gebhart/patrepeval huggingface dataset:
Nifedipine inhibits tumor necrosis factor-alpha-induced monocyte chemoattractant protein-1 overexpression by blocking NADPH oxidase-mediated reactive oxygen species generation. (2003)

There is a growing body of evidence that dihydropyridine-based calcium antagonists (DHPs) improve endothelial function, thus slowing the development and progression of atherosclerosis. However the molecular mechanisms by which DHPs normalize endothelial dysfunction, an initial step in atherosclerosis, are not fully understood. Monocyte recruitment and firm adhesion to endothelial cells play a central role in the pathogenesis of atherosclerosis. In this study, we investigated whether nifedipine, one of the most popular DHPs, could inhibit tumor necrosis factor-alpha (TNF-alpha)-induced reactive oxygen species (ROS) generation and subsequent monocyte chemoattractant protein-1 (MCP-1) expression in human umbilical vein endothelial cells (HUVEC). TNF-alpha significantly increased intracellular ROS generation in HUVEC, which was completely blocked by nifedipine. Nifedipine completely inhibited TNF-alpha-induced nicotinamide adenine dinucleotide phosphate (NADPH) oxidase activity in HUVEC. Furthermore, nifedipine was found to significantly inhibit upregulation of MCP-1 messenger RNA levels in TNF-alpha-exposed HUVEC. The results demonstrate that nifedipine could inhibit TNF-alpha-induced MCP-1 overexpression in HUVEC by suppressing NADPH oxidase-mediated ROS generation. Our present study suggests that nifedipine may play a protective role in the development and progression of atherosclerosis through its antioxidative properties.
Mitogen-activated Protein Kinase Kinase Kinase Kinase 4 as a Putative Effector of Rap2 to Activate the c-Jun N-terminal Kinase (2004)

Little is known about the specific signaling roles of Rap2, a Ras family small GTP-binding protein. In a search for novel Rap2-interacting proteins by the yeast two-hybrid system, we isolated isoform 3 of the human mitogen-activated protein kinase kinase kinase kinase 4 (MAP4K4), a previously described but uncharacterized isoform. Other isoforms of MAP4K4 in humans and mice are known as hematopoietic progenitor kinase (HPK)/germinal center kinase (GCK)-like kinase and Nck-interacting kinase, respectively. MAP4K4 belongs to the STE20 group of protein kinases and regulates c-Jun N-terminal kinase (JNK). MAP4K4 interacted with Rap2 through its C-terminal citron homology domain but did not interact with Rap1 or Ras. Interaction with Rap2 required the intact effector region of Rap2. MAP4K4 interacted preferentially with GTP-bound Rap2 over GDP-bound Rap2 in vitro. In cultured cells, MAP4K4 colocalized with Rap2, while a mutant MAP4K4 lacking the citron homology domain failed to do so. Furthermore, Rap2 enhanced MAP4K4-induced activation of JNK. These results suggest that MAP4K4 is a putative effector of Rap2 mediating the activation of JNK by Rap2.
Effect of dispersant on the flow energy of ceramic injection molding mixtures (1999)

The activation energy (E) of flow for zirconia-wax suspensions was characterized by using three different types of dispersing agents having different melting points. Experimental results suggest that the energy E shows a dispersant-dependent character over the temperature range of study. Above the melting point (T m ) of the dispersant, the suspensions exhibit a rheological behavior depending strongly upon the property of dispersant employed ; however, below the T m , suspension viscosity demonstrated a temperature dependence similar to that of the melt wax. A change in rheological mechanism due to the change in temperature appears evident, indicating a possible alternative to tailor the rheological property by interfacial adsorption of proprietary dispersant in highly-concentrated suspensions for particularly powder injection molding applications.
Bubble‐induced detachment of affinity‐adsorbed erythrocytes (2004)

It is desirable that cells adsorbed in affinity-separation processes be easily recovered from the adsorption surface, without excessive dilution, once contaminants have been removed. The present study investigates the use of gas-bubble-induced shear stress for the recovery of affinity-adsorbed human erythrocytes. This method has previously been demonstrated to be effective with yeast cells, where it allows cells to be attached, washed and detached under isocratic conditions. Concanavalin A (Con A), used as the binding agent, was attached to the inside of nylon tubes. Whole blood solution, diluted to an erythrocyte concentration of 1x10(8) x ml(-1) with PBS, was incubated with the Con A-nylon surface and then washed with PBS prior to elution. To effect elution, air bubbles of known volume were introduced to the buffer feed to the tubes and the effects of bubble size, bubble volume and bubble velocity on detachment being determined. The results obtained showed that the most significant parameter was bubble number, with up to 90% of attached cells being recovered using a five-bubble sequence. Microscopic examination showed no evidence of mechanical damage to the detached cells.
Knowledge-based system for relational normalization of GDBMS conceptual schemas (2003)

The knowledge-based system described attempts to entirely automatize the normalization process of a real-world database schema and to produce an equivalent, 'better' normalized scheme within the framework of a multilayered GDBMS (generalized database management system) architecture. The implemented system prototype has demonstrated the feasibility of the approach for small databases with simple schema, i.e. schemas with no high-level constructs. For more complex schemas, such as extended E/R schemas with generalization and aggregation high-level constructs, the project made apparent the need for the user to provide more domain-specific semantic knowledge beyond relation attributes, and functional and multivalued dependencies. The technical difficulties related to the interaction between high-level abstraction and normalization, the projection of global functional dependencies, and the management of the combinatorial explosion of decomposed relations have been analyzed.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Extracellular vesicles: their role in cancer biology and epithelial–mesenchymal transition (2016)

Cell-cell communication is critical across an assortment of physiological and pathological processes. Extracellular vesicles (EVs) represent an integral facet of intercellular communication largely through the transfer of functional cargo such as proteins, messenger RNAs (mRNAs), microRNA (miRNAs), DNAs and lipids. EVs, especially exosomes and shed microvesicles, represent an important delivery medium in the tumour micro-environment through the reciprocal dissemination of signals between cancer and resident stromal cells to facilitate tumorigenesis and metastasis. An important step of the metastatic cascade is the reprogramming of cancer cells from an epithelial to mesenchymal phenotype (epithelial-mesenchymal transition, EMT), which is associated with increased aggressiveness, invasiveness and metastatic potential. There is now increasing evidence demonstrating that EVs released by cells undergoing EMT are reprogrammed (protein and RNA content) during this process. This review summarises current knowledge of EV-mediated functional transfer of proteins and RNA species (mRNA, miRNA, long non-coding RNA) between cells in cancer biology and the EMT process. An in-depth understanding of EVs associated with EMT, with emphasis on molecular composition (proteins and RNA species), will provide fundamental insights into cancer biology.
In Vivo application and localization of transcranial focused ultrasound using dual-mode ultrasound arrays (2015)

Focused ultrasound (FUS) has been proposed for a variety of transcranial applications, including neuromodulation, tumor ablation, and blood-brain barrier opening. A flurry of activity in recent years has generated encouraging results demonstrating its feasibility in these and other applications. To date, monitoring of FUS beams has been primarily accomplished using MR guidance, where both MR thermography and elastography have been used. The recent introduction of real-time dual-mode ultrasound array (DMUA) systems offers a new paradigm in transcranial focusing. In this paper, we present first experimental results of ultrasound-guided transcranial FUS (tFUS) application in a rodent brain, both ex vivo and in vivo. DMUA imaging is used for visualization of the treatment region for placement of the focal spot within the brain. This includes the detection and localization of pulsating blood vessels at or near the target point(s). In addition, DMUA imaging is used to monitor and localize the FUS-tissue interactions in real time. In particular, a concave (40 mm radius of curvature), 32-element, 3.5-MHz DMUA prototype was used for imaging and tFUS application in ex vivo and in vivo rat models. The ex vivo experiments were used to evaluate the point spread function of the transcranial DMUA imaging at various points within the brain. In addition, DMUA-based transcranial ultrasound thermography measurements were compared with thermocouple measurements of subtherapeutic tFUS heating in rat brain ex vivo. The ex vivo setting was also used to demonstrate the capability of DMUA to produce localized thermal lesions. The in vivo experiments were designed to demonstrate the ability of the DMUA to apply, monitor, and localize subtherapeutic tFUS patterns that could be beneficial in transient blood-brain barrier opening. The results show that although the DMUA focus is degraded due to the propagation through the skull, it still produces localized heating effects within a sub-millimeter volume. In addition, DMUA transcranial echo data from brain tissue allow for reliable estimation of temperature change.
Biochemical basis of the beta-glucuronidase gene defect causing canine mucopolysaccharidosis VII (1999)

Mucopolysaccharidosis type VII (MPS VII), or Sly syndrome, is an autosomal recessive lysosomal storage disorder resulting from the deficiency in the activity of the enzyme beta-glucuronidase (GUSB). To characterize the biochemical and molecular defect in GUSB-deficient MPS VII dogs, we have measured lysosomal enzyme activities, analyzed distribution of glycosaminoglycans (GAGs), and estimated the size and abundance of the GUSB gene product at the mRNA and protein level in normal, homozygous affected, and heterozygous carrier retinal pigment epithelium (RPE) samples. Compared to normal, only 2-5% and 40-60% of GUSB activity was detected in the affected and the carrier samples, respectively. The decrease in GUSB activity resulted in storage of GAGs predominantly heparan sulfate and chondroitin sulfate. A slight increase in storage of GAGs was also observed in the carrier sample. Northern blot analysis of affected and carrier RPE samples detected a 2.4 kb GUSB transcript similar in size and abundance to that of normal controls. In western blot analysis using anti-human GUSB antibody, three bands of size 78, 56, and 38 kDa were detected in normal samples, which were present at lower intensity in the carrier RPE samples and absent in the MPS VII-affected RPE samples. These results suggest that the mutant GUSB gene causes a posttranscriptional defect and produces an unstable protein.
Exon structure of the gene encoding the human mannose-binding protein-associated serine protease light chain: comparison with complement C1r and C1s genes (1996)

Mannan or mannose-binding protein (MBP) requires a novel serine protease termed MBP-associated serine protease (MASP) for activation of the complement cascade. In this study, we analyzed MASP genomic clones and found that the light chain (catalytic domain) is encoded by six exons, whereas those of the complement C1 subunits, C1r and C1s, and the haptoglobin segment have been reported to be encoded by a single exon. We confirmed the intron-lacking sequence of C1r by analysis of its genome. These results, in conjunction with those obtained by constructing a phylogenetic tree for these proteins, suggest that the MASP gene is prototype and that the intron-lacking sequences of the other serine proteases have a more recent history.
High resolution structure of streptavidin in complex with a novel high affinity peptide tag mimicking the biotin binding motif (2007)

A novel peptide was designed which possesses nanomolar affinity of less than 20 nM for streptavidin. Therefore it was termed Nano-tag and has been used as an affinity tag for recombinant proteins. The minimized version of the wild type Nano-tag is a seven-amino acid peptide with the sequence fMDVEAWL. The three-dimensional structure of wild type streptavidin in complex with the minimized Nano-tag was analyzed at atomic resolution of 1.15 A and the details of the binding motif were investigated. The peptide recognizes the same pocket of streptavidin where the natural ligand biotin is bound, but the peptide requires significantly more space than biotin. Therefore the binding loop adopts an "open" conformation in order to release additional space for the peptide. The conformation of the bound Nano-tag corresponds to a 3(10) helix. However, the analysis of the intermolecular interactions of the Nano-tag with residues of the binding pocket of streptavidin reveals astonishing similarities to the biotin binding motif. In principle the three-dimensional conformation of the Nano-tag mimics the binding mode of biotin. Our results explain why the use of the Nano-tag in fusion with recombinant proteins is restricted to their N-terminus and we describe the special significance of the fMet residue for the high affinity binding mode.
Nickel(II) Complexes of N-Heterocyclic Carbenes (1997)

Nickel(II) complexes with N-heterocyclic carbenes are accessible through substitution of triphenylphosphine in NiX2(PPh3)2 (X = Cl, Br) by the free carbenes or by in situ deprotonation of the corresponding azolium salts with Ni(OAc)2 as the starting material. 1H and 13C NMR as well as X-ray crystallographic data are discussed.
Robust Acoustic Direction of Arrival Estimation Using ROOT-SRP-PHAT, a Realtime Implementation (2006)

Wideband robust direction of arrival estimation using microphone arrays is associated with computationally complex algorithms, unsuitable for implementation on low power devices. This paper improves on the computational complexity by devising an algorithm based on steered response interpolation combined with steered response power estimation employing root solving. The new algorithm is implemented in a PC-based realtime system and has been compared to Root-MUSIC and Far-Field SRP-PHAT. The comparison was performed with regards to computational load and robustness to noise and reverberation in a real room environment. The results show that the new algorithm is the most computationally efficient, while providing superior robustness compared to Root-MUSIC.
SYNTHESIS OF PYRIMIDINE AND AZOLOPYRIMIDINES AS BIODYNAMIC AGENTS (1999)

5-Cyano-6-(4-pyridyl)-2-thiouracil 1 has been synthesized and used as a precursor for the synthesis of mono and bicyclic pyrimidine derivatives 2-10 to evaluate their biodynamic properties. Pyrimidines, being an integral part of DNA and RNA imparts to diverse pharmacological properties, as effective bactericide, fungicide, viricide, insecticide . and meticide l - 3 • Certain pyrimidine derivatives are also known to display antimalarial 4 , antifilarial 5 and antileishmanial 6 activities. The biodynamic property of this ring system prompted us to design pyrimidine derivatives simulating pharmacophore and substituents responsible for diverse pharmacological activities. 5-Cyano-6-( 4-pyridyl)-2-thiouracil 1 was used as a precursor to synthesize various pyrimidine derivatives from the condensation-cyclization reaction of 4pyridyl carboxaldehyde, ethyl cyanoacetate and thiourea in the presence of potassium carbonate using ethanol as solvent. Alkylation of 1 with an equimolar amount of alkyl halide at 0-5°C in DMF using potassium carbonate as a base, produced 2-alkylthio4-oxo-6- (4-pyridyl)-3,4-dihydropyrimidine-5-carbo­ nitriles 2a-f while reaction with two equivalents of alkyl halide .at ambient temperature exclusively yielded 3-alkyl-2-alkylthio-4-oxo-6-( 4-pyridyl)-3,4dihydropyrimidiner- 5-carbonitriles 3a,b. Interaction of 1 with 1,2-dibromoethane in DMF in the presence of potassium carbonate led to the formation of 6-cyano7 -{ 4-pyridyl)-2,3 -dihydrothiazolo[3 ,2-a ]pyrimidin-5(11)­ one 4. Halogenation of 2-methylthio-4-oxo-6-( 4-pyridyl)3,4-dihydropyrimidine-5-carbonitrile 2a with phos­ phoryl chloride provided 4-chloro-2-methylthio-6-( 4pyridyl)pyrimidine-5-carbonitrile 5 which was highly prone to nucleophiles. Reaction of 5 with ethyl 2mercaptoacetate in the presence of base in alcohol afforded 3-amino-2-carboethoxy-6-carboethoxymethyl­ thio-4-( 4-pyridyl)thieno[2,3-dJpyrimidine 6 through tCDRl Communication No. 5799 substitutioncyclization reactions, while reaction with amine under similar reaction conditions yielded only substitution product 7. The high susceptibility of position-2 in 2a towards nucleophile, a reaction with excess of hydrazine hydrate at reflux temperature produced 2-hydrazino-4-oxo-6-( 4-pyridyl)-3 ,4-dihy­ dropyrimidine-5-carbonitrile 8 which underwent condensation-cyclization reactions in formic and acetic acid separately yielding 9a,b (Scheme I). The hydrazine 8 also on reaction with ethyl ethoxymethylenecyanoacetate and 2-carboethoxy-3,3dimethylthioacrylonitrile separately yielded 2-(3amino-4-carboethoxypyrazol-I-yl)-4-oxo-6-( 4-pyridyl)3,4-dihydropyrimidine-5-carbonitrile lOa and 2-(3amino-4-carboethoxy-5-methylthiopyrazol-I-yl)-4-oxo
Picosecond infrared spectroscopy of hot carriers in a modulation-dopedGa0.47In0.53As multiple-quantum-well structure (1988)

Intersubband scattering and cooling of hot carriers is investigated in an $n$-type modulation-doped ${\mathrm{Ga}}_{0.47}$${\mathrm{In}}_{0.53}$As/${\mathrm{Al}}_{0.48}$ ${\mathrm{In}}_{0.52}$As multiple-quantum-well structure. The nonlinear absorption is monitored in several picosecond pump-and-probe experiments after selective excitation of the electrons to the $n=2$ subband. In addition, the relaxation of hot electron-hole pairs created by interband absorption is studied. An upper limit of 3 ps for the lifetime of the electronic $n=2$ subband is estimated. The cooling is dominated by LO-phonon scattering; the energy loss rate is reduced by a factor of up to 130 compared to the value obtained from theoretical calculations.
Polymeric Micelles for Drug Delivery (2006)

Polymeric micelles are nanoscopic core/shell structures formed by amphiphilic block copolymers. Both the inherent and modifiable properties of polymeric micelles make them particularly well suited for drug delivery purposes. An emphasis of this review has been placed on both the description and characterization techniques of the physical properties of polymeric micelles. Relevant properties discussed include micellar association, morphology, size and stability. These properties and characterization techniques are included to provide context for the known advantages and applications of polymeric micelles for drug delivery. The advantages and applications discussed include solubilization of poorly soluble molecules, sustained release and size advantages, and protection of encapsulated substances from degradation and metabolism. The three most widely studied block copolymer classes are characterized by their hydrophobic blocks, and are poly(propylene oxide), poly(L-amino acid)s and poly(ester)s. These three classes of block copolymers are reviewed with multiple examples of current research in which formulation techniques with polymeric micelles have been applied to some of the most challenging molecules in the pharmaceutical industry. The polymeric micelles used for drug delivery in these examples have shown the abilities to attenuate toxicities, enhance delivery to desired biological sites and improve the therapeutic efficacy of active pharmaceutical ingredients.
Study of novel d1 alleles, defective mutants of the .ALPHA. subunit of heterotrimeric G-protein in rice (2009)

It has been shown that the disruption of the alpha-subunit gene of heterotorimeric G-proteins (Galpha) results in dwarf traits, the erection of leaves and the setting of small seeds in rice. These mutants are called d1. We have studied the expression profiles of the transcripts and translation products of rice Galpha in ten alleles of d1 including five additional alleles newly identified. By RT-PCR, the transcripts of the Galpha gene were detected in the all d1 alleles. By western blot, the Galpha proteins were not detected in the plasma membrane fractions of the d1 alleles with the exception of d1-4. In d1-4, one amino acid change in the GTP-binding box A of the Galpha protein was occurred and even in this case the Galpha protein was only just detectable in the plasma membrane fraction. Given that the Galpha protein did not accumulate in the plasma membrane fraction in d1-8 which has a deletion of just a single amino acid in the Galpha protein, it is likely that a proper conformation of the Galpha is necessary for accumulation of Galpha protein in the plasma membrane. Nine alleles of d1 showed a severer phenotype whilst d1-4 exhibited a mild phenotype with respect to seed size and elongation pattern of internodes. As brassinosteroid signaling was known to be partially impaired in d1s, the sensitivity to 24-epibrassinolide (24-epiBL) was compared among d1 alleles in a T65 genetic background. Only d1-4 showed responses similar to wild type rice. The results show that the d1-4 mutant is a mild allele in terms of the phenotype and mild hyposensitivity to the exogenously applied 24-epiBL.
ELK, a new protocol for efficient large-group key distribution (2002)

Secure media broadcast over the Internet poses unique security challenges. One problem is access control to a large number of subscribers in a public broadcast. A common solution is to encrypt the broadcast data and to disclose the decryption key to legitimate receivers only. However, how do we securely and efficiently establish a shared secret among the legitimate receivers? And most importantly, how can we efficiently update the group key securely if receivers join or leave? How can we provide reliability for key update messages in a way that scales up to large groups? Recent research makes substantial progress to address these challenges. Current schemes feature efficient key update mechanisms assuming that the key updates are communicated reliably to the receivers. In practice, however the principal impediment to achieve a scalable system is to distribute the key updates reliably to all receivers. We have designed and implemented ELK, a novel key distribution protocol, to address these challenges with the following features: ELK features perfectly reliable, super-efficient member joins; ELK uses smaller key update messages than previous protocols; ELK features a mechanism that allows short hint messages to be used for key recovery allowing a tradeoff of communication overhead with member computation; ELK proposes to append a small amount of key update information to data packets, such that the majority of receivers can recover from lost key update messages; and ELK allows to trade off security with communication overhead.