gebhart/patrepeval huggingface dataset:
Development and Validation of Digital Enzyme-Linked Immunosorbent Assays for Ultrasensitive Detection and Quantification of Clostridium difficile Toxins in Stool (2015)

The currently available diagnostics for Clostridium difficile infection (CDI) have major limitations. Despite mounting evidence that toxin detection is paramount for diagnosis, conventional toxin immunoassays are insufficiently sensitive and cytotoxicity assays too complex; assays that detect toxigenic organisms (toxigenic culture [TC] and nucleic acid amplification testing [NAAT]) are confounded by asymptomatic colonization by toxigenic C. difficile. We developed ultrasensitive digital enzyme-linked immunosorbent assays (ELISAs) for toxins A and B using single-molecule array technology and validated the assays using (i) culture filtrates from a panel of clinical C. difficile isolates and (ii) 149 adult stool specimens already tested routinely by NAAT. The digital ELISAs detected toxins A and B in stool with limits of detection of 0.45 and 1.5 pg/ml, respectively, quantified toxins across a 4-log range, and detected toxins from all clinical strains studied. Using specimens that were negative by cytotoxicity assay/TC/NAAT, clinical cutoffs were set at 29.4 pg/ml (toxin A) and 23.3 pg/ml (toxin B); the resulting clinical specificities were 96% and 98%, respectively. The toxin B digital ELISA was 100% sensitive versus cytotoxicity assay. Twenty-five percent and 22% of the samples positive by NAAT and TC, respectively, were negative by the toxin B digital ELISA, consistent with the presence of organism but minimal or no toxin. The mean toxin levels by digital ELISA were 1.5- to 1.7-fold higher in five patients with CDI-attributable severe outcomes, versus 68 patients without, but this difference was not statistically significant. Ultrasensitive digital ELISAs for the detection and quantification of toxins A and B in stool can provide a rapid and simple tool for the diagnosis of CDI with both high analytical sensitivity and high clinical specificity.
Fast Non-blocking N×N Optical Switch Using Diffractive MOEMS (2015)

We have developed a scalable free-space optical switch with a 12 microsecond reconfiguration time that can be implemented into an all-optical-cross connect for data communication architecture, or as a wavelength selective switch in a CDC ROADM for telecommunication networks. The foundation of the switch is the Texas Instruments DLP™ MOEMS that is used as a diffractive element displaying computer generated holograms to redirect the signal from any port to any port.
Purification, Characterisation and cDNA Cloning of an Antimicrobial Peptide from <i>Macadamia Integrifolia</i> (1997)

An antimicrobial peptide with no significant amino acid sequence similarity to previously described peptides has been isolated from the nut kernels of Macadcamia integrifolia. The peptide, termed MiAMP1, is highly basic with an estimated pI of 10.1, a mass of 8.1 kDa and contains 76 amino acids including 6 cysteine residues. A cDNA clone containing the entire coding region corresponding to the peptide was obtained. The deduced amino acid sequence of the cDNA indicated a 26-amino-acid signal peptide at the N-terminus of the preprotein. Purified MiAMP1 inhibited the growth of a variety of fungal, oomycete and gram-positive bacterial phytopathogens in vitro. Some pathogens exhibited close to 100% inhibition in less than 1 microM peptide (5 microg/ml). Antimicrobial activity was diminished against most, but not all, microbes in the presence of calcium and potassium chloride salts (1 mM and 50 mM, respectively). MiAMP1 was active against bakers yeast, was inactive against Escherichia coli and was non-toxic to plant and mammalian cells. Analysis of genomic DNA indicated that MiAMP1 was encoded on a single copy gene containing no introns. The MiAMP1 gene may prove useful in genetic manipulations to increase disease resistance in transgenic plants.
The proposed multimodal mechanism of action of cannabidiol (CBD) in epilepsy: modulation of intracellular calcium and adenosine-mediated signaling (P5.5-007) (2019)

We present preclinical evidence summarizing CBD’s leading mechanisms of action in epilepsy.
Towards photonic ink (P‐ink): a polychrome, fast response metallopolymer gel photonic crystal device (2003)

Abstract We demonstrate here a new kind of planarized and oriented colloidal photonic crystal device whose optical stop‐band position, width and intensity can be reversibly redox and solvent tuned over a broad wavelength range by an anisotropic expansion of the photonic lattice. The material is composed of silica microspheres in a matrix of crosslinked polyferrocenylsilane [1] , a metallopolymer network with a continuously variable state of oxidation [2] . Optical data was fitted using a scalar wave approximation, with a congruence to experimental data, allowing facile extraction of information concerning polymer swelling behaviour. The chemomechanical polychrome optical response of the material was exceptionally fast, attaining its fully swollen state from the dry shrunken state on a sub‐second time‐scale.
All-Organic Electrochromic Spandex (2010)

Herein we describe the preparation and characterization of reflective-type electrochromic devices using stretchable, conductive fabric electrodes. Two fabrics were used in this study: woven stainless steel mesh and Lycra spandex impregnated with a conducting polymer (poly[3,4-ethylenedioxythiophene]-poly[styrene sulfonate], PEDOT-PSS). Electrochromic polymers were prepared on the surface of these fabric electrodes and devices were assembled. The time taken for the electrochromic polymer to switch between colored states in devices prepared with stainless steel electrodes (conductivity ca. 9,800 S/cm) was ca. 0.3 s, whereas that using PEDOT-PSS loaded Lycra (conductivity ca. 0.1 S/cm) was a few seconds. The iris effect was evaluated for each of the device architectures, showing no effect for steel mesh/steel mesh devices and a propagating front for spandex-based devices. The electrochromic spandex functioned in solution while being stretched. In addition, stenciled devices were built. Such fabric electrochromic devices represent a critical step toward the realization of totally chameleonic fabric.
Multichannel phase-shifting lateral-shear interferometer (1985)

For lateral shearing interferometry, interferograms from two orthogonally sheared directions for complete optical path difference (OPD) are required. We are proposing a new approach for a real-time lateral shear interferometry by applying a phase-shifting method 1 to a double-frequency crossed-grating lateral shear interferometer (LSI). 2 The double-frequency crossed-grating LSI produces four interferograms, two from ±1 orders of x and y directions, respectively. If we introduce a constant phase-shift Δ to the interferograms in the opposite direction (+Δ for +1 orders and −Δ for −1 orders), the slope data of the OPD can be simultaneously calculated as arctangent values of the four intensity measurements. The instantaneous nature of phase shifting 3 to the multiple interferograms allows us to measure the wave fronts from pulsed light sources using array detectors and digital computer analysis.
In Silico Screening on the Three-dimensional Model of the Plasmodium vivax SUB1 Protease Leads to the Validation of a Novel Anti-parasite Compound (2013)

Widespread drug resistance calls for the urgent development of new antimalarials that target novel steps in the life cycle of Plasmodium falciparum and Plasmodium vivax. The essential subtilisin-like serine protease SUB1 of Plasmodium merozoites plays a dual role in egress from and invasion into host erythrocytes. It belongs to a new generation of attractive drug targets against which specific potent inhibitors are actively searched. We characterize here the P. vivax SUB1 enzyme and show that it displays a typical auto-processing pattern and apical localization in P. vivax merozoites. To search for small PvSUB1 inhibitors, we took advantage of the similarity of SUB1 with bacterial subtilisins and generated P. vivax SUB1 three-dimensional models. The structure-based virtual screening of a large commercial chemical compounds library identified 306 virtual best hits, of which 37 were experimentally confirmed inhibitors and 5 had Ki values of <50 μM for PvSUB1. Interestingly, they belong to different chemical families. The most promising competitive inhibitor of PvSUB1 (compound 2) was equally active on PfSUB1 and displayed anti-P. falciparum and Plasmodium berghei activity in vitro and in vivo, respectively. Compound 2 inhibited the endogenous PfSUB1 as illustrated by the inhibited maturation of its natural substrate PfSERA5 and inhibited parasite egress and subsequent erythrocyte invasion. These data indicate that the strategy of in silico screening of three-dimensional models to select for virtual inhibitors combined with stringent biological validation successfully identified several inhibitors of the PvSUB1 enzyme. The most promising hit proved to be a potent cross-inhibitor of PlasmodiumSUB1, laying the groundwork for the development of a globally active small compound antimalarial.
An FPGA-Based Vision Prosthesis Prototype: Implementing an Efficient Multiplexing Method for Addressing Electrodes (2005)

A prototype of an epi-retinal vision prosthesis based upon an efficient electrode addressing schema has been developed. This system has the ability to stimulate multiple electrode regions simultaneously, hence greatly improving the maximum rate of stimulation compared to many currently available neural stimulation devices based on serial stimulation protocols. To minimize the problem of cross talk between stimulating electrodes, a hexagon layout of electrodes was implemented. Basic tests were completed using a field programmable gate array logic system driving analogue circuitry to inject current into physiological saline via electrodes in hexagon arrangements and in a simple paired arrangement. The hexagon layout of electrodes was shown to clearly reduce the interaction between multiple current sources and hence cross talk.
ChemInform Abstract: PYRAZOLO(3,4‐D)PYRIMIDINE RIBONUCLEOSIDES AS ANTICOCCIDIALS. 1. SYNTHESIS AND D ACTIVITY OF SOME NUCLEOSIDES OF PURINES AND 4‐(ALKYLTHIO)PYRAZOLO(3,4‐D)PYRIMIDINES (1982)

Abstract Aus den Mercaptoverbindungen (I) erhält man die Thioverbindungen (II).
Biochemical Mechanism of FIT Proteins in Mediating Lipid Droplet Formation (2012)

The process of lipid droplet (LD) formation is an evolutionarily conserved process among all eukaryotes and plays an important role in both cellular physiology and disease. Recently, our lab discovered F at storage‐ I nducing T rans m embrane proteins 1 & 2 (FIT1/FITM1 and FIT2/FITM2) as an evolutionarily‐conserved family of proteins involved in fat storage. These proteins have distinct tissue distributions, are both exclusively localized to the endoplasmic reticulum, mediate triglyceride (TAG)‐rich LD accumulation when overexpressed, but do not synthesize TAG. Our lab has shown that FIT proteins purified in detergent micelles directly bind to TAG with specificity and saturation binding kinetics in order to mediate LD formation. A FIT2 gain‐of‐function mutant that forms larger LDs, FLL(157–9)AAA, showed a significant increase in TAG binding, while FIT1 and a FIT2 partial loss‐of‐function mutant, N80A, displayed abrogated TAG binding, producing smaller LDs relative to wild‐type FIT2. Here, we present biochemical evidence supporting a unique two‐step mechanism for LD formation via FIT2. Attempts to reconstitute the activity of FIT proteins will also be presented. In summary, FIT proteins are the first transmembrane domain‐containing proteins shown to bind TAG, a function that is important for FIT‐mediated LD formation.
High temperature regenerative H/sub 2/S sorbents (1988)

Efficient, regenerable sorbents for removal of H.sub.2 S from high temperature gas streams comprise porous, high surface area particles. A first class of sorbents comprise a thin film of binary oxides that form a eutectic at the temperature of the gas stream coated onto a porous, high surface area refractory support. The binary oxides are a mixture of a Group VB or VIB metal oxide with a Group IB, IIB or VIII metal oxide such as a film of V-Zn-O, V-Cu-O, Cu-Mo-O, Zn-Mo-O or Fe-Mo-O coated on an alumina support. A second class of sorbents consist of particles of unsupported mixed oxides in the form of highly dispersed solid solutions of solid compounds characterized by small crystallite size, high porosity and relatively high surface area. The mixed oxide sorbents contain one Group IB, IIB or VIIB metal oxide such as copper, zinc or manganese and one or more oxides of Groups IIIA, VIB or VII such as aluminum, iron or molybdenum. The presence of iron or aluminum maintains the Group IB, IIB or VIIB metal in its oxidized state. Presence of molybdenum results in eutectic formation at sulfidation temperature and improves the efficiency of the sorbent.
Growth Factors and Corneal Epithelium (1988)

Regeneration of corneal epithelium following injury is essential for visual rehabilitation. A limited number of approaches are available for treating patients who fail to heal epithelial injuries adequately. The presence of specific receptors for epidermal growth factor (EGF) on epithelial cells suggests that this potent mitogen may play a role in normal epithelial wound healing. Topical application of biosynthetic human EGF significantly accelerated epithelial regeneration in primates following epikeratophakia surgery. Epidermal growth factor alone and with fibronectin accelerated epithelial regeneration of rabbits following mild alkali burns. Since prolonged exposure of cells to EGF is necessary to induce mitosis, the dynamics of EGF in the eye and with various lenses was studied. When applied in methylcellulose-based eye drops, 90% of the EGF was lost from tear film within 10 min, while a small amount (10%) remained associated with conjuctival tissue. Soft contact lenses or epikeratophakia lenticles took up substantial amounts of EGF (50 μg) and released 85% of the EGF within 24 h, with a half-life of 4 h in vitro. Epidermal growth factor did not diffuse through corneas or lenticles and did not promote epithelial down-growth along sutures in primate corneas. These results suggest that biosynthetic growth factors may be useful in the treatment of some epithelial injuries.
Human T-Cell Leukemia (Lymphotropic) Retroviruses: The HTLV Family and their Role in Leukemias, Lymphomas and AIDS (1985)

The human T-cell leukemia/lymphoma (lymphotrophic) viruses comprise a family of human retroviruses whch exert disparate effects on human T-cells and which are associated with at least two forms of disease. HTLV-I and -II exert proliferative effects on T-cells, while the predominant effect of HTLV-III is a cytopathic one. Evidence for the association of HTLV-I with adult T-cell leukemia and for the association of HTLV-III with the acquired immunodeficiency syndrome is reviewed here. Current thoughts on possible mechanisms of these viral pathogenic effects are discussed.
A novel response of cancer cells to radiation involves autophagy and formation of acidic vesicles. (2001)

The mechanisms underlying neoplastic epithelial cell killing by ionizing radiation are largely unknown. We discovered a novel response to radiation manifested by autophagy and the development of acidic vesicular organelles (AVO). Acidification of AVO was mediated by the vacuolar H+-ATPase. Staining with the lysosomotropic agent acridine orange enabled us to quantify AVO accumulation and to demonstrate their time- and dose-dependent appearance. The appearance of AVO occurred in the presence of the pan-caspase inhibitor z-Val-Ala-Asp(Ome)-fluoromethyl ketone, but was inhibited by 3-methyladenine, an inhibitor of autophagy. The accretion of AVO in surviving progenies of irradiated cells, and the increased incidence of clonogenic death after inhibition of vacuolar H+-ATPase suggest that formation of acidic organelles represents a novel defense mechanism against radiation damage.
Interferon‐α and antisense K‐<i>ras</i> RNA combination gene therapy against pancreatic cancer (2004)

Interferon alpha (IFN-alpha) is used worldwide for the treatment of a variety of cancers. For pancreatic cancer, recent clinical trials using IFN-alpha in combination with standard chemotherapeutic drugs showed some antitumor activity of the cytokine, but the effect was not significant enough to enlist pancreatic cancer as a clinically effective target of IFN-alpha. In general, an improved therapeutic effect and safety are expected for cytokine therapy when given in a gene therapy context, because the technology would allow increased local concentrations of this cytokine in the target sites. In this study, we first examined the antiproliferative effect of IFN-alpha gene transduction into pancreatic cancer cells. The expression of IFN-alpha effectively induced growth suppression and cell death in pancreatic cancer cells, an effect which appeared to be more prominent when compared with other types of cancers and normal cells. Another strategy we have been developing for pancreatic cancer targets its characteristic genetic aberration, K-ras point mutation, and we reported that the expression of antisense K-ras RNA significantly suppressed the growth of pancreatic cancer cells. When these two gene therapy strategies are combined, the expression of antisense K-ras RNA significantly enhanced IFN-alpha-induced cell death (1.3- to 3.5-fold), and suppressed subcutaneous growth of pancreatic cancer cells in mice. Because the 2',5'-oligoadenylate synthetase/RNase L pathway, which is regulated by IFN and induces apoptosis of cells, is activated by double-strand RNA, it is plausible that the double-strand RNA formed by antisense and endogenous K-ras RNA enhanced the antitumor activity of IFN-alpha. This study suggested that the combination of IFN-alpha and antisense K-ras RNA is a promising gene therapy strategy against pancreatic cancer.
Antipsychotic activity of substituted .gamma.-carbolines (1987)

Several novel substituted gamma-carbolines were synthesized and examined in a series of in vitro and in vivo pharmacological tests to determine potential antipsychotic activity. Most compounds were orally active in blocking the conditioned avoidance response (CAR) in rats but did not antagonize apomorphine-induced stereotyped behavior. Compound 17 (Wy-47,384), a gamma-carboline with a 3-(3-pyridinyl)propyl side chain, was selected for development as an atypical antipsychotic agent because of its potent and selective profile in preclinical psychopharmacological tests. It blocked CAR in rats with an AB50 of 14 mg/kg po, showed weak affinity for the D2 receptor site (Ki = 104 nM), and showed differential potency in antagonizing apomorphine-induced stereotyped behavior (ED50 = 11 mg/kg ip) and climbing behavior (ED50 = 4 mg/kg ip). Such activities are suggestive of antipsychotic efficacy combined with a low potential for extrapyramidal side effect (EPS) liability.
Vascular ADAM17 as a Novel Therapeutic Target in Mediating Cardiovascular Hypertrophy and Perivascular Fibrosis Induced by Angiotensin II (2016)

Angiotensin II (AngII) has been strongly implicated in hypertension and its complications. Evidence suggests the mechanisms by which AngII elevates blood pressure and enhances cardiovascular remodeling and damage may be distinct. However, the signal transduction cascade by which AngII specifically initiates cardiovascular remodeling, such as hypertrophy and fibrosis, remains insufficiently understood. In vascular smooth muscle cells, a metalloproteinase ADAM17 mediates epidermal growth factor receptor transactivation, which may be responsible for cardiovascular remodeling but not hypertension induced by AngII. Thus, the objective of this study was to test the hypothesis that activation of vascular ADAM17 is indispensable for vascular remodeling but not for hypertension induced by AngII. Vascular ADAM17-deficient mice and control mice were infused with AngII for 2 weeks. Control mice infused with AngII showed cardiac hypertrophy, vascular medial hypertrophy, and perivascular fibrosis. These phenotypes were prevented in vascular ADAM17-deficient mice independent of blood pressure alteration. AngII infusion enhanced ADAM17 expression, epidermal growth factor receptor activation, and endoplasmic reticulum stress in the vasculature, which were diminished in ADAM17-deficient mice. Treatment with a human cross-reactive ADAM17 inhibitory antibody also prevented cardiovascular remodeling and endoplasmic reticulum stress but not hypertension in C57Bl/6 mice infused with AngII. In vitro data further supported these findings. In conclusion, vascular ADAM17 mediates AngII-induced cardiovascular remodeling via epidermal growth factor receptor activation independent of blood pressure regulation. ADAM17 seems to be a unique therapeutic target for the prevention of hypertensive complications.
300 mm SGOI/strain-Si for high-performance CMOS (2005)

In this article, a manufacturable material technology has been developed to produce highly uniform 300 mm SSOI substrates. The focus of this work has been on reducing defects in SGOI and strain Si layers, while maintaining high degree of relaxation/strain in these layers. Furthermore, physics of SGOI formation has been understood to the extent that key physical properties of the final SGOI layer can be accurately predicted based on the knowledge of the initial structure and subsequent processing.
Degenerate two-photon-absorption spectral studies of highly two-photon active organic chromophores (2004)

Degenerate two-photon absorption (TPA) spectral properties of five AFX chromophore solutions have been studied using a single and spectrally dispersed sub-picosecond white-light continuum beam. In a specially designed optical configuration, optical pathways inside the sample solution for different spectral components of the focused continuum beam were spatially separated from each other. Thus, the nondegenerate TPA processes coming from different spectral components can be eliminated, and the direct nonlinear absorption spectrum attributed to degenerate TPA processes can be readily obtained. Using this new technique, the complete TPA spectra for these five highly two-photon-active compounds (AF-380, AF-350, AF-295, AF-270, and AF-50) were obtained in the spectral range from 600 to 950 nm on an absolute scale of TPA cross section. The relationship between the molecular structures and their TPA spectral behaviors are discussed. In general the measured TPA spectra are not identical with the linear absorption spectra on the scale of absorbed photon(s) energy. Moreover, for some sample (such as AF-380), the TPA spectrum is totally different from the linear spectrum, which implies the difference of molecular transition pathways and selection rules for one- and two-photon excitation processes. At high excitation intensity levels (>or=15 GW/cm(2)), the saturation behavior of TPA transition can be observed obviously in AF-350 and AF-380 solutions that exhibit much higher nonlinear absorptivity than the other chromophores investigated.