gebhart/patrepeval huggingface dataset:
Noninvasive MRI-SERS Imaging in Living Mice Using an Innately Bimodal Nanomaterial (2010)

We report a novel nanomaterial (AuMN-DTTC) that can be used as a bimodal contrast agent for in vivo magnetic resonance imaging (MRI) and Raman spectroscopy. The probe consists of MRI-active superparamagnetic iron oxide nanoparticles, stably complexed with gold nanostructures. The gold component serves as a substrate for a Raman active dye molecule to generate a surface-enhanced Raman scattering (SERS) effect. The synthesized probe produces T2 weighted contrast and can be used as a SERS active material both in silico (in aqueous solution) and in vivo. A quantitative assessment of T2 relaxation times was obtained using multiecho MRI analysis. The T2 relaxation times of AuMN-DTTC and MN (dextran-coated iron oxide nanoparticles) were 29.23 + 1.45 and 31.58 + 1.7 ms, respectively. The SERS signature of AuMN-DTTC revealed peaks at 508, 629, 782, 844, 1080, 1108, 1135, and 1242 cm(-1). Intramuscular administration of the probe resulted in a decrease of the T2 relaxation time of muscle from 33.4 + 2.5 to 20.3 + 2.2 ms. SERS peaks were observed at 508, 629, 782, 844, 1080, 1108, 1135, and 1242 cm(-1), consistent with the in silico results. Our studies illustrate for the first time the design and in vivo application of a contrast agent, whose component modalities include MRI and SERS. The value of this agent lies in its innately bimodal nature and its application in vivo for molecular imaging applications.
Non-volatile memory for fast, reliable file systems (1992)

Article Non-volatile memory for fast, reliable file systems Share on Authors: Mary Baker View Profile , Satoshi Asami View Profile , Etienne Deprit View Profile , John Ouseterhout View Profile , Margo Seltzer View Profile Authors Info & Claims ASPLOS V: Proceedings of the fifth international conference on Architectural support for programming languages and operating systemsSeptember 1992 Pages 10–22https://doi.org/10.1145/143365.143380Online:01 September 1992Publication History 145citation2,042DownloadsMetricsTotal Citations145Total Downloads2,042Last 12 Months63Last 6 weeks9 Get Citation AlertsNew Citation Alert added!This alert has been successfully added and will be sent to:You will be notified whenever a record that you have chosen has been cited.To manage your alert preferences, click on the button below.Manage my AlertsNew Citation Alert!Please log in to your account Save to BinderSave to BinderCreate a New BinderNameCancelCreateExport CitationPublisher SiteGet Access
Inhibition of Natural Killer Cell Cytotoxicity and Interferon γ Production by the Envelope Protein of HIV and Prevention by Vasoactive Intestinal Peptide (2000)

Natural killer (NK) cell dysfunction is common in human immunodeficiency virus (HIV)-infected subjects, although its mechanisms are poorly understood. A direct effect of HIV envelope glycoprotein gp120 may be involved. We investigated the in vitro effects of gp120 on the major NK cell effector functions, natural cytotoxicity and cytokine production. In addition, the ability of the vasoactive intestinal peptide (VIP) to modulate these effects was investigated. Our results indicated that gp120 inhibits NK natural cytotoxicity and showed, for the first time, that the inhibition affects also the production of the proinflammatory cytokine interferon-gamma (IFN-gamma). Interestingly, the inhibitory effect on NK cell functions was obtained with gp120 at concentrations within the range measured in the serum of HIV-infected subjects. Furthermore, we showed that the inhibitory activity of gp120 can be prevented by coincubation with VIP, even if VIP has no stimulatory activity by itself. Taken together these data suggest that (1) an inhibitory effect of gp120 may account for the NK cell dysfunction in HIV-infected subjects; (2) the gp120-mediated decrease in IFN-gamma production by NK cells may contribute to the cytokine imbalance observed in HIV infection; and (3) VIP counteracts the inhibitory effect of gp120 on NK cell functions.
The Effect of pH on Potentially Lethal Damage Recovery in A549 Cells (1986)

The radiation sensitivity and potentially lethal damage recovery (PLDR) capacity of A549 human lung carcinoma cells have been studied. For unfed monolayer cultures, radiation sensitivity was greater in plateau phase than in log phase of growth. PLDR was observed when plateau-phase cells were held in their own spent medium postirradiation, such that the dose-response curve with 24 h holding was similar to that for log-phase cells plated immediately after irradiation. The high PLDR capacity of A549 plateau-phase cells (recovery factor between 40 and 70 for 24 h holding after 10 Gy) was reduced 10-fold or more by alkalinizing the pH of the spent medium immediately after irradiation from a value of 6.5 +/- 0.1 to a value of 7.6. Medium alkalinization resulted in an increase in the rate of glycolysis, with subsequent reacidification to a pH of 7.3 within 2 h of the pH adjustment. No change in cell cycle distribution was observed in the plateau-phase cultures up to 32 h after change of medium pH, and no increase in cell density was found after 48 h. A slight increase in the rate of incorporation of radiolabeled thymidine into acid-precipitable material was observed at 4 and 24 h after alkalinization of the medium. While it is not possible at present to define a mechanism for this pH effect, our results demonstrate that, at least for this cell line, variables such as medium pH and glucose concentration can profoundly influence the observation of PLDR.
Reduction of the onset response in high frequency nerve block with amplitude ramps from non-zero amplitudes (2009)

High frequency alternating current (HFAC) waveforms reversibly block conduction in mammalian peripheral nerves. The initiation of the HFAC produces an onset response in the nerve before complete block occurs. An amplitude ramp, starting from zero amplitude, is ineffective in eliminating this onset response. In fact, it makes the onset worse. We postulated that initiating the ramp from a non-zero amplitude would produce a different effect on the onset. This was tested in an in-vivo rat sciatic nerve model. HFAC was applied at supra block threshold amplitudes and then reduced to a lower amplitude (0%, 25% 50 %, 75% and 90% of the suprathreshold amplitude). The amplitude was then increased again to the original supra block threshold amplitude. This normally produces a second period of onset response if increased as a step. However, an amplitude ramp was successful in eliminating this onset. This was always possible for the ramps up from 50%, 75 % and 90% block threshold amplitude, but never from 0% or 25% of the block threshold amplitude. This maneuver can potentially be used to maintain complete nerve block, transition to partial block and then resume complete block without initiating another onset.
Regulation of the EphA2 Kinase by the Low Molecular Weight Tyrosine Phosphatase Induces Transformation (2002)

Intracellular signaling by protein tyrosine phosphorylation is generally understood to govern many aspects of cellular behavior. The biological consequences of this signaling pathway are important because the levels of protein tyrosine phosphorylation are frequently elevated in cancer cells. In the classic paradigm, tyrosine kinases promote tumor cell growth, survival, and invasiveness, whereas tyrosine phosphatases negatively regulate these same behaviors. Here, we identify one particular tyrosine phosphatase, low molecular weight tyrosine phosphatase (LMW-PTP), which is frequently overexpressed in transformed cells. We also show that overexpression of LMW-PTP is sufficient to confer transformation upon non-transformed epithelial cells. Notably, we show that the EphA2 receptor tyrosine kinase is a prominent substrate for LMW-PTP and that the oncogenic activities of LMW-PTP result from altered EphA2 expression and function. These results suggest a role for LMW-PTP in transformation progression and link its oncogenic potential to EphA2.
Organoapatites: Materials for artificial bone. I. Synthesis and microstructure (1992)

We have synthesized a new family of materials we termed organoapatites which may be useful in the formulation of artificial bone. These materials are synthesized by nucleation and growth of apatite crystals in media containing poly(amino acids) or synthetic organic polyelectrolytes using strict atmospheric, temperature, and pH control. The macromolecules used to synthesize the organoapatites include poly(L-lysine), poly(L-glutamic acid), and poly(sodium acrylate). The products were characterized by x-ray diffraction, scanning electron microscopy, surface area measurements, elemental analysis, and spectroscopic techniques. Organoapatites were found to contain large surface area morphologies with small crystallites which mature slowly based on analysis of Ca/P ratios. The organic macromolecules are thought to induce nucleation of crystals but also to quench their growth, thus becoming intimately dispersed in a mineral network. The organomineral particles harvested from the reaction medium contain polymer-netted microcrystals, and for this reason the synthetic approach can be used to modulate crystal maturation and biological response. It is likely that the preparative approach mimics some aspects of natural bone matrix synthesis and could be specially useful in the preparation of mineral implants containing intimate dispersions of small amounts of biomolecules such as growth factors, special drugs, or bioadhesives.
Fabrication of fillable microparticles and other complex 3D microstructures (2017)

Three-dimensional (3D) microstructures created by microfabrication and additive manufacturing have demonstrated value across a number of fields, ranging from biomedicine to microelectronics. However, the techniques used to create these devices each have their own characteristic set of advantages and limitations with regards to resolution, material compatibility, and geometrical constraints that determine the types of microstructures that can be formed. We describe a microfabrication method, termed StampEd Assembly of polymer Layers (SEAL), and create injectable pulsatile drug-delivery microparticles, pH sensors, and 3D microfluidic devices that we could not produce using traditional 3D printing. SEAL allows us to generate microstructures with complex geometry at high resolution, produce fully enclosed internal cavities containing a solid or liquid, and use potentially any thermoplastic material without processing additives.
New isoxazole derivatives with a potent and selective beta 2-adrenergic activity. (1986)

A series of 1-(3-subst-5-isoxazolyl)-2-alkylaminoethanol derivatives was synthesized and tested in order to evaluate the effectiveness of the isoxazole ring in replacing the catechol moiety of beta-adrenergic compounds. Direct binding studies and the influence on beta-receptors mediated responses in isolated guinea-pig atria and guinea-pig trachea were investigated to determine the pharmacological profile of the new derivatives. The results indicate that some derivatives with proper substitution in the isoxazole ring and in the aminoalcohol chain displayed a marked selectivity towards beta 2 tracheal receptors. In vivo studies confirmed this profile, and the derivative 1-(3-bromo-5-isoxazolyl)-2-tert.butyl aminoethanol hydrochloride was selected and further developed as a potential bronchodilatory agent.
"Universal" T helper cell determinants enhance immunogenicity of a Plasmodium falciparum merozoite surface antigen peptide (1992)

Synthetic peptide constructs containing a limited number of epitopes are being currently investigated as subunit vaccines against a variety of pathogens. However, because of widespread nonresponsiveness to most such constructs, possibly attributable to MHC restriction, the choice of appropriate carrier molecules to enhance immunogenicity of peptides constitutes an important and essential aspect of designing synthetic immunogens for human use. Widely used vaccines such as tetanus toxoid (TT) have not been uniformly effective as carrier proteins because of the phenomenon of epitope-specific suppression in which induction of an immune response against a synthetic peptide conjugated to TT is prevented by preexisting immunity to TT. Recently, T cell determinants that can be recognized in the context of several class II MHC molecules have been identified in tetanus toxin as well as in the circumsporozoite protein of a human malarial parasite, Plasmodium falciparum. Such determinants can be potentially used to circumvent the problem of epitope-specific suppression. In the present study we evaluated two such T cell determinants, viz., tt830-844 from tetanus toxin and CST3 from the malarial parasite, for their ability to help induce a boostable antibody response and to overcome genetic nonresponsiveness to a synthetic 20-residue construct containing a B cell and an overlapping T cell epitope from a major merozoite surface protein of P. falciparum. Our data provide support for the view that widely recognized T cell determinants may be used as universal carrier molecules for general vaccination.
Physical chemistry of surfaces (1998)

Capillarity. The Nature and Thermodynamics of Liquid Interfaces. Surface Films on Liquid Substrates. Electrical Aspects of Surface Chemistry. Long--Range Forces. Surfaces of Solids. Surfaces of Solids: Microscopy and Spectroscopy. The Formation of a New Phase--Nucleation and Crystal Growth. The Solid--Liquid Interface--Contact Angle. The Solid--Liquid Interface--Adsorption from Solution. Frication, Lubrication, and Adhesion. Wetting, Flotation, and Detergency. Emulsions, Foams, and Aerosols. Macromolecular Surface Films, Charged Films, and Langmuir--Blodgett Layers. The Solid--Gas Interface--General Considerations. Adsorption of Gases and Vapors on Solids. Chemisorption and Catalysis. Index.
Selective peptidic and peptidomimetic inhibitors of Candida albicans myristoylCoA: Protein N-myristoyltransferase: A new approach to antifungal therapy (1997)

MyristoylCoA: protein N-myristoyltransferase (NMT) catalyzes the cotranslational covalent attachment of a rare cellular fatty acid, myristate, to the N-terminal Gly residue of a variety of eukaryotic proteins. The myristoyl moiety is often essential for expression of the biological functions for these proteins. Attachment of C14:0 alone provides barely enough hydrophobicity to allow stable association with membranes. The partitioning of N-myrisotylproteins is therefore often modulated by "switches" that function through additional covalent or noncovalent modifications. Candida albicans, the principal cause of systemic fungal infection in immunocompromised humans, contains a single NMT gene that is essential for its viability. The functional properties of the acylCoA binding site of human and C. albicans NMT are very similar. However, there are distinct differences in their peptide binding sites. An ADP ribosylation factor (Arf) is included among the few cellular protein substrates of the fungal enzyme. Alanine scanning mutagenesis of an octapeptide derived from an N-terminal Arf sequence (GLYASKLS-NH2) disclosed that Gly1, Ser5, and Lys6 play predominant roles in binding. ALYASKLS-NH2 is an inhibitor competitive for peptide [Ki(app) = 15.3 +/- 6.4 microM] and noncompetitive for myristoylCoA. Remarkably, replacement of the N-terminal tetrapeptide with an 11-aminoundecanoyl group results in a competitive inhibitor (11-aminoundecanoyl-SKLS-NH2) that is approximately 40-fold more potent [Ki(app) = 0.40 +/- 0.03 microM] than the starting octapeptide. Removal of Leu-Ser from the C-terminus generates a competitive dipeptide inhibitor (11-aminoundecanoyl-SK-NH2) with a Ki(app) of 11.7 +/- 0.4 microM, equivalent to that of the starting octapeptide. A derivative dipeptide inhibitor containing a C-terminal N-cyclohexylethyl lysinamide moiety has the advantage of being more potent (IC50 = 0.11 +/- 0.03 microM) and resistant to digestion by cellular carboxypeptidases. Rigidifying the flexible aminoundecanoyl chain results in very potent general NMT inhibitors (IC50 = 40-50 nM). Substituting a 2-methylimidazole for the N-terminal amine and adding a benzylic alpha-methyl group with R stereochemistry to the rigidifying element produces even more potent inhibitors (IC50 = 20-50 nM) that are up to 500-fold selective for the fungal compared to human enzyme. A related less potent member of this series of compounds is fungistatic. Its growth inhibitory effects are associated with a reduction in cellular protein N-myristoylation, judged using cellular Arf as a reporter. These studies establish that NMT is a new antifungal target.
Comparison of the genome sequences ofListeria monocytogenesandListeria innocua: clues for evolution and pathogenicity (2003)

Listeria monocytogenes, an invasive opportunistic, food-borne pathogen, remains one of the leading causes of mortality from food-borne infections. The recently determined complete genome sequences of L. monocytogenes strain EGDe and of that of the closely related non-pathogenic species Listeria innocua strain CLIP11262 enhance our knowledge of the genetic basis of the virulence of L. monocytogenes and advance our understanding of the evolution of these Listeria species. Both genomes encode a high number of surface, transport and regulatory proteins. Comparison of the genome organisation revealed a perfect synteny between the two Listeria genomes. Comparison with other closely related bacteria also showed a high conservation in genome organisation among the Listeria, Staphylococcus and Bacillus group of low G+C content bacteria. Distinct G+C content of a number of strain-specific genes suggests intensive lateral gene transfer. The identification of a 55-kb locus encoding proteins with high homology to Salmonella enterica serovar Typhimurium vitamin B(12) synthesis proteins as well as those necessary for degradation of ethanolamine and propanediol further indicates acquisition of a complete metabolic pathway by horizontal gene transfer and a probable role of this locus in anaerobic growth in the host.
A Mouse Model with Features of Familial Combined Hyperlipidemia (1997)

Familial combined hyperlipidemia (FCHL) is a common inherited lipid disorder, affecting 1 to 2 percent of the population in Westernized societies. Individuals with FCHL have large quantities of very low density lipoprotein (VLDL) and low density lipoprotein (LDL) and develop premature coronary heart disease. A mouse model displaying some of the features of FCHL was created by crossing mice carrying the human apolipoprotein C-III (APOC3) transgene with mice deficient in the LDL receptor. A synergistic interaction between the apolipoprotein C-III and the LDL receptor defects produced large quantities of VLDL and LDL and enhanced the development of atherosclerosis. This mouse model may provide clues to the origin of human FCHL.
The Importance of Fracture Pattern in Guiding Therapeutic Decision-Making in Patients with Hemorrhagic Shock and Pelvic Ring Disruptions (2002)

Patients with signs of ongoing shock with SFP pelvic injury and hemoperitoneum require celiotomy as the initial intervention, as the hemorrhagic focus is predominantly intraperitoneal. In patients with UFP, even in the presence of hemoperitoneum, consideration should be given to angiography before celiotomy.
The contribution of mouse models to understanding the pathogenesis of spinal muscular atrophy (2011)

Spinal muscular atrophy (SMA), which is caused by inactivating mutations in the survival motor neuron 1 (SMN1) gene, is characterized by loss of lower motor neurons in the spinal cord. The gene encoding SMN is very highly conserved in evolution, allowing the disease to be modeled in a range of species. The similarities in anatomy and physiology to the human neuromuscular system, coupled with the ease of genetic manipulation, make the mouse the most suitable model for exploring the basic pathogenesis of motor neuron loss and for testing potential treatments. Therapies that increase SMN levels, either through direct viral delivery or by enhancing full-length SMN protein expression from the SMN1 paralog, SMN2, are approaching the translational stage of development. It is therefore timely to consider the role of mouse models in addressing aspects of disease pathogenesis that are most relevant to SMA therapy. Here, we review evidence suggesting that the apparent selective vulnerability of motor neurons to SMN deficiency is relative rather than absolute, signifying that therapies will need to be delivered systemically. We also consider evidence from mouse models suggesting that SMN has its predominant action on the neuromuscular system in early postnatal life, during a discrete phase of development. Data from these experiments suggest that the timing of therapy to increase SMN levels might be crucial. The extent to which SMN is required for the maintenance of motor neurons in later life and whether augmenting its levels could treat degenerative motor neuron diseases, such as amyotrophic lateral sclerosis (ALS), requires further exploration.
Detection of Multiple Sclerosis from Exhaled Breath Using Bilayers of Polycyclic Aromatic Hydrocarbons and Single-Wall Carbon Nanotubes (2011)

A cross-reactive array of polycyclic aromatic hydrocarbons and single wall carbon nanotube bilayers was designed for the detection of volatile organic compounds (tentatively, hexanal and 5-methyl-undecane) that identify the presence of disease in the exhaled breath of patients with multiple sclerosis. The sensors showed excellent discrimination between hexanal, 5-methyl-undecane, and other confounding volatile organic compounds. Results obtained from a clinical study consisting of 51 volunteers showed that the sensors could discriminate between multiple sclerosis and healthy states from exhaled breath samples with 85.3% sensitivity, 70.6% specificity, and 80.4% accuracy. These results open new frontiers in the development of a fast, noninvasive, and inexpensive medical diagnostic tool for the detection and identification of multiple sclerosis. The results could serve also as a launching pad for the discrimination between different subphases or stages of multiple sclerosis as well as for the identification of multiple sclerosis patients who would respond well to immunotherapy.
New Approach for Oral Administration of Insulin With Polyalkylcyanoacrylate Nanocapsules as Drug Carrier (1988)

Polyalkylcyanoacrylate nanocapsules (mean size 220 nm), composed of spheric polymeric structures, have been used as a drug carrier for insulin. The rate of encapsulation of insulin is 54.9%, and we studied the therapeutic efficiency of the nanocapsules in diabetic and normal rats. When administered subcutaneously, insulin-loaded nanocapsules prolonged the hypoglycemic effect of insulin; the duration of this effect increased with the doses. When administered orally by force-feeding to diabetic rats, insulin nanocapsules (12.5, 25, and 50 U/kg) decreased fasted glycemia 50-60% by day 2. This effect was maintained for 6 or 20 days with 12.5 or 50 U/kg, respectively. Only the dose of 100 U/kg decreased fed glycemia by 25% in diabetic rats. In normal rats, hyperglycemia induced by an oral glucose load was reduced by 50% with the same dose of oral insulin nanocapsules. We concluded that polyalkylcyanoacrylate nanocapsules preserve the therapeutic effect of insulin when administered orally and prolong this effect when administered subcutaneously and orally.