gebhart/patrepeval huggingface dataset:
Observing Real-Time Molecular Event Dynamics of Apoptosis in Living Cancer Cells using Nuclear-Targeted Plasmonically Enhanced Raman Nanoprobes (2014)

Apoptosis is a biological process that plays important roles in embryogenesis, aging, and various diseases. During the process of apoptosis, cells undergo a series of morphological and molecular events such as blebbing, cell shrinkage, proteolysis, and nuclear DNA fragmentation. Investigating these events on a molecular level is crucial for gaining a more complete understanding of the intricate mechanism of apoptosis; however, the simultaneous direct observation of morphological and molecular events in real-time on a single living cell scale still remains a challenge. Herein, we directly monitored morphological and molecular events during cellular apoptosis in real-time after the treatment of an apoptosis-inducing agent, by utilizing our previously described plasmonically enhanced Rayleigh/Raman spectroscopic technique. Spectroscopic analysis of the DNA/protein composition around the cell nucleus revealed the occurrence and dynamics of three apoptotic molecular events: protein denaturation, proteolysis, and DNA fragmentation. The molecular event dynamics were used to create a temporal profile of apoptotic events in single cells. It is found that the sequence of events occurring in the apoptotic process induced by hydrogen peroxide addition is protein denaturation through disulfide bond breakage as well as DNA fragmentation, followed in time by protein unraveling with hydrophobic amino acid exposure, and finally protein degradation. These results demonstrate the potential of using this time-dependent plasmonically enhanced vibrational imaging technique to study the detailed mechanism of other apoptosis molecular pathways induced by different agents (e.g., anticancer drugs). A note is given in the conclusion discussing the expected large difference between the SERS spectrum of biological molecules in solution and that observed in live cells which are enhanced by the plasmonic field of the aggregated nanoparticles.
Monitoring Gene Therapy by External Imaging of mRNA: Pilot Study on Murine Erythropoietin (2007)

Gene therapy is anticipated as being an important medical development. Essential to its effectiveness is the appropriate activity (protein expression) in the expected target cells. A noninvasive diagnostic procedure of successful gene expression will be of paramount importance to validate its use or its misuse (eg, sports gene doping). Externally detectable labeled oligonucleotide hybridizing with the messenger RNA generated by the transferred gene has been proposed as a possibility to monitor successful gene therapy. The authors selected the erythropoietin gene (Epo) for a pilot study on erythropoietin protein expression in mouse muscle. Oligonucleotides of peptide nucleic acid (PNA) type capable of antisense binding to unique murine Epo-mRNA sequences were synthesized by solid phase methods, and elongated at the N-terminus with the HIV Tat (48-60) cell penetrating peptide. They were labeled with fluorescence and radioactive tags to verify penetration and longer half-life properties in Epo gene transfected C2C12 mouse muscle cells as compared with corresponding wild-type cells. Downregulation of newly expressed erythropoietin protein in such cells additionally confirmed the penetration and hybridizing properties of the selected labeled oligonucleotide. I-labeled Tat-PNAs were intravenously injected into mice that had previously received the Epo gene into the right tibialis muscle by DNA electrotransfer. Preferential accumulation of radioactivity in the transferred limb as compared with the contralateral limb was ascertained, especially for I-Tat-CTA CGT AGA CCA CT (labeled Tat-PNA 1). This study provides experimental data to support the potential use of external noninvasive image detection to monitor gene therapy. The extension of the approach to more sensitive methods for whole-body external detection such as positron emission tomography appears feasible.
An investigation into the expressive power of PDDL2.1 (2004)

The planning domain language PDDL2.1, used in the 3rd International Planning Competition, has sparked off some controversy in the planning community as researchers consider its expressive power and the ease with which interesting domain models can be constructed in the language. In this paper we show that the expressive power of PDDL2.1 is much greater than is commonly believed. We demonstrate that PDDL2.1 can model many of the domain features often claimed to lie beyond its modelling capability. In so doing we provide a means by which powerful domain features and language constructs can be given a semantics in terms of the canonical basis of PDDL2.1.
Control of Butanol Formation in Clostridium acetobutylicum by Transcriptional Activation (2002)

The sol operon of Clostridium acetobutylicum is the essential transcription unit for formation of the solvents butanol and acetone. The recent proposal that transcriptional regulation of this operon is controlled by the repressor Orf5/SolR (R. V. Nair, E. M. Green, D. E. Watson, G. N. Bennett, and E. T. Papoutsakis, J. Bacteriol. 181:319-330, 1999) was found to be incorrect. Instead, regulation depends on activation, most probably by the multivalent transcription factor Spo0A. The operon is transcribed from a single promoter. A second signal identified in primer extension studies results from mRNA processing and can be observed only in the natural host, not in a heterologous host. The first structural gene in the operon (adhE, encoding a bifunctional butyraldehyde/butanol dehydrogenase) is translated into two different proteins, the mature AdhE enzyme and the separate butanol dehydrogenase domain. The promoter of the sol operon is preceded by three imperfect repeats and a putative Spo0A-binding motif, which partially overlaps with repeat 3 (R3). Reporter gene analysis performed with the lacZ gene of Thermoanaerobacterium thermosulfurigenes and targeted mutations of the regulatory region revealed that the putative Spo0A-binding motif, R3, and R1 are essential for control. The data obtained also indicate that an additional activator protein is involved.
Ocular inflammation in patients using soft contact lenses (1982)

• Soft contact lenses cleaned and stored in thimerosalcontaining solutions may produce an ocular inflammatory process and, if untreated, corneal neovascularization. We examined 38 patients who were using soft contact lenses and found that 31 patients had positive ocular provocation test results to a thimerosal-preserved artificial tears solution. Delayed hypersensitivity to thimerosal was demonstrated by positive patch tests in 27 patients. Avoidance of thimerosal and the use of unit-dose sterile saline solutions has resulted in complete resolution of ocular symptoms. (<i>Arch Dermatol</i>1982;118:147-149)
Reactivity‐Based One‐Pot Synthesis of Oligomannoses: Defining Antigens Recognized by 2G12, a Broadly Neutralizing Anti‐HIV‐1 Antibody (2004)

An HIV-1 vaccine may eventually be developed from oligomannoses synthesized by a reactivity-based one-pot self-condensation strategy. The compounds were tested for their ability to inhibit the binding of gp120 to the broadly neutralizing HIV-1 antibody 2G12. New epitope mimics (see structure for example) were identified that inhibit this binding as well as, or better than the natural epitope Man9GlcNAc2 (Man=mannose, Glc=glucose).
Synthesis and Antifungal Activity of Novel Cationic Pneumocandin Bo Derivatives (1994)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTSynthesis and Antifungal Activity of Novel Cationic Pneumocandin Bo DerivativesF. Aileen Bouffard, Robert A. Zambias, James F. Dropinski, James M. Balkovec, Milton L. Hammond, George K. Abruzzo, Kenneth F. Bartizal, Jean A. Marrinan, Myra B. Kurtz, and Cite this: J. Med. Chem. 1994, 37, 2, 222–225Publication Date (Print):January 1, 1994Publication History Published online1 May 2002Published inissue 1 January 1994https://pubs.acs.org/doi/10.1021/jm00028a003https://doi.org/10.1021/jm00028a003research-articleACS PublicationsRequest reuse permissionsArticle Views659Altmetric-Citations94LEARN 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-AlertscloseSupporting Info (1)»Supporting Information Supporting Information Get e-Alerts
Synthesis and Characterization of Hollow Silica Spheres (2015)

The synthesis and characterization of mono-dispersed silica hollow spheres using polystyrene (PS) spheres as template from the hydrolysis and condensation of tetraethylorthosilicate (TEOS) is presented. Successive washing steps with toluene and subsequent calcination at different temperatures were performed, in order to remove the PS template. Furthermore, the PS core removal was studied using different calcination temperatures, but without the prior washing with toluene. The morphology of the materials was studied by scanning electron microscopy and by transmission electron microscopy. A shell formed by silica nanoparticles with 50 nm diameter, being the layer of 100 nm thickness, was observed when using a lowconcentration of catalyst in the sol-gel reaction. The textural properties of the silica coating, obtained from N2 adsorption-desorption isotherms, depend on the catalyst amount added for the TEOS hydrolysis. From the Fourier transform infrared spectra and the results of the thermogravimetric analyses, it was found that the almost complete removal of the polystyrene core can be directly achieved by calcining at 500 °C,without the need of carrying out any washing andminimizing the formation of cracks in the silica hollow spheres.
Platelet GPIIb/IIIa antagonists: the first anti-integrin receptor therapeutics. (1997)

The platelet glycoprotein GPIIb/IIIa ( IIb 3 ) antagonist c7E3 Fab (the Fab fragment of the mouse/human chimeric monoclonal antibody 7E3; abciximab; ReoPro) was approved for human use in the United States in December 1994 based on its safety and its efficacy in reducing the risk of ischemic complications after percutaneous coronary intervention (PCI; 1 angioplasty or atherectomy) (1, 2). The success of this agent reflects our emerging ability to identify adhesion molecules as therapeutic targets, and then construct effective inhibitors that meet the stringent safety standards required for a new drug. As the first rationally designed antiplatelet and anti-integrin receptor drug, c7E3 Fab serves as a prototype for other anti-integrin receptor, and more generally, antiadhesion receptor, agents designed to treat and/or prevent human disease.
Pericardial Tamponade Following Percutaneous Left Ventricular Puncture (1959)

A case of pericardial tamponade following percutaneous left ventricular puncture for the assessment of aortic stenosis is presented. Technical factors pertinent to the etiology of the complication are discussed. Emphasis is placed on the fact that current enthusiasm for percutaneous ventricular puncture should be tempered with an awareness of the associated complications that may ensue and require immediate definitive therapy in an environment well equipped for their management.
Cyclodextrin Functionalized Graphene Nanosheets with High Supramolecular Recognition Capability: Synthesis and Host−Guest Inclusion for Enhanced Electrochemical Performance (2010)

Cyclodextrins (CDs) are oligosaccharides composed of six, seven, or eight glucose units (alpha-, beta-, or gamma-CD, respectively), which are toroidal in shape with a hydrophobic inner cavity and a hydrophilic exterior. These interesting characteristics can enable them to bind selectively various organic, inorganic and biological guest molecules into their cavities to form stable host-guest inclusion complexes or nanostructured supramolecular assemblies in their hydrophobic cavity. On the other hand graphene nanosheet (GN), a rising-star material, holds great promise for potential applications in many technological fields due to its high surface areas, low cost, and high conductivity. If GNs are modified with CDs, it is possible to obtain new materials simultaneously possessing unique properties of GNs and cyclodextrins through combining their individual obvious advantages. In this article, we demonstrate for the first time a simple wet-chemical strategy for the preparation of CD-graphene organic-inorganic hybrid nanosheets (CD-GNs), which exhibited high solubility and stability in polar solvent. The obtained CD-GNs were characterized by UV-vis spectroscopy, static contact angle measurement, thermogravimetric analysis, X-ray photoelectron spectroscopy, Fourier transform infrared spectroscopy, Raman spectroscopy, atomic force microscopy, transmission electron microscopy, and electrochemical impedance spectroscopy, which confirmed that CD had been effectively functionalized on the surface of GNs. Furthermore, the formation mechanism of CD-GNs was also discussed. Interestingly, GNs here could load a number of CD molecules, which was very important for greatly enhancing the supramolecular function of CDs. Electrochemical results obviously reveal that CD-graphene organic-inorganic hybrid nanosheets could exhibit very high supramolecular recognition and enrichment capability and show much higher electrochemical response toward eight probe molecules (biomolecules and drugs) than unmodified GNs and carbon nanotubes, which is probably caused by the synergetic effects from GNs (high conductivity and high surface area) and CD molecules (host-guest recognition and enrichment).
Studies on Organic Sulfur Compounds. XIV. The Reaction of N-Alkoxy-carbonyl-N'-(2-thiazolyl) thioureas with Some Oxidants (1973)

N-Alkoxycarbonyl-N'-(2-thiazolyl) thioureas were reacted with some oxidants, such as bromine, benzoyl peroxide, hypobromous acid and N-bromosuccinimide, to afford 2-alkoxycarbonylimino-thiazolo [3, 2-b] thiadiazolines (X). Furthermore, from the reaction mixtures of N-ethoxycarbonyl-N'-(2-thiazolyl) thiourea (12) with bromine in chloroform, N-ethoxycarbonylimino-thiazolo [3, 2-b] thiadiazoline hydrobromide monohydrate (14) was obtained, which was easily dehydrobrominated to form 2-ethoxycarbonylimino-thiazolo-[3, 2-b] thiadiazoline (13) by treatment with large quantities of water. This paper describes particularly in detail about the structures of 13 and 14.
Tat protein from HIV-1 binds to Mycobacterium avium via a bacterial integrin. Effects on extracellular and intracellular growth. (1994)

We examined the interaction between HIV-1 Tat protein and the opportunistic pathogen Mycobacterium avium. AIDS-associated strains of M. avium were shown to bind Tat protein quite avidly in an attachment assay. The attachment of M. avium to Tat was shown to occur via the integrin alpha 5 beta 1 present on the mycobacterial cell surface. M. avium strains were shown to bind the viral Tat protein with high affinity in a specific fashion (600 binding sites with a Kd of 1 to 5 nM). M. avium coated with Tat protein were shown to be more infective for human alveolar macrophages than untreated M. avium. Other HIV-1 Ags had no such effects (e.g., p24, p17). Examination of the cytokine profile of infected macrophages showed that M. avium-Tat complexes induced higher levels of TGF beta-1 (TGF beta 1) than M. avium alone or M. avium that had been in contact with other viral proteins. Conditioned media from HIV-1-infected H9 cells released a factor that enhanced M. avium intramacrophage growth, and was partially neutralized by an anti-Tat Ab. Finally, Tat protein (purified or present in conditioned media from infected cells) moderately enhanced the growth of M. avium strains in extracellular media, and exposure of M. avium to Tat protein in the presence of IL-6 enhanced the growth of AIDS-associated strains. These data argue for an interaction between the Tat viral product and the opportunistic pathogen M. avium which may contribute to the exquisite susceptibility of AIDS subjects to this pathogen.
Apolipoprotein A1 Forms 5/5 and 5/4 Antiparallel Dimers in Human High-density Lipoprotein (2019)

Apolipoprotein A1 (APOA1), the major protein of high-density lipoprotein (HDL), contains 10 helical repeats that play key roles in protein-protein and protein-lipid interactions. The current structural model for HDL proposes that APOA1 forms an antiparallel dimer in which helix 5 in monomer 1 associates with helix 5 in monomer 2 along a left-left (LL5/5) interface, forming a protein complex with a 2-fold axis of symmetry centered on helix 5. However, computational studies suggest that other orientations are possible. To test this idea, we used a zero-length chemical cross-linking reagent that forms covalent bonds between closely apposed basic and acidic residues. Using proteolytic digestion and tandem mass spectrometry, we identified amino acids in the central region of the antiparallel APOA1 dimer of HDL that were in close contact. As predicted by the current model, we found six intermolecular cross-links that were consistent with the antiparallel LL5/5 registry. However, we also identified three intermolecular cross-links that were consistent with the antiparallel LL5/4 registry. The LL5/5 is the major structural conformation of the two complexes in both reconstituted discoidal HDL particles and in spherical HDL from human plasma. Molecular dynamic simulations suggest that that LL5/5 and LL5/4 APOA1 dimers possess similar free energies of dimerization, with LL5/5 having the lowest free energy. Our observations indicate that phospholipidated APOA1 in HDL forms different antiparallel dimers that could play distinct roles in enzyme regulation, assembly of specific protein complexes, and the functional properties of HDL in humans.
Ca(2+)-activated K+ transport in erythrocytes. Comparison of binding and transport inhibition by scorpion toxins. (1993)

We have investigated the interactions of synthetic charybdotoxin (ChTX), synthetic iberiotoxin (IbTX), and recombinant mutant ChTX peptides with the Ca(2+)-activated K+ channel (Gardos pathway) in human and rabbit erythrocytes. We measured the binding of 125I-ChTX to erythrocytes, the displacement of bound 125I-ChTX by unlabeled toxin and analogs, and then compared these data with isotopic and electrical indices of channel activity measured under the same conditions. We found that a major portion of 125I-ChTX bound to red cells was displaceable by excess unlabeled ChTX. This specific 125I-ChTX binding to human red cells was markedly increased in low ionic strength conditions as compared with that measured at physiological ionic strength and at alkaline pH as compared with normal pH. At pH 8 and low ionic strength, specific binding could be described most simply as a single class of sites of Kd = 94 +/- 49 pM and Bmax = 120 +/- 36 sites/cell (n = 3). Ca(2+)-activated 86Rb influx measured under identical conditions revealed an ID50 for ChTX of 21 +/- 15 pM (n = 6) at low ionic strength and 4 +/- 2.4 nM (n = 4) at physiological ionic strength. Similar studies in rabbit erythrocytes at low ionic strength revealed a Kd for 125I-ChTX = 37 +/- 17 pM, with 126 +/- 24 binding sites/cell and an ID50 for inhibition of 86Rb influx by ChTX = 25 pM. Whereas IbTX neither inhibited Ca(2+)-activated 86Rb influx nor displaced 125I-ChTX in human red cells, it partially displaced 125I-ChTX and partially inhibited 86Rb influx in rabbit red cells. Studies with recombinant mutant ChTX peptides showed that the mutant toxin K27Q was inactive as a transport inhibitor and displayed a large reduction in ability to displace 125I-ChTX. The mutation K31Q resulted in abolition of ionic strength dependence of the inhibitory effect on the Ca(2+)-activated K+ permeability. In view of the similarity between the 125I-ChTX binding constant and the transport inhibition constant of ChTX, we examined the potency of 125I-ChTX as a transport inhibitor. 125I-ChTX inhibited Ca(2+)-activated K+ transport with ID50 values of 3.3 +/- 1 nM (n = 7) at low ionic strength and 4.1 +/- 3 nM (n = 6) at physiologic ionic strength. Thus, at physiologic ionic strength 125I-ChTX and ChTX are indistinguishable as inhibitors of erythroid Ca(2+)-activated K+ transport. However, iodination of Y36 is associated with abolition of the 200-fold increase in inhibitory potency shown by ChTX at low ionic strength.
A leaky blood–brain barrier, fibrinogen infiltration and microglial reactivity in inflamed Alzheimer’s disease brain (2008)

This study has used immunohistochemical examination of tissue obtained from Alzheimer's disease (AD) brains and rat hippocampus injected with Abeta(1-42) peptide to determine effects of induced inflammatory reactivity on integrity of blood-brain barrier (BBB) and viability of neurons. Tissue from AD, but not non-demented, brains exhibited a diffuse pattern of staining for fibrinogen and immunoglobulin (IgG) indicative of BBB leakiness with considerable fibrinogen immunoreactivity (ir) appearing in association with Abeta deposits. Immunostaining for the endothelial cell specific glycoprotein, von Willebrand factor, showed morphological evidence for altered blood vessels in AD tissue. AD brains also demonstrated extensive areas of fibrinogen ir in association with microglial reactivity. In vivo, intra-hippocampal injection of Abeta(1-42) caused time-dependent (1-7 days after injection) increases in double staining of fibrinogen with areas of microgliosis. Two independent pharmacological strategies were employed to examine how Abeta(1-42) stimulation (7 days injection) may be linked to neurodegeneration. The defibrinogenating compound, ancrod, reduced inflammatory reactivity, levels of parenchymal fibrinogen and IgG, and was neuroprotective. These results prompted use of Abeta(1-42) plus fibrinogen as a novel in vivo inflammatory stimulus and this combination significantly enhanced inflammatory reactivity, vascular perturbations and neuronal damage compared to Abeta(1-42) alone. A second approach, using anti-Mac-1 (antibody for antigen CD11b) to block activation of microglia, was highly effective in attenuating effects of Abeta(1-42) plus fibrinogen amplification of inflammatory and vascular responses and conferred significant neuroprotection. The overall findings from study of AD tissue and in vivo in Abeta(1-42) and Abeta(1-42) plus fibrinogen stimulated rat hippocampus suggest microglial responses to promote increased extravasation of blood protein as a critical component in amplifying inflammatory reactivity and causing neuronal damage in inflamed AD brain.