gebhart/patrepeval huggingface dataset:
Efficient Repair of Genomic Double-Strand Breaks by Homologous Recombination between Directly Repeated Sequences in the Plant Genome (2002)

Previous studies demonstrated that in somatic plant cells, homologous recombination (HR) is several orders of magnitude less efficient than nonhomologous end joining and that HR is little used for genomic double-strand break (DSB) repair. Here, we provide evidence that if genomic DSBs are induced in close proximity to homologous repeats, they can be repaired in up to one-third of cases by HR in transgenic tobacco. Our findings are relevant for the evolution of plant genomes because they indicate that sequences containing direct repeats such as retroelements might be less stable in plants that harbor active mobile elements than anticipated previously. Furthermore, our experimental setup enabled us to demonstrate that transgenic sequences flanked by sites of a rare cutting restriction enzyme can be excised efficiently from the genome of a higher eukaryote by HR as well as by nonhomologous end joining. This makes DSB-induced recombination an attractive alternative to the currently applied sequence-specific recombination systems used for genome manipulations, such as marker gene excision.
Skeletal Muscle Fatigue: Cellular Mechanisms (2008)

Repeated, intense use of muscles leads to a decline in performance known as muscle fatigue. Many muscle properties change during fatigue including the action potential, extracellular and intracellular ions, and many intracellular metabolites. A range of mechanisms have been identified that contribute to the decline of performance. The traditional explanation, accumulation of intracellular lactate and hydrogen ions causing impaired function of the contractile proteins, is probably of limited importance in mammals. Alternative explanations that will be considered are the effects of ionic changes on the action potential, failure of SR Ca2+ release by various mechanisms, and the effects of reactive oxygen species. Many different activities lead to fatigue, and an important challenge is to identify the various mechanisms that contribute under different circumstances. Most of the mechanistic studies of fatigue are on isolated animal tissues, and another major challenge is to use the knowledge generated in these studies to identify the mechanisms of fatigue in intact animals and particularly in human diseases.
Control of Spoken Vowel Acoustics and the Influence of Phonetic Context in Human Speech Sensorimotor Cortex (2014)

Speech production requires the precise control of vocal tract movements to generate individual speech sounds (phonemes) which, in turn, are rapidly organized into complex sequences. Multiple productions of the same phoneme can exhibit substantial variability, some of which is inherent to control of the vocal tract and its biomechanics, and some of which reflects the contextual effects of surrounding phonemes ("coarticulation"). The role of the CNS in these aspects of speech motor control is not well understood. To address these issues, we recorded multielectrode cortical activity directly from human ventral sensory-motor cortex (vSMC) during the production of consonant-vowel syllables. We analyzed the relationship between the acoustic parameters of vowels (pitch and formants) and cortical activity on a single-trial level. We found that vSMC activity robustly predicted acoustic parameters across vowel categories (up to 80% of variance), as well as different renditions of the same vowel (up to 25% of variance). Furthermore, we observed significant contextual effects on vSMC representations of produced phonemes that suggest active control of coarticulation: vSMC representations for vowels were biased toward the representations of the preceding consonant, and conversely, representations for consonants were biased toward upcoming vowels. These results reveal that vSMC activity for phonemes are not invariant and provide insight into the cortical mechanisms of coarticulation.
Chemotherapy of advanced ovarian cancer. (1998)

Combination chemotherapy with paclitaxel plus a platinum compound (carboplatin or cisplatin) is the current regimen of choice for the treatment of advanced epithelial ovarian cancer. The two most widely used combinations are paclitaxel (135 mg/m2, 24-hour infusion) plus cisplatin (75 mg/m2) or paclitaxel (175 mg/m2, 3-hour infusion) plus carboplating dosed to an area under curve of 7.5. Randomized trials are in progress comparing these two regimens. Numerous other clinical issues remain regarding how to maximize the effectiveness of this therapy, including dose and schedule, duration of treatment, route of administration, and incorporation of other agents with novel mechanisms of cytotoxicity. New agents currently undergoing evolution as part of novel induction regimens have been shown to have significant activity in recurrent ovarian cancer and include topotecan, gemcitabine, oral etoposide, and encapsulated doxorubicin.
Microfabrication in silicon microphysiometry (1994)

Over the past 5 years, microphysiometry has proved an effective means for detecting physiological changes in cultured cells, particularly as a functional assay for the activation of many cellular receptors. To demonstrate the clinical relevance of this method, we have used it to detect bacterial antibiotic sensitivity and to discriminate between bacteriostatic and bacteriocidal concentrations. The light-addressable potentiometric sensor, upon which microphysiometry is based, is well suited for structural manipulations based on photolithography and micromachining, and we have begun to take advantage of this capability. We present results from a research instrument with eight separate assay channels on a 5-cm2 chip. We discuss the planned evolution of the technology toward high-through-put instruments and instruments capable of performing single-cell measurements.
A Mild Amide to Carbamate Transformation (1997)

ADVERTISEMENT RETURN TO ISSUEPREVNoteNEXTA Mild Amide to Carbamate TransformationMark J. Burk and John G. AllenView Author Information Paul M. Gross Chemical Laboratory, Duke University, Durham, North Carolina 27708-0348 Cite this: J. Org. Chem. 1997, 62, 20, 7054–7057Publication Date (Web):October 3, 1997Publication History Received20 May 1997Published online3 October 1997Published inissue 1 October 1997https://pubs.acs.org/doi/10.1021/jo970903jhttps://doi.org/10.1021/jo970903jbrief-reportACS PublicationsCopyright © 1997 American Chemical SocietyRequest reuse permissionsArticle Views3281Altmetric-Citations119LEARN 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 InRedditEmail Other access optionsGet e-AlertscloseSupporting Info (1)»Supporting Information Supporting Information SUBJECTS:Amides,Crystal cleavage,Hydrolysis,Organic compounds,Organic reactions Get e-Alerts
Current-Induced Switching of Perpendicularly Magnetized Magnetic Layers Using Spin Torque from the Spin Hall Effect (2012)

We show that in a perpendicularly magnetized Pt/Co bilayer the spin-Hall effect (SHE) in Pt can produce a spin torque strong enough to efficiently rotate and switch the Co magnetization. We calculate the phase diagram of switching driven by this torque, finding quantitative agreement with experiments. When optimized, the SHE torque can enable memory and logic devices with similar critical currents and improved reliability compared to conventional spin-torque switching. We suggest that the SHE torque also affects current-driven magnetic domain wall motion in Pt/ferromagnet bilayers.
An Integrated Multiassay Approach to the Discovery of Small-Molecule N-Type Voltage-Gated Calcium Channel Antagonists (2010)

Abstract The N-type voltage-gated calcium channel (Cav2.2) has been intensively explored as a target for novel, small-molecule analgesic drugs because of its distribution in the pain pathway and its role in nociceptive processing. For example, Cav2.2 is localized at presynaptic terminals of pain fibers in the dorsal horn, and it serves as a downstream effector of μ-opioid receptors. Most importantly, antagonism of the channel by the highly specific and potent Cav2.2 blocker ω-conotoxin MVIIA (ziconotide) produces clinical efficacy in the treatment of severe, intractable pain. To identify novel small-molecule Cav2.2 inhibitors, we developed new tools and screening methods critical to enhance the efficiency and probability of success. First, we established and characterized a new cell line stably expressing the three subunits of the Cav2.2, including an α-subunit splice variant that is uniquely expressed by dorsal root ganglion neurons. Second, using this cell line, we validated and employed a fluorescence-based calcium flux assay. Third, we developed a new "medium-throughput" electrophysiology assay using QPatch-HT to provide faster turnaround on high-content electrophysiology data that are critical for studying ion channel targets. Lastly, we used a therapeutically relevant, ex vivo spinal cord calcitonin gene-related peptide-release assay to confirm activities in the other assays. Using this approach we have identified compounds exhibiting single-digit nM IC₅₀ values and with a positive correlation across assay methods. This integrated approach provides a more comprehensive evaluation of small-molecule N-type inhibitors that may lead to improved therapeutic pharmacology.
The IL Sequence in the LLKIL Motif in CXCR2 Is Required for Full Ligand-induced Activation of Erk, Akt, and Chemotaxis in HL60 Cells (2006)

The chemotaxis of differentiated HL60 cells stably expressing CXCR2 was examined in a microfluidic gradient device where the steepness of the CXCL8 chemokine gradient was varied from 2 pg/ml/mum (0-1 ng/ml over a width of 500 microm) to 50 pg/ml/microm (0-25 ng/ml over 500 microm). The differentiated HL60 cells stably expressing CXCR2 exhibited little chemotaxis in response to a 0-1 ng/ml gradient, but displayed an increasing chemotactic response as the gradient steepness increased from 0 to 5, 0 to 10, and 0 to 25 ng/ml, demonstrating that steepness of gradient is a major determinant of the relative ability of cells to persistently migrate up a chemotactic gradient. When HL60 cells expressed CXCR2 mutated in the C terminus LLKIL motif (IL to AA), ligand-induced internalization of receptors was reduced 50%, whereas cell migration along the gradient of CXCL8 was completely lost. Although both mutant and wild-type receptors could mediate Akt and Erk activation in response to CXCL8, the level of activation of these two kinases was much lower in the cell line expressing the mutant receptors. These data imply that the IL amino acid residues in the LLKIL motif are very important for activation of the signal transduction cascade, which is necessary for cells to sense the chemokine gradient and respond with chemotaxis. Moreover, because mutation of the IL residues in the LLKIL motif resulted in only 50% reduction in receptor internalization, and a 50% reduction in Akt and Erk phosphorylation, but a complete loss of chemotactic response, the data imply that IL amino acid residues in the LLKIL motif are key either for amplification or oscillation of crucial signaling events or for establishment of a threshold for signals required for chemotaxis.
Purification and characterization of aminoglycoside 3'-phosphotransferase type IIa and kinetic comparison with a new mutant enzyme (1994)

Aminoglycoside 3'-phosphotransferase [APH(3')s] provide an important means for high-level resistance to neomycin- and kanamycin-type aminoglycoside antibiotics. A four-step purification which affords milligram quantities of homogeneous APH(3') type IIa [APH(3')-IIa] is described. The kinetic parameters for the turnover of five substrates by the enzyme were determined, and the pH dependence and metal activation for catalysis were investigated. All five cysteines in the amino acid sequence of the enzyme exist in their reduced forms; hence, there are no disulfide bonds in the protein. Modification of the cysteine thiols by S-cyanylation showed essentially no effect on the enzymatic activity. A mutant enzyme derived from APH-3'-IIa, which possesses a conservative Glu-182-Asp point mutation and which provides diminished resistance to G418 (R. L. Yenofsky, M. Fine, and J. W. Pellow, Proc. Natl. Acad. Sci. USA 87:3435-3439, 1990), was also purified to homogeneity. Kinetic analysis of this mutant protein indicated an increase of approximately ninefold in the Km for Mg2+ ATP. Insofar as Km may approximate Ks, this finding argues for the involvement of residue 182 in the binding of Mg2+ ATP. Thus, purified APH(3')-IIa and a point mutant derivative enzyme were characterized enzymologically, and the roles of metal cofactors and the five reduced cysteine residues were probed in the wild-type enzyme.
Soluble CD137 (4-1BB) Ligand Is Released Following Leukocyte Activation and Is Found in Sera of Patients with Hematological Malignancies (2001)

Expression of CD137 ligand (4-1BBL), a member of the TNF family of proteins, has been reported on several types of APCs, various carcinoma cells, and can be induced on activated T cells. In this study, we report that the soluble ligand was released constitutively at low levels from leukocytes and at higher levels following cellular activation. Release from cells was blocked by addition of a metalloproteinase inhibitor which concomitantly caused the accumulation of 4-1BBL on the cell surface. In addition, we show that a soluble form of 4-1BBL was present at high levels in the sera of some patients with various hematological diseases, but only at low levels in healthy donors. Soluble 4-1BBL was active in that it competed with recombinant 4-1BBL for binding to the 4-1BB receptor and was able to costimulate IL-2 and IFN-gamma release from peripheral T cells. These results indicate that the release of soluble 4-1BBL from the cell surface is mediated by one or more sheddases and likely regulates 4-1BB-4-1BBL interactions between cells in vivo. Cleavage of 4-1BBL to an active soluble form would alter both proximal and distal cellular responses, including cell survival and costimulatory or inflammatory responses, that are mediated through the 4-1BB pathway. This, in turn, would likely alter disease progression or outcome.
Enzyme immobilization by condensation copolymerization into crosslinked polyacrylamide gels (1980)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTEnzyme immobilization by condensation copolymerization into crosslinked polyacrylamide gelsAlfred Pollak, Hugh Blumenfeld, Michael Wax, Richard L. Baughn, and George M. WhitesidesCite this: J. Am. Chem. Soc. 1980, 102, 20, 6324–6336Publication Date (Print):September 1, 1980Publication History Published online1 May 2002Published inissue 1 September 1980https://pubs.acs.org/doi/10.1021/ja00540a026https://doi.org/10.1021/ja00540a026research-articleACS PublicationsRequest reuse permissionsArticle Views2239Altmetric-Citations231LEARN 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 InRedditEmail Other access optionsGet e-Alertsclose Get e-Alerts
Self-reports of pain intensity and direct observations of pain behavior: when are they correlated? (2003)

Meta-analytic techniques were utilized to investigate the relationship between self-reports of pain intensity and direct observations of pain behavior. Estimation of the overall effect size from 29 studies and 85 effect sizes yielded a moderately positive association, z=0.26. High variability across studies permitted a random-effects moderator analysis that determined chronicity of pain, the timing of the pain assessment, the use of global measures of pain behavior, and pain site significantly moderate the relationship between self-reports of pain intensity and direct observations of pain behavior. These findings indicate that self-reports of pain intensity and direct observations of pain behavior are more likely to be significantly related to each other when the individual being studied has acute pain (z=0.35), when the self-report of pain intensity data are collected soon after the observation of pain behavior (z=0.40), when global composite measures are used to quantify pain behavior (z=0.37), and when the person being observed suffers from chronic low back pain (z=0.30). Other factors not found to be significant moderators include: extent of observer training, relevance of the pain-inducing task, and pain behavior observation measure used. The implications of the findings for the assessment of pain are discussed.
Adenovirus Infections in Human Immunodeficiency Virus-Positive Patients: Clinical Features and Molecular Epidemiology (1995)

Prospective surveillance of 63 human immunodeficiency virus (HIV)-positive patients and 9 HIV-negative partners over 5-27 months yielded 51 adenoviruses from 18 HIV-positive patients. These were serotyped and compared by restriction enzyme analysis (REA) together with 24 isolates from 19 other HIV-positive patients. The actuarial risk of infection at 1 year in HIV-positive patients was 28% (17% with entry CD4 cell count of > 200/mm3 and 38% with CD4 cell count of < or = 200/mm3, P = .03). The most frequent site of infection was gastrointestinal (17/18 patients) with mainly subgenus D adenoviruses, while urinary infection was caused by subgenus B or D. Prolonged fecal excretion (2-27 months) was associated with CD4 cell counts < 150/mm3. Identical strains were seen in 2 HIV-positive partners and 2 unrelated patients. Gastrointestinal infection was temporally associated with diarrhea in only 7 (41%) of 17 cases. The remainder (59%) were asymptomatic or minimally symptomatic, and diarrhea was often caused by other opportunistic pathogens.
Prediction and Molecular Modeling of T-cell Epitopes Derived from Placental Alkaline Phosphatase for use in Cancer Immunotherapy (2006)

Abstract In our ongoing efforts to combat cancer, peptide-based tumor vaccines are promising as one of the several alternatives used for cancer immunotherapy and immunoprevention. We have attempted to identify T-cell epitopes suitable for the development of a peptide-based cancer vaccine directed towards placental isozyme of alkaline phosphatase (PLAP), an oncofetal antigen. After identifying amino acid residues specific to PLAP and distinct from other close PLAP homologs, we have used sequence-based immunoinformatics tools (BIMAS and SYF- PEITHI) and conducted molecular modeling studies using InsightII to investigate the binding affinity of the epitopes containing the unique residues with respective MHC class I molecules. Promiscuous epitopes binding to different alleles of different class I HLA loci were analyzed to get a population coverage that is widespread. Binding affinity deduced from the modeling studies corroborated the status of most of the epitopes scoring high in BIMAS and SYFPEITHI. We have thus identified specific epitopes from PLAP that have a potential for binding to their respective MHC class I alleles with high affinity. These peptides would be analysed in experiments to demonstrate their involvement in the induction of primary cytotoxic T-cell responses in vitro, using respective HLA-restricted T-cells in our way towards the development of an effective anti-cancer vaccine in a background of diverse MHC haplotypes.
Partial DPSK with excellent filter tolerance and OSNR sensitivity (2006)

Tolerance to optical filtering of a DPSK system can be increased significantly by decreasing the differential delay of the traditional MZI-demodulator to less than one bit-period. It is shown that a 43 Gbit/s DPSK signal can support 50 GHz channel spacing if the delay is decreased to 65% of a bit-period.
Fibroblast Growth Factor (FGF)-2 and FGF Receptor 3 Are Required for the Development of the Substantia Nigra, and FGF-2 Plays a Crucial Role for the Rescue of Dopaminergic Neurons after 6-Hydroxydopamine Lesion (2007)

Basic fibroblast growth factor (FGF-2) is involved in the development and maintenance of the nervous system. Exogenous administration of FGF-2 increased dopaminergic (DA) graft survival in different animal models of Parkinson's disease. To study the physiological function of the endogenous FGF-2 system, we analyzed the nigrostriatal system of mice lacking FGF-2, mice overexpressing FGF-2, and FGF-receptor-3 (FGFR3)-deficient mice both after development and after 6-hydroxydopamine lesion. FGFR3-deficient mice (+/-) displayed a reduced number of DA neurons compared with the respective wild type. Whereas absence of FGF-2 led to significantly increased numbers of DA neurons, enhanced amount of the growth factor in mice overexpressing FGF-2 resulted in less tyrosine hydroxylase expression and a reduced DA cell density. The volumes of the substantia nigra were enlarged in both FGF-2(-/-) and in FGF-2 transgenic mice, suggesting an important role of FGF-2 for the establishment of the proper number of DA neurons and a normal sized substantia nigra during development. In a second set of experiments, the putative relevance of endogenous FGF-2 after neurotoxin application was investigated regarding the number of rescued DA neurons after partial 6-OHDA lesion. Interestingly, the results after lesion were directly opposed to the results after development: significantly less DA neurons survived in FGF-2(-/-) mice compared with wild-type mice. Together, the results indicate that FGFR3 is crucially involved in regulating the number of DA neurons. The lack of FGF-2 seems to be (over)compensated during development, but, after lesion, compensation mechanisms fail. The transgenic mice showed that endogenous FGF-2 protects DA neurons from 6-OHDA neurotoxicity.