gebhart/patrepeval huggingface dataset:
A cDNA encoding protein kinase C identifies two species of mRNA in brain and GH3 cells. (1986)

Antiserum raised against purified protein kinase C (the Ca2+/phospholipid-dependent enzyme) (Ballester, R., and rosen, O. M. (1985) J. Biol. Chem. 260, 15194-15199) was used to screen a rat brain cDNA library in the prokaryotic expression vector lambda gt11. Three positive clones were isolated and shown to have overlapping restriction endonuclease maps. The positive recombinant phage with the longest cDNA insert (1.4 kilobases (kb)) was used for production of a beta-galactosidase fusion protein. Rabbit antiserum raised against the fusion protein recognized a single rat brain polypeptide of Mr 80,000 which was identified as protein kinase C by the following criteria: electrophoretic co-migration with purified protein kinase C, partial co-purification with protein kinase C, and disappearance from the cytosol of phorbol 12-myristate 13-acetate-treated GH3 cells. The nick-translated cDNA hybridized with two mRNAs, 8 kb and 3.5 kb, whose tissue distribution was in agreement with that reported for protein kinase C activity. Hybrid selection with immobilized cDNA identified mRNA encoding a protein of Mr 80,000 that could be precipitated by antibody to purified protein kinase C. Treatment of GH3 cells with phorbol 12-myristate 13-acetate, which promotes translocation and subsequent degradation of protein kinase C, did not alter the level of either message.
Live bacterial vaccines--a review and identification of potential hazards. (2006)

The use of live bacteria to induce an immune response to itself or to a carried vaccine component is an attractive vaccine strategy. Advantages of live bacterial vaccines include their mimicry of a natural infection, intrinsic adjuvant properties and their possibility to be administered orally. Derivatives of pathogenic and non-pathogenic food related bacteria are currently being evaluated as live vaccines. However, pathogenic bacteria demands for attenuation to weaken its virulence. The use of bacteria as vaccine delivery vehicles implies construction of recombinant strains that contain the gene cassette encoding the antigen. With the increased knowledge of mucosal immunity and the availability of genetic tools for heterologous gene expression the concept of live vaccine vehicles gains renewed interest. However, administration of live bacterial vaccines poses some risks. In addition, vaccination using recombinant bacteria results in the release of live recombinant organisms into nature. This places these vaccines in the debate on application of genetically modified organisms. In this review we give an overview of live bacterial vaccines on the market and describe the development of new live vaccines with a focus on attenuated bacteria and food-related lactic acid bacteria. Furthermore, we outline the safety concerns and identify the hazards associated with live bacterial vaccines and try to give some suggestions of what to consider during their development.
A Powerful Combinatorial Screen to Identify High‐Affinity Terbium(III)‐Binding Peptides (2003)

Lanthanide-binding tags (LBTs) are protein fusion partners consisting of encoded amino acids that bind lanthanide ions with high affinity. Herein, we present a new screening methodology for the identification of new LBT sequences with high affinity for Tb(3+) ions and intense luminescence properties. This methodology utilizes solid-phase split-and-pool combinatorial peptide synthesis. Orthogonally cleavable linkers allow an efficient two-step screening procedure. The initial screen avoids the interference caused by on-bead screening by photochemically releasing a portion of the peptides into an agarose matrix for evaluation. The secondary screen further characterizes each winning sequence in a defined aqueous solution. Employment of this methodology on a series of focused combinatorial libraries yielded a linear peptide sequence of 17 encoded amino acids that demonstrated a 140-fold increase in affinity (57 nM dissociation constant, K(D)) over previously reported lanthanide-binding peptides. This linear sequence was macrocyclized by introducing a disulfide bond between flanking cysteine residues to produce a peptide with a 2-nM apparent dissociation constant for Tb(3+) ions.Supporting information for this article is available on the WWW under http://www.chemphyschem.org or from the author.
iCaRL: Incremental Classifier and Representation Learning (2017)

A major open problem on the road to artificial intelligence is the development of incrementally learning systems that learn about more and more concepts over time from a stream of data. In this work, we introduce a new training strategy, iCaRL, that allows learning in such a class-incremental way: only the training data for a small number of classes has to be present at the same time and new classes can be added progressively. iCaRL learns strong classifiers and a data representation simultaneously. This distinguishes it from earlier works that were fundamentally limited to fixed data representations and therefore incompatible with deep learning architectures. We show by experiments on CIFAR-100 and ImageNet ILSVRC 2012 data that iCaRL can learn many classes incrementally over a long period of time where other strategies quickly fail.
<title>Laser optoacoustic tomography of layered tissues: signal processing</title> (1997)

Laser optoacoustic imaging experiments in biological tissues in vivo are presented along with the theoretical signal analysis procedure. The laser optoacoustic imaging system (LOIS) can operate in the reflection mode with emphasis on high z-axial (in-depth) resolution (up to 10 - 20 micrometers). Two examples of LOIS applications for non- invasive in vivo medical diagnostics are presented and discussed: (1) characterization of layered structure of port- wine stains, and (2) measurements of skin melanoma thickness. Potential miniaturization of LOIS for endoscopy applications is also discussed. The z-axial profiles of laser-induced pressure were shown to contain diagnostic information on location, dimensions and optical properties of tissue layers. Time-resolved signals detected by piezoelectric transducers were corrected for distortions such as diffraction and acoustic attenuation that occur upon pressure wave propagation in tissue. Wavelet transform applied to signals of laser- induced acoustic emission yielded high contrast pressure profiles with substantial signal-to-noise ratio.
T/Tn Antigen Vaccine is Effective and Safe in Preventing Recurrence of Advanced Human Breast Carcinoma (1994)

For nearly 20 yrs, we used T/Tn antigen vaccine in safe, specific, effective, long-term intradermal vaccination against recurrence of advanced breast carcinoma. Treatment is ad infinitum. All 18 breast carcinoma patients treated, pTNM Stages IV (6), III (6), and II (6), survived > 5 yrs postoperatively; 10 survived > 10 to > 18 yrs; of the latter, three patients each are Stages III and IV. Five additional 5 yr survivors have not yet reached 10 yrs. The probability that our survival results are due to chance, with NCI "1991 Standard PDQ Data" as control, for all three stages taken together is: 5-yr survival: p < 1 x 10(-8); 10-yr survival: p < 1 x 10(-5). There were no untoward side effects. The vaccination area presented as a delayed-type hypersensitivity reaction, but at variance with the PPD reaction, with significant inflammation, increase of helper T lymphocytes and decrease of the T suppressor/cytotoxic cell ratio.
Dynamic wavelength tuning characteristics of the 1.5-μm three-section DBR lasers: analysis and experiment (1995)

We present a detailed theoretical analysis of the static and dynamic tuning characteristics of 1.55-/spl mu/m region three-section tunable DBR lasers under discrete tuning and under continuous tuning. We have analyzed the oscillating wavelength, the Bragg wavelength, and output power characteristics using the rate equation that considers the thermal effect, simultaneously analyzed the heat transfer equation, considering the heat transfer among passive waveguides, the LD chip, the submount, and the heat sink. We experimentally confirm the static and dynamic wavelength tuning characteristics using a highly accurate heterodyne measurement system. Static and dynamic characteristics simulated using the three-section DBR laser model and the thermal model agree with the experimental results presented in this paper.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Biomarkers of Cervicovaginal Inflammation for the Assessment of Microbicide Safety (2009)

The human cervicovaginal mucosa is the primary target of HIV-1 infection during male to female transmission. This tissue contains the the full spectrum of cell types and immune modulators that comprise both the innate and adaptive arms of the immune system. Mounting evidence indicates that mucosal epithelial cells are sentinels of the female reproductive tract, producing innate immune mediators that control the vaginal microflora under normal conditions. Recent studies, however, indicate that certain factors secreted in response to another pathogen or after exposure to a vaginal product may in fact enhance infection by HIV-1. Mucosal inflammation and CD4 cell activation as well as disruption of TLR function and epithelial integrity represent potential causes for such effect. It is therefore important to make sure that vaginal products, including microbicides, do not disrupt the structure or function of the cervicovaginal mucosa. Although a number of biomarkers have been linked to microbicide-induced cervicovaginal inflammation and many of these markers have been measured in preclinical and clinical assays, there are currently no data that demonstrate a correlation between any one marker and susceptibility to HIV-1 infection in humans. To date, the lack of a validated biomarker of cervicovaginal safety represents a gap in the knowledge base that hinders the rational and expeditious selection of microbicide candidates entering clinical trials. Current discovery efforts and preclinical assessment of microbicide safety use an integrated sequential evaluation system that includes cell-based models, explant-based models, and animal-based models. Relevant research in these areas is yielding new assays and biomarkers that, if validated, will be essential to the rational selection of microbicide candidates for efficacy trials.
Iron Oxide Nanoparticles for Magnetically-Guided and Magnetically-Responsive Drug Delivery (2015)

In this review, we discuss the recent advances in and problems with the use of magnetically-guided and magnetically-responsive nanoparticles in drug delivery and magnetofection. In magnetically-guided nanoparticles, a constant external magnetic field is used to transport magnetic nanoparticles loaded with drugs to a specific site within the body or to increase the transfection capacity. Magnetofection is the delivery of nucleic acids under the influence of a magnetic field acting on nucleic acid vectors that are associated with magnetic nanoparticles. In magnetically-responsive nanoparticles, magnetic nanoparticles are encapsulated or embedded in a larger colloidal structure that carries a drug. In this last case, an alternating magnetic field can modify the structure of the colloid, thereby providing spatial and temporal control over drug release.
Glutamate and other CSF amino acids in Alzheimer's disease (1992)

The authors compared CSF amino acid levels of 10 patients with mild to moderate dementia and probable Alzheimer's disease who had never received antidepressant or neuroleptic medication with those of 10 normal subjects of similar age. The Alzheimer's patients had significantly higher levels of CSF glutamate. This finding was not related to age, sex, or severity of dementia. Elevated CSF glutamate may reflect greater glutamatergic activity early in the course of Alzheimer's disease. The authors speculate that the excitotoxic effects of glutamate may contribute to progressive neuronal loss in Alzheimer's disease.
AlGaN/GaN HEMTs on SiC with f/sub T/ of over 120 GHz (2002)

AlGaN/GaN high electron mobility transistors (HEMTs) grown on semi-insulating SiC substrates with a 0.12 μm gate length have been fabricated. These 0.12-μm gate-length devices exhibited maximum drain current density as high as 1.23 A/mm and peak extrinsic transconductance of 314 mS/mm. The threshold voltage was -5.2 V. A unity current gain cutoff frequency (f <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">T</sub> ) of 121 GHz and maximum frequency of oscillation (f <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">max</sub> ) of 162 GHz were measured on these devices. These f <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">T</sub> and f <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">max</sub> values are the highest ever reported values for GaN-based HEMTs.
Proteomic and Bioinformatic Characterization of Extracellular Vesicles Released from Human Macrophages upon Influenza A Virus Infection (2016)

Influenza A viruses (IAVs) are aggressive pathogens that cause acute respiratory diseases and annual epidemics in humans. Host defense against IAV infection is initiated by macrophages, which are the principal effector cells of the innate immune system. We have previously shown that IAV infection of human macrophages is associated with robust secretion of proteins via conventional and unconventional protein release pathways. Here we have characterized unconventional, extracellular vesicle (EV)-mediated protein secretion in human macrophages during IAV infection using proteomics, bioinformatics, and functional studies. We demonstrate that at 9 h postinfection a robust EV-mediated protein secretion takes place. We identified 2359 human proteins from EVs of IAV-infected macrophages compared with 1448 proteins identified from EVs of control cells. Bioinformatic analysis shows that many proteins involved in translation, like components of spliceosome machinery and the ribosome, are secreted in EVs in response to IAV infection. Our data also shows that EVs derived from IAV-infected macrophages contain fatty acid-binding proteins, antiviral cytokines, copper metabolism Murr-1 domain proteins, and autophagy-related proteins. In addition, our data suggest that secretory autophagy plays a role in activating EV-mediated protein secretion during IAV infection.
Impact of a New Direct-Fed Microbial on Intake and Ruminal pH (2009)

Phencyclidine was previously shown to allosterically increase the apparent affinity of the dihydropyridine ( [3H]nitrendipine) calcium antagonist binding site in a lysed synaptosomal membrane preparation of rat forebrain. Treatment of a similar preparation of mouse forebrain with 4-isothiocyanato-1-(1-phenylcyclohexyl) piperidine (FOURPHIT), an acylating phencyclidine derivative, resulted in a concentration dependent (0.1-10 microM), irreversible, increase in the apparent affinity of [3H]nitrendipine in contrast to the effects of phencyclidine which were reversible. The FOURPHIT isomer, 1-[1-(3-isothiocyanatophenyl) cyclohexyl] piperidine (METAPHIT), (10 microM) also irreversibly increased the apparent affinity of [3H]nitrendipine, but was much less efficacious than FOURPHIT. Phencyclidine blocked the irreversible increase in the apparent affinity of [3H]nitrendipine produced by FOURPHIT. The interactions of multivalent cations and the calcium antagonist diltiazem with the [3H]nitrendipine binding site were altered following treatment of membranes with FOURPHIT. These studies suggest that FOURPHIT irreversibly interacts with the same sites as PCP, and thus may be a useful tool with which to further probe both the behavioral and biochemical interactions between phencyclidine and the dihydropyridine calcium antagonist binding site.
Improvement of Pharmacological Properties of Irreversible Thyroid Receptor Coactivator Binding Inhibitors (2009)

We have previously reported the discovery and preliminary structure activity relationships of a series of beta-aminoketones that disrupt the binding of coactivators to TR. However, the most active compounds had moderate inhibitory potency and relatively high cytotoxicity, resulting in narrow therapeutic index. Additionally, preliminary evaluation of in vivo toxicology revealed a significant dose related cardiotoxicity. Here we describe the improvement of pharmacological properties of thyroid hormone receptor coactivator binding inhibitors. A comprehensive survey of the effects of substitutents in key areas of the molecule was carried out based on mechanistic insight from the earlier report. This study revealed that both electron withdrawing and hydrophobic substituents on the aromatic ring led to higher potency. On the other hand, moving from an alkyl to a sulfonyl alkyl side chain led to reduced cytotoxicity. Finally, utilization of amine moieties having low pK(a)'s resulted in lowered ion channel activity without any loss of pharmacological activity.
Parabacteroides gordonii sp. nov., isolated from human blood cultures (2009)

Three bacterial strains that had been isolated from human blood cultures, MS-1(T), MS-2 and MS-3, were characterized for their phenotypic and biochemical features, cellular fatty acid profiles, menaquinone profiles and phylogenetic positions based on 16S rRNA gene sequence analysis. 16S rRNA gene sequence analysis showed that the isolates were members of the genus Parabacteroides. These isolates were most closely related to Parabacteroides goldsteinii JCM 13446(T), with 95.9 % 16S rRNA gene sequence similarity. The levels of sequence similarity among the three strains were 99.7-100 %. The isolates were obligately anaerobic, non-pigmented, non-spore-forming, non-motile, Gram-negative and rod-shaped. The strains grew on media containing 20 % bile. These strains could be differentiated from P. goldsteinii by their ability to ferment l-arabinose and inabilities to ferment cellobiose, l-rhamnose and trehalose or to hydrolyse aesculin. The major menaquinone of the isolates was MK-10. Based on these data, we propose a novel Parabacteroides species, Parabacteroides gordonii sp. nov. The type strain is MS-1(T) (=JCM 15724(T) =CCUG 57478(T)).
The metal‐dependent conformational changes in Factor IX associated with phospholipid binding. (1993)

Factor IX undergoes two sequential metal-ion-dependent conformational transitions [Liebman, H.A. (1987) J. Biol. Chem. 262, 7605-7612]. The first transition is metal ion dependent, but cation nonselective. The second transition is metal ion selective for Ca(II) or Sr(II) and associated with the expression of conformational determinants necessary for phospholipid membrane binding. Using antibodies raised against a synthetic peptide containing Factor IX amino acid residues 28-46, it was demonstrated that the aromatic-amino-acid-stack domain (amino acid residues 41-46) of Factor IX is surface exposed in the metal-free conformer and internalized with the initial metal-ion-dependent conformational transition. The metal-ion-induced internalization of this region of Factor IX protects the tryptophan at position 42 from oxidation by N-bromosuccinimide. The oxidation of Factor IX tryptophan residues is associated with the rapid loss of coagulant activity, but protection of Trp42 allows for the continued expression of the Ca(II)-specific antigenic determinants on Factor IX and the retention of phospholipid binding. These results suggest that the Trp42 residue located in the aromatic amino acid stack domain of human Factor IX is internalized with the metal-ion-dependent conformational transition and is essential for the expression of the phospholipid membrane binding site on Factor IX.
Benzotriazole-Mediated Synthesis of Aza-peptides: En Route to an Aza-Leuenkephalin Analogue (2013)

Novel N-(N-Pg-azadipeptidoyl)benzotriazoles 20a-e couple efficiently with α-amino acids 21a-e, dipeptides 22a-c, aminoxyacetic acid 23a, depsidipeptide 23b, and α-hydroxy-β-phenylpropionic acid 27 yielding, respectively, azatripeptides 24a-g, azatetrapeptides 25a,b, a hybrid azatripeptide with an oxyamide bond 26a, a hybrid azatetrapeptide with an ester bond 26b, and a hybrid azatripeptide with an ester bond 28. A new protocol for the synthesis of N-Pg-azatripeptides 33a,b and 35a,b, each containing a natural amino acid at the N-terminus, avoids the low coupling rates of the aza-amino acid residue and enables the solution-phase synthesis of an azaphenylalanine analogue of Leu-enkephalin 40.
Uptake/Efflux Transport of Tramadol Enantiomers andO‐Desmethyl‐Tramadol: Focus onP‐Glycoprotein (2009)

The analgesic effect of tramadol (TMD) results from the monoaminergic effect of its two enantiomers, (+)-TMD and (-)-TMD as well as its opioid metabolite (+)-O-desmethyl-tramadol (M1). P-glycoprotein (P-gp) might be of importance in the analgesic and tolerability profile variability of TMD. Our study investigated the involvement of P-gp in the transepithelial transport of (+)-TMD, (-)-TMD and M1, using a Caco-2 cell monolayer model. The bidirectional transport of racemic TMD and M1 (1-100 microM) across the monolayers was investigated at two pH conditions (pH 6.8/7.4 and 7.4/7.4) in the presence and absence of P-gp inhibitor cyclosporine A (10 microM) and assessed with the more potent and specific P-gp inhibitor GF120918 (4 microM). Analytical quantification was performed by liquid chromatography coupled to the fluorescence detector. A net secretion of (+)-TMD, (-)-TMD and M1 was observed when a pH gradient was applied (TR: P(app)(B - A)/P(app)(A - B): 1.8-2.7; P < 0.05). However, the bidirectional transport of all compounds was equal in the non-gradient system. In the presence of P-gp inhibitors, a slight but significant increase of secretory flux was observed (up to 26%; P < 0.05) at both pH conditions. In conclusion, (+)-TMD, (-)-TMD and M1 are not P-gp substrates. However, proton-based efflux pumps may be involved in limiting the gastrointestinal absorption of TMD enantiomers as well as enhancing TMD enantiomers and M1 renal excretion. A possible involvement of uptake carriers in the transepithelial transport of TMD enantiomers and M1 is suggested.
Synthesis and chemistry of cationic d sup O metal alkyl complexes (1990)

The objective of this project is to synthesize cationic, d{sup 0} organometallic complexes and to study their role in catalytic olefin polymerization and oxidation chemistry, and in C-H activation chemistry. Attention is focused on complexes which incorporate highly unsaturated Lewis acidic metal centers and reactive alkyl or oxo ligands. These features combine to promote coordination and subsequent reaction of olefins and of ligand C-H bonds. In the first budget period of this project significant progress has been made in the synthesis of highly unsaturated cationic Zr(IV) alkyls, cationic Ti and Hf alkyls, and Re oxo alkyls, and a very general approach to productive ligand C-H bond activation chemistry has been explored.