gebhart/patrepeval huggingface dataset:
Molecular Abnormalities in Chronic Myeloid Leukemia: Deregulation of Cell Growth and Apoptosis (2000)

Chronic myeloid leukemia (CML) is a disease of the hematopoietic system, characterized by the presence of the Bcr-Abl oncoprotein. The main characteristics of this disease include adhesion independence, growth factor independence, and resistance to apoptosis. Loss or mutation of the tumor suppressor gene, p53, is one of the most frequent secondary mutations in CML blast crisis. The transition between chronic phase and blast crisis is associated with increased resistance to apoptosis correlating with poor prognosis. This review focuses on the involvement of these two oncoproteins in the development and progression of the apoptotic-resistant phenotype in CML.
Asymmetric Syntheses of Fused Bicyclic Lactams (2001)

ADVERTISEMENT RETURN TO ISSUEPREVNoteNEXTAsymmetric Syntheses of Fused Bicyclic LactamsSung H. Lim, Sunghoon Ma, and Peter BeakView Author Information Department of Chemistry, University of Illinois at Urbana-Champaign, Urbana, Illinois 61801 [email protected]Cite this: J. Org. Chem. 2001, 66, 26, 9056–9062Publication Date (Web):November 30, 2001Publication History Received29 August 2001Published online30 November 2001Published inissue 1 December 2001https://pubs.acs.org/doi/10.1021/jo0108865https://doi.org/10.1021/jo0108865brief-reportACS PublicationsCopyright © 2001 American Chemical SocietyRequest reuse permissionsArticle Views2342Altmetric-Citations83LEARN 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 SUBJECTS:Amides,Anions,Catalysts,Metathesis,Molecular structure Get e-Alerts
Intraocular Delivery of Oligonucleotides (2005)

Anti-mRNA and particularly antisense oligonucleotides are molecules able to inhibit gene expression after intracellular penetration being potentially very interesting for the treatment of ocular diseases where growth factors are involved such as ocular scarring diseases or for the inhibition of viral multiplication. In most cases, the site of action of oligonucleotides has shown to be the posterior segment of the eye and these molecules are injected mainly by the intravitreal route. However, oligonucleotides are poorly stable in biological fluids, have a low intracellular penetration and are quickly eliminated form the vitreous. These issues request repeated administration of oligonucleotides which are able to induce severe damages to the retina. This is the reason why drug delivery systems were developed to improve the stability and intracellular penetration of oligonucleotides and, by sustained release, to increase their long term activity in the treatment of ocular diseases.
Precise eye localization with improved SDM (2015)

In this paper, we propose a precise and fast eye center localization method. The method is based on SDM [1] algorithm, which has achieved impressive performance in face alignment area. In this work, we further improve the basic SDM algorithm in two aspects: 1) employ the coarse to fine strategy to enhance the robustness to initialization; 2) utilize multiple nonlinear features to ensure the robustness while improve the accuracy. Experimental results on BioID database shows that our improved SDM achieves preferable localization accuracy against the state-of-the-art methods at a speed as fast as 2ms to locate two eyes.
Natural anti-inflammatory agents for pain relief (2010)

The use of both over-the-counter and prescription nonsteroidal medications is frequently recommended in a typical neurosurgical practice. But persistent long-term use safety concerns must be considered when prescribing these medications for chronic and degenerative pain conditions. This article is a literature review of the biochemical pathways of inflammatory pain, the potentially serious side effects of nonsteroidal drugs and commonly used and clinically studied natural alternative anti-inflammatory supplements. Although nonsteroidal medications can be effective, herbs and dietary supplements may offer a safer, and often an effective, alternative treatment for pain relief, especially for long-term use.
Phase I Trial of the Anti–Lewis Y Drug Immunoconjugate BR96-Doxorubicin in Patients With Lewis Y–Expressing Epithelial Tumors (2000)

BR96-Dox provides a unique strategy to deliver doxorubicin to Le(Y)-expressing tumor and was well tolerated at doses of 700 mg/m(2) every 3 weeks. BR96-Dox was not associated with the typical side-effect profile of native doxorubicin and can potentially deliver high doses of doxorubicin to antigen-expressing tumors. A phase II study in doxorubicin-sensitive tumors is warranted.
Template-assisted synthesis of adenine-mutagenized cDNA by a retroelement protein complex (2018)

Diversity-generating retroelements (DGRs) create unparalleled levels of protein sequence variation through mutagenic retrohoming. Sequence information is transferred from an invariant template region (TR), through an RNA intermediate, to a protein-coding variable region. Selective infidelity at adenines during transfer is a hallmark of DGRs from disparate bacteria, archaea, and microbial viruses. We recapitulated selective infidelity in vitro for the prototypical Bordetella bacteriophage DGR. A complex of the DGR reverse transcriptase bRT and pentameric accessory variability determinant (Avd) protein along with DGR RNA were necessary and sufficient for synthesis of template-primed, covalently linked RNA-cDNA molecules, as observed in vivo. We identified RNA-cDNA molecules to be branched and most plausibly linked through 2'-5' phosphodiester bonds. Adenine-mutagenesis was intrinsic to the bRT-Avd complex, which displayed unprecedented promiscuity while reverse transcribing adenines of either DGR or non-DGR RNA templates. In contrast, bRT-Avd processivity was strictly dependent on the template, occurring only for the DGR RNA. This restriction was mainly due to a noncoding segment downstream of TR, which specifically bound Avd and created a privileged site for processive polymerization. Restriction to DGR RNA may protect the host genome from damage. These results define the early steps in a novel pathway for massive sequence diversification.
Describing the Diffusion of Guest Molecules Inside Porous Structures (2009)

The design and development of many emerging separation and catalytic process technologies require a proper quantitative description of diffusion of mixtures of guest molecules within meso- and microporous structures. In mesoporous materials with pore sizes 2 nm < dp < 50 nm, there is a central core region where the influence of interactions of the molecules with the pore wall is either small or negligible; mesopore diffusion is governed by a combination of molecule−molecule and molecule−pore wall interactions. Within micropores with dp < 2 nm, the guest molecules are always within the influence of the force field exerted with the wall; we have to reckon with the motion of adsorbed molecules, and there is no “bulk” fluid region. This article presents a unified, phenomenological, description of diffusion inside meso- and microporous structures using concepts and ideas that originate from James Clerk Maxwell and Josef Stefan. With the aid of extensive data sets of molecular dynamic simulations of unary and mixture diffusion in a wide variety of materials such as zeolites, metal-organic frameworks, covalent organic frameworks, carbon nanotubes, and cylindrical silica pores with a diverse range of pore topologies and pore sizes, we derive a molecular-level understanding of the various coefficients that arise in the phenomenological Maxwell−Stefan diffusion formulation. This understanding helps us to explain and describe a variety of experimental data and observations. We also demonstrate how a molecular level understanding aids separation and reaction process development.
Localization of HIV-1 RNA in mammalian nuclei. (1996)

The Rev protein of human immunodeficiency virus type 1 (HIV-1) facilitates the nuclear export of unspliced and partially spliced viral RNAs. In the absence of Rev, these intron-containing HIV-1 RNAs are retained in the nucleus. The basis for nuclear retention is unclear and is an important aspect of Rev regulation. Here we use in situ hybridization and digital imaging microscopy to examine the intranuclear distributions of intron-containing HIV RNAs and to determine their spatial relationships to intranuclear structures. HeLa cells were transfected with an HIV-1 expression vector, and viral transcripts were localized using oligonucleotide probes specific for the unspliced or spliced forms of a particular viral RNA. In the absence of Rev, the unspliced viral RNAs were predominantly nuclear and had two distinct distributions. First, a population of viral transcripts was distributed as approximately 10-20 intranuclear punctate signals. Actinomycin D chase experiments indicate that these signals represent nascent transcripts. A second, stable population of viral transcripts was dispersed throughout the nucleoplasm excluding nucleoli. Rev promoted the export of this stable population of viral RNAs to the cytoplasm in a time-dependent fashion. Significantly, the distributions of neither the nascent nor the stable populations of viral RNAs coincided with intranuclear speckles in which splicing factors are enriched. Using splice-junction-specific probes, splicing of human beta-globin pre-mRNA occurred cotranscriptionally, whereas splicing of HIV-1 pre-mRNA did not. Taken together, our results indicate that the nucleolus and intranuclear speckles are not involved in Rev regulation, and provide further evidence that efficient splicing signals are critical for cotranscriptional splicing.
Genetic Analysis of Influenza Virus NS1 Gene: a Temperature-Sensitive Mutant Shows Defective Formation of Virus Particles (2005)

To perform a genetic analysis of the influenza A virus NS1 gene, a library of NS1 mutants was generated by PCR-mediated mutagenesis. A collection of mutant ribonucleic proteins containing the nonstructural genes was generated from the library that were rescued for an infectious virus mutant library by a novel RNP competition virus rescue procedure. Several temperature-sensitive (ts) mutant viruses were obtained by screening of the mutant library, and the sequences of their NS1 genes were determined. Most of the mutations identified led to amino acid exchanges and concentrated in the N-terminal region of the protein, but some of them occurred in the C-terminal region. Mutant 11C contained three mutations that led to amino acid exchanges, V18A, R44K, and S195P, all of which were required for the ts phenotype, and was characterized further. Several steps in the infection were slightly altered: (i) M1, M2, NS1, and neuraminidase (NA) accumulations were reduced and (ii) NS1 protein was retained in the nucleus in a temperature-independent manner, but these modifications could not justify the strong virus titer reduction at restrictive temperature. The most dramatic phenotype was the almost complete absence of virus particles in the culture medium, in spite of normal accumulation and nucleocytoplasmic export of virus RNPs. The function affected in the 11C mutant was required late in the infection, as documented by shift-up and shift-down experiments. The defect in virion production was not due to reduced NA expression, as virus yield could not be rescued by exogenous neuraminidase treatment. All together, the analysis of 11C mutant phenotype may indicate a role for NS1 protein in a late event in virus morphogenesis.
Effects of Acute Nicotine Administration on Cognitive Event-Related Potentials in Tacrine-Treated and Non-Treated Patients with Alzheimer’s Disease (2002)

Earlier studies of cognitive event-related brain potentials (ERPs) reporting diminished amplitudes and delayed latencies of the P300 potential in dementia of the Alzheimer type (DAT), together with independent findings of the P300- and performance-enhancing properties of nicotine in normal adults, stimulated this study to explore the single-dose effects of nicotine on auditory and visual P300s in DAT. Thirteen patients, 6 currently receiving treatment with the cholinesterase inhibitor tacrine (tetrahydroaminoacridine; THA) and the remaining being medication free, were administered 2 mg of nicotine polacrilex under double-blind, randomized, placebo-controlled conditions. Prior to nicotine administration, THA-treated patients exhibited shorter auditory P300 latencies than non-treated patients. Acutely administered nicotine failed to alter auditory P300, but increased the amplitudes of visual P300s in both DAT patient groups. Neither THA treatment nor single-dose nicotine altered behavioural performance in the visual and auditory task paradigms. The results are discussed in relation to nicotinic cholinergic, attentional and cognitive processes in DAT.
Complete set of steady states for the general stoichiometric dynamical system (1981)

The complete set of steady states for rate constants in the range 0?ki&amp;lt;∞ and concentrations in the range 0?Xi&amp;lt;∞ is given explicitly in parametric form for the general chemical reaction system. The only assumptions are that the stoichiometries are real numbers, and the reaction rates are proportional to functions of class Ck, k≳0; the functions are assumed to be positive in the interior of the domain. Hence, these results apply far more generally than just to chemical systems and should be valid for many ecological and economic models as well. The set of steady states in the interior of the domain is in general a simply connected differentiable manifold M of dimension n+r−d, where n = number of species, r = number of reactions, and d = rank ν (ν = stoichiometric matrix). The full set of steady states M* consists of those in the interior (M) plus a frequently very complicated set of steady states lying in the boundary. M* is the union of a set of differentiable manifolds but is not itself a differentiable manifold in general. If the reaction rate laws are all monomials (i.e., products of concentrations raised to some ’’order of kinetics’’), a working APL algorithm is given which provides enough information to construct explicitly the set of manifolds comprising M*. This algorithm is used to treat an early version of the Belousov–Zhabotinski reaction mechanism. The algorithm may be used for more general rate laws with minor modifications.
Photovoltaic properties of n-CdSe/p-ZnTe heterojunctions (1976)

Measurements of the diffusion potential, depletion layer width, and bias dependence of quantum efficiency for n-CdSe/p-ZnTe heterojunctions are used to construct a band diagram for the junction and to propose a current transport model. A new value of the electron affinity of CdSe is indicated by measurements of the open-circuit voltage at low temperatures and high intensities. The saturation current density J0 is controlled by a thermal activation energy of 0.8 eV, corresponding to electron flow to the interface where recombination occurs through interface states. Performance as photovoltaic cells is limited by the short diffusion length of holes in CdSe.
Peptidyl diazomethyl ketones are specific inactivators of thiol proteinases. (1981)

Peptidyl diazomethyl ketones are specific inactivators of thiol proteinases being unreactive toward other classes of proteinases. Variation of the peptide portion of the reagents has provided affinity labels for the selective inactivation of the thiol endopeptidase cathepsin B, streptococcal proteinase, and clostripain and for the aminodipeptidase cathepsin C. Comparison of rates of inactivation of cathepsin B and streptococcal proteinase revealed a similarity in specificity, both enzymes showing a preference for a phenylalanine residue in the penultimate position of the peptide portion of the reagent. Reagents not satisfying the specificity of a particular thiol proteinase either did not inactivate or did so only very slowly. In some cases, the reagents bound to the enzyme in a manner unproductive for alkylation but productive for substrate behavior leading to destruction of the inhibitor by cleavage of the peptide portion. Thus, benzyloxycarbonyl-Phe-Gly-Phe diazomethyl ketone was rapidly cleaved by cathepsin B into benzyloxycarbonyl-Phe-Gly and phenylalanine diazomethyl ketone. Clostripain, an enzyme of trypsin-like specificity, was selectively inactivated by benzyloxycarbpnyl-Lys diazomethyl ketone at micromolar concentrations, but was inactivated extremely slowly by 2.5 x 10/sup -4/ M benzyloxycarbonyl-Phe-Ala diazomethyl ketone, a very effective inactivated by Gly-Phe diazomethyl ketone in the range of 10/sup -7/ to 10/sup -8/ M.more » By comparison, peptidyl diazomethyl ketones with blocked NH/sub 2/ terminals were considerably less effective. Peptidyl diazomethyl ketones are unreactive with such thiols as mercaptoethanol and glutathione.« less
IgG subclass-independent improvement of antibody-dependent cellular cytotoxicity by fucose removal from Asn297-linked oligosaccharides (2005)

Fucose depletion from oligosaccharides of human IgG1-type antibodies results in a great enhancement of antibody-dependent cellular cytotoxicity (ADCC). The aim of this study was to clarify the effect of fucose removal on effector functions of all human IgG subclasses. A panel of anti-CD20 chimeric antibodies having a matched set of human heavy chain subclasses with different fucose contents in their oligosaccharides was constructed using wild-type and fucosyltransferase-knockout Chinese hamster ovary cells as host cells. As found previously for IgG1, fucose-negative variant of IgG2, IgG3, and IgG4 exhibited enhanced ADCC and FcgammaRIIIa binding compared with their highly fucosylated counterparts. In contrast, fucose removal did not affect complement-dependent cytotoxicity (CDC) of any IgGs. Consequently, fucose removal from IgG2 and IgG4 resulted in a unique effector function profile; they had potent ADCC and no CDC. In conclusion fucose depletion can provide a panel of IgGs with enhanced ADCC without an impact on other inherent properties specific for each IgG subclass, such as CDC.
Growth factors, oncogenes, and multistage carcinogenesis (1987)

This paper presents evidence that the full repertoire of cellular genes involved in the carcinogenic process is several times larger than that of the known list of proto-oncogenes. Furthermore, this repertoire includes genes whose normal function is related to growth stimulation, as well as genes whose normal function is to inhibit growth or induce terminal differentiation. Multistage carcinogenesis probably results from a complex series of changes in both categories of genes. Despite this complexity, carcinogenesis can be conceived in terms of disturbances in biochemical functions that normally control the expression or function of growth factors, receptors, and pathways of signal transduction. Several protein kinases play a central role in the process of signal transduction. Our laboratory has recently isolated cDNA clones for the enzyme protein kinase C (PKC). These clones should be useful for clarifying the role of PKC in growth control and tumor promotion. Finally, the existence of genes whose normal function is to inhibit cell growth provides a rationale for new strategies of cancer prevention and treatment.
Adiponectin Stimulates Angiogenesis in Response to Tissue Ischemia through Stimulation of AMP-activated Protein Kinase Signaling (2004)

Obesity is a risk factor for the development of cardiovascular diseases that are associated with impaired angiogenesis. Adiponectin is an adipocyte-specific adipocytokine with anti-atherogenic and anti-diabetic properties, and its plasma levels are reduced in association with obesity-linked diseases. Here, we investigated whether adiponectin regulates angiogenesis in response to tissue ischemia using adiponectin knock-out (KO) mice. Angiogenic repair of ischemic hind limbs was impaired in adiponectin-KO mice compared with wild-type (WT) mice as evaluated by laser Doppler flow method and capillary density analyses. Adenovirus-mediated supplement of adiponectin accelerated angiogenic repair in both adiponectin-KO and WT mice. Intramuscular injection of an adenovirus encoding dominant-negative AMP-activated kinase diminished the improvement in limb perfusion seen in WT mice and abolished the adiponectin-induced enhancement of perfusion. These data indicate that adiponectin can function to stimulate angiogenesis in response to ischemic stress by promoting AMP-activated kinase signaling. Therefore, adiponectin may be useful in the treatment for obesity-related vascular deficiency diseases.
Abrogation of Cisplatin-Induced Programmed Cell Death in Human Breast Cancer Cells by Epidermal Growth Factor Antisense RNA (1997)

These data indicate that a critical level of EGF-R signaling, which is amplified in some common human cancers, is necessary for cisplatin-mediated apoptosis in tumor cells and suggest an inhibitory effect of this pathway on the repair of cisplatin-damaged DNA.
Solution Structure of PAFP-S:  A New Knottin-Type Antifungal Peptide from the Seeds of Phytolacca americana, (2001)

The three-dimensional solution structure of PAFP-S, an antifungal peptide extracted from the seeds of Phytolacca americana, was determined using 1H NMR spectroscopy. This cationic peptide contains 38 amino acid residues. Its structure was determined from 302 distance restraints and 36 dihedral restraints derived from NOEs and coupling constants. The peptide has six cysteines involved in three disulfide bonds. The previously unassigned parings have now been determined from NMR data. The solution structure of PAFP-S is presented as a set of 20 structures using ab initio dynamic simulated annealing, with an average RMS deviation of 1.68 A for the backbone heavy atoms and 2.19 A for all heavy atoms, respectively. For the well-defined triple-stranded beta-sheet involving residues 8-10, 23-27, and 32-36, the corresponding values were 0.39 and 1.25 A. The global fold involves a cystine-knotted three-stranded antiparallel beta-sheet (residues 8-10, 23-27, 32-36), a flexible loop (residues 14-19), and four beta-reverse turns (residues 4-8, 11-14, 19-22, 28-32). This structure features all the characteristics of the knottin fold. It is the first structural model of an antifungal peptide that adopts a knottin-type structure. PAFP-S has an extended hydrophobic surface comprised of residues Tyr23, Phe25, Ile27, Tyr32, and Val34. The side chains of these residues are well-defined in the NMR structure. Several hydrophilic and positively charged residues (Arg9, Arg38, and Lys36) surround the hydrophobic surface, giving PAFP-S an amphiphilic character which would be the main structural basis of its biological function.
Taser X26 Discharges in Swine: Ventricular Rhythm Capture is Dependent on Discharge Vector (2008)

For most transcardiac vectors, Taser X26 caused immediate ventricular rhythm capture. This usually reverted spontaneously to sinus rhythm but potentially fatal VF was seen with two vectors. For some non-transcardiac vectors, capture was also seen but with a significantly (p < 0.0001) decreased incidence.