guests to be removed or exchanged without destruction of the porous framework. X-ray powder diffraction, solid-state NMR (13C CP MAS and static), gas chromatography, and thermogravimetry analyses reveal that this material is highly selective to alcohols because of the coordination environment adopted by Zn(II) within its framework. Other molecular inclusions such as tetrahydrofuran, methyl ethyl ketone, acetonitrile, and acetone are not permitted into the channels, due to the specific electronic demands of the Zn(II) center and its ability to direct the inclusion process even in cases where incoming molecules have the appropriate shape and size for inclusion.
Mutations That Decrease DNA Binding of the Processivity Factor of the Herpes Simplex Virus DNA Polymerase Reduce Viral Yield, Alter the Kinetics of Viral DNA Replication, and Decrease the Fidelity of DNA Replication (2007)

The processivity subunit of the herpes simplex virus DNA polymerase, UL42, is essential for viral replication and possesses both Pol- and DNA-binding activities. Previous studies demonstrated that the substitution of alanine for each of four arginine residues, which reside on the positively charged surface of UL42, resulted in decreased DNA binding affinity and a decreased ability to synthesize long-chain DNA by the polymerase. In this study, the effects of each substitution on the production of viral progeny, viral DNA replication, and DNA replication fidelity were examined. Each substitution mutant was able to complement the replication of a UL42 null mutant in transient complementation assays and to support the replication of plasmid DNA containing herpes simplex virus type 1 (HSV-1) origin sequences in transient DNA replication assays. Mutant viruses containing each substitution and a lacZ insertion in a nonessential region of the genome were constructed and characterized. In single-cycle growth assays, the mutants produced significantly less progeny virus than the control virus containing wild-type UL42. Real-time PCR assays revealed that these UL42 mutants synthesized less viral DNA during the early phase of infection. Interestingly, during the late phase of infection, the mutant viruses synthesized larger amounts of viral DNA than the control virus. The frequencies of mutations of the virus-borne lacZ gene increased significantly in the substitution mutants compared to those observed for the control virus. These results demonstrate that the reduced DNA binding of UL42 is associated with significant effects on virus yields, viral DNA replication, and replication fidelity. Thus, a processivity factor can influence replication fidelity in mammalian cells.
Bone Marrow Angiogenesis and Progression in Multiple Myeloma: Clinical Significance and Therapeutic Approach (2003)

It is now well established that solid tumors depend on angiogenesis. Promoters and inhibitors of angiogenesis are in balance and antiangiogenic strategies aim at repressing the angiogenic process, thus retarding solid tumor progression. Recent data suggest the importance of angiogenesis in hematologic malignancies and several studies reveal an increased angiogenesis in active multiple myeloma. Angiogenesis seems to be a prominent feature of MM progression, and seems to be correlated with the prognosis and the resistance of MM to chemotherapy. Numerous cell populations and cytokines are involved in angiogenesis in multiple myeloma and antiangiogenic therapy with thalidomide is effective in patients with refractory or relapsed disease. The combination of thalidomide and of other immunomodulatory agents with other therapeutic regimens could lead to more effective management of patients with multiple myeloma.
Neurotrophin Regulation of β-Actin mRNA and Protein Localization within Growth Cones (1999)

Neurotrophins play an essential role in the regulation of actin-dependent changes in growth cone shape and motility. We have studied whether neurotrophin signaling can promote the localization of beta-actin mRNA and protein within growth cones. The regulated localization of specific mRNAs within neuronal processes and growth cones could provide a mechanism to modulate cytoskeletal composition and growth cone dynamics during neuronal development. We have previously shown that beta-actin mRNA is localized in granules that were distributed throughout processes and growth cones of cultured neurons. In this study, we demonstrate that the localization of beta-actin mRNA and protein to growth cones of forebrain neurons is stimulated by neurotrophin-3 (NT-3). A similar response was observed when neurons were exposed to forskolin or db-cAMP, suggesting an involvement of a cAMP signaling pathway. NT-3 treatment resulted in a rapid and transient stimulation of PKA activity that preceded the localization of beta-actin mRNA. Localization of beta-actin mRNA was blocked by prior treatment of cells with Rp-cAMP, an inhibitor of cAMP-dependent protein kinase A. Depolymerization of microtubules, but not microfilaments, inhibited the NT-3-induced localization of beta-actin mRNA. These results suggest that NT-3 activates a cAMP-dependent signaling mechanism to promote the microtubule-dependent localization of beta-actin mRNA within growth cones.
Thyroid Hormone Regulation of Hepatic Genes in Vivo Detected by Complementary DNA Microarray (2000)

The liver is an important target organ of thyroid hormone. However, only a limited number of hepatic target genes have been identified, and little is known about the pattern of their regulation by thyroid hormone. We used a quantitative fluorescent cDNA microarray to identify novel hepatic genes regulated by thyroid hormone. Fluorescent-labeled cDNA prepared from hepatic RNA of T3-treated and hypothyroid mice was hybridized to a cDNA microarray, representing 2225 different mouse genes, followed by computer analysis to compare relative changes in gene expression. Fifty five genes, 45 not previously known to be thyroid hormone-responsive genes, were found to be regulated by thyroid hormone. Among them, 14 were positively regulated by thyroid hormone, and unexpectedly, 41 were negatively regulated. The expression of 8 of these genes was confirmed by Northern blot analyses. Thyroid hormone affected gene expression for a diverse range of cellular pathways and functions, including gluconeogenesis, lipogenesis, insulin signaling, adenylate cyclase signaling, cell proliferation, and apoptosis. This is the first application of the microarray technique to study hormonal regulation of gene expression in vivo and should prove to be a powerful tool for future studies of hormone and drug action.
Oxygen-induced p-type doping of a long individual single-walled carbon nanotube (2005)

The effect of oxygen adsorption on a nanotube-based field effect transistor have been controversial as to whether it induces p-type doping of the nanotube body or the work function increase in the metal electrode. Here we report a transport measurement showing that a long individual single-walled nanotube can be doped as p-type upon oxygen adsorption. We discuss that, despite the fact that the charge transfer between the nanotube and O2 adsorbator has not been agreed to date, the effect of oxygen adsorption should still be interpreted as inducing p-type doping in the nanotube body. The n-type doping by NH3 adsorption is also measured for the purpose of comparison. Based on these observations, we suggest that, while the Schottky barrier management could be more effective for the transistor with a short nanotube, the doping effect could be more influential in devices with longer nanotubes.
High-density magnetic recording: a driving force for HDTV? (1990)

Rotary digital magnetic tape recorders are being used for both audio (DAT), and for data (Exabyte 8 mm drive). In both of these commercially available products, the areal storage density approaches 100,000,000 bits/square inch at acceptable error rates. The characteristics of a helical-scan recorder with even higher areal densities designed for HDTV use is described. A complete digital HDTV system is described along with the constraints and requirements of the various functional components. In addition, the current state of HDTV being proposed in America is also described. >
Anaphylatoxin Formation in Sepsis (1988)

Complement activation and anaphylatoxin formation were studied in 27 septic patients. The patients were treated with antibiotics and high-dose corticosteroids. Blood samples were drawn on admission and every week thereafter. Plasma levels of complement components C1INH, C3, C4, and C5 were low before the start of treatment but were above normal one week later in both successfully and unsuccessfully treated patients. In contrast, plasma levels of anaphylatoxins C3a/C3adesArg and C5a/C5adesArg were elevated on admission. After successful treatment, plasma levels of C3a/C3adesArg and C5a/C5adesArg returned to normal within one week. Nine patients had ongoing sepsis one week after the start of treatment and a persistent rise in anaphylatoxin concentration. They developed multisystem organ failure with respiratory, hepatic, and renal insufficiency. In vitro studies of Escherichia coli incubation in fresh serum indicated a dose-related formation of C3a/C3adesArg and C5a/C5adesArg. High concentrations of methylprednisolone inhibited the anaphylatoxin formation in vitro.