gebhart/patrepeval huggingface dataset:
Novel Effects of FCCP [Carbonyl Cyanide <i>p</i>‐(Trifluoromethoxy)phenylhydrazone] on Amyloid Precursor Protein Processing (1999)

Amyloidogenic processing of the beta-amyloid precursor protein (APP) has been implicated in the pathology of Alzheimer's disease. Because it has been suggested that catabolic processing of the APP holoprotein occurs in acidic intracellular compartments, we studied the effects of the protonophore carbonyl cyanide p-(trifluoromethoxy)phenylhydrazone (FCCP) and the H+-ATPase inhibitor bafilomycin A1 on APP catabolism in human embryonic kidney 293 cells expressing either wild-type or "Swedish" mutant APP. Unlike bafilomycin A1, which inhibits beta-amyloid production in cells expressing mutant but not wild-type APP, FCCP inhibited beta-amyloid production in both cell types. Moreover, the effects of FCCP were independent of alterations in total cellular APP levels or APP maturation, and the concentrations used did not alter either cellular ATP levels or cell viability. Bafilomycin A1, which had no effect on beta-amyloid production in wild-type cells, inhibited endocytosis of fluorescent transferrin, whereas concentrations of FCCP that inhibited beta-amyloid production in these cells had no effect on endosomal function. Thus, in wild-type-expressing cells it appears that the beta-amyloid peptide is not produced in the classically defined endosome. Although bafilomycin A1 decreased beta-amyloid release from cells expressing mutant APP but not wild-type APP, it altered lysosomal function in both cell types, suggesting that in normal cells beta-amyloid is not produced in the lysosome. Although inhibition of beta-amyloid production by bafilomycin A1 in mutant cells may occur via changes in endosomal/lysosomal pH, our data suggest that FCCP inhibits wild-type beta-amyloid production by acting on a bafilomycin A1-insensitive acidic compartment that is distinct from either the endosome or the lysosome.
Proteolysates from slaughter‐house blood (1982)

Abstract Previous studies have shown the anticlotting effect of papain on slaughter‐house blood to be due to its proteolytic activity on fibrin. This has suggested its possible use in a protein recovery process. Blood proteolysate has been obtained using microbial proteases or papain; the haemolysis of the cells was then effected and the haem extracted with acidified acetone to decolourise the product.
Chinese hamster ovary cells with constitutively expressed sialidase antisense RNA produce recombinant dnase in batch culture with increased sialic acid (1998)

Under some cell culture conditions, recombinant glycoprotein therapeutics expressed in Chinese hamster ovary (CHO) cells lose sialic acid during the course of the culture (Sliwkowski et al., 1992; Munzert et al., 1996). A soluble sialidase of CHO cell origin degrades the expressed recombinant protein and has been shown to be released into the culture fluid as the viability of the cells decreases. To reduce the levels of the sialidase and to prevent desialylation of recombinant protein, a CHO cell line has been developed that constitutively expresses sialidase antisense RNA. Several antisense expression vectors were prepared using different regions of the sialidase gene. Co-transfection of the antisense constructs with a vector conferring puromycin resistance gave rise to over 40 puromycin resistant clones that were screened for sialidase activity. A 5' 474 bp coding segment of the sialidase cDNA, in the inverted orientation in an SV 40-based expression vector, gave maximal reduction of the sialidase activity to about 40% wild-type values. To test if this level of sialidase would lead to increased sialic acid content of an expressed recombinant protein, the 474 antisense clone was employed as a host for expression of human DNase as a model glycoprotein. The sialic acid content of the DNase produced in the antisense cultures was compared with material made in the wild-type parental cell line. About 20-37% increase in sialic acid content, or 0.6-1.1 mole of additional sialic acid out of a total of 3.0 mole on the product, was found on the DNase made in the antisense cell lines.
Multi-Style Transfer with Discriminative Feedback on Disjoint Corpus (2021)

Navita Goyal, Balaji Vasan Srinivasan, Anandhavelu N, Abhilasha Sancheti. Proceedings of the 2021 Conference of the North American Chapter of the Association for Computational Linguistics: Human Language Technologies. 2021.
ChemInform Abstract: Two‐Photon Fluorescent Probes for Metal Ions. (2011)

Abstract Review: 61 refs.
N-Substituted 4β-Methyl-5-(3-hydroxyphenyl)-7α-amidomorphans Are Potent, Selective κ Opioid Receptor Antagonists (2006)

In a previous study, we identified (-)-N-[(1R,4S,5S,7R)-5-(3-hydroxyphenyl)-4-methyl-2-(3-phenylpropyl)-2-azabicyclo[3.3.1]non-7-yl]-3-(1-piperidinyl)propanamide (5a, KAA-1) as the first potent and selective kappa opioid receptor antagonist from the 5-(3-hydroxyphenyl)morphan class of opioids. In this study we report an improved synthesis of this class of compounds. The new synthetic method was used to prepare analogues 5b-r where the morphan N-substituent and 7alpha-amido group were varied. Most of the analogues showed sub-nanomolar potency for the kappa opioid receptor and were highly selective relative to the mu and delta opioid receptors. (-)-3-(3,4-Dihydroisoquinolin-2(1H)-yl)-N-{(1R,4S,5S,7R)-5-(3-hydroxyphenyl)-4-methyl-2-[2-(2-methylphenyl)ethyl]-2-azabicyclo[3.3.1]non-7-yl}propanamide (5n, MTHQ) is at least as potent and selective as nor-BNI as a kappa opioid receptor antagonist in the [35S]GTP-gamma-S in vitro functional test.
Towards inline spatially resolved temperature sensing in thermal ablation with chirped fiber Bragg grating (2016)

We investigate the theory and feasibility of an inline spatially resolved temperature sensor, suitable for thermal ablation monitoring. The sensor is based o a chirped fiber Bragg grating (CFBG). The CFBG is modelled as a chain of Bragg gratings, each sensitive to local temperature variations. By using a combination of iterative and statistical optimization techniques, it is possible to use demodulate the CFBG, in case of a Gaussian-like spatial temperature profile. A feasibility test based on CFBG simulation shows that the CFBG returns error <;1 mm on cellular damage threshold spatial estimation and good noise resilience.
Synthesis and <sup>11</sup>C‐labelling of (<i>E</i>,<i>E</i>)‐1‐(3′,4′‐dihydroxystyryl)‐4‐(3′‐methoxy‐4′‐hydroxystyryl) benzene for PET imaging of amyloid deposits<sup>†</sup> (2002)

Abstract Carboxylic acid derivatives of the amyloid‐binding dye Congo red do not enter the brain well and are thus unable to serve as in vivo amyloid‐imaging agents. A neutral amyloid probe, ( E , E )‐1‐(3′,4′‐dihydroxystyryl)‐4‐(3′‐methoxy‐4′‐hydroxystyryl)benzene ( 3 ), devoid of any carboxylate groups has been designed and synthesized via a 12‐step reaction sequence with a total yield of 30%. The unsymmetric compound 3 has also been labelled with C‐11 via [ 11 C]methyl iodide ([ 11 C]CH 3 I) methylation of a symmetric 4,4′‐dimesyl protected precursor followed by deprotection. Preliminary evaluation indicated that compound 3 selectively stained plaques and neurofibrillary tangles in post‐mortem AD brain, and exhibited good binding affinity ( K i =38±8 nM) for A β (1–40) fibrils in vitro . In vivo pharmacokinetic studies indicated that [ 11 C] 3 exhibited higher brain uptake than its carboxylic acid analogs and good clearance from normal control mouse brain. [ 11 C] 3 also exhibited specific in vivo binding to pancreatic amyloid deposits in the NOR‐beta transgenic mouse model. These results justify further investigation of 3 and similar derivatives as surrogate markers for in vivo quantitation of amyloid deposits. Copyright © 2002 John Wiley & Sons, Ltd.
Novel Nonimidazole Histamine H<sub>3</sub> Receptor Antagonists:  1-(4-(Phenoxymethyl)benzyl)piperidines and Related Compounds (2003)

In an extension of very recently published studies on successful imidazole replacements in some series of histamine H(3) receptor antagonists, we report on a new class of lipophilic nonimidazole antagonist having an aliphatic tertiary amino moiety connected to a benzyl template substituted in the 4-position by a phenoxymethyl group. The structural modifications were performed with the intention to avoid possible negative side effects reported for other series of antagonists. The novel compounds combine different characteristics of recently developed histamine H(3) receptor antagonists. The compounds were screened for their affinity in a binding assay for the human histamine H(3) receptor stably expressed in CHO-K1 cells and tested for their in vivo potency in the central nervous system of mice after oral administration. Different substitution patterns on the phenoxy group were used to optimize in vitro and/or in vivo potency leading to some compounds with low nanomolar affinity and high oral in vivo potency. Modifications of the basic piperidino moiety were performed by ring expansion, contraction, and opening. Selected compounds exhibited selectivity in functional assays on isolated organs of guinea-pig for H(3) vs H(1) and H(2) receptors. Unexpectedly, some of the novel antagonists also showed a slight preference for the human histamine H(3) receptor compared to their affinities for the guinea-pig H(3) receptor.
Sphingomyelin enhances chemotherapy efficacy and increases apoptosis in human colonic tumor xenografts (2002)

Evidence suggests that ceramide, generated from a distinct subcellular pool of sphingomyelin (SM) by the action of sphingomyelinases, may be used by cells to propagate apoptotic signals in response to a variety of cytotoxic agents. Since most tumor cells have altered lipid metabolism, it is possible that the intracellular pool of SM used for signaling is decreased. To overcome this, we have attempted to increase the SM content of all intracellular compartments with exogenous SM and examined the impact on 5-fluorouracil (5FU) and irinotecan chemosensitivity. Our data suggest that the efficacy of these two chemotherapeutics for the treatment of HT-29, HCT15 and GW-39 human colonic tumor xenografts can be enhanced by the use of exogenous SM. Furthermore, this enhancement may be due to a reversal of the attenuation of the apoptotic signal found in cancer cells without inducing significant hematopoietic, hepatic or renal toxicity.
The promoter of the <i>Arabidopsis thaliana Cel1</i> endo‐1,4‐β glucanase gene is differentially expressed in plant feeding cells induced by root‐knot and cyst nematodes (2004)

SUMMARY Transgenic tobacco and Arabidopsis thaliana carrying the Arabidopsis endo-1,4-beta-glucanase (EC 3.2.1.4) Cel1 promoter fused to the beta-glucuronidase (GUS) reporter gene were infected with the root-knot nematode, Meloidogyne incognita, and either the tobacco cyst nematode, Globodera tabacum (tobacco), or beet cyst nematode, Heterodera schachtii (Arabidopsis). Cel1-driven GUS expression was detected in cell elongation zones of noninfected plants and within feeding sites (giant-cells) induced in roots of both plant hosts by M. incognita. The first detectable signs of Cel1 expression within developing giant-cells occurred at the onset of giant-cell formation and continued throughout the M. incognita life cycle. UidA (Gus) transcripts were detectable within giant-cells induced in tobacco roots at 11-13 days postinoculation with M. incognita as determined by in situ mRNA hybridization. By contrast, expression of the Cel1 promoter was not detected within developing syncytia induced in tobacco or Arabidopsis roots by G. tabacum and H. schachtii, respectively, at any time point. The results demonstrate specific regulation of cell wall-degrading enzymes that may be required for cell wall modifications during feeding cell formation by sedentary endoparasitic nematodes. Differential expression of Cel1 by cyst and root-knot nematodes further supports underlying mechanistic differences in giant-cell and syncytium formation.
Scanning Electrochemical Cell Microscopy Platform for Ultrasensitive Photoelectrochemical Imaging (2015)

The development of techniques for nanoscale structure-activity correlations is of major importance for the fundamental understanding and rational design of (photo)electrocatalysts. However, the low conversion efficiency of characteristic materials generates tiny photoelectrochemical currents at the submicrometer to nanoscale, in the fA range, which are challenging to detect and measure accurately. Here, we report the coupling of scanning electrochemical cell microscopy (SECCM) with photoillumination, to create a submicrometer spatial resolution cell that opens up high resolution structure-(photo)activity measurements. We demonstrate the capabilities of the technique as a tool for: (i) high spatial resolution (photo)activity mapping using an ionic liquid electrolyte at a thin film of TiO2 aggregates, commonly used as a photoanode in dye sensitized solar cells (DSSCs) and (ii) in situ (photo)activity measurements of an electropolymerized conjugated polymer on a transparent Au substrate in a controlled atmospheric environment. Quantitative data, including localized (photo)electrochemical transients and external quantum efficiency (EQE), are extracted, and prospects for further technique development and enhancement are outlined.
Cell-aware Production test results from a 32-nm notebook processor (2012)

This paper describes a new approach for significantly improving overall defect coverage for CMOS-based designs. We present results from a defect-oriented cell-aware (CA) library characterization and pattern-generation flow and its application to 1,900 cells of a 32-nm technology. The CA flow enabled us to detect cell-internal bridges and opens that caused static, gross-delay, and small-delay defects. We present highvolume production test results from a 32-nm notebook processor to which CA test patterns were applied, including the defect rate reduction in PPM that was achieved after testing 800,000 parts. We also present cell-internal diagnosis and physical failure analysis results from one failing part.
Phase-contrast X-ray CT. (1996)

X-ray transmission imaging that creates image contrast from the distribution of the X-ray absorption coefficient is not sensitive to materials consisting of light elements such as hydrogen, carbon, nytrogen, and oxygen. On the other hand, the X-ray phase shift caused by the light elements is substantial enough to be detected even when absorption is almost zero. Hence, phase-contrast X-ray imaging is a promissing technique for observing the structure inside biological soft tissues without the need for staining and without serious radiation exposure. Using fringe scanning X-ray interferometry, the X-ray phase shift caused by an object was measured. Three-dimensional image reconstruction of cancerous tissues using the measured phase shifts was enabled under tomographic configuration phase-contrast X-ray computed tomography (CT) .
The Major Protein Arginine Methyltransferase in Trypanosoma brucei Functions as an Enzyme-Prozyme Complex (2016)

Prozymes are catalytically inactive enzyme paralogs that dramatically stimulate the function of weakly active enzymes through complex formation. The two prozymes described to date reside in the polyamine biosynthesis pathway of the human parasite <i>Trypanosoma brucei</i>, an early branching eukaryote that lacks transcriptional regulation and regulates its proteome through posttranscriptional and posttranslational means. Arginine methylation is a common posttranslational modification in eukaryotes catalyzed by protein arginine methyltransferases (PRMTs) that are typically thought to function as homodimers. We demonstrate that a major <i>T. brucei</i> PRMT, <i>Tb</i>PRMT1, functions as a heterotetrameric enzyme-prozyme pair. The inactive PRMT paralog, <i>Tb</i>PRMT1<sup>PRO</sup>, is essential for catalytic activity of the <i>Tb</i>PRMT1<sup>ENZ</sup> subunit. Mutational analysis definitively demonstrates that TbPRMT1<sup>ENZ</sup> is the cofactor-binding subunit and carries all catalytic activity of the complex. Our results are the first demonstration of an obligate heteromeric PRMT, and they suggest that enzyme-prozyme organization is expanded in trypanosomes as a posttranslational means of enzyme regulation.
Automatic phase alignment for a fully integrated cartesian feedback power amplifier system (2003)

A phase-alignment system is used in the first reported IC to fully integrate a power amplifier, Cartesian feedback linearization circuitry, and a phase-alignment system. The phase-alignment system consumes 8.8 mW from a 2.5-V supply and employs a new technique for offset-free analog multiplication that enables it to function without manual trimming. Phase alignment of better than 9° is maintained for drifts as large as ±90°. We demonstrate how the phase-alignment system improves the stability margins of the fully integrated Cartesian feedback system. The power amplifier itself, integrated on the same die, operates at 2 GHz and delivers a maximum of 14.2 dBm of output power into a 50-/spl Omega/ load. The IC was fabricated in a 0.25-μm CMOS process.
Synthesis and Photochromic Properties of Methoxy Substituted 2,2-Diaryl-2H-naphtho[1,2-b]pyrans (2004)

A series of methoxy-substituted 2,2-di(4-methoxyphenyl)-2Hnaphtho[1,2-b]pyrans has been synthesised from 3-alkoxycarbonyl-1-naphthols and 1,1-di(4-methoxyphenyl)prop-2-yn-1-ol.The influence of the methoxy group on the wavelength of maximum absorption and the stability of the ringopened naphthopyrans is discussed.
Organometallic Compounds with Biological Activity: A Very Selective and Highly Potent Cellular Inhibitor for Glycogen Synthase Kinase 3 (2006)

A chiral second-generation organoruthenium half-sandwich compound is disclosed that shows a remarkable selectivity and cellular potency for the inhibition of glycogen synthase kinase 3 (GSK-3). The selectivity was evaluated against a panel of 57 protein kinases, in which no other kinase was inhibited to the same extent, with a selectivity window of at least tenfold to more than 1000-fold at 100 microM ATP. Furthermore, a comparison with organic GSK-3 inhibitors demonstrated the superior cellular activity of this ruthenium compound: wnt signaling was fully induced at concentrations down to 30 nM. For comparison, the well-established organic GSK-3 inhibitors 6-bromoindirubin-3'-oxime (BIO) and kenpaullone activate the wnt pathway at concentrations that are higher by around 30-fold and 100-fold, respectively. The treatment of zebrafish embryos with the organometallic inhibitor resulted in a phenotype that is typical for the inhibition of GSK-3. No phenotypic change was observed with the mirror-imaged ruthenium complex. The latter does not, in fact, show any of the pharmacological properties for the inhibition of GSK-3. Overall, these results demonstrate the potential usefulness of organometallic compounds as molecular probes in cultured cells and whole organisms.
Processing and Properties of Strong and Non-rigid Calcium Phosphate Cement (2002)

A calcium phosphate cement (CPC) sets to form hydroxyapatite and has been used in dental and craniofacial applications. However, when CPC was used in periodontal repair, tooth mobility resulted in the fracture and exfoliation of the brittle implants. The aim of this study was to develop CPC-chitosan lactate composites with higher strength and increased strain before failure. It was hypothesized that the incorporation of chitosan lactate would render CPC non-rigid with improved properties. Two-way ANOVA showed significant effects of chitosan lactate and powder:liquid ratio (p < 0.001) on flexural strength, strain-at-peak-load, work-of-fracture, and elastic modulus. At powder:liquid = 2, the strength (mean +/- SD; n = 6) at 20% chitosan lactate was 15.7 +/- 1.3 MPa, higher than 4.9 +/- 1.4 MPa of CPC without chitosan lactate. At powder:liquid = 1, the strain-at-peak-load was 0.2% for CPC without chitosan lactate; it increased to 15.8% for CPC containing 15% chitosan lactate. The work-of-fracture was increased by more than ten times. The novel strong and non-rigid CPC may provide compliance for tooth mobility without fracturing the implant, and may also extend the use of CPC into the repair of larger defects in stress-bearing locations.
Laboratory aspects of Lyme borreliosis (1988)

Lyme borreliosis (Lyme disease), a common tick-borne disorder of people and domestic animals in North America and Europe, is caused by the spirochete Borrelia burgdorferi. Following the discovery and initial propagation of this agent in 1981 came revelations that other tick-associated infectious disorders are but different forms of Lyme borreliosis. A challenge for the clinician and microbiology laboratory is confirmation that a skin rash, a chronic meningitis, an episode of myocarditis, or an arthritic joint is the consequence of B. burgdorferi infection. The diagnosis of Lyme borreliosis may be established by (i) directly observing the spirochete in host fluid or tissue, (ii) recovering the etiologic spirochete from the patient in culture medium or indirectly through inoculation of laboratory animals, or (iii) carrying out serologic tests with the patient's serum or cerebrospinal fluid. The last method, while lacking in discriminatory power, is the most efficacious diagnostic assay for most laboratories at present.
SRNL POROUS WALL GLASS MICROSPHERES (2008)

The Savannah River National Laboratory (SRNL) has developed a new medium for storage of hydrogen and other gases. This involves fabrication of thin, Porous Walled, Hollow Glass Microspheres (PW-HGMs), with diameters generally in the range of 1 to several hundred microns. What is unique about the glass microballons is that porosity has been induced and controlled within the thin, one micron thick walls, on the scale of 10 to several thousand Angstroms. This porosity results in interesting properties including the ability to use these channels to fill the microballons with special absorbents and other materials, thus providing a contained environment even for reactive species. Gases can now enter the microspheres and be retained on the absorbents, resulting in solid-state and contained storage of even reactive species. Also, the porosity can be altered and controlled in various ways, and even used to filter mixed gas streams within a system. SRNL is involved in about a half dozen different programs involving these PW-HGMs and an overview of some of these activities and results emerging are presented.
Novel Prodrug Approach for Tertiary Amines:  Synthesis and Preliminary Evaluation of <i>N</i>-Phosphonooxymethyl Prodrugs (1999)

The synthesis and preliminary evaluation of a novel prodrug approach for improving the water solubility of drugs containing a tertiary amine group are reported. The prodrug synthesis involves a nucleophilic substitution reaction between the parent tertiary amine and a novel derivatizing reagent, di-tert-butyl chloromethyl phosphate, resulting in formation of the quaternary salt. The tertiary butyl groups are easily removed under acidic conditions with trifluoroacetic acid giving the N-phosphonooxymethyl prodrug in the free phosphoric acid form, which can subsequently be converted to the desired salt form. The synthesis was successfully applied to a model compound (quinuclidine) and to three tertiary amine-containing drugs (cinnarizine, loxapine, and amiodarone). The prodrugs were designed to undergo a two-step bioreversion process. The first step was an enzyme-catalyzed rate-determining dephosphorylation followed by spontaneous chemical breakdown of the N-hydroxymethyl intermediate to give the parent drug. Selected prodrugs were shown to be substrates for alkaline phosphatase in vitro. A preliminary in vivo study confirmed the ability of the cinnarizine prodrug to be rapidly and completely converted to cinnarizine in a beagle dog following iv administration.