gebhart/patrepeval huggingface dataset:
Dose escalation of the hypoxic cell sensitizer etanidazole combined with ifosfamide, carboplatin, etoposide, and autologous hematopoietic stem cell support. (1998)

Multiple mechanisms of drug resistance contribute to treatment failure. Although high-dose therapy attempts to overwhelm these defenses pharmacologically, this approach is only successful in a fraction of treated patients. Many drug resistance mechanisms are shared between malignant and normal cells, but the expression of various drug resistance mechanisms associated with hypoxia is largely confined to tumor tissue. Thus, reversal of this mechanism is likely to provide a therapeutic advantage to the host. This study was designed to define the dose-limiting toxicities and maximum tolerated dose of etanidazole when it is given concurrently with high-dose ifosfamide, carboplatin, and etoposide (ICE), with hematopoietic stem cell support. The maximum tolerated doses of high-dose ICE were administered concurrently with dose escalations of etanidazole, a hypoxic cell sensitizer. All agents were given by 96-h continuous i.v. infusion beginning on day -7. Mesna uroprotection was provided. Autologous marrow and cytokine mobilized peripheral blood progenitor cells were reinfused on day 0. Granulocyte colony-stimulating factor was administered following reinfusion until the granulocytes recovered to > 1000/microliter. Fifty-five adults with advanced malignancies were enrolled in cohorts of five to nine patients. Four dose levels of etanidazole between 3 and 5.5 g/m2/day (12, 16, 20, and 22 g/m2 total doses) and two doses of carboplatin (1600 and 1800 mg/m2 total doses) were evaluated. Seven patients died of organ toxicity (13%); two each from veno-occlusive disease of liver and sepsis; and one each from sudden death, renal failure, and refractory thrombocytopenic hemorrhage. Five deaths occurred at the top dose level. One additional patient suffered a witnessed cardiorespiratory arrest from ventricular fibrillation and was resuscitated. Dose-dependent and largely reversible peripheral neuropathy was observed consisting of two syndromes: severe cramping myalgic/neuralgic pain, predominantly in stocking glove distribution, occurring between day -3 and day 0, and a sensory peripheral neuropathy with similar distribution peaking around day +60. The maximal achievable dose of etanidazole (16 g/m2 dose level) resulted in a mean serum level of 38 micrograms/ml (25-55 micrograms/ml). Etanidazole significantly enhanced host toxicity of high-dose ICE. Effective modulatory doses of etanidazole could not be given with acceptable toxicity using this schedule.
MASS SPECTRAL INVESTIGATIONS ON MICROORGANISMS (2000)

Bacterial cells undergo lysis readily, when suspended in mild aqueous acids, and release the cellular proteins along with other biomolecules. Molecular masses of the protein biomarkers released in-situ from individual intact bacterial cells could be directly measured by mass spectrometry. Limited sample clean up may be required at times, prior to mass spectral analysis, to remove any ionizable impurities such as salts, buffers and deergents. The marker proteins specific for individual genus, species and strains were determined by the comparison of the biomarkers measured for several closely related organisms. Even though there is a probability of over 4000 cellular proteins expressed in any single bacterial cell, only a small fraction of the projected marker proteins are identified consistently during the process. This could be due to the variation in the ionization properties of the proteins and the limited energy available to prompt their ionization. Variation in the sample processing and culture conditions had little effect in the marker proteins observed during the process. This experimental procedure enables the distinction of gram positive as well as gram negative cellular pathogens and their corresponding non-pathogenic counterparts. The identity of few bacterial cells present in unknown samples can be easily, rapidly and accurately established by adopting a procedure involving simple sample processing followed by direct mass spectral analysis and data processing. Thus, an uncomplicated approach has been developed to resolve a complex problem involving cellular pathogens. This method has enormous application potential in the rapid identification and subsequent prevention of any potential health hazard caused by the pathogenic bacteria, either under natural or induced conditions. There is a great potential for the total automation of the entire process in the future for simpler but more effective unattended operations in the laboratory as well as in the field.
Generalized Functional Model for Three-Phase PWM Inverter/Rectifier Converters (1987)

The traditional circuit-based analysis of static power converters has proven to be unsuitable for handling the design requirements of the ever-growing number of circuit topologies. This situation has prompted the introduction and use of analysis methods based on converter function rather than circuit configuration. Such a method is presented, the novel feature of which is that it is simultaneously applicable to a group of converter families instead of individual converters. The resulting advantages are obvious, and they are conclusively demonstrated here.
Modeling the Function of Bacterial Virulence Factors in <i>Saccharomyces cerevisiae</i> (2004)

Our understanding of the molecular mechanisms of bacterial pathogenesis has been shaped largely by what we have learned from genetic screens. Transposon mutagenesis, in particular, has streamlined genetic analysis and led to the identification of a multitude of virulence factors in a wide range of
Optical Coatings for High Energy ZnSe Laser Windows (1974)

The development of surface finishing and coating technology at 10.6 microm for polycrystalline ZnSe laser windows is presented. Optical evaluation of the coated windows shows that the 10.6-microm absorption and reflection can be held to less than 0.1% per surface. Surface finishing procedures, theoretical coating designs, and recent experimental results for antireflection coatings for ZnSe are presented.
Prior polyvascular disease: risk factor for adverse ischaemic outcomes in acute coronary syndromes (2009)

Prior polyvascular disease increases the risk of in-hospital adverse events, including mortality. Identification of these patients in clinical trial and real world populations may provide an opportunity to reduce their excess risk with intensive secondary prevention efforts.
Time-lapse image registration using the local similarity attribute (2009)

Abstract We present a method to register time-lapse seismic images based on the local-similarity attribute. We define registration as an automatic point-by-point alignment of time-lapse images. Stretching and squeezing a monitor image and computing its local similarity to the base image allows us to detect an optimal registration even in the presence of significant velocity changes in the overburden. A by-product of this process is an estimate of the ratio of the interval seismic velocities in the reservoir interval. We illustrate the proposed method and demonstrate its effectiveness using both synthetic experiments and real data from a time-lapse experiment in the Duri field, Indonesia.
Correlation of translocation of tight junction protein Zonula occludens-1 and activation of epidermal growth factor receptor in the regulation of invasion of pancreatic cancer cells. (2005)

Mitogen-activated protein kinase signal transduction pathway was isolated as a potential factor related to cancer cell dissociation in dissociated (PC-1.0 and AsPC-1) and non-dissociated (PC-1 and Capan-2) pancreatic cancer cells in our previous works. On the other hand, changes of structure and function of tight junction (TJ) are reported to be correlated with carcinogenesis and tumor development. In this study, the translocation of TJ protein Zonula occludens-1 (ZO-1) and the activation of epidermal growth factor receptor (EGFR) were examined to demonstrate the involvement and correlation of TJ protein translocation and EGFR activation in the cell dissociation and subsequent invasion of pancreatic cancer. Immunocytochemistry, fluorescence intensity analysis and in vitro invasion assay were performed in dissociated and non-dissociated pancreatic cancer cells. The obvious translocation of cell-cell junction localized ZO-1 protein to the cytoplasm and nucleus, simultaneous activation of EGFR, as well as the dissociation of cell colonies of non-dissociated pancreatic cancer cells were induced by dissociation factor treatment. However, EGFR inhibitor, AG1478, treatment significantly induced the redistribution of ZO-1 protein to the sites of cell-cell junction and the cell aggregation, as well as simultaneous suppression of EGFR activation in both the dissociated and the non-dissociated pancreatic cancer cells. In addition, AG1478 treatment markedly enhanced the in vitro invasion of non-dissociated pancreatic cancer cells. Translocation of TJ protein ZO-1 is closely involved in the induction of invasion through EGFR activation in pancreatic cancer cells.
Fabrication of Patterned Multicomponent Protein Gradients and Gradient Arrays Using Microfluidic Depletion (2003)

We demonstrate that depletion effects in the fluids used to fill a poly(dimethylsiloxane) microfluidic device can be used in conjunction with its design rules to generate patterned protein gradients. The linear portions of these structures can be designed to present gradients of bound protein coverage-varying from near-saturation to effectively zero-over distances ranging from a few hundred micrometers to more than 1 cm by design. Such patterns can be developed in a simple, single-channel form as well as in a multichannel gradient array of more complex design. The patterning protocols also support the use of multiple protein sources, and we demonstrate an assembly process mediated by a protein that inhibits adsorption to generate a gradient array in pixel form. We describe examples of multiple protein gradient patterns along with simple immunoassays to illustrate the scope of the methodology, the activity of the patterned proteins, and their recognition in gradient form on a surface. These gradients should prove useful to studies in biosensor and bioassay development and as substrates for cell culture to study growth and motility.
Effect of Polyphenols on Production of Steroid Hormones from Human Adrenocortical NCI-H295R Cells (2013)

Modulating steroid hormone levels is a curative and preventive measure for Cushing's syndrome, aldosteronism, and various stress-triggered symptoms. Polyphenols have been reported to inhibit steroidogenic enzymes such as 3β-hydroxysteroid dehydrogenase (3β-HSD) and aromatase. However, evidence for their inhibitory effects is fragmentary because it has been determined in studies with small groups of steroid hormones. To investigate the effects of steroids on complete steroidogenic pathways, comprehensive analysis of steroid hormones is necessary. Here we cultured forskolin-stimulated NCI-H295R, a human adrenocortical carcinoma cell line, in the presence of a polyphenol and employed GC-MS to simultaneously determine the levels of nine steroid hormones (pregnenolone, progesterone, deoxycorticosterone, aldosterone, 17α-hydroxyprogesterone, dehydroepiandrosterone, androstenedione, testosterone, and estradiol) in cell culture supernatant. We found that daidzein, genistein, apigenin, hesperetin, naringenin, and eriodictyol significantly reduced deoxycorticosterone and androstenedione levels (p<0.05), suggesting inhibition of 3β-HSD by these polyphenols. Apigenin was more potent than other polyphenols in increasing the levels of pregnenolone and 17α-hydroxyprogesterone, suggesting that it inhibits cytochrome P450 (CYP) 17 and CYP21, as well as 3β-HSD. Real-time reverse transcription polymerase chain reaction showed that apigenin significantly downregulated the expression levels of 3β-HSD, CYP17, and CYP21 mRNA (p<0.05). This is the first study to demonstrate the inhibitory effects of apigenin on CYP17 and CYP21.
Application of Phase-shifting Method using Fourier Transform to Measurement of In-plane Displacement by Speckle Interferometry (2005)

Phase-shifting method using Fourier transform (PSM/FT) has been applied to measurement of in-plane displacement of a specimen. Thirty-two interference fringe patterns each of which has different phase of radian have been gathered from a specimen with in-plane displacement. Low-pass filtering by 2-D Fourier transform is used to suppress spatial noise of the fringe patterns. Fourier transform for PSM/FT is performed by use of the low-pass filtered 32 fringe patterns. Two kinds of specimens are used for experiment. One is a rectangular steel plate and the other one is a rectangular steel plate containing a circular hole at the center. In-plane displacement of each specimen is measured by PSM/FT, and calculated by finite element method (ANSYS) for comparison. The results are quite comparable, so that PSM/FT can be applied to measurement of in-plane displacement.
Assessment of the serotonin reuptake blocking property of YM992: Electrophysiological studies in the rat hippocampus and dorsal raphe (1999)

YM992 is a selective serotonin (5-HT) reuptake inhibitor and a 5-HT(2A) antagonist with potential antidepressant activity. As expected from a 5-HT reuptake inhibitor, which induces an accumulation of 5-HT in the dorsal raphe, YM992 inhibited the firing activity of these 5-HT neurons (ED50: 2.0+/-0.2 mg/kg, i.v.). This effect was reversed by the 5-HT(1A) antagonist WAY 100635. YM992 also dose-dependently prolonged the time for CA3 neurons to recover 50% of their firing rate following microiontophoretic applications of 5-HT, a reliable index of the function of the 5-HT reuptake carrier. In a second series of experiments, the adaptative properties of 5-HT neurons were examined during sustained administration of YM992 (20 mg/kg/day, s.c., delivered by osmotic minipumps) after 2 days of treatment. YM992 decreased by more than 60% the firing activity of the 5-HT neurons. There was a partial recovery of firing after 7 days and a complete one after 14 days of treatment in the presence of the minipump still delivering the drug. In a third series of experiments, the sensitivity of pre- and postsynaptic 5-HT(1A) receptors in the dorsal raphe and the dorsal hippocampus were assessed. The results showed that YM992 attenuated the inhibitory effect of intravenous administration of LSD and the 5-HT(1A) agonist 8-OH-DPAT on the firing activity of 5-HT neurons. As did the selective 5-HT reuptake inhibitor fluvoxamine, YM992 markedly increased the effectiveness of the electrical stimulation of ascending 5-HT fibres on firing activity of the postsynaptic hippocampus pyramidal neurons. This enhancement of 5-HT neurotransmission by YM992 was attributable to a desensitization of the terminal 5-HT(1B) autoreceptors since the postsynaptic 5-HT(1A) receptors in the hippocampus remained normosensitive.
HDAC2 as a new target to improve schizophrenia treatment (2012)

Keywords:: 5-HT2A receptorantipsychotic drugsepigeneticsG protein-coupled receptorhistone deacetylasemetabotropic glutamate 2 receptorschizophreniaserotonin
A Simple Chemical Method for the Preparation of Silver Surfaces for Efficient SERS (2002)

The relatively well-known mirror reaction method of forming silver films has been used to produce substrates for surface enhanced Raman scattering (SERS). The simple and convenient method produces a thin metal film on silicon that shows an order of magnitude superior surface enhancement properties when compared to a conventional SERS substrate made by vacuum evaporation. Of particular interest is that the method is ideal for coating atomic force microscope probes for apertureless scanning near-field spectroscopy which is usually made difficult by the damage caused by evaporative coating and annealing.
<title>Body language user interface (BLUI)</title> (1998)

We analyze a 3D skeletal representation of the user in spatial and temporal domains as a tool necessary to recognizing the gestures of drawing, picking and grabbing. The mechanisms of visual perception that are called upon in the imaginative process of artistic creation use those same tactile and kinesthetic pathways and structures in the brain which are employed when we manipulate the 3D world. We see, in fact, with our sensual bodies as well as with our eyes. Our interface is built on an analysis of pointing and gesturing and how they related to the perception of form in space. We report on our progress in implementing a body language user interface for artistic computer interaction, i.e., an human/computer interaction based on an analysis of how an artist uses her body in the act of creation. Using two synchronous TV cameras, we have videotaped an environment into which an artist moves, assumes a canonical (Da Vinci) pose and subsequently makes a series of simple gestures. The video images are processed to generate an animated 3D skeleton that corresponds to the skeleton of the artist. The locus of the path taken by the drawing hand is the source of a trace of particles. Our presentation shows the two simultaneous videos, the associated animated 3D skeleton, that skeleton as an instance of motion capture for a constrained model of a human skeleton and the trace of the path taken by the drawing hand.
Zinc-iron sulphide mineralization in tubes of hydrothermal vent worms (2001)

Nanocrystalline zinc-iron sulphide minerals were found within tubes of Alvinella pompejana , collected at 9°N on the East Pacific Rise, in a preliminary study carried out by conventional analytical transmission electron microscopy. Their structure is consistent with either the sphalerite or wurtzite polymorphs of ZnS. In contrast with sulphides usually observed in deep-sea hydrothermal environments, the unique sulphide observed within the exoskeleton of the pompeii worms has a (Zn 0.88 Fe 0.12 )S composition. The zinc-iron sulphide nanocrystals are grouped in submicrometer-sized clusters which form layers, concentrically to the proteinaceous tube axis. This is the first characterization of minerals precipitated within a biological matrix from hydrothermal vents organisms. These minerals represent a new example of zinc-iron biologically induced mineralization. Such layers of nanocrystalline zinc-iron sulphide minerals could be used as valuable markers of annelid tubes, in the growing field of studies focusing on fossilized paleo-hydrothermal vent systems.
Phage display screening for peptidic chitinase inhibitors (2008)

A phage display library with disulfide-cyclized peptides was screened for peptides binding to chitinases from Serratia marcescens. One of those peptides was found to efficiently inhibit chitinase A and two others were inhibitors of chitinase B. Complete substitutional analysis of all three peptides using cellulose-bound peptide spot synthesis revealed key interaction positions and allowed optimization of the chitinase B inhibitory peptides towards higher affinity, with inhibitory constants in the lower nanomolar range. Inhibition by all peptides proved to be competitive and highly specific for the chitinase used to select them, as shown with a series of chitinases from different organisms.
Discovery of (−)-7-Methyl-2-<i>exo</i>-[3′-(6-[<sup>18</sup>F]fluoropyridin-2-yl)-5′-pyridinyl]-7-azabicyclo[2.2.1]heptane, a Radiolabeled Antagonist for Cerebral Nicotinic Acetylcholine Receptor (α4β2-nAChR) with Optimal Positron Emission Tomography Imaging Properties (2008)

Several isomers of 7-methyl-2-exo-([(18)F]fluoropyridinyl-5'-pyridinyl)-7-azabicyclo[2.2.1]heptane have been developed as radioligands with optimized brain kinetics for PET imaging of nAChR. The binding assay demonstrated that all isomers are beta-nAChR selective ligands with Ki = 0.02-0.3 nM. The experimental lipophilicity values of all isomers were in the optimal range for the cerebral radioligands (log D7.4= 0.67-0.99). The isomers with higher binding affinity manifested slow baboon brain kinetics, whereas the isomer with the lowest binding affinity (Ki = 0.3 nM) ((-)-7-methyl-2- exo-[3'-(6-[(18)F]fluoropyridin-2-yl)-5'-pyridinyl]-7-azabicyclo[2.2.1]heptane, [(18)F](-)-6c) and greatest lipophilicity (log D 7.4 = 0.99) exhibited optimal brain kinetics. [(18)F](-)-6c manifests a unique combination of the optimally rapid brain kinetics, high BP and brain uptake, and favorable metabolic profile. Pharmacological studies showed that (-)-6c is an alpha4beta2-nAChR antagonist with low side effects in mice. This combination of imaging properties suggests that [(18)F]-(-)- 6c is a potentially superior replacement for 2-[(18)F]fluoro-A-85380 and 6-[(18)F]fluoro-A-85380, the only available nAChR PET radioligands for humans.
Extracellular Vesicles: Potential Roles in Regenerative Medicine (2014)

Extracellular vesicles (EV) consist of exosomes, which are released upon fusion of the multivesicular body with the cell membrane, and microvesicles, which are released directly from the cell membrane. EV can mediate cell-cell communication and are involved in many processes, including immune signaling, angiogenesis, stress response, senescence, proliferation, and cell differentiation. The vast amount of processes that EV are involved in and the versatility of manner in which they can influence the behavior of recipient cells make EV an interesting source for both therapeutic and diagnostic applications. Successes in the fields of tumor biology and immunology sparked the exploration of the potential of EV in the field of regenerative medicine. Indeed, EV are involved in restoring tissue and organ damage, and may partially explain the paracrine effects observed in stem cell-based therapeutic approaches. The function and content of EV may also harbor information that can be used in tissue engineering, in which paracrine signaling is employed to modulate cell recruitment, differentiation, and proliferation. In this review, we discuss the function and role of EV in regenerative medicine and elaborate on potential applications in tissue engineering.
Cover Image (2017)

The cover image, by Xiao Chen et al., is based on the Research Article Revisiting the structural collapse of a 52.3 m composite wind turbine blade in a full-scale bending test, DOI 10.1002/we.2087.
Mucosal immunity in the brushtail possum (<i>Trichosurus vulpecula</i>): Detection of antibody in serum and at female reproductive sites after intranasal immunization (2002)

Vaccination strategies for the brushtail possum, which rely upon stimulation of mucosal immunity, are being developed for biocontrol purposes. As little is known about how to stimulate possum immune responses via a mucosal site, groups of possums were immunized intranasally with keyhole limpet haemocyanin (KLH) alone or in combination with known or novel mucosal adjuvants. Antigen-specific antibody titres in female reproductive secretions were measured by ELISA and compared with antibody titres in the serum. Antigen-induced lymphocyte proliferative responses were measured as an indicator of cell-mediated responses. Intranasal immunization with KLH alone stimulated a weak serum antibody response that was significantly increased when KLH was given with cholera toxin subunit B (CTB), recombinant possum tumour necrosis factor alpha (TNF alpha) or live Mycobacterium bovis bacillus Calmette Guerin (BCG). Antibody titres in secretions from ovarian follicles and the uterus were very low in animals administered KLH alone. Significantly higher antibody titres to KLH were present in the reproductive secretions of possums immunized with KLH plus CTB, BCG or heat-killed Mycobacterium vaccae. Antibody titres were lower in mucosal secretions than in the serum, but there was a significant correlation between the two. In addition, coadministration of live BCG with KLH produced a strong antigen-specific cell-mediated response to KLH. This study has shown that an immune response to a protein antigen can be stimulated in possums by intranasal immunization and that antigen-specific antibodies can be detected in secretions from the female reproductive tract.