gebhart/patrepeval huggingface dataset:
α-RgIA:  A Novel Conotoxin That Specifically and Potently Blocks the α9α10 nAChR, (2006)

The alpha9 and alpha10 nicotinic acetylcholine receptor (nAChR) subunits assemble to form the alpha9alpha10 nAChR subtype. This receptor is believed to mediate cholinergic synaptic transmission between efferent olivocochlear fibers and the hair cells of the cochlea. In addition alpha9 and/or alpha10 expression has been described in dorsal root ganglion neurons, lymphocytes, skin keratinocytes, and the pars tuberalis of the pituitary. Specific antagonists that selectively block the alpha9alpha10 channel could be valuable tools for elucidating its role in these diverse tissues. This study describes a novel alpha-conotoxin from the Western Atlantic species Conus regius, alpha-conotoxin RgIA (alpha-RgIA), that is a subtype specific blocker of the alpha9alpha10 nAChR. alpha-RgIA belongs to the alpha4/3 subfamily of the alpha-conotoxin family; sequence and subtype specificity comparisons between alpha-RgIA and previously characterized alpha4/3 toxins indicate that the amino acids in the C-terminal half of alpha-RgIA are responsible for its preferential inhibition of the alpha9alpha10 nAChR subtype.
Characterization of a Novel β-Galactosidase from Bifidobacterium adolescentis DSM 20083 Active towards Transgalactooligosaccharides (2000)

This paper reports on the effects of both reducing and nonreducing transgalactooligosaccharides (TOS) comprising 2 to 8 residues on the growth of Bifidobacterium adolescentis DSM 20083 and on the production of a novel beta-galactosidase (beta-Gal II). In cells grown on TOS, in addition to the lactose-degrading beta-Gal (beta-Gal I), another beta-Gal (beta-Gal II) was detected and it showed activity towards TOS but not towards lactose. beta-Gal II activity was at least 20-fold higher when cells were grown on TOS than when cells were grown on galactose, glucose, and lactose. Subsequently, the enzyme was purified from the cell extract of TOS-grown B. adolescentis by anion-exchange chromatography, adsorption chromatography, and size-exclusion chromatography. Beta-Gal II has apparent molecular masses of 350 and 89 kDa as judged by size-exclusion chromatography and sodium dodecyl sulfate-polyacrylamide gel electrophoresis, respectively, indicating that the enzyme is active in vivo as a tetramer. Beta-Gal II had an optimal activity at pH 6 and was not active below pH 5. Its optimum temperature was 35 degrees C. The enzyme showed highest V(max) values towards galactooligosaccharides with a low degree of polymerization. This result is in agreement with the observation that during fermentation of TOS, the di- and trisaccharides were fermented first. Beta-Gal II was active towards beta-galactosyl residues that were 1-->4, 1-->6, 1-->3, and 1 <--> 1 linked, signifying its role in the metabolism of galactooligosaccharides by B. adolescentis.
Grayscale photomask fabricated by laser direct writing in metallic nano-films (2009)

The grayscale photomask plays a key role in grayscale lithography for creating 3D microstructures like micro-optical elements and MEMS structures, but how to fabricate grayscale masks in a cost-effective way is still a big challenge. Here we present novel low cost grayscale masks created in a two-step method by laser direct writing on Sn nano-films, which demonstrate continuous-tone gray levels depended on writing powers. The mechanism of the gray levels is due to the coexistence of the metal and the oxides formed in a laser-induced thermal process. The photomasks reveal good technical properties in fabricating 3D microstructures for practical applications.
Humidity‐Compensating Sensor for Volatile Organic Compounds Using Stacked Porous Silicon Photonic Crystals (2008)

Abstract One‐dimensional photonic crystals constructed from multilayered stacks of porous Si are used as sensors for gas‐phase volatile organic compounds (VOCs). The ability of a double‐stack structure to provide compensation for drift due to changing relative humidity (RH) is investigated. In this approach, two separate photonic crystals (dielectric stacks) are etched into a crystalline Si substrate, one on top of the other. The top stack is chemically modified to be hydrophobic (by hydrosilylation with dodecene) and the bottom stack is made hydrophilic (by hydrosilylation with undecylenic acid). It is shown that the optical spectrum of the double‐stack structure provides an effective means to discriminate VOCs from water vapor. In this approach, shifts in the peak frequencies from both photonic crystals are measured simultaneously. Because the two stacks respond differently to water and to VOC, the effect of changing humidity can be nulled by calculating the weighted difference between the two peak frequencies. Reliable determination of the concentration of VOC vapor in nitrogen over a range of RH values (25% &lt; RH &lt; 75%) is demonstrated. The ability of the double‐stack structure to discriminate between water vapor and VOCs is quantified for four different VOCs: toluene, dimethyl methylphosphonate (DMMP), heptane, and ethanol.
Formation of stable microspikes containing actin and the 55 kDa actin bundling protein, fascin, is a consequence of cell adhesion to thrombospondin-1: implications for the anti-adhesive activities of thrombospondin-1 (1995)

The organisation of the actin cytoskeleton was examined in H9c2 and human intestinal smooth muscle cells adherent on fibronectin or thrombospondin-1. Whereas cells adherent on fibronectin adopted a polygonal shape and rapidly assembled prominent stress fibres and focal contacts, cells adherent on thrombospondin-1 assumed a more irregular morphology with large lamellae containing radial actin microspikes. Focal contacts were not detected in cells adherent on thrombospondin-1, as determined by indirect immunofluorescence staining for vinculin and other focal contact components. Instead, the radial microspikes stained positively for the actin-bundling protein, 55 kDa/fascin, and myosins. In cells adherent on fibronectin, 55 kDa/fascin immunoreactivity was diffuse and tended to be concentrated in the perinuclear region. In long-term adherent cells cultured in serum-containing medium, 55 kDa/fascin was detected in membrane ruffles, in stress fibres and in the perinuclear region. The microspikes formed within 40 minutes of plating cells on thrombospondin-1 and remained present when cells were treated with sodium orthovandate and hydrogen peroxide to increase intracellular phosphotyrosine levels. Indeed, although vanadate-treated cells tended to retract, the microspikes became more prominent and showed an increased intensity of staining for fascin. Under these conditions, a proportion of the microspikes did not appear to be in contact with the substratum: these spikes stained weakly for focal adhesion kinase, talin and vinculin. Cells treated with genistein also spread and formed fascin-containing microspikes which tended to be more slender than those of control cells. In contrast, cells adherent on fibronectin displayed a complex rearrangement of the actin cytoskeleton and a transient enrichment of 55 kDa/fascin-containing structures at the cell surface when treated with sodium orthovanadate and hydrogen peroxide. These observations indicate that cell interactions with fibronectin or thrombospondin-1 send distinct organisational signals to the actin cytoskeleton and may offer a mechanistic framework for further investigations of the anti-adhesive properties of thrombospondin-1.
Src homology-2 domains: Structure, mechanisms, and drug discovery (1998)

Src homology-2 (SH2) domains and their associated catalytic or noncatalytic proteins constitute critical signal transduction targets for drug discovery. Such SH2 proteins are found in the regulation of a number of cellular processes, including growth, mitogenesis, motility, metabolism, immune response, and gene transcription. From the relationship of tyrosine phosphorylation and intracellular regulation by protein–tyrosine kinases (PTKs) and protein–tyrosine phosphatases (PTPs), the dynamic and reversible binding interactions of SH2 domain containing proteins with their cognate phosphotyrosine (pTyr) containing proteins provide a third dimensionality to the orchestration of signal transduction pathways that exist as a result of pTyr formation, degradation, and molecular recognition events. This review highlights several key research achievements impacting our current understanding of SH2 structure, mechanisms, and drug discovery that underlie the role(s) of SH2 domains in signal transduction processes, cellular functions, and disease states. © 1998 John Wiley & Sons, Inc. Biopoly 47: 243–261, 1998
What Part of NO Don't You Understand? Some Answers to the Cardinal Questions in Nitric Oxide Biology (2010)

Nitric oxide (NO) regulates biological processes through signaling mechanisms that exploit its unique biochemical properties as a free radical. For the last several decades, the key aspects of the chemical properties of NO relevant to biological systems have been defined, but it has been a challenge to assign these to specific cellular processes. Nevertheless, it is now clear that the high affinity of NO for transition metal centers, particularly iron, and the rapid reaction of NO with oxygen-derived free radicals can explain many of its biological and pathological properties. Emerging studies also highlight a growing importance of the secondary metabolites of NO-dependent reactions in the post-translational modification of key metabolic and signaling proteins. In this minireview, we emphasize the current understanding of the biochemistry of NO and place it in a biological context.
Plastic microring lasers on fibers and wires (1998)

Photopumped, pulsed, narrow line laser emission is demonstrated using cylindrical microcavities formed by π-conjugated polymer thin films wrapped around thin glass optical fibers and metal wires with various diameters D. A variety of cavity-dependent resonant laser mode structures were observed, which for D&amp;lt;10 μm contain a single resonant spectral line of less than 1 Å in width. The microring lasers are also characterized by a well-defined, very low threshold excitation intensity, at which beam directionality and polarization degree dramatically increase. These findings open up the fields of lasers and fiber optics to organic materials.
Boosting-Based Multimodal Speaker Detection for Distributed Meetings (2006)

Speaker detection is a very important task in distributed meeting applications. This paper discusses a number of challenges we met while designing a speaker detector for the Microsoft RoundTable distributed meeting device, and proposes a boosting-based multimodal speaker detection (BMSD) algorithm. Instead of performing sound source localization (SSL) and multi-person detection (MPD) separately and subsequently fusing their individual results, the proposed algorithm uses boosting to select features from a combined pool of both audio and visual features simultaneously. The result is a very accurate speaker detector with extremely high efficiency. The algorithm reduces the error rate of SSL-only approach by 47%, and the SSL and MPD fusion approach by 27%
Phosphatidylinositol 3-Kinase/AKT-mediated Activation of Estrogen Receptor α (2001)

Estrogen receptors (ERs) mediate most of the biological effects of estrogen in mammary and uterine epithelial cells by binding to estrogen response elements in the promoter region of target genes or through protein-protein interactions. Anti-estrogens such as tamoxifen inhibit the growth of ER-positive breast cancers by reducing the expression of estrogen-regulated genes. However, anti-estrogen-resistant growth of ER-positive tumors remains a significant clinical problem. Here we show that phosphatidylinositol (PI) 3-kinase and AKT activate ERalpha in the absence of estrogen. Although PI 3-kinase increased the activity of both estrogen-independent activation function 1 (AF-1) and estrogen-dependent activation function 2 (AF-2) of ERalpha, AKT increased the activity of only AF-1. PTEN and a catalytically inactive AKT decreased PI 3-kinase-induced AF-1 activity, suggesting that PI 3-kinase utilizes AKT-dependent and AKT-independent pathways in activating ERalpha. The consensus AKT phosphorylation site Ser-167 of ERalpha is required for phosphorylation and activation by AKT. In addition, LY294002, a specific inhibitor of the PI 3-kinase/AKT pathway, reduced phosphorylation of ERalpha in vivo. Moreover, AKT overexpression led to up-regulation of estrogen-regulated pS2 gene, Bcl-2, and macrophage inhibitory cytokine 1. We demonstrate that AKT protects breast cancer cells from tamoxifen-induced apoptosis. Taken together, these results define a molecular link between activation of the PI 3-kinase/AKT survival pathways, hormone-independent activation of ERalpha, and inhibition of tamoxifen-induced apoptotic regression.
Algorithm-based low-power and high-performance multimedia signal processing (1998)

Low power and high performance are the two most important criteria for many signal-processing system designs, particularly in real-time multimedia applications. There have been many approaches to achieve these two design goals at many different implementation levels ranging from very-large-scale-integration fabrication technology to system design. We review the works that have been done at various levels and focus on the algorithm-based approaches for low-power and high-performance design of signal processing systems. We present the concept of multirate computing that originates from filterbank design, then show how to employ it along with the other algorithmic methods to develop low-power and high-performance signal processing systems. The proposed multirate design methodology is systematic and applicable to many problems. We demonstrate that multirate computing is a powerful tool at the algorithmic level that enables designers to achieve either significant power reduction or high throughput depending on their choice. Design examples on basic multimedia processing blocks such as filtering, source coding, and channel coding are given. A digital signal-processing engine that is an adaptive reconfigurable architecture is also derived from the common features of our approach. Such an architecture forms a new generation of high-performance embedded signal processor based on the adaptive computing model. The goal of this paper is to demonstrate the flexibility and effectiveness of algorithm-based approaches and to show that the multirate approach is an effective and systematic design methodology to achieve low-power and high throughput signal processing at the algorithmic and architectural level.
The design of organic gelators: Solution and solid state properties of a family of bis-ureas (1998)

A family of bis-urea derivatives has been synthesized and shown to function as effective gelators in certain organic solvents. The X-ray structure of one bis-urea shows a cylindrical hydrogen bonding network with extensive interdigitation of the alkyl esters which project from the central rod.
Two peptides related to platelet-derived growth factor are present in human wound fluid. (1989)

Platelet-derived growth factor (PDGF) has been suggested to play an important role in wound healing. In this study wound fluid collected from patients after radical mastectomy was analyzed for PDGF-related factors. Analysis revealed the presence of two PDGF-related peptides of 16-17 kDa and 34-36 kDa. These PDGF-related peptides were purified by using anti-PDGF immunoaffinity techniques and found to possess both chemotactic and mitogenic activities for NIH 3T3 cells in vitro. Surprisingly, we could not detect authentic native PDGF (30 kDa) or PDGF A or B chain in any of the wound-fluid samples examined. These results indicate that PDGF-related peptides are present in normal human wound fluid, whereas PDGF A- and B-chain peptides are absent or only present in trace amounts relative to the total PDGF-related biological activity.
MAp44, a Human Protein Associated with Pattern Recognition Molecules of the Complement System and Regulating the Lectin Pathway of Complement Activation (2009)

Essential effector functions of innate immunity are mediated by complement activation initiated by soluble pattern recognition molecules: mannan-binding lectin (MBL) and the ficolins. We present a novel, phylogenetically conserved protein, MAp44, which is found in human serum at 1.4 microg/ml in Ca(2+)-dependent complexes with the soluble pattern recognition molecules. The affinity for MBL is in the nanomolar range (K(D) = 0.6 nM) as determined by surface plasmon resonance. The first eight exons of the gene for MAp44 encode four domains shared with MBL-associated serine protease (MASP)-1 and MASP-3 (CUB1-EGF-CUB2-CCP1), and a ninth exon encodes C-terminal 17 aa unique to MAp44. mRNA profiling in human tissues shows high expression in the heart. MAp44 competes with MASP-2 for binding to MBL and ficolins, resulting in inhibition of complement activation. Our results add a novel mechanism to those known to control the innate immune system.
Brief Report: Interferon-γ Induces Expansion of Lin−Sca-1+C-Kit+ Cells (2009)

The balance between Th1 and Th2 cells is critical for homeostasis of the immune system. Th1 cells can also regulate hematopoietic progenitor cell homeostasis by production of oncostatin M. Here we show that Th1 cell products, but not those of Th2 cells, caused a rapid expansion of lineage(-)Sca-1(+)C-kit(+) (LSK) cells in vivo and in vitro. Among Th1 cytokines, interferon-gamma (IFNgamma) was found to play a major role in this expansion by activating the expression of Sca-1 in lineage(-)Sca-1(-)C-kit(+) cells. This process was dependent on IFNgammaR1 signaling and the STAT1 pathway. Furthermore, those IFNgamma-induced LSK cells had a higher proliferation potential than control LSK cells. In addition, while the overall production of colony-forming units in bone marrow was decreased after IFNgamma treatment, the sorted LSK cells could give rise to a higher yield of colony-forming units. Finally, the IFNgamma-induced hematopoiesis was biased toward the differentiation of myeloid lineages. Therefore, our findings demonstrated a novel role of IFNgamma in activating hematopoietic progenitor cells and provide a new insight into the clinical application of interferon.
Sterile Inflammation in Acetaminophen-induced Liver Injury Is Mediated by Cot/tpl2 (2013)

Cot/tpl2 (MAP3K8) activates MKK1/2-Erk1/2 following stimulation of the Toll-like/IL-1 receptor superfamily. Here, we investigated the role of Cot/tpl2 in sterile inflammation and drug-induced liver toxicity. Cot/tpl2 KO mice exhibited reduced hepatic injury after acetaminophen challenge, as evidenced by decreased serum levels of both alanine and aspartate aminotransferases, decreased hepatic necrosis, and increased survival relative to Wt mice. Serum levels of both alanine and aspartate aminotransferases were also lower after intraperitoneal injection of acetaminophen in mice expressing an inactive form of Cot/tpl2 compared with Wt mice, suggesting that Cot/tpl2 activity contributes to acetaminophen-induced liver injury. Furthermore, Cot/tpl2 deficiency reduced neutrophil and macrophage infiltration in the liver of mice treated with acetaminophen, as well as their hepatic and systemic levels of IL-1α. Intraperitoneal injection of damage-associated molecular patterns from necrotic hepatocytes also impaired the recruitment of leukocytes and decreased the levels of several cytokines in the peritoneal cavity in Cot/tpl2 KO mice compared with Wt counterparts. Moreover, similar activation profiles of intracellular pathways were observed in Wt macrophages stimulated with Wt or Cot/tpl2 KO damage-associated molecular patterns. However, upon stimulation with damage-associated molecular patterns, the activation of Erk1/2 and JNK was deficient in Cot/tpl2 KO macrophages compared with their Wt counterparts; an effect accompanied by weaker release of several cytokines, including IL-1α, an important component in the development of sterile inflammation. Taken together, these findings indicate that Cot/tpl2 contributes to acetaminophen-induced liver injury, providing some insight into the underlying molecular mechanisms.
Albumin Binding of Short Cationic Antimicrobial Micropeptides and Its Influence on the in Vitro Bactericidal Effect (2007)

The interactions between a range of small cationic antibacterial tripeptides and bovine and human serum albumin in a buffered aqueous solution at 25 degrees C have been studied using isothermal titration calorimetry. Results from the binding study indicate a single binding site on albumin with a dissociation constant between 4.3 and 22.2 microM for the different peptides. In a theoretical mouse model, a dissociation constant in this range corresponds to 95% albumin binding. The effect of this albumin interaction on the antibacterial capacity of the peptides against Staphylococcus aureus, strain ATCC 25923 was studied by including albumin in the assays at a 0.55 mM concentration. Presence of albumin induced a 10-fold increase of the minimal inhibitory concentration for the bulk of the peptides. Albumin itself has no effect on the bacterial growth and this increase is entirely ascribed to a strong competing protein binding. Collectively these results indicate that these antibacterial peptides do bind to albumin and that this binding strongly reduces the effective concentration of peptides available to combat bacteria.
Identification of the Second Membrane-type Matrix Metalloproteinase (MT-MMP-2) Gene from a Human Placenta cDNA Library (1995)

Membrane-type matrix metalloproteinase (MT-MMP), which we have identified recently, is unique in its transmembrane (TM) domain at the C terminus and mediates activation of pro-gelatinase A on the cell surface (Sato, H., Takino, T., Okada, Y., Cao, J., Shinagawa, A., Yamamoto, E., and Seiki, M. (1994) Nature 370, 61-65; Takino, T., Sato, H., Yamamoto, E., and Seiki, M. (1995) Gene (Amst.) 115, 293-298). In addition to MT-MMP, a novel MMP-related cDNA of 2.1 kilobases was isolated from a human placenta cDNA library. The cDNA contains an open reading frame for a new MMP. The deduced protein composed of 604 amino acids was closely related to MT-MMP in the amino acid sequence (66% homology at the catalytic domains) and has a potential TM domain at the C terminus. Monoclonal antibodies raised against the synthetic peptide recognized a 64-kDa protein as the major product in the transfected cells. TIMP-1 fused with the potential TM domain was localized on the cell surface while native TIMP-1 is in the culture medium. Thus, we called the second membrane-type MMP, MT-MMP-2 and renamed MT-MMP, MT-MMP-1. MT-MMP-1 and -2 are thought to form a distinct membrane-type subclass in the MMP family since all the others are secreted as soluble forms. Like MT-MMP-1, expression of MT-MMP-2 induced processing of pro-gelatinase A (68-kDa in gelatin zymography) into the activated form of 62-kDa fragments through a 64-kDa intermediate form. Expression of MT-MMP-2 mRNA was at the highest levels in the brain where MT-MMP-1 was at the lowest level compared to other tissues. MT-MMP-1 and -2 are thought to be utilized for extracellular matrix turnover on the surface of cells under different genetic controls.
The OAKLEY Key Determination Protocol (1998)

This document describes a protocol, named OAKLEY, by which two authenticated parties can agree on secure and secret keying material. The basic mechanism is the Diffie-Hellman key exchange algorithm. The OAKLEY protocol supports Perfect Forward Secrecy, compatibility with the ISAKMP protocol for managing security associations, user-defined abstract group structures for use with the Diffie-Hellman algorithm, key updates, and incorporation of keys distributed via out-of-band mechanisms.