gebhart/patrepeval huggingface dataset:
Prime Editing Efficiency and Fidelity are Enhanced in the Absence of Mismatch Repair (2021)

Abstract Prime editing (PE) is a powerful genome engineering approach that enables the introduction of base substitutions, insertions and deletions into any given genomic locus. However, the efficiency of PE varies widely and depends not only on the genomic region targeted, but also on the genetic background of the edited cell. To determine which cellular factors affect PE efficiency, we carried out a focused genetic screen targeting 32 DNA repair factors, spanning all reported repair pathways. We show that, depending on cell line and type of edit, ablation of mismatch repair (MMR) affords a 2-17 fold increase in PE efficiency, across several human cell lines, types of edits and genomic loci. The accumulation of the key MMR factors MLH1 and MSH2 at PE sites argues for direct involvement of MMR in PE control. Our results shed new light on the mechanism of PE and suggest how its efficiency might be optimised.
Vessel caliber and branch-angle of human coronary artery branch-points. (1976)

Measurements were made of parent and branch vessel diameters and of the included angles of branch-points from postmortem human coronary arteriograms to determine the usefulness of theoretical equations predicting the relationships between parent and branch vessel caliber and between arterial caliber and branch-angle. The formulas were based on the concept that blood vessel size and arrangement provided for blood flow with minimum energy loss. Size relationships between parent vessel and its branches were determined for 42 left main and 53 other epicardial coronary artery branch-points in hearts with angiographically normal arteries. Left main coronary artery branch-points were studied in 68 hearts with various degrees of angiographically defined coronary artery disease. Measured diameters (D) of parent and branch vessels corresponded well to the theoretical formula: (DParent)3 = (DBranch1)3 + (DBranch2)3....,in angiographically normal coronary arteries. The exponent, on the average, is less with increasing grades of vascular disease for left main coronary artery branch-points. Mean area ratio, the sum of the cross-sectional area of the branches divided by the area of parent vessel, decreased with greater arteriographic disease. Area ratio varies with changes in the relative calibers of branch vessels. Fifty-seven branch-angles were determined by graphic analysis of postmortem biplane coronary arteriograms. No relationship could be found between branch-angle and vessel caliber. The included angle between branches varied from 32 degrees to 124 degrees without respect to relative or absolute vessel calibers. The results of these postmortem measurements on human coronary arteriogram suggest that coronary artery caliber may adjust to minimize energy loss at the branch-point but that branch-angle is determined by other factors. Restudy of arteriograms suggests that branch-angle may be determined by branch vessel destination.
Unusually Stable Palladium(IV) Complexes:  Detailed Mechanistic Investigation of C−O Bond-Forming Reductive Elimination (2005)

This communication describes the synthesis of a family of unusually stable palladium(IV) complexes containing two chelating 2-phenylpyridine ligands and two benzoates. These complexes undergo clean C-O bond-forming reductive elimination upon heating, and the mechanism of this catalytically relevant process has been studied in detail. Solvent effects, crossover experiments, Eyring plots (which show DeltaS of -1.4 +/- 1.9 and 4.2 +/- 1.4 in CDCl3 and DMSO, respectively), and Hammett analysis (which shows rho = -1.36 +/- 0.04 upon substitution of the para-benzoate substituent) all suggest that reductive elimination does not proceed via initial dissociation of a benzoate ligand. Instead, an unusual mechanism involving pre-equilibrium dissociation of the N-arm of the phenylpyridine ligand is proposed.
Mutational analysis of the phototransduction pathway of Chlamydomonas reinhardtii. (1995)

Chlamydomonas has two photobehavioral responses, phototaxis and photoshock. Rhodopsin is the photoreceptor for these responses and the signal transduction process involves transmembrane Ca2+ fluxes. This causes transient changes in flagellar beating, ultimately resulting in phototaxis or photoshock. To identify components that make up this signal transduction pathway, we generated nonphototactic strains by insertional mutagenesis. Seven new phototaxis genes were identified (ptx2-ptx8); alleles of six of these are tagged by the transforming DNA and therefore should be easily cloned. To order the mutants in the pathway, we characterized them electrophysiologically, behaviorally, and structurally, ptx5, ptx6, and ptx7 have normal light-induced photoreceptor currents (PRC) and flagellar currents (FC) but their pattern of swimming does not change in the normal manner when the intraflagellar Ca2+ concentration is decreased, suggesting that they have defects in the ability of their axonemes to respond to changes in Ca2+ concentration. ptx2 and ptx8 lack the FC but have normal PRCs, suggesting that they are defective in the flagellar Ca2+ channel or some factor that regulates it. ptx4 mutants have multiple eye-spots. ptx3 mutants are defective in a component essential for phototaxis but bypassed during photoshock; this component appears to be located downstream of the PRC but upstream of the axoneme.
GIS-Aided Zoning of Natural Groundwater Recharge Potential in Yasu River Basin, Japan (2001)

A method of identifying regions with relatively high and low natural groundwater recharge potential in a recharge area is developed using GIS technique. Annual precipitation, annual surface runoff and annual evapotranspiration are regarded as influencing factors to groundwater recharge by considering water balance in each spatial unit. Estimation of distributed values of these factors, which are converted to scores ranging within 0 through 1, is performed with easily available data. This method is successfully applied to Yasu river basin, Shiga Prefecture, Japan, revealing two facts : (1) paddy fields play an important role to recharge groundwater ; and (2) change of land use during the period of 1965 to 1995 has increased the area with low recharge by almost 40%.
Oxygen free radicals (1991)

The alpha-tocopherol treatment improves survival in sepsis. RBC deformability during sepsis is prevented by alpha-tocopherol, suggesting that free radicals may cause the decrease in RBC deformability. This study provides indirect evidence that decreased RBC deformability may play a role in the physiologic peripheral shunting and decreased microcirculatory flow that occurs during sepsis.
Homozygous Deletions and Chromosome Amplifications in Human Lung Carcinomas Revealed by Single Nucleotide Polymorphism Array Analysis (2005)

Genome-wide copy number changes were analyzed in 70 primary human lung carcinoma specimens and 31 cell lines derived from human lung carcinomas, with high-density arrays representing approximately 115,000 single nucleotide polymorphism loci. In addition to previously characterized loci, two regions of homozygous deletion were found, one near the PTPRD locus on chromosome segment 9p23 in four samples representing both small cell lung carcinoma (SCLC) and non-small cell lung carcinoma (NSCLC) and the second on chromosome segment 3q25 in one sample each of NSCLC and SCLC. High-level amplifications were identified within chromosome segment 8q12-13 in two SCLC specimens, 12p11 in two NSCLC specimens and 22q11 in four NSCLC specimens. Systematic copy number analysis of tyrosine kinase genes identified high-level amplification of EGFR in three NSCLC specimens, FGFR1 in two specimens and ERBB2 and MET in one specimen each. EGFR amplification was shown to be independent of kinase domain mutational status.
Closure of rabbit ileum enterotomies with the argon and CO2 lasers: Bursting pressures and histology (1988)

In this study, we examined short-term strength and histology of experimental argon and CO2 laser-welded and control-sutured enterotomies in a rabbit model. Longitudinal 1.0-cm enterotomies were closed with the argon laser at 0.5 (n = 10) or 1.0 (n = 10) W power and a spot diameter of 2.8 mm resulting in energy fluences of 230 and 450 J/cm2, respectively. Similar enterotomies were closed using the CO2 laser at 0.5 (n = 10) or 1.0 (n = 10) W power and a spot diameter of 1.2 mm, resulting in energy fluences of 1,360 and 2,730 J/cm2. In all closures, continuous wave laser was delivered for 30 seconds. Using a pressure-monitored infusion system with normal saline, the pressure required to burst each weld as well as sutured controls (n = 10) was recorded approximately 1 minute following fusion. Mean bursting pressures for the argon laser at 0.5 W and 1.0 W were 34.1 +/- 19.4 mm Hg (mean +/- SD) and 17.3 +/- 8.3 mm Hg, respectively, and for the CO2 laser were 23.5 +/- 12.0 mm Hg and 31.8 +/- 15.6 mm Hg, respectively. Sutured controls leaked at 45.2 +/- 12.0 mm Hg. With the exception of argon-laser welds at an energy fluence of 450 J/cm2, which were less than sutured repairs, the bursting pressures for welded closures were not significantly different from the sutured controls (Student's t distribution, P less than .05). Histologic examination of both types of welds demonstrated a fibrin and red blood cell coagulum bridging the anastomosis, with some evidence of mild thermal injury at the mucosa.(ABSTRACT TRUNCATED AT 250 WORDS)
Metabolism of (R,S)-1,3-butanediol acetoacetate esters, potential parenteral and enteral nutrients in conscious pigs (1995)

The (R,S)-1,3-butanediol-acetoacetate monoesters and diester are nonionized sodium-free precursors of ketone bodies (beta-hydroxybutyrate and acetoacetate). They represent a convenient form of ketone body administration for parenteral and enteral nutrition. We have studied the metabolism of the esters in the conscious pig, an animal in which ketogenesis is congenitally impaired. Some pigs were infused for 3 h, intravenously or intragastrically, with the esters or with (R,S)-1,3-butanediol at 30% of the hourly caloric requirement. Other pigs were given intragastric boluses of esters or of (R,S)-1,3-butanediol at 15% of the daily caloric requirement. Our data show that continuous infusion of the esters at 30% of the caloric requirement leads to low concentrations of (R,S)-1,3-butanediol (0.1 mM) and total ketone bodies (0.5 mM). In pigs given intragastric boluses of esters at 15% of the daily caloric requirement, concentrations of (R,S)-1,3-butanediol and total ketone bodies peaked briefly at 2-3 and 5 mM, respectively. No deleterious side effects were observed in any group, including no hypoglycemia and no acidosis. Thus the (R,S)-1,3-butanediol acetoacetate esters appears to be well utilized as a nutrient by the pig despite its impaired ketogenesis.
Visual Motion Estimation and Terrain Modeling for Planetary Rovers (2005)

The next round of planetary missions will require increased autonomy to enable exploration rovers to travel great distances with limited aid from a human operator. For autonomous operations at this scale, localization and terrain modeling become key aspects of onboard rover functionality. Previous Mars rover missions have relied on odometric sensors such as wheel encoders and inertial measurement units/gyros for on-board motion estimation. While these offer a simple solution, they are prone to wheel-slip in loose soil and drift of biases, respectively. Alternatively, the use of visual landmarks observed by stereo cameras to localize a rover offers a more robust solution but at the cost of increased complexity. Additionally rovers will need to create photo-realistic three-dimensional models of visited sites for autonomous operations on-site and mission planning on Earth. 1.
Einfach koordinierte Palladiumspezies als Katalysatoren in Kreuzkupplungen (2004)

Abstract Palladiumvermittelte Kreuzkupplungen sind nützliche metallorganische Transformationen zur Knüpfung von C‐C‐, C‐N‐, C‐O‐ und C‐S‐Bindungen. Obgleich sie bei Laborsynthesen häufig eingesetzt werden, haben sie keine bedeutende industrielle Anwendung gefunden, denn bis vor kurzem waren nur Verfahren für die reaktiven Arylbromide und ‐iodide bekannt, die teurer und weniger leicht erhältlich sind als die entsprechenden Arylchloride. In den letzten Jahren wurden neue Katalysatoren entwickelt, die auch weniger reaktive und sterisch gehinderte Arylchloride aktivieren. Diese Systeme beruhen auf Palladiumkomplexen mit elektronenreichen und sperrigen Phosphin‐ oder Carbenliganden. Die erhöhte Reaktivität dieser Systeme wurde dem Vorliegen von ungesättigten und reaktiven [PdL]‐Spezies zugeschrieben, die Ar‐X bereitwillig unter Bildung von [Pd(Ar)X(L)] oxidativ addieren.
Photoelectrochemical Lab-on-Paper Device Based on an Integrated Paper Supercapacitor and Internal Light Source (2013)

In this work, a photoelectrochemical (PEC) method was introduced into a microfluidic paper-based analytical device (μ-PAD), and thus, a truly low-cost, simple, portable, and disposable microfluidic PEC origami device (μ-PECOD) with an internal chemiluminescence light source and external digital multimeter (DMM) was demonstrated. The PEC responses of this μ-PECOD were investigated, and the enhancements of photocurrents in μ-PECOD were observed under both external and internal light sources compared with that on a traditional flat electrode counterpart. As a further amplification of the generated photocurrents, an all-solid-state paper supercapacitor was constructed and integrated into the μ-PECOD to collect and store the generated photocurrents. The stored electrical energy could be released instantaneously through the DMM to obtain an amplified (∼13-fold) and DMM-detectable current as well as a higher sensitivity than the direct photocurrent measurement, allowing the expensive and sophisticated electrochemical workstation or lock-in amplifier to be abandoned. As a model, sandwich adenosine triphosphate (ATP)-binding aptamers were taken as molecular reorganization elements on this μ-PECOD for the sensitive determination of ATP in human serum samples in the linear range from 1.0 pM to 1.0 nM with a detection limit of 0.2 pM. The specificity, reproducibility, and stability of this μ-PECOD were also investigated.
McrA and McrB restriction phenotypes of someE.colistrains and implications for gene cloning (1988)

The McrA and McrB (modified cytosine restriction) systems of E. coli interfere with incoming DNA containing methylcytosine. DNA from many organisms, including all mammalian and plant DNA, is expected to be sensitive, and this could interfere with cloning experiments. The McrA and B phenotypes of a few strains have been reported previously (1-4). The Mcr phenotypes of 94 strains, primarily derived from E. coli K12, are tabulated here. We briefly review some evidence suggesting that McrB restriction of mouse-modified DNA does occur in vivo and does in fact interfere with cloning of specific mouse sequences.
Model-based and empirical evaluation of multimodal interactive error correction (1999)

Our research addresses the problem of error correction in speech user interfaces. Previous work hypothesized that switching modality could speed up interactive correction of recognition errors (so-called multimodal error correction). We present a user study that compares, on a dictation task, multimodal error correction with conventional interactive correction, such as speaking again, choosing Tom a list, and keyboard input. Results show that multimodal correction is faster than conventional correction without keyboard input, but slower than correction by typing for users with good typing skills. Furthermore, while users initially prefer speech, they learn to avoid ineffective correction modalities with experience. To extrapolate results from this user study we developed a performance model of multimodal interaction that predicts input speed including time needed for error correction. We apply the model to estimate the impact of recognition technology improvements on correction speeds and the influence of recognition accuracy and correction method on the productivity of dictation systems. Our model is a first step towards formalizing multimodal (recognition-based) interaction.
Interactive multi-user multimedia environments on the Internet: an overview of DAMSEL and its implementation (2002)

The paper presents an overview of DAMSEL and it's implementation. DAMSEL comprises an embeddable dynamic multimedia specification language, and a software architecture suitable for multi user interactive multimedia environments. The goal of DAMSEL is to explore language constructs and execution environments for next generation interactive multimedia applications. The constructs of DAMSEL include primitives for event driven temporal specification-supporting causation and inhibition. Specifications allow behavioral parameters to be chosen, enabling very powerful temporal relations to be defined. Other constructs support the modification, and analysis of multimedia data, and high level abstractions for connections to user interfaces. Further, DAMSEL constructs support conditional and constraint logics, enabling more complex specifications than currently possible. DAMSEL is being implemented using a java implementation of the CORBA standard.
Interaction of Calicheamicin with Duplex DNA: Role of the Oligosaccharide Domain and Identification of Multiple Binding Modes (1994)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTInteraction of Calicheamicin with Duplex DNA: Role of the Oligosaccharide Domain and Identification of Multiple Binding ModesLuigi Gomez Paloma, Jarrod A. Smith, Walter J. Chazin, and K. C. NicolaouCite this: J. Am. Chem. Soc. 1994, 116, 9, 3697–3708Publication Date (Print):May 1, 1994Publication History Published online1 May 2002Published inissue 1 May 1994https://pubs.acs.org/doi/10.1021/ja00088a005https://doi.org/10.1021/ja00088a005research-articleACS PublicationsRequest reuse permissionsArticle Views306Altmetric-Citations88LEARN 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
CD4‐like molecules in human sperm (1990)

The expression of a molecule recognized by CD4 monoclonal antibodies was investigated on human sperm using immunolabelling, biochemical and immunochemical methods. Flow cytometry detected a significant fluorescence signal. SDS-PAGE analysis and Western blotting identified a molecule of 60 kDa, consistent with a CD4-like structure as confirmed after selective immunoseparation. Additional bands reacting with anti-CD4 were found in sperm extracts (73 kDa) and seminal fluid (90 kDa). These data indicate that sperm express a molecule similar to the receptor for HIV described on mononuclear cells.
Naphthalocyanine-reconstituted LDL nanoparticles for in vivo cancer imaging and treatment. (2007)

Low density lipoproteins (LDLs) are naturally occurring nanoparticles that are biocompatible, biodegradable and non-immunogenic. Moreover, the size of LDL particle is precisely controlled (approximately 22 nm) by its apoB-100 component, setting them apart from liposomes and lipid micelles. LDL particles have long been proposed as a nanocarrier for targeted delivery of diagnostics and therapeutics to LDL receptor (LDLR)-positive cancers. Here, we report the design and synthesis of a novel naphthalocyanine (Nc)-based photodynamic therapy (PDT) agent, SiNcBOA, and describe its efficient reconstitution into LDL core (100:1 payload). Possessing a near-infrared (NIR) absorption wavelength (> 800 nm) and extremely high extinction coefficient (> 10(5) M(-1)cm(-1)), SiNcBOA holds the promise of treating deeply seated tumors. Reconstituted LDL particles (r-Nc-LDL) maintain the size and shape of native LDL as determined by transmission electron microscopy, and also retain their LDLR-mediated uptake by cancer cells as demonstrated by confocal microscopy. Its preferential uptake by tumor vs normal tissue was confirmed in vivo by noninvasive optical imaging technique, demonstrating the feasibility of using this nanoparticle for NIR imaging-guided PDT of cancer.
Varroa destructor : research avenues towards sustainable control (2012)

SummaryPollination by honey bees plays a key role in the functioning of ecosystems and optimisation of agricultural yields. Severe honey bee colony losses worldwide have raised concerns about the sustainability of these pollination services. In many cases, bee mortality appears to be the product of many interacting factors, but there is a growing consensus that the ectoparasitic mite Varroa destructor plays the role of the major predisposing liability. We argue that the fight against this mite should be a priority for future honey bee health research. We highlight the lack of efficient control methods currently available against the parasite and discuss the need for new approaches. Gaps in our knowledge of the biology and epidemiology of the mite are identified and a research road map towards sustainable control is drawn. Innovative and challenging approaches are suggested in order to stimulate research efforts and ensure that honey bees will be able to sustainably fulfil their role in the ecosystem.
Inhibitory and stimulatory effects of IL-10 on human CD8+ T cells. (1998)

IL-10 is a well-documented immunosuppressant that inhibits macrophage-dependent Ag presentation and CD4+ T cell proliferation in vitro. We report that IL-10 inhibits alloantigen-specific proliferative responses and induces a long lasting anergic state in human purified CD8+ T cells when added concomitantly with the Ag in the presence of APC. Moreover, the generation of allospecific cytotoxic activity is inhibited by IL-10. These effects are indirect and are mediated through inhibition of the costimulatory functions of APC. In contrast, IL-10 has no direct inhibitory effects on the proliferation of purified CD8+ T cells activated by anti-CD3 mAb and promotes the growth of activated CD8+ T cells in combination with low doses of IL-2. Taken together, these results indicate that IL-10 has differential effects on CD8+ T cells depending on their state of activation, which may explain both the enhancing and inhibitory effects observed after IL-10 treatment in different in vivo experimental models.
Prevention and reversal of nephritis in MRL/lpr mice with a single injection of C‐reactive protein (2005)

These findings demonstrate that systemic suppression of autoimmunity is initiated by a single injection of CRP. Long-term maintenance of CRP-mediated protection was reversed by injection of an anti-CD25 monoclonal antibody but not by macrophage depletion, suggesting that disease suppression is maintained by CD25-bearing T cells.