gebhart/patrepeval huggingface dataset:
A Tumorigenic Subpopulation with Stem Cell Properties in Melanomas (2005)

Recent studies suggest that cancer can arise from a cancer stem cell (CSC), a tumor-initiating cell that has properties similar to those of stem cells. CSCs have been identified in several malignancies, including those of blood, brain, and breast. Here, we test whether stem cell-like populations exist in human melanomas. In approximately 20% of the metastatic melanomas cultured in growth medium suitable for human embryonic stem cells, we found a subpopulation of cells propagating as nonadherent spheres, whereas in standard medium, adherent monolayer cultures were established. Individual cells from melanoma spheres (melanoma spheroid cells) could differentiate under appropriate conditions into multiple cell lineages, such as melanocytic, adipocytic, osteocytic, and chondrocytic lineages, which recapitulates the plasticity of neural crest stem cells. Multipotent melanoma spheroid cells persisted after serial cloning in vitro and transplantation in vivo, indicating their ability to self-renew. Furthermore, they were more tumorigenic than adherent cells when grafted to mice. We identified similar multipotent spheroid cells in melanoma cell lines and found that the stem cell population was enriched in a CD20+ fraction of melanoma cells. Based on these findings, we propose that melanomas can contain a subpopulation of stem cells that contribute to heterogeneity and tumorigenesis. Targeting this population may lead to effective treatments for melanomas.
Humanized antibodies against the α-chain of the IL-2 receptor and against the β-chain shared by the IL-2 and IL-15 receptors in a monkey uveitis model of autoimmune diseases (1997)

We studied the efficacy and tolerance of humanized Ab interfering with the signal of the IL-2 and IL-15 receptors in a primate model of experimental autoimmune uveoretinitis. The inhibitory effects of humanized anti-Tac (HAT), an anti-IL-2R alpha-chain Ab, and HuMik beta1, an Ab directed at the beta-chain shared by the receptors of IL-2 and IL-15, were tested in culture on the proliferative response of monkey Con A-blast lymphocytes stimulated with IL-2 or IL-15. Uveitis was induced in cynomolgus monkeys by immunization with human recombinant retinal S-antigen. Treatment was initiated at the first sign of disease and consisted of HAT and HuMik beta1, alone or in combination, or vehicle control given by i.v. injection twice a week for 4 wk. Disease was evaluated by ocular funduscopy. The results in culture showed a significant dose-dependent inhibition of the IL-2-driven proliferation of lymphocytes by HAT. HuMik beta1 alone was ineffective against IL-2 stimulation, but had a marked potentiating effect in combination with HAT, independent of IL-15 signaling. IL-15-driven proliferation was inhibited by HuMik beta1, but not by HAT alone or in combination. In monkeys, experimental autoimmune uveoretinitis evolution was significantly inhibited by HAT treatment. HuMik beta1 alone had no effect on the disease. However, when used in combination, the two Ab markedly reduced the severity of ocular inflammation. The Ab were well tolerated. Only three monkeys, treated with HAT alone, made an Ab response against the injected Ab.
Comparative Pharmacokinetic and Electrocardiographic Effects of Intratracheal and Intravenous Administration of Flecainide in Anesthetized Pigs (2018)

Abstract: We compared the pharmacokinetic (PK) profile and electrocardiographic (ECG) changes in response to intratracheal instillation of flecainide acetate into the left atrium and ventricle with intravenous (IV) flecainide acetate administration. In 12 closed-chest anesthetized Yorkshire pigs, we monitored the QRS complex and PR, JT c , and QT c intervals during sinus rhythm and correlated changes with venous plasma drug concentrations before and at 2, 5, 10, 15, and 30 minutes after drug administration. Intratracheal instillation of flecainide (0.75 and 1.5 mg/kg, rapid bolus) caused dose/concentration-dependent increases in the QRS complex duration of 10% and 19%, respectively, at 2 minutes, coinciding with peak venous plasma levels (1688 ± 177 and 2808 ± 217 ng/mL, respectively). IV infusion of flecainide (2 mg/kg) over 2 or 10 minutes similarly prolonged QRS complexes and PR intervals (both, P &lt; 0.001). Intratracheal flecainide instillation increased PR interval briefly at 5 minutes. Neither intratracheal nor IV flecainide affected JT c or QT c intervals. Thus, the PK pattern of intratracheal instillation of flecainide is comparable to IV administration, although the absolute plasma concentrations were higher with IV infusion. Both modes of delivery elicited ECG changes that were consistent with the expected pharmacological activity of flecainide.
A Novel Energy-Balanced Dynamic Routing Algorithm for Wireless Sensor Networks (2014)

Wireless sensor networks (WSNs) is taking an increasing role in our lives. Because the energy of the sensors is limited how to efficiently use the energy to prolong the lifecycle of the sensor networks is very important. In this paper, a novel energy-balanced dynamic routing algorithm based on ACO is proposed. The novel routing algorithm can dynamically choose routing according to the residual energy of the sensors and the sensors with more power is taken more data transfer tasks. The simulation results show that the proposed routing algorithm can effectively balance energy consumption and prolong the lifecycle of the networks.
Evaluation of the cyclic behavior of aircraft turbine disk alloys (1978)

Postnatal development of the K+-stimulated release of [3H]GABA in rat cortex slices was compared to the density of Gray type 2 synapses (which correlate with GABAergic synapses in rat cortex). The [3H]GABA release system develops earlier than the inhibitory synapses which suggests that, at least in the young cortical tissue, a large part of the release mechanism is associated with other than synaptic structures.
Lactisole Interacts with the Transmembrane Domains of Human T1R3 to Inhibit Sweet Taste (2005)

The detection of sweet-tasting compounds is mediated in large part by a heterodimeric receptor comprised of T1R2+T1R3. Lactisole, a broad-acting sweet antagonist, suppresses the sweet taste of sugars, protein sweeteners, and artificial sweeteners. Lactisole's inhibitory effect is specific to humans and other primates; lactisole does not affect responses to sweet compounds in rodents. By heterologously expressing interspecies combinations of T1R2+T1R3, we have determined that the target for lactisole's action is human T1R3. From studies with mouse/human chimeras of T1R3, we determined that the molecular basis for sensitivity to lactisole depends on only a few residues within the transmembrane region of human T1R3. Alanine substitution of residues in the transmembrane region of human T1R3 revealed 4 key residues required for sensitivity to lactisole. In our model of T1R3's seven transmembrane helices, lactisole is predicted to dock to a binding pocket within the transmembrane region that includes these 4 key residues.
The Effects of Mild Perioperative Hypothermia on Blood Loss and Transfusion Requirement (2008)

Even mild hypothermia (<1 degree C) significantly increases blood loss by approximately 16% (4-26%) and increases the relative risk for transfusion by approximately 22% (3-37%). Maintaining perioperative normothermia reduces blood loss and transfusion requirement by clinically important amounts.
Microglial activation and dopamine terminal loss in early Parkinson's disease (2005)

Neuroinflammatory glial response may contribute to degenerative processes in Parkinson's disease (PD). To investigate changes in microglial activity associated with changes in the presynaptic dopamine transporter density in the PD brain in vivo, we studied 10 early-stage drug-naive PD patients twice using positron emission tomography with a radiotracer for activated microglia [(11)C](R)-PK11195 and a dopamine transporter marker [(11)C]CFT. Quantitative levels of binding potentials (BPs) of [(11)C](R)-PK11195 and [(11)C]CFT in the nigrostriatal pathway were estimated by compartment analyses. The levels of [(11)C](R)-PK11195 BP in the midbrain contralateral to the clinically affected side were significantly higher in PD than that in 10 age-matched healthy subjects. The midbrain [(11)C](R)-PK11195 BP levels significantly correlated inversely with [(11)C]CFT BP in the putamen and correlated positively with the motor severity assessed by the Unified Parkinson's Disease Rating Scale in PD. In healthy subjects, the [(11)C](R)-PK11195 BP in the thalamus and midbrain showed an age-dependent increase. In vivo demonstration of parallel changes in microglial activation and corresponding dopaminergic terminal loss in the affected nigrostriatal pathway in early PD supports that neuroinflammatory responses by intrinsic microglia contribute significantly to the progressive degeneration process of the disease and suggests the importance of early therapeutic intervention with neuroprotective drugs.
Metabolic activation and deactivation of arylamine carcinogens by recombinant human NAT1 and polymorphic NAT2 acetyltransferases (1993)

A genetic polymorphism at the NAT2 gene locus, encoding for polymorphic N-acetyltransferase (NAT2), segregates individuals into rapid, intermediate or slow acetylator phenotypes. Both rapid and slow acetylator phenotypes have been associated with increased incidence of cancer in certain target organs related to arylamine exposure, suggesting a role for acetylation in both the activation and deactivation of arylamine carcinogens. A second gene (NAT1) encodes for a different acetyltransferase isozyme (NAT1) that is not subject to the classical acetylation polymorphism. In order to assess the relative ability of NAT1 and NAT2 to activate and deactivate arylamine carcinogens, we tested the capacity of recombinant human NAT1 and NAT2, expressed in Escherichia coli XA90 strains DMG100 and DMG200 respectively, to catalyze the N-acetylation (deactivation) and O-acetylation (activation) of a variety of carbocyclic and heterocyclic arylamine carcinogens. Both NAT1 and NAT2 catalyzed the N-acetylation of each of the 17 arylamines tested. Rates of N-acetylation by NAT1 and NAT2 were considerably lower for heterocyclic arylamines such as 2-amino-3-methyl-imidazo[4,5-f]quinoline (IQ), particularly those (e.g. IQ) with steric hindrance to the exocyclic amino group. For carbocyclic arylamines such as 4-aminobiphenyl and beta-naphthylamine, the apparent affinity was significantly (P < 0.05) higher for NAT2 than NAT1. NAT1/NAT2 activity ratios and clearance calculations suggest a significant role for the polymorphic NAT2 in the N-acetylation of carbocyclic arylamine carcinogens. Both NAT1 and NAT2 catalyzed acetyl coenzyme A-dependent O-acetylation of N-hydroxy-2-aminofluorene and N-hydroxy-4-aminobiphenyl to yield DNA adducts. NAT1 catalyzed paraoxon-resistant, intramolecular N,O-acetyltransferase-mediated activation of N-hydroxy-2-acetylaminofluorene and N-hydroxy-4-acetylaminobiphenyl at low rates; catalysis by NAT2 was not readily detectable in the presence of paraoxon. In summary these studies strongly suggest that the human acetylation polymorphism influences both the metabolic activation (O-acetylation) and deactivation (N-acetylation) of arylamine carcinogens via polymorphic expression of NAT2. These findings lend mechanistic support for human epidemiological studies suggesting associations between both rapid and slow acetylator phenotype and cancers related to arylamine exposure.
A Hand‐held Fiber‐optic Implement for the Site‐specific Delivery of Photosensitizer and Singlet Oxygen (2011)

We have constructed a fiber optic device that internally flows triplet oxygen and externally produces singlet oxygen, causing a reaction at the (Z)-1,2-dialkoxyethene spacer group, freeing a pheophorbide sensitizer upon the fragmentation of a reactive dioxetane intermediate. The device can be operated and sensitizer photorelease observed using absorption and fluorescence spectroscopy. We demonstrate the preference of sensitizer photorelease when the probe tip is in contact with octanol or lipophilic media. A first-order photocleavage rate constant of 1.13 h(-1) was measured in octanol where dye desorption was not accompanied by readsorption. When the probe tip contacts aqueous solution, the photorelease was inefficient because most of the dye adsorbed on the probe tip, even after the covalent ethene spacer bonds have been broken. The observed stability of the free sensitizer in lipophilic media is reasonable even though it is a pyropheophorbide-a derivative that carries a p-formylbenzylic alcohol substituent at the carboxylic acid group. In octanol or lipid systems, we found that the dye was not susceptible to hydrolysis to pyropheophorbide-a, otherwise a pH effect was observed in a binary methanol-water system (9:1) at pH below 2 or above 8.
DNA and Protein Microarrays and their Contributions to Proteomics and Genomics (2001)

Knowledge in genomics and proteomics has exploded in the last two decades. This is in part due to key developments that have revolutionized the possibilities of bioanalytics such as the introduction of polymerase chain reaction (PCR) in the mid 80s that formed the base for the massively parallel sequencing of the genomes.A few years ago DNA and protein microarray analysis were added to the toolbox of life sciences analytics. These technologies already proved to be ideal tools for the identification of gene targets, the simultaneous measurement of the expression of a high number of genes or proteins, and the increase of the level of understanding of the biological functions of genes and proteins. A small number of experiments are now sufficient to obtain information on gene or protein expression which could not be obtained by using conventional bioanalytical technologies or which required an extremely high experimental effort. In the future applications, high sensitivity DNA and protein microarrays will allow low abundant genes and proteins to be monitored that so far have been inaccessible to current microarray technologies and thus will generate a new dimension of genomic and proteomic information.
Bactericidal/permeability-increasing protein ameliorates acute lung injury in porcine endotoxemia (1994)

Bactericidal/permeability-increasing protein (BPI), a cationic protein isolated from human neutrophils, binds lipopolysaccharide (LPS), kills gram-negative bacteria, and neutralizes many of the effects of LPS in vitro and in vivo. We hypothesized that a recombinant 23-kDa NH2-terminal fragment of BPI (BPI23) would reduce acute lung injury in endotoxemic pigs. At -18 h, pigs received an intravenous priming dose of LPS (20 micrograms/kg). Anesthetized ventilated swine were randomized to receive 1) no further treatment (n = 4); 2) LPS (250 micrograms/kg over 50 min) and BPI23 (3-mg/kg bolus and 3 mg/kg over 60 min) (n = 6); or 3) LPS and thaumatin, a cationic protein devoid of LPS neutralizing activity that has a molecular mass and isoelectric point that are similar to that of BPI23 (n = 7). BPI23 treatment significantly ameliorated LPS-induced hypoxemia, functional upregulation of opsonin receptors on circulating phagocytes, and alveolitis but had no effect on the elaboration of tumor necrosis factor-alpha or thromboxane A2. The salutory effects of BPI23 on acute lung injury in endotoxemic pigs may be mediated, at least in part, by inhibition of direct activation of phagocytes by LPS.
META060 inhibits osteoclastogenesis and matrix metalloproteinases in vitro and reduces bone and cartilage degradation in a mouse model of rheumatoid arthritis (2010)

Our findings indicate that META060 reduces swelling in a model of acute inflammation and inhibits bone and cartilage destruction in a model of chronic inflammation. Its efficacy is associated with the inhibition of multiple protein kinases, including Syk, Btk, PI 3-kinase, and GSK3. These results warrant further clinical testing of META060 for its therapeutic potential in the treatment of inflammatory diseases.
2′-Fluoropyrimidine RNA-based Aptamers to the 165-Amino Acid Form of Vascular Endothelial Growth Factor (VEGF165) (1998)

Vascular endothelial growth factor (VEGF) has been implicated in the pathological induction of new blood vessel growth in a variety of proliferative disorders. Using the SELEX process (systematic evolution of ligands by exponential enrichment), we have isolated 2'-F-pyrimidine RNA oligonucleotide ligands (aptamers) to human VEGF165. Representative aptamers from three distinct sequence families were truncated to the minimal sequence capable of high affinity binding to VEGF (23-29 nucleotides) and were further modified by replacement of 2'-O-methyl for 2'-OH at all ribopurine positions where the substitution was tolerated. Equilibrium dissociation constants for the interaction of VEGF with the truncated, 2'-O-methyl-modified aptamers range between 49 and 130 pM. These aptamers bind equally well to murine VEGF164, do not bind to VEGF121 or the smaller isoform of placenta growth factor (PlGF129), and show reduced, but significant affinity for the VEGF165/PlGF129 heterodimer. Cysteine 137 in the exon 7-encoded domain of VEGF165 forms a photo-inducible cross-link to a single uridine residue in each of the three aptamers. The aptamers potently inhibit the binding of VEGF to the human VEGF receptors, KDR and Flt-1, expressed by transfected porcine aortic endothelial cells. Furthermore, one of the aptamers is able to significantly reduce intradermal VEGF-induced vascular permeability in vivo.
Fabrication and characterization of carbon nanotube FETs (2005)

We have fabricated carbon nanotube (CNT) FETs using position-controlled growth technique. The CNT-FETs showed p-type conduction. The chirality of the CNT FET channel was determined by using microphotocurrent spectroscopy. Novel peapods FETs with fullerenes inserted in the CNTs were also fabricated. They showed ambipolar <i>I-V</i> characteristics with both n- and p-type conductions depending on the gate voltage. The ambipolar behavior was explained based on the Schottky-barrier-controlled transistor model, where the transistor action occurs primarily by changing the Schottky contact resistance by the gate voltage. It has been shown that the bandgap of the peapod FETs was dependent on what kind of fullerene was inserted in the CNT channel. We have also demonstrated that it was possible to control the conduction type of the FET channel by choosing contact metal with different work function without any doping in the CNT channel.
Expression of the macrophage scavenger receptor, a multifunctional lipoprotein receptor, in microglia associated with senile plaques in Alzheimer's disease. (1996)

The macrophage scavenger receptor is a multifunctional receptor whose ligands include oxidized low density lipoprotein (LDL), as well as several other polyanionic macromolecules. Although the capacity of the receptor to bind modified LDL has implicated it in the process of atherosclerosis, its physiological role remains uncertain. We have examined human brain for expression of macrophage scavenger receptor as part of ongoing studies of lipoprotein receptors in the central nervous system. The receptor is expressed on microglia, but not on astrocytes, neurons, or vessel-associated structures. In Alzheimer disease, there is strong expression of the scavenger receptor in association with senile plaques.
Increased Expression of the Relaxin Receptor (LGR7) in Human Endometrium during the Secretory Phase of the Menstrual Cycle (2004)

Relaxin (RLX) is a structural homolog of insulin that is the ligand for the LGR7 receptor. Although the 6k peptide is produced by the ovaries to cause connective tissue remodeling of the rodent and pig reproductive tracts to facilitate parturition, in human reproduction, the role of RLX is less well understood. Binding of human gene 2 (H2) [(33)P]-RLX, expression of RLX peptides and the LGR7 receptor was examined in the human uterus at different stages of the menstrual cycle. A significant increase in RLX receptor binding in endometrium was identified by quantitative autoradiography in the secretory compared with the proliferative phase. H2RLX competed with [(33)P]-H2RLX binding with higher affinity than porcine RLX during both the proliferative and secretory phases. Increased LGR7 receptor gene expression during the secretory phase paralleled the changes in [(33)P]-H2RLX binding. Human gene 1 RLX transcripts were not detected in the uterus, and H2RLX gene expression was low and not influenced by the stage of the menstrual cycle. The studies show that binding to and gene expression of the LGR7 RLX receptor changes markedly with the phases of the menstrual cycle, suggesting a specific role for the hormone in the physiology of the human uterus.
Fusion of biomimetic stealth probes into lipid bilayer cores (2010)

Many biomaterials are designed to regulate the interactions between artificial and natural surfaces. However, when materials are inserted through the cell membrane itself the interface formed between the interior edge of the membrane and the material surface is not well understood and poorly controlled. Here we demonstrate that by replicating the nanometer-scale hydrophilic-hydrophobic-hydrophilic architecture of transmembrane proteins, artificial "stealth" probes spontaneously insert and anchor within the lipid bilayer core, forming a high-strength interface. These nanometer-scale hydrophobic bands are readily fabricated on metallic probes by functionalizing the exposed sidewall of an ultrathin evaporated Au metal layer rather than by lithography. Penetration and adhesion forces for butanethiol and dodecanethiol functionalized probes were directly measured using atomic force microscopy (AFM) on thick stacks of lipid bilayers to eliminate substrate effects. The penetration dynamics were starkly different for hydrophobic versus hydrophilic probes. Both 5- and 10 nm thick hydrophobically functionalized probes naturally resided within the lipid core, while hydrophilic probes remained in the aqueous region. Surprisingly, the barrier to probe penetration with short butanethiol chains (E(o,5 nm) = 21.8k(b)T, E(o,10 nm) = 15.3k(b)T) was dramatically higher than longer dodecanethiol chains (E(o,5 nm) = 14.0k(b)T, E(o,10 nm) = 10.9k(b)T), indicating that molecular mobility and orientation also play a role in addition to hydrophobicity in determining interface stability. These results highlight a new strategy for designing artificial cell interfaces that can nondestructively penetrate the lipid bilayer.
MICROBIAL HYDROLYSIS OF POLYSACCHARIDES (1996)

Microorganisms are efficient degraders of starch, chitin, and the polysaccharides in plant cell walls. Attempts to purify hydrolases led to the realization that a microorganism may produce a multiplicity of enzymes, referred to as a system, for the efficient utilization of a polysaccharide. In order to fully characterize a particular enzyme, it must be obtained free of the other components of a system. Quite often, this proves to be very difficult because of the complexity of a system. This realization led to the cloning of the genes encoding them as an approach to eliminating other components. More than 400 such genes have been cloned and sequenced, and the enzymes they encode have been grouped into more than 50 families of related amino acid sequences. The enzyme systems revealed in this manner are complex on two quite different levels. First, many of the individual enzymes are complex, as they are modular proteins comprising one or more catalytic domains linked to ancillary domains that often include one or more substrate-binding domains. Second, the systems are complex, comprising from a few to 20 or more enzymes, all of which hydrolyze a particular substrate. Systems for the hydrolysis of plant cell walls usually contain more components than systems for the hydrolysis of starch and chitin because the cell walls contain several polysaccharides. In general, the systems produced by different microorganisms for the hydrolysis of a particular polysaccharide comprise similar enzymes from the same families.