gebhart/patrepeval huggingface dataset:
Burkholderia cenocepacia Type VI Secretion System Mediates Escape of Type II Secreted Proteins into the Cytoplasm of Infected Macrophages (2012)

Burkholderia cenocepacia is an opportunistic pathogen that survives intracellularly in macrophages and causes serious respiratory infections in patients with cystic fibrosis. We have previously shown that bacterial survival occurs in bacteria-containing membrane vacuoles (BcCVs) resembling arrested autophagosomes. Intracellular bacteria stimulate IL-1β secretion in a caspase-1-dependent manner and induce dramatic changes to the actin cytoskeleton and the assembly of the NADPH oxidase complex onto the BcCV membrane. A Type 6 secretion system (T6SS) is required for these phenotypes but surprisingly it is not required for the maturation arrest of the BcCV. Here, we show that macrophages infected with B. cenocepacia employ the NLRP3 inflammasome to induce IL-1β secretion and pyroptosis. Moreover, IL-1β secretion by B. cenocepacia-infected macrophages is suppressed in deletion mutants unable to produce functional Type VI, Type IV, and Type 2 secretion systems (SS). We provide evidence that the T6SS mediates the disruption of the BcCV membrane, which allows the escape of proteins secreted by the T2SS into the macrophage cytoplasm. This was demonstrated by the activity of fusion derivatives of the T2SS-secreted metalloproteases ZmpA and ZmpB with adenylcyclase. Supporting this notion, ZmpA and ZmpB are required for efficient IL-1β secretion in a T6SS dependent manner. ZmpA and ZmpB are also required for the maturation arrest of the BcCVs and bacterial intra-macrophage survival in a T6SS-independent fashion. Our results uncover a novel mechanism for inflammasome activation that involves cooperation between two bacterial secretory pathways, and an unanticipated role for T2SS-secreted proteins in intracellular bacterial survival.
Peptergents:  Peptide Detergents That Improve Stability and Functionality of a Membrane Protein, Glycerol-3-phosphate Dehydrogenase (2005)

Toward enhancing in vitro membrane protein studies, we have utilized small self-assembling peptides with detergent properties ("peptergents") to extract and stabilize the integral membrane flavoenzyme, glycerol-3-phosphate dehydrogenase (GlpD), and the soluble redox flavoenzyme, NADH peroxidase (Npx). GlpD is a six transmembrane spanning redox enzyme that catalyzes the oxidation of glycerol-3-phosphate to dihydroxyacetone phosphate. Although detergents such as n-octyl-beta-D-glucpyranoside can efficiently solubilize the enzyme, GlpD is inactivated within days once reconstituted into detergent micelles. In contrast, peptergents can efficiently extract and solubilize GlpD from native Escherichia coli membrane and maintain its enzymatic activity up to 10 times longer than in traditional detergents. Intriguingly, peptergents also extended the activity of a soluble flavoenzyme, Npx, when used as an additive. Npx is a flavoenzyme that catalyzes the two-electron reduction of hydrogen peroxide to water using a cysteine-sulfenic acid as a secondary redox center. The lability of the peroxidase results from oxidation of the sulfenic acid to the sulfinic or sulfonic acid forms. Oxidation of the sulfenic acid, the secondary redox center, results in inactivation, and this reaction proceeds in vitro even in the presence of reducing agents. Although the exact mechanism by which peptergents influence solution stability of Npx remains to be determined, the positive effects may be due to antioxidant properties of the peptides. Peptide-based detergents can be beneficial for many applications and may be particularly useful for structural and functional studies of membrane proteins due to their propensity to enhance the formation of ordered supramolecular assemblies.
Original Synthesis of Linear, Branched and Cyclic Oligoglycerol Standards (2001)

A variety of authentic standards of linear, branched and cyclic oligomers of glycerol, with well-defined structures and degrees of polymerisation from 2 to 5, have been efficiently synthesised. Linear oligomers were obtained by means of a convergent approach based on regioselective opening of bis(epoxides) with solketal; branched compounds were synthesised using oxidative cleavage of the corresponding anhydrohexitols as the key step. A 6-exo-trig halocyclisation reaction involving heteroatom-tethered unsaturated alcohols permitted an efficient synthesis of the precursors of selected cyclic dimers; larger cyclic oligomers were prepared by two one-pot Williamson reactions using a ditriflate derived from diglycerol. All these methodologies permitted further scaling up.
20-Channel micro-optic grating demultiplexer for 1.1–1.6 μm band using a small focusing parameter graded-index rod lens (1982)

A 20-channel micro-optic grating demultiplexer with a single-mode input fibre has been developed for 1.1–1.6 μm band using a newly developed graded-index (Selfoc) rod lens with a small focusing parameter and an Si-etched reflection grating. Insertion losses were 1.9 to 3.5 dB. Isolation between adjacent channels was less than −20 dB.
Epidermal Growth Factor Receptor Signaling to Erk1/2 and STATs Control the Intensity of the Epithelial Inflammatory Responses to Rhinovirus Infection (2008)

Rhinovirus infection is the most common cause of acute exacerbations of inflammatory lung diseases, such as asthma and chronic obstructive pulmonary disease, where it provokes steroid refractory and abnormally intense neutrophilic inflammation that can be life threatening. Epidermal growth factor receptor (EGFR) expression correlates with disease severity and neutrophil infiltration in these conditions. However, the role of EGFR signaling in rhinovirus infection is unknown. We measured the key determinants of neutrophilic inflammation interleukin (IL)-8 and ICAM-1 in rhinovirus (RV16 serotype)-infected bronchial epithelial cells, BEAS-2B. RV16 infection stimulated IL-8 and ICAM-1 expression, which was further elevated (2-fold) by transient up-regulation of EGFR levels. Detection of viral RNA by quantitative real time PCR confirmed that enhanced expression was not associated with increased viral replication. EGFR ligands (epiregulin, amphiregulin, and heparin-binding epidermal growth factor) were induced by RV16 infection, and inhibition of metalloproteases responsible for ligand shedding partially suppressed this response. The EGFR inhibitor AG1478, completely blocked IL-8 and ICAM-1 expression to basal levels, as did the specific Erk1/2 inhibitor U0126. The p38 mitogen-activated protein kinase inhibitor SB203580 blocked IL-8 secretion but not ICAM-1 expression, whereas the PI3K inhibitor wortmannin was ineffective in both responses. Kinase inactive K721R EGFR, which is selectively deficient in STAT signaling, reversed RV16 responses associated with EGFR overexpression. In conclusion, RV16 infection rapidly promotes induction of EGFR ligands and utilizes EGFR signaling to increase IL-8 and ICAM-1 levels. These results suggest that targeting EGFR may provide a selective therapy that dampens neutrophil-driven inflammation without compromising essential antiviral pathways mediated by pathogen recognition receptors such as TLR3.
Thermoplastic polyurethane elastomers from bio-based poly(δ-decalactone) diols (2013)

Bio-based poly(δ-decalactone) is an amorphous, low glass transition temperature (Tg) material and it is an aliphatic polyester (Martello et al., ACS Macro Lett., 2011) that can be utilized as a soft segment in thermoplastic polyurethanes (TPU). We describe the synthesis and purification of low molar mass poly(δ-decalactone) diols (PdDL), as well as the synthesis and characterization of new PdDL-based TPUs. The PdDLs obtained were characterized by proton nuclear magnetic resonance (1H-NMR) spectroscopy and matrix-assisted laser desorption ionization mass spectroscopy. Three different PdDLs were prepared and their molar masses calculated from 1H-NMR spectroscopy were: Mn ≈ 1300, 1800 and 2700 g mol−1. These three PdDLs were reacted with 4,4′-methylenebis(phenyl isocyanate) and two different chain extenders (1,4-butanediol and water), to synthesize polyester-based TPUs. The TPUs made from PdDLs with Mn of 1800 and 2700 exhibit good elastomeric properties and their Tg values are around −40 °C. With water as chain extender urea bonds were created, which gave TPUs with higher modulus, higher stress at break and lower hysteresis.
Vacuum-Free, Maskless Patterning of Ni Electrodes by Laser Reductive Sintering of NiO Nanoparticle Ink and Its Application to Transparent Conductors (2014)

We introduce a method for direct patterning of Ni electrodes through selective laser direct writing (LDW) of NiO nanoparticle (NP) ink. High-resolution Ni patterns are generated from NiO NP thin films by a vacuum-free, lithography-free, and solution-processable route. In particular, a continuous wave laser is used for the LDW reductive sintering of the metal oxide under ambient conditions with the aid of reducing agents in the ink solvent. Thin (∼ 40 nm) Ni electrodes of glossy metallic surfaces with smooth morphology and excellent edge definition can be fabricated. By applying this method, we demonstrate a high transmittance (>87%), electrically conducting panel for a touch screen panel application. The resistivity of the Ni electrode is less than an order of magnitude higher compared to that of the bulk Ni. Mechanical bending test, tape-pull test, and ultrasonic bath test confirm the robust adhesion of the electrodes on glass and polymer substrates.
Proteases and emphysema (2005)

The idea that a single protease or a single type of inflammatory cell is responsible for human emphysema is unlikely to be true; rather, there are complex interactions among proteases, and between proteases and other mediators. The problem at this time is attempting to sort out the numerous candidate effector agents and to determine which of the animal models are relevant to human disease, since there may be considerable discrepancies in the types of proteases and their roles between laboratory animals and humans. There is now good evidence from animal models that antiproteolytic therapy can be of benefit in ameliorating cigarette smoke-induced emphysema.
Activity of paclitaxel liposome formulations against human ovarian tumor xenografts (1997)

Although the current clinical formulation of paclitaxel (Taxol) is an important new anti-cancer agent, it has significant side effects, some of which are related to its formulation in Cremophor/ethanol. Paclitaxel is difficult to formulate for i.v. administration because of its poor aqueous solubility. Here, we report the therapeutic effects of 2 liposome formulations of paclitaxel against human ovarian A121 tumor growing as an s.c. xenograft in athymic nude mice. The liposome formulations used were ETL and TTL, which have I or 3 lipid components, respectively. TTL was used as a reconstituted lyophilate or as a stable aqueous suspension. ETL was used as a reconstituted lyophilate only. Both paclitaxel-liposome formulations were much better tolerated than Taxol after i.v. or i.p. administration. The acute reactions seen after Taxol administration did not occur when paclitaxel-liposome formulations were administered. All ETL and TTL preparations significantly delayed A121 tumor growth similarly to Taxol at equivalent doses and schedules. Based on pharmacokinetic data, it is possible that paclitaxel rapidly dissociates from ETL or TTL after i.v. administration and distributes in a manner similarly to Taxol. ETL and TTL formulations may be useful clinically not only for eliminating toxic effects of the Cremophor/ethanol vehicle but also for allowing alterations in route and schedule of drug administration.
Novel functions and signalling pathways for GDNF (2003)

Glial-cell-line-derived neurotrophic factor (GDNF) was originally identified as a survival factor for midbrain dopaminergic neurons. GDNF and related ligands, neurturin (NRTN), artemin (ARTN) and persephin (PSPN), maintain several neuronal populations in the central nervous systems, including midbrain dopamine neurons and motoneurons. In addition, GDNF, NRTN and ARTN support the survival and regulate the differentiation of many peripheral neurons, including sympathetic, parasympathetic, sensory and enteric neurons. GDNF has further critical roles outside the nervous system in the regulation of kidney morphogenesis and spermatogenesis. GDNF family ligands bind to specific GDNF family receptor alpha (GFRalpha) proteins, all of which form receptor complexes and signal through the RET receptor tyrosine kinase. The biology of GDNF signalling is much more complex than originally assumed. The neurotrophic effect of GDNF, except in motoneurons, requires the presence of transforming growth factor beta, which activates the transport of GFRalpha1 to the cell membrane. GDNF can also signal RET independently through GFR1alpha. Upon ligand binding, GDNF in complex with GFRalpha1 may interact with heparan sulphate glycosaminoglycans to activate the Met receptor tyrosine kinase through cytoplasmic Src-family kinases. GDNF family ligands also signal through the neural cell adhesion molecule NCAM. In cells lacking RET, GDNF binds with high affinity to the NCAM and GFRalpha1 complex, which activates Fyn and FAK.
A Transgenic Mouse with a Deletion in the Collagenous Domain of Adiponectin Displays Elevated Circulating Adiponectin and Improved Insulin Sensitivity (2003)

Adiponectin is a plasma protein expressed exclusively in adipose tissue. Adiponectin levels are linked to insulin sensitivity, but a direct effect of chronically elevated adiponectin on improved insulin sensitivity has not yet been demonstrated. We identified a dominant mutation in the collagenous domain of adiponectin that elevated circulating adiponectin values in mice by 3-fold. Adiponectinemia raised lipid clearance and lipoprotein lipase activity, and suppressed insulin-mediated endogenous glucose production. The induction of adiponectin during puberty and the sexual dimorphism in adult adiponectin values were preserved in these transgenic animals. As a result of elevated adiponectin, serum PRL values and brown adipose mass both increased. The effects on carbohydrate and lipid metabolism were associated with elevated phosphorylation of 5'-AMP-activated protein kinase in liver and elevated expression of peroxisomal proliferator-activated receptor gamma2, caveolin-1, and mitochondrial markers in white adipose tissue. These studies strongly suggest that increasing endogenous adiponectin levels has direct effects on insulin sensitivity and may induce similar physiological responses as prolonged treatment with peroxisomal proliferator-activated receptor gamma agonists.
Development of a Chemiluminescence-Based Ribonuclease Protection Assay (2002)

The ribonuclease protection assay (RPA) is a widely used method for the detection and quantification of specific mRNA transcripts in a complex mixture of total RNA or mRNA molecules. While exhibiting many advantages over other RNA detection methods, RPAs are traditionally performed using radiolabeled probes that often require gel purification steps and lengthy exposure times to visualize results. Moreover, these probes can only be used for 1-2 weeks because of their short isotopic half-life and radiolysis. We report a method that improves the traditional RPA by replacing radiolabeled probes with biotinylated probes and lengthy exposure times with quick, streptavidin/HRP-based chemiluminescent detection technology. Biotinylated probes can be used without get purification and are stable for years, as opposed to weeks. Most importantly, our streptavidin/HRP-based chemiluminescent technology enables us to achieve sensitivity results similar to radioactive RPAs and to detect multiple transcripts in a single sample more efficiently. Furthermore, this new protocol addresses and eliminates the one major drawback unique to using biotinylated probes in chemiluminescent RPAs: a confounding artifact, not seen when running radioactive RPAs but commonly detected when using certain biotinylated rare message probes.
Automated Multi-Well Device to Measure Transepithelial Electrical Resistances under Physiological Conditions (2004)

Measurement of transendothelial or transepithelial electrical resistances (TERs) is a straightforward in situ experimental approach to monitor the expression or modulation of barrier-forming cell-to-cell contacts (tight junctions) in cultured cells grown on porous filters. Although widely accepted, there is currently no device available to automatically measure the time course of TERs under ordinary cell culture conditions (37 degrees C, 5% or 10% CO2). This paper describes a development from our laboratory that is capable of following in parallel the TERs of several filter-grown cell layers with time and in an entirely computer-controlled fashion. The cell cultures can be followed even in long-term experiments without any manual assistance or opening of the incubator Besides reading TER values, this approach also returns the electrical capacitance of the cell layers, which is indicative of the expression of microvilli and other membrane extrusions. The device is based on reading the frequencydependent impedance of the cell layer, followed by equivalent circuit modeling to extract the cell-related parameters. It is compatible with several multi-well formats (up to 96 wells) and controlled by custom-designed software that reads, analyzes, and presents the data.
Reactive power minimization of dual active bridge DC/DC converter with triple phase shift control using neural network (2014)

Reactive power flow increases dual active bridge (DAB) converter RMS current leading to an increase in conduction losses especially in high power applications. This paper proposes a new optimized triple phase shift (TPS) switching algorithm that minimizes the total reactive power of the converter. The algorithm iteratively searches for TPS control variables that satisfy the desired active power flow while selecting the operating mode with minimum reactive power consumption. This is valid for the whole range of converter operation. The iterative algorithm is run offline for the entire active power range (-1pu to 1pu) and the resulting data is used to train an open loop artificial neural network controller to reduce computational time and memory allocation necessary to store the data generated. To validate the accuracy of the proposed controller, a 500-MW 300kV/100kV DAB model is simulated in Matlab/Simulink, as a potential application for DAB in DC grids.
Suppression of myeloid transcription factors and induction of STAT response genes by AML-specific Flt3 mutations (2003)

The receptor tyrosine kinase Flt3 is expressed and functionally important in early myeloid progenitor cells and in the majority of acute myeloid leukemia (AML) blasts. Internal tandem duplications (ITDs) in the juxtamembrane domain of the receptor occur in 25% of AML cases. Previously, we have shown that these mutations activate the receptor and induce leukemic transformation. In this study, we performed genome-wide parallel expression analyses of 32Dcl3 cells stably transfected with either wild-type or 3 different ITD isoforms of Flt3. Comparison of microarray expression analyses revealed that 767 of 6586 genes differed in expression between FLT3-WT- and FLT3-ITD-expressing cell lines. The target genes of mutationally activated Flt3 resembled more closely those of the interleukin 3 (IL-3) receptor than those of ligand-activated Flt3. The serine-threonine kinase Pim-2 was up-regulated on the mRNA and the protein level in Flt3-ITD-expressing cells. Further experiments indicated that Pim-2 function was important for clonal growth of 32D cells. Several genes repressed by the mutations were found to be involved in myeloid gene regulation. Pu.1 and C/EBPalpha, both induced by ligand-activation of wild-type Flt3, were suppressed in their expression and function by the Flt3 mutations. In conclusion, internal tandem duplication mutations of Flt3 activate transcriptional programs that partially mimic IL-3 activity. Interestingly, other parts of the transcriptional program involve novel, IL-3-independent pathways that antagonize differentiation-inducing effects of wild-type Flt3. The identification of the transcriptional program induced by ITD mutations should ease the development of specific therapies.
A Conserved Asparagine Residue in Transmembrane Segment 1 (TM1) of Serotonin Transporter Dictates Chloride-coupled Neurotransmitter Transport (2011)

Na(+)- and Cl(-)-dependent uptake of neurotransmitters via transporters of the SLC6 family, including the human serotonin transporter (SLC6A4), is critical for efficient synaptic transmission. Although residues in the human serotonin transporter involved in direct Cl(-) coordination of human serotonin transport have been identified, the role of Cl(-) in the transport mechanism remains unclear. Through a combination of mutagenesis, chemical modification, substrate and charge flux measurements, and molecular modeling studies, we reveal an unexpected role for the highly conserved transmembrane segment 1 residue Asn-101 in coupling Cl(-) binding to concentrative neurotransmitter uptake.
MOS switched capacitor ladder filters (1978)

A new technique for designing precision, fully integrated, high-order filters using standard MOS technology is described. Switched capacitor integrators have been used to realize long time constants in small areas, and by interconnecting these integrators in a `leapfrog' configuration, monolithic high-order filters have been implemented with transfer functions that are very insensitive to component variations. Experimental results are presented for an NMOS fifth-order Chebyshev low-pass ladder filter with 0.1-dB passband ripple, a cutoff frequency of 3.4 kHz when clocked at 128 kHz, and a dynamic range of 83 dB. An efficient method for implementing transmission zeros is also presented, along with a complete design example, and additional experimental results for a third-order elliptic low-pass ladder filter which achieved 90-dB dynamic range, with a total power dissipation of 18 mW in a die area of 4400 mil/SUP 2/.
Temporally Regulated and Tissue-Specific Gene Manipulations in the Adult and Embryonic Heart Using a Tamoxifen-Inducible Cre Protein (2001)

The advent of conditional and tissue-specific recombination systems in gene-targeted or transgenic mice has permitted an assessment of single gene function in a temporally regulated and cell-specific manner. Here we generated transgenic mice expressing a tamoxifen-inducible Cre recombinase protein fused to two mutant estrogen-receptor ligand-binding domains (MerCreMer) under the control of the alpha-myosin heavy chain promoter. These transgenic mice were crossed with the ROSA26 lacZ-flox-targeted mice to examine Cre recombinase activity and the fidelity of the system. The data demonstrate essentially no Cre-mediated recombination in the embryonic, neonatal, or adult heart in the absence of inducing agent but >80% recombination after only four tamoxifen injections. Expression of the MerCreMer fusion protein within the adult heart did not affect cardiac performance, cellular architecture, or expression of hypertrophic marker genes, demonstrating that the transgene-encoded protein is relatively innocuous. In summary, MerCreMer transgenic mice represent a tool for temporally regulated inactivation of any loxP-targeted gene within the developing and adult heart or for specifically directing recombination and expression of a loxP-inactivated cardiac transgene in the heart.