gebhart/patrepeval huggingface dataset:
CRISPR-Cas9 Based Genome Engineering: Opportunities in Agri-Food-Nutrition and Healthcare (2015)

Recently developed strategies and techniques that make use of the vast amount of genetic information to perform targeted perturbations in the genome of living organisms are collectively referred to as genome engineering. The wide array of applications made possible by the use of this technology range from agriculture to healthcare. This, along with the applications involving basic biological research, has made it a very dynamic and active field of research. This review focuses on the CRISPR system from its discovery and role in bacterial adaptive immunity to the most recent developments, and its possible applications in agriculture and modern medicine.
Folate status of rheumatoid arthritis patients receiving long‐term, low‐dose methotrexate therapy (1987)

The folate status of 29 healthy control subjects, 16 rheumatoid arthritis (RA) patients taking methotrexate (MTX), and 20 RA patients who were not being treated with MTX was estimated by an assay of the folate-dependent enzymatic synthesis of serine from formate and glycine, which is termed the C1 index. Analysis of variance demonstrated that the specific activity of the enzyme system in lymphocytes was significantly lower in the MTX-treated group, with an activity approximately one-half that of the control and the non-MTX-treated groups. Since the C1 index is one of the first biochemical parameters found to be different between MTX-treated and non-MTX-treated groups, alterations in folate-mediated amino acid metabolism may be involved in the mechanism of response to MTX therapy. Use of the C1 index may assist in the development of protocols which preserve the efficacy of MTX therapy while minimizing toxicity.
Impact of crystal polymorphism on the systemic bioavailability of rifaximin, an antibiotic acting locally in the gastrointestinal tract, in healthy volunteers (2014)

Rifaximin-α, a crystal polymorph, does differ from the amorphous form, the latter being systemically more bioavailable. In this regard, care must be taken when using - as a medicinal product - a formulation containing even small amounts of amorphous form, which may alter the peculiar pharmacologic properties of this poorly absorbed antibiotic.
Immunoperoxidase localization of fibronectin during odontoblast differentiation. An ultrastructural study. (1989)

Immunoperoxidase labeling of fibronectin in one-day-old mouse first lower molars allowed to visualize a striking redistribution of this glycoprotein during terminal cytodifferentiation of odontoblasts. The modifications involved both extracellular and cell surface localizations. The possible roles of these modifications in terminal differentiation of odontoblasts are discussed.
Levodopa‐induced dyskinesia in Parkinson disease: Sleep matters (2018)

Our data demonstrate a strong pathophysiological association between sleep and PD. Given that SWA may be a surrogate for synaptic strength, our data suggest that DYS patients do not have adequate synaptic downscaling. Further analysis is needed to determine the effect of drugs that can enhance cortical SWA in LID. Ann Neurol 2018;84:905-917.
Linear and star-shaped pyrazine-containing acene dicarboximides with high electron-affinity (2012)

A series of linear and star-shaped pyrazine-containing acene molecules 1a-b, 2a-b and 3 substituted by dicarboximide groups are synthesized via condensation reactions between o-diamine and dione. High electron affinity (up to 4.01 eV) is achieved due to the introduction of an electron-deficient pyrazine moiety and the attachment of electron-withdrawing dicarboximide groups. Some of these molecules show thermal liquid crystalline behavior and their space-charge limited current mobilities are measured. The high electron affinity and liquid crystalline property qualify them as promising electron transporting materials in organic optoelectronic devices.
EVALUATION OF TEXTILE DETERGENT EFFICIENCY OF MICROEMULSIONS IN SYSTEMS OF WATER NONIONIC SURFACTANT AND HYDROCARBON AT LOW TEMPERATURE (1985)

ABSTRACT Washing efficiency of microemulsions in water/nonionic surfactant/hydrocarbon systems has been evaluated. Such microemulsions have proved to have an excellent performance as cleaning systems in conditions of minimum mechanical energy and at low temperatures. Their behaviour in the presence of small amounts of an ionic surfactant as well as the modifications promoted by the presence of builders have also been investigated.
Safety of Recombinant Human Growth Hormone (2010)

With an increasing spectrum of indications for growth hormone (GH), knowledge of the short- and long-term safety of this treatment is essential. In this chapter we review the main adverse effects that have been demonstrated or discussed after long-term GH treatment in children. It is well recognized that plasma insulin concentrations increase during GH treatment. The incidence of type 2 diabetes is raised during GH treatment, especially in subjects with other risk factors. Recommendations include assessing glucose tolerance by measuring plasma glucose and HbA1c before and during treatment. There is no consensus on the indications for insulin measurement and/or oral glucose tolerance tests. Other recognized short-term complications of GH treatment include pseudo-tumour cerebri, otitis media (Turner syndrome), and orthopaedic problems such as worsening of scoliosis and slipped femoral epiphysis. There are reports of sudden death within the first 6 months of treatment in children with Prader-Willi syndrome, mostly associated with severe obesity. Large cohort follow-up studies suggest that children treated with GH following childhood cancer treatment do not have a greater number of relapses, but there may be a higher incidence of second primary tumours in the early years of GH therapy. A cohort treated with human pituitary GH showed a higher incidence of tumours, and a GH effect on tumorigenesis has been seen in follow-up studies of acromegaly raising the question of whether de novo cancer risk may be increased. A new prospective pan-European safety surveillance study (SAGhE) has been launched to address these essential questions. The role of monitoring the IGF-1 response (total or free concentrations) to GH treatment to predict long-term safety is unclear at present. Attempts to target IGF-1 levels within the normal range may result in the use of excessive doses of GH. In general, higher dosage GH regimens may be associated with supraphysiological IGF-1 levels.
The calmodulin‐binding site of the plasma membrane Ca<sup>2+</sup> pump interacts with the transduction domain of the enzyme (1992)

Calpain proteolysis of the plasma membrane Ca2+ pump removes a C-terminal 14-kDa portion which includes the calmodulin-binding domain. This produces a fully activated 124-kDa fragment, which can be inhibited by synthetic versions of the calmodulin-binding domain. The inhibition is strongest when Trp-8 in the latter domain is replaced by a Tyr residue (Falchetto, R., Vorherr, T., Brunner, J., & Carafoli, E., 1991, J. Biol. Chem. 266, 2930-2936). In the present study, the N-terminus of the 28-residue synthetic calmodulin-binding domain was acetylated with 3H-acetic anhydride, and Phe in position 25 was replaced by a phenylalanine derivatized with a diazirine-based, photoactivatable carbene precursor. This peptide (C28WC*) inhibited the fully active 124-kDa fragment of the pump and became cross-linked to it upon photolysis. After proteolysis of the fragment with Asp-N or Staphylococcus aureus V8 (Glu-C) protease, labeled peptides were isolated by reversed-phase high-performance liquid chromatography and subjected to Edman sequence analysis. The peptides originated from a region of the pump located within the unit protruding into the cytoplasm between transmembrane domain two and three. This unit has been proposed to be the site of the energy transduction domain, which would couple the ATP hydrolysis to Ca2+ translocation.
Neuroprotection against Traumatic Brain Injury by Xenon, but Not Argon, Is Mediated by Inhibition at the N-Methyl-d-Aspartate Receptor Glycine Site (2013)

Xenon neuroprotection against traumatic brain injury can be reversed by increasing the glycine concentration, consistent with inhibition at the N-methyl-D-aspartate receptor glycine site playing a significant role in xenon neuroprotection. Argon and xenon do not act via the same mechanism.
Development of a genetic system for the deep-sea psychrophilic bacterium Pseudoalteromonas sp. SM9913 (2014)

A conjugal transfer system was constructed in Pseudoalteromonas sp. SM9913 with a wide temperature range for selection and a high transfer efficiency, which will lay the foundation of genetic manipulation in this strain. The epsT gene of SM9913 was successfully deleted with no selective marker left in the chromosome of the host, which thus make it possible to knock out other genes in the same host. The construction of a gene knockout system for Pseudoalteromonas sp. SM9913 will contribute to the understanding of the molecular mechanism of how Pseudoalteromonas adapt to the deep-sea environment.
Protonation of the Heterocyclic Cp-Anion Equivalent [Pyrrolyl-B(C6F5)3]Li − Formation of a Useful Neutral Brønsted Acid for the Generation of Homogeneous Metallocene Ziegler Catalysts (2001)

N-pyrrolyllithium (1) adds to B(C6F5)3 to yield [(C4H4N)B(C6F5)3]Li (3). The corresponding monoetherate (3·OEt2) was characterized by X-ray diffraction and shows an η5 coordination of the pyrrolyl moiety to the lithium cation. Treatment of 3 with HCl in ether leads to H+ addition at a pyrrolyl α-position to yield the neutral dipolar Brønsted acid system [(C4H5N)B(C6F5)3] (4). The reagent 4 can be used to protonate Cp2Zr(CH3)3 to yield [Cp2Zr(CH3)+(C4H4N)B(C6F5)3−] (6) and methane. H+ transfer from 4 to (butadiene)zirconocene results in the formation of the (π-allyl)metallocene salt [(C4H7)ZrCp2+(C4H4N)B(C6F5)3−] (8). In analogous reactions, the neutral Brønsted acid was employed as a protonating activator component for the generation of homogeneous Ziegler catalysts derived from a variety of (butadiene)- or (dimethyl)ansa-metallocenes. The systems generated by treatment with 4 show comparable activities in ethene or propene polymerization reactions as conventionally generated Group 4 metallocene Ziegler catalysts.
Glottal source estimation: Methods of applying the LF-model to inverse filtering (1993)

The incorporation of the LF model into closed-phase inverse filtering based estimation of glottal source waveforms is considered. The LF model is a five-parameter model representing the effective voice source over open and closed glottal phases. Three techniques for LF model fitting are described: two based on Prony's method and one using gradient descent. The estimation methods are evaluated using glottal flow waveforms obtained synthetically and through inverse filtering. Under appropriate conditions, all of the estimation methods produce good fits of the LF model to the inverse filtered waveform. In noise, gradient descent produces more consistent fits than the more tractable Prony-based techniques.< <ETX>></ETX>
Living Cationic Polymerization of α-Methylstyrene. 2. Synthesis of Block and Random Copolymers with 2-Chloroethyl Vinyl Ether and End-Functionauzed Polymers† (1994)

Abstract Both AB and BA block copolymers of α-methylstyrene (αMeSt) and 2-chloroethyl vinyl ether (CEVE) were synthesized by the sequential living cationic polymerization initiated with the HCl-CEVE adduct (1a)/SnBr4 system in CH2Cl2 at -78°C. αMeSt-CEVE (AB) block copolymers with narrow molecular weight distributions ([Mbar]w/[Mbar]n ∼ 1.15) were obtained when αMeSt was polymerized first, followed by addition of CEVE to the resulting αMeSt living polymer solution. The reverse order of monomer addition, from CEVE to αMeSt, also led to a BA-type block copolymer. In the polymerization of a mixture of the two monomers, almost random copolymers were obtained. Living polymerizations of αMeSt were also induced with functional initiating systems, HCl-functionalized vinyl ether adducts (1b-1d)/SnBr4, to give end-function-alized poly(αMeSt)s with a methacrylate, an acetate, or a phthalimide terminal.
Synthese von cis-und trans-4-Cyanocyclohexanol / Synthesis of cis-and trans-4-Cyanocyclohexanol (1980)

Abstract The synthesis of cis-and trans-4-cyanocyclohexanol 2 a and 2 b is described for the first time. Their stereochemistry has been determined by 1 H NMR spectroscopy.
Polarization induced hole doping in graded Al<i>x</i>Ga1−<i>x</i>N (<i>x</i> = 0.7 ∼ 1) layer grown by molecular beam epitaxy (2013)

Polarization induced hole doping on the order of ∼1018 cm−3 is achieved in linearly graded AlxGa1−xN (x = 0.7 ∼ 1) layer grown by molecular beam epitaxy. Graded AlxGa1−xN and conventional Al0.7Ga0.3N layers grown on AlN are beryllium (Be) doped via epitaxial growth. The hole concentration in graded AlxGa1−xN:Be (x = 0.7 ∼ 1) layers demonstrates that polarization generates hole charges from Be dopant. The Al0.7Ga0.3N layer is not conductive owing to the absence of carriers generated from the Be dopant without the inducement of polarization. Polarization doping provides an approach to high efficiency p-type doping in high Al composition AlGaN.
Structural basis for the regulation of UDP-N-acetyl-alpha-D-galactosamine: polypeptide N-acetylgalactosaminyl transferase-3 gene expression in adenocarcinoma cells. (1999)

The UDP-N-acetyl-alpha-D-galactosamine: polypeptide N-acetylgalactosaminyl transferase-3 (Gal NAc-T3) gene, a member of the Gal NAc transferase gene family, is expressed in a tissue-specific manner. To elucidate the function of this gene, we have focused on the molecular mechanism underlying regulation of gene expression. We have cloned Gal NAc-T3 cDNA and used it to show that Gal NAc-T3 mRNA is expressed in tumor cell lines derived from secretory epithelial tissue adenocarcinomas but not in cell lines derived from bladder and epidermoid carcinomas. Using a polyclonal antibody to Gal NAc-T3, we observed protein expression in adenocarcinoma but not non-adenocarcinoma cell lines, and in breast carcinoma cells but not in normal breast tissue. We used Gal NAc-T3 cDNA to isolate three overlapping genomic clones containing the 5'-portion of the human Gal NAc-T3 gene, and we sequenced 1.6 kb around the first exon. A transient expression assay using the luciferase gene showed that promoter activity was much higher in MCF-7 cells than in KB cells. In vivo footprint experiments showed significant protection of a distal GC box, an NRF-1 site, and an AP-2 site in MCF-7 cells. A novel stem and loop structure extending from nucleotide -103 to nucleotide -165 and contiguous to these transcription factor binding sites seemed to be functional in regulating Gal NAc-T3 gene transcription, and a KMnO4 footprint experiment showed that this stem and loop structure could be formed in vivo. We also observed dimethyl sulfate hypersensitive sites in the untranslated region around nucleotide +50 in MCF-7 but not in KB cells. These findings indicate that Gal NAc-T3 gene expression is regulated by multiple systems, including transcription factor binding sites and a stem-and-loop structure, and that this regulation is restricted to cell lines derived from epithelial gland adenocarcinomas but not cells derived from nonsecretory epithelial tissue carcinomas. In addition, our immunohistochemical results suggest that our anti-Gal NAc-T3 antibody may be useful for diagnostic purposes in the early stages of breast cancer.
Eye defects in receptor protein‐tyrosine phosphatase α knock‐down zebrafish (2002)

Abstract Receptor protein‐tyrosine phosphatase alpha (RPTPα) is highly expressed in the developing retina of different species, but little is known about its function there. Here, we report that injection of antisense morpholinos in zebrafish embryos reduced RPTPα expression to almost nondetectable levels up to 3 days postfertilization (dpf). RPTPα was detectable again from 4 dpf onward. RPTPα knock‐down resulted in smaller eyes. Examination of sections of the retina at different developmental stages demonstrated that already at 28 hours postfertilization (hpf) fewer cells were present in the retina of RPTPα‐morpholino–injected embryos. At 3 dpf, the layered organization of the retina was absent. In addition, the morphology and labeling with an axon specific antibody, acetylated tubulin, demonstrated that most cells appeared to be undifferentiated. Strikingly, at 5 dpf the lamination of the retina was partially restored, concomitant with re‐expression of RPTPα protein. Although cells in the retina were now differentiated, the layering of the retina remained disrupted and significant gaps were observed in the amacrine cell layer. Therefore, knock‐down of RPTPα protein provides evidence that RPTPα is essential for normal retinal development. © 2002 Wiley‐Liss, Inc.
A wide frequency range, rugged silicon micro accelerometer with overrange stops (2002)

A rugged and wide frequency range silicon micro accelerometer with integral overrange stops has been developed for use in anthropomorphic test dummies and on vehicles for crash and sled safety testing. The accelerometer utilizes a monolithic piezoresistive cantilever type sensor crafted on [110] silicon wafer. Taking advantage of the unique vertical wall etching capability on [110] silicon, the geometry of the hinge, mass, and stop-gap can be defined precisely. It is limited only by the photolithographic accuracy instead of the etching time control. The piezoresistive gages are etch freed from the silicon wafer. Their cross sectional area is very small, 0.6 /spl mu/m by 4.2 /spl mu/m, thus needing very little strain energy to produce a useful signal. By locating them at an appropriate distance apart from the centrally support hinge, the gages are very efficient in picking up the acceleration force. A high sensitivity (nominally 0.2 mV/g) yet wide frequency range (nominally resonate at 28 kHz) sensor can be obtained. The etch freed gages enable the accelerometer to stabilize (or warm up) in less than 15 /spl mu/s after power on. It also has minimal thermal zero shifts of /spl plusmn/6 mV in a wide temperature range from -54 to +100/spl deg/C. Furthermore, the vertical wall etching capability on [110] silicon allows very narrow gaps between the mass tip and surrounding rim to "stop" the mass tip from traveling too far. These "overrange stops" protect the sensor from excessive g shock. The accelerometer demonstrates survivability under repeated high g shock in excess of 10000 g.
Cloning and sequencing of a cDNA encoding the mouse brain-type cannabinoid receptor protein (1995)

Mouse brain-type cannabinoid receptor (CB1) cDNA was cloned and sequenced. Comparison to rat and human CB1 sequences showed extensive homology (>96%) both at the nucleotide and protein levels implicating the importance of this protein in mammalian brain physiology.
CHARACTERISTICS OF CANADIAN LARD (1947)

Mean values for measured properties of 33 samples of lard obtained from 26 packing plants across Canada were: iodine number, 58.7; saponification number, 193.9; melting point, 43.5 °C.; smoke point, 382° F.; colour, 8.8Y, 1.6R; unsaponifiable matter, 0.43%; fatty acid composition: saturated, 45.6%, oleic, 44.7%, linoleic, 8.7%, linolenic, 0.6%, arachidonic, 0.4%; storage life at 26.7 °C., 9.2 weeks; Swift stability, 3.5 hr.; iodimetric peroxide, 1.6 ml. of 0.002 N thiosulphate per gm.; ferrometric peroxide, 9.7 m.e. per kgm.; Kreis test, 9.9; Stamm test, 2.3; alpha-dicarbonyl test, 3.4; free fatty acid, 0.4%; fluorescence, 79.2. The distribution of values is shown by histograms.Simple correlation coefficients computed between measured properties showed the following to be associated: melting point with iodine number; free fatty acid content with melting point, smoke point, and red colour; storage life at 26.7 °C. with log of Swift stability and initial ferrometric peroxide, Kreis, and alpha-dicarbonyl values.
Predicting the Future: Advantages of Semilocal Units (1991)

In investigating gaussian radial basis function (RBF) networks for their ability to model nonlinear time series, we have found that while RBF networks are much faster than standard sigmoid unit backpropagation for low-dimensional problems, their advantages diminish in high-dimensional input spaces. This is particularly troublesome if the input space contains irrelevant variables. We suggest that this limitation is due to the localized nature of RBFs. To gain the advantages of the highly nonlocal sigmoids and the speed advantages of RBFs, we propose a particular class of <i>semilocal</i> activation functions that is a natural interpolation between these two families. We present evidence that networks using these <i>gaussian bar</i> units avoid the slow learning problem of sigmoid unit networks, and, very importantly, are more accurate than RBF networks in the presence of irrelevant inputs. On the Mackey-Glass and Coupled Lattice Map problems, the speedup over sigmoid networks is so dramatic that the difference in training time between RBF and gaussian bar networks is minor. Gaussian bar architectures that superpose <i>composed gaussians</i> (gaussians-of-gaussians) to approximate the unknown function have the best performance. We postulate that an interesing behavior displayed by gaussian bar functions under gradient descent dynamics, which we call <i>automatic connection pruning</i>, is an important factor in the success of this representation.
A functional angiotensin II receptor-GFP fusion protein: evidence for agonist-dependent nuclear translocation (2000)

We constructed an expression vector for a fusion protein [ANG II type 1a receptor-green fluorescent protein (AT(1a)R-GFP)] consisting of enhanced GFP attached to the COOH terminus of the rat AT(1a)R. Chinese hamster ovary (CHO) cells transfected with AT(1a)R-GFP demonstrated specific, high-affinity (125)I-labeled ANG II binding (IC(50) 21 nM). ANG II exposure stimulated sodium-proton exchange and cytoplasmic calcium release to a similar extent in cells transfected with AT(1a)R or AT(1a)R-GFP; these responses were desensitized by prior exposure to ANG II and were sensitive to the AT(1)R blocker losartan. ANG II-driven internalization of AT(1a)R-GFP in transfected CHO cells was demonstrated both by radioligand binding and by laser scanning confocal microscopy. Colocalization of GFP fluorescence with that of the nuclear stain TOTO-3 in confocal images was increased more than twofold after 1 h of ANG II exposure. We conclude that AT(1a)R-GFP exhibits similar pharmacological behavior to that of the native AT(1a)R. Our observations also support previous evidence for the presence of AT(1a)R in the nucleus and suggest that the density of AT(1a)R in the nucleus may be regulated by exposure to its ligand.
Themed issue: Optofluidics (2012)

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