gebhart/patrepeval huggingface dataset:
Homology-mediated end joining-based targeted integration using CRISPR/Cas9 (2017)

Targeted integration of transgenes can be achieved by strategies based on homologous recombination (HR), microhomology-mediated end joining (MMEJ) or non-homologous end joining (NHEJ). The more generally used HR is inefficient for achieving gene integration in animal embryos and tissues, because it occurs only during cell division, although MMEJ and NHEJ can elevate the efficiency in some systems. Here we devise a homology-mediated end joining (HMEJ)-based strategy, using CRISPR/Cas9-mediated cleavage of both transgene donor vector that contains guide RNA target sites and ∼800 bp of homology arms, and the targeted genome. We found no significant improvement of the targeting efficiency by the HMEJ-based method in either mouse embryonic stem cells or the neuroblastoma cell line, N2a, compared to the HR-based method. However, the HMEJ-based method yielded a higher knock-in efficiency in HEK293T cells, primary astrocytes and neurons. More importantly, this approach achieved transgene integration in mouse and monkey embryos, as well as in hepatocytes and neurons in vivo, with an efficiency much greater than HR-, NHEJ- and MMEJ-based strategies. Thus, the HMEJ-based strategy may be useful for a variety of applications, including gene editing to generate animal models and for targeted gene therapies.
Pharmacogenomics and Translational Simulations to Bridge Indications for an Anti-Interferon-α Receptor Antibody (2013)

A type I interferon (IFN) gene signature shared by systemic lupus erythematous (SLE) and systemic sclerosis (SSc) was used to evaluate an anti-type I IFN-α receptor (IFN-αR) monoclonal antibody, MEDI-546, in a phase I trial in SSc. MEDI-546 suppressed IFN signature in blood and skin of SSc patients in a dose-dependent manner. To bridge clinical indications to SLE, we developed a model incorporating (i) pharmacokinetics (PK) and pharmacodynamics (PD) in SSc patients, (ii) internalization kinetics of MEDI-546/IFN-αR complex, and (iii) the different IFN signatures between SSc and SLE. Simulations predicted that i.v. administration of MEDI-546 at 300- or 1,000-mg monthly doses could suppress IFN signature in blood to levels of healthy subjects in 53 and 68% of SLE patients, respectively. An innovative approach utilizing a novel biomarker characterized the PD of MEDI-546 by modeling and simulation and allowed rapid progression of MEDI-546 from a phase I study in SSc to a randomized, multiple-dose phase II trial.
Mutation Detection by PCR, GC-Clamps, and Denaturing Gradient Gel Electrophoresis (1989)

Denaturing gradient gel electrophoresis (DGGE) allows the separation of DNA molecules differing by as little as a single base change.1-5 The separation is based on the melting properties of DNA in solution. DNA molecules melt in discrete segments, called melting domains, when the *temperature or denaturant concentration is raised. Melting domains vary from about 25 base pairs (bp) to several hundred bp in length, and each melts cooperatively at a distinct temperature called a Tm. Due to the considerable contribution of stacking interactions between adjacent bases on a DNA strand to double helical stability, the Tm of a melting domain is highly dependent on its nucleotide sequence. The Tms of DNA fragments differing by even very small changes, such as a single base substitution, can differ by as much as 1.5°C. In the DGGE system, DNA fragments are electrophoresed through a polyacrylamide gel that contains a linear gradient, from top to bottom, of increasing DNA denaturant concentration. As a DNA fragment enters the concentration of denaturant where its lowest temperature melting domain melts (equivalent to the Tm of the domain), the molecule forms a branched structure that has a retarded mobility in the gel matrix. If the gradient conditions are chosen properly, DNA fragments differing by single base changes begin branching, and hence slowing down, at different positions in the gel, resulting in the separation of the fragments at the end of the electrophoretic run.
Coordinated Electrical Pacing of Vocal Cord Abductors in Recurrent Laryngeal Nerve Paralysis (1985)

Electrodes were placed into the posterior cricoarytenoid and diaphragmatic muscles of five tracheostomized dogs. With the use of a sensor that would selectively detect diaphragmatic electromyographic activity, this activity served as a trigger and was amplified and interfaced with a muscle stimulator attached to electrodes placed in the posterior cricoarytenoid muscles. In all animals obvious physiologic synchrony of vocal fold abduction and a reduction of the negative inspiratory intratracheal pressure were observed during electrical pacing. This represents a preliminary step in the development of an alternative approach to the patient with bilateral recurrent laryngeal nerve paralysis.
Room-temperature continuous-wave operation of a single-layered 1.3 μm quantum dot laser (1999)

Room-temperature continuous-wave operation of a 1.3 μm quantum dot laser is reported. The threshold current for a single layer active region with p–up mounting is only 4.1 mA with a threshold current density of 45 A/cm2. The minimum room temperature threshold current density is 25 A/cm2 for pulsed operation. Cryogenic and temperature dependent measurements are performed on broad-area lasers fabricated from the same active material. At 4 K the broad-area threshold current density for uncoated facets is 6 A/cm2.
Seeing Through The Brain (2013)

RETURN TO ISSUEPREVNewsNEXTSeeing Through The BrainCite this: Chem. Eng. News 2013, 91, 15, 9Publication Date (Print):April 15, 2013Publication History Published online31 March 2014Published inissue 15 April 2013https://pubs.acs.org/doi/10.1021/cen-09115-notw9https://doi.org/10.1021/cen-09115-notw9newsACS PublicationsCopyright © 2013 Chemical & Engineering NewsArticle Views7Altmetric-Citations-LEARN 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 options SUBJECTS:Central nervous system Get e-Alerts
ChemInform Abstract: Preparation of 3e,4,5,6e,7,8‐Hexahydro[2.2]paracyclophane. (1998)

Abstract ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
Survival of Honey Bee (Hymenoptera: Apidae) Spermatozoa Incubated at Room Temperature from Drones Exposed to Miticides (2008)

We conducted research to examine the potential impacts of coumaphos, fluvalinate, and Apilife VAR (Thymol) on drone honey bee, Apis mellifera L. (Hymenoptera: Apidae), sperm viability over time. Drones were reared in colonies that had been treated with each miticide by using the dose recommended on the label. Drones from each miticide treatment were collected, and semen samples were pooled. The pooled samples from each treatment were subdivided and analyzed for periods of up to 6 wk. Random samples were taken from each treatment (n = 6 pools) over the 6-wk period. Sperm viability was measured using dual-fluorescent staining techniques. The exposure of drones to coumaphos during development and sexual maturation significantly reduced sperm viability for all 6 wk. Sperm viability significantly decreased from the initial sample to week 1 in control colonies, and a significant decrease in sperm viability was observed from week 5 to week 6 in all treatments and control. The potential impacts of these results on queen performance and failure are discussed.
Factors Expressed by Murine Embryonic Pancreatic Mesenchyme Enhance Generation of Insulin-Producing Cells From hESCs (2013)

Islet transplantation has proven to be a successful strategy to restore normoglycemia in patients with type 1 diabetes (T1D). However, the dearth of cadaveric islets available for transplantation hampers the widespread application of this treatment option. Although human embryonic stem cells and induced pluripotent stem cells are capable of generating insulin-producing cells in vitro when provided with the appropriate inductive cues, the insulin-expressing cells that develop behave more like immature β-cells with minimal sensitivity to glucose stimulation. Here, we identify a set of signaling factors expressed in mouse embryonic mesenchyme during the time when foregut and pancreatic progenitors are specified and test their activities during in vitro differentiation of human embryonic stem cells. Several of the identified factors work in concert to expand the pancreatic progenitor pool. Interestingly, transforming growth factor (TGF)-β ligands, most potent in inducing pancreatic progenitors, display strong inhibitory effects on subsequent endocrine cell differentiation. Treatment with TGF-β ligands, followed by the addition of a TGF-β receptor antagonist, dramatically increased the number of insulin-producing cells in vitro, demonstrating the need for dynamic temporal regulation of TGF-β signaling during in vitro differentiation. These studies illustrate the need to precisely mimic the in vivo conditions to fully recapitulate pancreatic lineage specification in vitro.
Spatio-Temporal Optimization of Seasonal Vaccination Using a Metapopulation Model of Influenza (2017)

Prophylactic interventions such as vaccine allocation are one of the most effective public health policy planning tools. The supply of vaccines is limited, and an importantproblem is when and how to allocate the available vaccination supply, referred to as the Vaccine Allocation Problem. The spread of epidemics is modeled by the SEIR process, which has a very complex dynamics, and depends on human contacts and mobility. This makes the design of efficient solutions tovaccine allocation problem to minimize the number of infections a very challenging problem. In particular, this requires good models for human mobility, and optimization tools for vaccine allocation.In this paper, we study the vaccine allocation problem in the context of seasonal Influenza spread inthe United States. We develop a novel national scale flu model that integrate both short andlong distance travel, which are known to be important determinants of the spread of Influenza. We also design a greedy algorithm for allocating the vaccine supply at a county level. Our results show significant improvement over the current baseline, whichinvolves allocating vaccines based on the state population.
Reaction of 2‐halogeno‐4‐phenylpyrimidines with potassium amide in liquid ammonia. On the possible occurrence of two SN(ANRORC)‐mechanisms (1974)

Abstract On amination of 2‐X‐4‐phenylpyrimidine (X=F, Cl, 1) with potassium amide in liquid ammonia at −75°. 2‐amino‐4‐phenylpyrimidine is obtained as main product, together with some 3‐amino‐3‐phenylacrylonitrile. It was proved using 2‐halogeno‐4‐phenyl‐[1,3‐ 15 N]‐pyrimidines that the displacement reaction occurs for the greater part via an S N (ANRORC)‐mechanism (82% for X=F, 88% for X=Cl and 73% for X=1). It was further found that the 3‐amino‐3‐phenylacrylonitrile, obtained from the 15 N‐labelled pyrimidines. does not contain 15 N. This very unexpected result is discussed.
Immunochemical Properties of Ubiquitin Conjugates in the Paired Helical Filaments of Alzheimer Disease (1989)

Immunocytochemical and peptide sequencing studies indicate that the regulatory protein ubiquitin (Ub) is incorporated into the paired helical filaments (PHF) of Alzheimer disease. In this study, we showed that some antibodies raised to PHF recognize epitopes of Ub. Analysis of the Ub sequences recognized by the antibodies raised to PHF, along with the known specificity of several monoclonal antibodies raised to artificial Ub conjugates, indicates the immunochemical representation of Ub residues 34-76 in PHF. The Ub epitopes recognized by antibodies raised to PHF are distinct from those recognized by antibodies raised to artificial Ub conjugates in two respects. First, antibodies that are raised to PHF and that recognize Ub react with PHF equally, whether denatured or not, whereas those raised to artificial Ub conjugates show greater reaction after denaturation. Second, mapping of the epitopes recognized by two monoclonal antibodies to PHF onto Ub indicates a distinction in the Ub residues recognized, compared with monoclonal antibodies raised to artificial Ub conjugates. The proximity of their epitopes to the site of conjugation, as well as their affinity for PHF polypeptides, suggests that the PHF antibodies that recognize Ub may be directed specifically to Ub epitopes defined by the protein conjugated to Ub.
Efficacy of radiofrequency catheter ablation for ventricular tachycardia in healed myocardial infarction (1998)

Radiofrequency catheter ablation has been useful in the treatment of ventricular tachycardia (VT) in selected patients with healed myocardial infarction. Previous studies have demonstrated success rates of 60% to 96% for targeted VT morphologies; however, these studies included patients only after they have had successful mapping procedures and have received radiofrequency lesions. All patients referred for VT ablation from July 1992 to November 1996 were included in this analysis on an intention-to-treat basis. Ninety-five procedures were performed in 66 patients for 77 distinct presentations with tolerated, sustained VT. Fifty-five procedures were successful (58%) and 40 procedures failed. Reasons for procedural failure included failed radiofrequency application despite adequate VT mapping (21 procedures), no tolerated VT induced (12), and aborted procedures due to complications or technical difficulties (7). Fifty-five patients (71%) eventually had a successful VT ablation, although 10 required > 1 procedure. This analysis revealed factors that contribute to failure of VT ablation procedures in addition to inadequate mapping and lesion formation. Procedural difficulties, particularly the inability to induce tolerated VT, frequently prevent successful catheter ablation in patients who present with tolerated, sustained VT.
Binding diversity of monoclonal antibodies toα(2 → 8) polysialic acid conjugated to outer membrane vesicle via adipic acid dihydrazide (1996)

Murine monoclonal antibodies (mAbs) were generated using group B Neisseria meningitidis and Escherichia coli K1 polysaccharides (PSs) conjugated to outer membrane vesicle (OMV) via adipic acid dihydrazide, and were used to identify the immunodeterminants expressed on these capsular PSs. Ten mAbs representative of IgM and all subclasses of IgG were obtained which recognized diverse immunodeterminants on alpha(2-->8) polysialic acid (PSA). The specificity of mAbs to different antigenic determinants was assessed by their differential binding to PSA attached to a solid phase by different methods and confirmed by absorption studies. Two mAbs from the E. coli K1 fusion were directed to the O-acetyl epitope and the rest reacted with both the PSs only when attached to a solid phase by certain means. The methods by which PSA was coated on the solid phase had an impact on the epitope expression and binding pattern. At the concentrations used, the O-acetyl-specific mAbs, IgG1 and IgG3 mAbs were not bactericidal against group B N. meningitidis, whereas other mAbs were. The conjugates B and K1 PSs present to the murine immune system different antigenic determinants, some of which elicit bactericidal antibodies.
Phosphate concentration regulates transcription of the Acinetobacter polyhydroxyalkanoic acid biosynthetic genes (1995)

The polyhydroxyalkanoic acid (PHA) biosynthetic gene locus was cloned and characterized from an Acinetobacter sp. isolated from activated sludge. Nucleotide sequence analysis identified three clustered genes, phaAAc (encoding a beta-ketothiolase), phaBAc (encoding an acetoacetyl coenzyme A reductase), and phaCAc (encoding a PHA synthase). In addition, an open reading frame (ORF1) with potential to encode a 13-kDa protein was identified within this locus. The sequence of the putative translational product of ORF1 does not show significant similarity to any sequences in the database. A plasmid containing the Acinetobacter pha locus conferred the ability to accumulate poly-beta-hydroxybutyrate on its Escherichia coli host. These genes appear to lie in an operon transcribed by two promoters upstream of phaBAc, an apparent constitutive promoter, and a second promoter induced by phosphate starvation and under pho regulon control. These as well as a number of additional potential transcription start points were identified by a combination of primer extension and promoter-chloramphenicol acetyltransferase gene fusion studies carried out in Acinetobacter or E. coli transformants.
Transient immunosuppression with FK506 permits long-term expression of therapeutic genes introduced into the liver using recombinant adenoviruses in the rat (1997)

The host immune response limits the duration of expression of adenovirally transduced genes and precludes long-term gene expression upon re-administration of the virus. In this study we wished to evaluate whether short-term immunosuppression of the host, at the time of recombinant virus administration, would allow expression of the therapeutic gene product upon virus reinjection. Gunn rats were used as recipients of recombinant adenoviruses expressing human BUGT (Ad-hBUGT) or E. coli beta-galactosidase (Ad-LacZ). Rats were treated with FK506 (1-1.5 mg/kg, per OS daily) for three days beginning 24 hours before each virus injection. Control groups did not receive any immunosuppressant. The serum bilirubin level was reduced from 7.1 +/- 0.75 mg/dL to 2.0 +/- 0.7 mg/dL within two days of viral injection in both FK506 treated and control groups, and then gradually increased in 6 weeks. FK506-treated rats had low or undetectable antibody titers against the recombinant adenovirus and minimal or no cytotoxic T lymphocyte (CTL) response against adenovirus-infected cells. The tolerized rats received two subsequent injections 42 and 98 days after the first injection, which reduced the bilirubin levels again to 2.0 +/- 0.56 and 2.2 +/- 0.61 mg/dL, respectively. In contrast, control rats developed high titer neutralizing antibodies and a CTL response, and their serum bilirubin levels were not reduced following subsequent injections. We conclude that short-term FK506 treatment around the time of virus administration prevents the host immune response, permitting long-term gene therapy by repeated administration of the recombinant virus.
Nijmegen breakage syndrome gene (NBS1) alterations and its protein (nibrin) expression in human ovarian tumours (2002)

We looked for NBS1 gene (602667) alterations and changes in nibrin expression in 162 human gynaecological tumours, mostly ovarian. Exons 6–8 and 10 of the NBS1 gene were evaluated by the SSCP and direct sequencing method. Nibrin expression was detected immunohistochemically with the use of the p95NBS1 (Ab‐1) antibody. The 657del5 mutation (Slavic mutation) was found in two of 117 carcinomas studied (1.7%) – in both cases it was present in the germline; one of these tumours showed loss of heterozygosity (LOH) for the 657del5 mutation and loss of nibrin expression. We have found three types of novel germline intron variants: (1) two concomitant transitions (G to A) at bases 14009 and 14256; (2) C to T transition at base 13998; (3) G to C transversion at base 20035. Among the carcinomas studied, the intron variants were associated with a clear cell histological type ( p = 0.004). Our results may suggest that NBS1 gene alterations contribute to the development of rare ovarian carcinomas. LOH for 657del5 in tumour tissue may support the hypothesis that the NBS1 gene functions as a tumour suppressor.
Antimicrobial and Promicrobial Agents (2000)

I. Introduction ...........................................................................................................................401 A. Definition of Antimicrobial and Promicrobial Agents .............................................401 B. Background on Use of Antimicrobials .....................................................................402 C. Background on Use of Promicrobials ......................................................................404II. Antimicrobial Agents ............................................................................................................405 A. Efficacy of Antimicrobials as Growth Promoters ....................................................405 B. Efficacy of Antimicrobials on Reproductive Efficiency...........................................409 C. Mode of Action of Antimicrobials ...........................................................................409
NRD convertase: a putative processing endoprotease associated with the axoneme and the manchette in late spermatids (1996)

N-arginine dibasic convertase is a novel metalloendopeptidase which selectively cleaves at the N terminus of arginine residues in paired basic amino acids. Although present in brain and several other tissues, NRD convertase is particularly abundant in testis, where its expression appeared to be restricted to germ cells. Low levels of both mRNA and its corresponding protein were detected early in spermatogenesis. However, a marked accumulation of the protein was observed during late steps (14 to 19) of spermiogenesis. By electron microscopy, the NRD convertase immunoreactivity was localized in the cytoplasm of elongating and elongated spermatids, with a noticeable concentration at the level of two microtubular structures, i.e. the manchette and the axoneme. These observations strongly support the hypothesis that NRD convertase is involved in processing events potentially associated with the morphological transformations occurring during spermiogenesis.
High Performance Shape Memory Epoxy/Carbon Nanotube Nanocomposites (2015)

A series of shape memory nanocomposites based on diglycidyl ether of bisphenol A (DGEBA) E51/methylhexahydrophthalic anhydride (MHHPA)/multiwalled carbon nanotube (MWCNT) with various stoichiometric ratios (rs) of DGEBA/MHHPA from 0.5 to 1.2 and filler contents of 0.25 and 0.75 wt % are fabricated. Their morphology, curing kinetics, phase transition, mechanical properties, thermal conduction, and shape memory behaviors are systematically investigated. The prepared materials show a wide range of glass transition temperatures (Tg) of ca. 65-140 °C, high flexural modulus (E) at room temperature up to ca. 3.0 GPa, high maximum stress (σm) up to ca. 30 MPa, high strain at break (εb) above 10%, and a fast recovery of 32 s. The results indicate that a small amount of MWCNT fillers (0.75 wt %) can significantly increase all three key mechanical properties (E, σm, and εb) at temperatures close to Tg, the recovery rate, and the repetition stability of the shape memory cycles. All of these remarkable advantages make the materials good candidates for the applications in aerospace and other important fields.