gebhart/patrepeval huggingface dataset:
Ring-Opening Metathesis Polymerization with the Second Generation Hoveyda–Grubbs Catalyst: An Efficient Approach toward High-Purity Functionalized Macrocyclic Oligo(cyclooctene)s (2013)

Herein, we present a facile and general strategy to prepare functionalized macrocyclic oligo(cyclooctene)s (cOCOEs) in high purity and high yield by exploiting the ring-opening metathesis polymerization (ROMP) intramolecular backbiting process with the commercially available second generation Hoveyda-Grubbs (HG2) catalyst. In the first instance, ROMP of 5-acetyloxycyclooct-1-ene (ACOE) followed by efficient quenching and removal of the catalyst using an isocyanide derivative afforded macrocyclic oligo(5-acetyloxycyclooct-1-ene) (cOACOE) in high yield (95%), with a weight-average molecular weight (Mw) of 1.6 kDa and polydispersity index (PDI) of 1.6, as determined by gel permeation chromatography (GPC). The structure and purity of the macrocycles were confirmed by NMR spectroscopy and elemental analysis, which indicated the complete absence of end-groups. This was further supported by GPC-matrix assisted laser desorption ionization time-of-flight mass spectroscopy (GPC-MALDI ToF MS), which revealed the exclusive formation of macrocyclic derivatives composed of up to 45 repeat units. Complete removal of residual ruthenium from the macrocycles was confirmed by inductively coupled plasma atomic emission spectroscopy (ICP-AES). The same methodology was subsequently extended to the ROMP of 5-bromocyclooct-1-ene and 1,5-cyclooctadiene to prepare their macrocyclic derivatives, which were further derivatized to produce a library of functionalized macrocyclic oligo(cyclooctene)s. A comparative study using the second and third generation Grubbs catalysts in place of the HG2 catalyst for the polymerization of ACOE provided macrocycles contaminated with linear species, thus indicating that the bidendate benzylidene ligand of the Hoveyda-Grubbs catalyst plays an important role in the observed product distributions.
Charge Carrier Lifetimes Exceeding 15 μs in Methylammonium Lead Iodide Single Crystals (2016)

The charge carrier lifetime in organic-inorganic perovskites is one of the most important parameters for modeling and design of solar cells and other types of devices. In this work, we use CH3NH3PbI3 single crystal as a model system to study optical absorption, charge carrier generation, and recombination lifetimes. We show that commonly applied photoluminescence lifetime measurements may dramatically underestimate the intrinsic carrier lifetime in CH3NH3PbI3, which could be due to severe charge recombination at the crystal surface and/or fast electron-hole recombination close to the surface. By using the time-resolved microwave conductivity technique, we investigated the lifetime of free mobile charges inside the crystals. Most importantly, we find that for homogeneous excitation throughout the crystal, the charge carrier lifetime exceeds 15 μs. This means that the diffusion length in CH3NH3PbI3 can be as large as 50 μm if it is no longer limited by the dimensions of the crystallites.
The Min (multiple intestinal neoplasia) mutation: its effect on gut epithelial cell differentiation and interaction with a modifier system. (1992)

Min is a fully penetrant dominant mutation that leads to the development of multiple intestinal adenomas throughout the duodenal-to-colonic axis. Min/+ C57BL6/J mice have an average life-span of 120 d. Multi-label immunocytochemical studies of these lesions demonstrate patches of differentiated enterocytes, and scattered enteroendocrine, goblet and Paneth cells. Expression of endogenous marker genes within these differentiated cells can be directly correlated with the position occupied by the adenoma along the duodenal-to-colonic axis and mirrors the regional differentiation of the normal gut epithelium. The presence of multiple lineages in adenomas together with their retention of spatial information suggests that tumorigenesis in Min/+ mice may be initiated in a multipotent stem cell normally located at the base of intestinal crypts. To study the time-dependent properties of these tumors, genetic conditions were sought in which Min/+ animals could survive for up to 300 d. Min is fully penetrant in hybrids with either AKR/J or MA/MyJ. However, the hybrids demonstrate a reduction in the number of intestinal adenomas. Preliminary backcross analysis is consistent with a single major modifier locus unlinked to Min in both the AKR/J and MA/MyJ strains. The increased lifespan of the hybrid animals is also associated with the development of invasive tumors. New tumors do not arise continuously over the lifespan of these animals; instead all adenomas appear to be established by 100 d of age or sooner. These studies indicate that the Min/+ mouse is a powerful model system for analyzing the mechanisms that establish and maintain a balance between proliferation and differentiation in the continuously renewing gut epithelium and for an assessment of the multi-step hypothesis of intestinal neoplasia.
Calcitermin, a novel antimicrobial peptide isolated from human airway secretions (2001)

The human airways are protected from pathogenic colonization by a blanket of fluid impregnated with innate antimicrobial effector molecules. Among several previously uncharacterized components, we isolated a peptide that had activity primarily targeting Gram-negative bacteria. We named the peptide 'calcitermin' since its amino acid sequence and mass were equivalent to the 15 C-terminal residues of the S100 protein, calgranulin C. The antimicrobial activity of calcitermin was enhanced in acidic buffers (pH 5.4) and in the presence of micromolar concentrations of ZnCl(2). Analysis revealed a putative zinc-binding consensus sequence as well as an alpha-helical conformation in structure-promoting solvents.
Long-Term Sensitization of a Defensive Withdrawal Reflex in Aplysia (1973)

When a weak tactile stimulus is applied to the siphon of Aplysia californica, the animal withdraws the siphon between the parapodia. This defensive withdrawal reflex can be facilitated (sensitized) if the animal is previously given 4 days of training, consisting of four brief noxious stimuli each day. The sensitization of this reflex can last for up to 3 weeks after training and is mediated by the abdominal ganglion which also mediates long-term habituation. This preparation may provide a system for analyzing the neural mechanism of long-term behavioral modifications of complexity which is intermediate between habituation and associative learning.
Autophagy negatively regulates cancer cell proliferation via selectively targeting VPRBP (2012)

There have been multiple lines of evidence suggesting that autophagy selectively targets signalling proteins and regulates cancer cell signalling in addition to bulk clearance of long-lived proteins and organelles. Protein degradation through autophagy requires receptor protein LC3B to sequester the substrates into the autophagosome. In the present study, we screened LC3B (light-chain 3B)-binding partners and identified autophagic substrates in cancer cells. With lung cancer NCI-H1975 and oesophageal cancer KYSE30 cell lines as models, we found that VPRBP (viral protein R-binding protein) was a novel LC3B-binding protein through GST (glutathione transferase)-LC3B pull-down combined with LC-MS/MS (liquid chromatography-tandem MS) methods. Co-immunoprecipitation assay showed that VPRBP-LC3/p62 were in the same protein complex as the two cell lines. Induction of autophagy led to a down-regulation of VPRPB, which could be rescued by the inhibition of autophagy degradation by BFA1 (bafilomycin A1) and by the disruption of autophagy through ATG5-knockdown. We also found that induction of autophagy promotes VPRBP-LC3/p62 interaction. Immunohistochemical examination of human NSCLC (non-small cell lung cancer) tissues showed that VPRBP was positively correlated with p62 and negatively correlated with LC3B. Moreover, p62 and VPRBP were associated with poor prognosis in lung ADC (adenocarcinoma) (p62, P=0.019; VPRBP, P=0.005). Patients with low expression of both p62 and VPRBP showed the best prognosis.
Detecting Individual Sites Subject to Episodic Diversifying Selection (2012)

The imprint of natural selection on protein coding genes is often difficult to identify because selection is frequently transient or episodic, i.e. it affects only a subset of lineages. Existing computational techniques, which are designed to identify sites subject to pervasive selection, may fail to recognize sites where selection is episodic: a large proportion of positively selected sites. We present a mixed effects model of evolution (MEME) that is capable of identifying instances of both episodic and pervasive positive selection at the level of an individual site. Using empirical and simulated data, we demonstrate the superior performance of MEME over older models under a broad range of scenarios. We find that episodic selection is widespread and conclude that the number of sites experiencing positive selection may have been vastly underestimated.
ATP-Binding Cassette Transporter A1 (ABCA1) in Macrophages: A Dual Function in Inflammation and Lipid Metabolism? (1999)

Activated lipid-laden macrophages in the vascular wall are key modulators of the inflammatory processes underlying atherosclerosis. We demonstrate here that the ATP-binding cassette (ABC) transporter ABCA1 is induced during differentiation of human monocytes into macrophages. ABCA1 has been implicated in macrophage interleukin-1beta secretion and apoptosis. Moreover, ABCA1 mRNA and protein levels are strongly upregulated by uptake of modified LDL and downregulated by HDL(3)-mediated lipid efflux in macrophages. Mutation analysis in patients with the classical Tangier disease (TD), a monogenetic disorder characterized by hypersplenism, macrophage accumulation and deposition of cholesteryl esters in the reticuloendothelial system, low plasma HDL and premature atherosclerosis, revealed deleterious mutations in their ABCA1 gene. The localization pattern of the mutations within the ABCA1 protein appears to determine the tropism for either the reticuloendothelial system, as seen in the classical TD phenotype, or the artery wall, as in the case of HDL deficiency in the absence of splenomegaly. In a comprehensive analysis of the expression and regulation of all currently known human ABC transporters, we identified additional cholesterol-responsive genes that are induced during monocyte differentiation into macrophages. Our results indicate a dual regulatory function for ABCA1 in macrophage lipid metabolism and inflammation.
Ullmann condensation using copper or copper oxide as the reactant. Arylation of active hydrogen compounds (imides, amides, amines, phenol, benzoic acid, and phenylacetylene) (1983)

Ullmann condensation using Cu or copper oxide as the reactant and using no base has been studied. Reactions of active N—H, O—H, and C—H compounds, RZH (imides, amides, amines, phenol, benzoic acid, and phenylacetylene), with mixtures of aryl halides and more than a stoichiometric amount of Cu or copper oxide (Cu 2 O or CuO) without addition of base lead to facile arylation of the active hydrogen compounds. In the arylation reaction Cu and copper oxides serve not only as the catalyst but also as the acceptor of halogen from aryl halide. The reactivity of phenyl halide, PhX, increases in the order PhCl &lt; PhBr &lt; Phl. Cu generally gives higher yields than Cu 2 O and CuO and, of the two copper oxides, Cu 2 O has the higher activity. The stronger the acidity of the active hydrogen compound (RZH), the more easily the compound is phenylated by the mixture of PhX and Cu; a roughly linear correlation between T i , the temperature where the phenylation starts, and the pK a value of the active hydrogen compound has been observed. A mechanism involving initial formation of an RZ—Cu species by the reaction between RZH and Cu or copper oxide and ensuing attack of organic halide at the RZ—Cu species is proposed.
Sensory neuron targeting by self-complementary AAV8 via lumbar puncture for chronic pain (2008)

Lumbar puncture (LP) is an attractive route to deliver drugs to the nervous system because it is a safe bedside procedure. Its use for gene therapy has been complicated by poor vector performance and failure to target neurons. Here we report highly effective gene transfer to the primary sensory neurons of the dorsal root ganglia (DRGs) with self-complementary recombinant adeno-associated virus serotype 8 (sc-rAAV8) modeling an LP. Transgene expression was selective for these neurons outlining their cell bodies in the DRGs and their axons projecting into the spinal cord. Immunohistochemical studies demonstrated transduction of cells positive for the nociceptive neuron marker vanilloid receptor subtype 1, the small peptidergic neuron markers substance P and calcitonin gene-related peptide, and the nonpeptidergic neuron marker griffonia simplicifolia isolectin B4. We tested the efficacy of the approach in a rat model of chronic neuropathic pain. A single administration of sc-rAAV8 expressing the analgesic gene prepro-beta-endorphin (ppbetaEP) led to significant (P < 0.0001) reversal of mechanical allodynia for >/=3 months. The antiallodynic effect could be reversed by the mu-opioid antagonist naloxone 4 months after gene transfer (P < 0.001). Testing of an alternative nonopioid analgesic gene, IL-10, alone or in combination with ppbetaEP was equally effective (P < 0.0001). All aspects of the procedure, such as the use of an atraumatic injection technique, isotonic diluent, a low-infusion pressure, and a small injection volume, are consistent with clinical practice of intrathecal drug use. Therefore, gene transfer by LP may be suitable for developing gene therapy-based treatments for chronic pain.
From Phage Display to Nanoparticle Delivery: Functionalizing Liposomes with Multivalent Peptides Improves Targeting to a Cancer Biomarker (2012)

Phage display is commonly used to isolate peptides that bind to a desired cell type. While chemical synthesis of selected peptides often results in ligands with low affinity, a multivalent tetrameric presentation of the peptides dramatically improves affinity. One of the primary uses of these peptides is conjugation to nanoparticle-based therapeutics for specific delivery to target cell types. We set out to optimize the path from phage display peptide selection to peptide presentation on a nanoparticle surface for targeted delivery. Here, we examine the effects of peptide valency, density, and affinity on nanoparticle delivery and therapeutic efficacy, using the α(v)β(6)-specific H2009.1 peptide as a model phage-selected peptide and liposomal doxorubicin as a model therapeutic nanoparticle. Liposomes displaying the higher affinity multivalent H2009.1 tetrameric peptide demonstrate 5-10-fold higher drug delivery than liposomes displaying the lower affinity monomeric H2009.1 peptide, even when the same number of peptide subunits are displayed on the liposome. Importantly, a 6-fold greater toxicity is observed toward α(v)β(6)-expressing cells for liposomes displaying tetrameric verses monomeric H2009.1 peptides. Additionally, liposomal targeting and toxicity increase with increasing concentrations of H2009.1 tetrameric peptide on the liposome surface. Thus, both the multivalent peptide and the multivalent liposome scaffold work together to increase targeting to α(v)β(6)-expressing cells. This multilayered approach to developing high affinity targeted nanoparticles may improve the utility of moderate affinity peptides. As tetramerization is known to increase affinity for a variety of phage-selected peptides, it is anticipated that the tetrameric scaffold may act as a general method for taking peptides from phage display to nanoparticle display.
Rapid Detection of Herpes Simplex Virus DNA in Genital Ulcers by Real-Time PCR Using SYBR Green I Dye as the Detection Signal (2002)

We have evaluated a real-time PCR procedure based on the LightCycler technology for rapid detection of herpes simplex virus (HSV) in genital lesions. Two sets of primers, corresponding to the thymidine kinase and DNA polymerase regions, were used for the amplification reactions in separate capillaries containing the SYBR Green I dye as detection signal. In 28 of 118 samples (24%), HSV was isolated by conventional cell culture. All cell culture-positive samples were also positive by real-time PCR. Six additional cell culture-negative samples were positive by PCR with both sets of primers. Total processing time was less than 3 h. Real-time PCR using SYBR Green I as detection signal is a sensitive procedure for the rapid diagnosis of HSV in genital lesions.
A Noninfectious Simian/Human Immunodeficiency Virus DNA Vaccine That Protects Macaques against AIDS (2005)

Simian/human immunodeficiency virus SHIV(KU2) replicates with extremely high titers in macaques. In order to determine whether the DNA of the viral genome could be used as a vaccine if the DNA were rendered noninfectious, we deleted the reverse transcriptase gene from SHIVKU2 and inserted this DNA (DeltartSHIVKU2) into a plasmid that was then used to test gene expression and immunogenicity. Transfection of Jurkat and human embryonic kidney epithelial (HEK 293) cells with the DNA resulted in production of all of the major viral proteins and their precursors and transient export of a large quantity of the Gag p27 into the supernatant fluid. As expected, no infectious virus was produced in these cultures. Four macaques were injected intradermally with 2 mg of the DNA at 0, 8, and 18 weeks. The animals developed neutralizing antibodies and low enzyme-linked immunospot assay (E-SPOT) titers against SHIVKU2. These four animals and two unvaccinated control animals were then challenged with heterologous SHIV89.6P administered into their rectums. The two control animals developed viral RNA titers exceeding 10(6) copies/ml of plasma, and these titers were accompanied by the loss of CD4+ T cells by 2 weeks after challenge. The two control animals died at weeks 8 and 16, respectively. All four of the immunized animals became infected with the challenge virus but developed lower titers of viral RNA in plasma than the control animals, and the titers decreased over time in three of the four macaques. The fourth animal remained viremic and died at week 47. Whereas the control animals failed to develop E-SPOT responses, all four of the immunized animals developed anamnestic E-SPOT responses after challenge. The animal that died developed the highest E-SPOT response and was the only one that produced neutralizing antibodies against the challenge virus. These results established that noninfectious DNA of pathogenic SHIV could be used as a vaccine to prevent AIDS, even though the immunological assays used did not predict the manner in which the challenge virus would replicate in the vaccinated animals.
Biotransformation of Total Saponins in Siraitia Fructus by Human Intestinal Microbiota of Normal and Type 2 Diabetic Patients: Comprehensive Metabolite Identification and Metabolic Profile Elucidation Using LC-Q-TOF/MS (2017)

Siraitia fructus, known as Luo-Han-Guo (LHG) in Chinese, shows good antidiabetic activity. Gut microbiota have emerged as parameter of the pathophysiology of type 2 diabetes (t2D) mellitus. In this study, in vitro biotransformation of LHG extract by t2D and normal human intestinal microbiota was analyzed using ultraperformance liquid chromatography with time-of-flight mass spectrometry. A total of 19 and 12 metabolites were characterized in t2D and normal human intestinal microbiota, respectively. These metabolites were formed by a series of metabolic reactions including deglycosylation, oxidation, isomerization, and/or deoxidation. The metabolite classes of LHG extract in normal and t2D human intestinal microbiota were nearly the same, but oxidation and isomerization reactions were usually present in t2D human intestinal bacteria. This might be due to metabolic activation by pathological human intestinal bacteria. Our study indicates that there are differences in the biotransformation of LHG extract in normal and t2D human intestinal bacteria.
Non‐Haloaluminate Room‐Temperature Ionic Liquids in Electrochemistry—A Review (2004)

Some twenty-five years after they first came to prominence as alternative electrochemical solvents, room temperature ionic liquids (RTILs) are currently being employed across an increasingly wide range of chemical fields. This review examines the current state of ionic liquid-based electrochemistry, with particular focus on the work of the last decade. Being composed entirely of ions and possesing wide electrochemical windows (often in excess of 5 volts), it is not difficult to see why these compounds are seen by electrochemists as attractive potential solvents. Accordingly, an examination of the pertinent properties of ionic liquids is presented, followed by an assessment of their application to date across the various electrochemical disciplines, concluding with an outlook viewing current problems and directions.
Thermal and Light Control of the Sol-Gel Phase Transition in Cholesterol-Based Organic Gels. Novel Helical Aggregation Modes As Detected by Circular Dichroism and Electron Microscopic Observation (1994)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTThermal and Light Control of the Sol-Gel Phase Transition in Cholesterol-Based Organic Gels. Novel Helical Aggregation Modes As Detected by Circular Dichroism and Electron Microscopic ObservationKazutaka Murata, Masayoshi Aoki, Tsuyoshi Suzuki, Takaaki Harada, Hirosuke Kawabata, Takashi Komori, Fumio Ohseto, Keiko Ueda, and Seiji ShinkaiCite this: J. Am. Chem. Soc. 1994, 116, 15, 6664–6676Publication Date (Print):July 1, 1994Publication History Published online1 May 2002Published inissue 1 July 1994https://pubs.acs.org/doi/10.1021/ja00094a023https://doi.org/10.1021/ja00094a023research-articleACS PublicationsRequest reuse permissionsArticle Views4592Altmetric-Citations702LEARN 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
Vestibular Meniere's Disease (1985)

The clinical entity of vestibular Meniere's disease (VMD) is assessed and described. Twenty percent of cases eventuating in typical Meniere's disease presented with VMD first. In other patients VMD alone persisted for many years (30 or more). VMD, usually unilateral, is characterized by recurrent episodes of vertigo typical of classical Meniere's disease. Positional vertigo can occur between or during episodes. Aural pressure is second to vertigo in importance, and electronystagmographic findings are third. Although hearing is normal, tinnitus or loudness intolerance may be present. Concepts of pathogenesis are discussed.