gebhart/patrepeval huggingface dataset:
Peroxisome Proliferator–Activated Receptor α Induces NADPH Oxidase Activity in Macrophages, Leading to the Generation of LDL with PPAR-α Activation Properties (2004)

Peroxisome proliferator-activated receptors (PPARs) are nuclear receptors controlling lipid and glucose metabolism as well as inflammation. PPARs are expressed in macrophages, cells that also generate reactive oxygen species (ROS). In this study, we investigated whether PPARs regulate ROS production in macrophages. Different PPAR-alpha, but not PPAR-gamma agonists, increased the production of ROS (H2O2 and ) in human and murine macrophages. PPAR-alpha activation did not induce cellular toxicity, but significantly decreased intracellular glutathione levels. The increase in ROS production was not attributable to inherent prooxidant effects of the PPAR-alpha agonists tested, but was mediated by PPAR-alpha, because the effects were lost in bone marrow-derived macrophages from PPAR-alpha-/- mice. The PPAR-alpha-induced increase in ROS was attributable to the induction of NADPH oxidase, because (1) preincubation with the NADPH oxidase inhibitor diphenyleneiodinium prevented the increase in ROS production; (2) PPAR-alpha agonists increased production measured by superoxide dismutase-inhibitable cytochrome c reduction; (3) PPAR-alpha agonists induced mRNA levels of the NADPH oxidase subunits p47(phox), p67phox, and gp91phox and membrane p47phox protein levels; and (4) induction of ROS production was abolished in p47phox-/- and gp91phox-/- macrophages. Finally, induction of NADPH oxidase by PPAR-alpha agonists resulted in the formation of oxidized LDL metabolites that exert PPAR-alpha-independent proinflammatory and PPAR-alpha-dependent decrease of lipopolysaccharide-induced inducible nitric oxide synthase expression in macrophages. These data identify a novel mechanism of autogeneration of endogenous PPAR-alpha ligands via stimulation of NADPH oxidase activity.
Hearing Your Voice is Not Enough (2017)

Voice biometrics is drawing increasing attention as it is a promising alternative to legacy passwords for mobile authentication. Recently, a growing body of work shows that voice biometrics is vulnerable to spoofing through replay attacks, where an adversary tries to spoof voice authentication systems by using a pre-recorded voice sample collected from a genuine user. In this work, we propose VoiceGesture, a liveness detection system for replay attack detection on smartphones. It detects a live user by leveraging both the unique articulatory gesture of the user when speaking a passphrase and the mobile audio hardware advances. Specifically, our system re-uses the smartphone as a Doppler radar, which transmits a high frequency acoustic sound from the built-in speaker and listens to the reflections at the microphone when a user speaks a passphrase. The signal reflections due to user's articulatory gesture result in Doppler shifts, which are then analyzed for live user detection. VoiceGesture is practical as it requires neither cumbersome operations nor additional hardware but a speaker and a microphone that are commonly available on smartphones. Our experimental evaluation with 21 participants and different types of phones shows that it achieves over 99% detection accuracy at around 1% Equal Error Rate (EER). Results also show that it is robust to different phone placements and is able to work with different sampling frequencies.
Anti-Angiogenesis Drugs in Diabetic Retinopathy (2011)

The vascular endothelial growth factor (VEGF) plays a key role in the development of proliferative diabetic retinopathy (PDR) and diabetic macular edema (DME), resulting in a significant visual loss among patients with diabetes mellitus. Systemic VEGF-A and the interplay between membrane-bound VEGF receptors and VEGF-R1 (soluble form) are key to angiogenesis and vasculogenesis. Furthermore, patients with diabetes have a higher risk of hypertension and proteinuria, two surrogate markers of systemic VEGF inhibition. Pegaptanib, ranibizumab, bevacizumab and roboxistaurin are the currently available anti-VEGF agents. Agents with activity occurring later down the angiogenic pathway and those drugs with potential to synergize with anti-VEGF-A technologies are being developed. In recent years, inhibition of ocular VEGF has emerged as a promising treatment modality for diabetes and is currently undergoing evaluation in clinical trials. A potential role for these anti-VEGF agents in the prevention of PDR and DME are also emerging.
The future of MEMS in telecommunications networks (2000)

The move toward dense wavelength-division-multiplexed networks provides an application-rich environment for MEMS components and systems. In many crucial component applications, there are no clear technological winners, leaving room for new technologies such as MEMS to create inroads. In this paper, wavelength-division-multiplexed networks and their evolution are discussed and examples of several MEMS devices being developed for telecommunication systems are presented.
An experimental study of mechanism and specificity of peptide nucleic acid (PNA) binding to duplex DNA (1999)

We investigated the mechanism and kinetic specificity of binding of peptide nucleic acid clamps (bis-PNAs) to double-stranded DNA (dsDNA). Kinetic specificity is defined as a ratio of initial rates of PNA binding to matched and mismatched targets on dsDNA. Bis-PNAs consist of two homopyrimidine PNA oligomers connected by a flexible linker. While complexing with dsDNA, they are known to form P-loops, which consist of a [PNA]2-DNA triplex and the displaced DNA strand. We report here a very strong pH-dependence, within the neutral pH range, of binding rates and kinetic specificity for a bis-PNA consisting of only C and T bases. The specificity of binding reaches a very sharp and high maximum at pH 6.9. In contrast, if all the cytosine bases in one of the two PNA oligomers within the bis-PNA are replaced by pseudoisocytosine bases (J bases), which do not require protonation to form triplexes, a weak dependence on pH of the rates and specificity of the P-loop formation is observed. A theoretical analysis of the data suggests that for (C+T)-containing bis-PNA the first, intermediate step of PNA binding to dsDNA occurs via Hoogsteen pairing between the duplex target and one oligomer of bis-PNA. After that, the strand invasion occurs via Watson-Crick pairing between the second bis-PNA oligomer and the homopurine strand of the target DNA, thus resulting in the ultimate formation of the P-loop. The data for the (C/J+T)-containing bis-PNA show that its high affinity to dsDNA at neutral pH does not seriously compromise the kinetic specificity of binding. These findings support the earlier expectation that (C/J+T)-containing PNA constructions may be advantageous for use in vivo.
In Vivo Imaging of Membrane-Associated Glycans in Developing Zebrafish (2008)

Glycans are attractive targets for molecular imaging but have been inaccessible because of their incompatibility with genetically encoded reporters. We demonstrated the noninvasive imaging of glycans in live developing zebrafish, using a chemical reporter strategy. Zebrafish embryos were treated with an unnatural sugar to metabolically label their cell-surface glycans with azides. Subsequently, the embryos were reacted with fluorophore conjugates by means of copper-free click chemistry, enabling the visualization of glycans in vivo at subcellular resolution during development. At 60 hours after fertilization, we observed an increase in de novo glycan biosynthesis in the jaw region, pectoral fins, and olfactory organs. Using a multicolor detection strategy, we performed a spatiotemporal analysis of glycan expression and trafficking and identified patterns that would be undetectable with conventional molecular imaging approaches.
Molecular Requirements for the Inhibition of the Tetracycline Antiport Protein and the Effect of Potent Inhibitors on the Growth of Tetracycline-Resistant Bacteria (1994)

Forty-seven compounds and tetracycline (Tc) structural analogues were tested for their ability to interfere with [3H]Tc uptake in everted inner membrane vesicles derived from Tc-resistant Escherichia coli D1-209, bearing the class B tetracycline resistance efflux protein (Tet protein). For effective inhibition of Tc uptake, the molecule had to have an intact ABCD tetracyclic carbon skeleton and a conjugated phenolic beta-diketone substructure at positions 10-12a with the subsequent development of keto-enol tautomerization. Molecular variations at carbon positions 2, 4, 5, 6, 7, 8, and 9 did not decrease, and some increased, the inhibitory activity as compared to that of Tc. Among these compounds, the highest inhibition of uptake occurred with certain position 6 and 13 derivatives of 5-hydroxytetracycline. In a group of 13-(propylthio) derivatives of 5-OH-Tc [13-propyl, 13-(3-chloropropyl), and 13-(2-carboxyethyl)] there was a correlation between uptake inhibitory activity and antibacterial activity. The 13-(3-chloropropyl) derivative, with the best efflux inhibitory activity, exhibited synergistic activity when tested in combination with doxycycline against Tc-resistant E. coli bearing the class A or B determinant, against Staphylococcus aureus bearing class K, and against Enterococcus faecalis bearing the class L determinant. The 13-propyl analogue also showed high transport blocking activity and showed synergistic antibacterial activity against E. coli bearing the class A determinant and additive activity against the other Tc-resistant bacteria. The synergistic antibacterial activity of these compounds was not shown by the 13-[(2-carboxyethyl)thio] homologue, whose efflux blocking activity was 70-fold less. These findings suggest that multiple sites on the Tc molecule are available for synthetic modification toward the development of an effective Tc blocking agent. Such compounds, used alone or in combination with a standard tetracycline, show improved antibacterial activity.
155 Mbit/s transmission using ASE-injected Fabry-Perot laser diode in WDM-PON over 70°C temperature range (2003)

Thermal reliability of an uncooled Fabry-Perot laser diode (F-PLD) wavelength-locked to spectrum-sliced amplified spontaneous emission (ASE) as a source for wavelength division multiplexed-passive optical networks (WDM-PONs) is presented. An F-PLD with narrow mode spacing and asymmetric facet reflectivity relieved temperature dependency of transmission and power requirement of ASE injection. The chip temperature range of error-free transmission at 155 Mbit/s extended over 70°C with −22 dBm ASE injection.
Ethylene Perception by the ERS1 Protein in Arabidopsis (2000)

Ethylene perception in Arabidopsis is controlled by a family of five genes, including ETR1, ERS1 (ethylene response sensor 1), ERS2, ETR2, and EIN4. ERS1, the most highly conserved gene with ETR1, encodes a protein with 67% identity to ETR1. To clarify the role of ERS1 in ethylene sensing, we biochemically characterized the ERS1 protein by heterologous expression in yeast. ERS1, like ETR1, forms a membrane-associated, disulfide-linked dimer. In addition, yeast expressing the ERS1 protein contains ethylene-binding sites, indicating ERS1 is also an ethylene-binding protein. This finding supports previous genetic evidence that isoforms of ETR1 also function in plants as ethylene receptors. Further, we used the ethylene antagonist 1-methylcyclopropene (1-MCP) to characterize the ethylene-binding sites of ERS1 and ETR1. We found 1-MCP to be both a potent inhibitor of the ethylene-induced seedling triple response, as well as ethylene binding by yeast expressing ETR1 and ERS1. Yeast expressing ETR1 and ERS1 showed nearly identical sensitivity to 1-MCP, suggesting that the ethylene-binding sites of ETR1 and ERS1 have similar affinities for ethylene.
Inhibition of human immunodeficiency virus type 1 expression by a hairpin ribozyme. (1992)

Ribozymes are RNAs that possess the dual properties of RNA sequence-specific recognition, analogous to conventional antisense molecules, and RNA substrate destruction via site-specific cleavage. The cleavage reaction is catalytic in that more than one substrate molecule is processed per ribozyme molecule. We have designed a hairpin ribozyme that cleaves human immunodeficiency virus type 1 (HIV-1) RNA in the leader sequence (at nucleotides +111/112 relative to the transcription initiation site). The ribozyme was tested in vitro and gave efficient and specific cleavage of RNA containing the leader sequence. To test the antiviral efficacy of this ribozyme, we have cotransfected into HeLa cells HIV-1 proviral DNA and a plasmid expressing the ribozyme from the human beta-actin promoter. HIV-1 expression was inhibited as measured by p24 antigen levels and reduced Tat activity. The antiviral effect of the ribozyme appears to be specific and results from directed RNA cleavage; activity requires both a target sequence and a functional RNA catalytic center. These results suggest that this HIV-1-directed hairpin ribozyme may be useful as a therapeutic agent.
Adaptive Triangular Meshes for Cloth Simulation (2005)

Significant progress has been achieved over the last decade in the realistic animation of garments. However it is still a very costly process in terms of computational resources. Since wrinkles and vast smooth areas co-exist commonly, it is tempting to reduce computational cost by avoiding redundant tessellation at the smooth areas. In this paper we present a method for dynamic adaptation of triangular meshes suitable for the most elaborated cloth simulation approaches, such as finite-element based or alike. We use bottom-up approach to mesh refinement, which does not require precomputation and storage of multiresolution hierarchy. The hierarchy is constructed in runtime using √3-refinement rule. The hierarchy is essential to allow reverting of the refinement locally. Local mesh refinement and simplification are triggered by curvature-induced criterion, where the curvature is estimated using methods of discrete differential geometry. In the existing literature of adaptive meshes only the formulas for estimating the discrete mean curvature at the inner mesh vertices can be found. We extend it to the triangulated 2-manifolds with boundary, such as cloth meshes. The results demonstrated are the realistic animation of garment worn by a walking mannequin generated with Baraff-Witkin type cloth solver enhanced with our mesh adaptation scheme.
Biosynthesis of Methanopterin (1996)

This paper establishes the pathway for the biosynthesis of methanopterin in Methanosarcina thermophila to proceed by the following series of reactions. First, 5-phospho-α-d-ribosyl diphosphate (PRPP) and 4-aminobenzoic acid condense together to produce 4-(β-d-ribofuranosyl)aminobenzene 5‘-phosphate, which then reacts with 6-hydroxymethyl-7,8-H2pterin pyrophosphate to produce 7,8-H2pterin-6-ylmethyl-4-(β-d-ribofuranosyl)aminobenzene 5‘-phosphate (3‘). Compound 3‘ is then reduced to 7,8-H2pterin-6-ylmethyl-1-(4-aminophenyl)-1-deoxy-d-ribitol 5‘-phosphate (4‘) in a reaction stimulated by the addition of FMN or factor F420. Dephosphorylation of compound 4‘ leads to 7,8-H2pterin-6-ylmethyl-1-(4-aminophenyl)-1-deoxy-d-ribitol (5‘). Compound 5‘ then condenses with another molecule of PRPP to form 7,8-H2pterin-6-ylmethyl-1-(4-aminophenyl)-1-deoxy-5-[1-α-d-ribofuranosyl 5-phosphate]-d-ribitol (9‘). Compound 9‘, in the presence of ATP, then condenses with (S)-2-hydroxyglutaric acid to form demethylated H2methanopterin, a known precursor to methanopterin. The occurrence of this pathway was confirmed by (a) the chemical and/or biochemical synthesis of most of the proposed intermediates, (b) the detection of these intermediates in cell-free extracts, and (c) by the measurement of their conversion to demethylated methanopterin and/or other intermediates in the pathway.
Prime editing efficiently generates W542L and S621I double mutations in two ALS genes in maize (2020)

Abstract A novel and universal CRISPR/Cas-derived precision genome-editing technology named prime editing was developed. However, low efficiency of prime editing was shown in transgenic rice lines. We reasoned that enhancing pegRNA expression would improve prime-editing efficiency. In this report, we describe two strategies for enhancing pegRNA expression. We constructed a prime-editing vector harboring two pegRNA variants for W542L and S621I double mutations in ZmALS1 and ZmALS2 . Compared with previous reports in rice, we achieved much higher prime-editing efficiency in maize. Our results are inspiring and provide a direction for the optimization of plant prime editors.
Effects of clipping and filtering on the performance of OFDM (1998)

Orthogonal frequency division multiplexing (OFDM) is an attractive technique for wireless communication applications. However, an OFDM signal has a large peak-to-mean envelope power ratio, which can result in significant distortion when passed through a nonlinear device, such as a transmitter power amplifier. We investigate, through extensive computer simulations, the effects of clipping and filtering on the performance of OFDM, including the power spectral density, the crest factor, and the bit-error rate. Our results show that clipping and filtering is a promising technique for the transmission of OFDM signals using realistic linear amplifiers.
Glucagon-Like Peptide-1 Synthetic Analogs: New Therapeutic Agents for Use in the Treatment of Diabetes Mellitus (2003)

Glucagon-like peptide-1-(7-36)-amide (GLP-1) is a potent blood glucose-lowering hormone now under investigation for use as a therapeutic agent in the treatment of type 2 (adult onset) diabetes mellitus. GLP-1 binds with high affinity to G protein-coupled receptors (GPCRs) located on pancreatic beta-cells, and it exerts insulinotropic actions that include the stimulation of insulin gene transcription, insulin biosynthesis, and insulin secretion. The beneficial therapeutic action of GLP-1 also includes its ability to act as a growth factor, stimulating formation of new pancreatic islets (neogenesis) while slowing beta-cell death (apoptosis). GLP-1 belongs to a large family of structurally-related hormones and neuropeptides that include glucagon, secretin, GIP, PACAP, and VIP. Biosynthesis of GLP-1 occurs in the enteroendocrine L-cells of the distal intestine, and the release of GLP-1 into the systemic circulation accompanies ingestion of a meal. Although GLP-1 is inactivated rapidly by dipeptidyl peptidase IV (DDP-IV), synthetic analogs of GLP-1 exist, and efforts have been directed at engineering these peptides so that they are resistant to enzymatic hydrolysis. Additional modifications of GLP-1 incorporate fatty acylation and drug affinity complex (DAC) technology to improve serum albumin binding, thereby slowing renal clearance of the peptides. NN2211, LY315902, LY307161, and CJC-1131 are GLP-1 synthetic analogs that reproduce many of the biological actions of GLP-1, but with a prolonged duration of action. AC2993 (Exendin-4) is a naturally occurring peptide isolated from the lizard Heloderma, and it acts as a high affinity agonist at the GLP-1 receptor. This review summarizes structural features and signal transduction properties of GLP-1 and its cognate beta-cell GPCR. The usefulness of synthetic GLP-1 analogs as blood glucose-lowering agents is discussed, and the applicability of GLP-1 as a therapeutic agent for treatment of type 2 diabetes is highlighted.
Stabilization of the merocyanine form of photochromic compounds in fluoro alcohols is due to a hydrogen bond (1998)

Fluoroalcohols [1,1,1,3,3,3-hexafluoropropan-2-ol (HFP), 2,2,2-trifluoroethanol (TFE) and 2-fluoroethanol (FE)], acting as Lewis acids, stabilize the π-conjugated, colored merocyanine forms of spiropyran and spirooxazine photochromic compounds as metal ions do.
Unsupervised adaptation using structural Bayes approach (2002)

It is well-known that the performance of recognition systems is often largely degraded when there is a mismatch between the training and testing environment. It is desirable to compensate for the mismatch when the system is in operation without any supervised learning. Previously, a structural maximum a posteriori (SMAP) adaptation approach, in which a hierarchical structure in the parameter space is assumed, was proposed. In this paper, this SMAP method is applied to unsupervised adaptation. A novel normalization technique is also introduced as a front end for the adaptation process. The recognition results showed that the proposed method was effective even when only one utterance from a new speaker was used for adaptation. Furthermore, an effective way to combine the supervised adaptation and the unsupervised adaptation was investigated to reduce the need for a large amount of supervised learning data.
Evaluation of Clostridium novyi–NT spores in dogs with naturally occurring tumors (2011)

Results indicated that C. novyi-NT can germinate within tumors of dogs. Toxicosis, although common and sometimes severe, was manageable with treatment. Further studies in dogs with superficial tumors may allow for continued dose escalation and provide information for use in clinical trials in veterinary and human oncology.
Understanding migraine: Potential role of neurogenic inflammation (2016)

Neurogenic inflammation, a well-defined pathophysiologial process is characterized by the release of potent vasoactive neuropeptides, predominantly calcitonin gene-related peptide (CGRP), substance P (SP), and neurokinin A from activated peripheral nociceptive sensory nerve terminals (usually C and A delta-fibers). These peptides lead to a cascade of inflammatory tissue responses including arteriolar vasodilation, plasma protein extravasation, and degranulation of mast cells in their peripheral target tissue. Neurogenic inflammatory processes have long been implicated as a possible mechanism involved in the pathophysiology of various human diseases of the nervous system, respiratory system, gastrointestinal tract, urogenital tract, and skin. The recent development of several innovative experimental migraine models has provided evidence suggestive of the involvement of neuropeptides (SP, neurokinin A, and CGRP) in migraine headache. Antidromic stimulation of nociceptive fibers of the trigeminal nerve resulted in a neurogenic inflammatory response with marked increase in plasma protein extravasation from dural blood vessels by the release of various sensory neuropeptides. Several clinically effective abortive antimigraine medications, such as ergots and triptans, have been shown to attenuate the release of neuropeptide and neurogenic plasma protein extravasation. These findings provide support for the validity of using animal models to investigate mechanisms of neurogenic inflammation in migraine. These also further strengthen the notion of migraine being a neuroinflammatory disease. In the clinical context, there is a paucity of knowledge and awareness among physicians regarding the role of neurogenic inflammation in migraine. Improved understanding of the molecular biology, pharmacology, and pathophysiology of neurogenic inflammation may provide the practitioner the context-specific feedback to identify the novel and most effective therapeutic approach to treatment. With this objective, the present review summarizes the evidence supporting the involvement of neurogenic inflammation and neuropeptides in the pathophysiology and pharmacology of migraine headache as well as its potential significance in better tailoring therapeutic interventions in migraine or other neurological disorders. In addition, we have briefly highlighted the pathophysiological role of neurogenic inflammation in various other neurological disorders.