gebhart/patrepeval huggingface dataset:
Peroxisome proliferator-activated receptor-? as a target for wound healing drugs (2004)

Healing of cutaneous wounds, which is crucial for survival after an injury, proceeds via a well-tuned pattern of events including inflammation, re-epithelialisation, and matrix and tissue remodelling. These events are regulated spatio-temporally by a variety of growth factors and cytokines. The inflammation that immediately follows injury increases the expression of peroxisome proliferator-activated receptor (PPAR)-β in the wound edge keratinocytes and triggers the production of endogenous PPARβ ligands that activate the newly produced receptor. This elevated PPARβ activity results in increased resistance of the keratinocytes to the apoptotic signals released during wounding, allowing faster re-epithelialisation. The authors speculate that, in parallel, ligand activation of PPARβ in infiltrated macrophages attenuates the inflammatory response, which also promotes repair. Thus, current understanding of the roles of PPARβ in different cell types implicated in tissue repair has revealed an intriguing intercellular cross-talk that coordinates, spatially and temporally, inflammation, keratinocyte survival, proliferation and migration, which are all essential for efficient wound repair. These novel insights into the orchestrating roles of PPARβ during wound healing may be helpful in the development of drugs for acute and chronic wound disorders.
Generation and detection of broadband laser generated ultrasound from low-power laser sources (2001)

This paper presents the basic principles of the laser generation of ultrasound (LGU) through thermal conversion and illustrates the approaches to its use in material evaluation using the broadband features of the source. Traditional LGU involves high energy optical pulse irradiation which often induces surface damage, especially in carbon or glass fiber composites. We therefore expand the concept into low power excitations using laser diode sources. This enables excitation without damage but requires coded temporal signals. Arrays of semiconductor laser sources can also produce very broadband acoustic signals, both temporally and spatially. Piezoelectric sources are usually the opposite constrained in both space and time. This basic observation opens new avenues of material investigation, some of which feature in this paper.
Revisiting the quorum-sensing hierarchy in Pseudomonas aeruginosa: the transcriptional regulator RhlR regulates LasR-specific factors (2009)

Pseudomonas aeruginosa uses the two major quorum-sensing (QS) regulatory systems las and rhl to modulate the expression of many of its virulence factors. The las system is considered to stand at the top of the QS hierarchy. However, some virulence factors such as pyocyanin have been reported to still be produced in lasR mutants under certain conditions. Interestingly, such mutants arise spontaneously under various conditions, including in the airways of cystic fibrosis patients. Using transcriptional lacZ reporters, LC/MS quantification and phenotypic assays, we have investigated the regulation of QS-controlled factors by the las system. Our results show that activity of the rhl system is only delayed in a lasR mutant, thus allowing the expression of multiple virulence determinants such as pyocyanin, rhamnolipids and C(4)-homoserine lactone (HSL) during the late stationary phase. Moreover, at this stage, RhlR is able to overcome the absence of the las system by activating specific LasR-controlled functions, including production of 3-oxo-C(12)-HSL and Pseudomonas quinolone signal (PQS). P. aeruginosa is thus able to circumvent the deficiency of one of its QS systems by allowing the other to take over. This work demonstrates that the QS hierarchy is more complex than the model simply presenting the las system above the rhl system.
Electronically controlled optical beam-steering by an active phased array of metallic nanoantennas (2013)

An optical phased array of nanoantenna fabricated in a CMOS compatible silicon photonics process is presented. The optical phased array is fed by low loss silicon waveguides with integrated ohmic thermo-optic phase shifters capable of 2π phase shift with ∼ 15 mW of applied electrical power. By controlling the electrical power to the individual integrated phase shifters fixed wavelength steering of the beam emitted normal to the surface of the wafer of 8° is demonstrated for 1 × 8 phased arrays with periods of both 6 and 9 μm.
Effects of selective vagal and stellate ganglion stimulation on atrial refractoriness (1974)

This study reports results of selective right and left vagosympathetic trunk (VST) and stellate ganglion stimulation (supra-maximal intensity) on atrial refractory period (ARP) in dogs. The effect of selective stellate stimulation on A-V conduction was also evaluated. During right and left VST stimulation, the region of the sinus node exhibited greater ARP shortening than most of the tested sites on the right atrium and all of the tested sites on the left atrium. The right VST exerted a greater effect on the right atrium than on the left atrium. Right VST stimulation shortened ARP at most tested right atrial sites more than did left VST stimulation. Selective vagal stimulation could result in three-fold difference in ARPs at the same electrode site. During right or left stellate ganglion stimulation, the refractory period change at any atrial site was usually minimal and often did not change at all. Supra-maximal right or left stellate stimulation shortened A-H (nodal) conduction by 50% or more in some experiments but shortened conduction time distal to the bundle of His by only 1 to 3 msec.
Identity of Osteoclastogenesis Inhibitory Factor (OCIF) and Osteoprotegerin (OPG): A Mechanism by which OPG/OCIF Inhibits Osteoclastogenesisin Vitro1 (1998)

The morphogenesis and remodeling of bone depends on the integrated activity of osteoblasts that form bone and osteoclasts that resorb bone. We previously reported the isolation of a new cytokine termed osteoclastogenesis inhibitory factor, OCIF, which specifically inhibits osteoclast development. Here we report the cloning of a complementary DNA of human OCIF. OCIF is identical to osteoprotegerin (OPG), a soluble member of the tumor-necrosis factor receptor family that inhibits osteoclastogenesis. Recombinant human OPG/OCIF specifically acts on bone tissues and increases bone mineral density and bone volume associated with a decrease of active osteoclast number in normal rats. Osteoblasts or bone marrow-derived stromal cells support osteoclastogenesis through cell-to-cell interactions. A single class of high affinity binding sites for OPG/OCIF appears on a mouse stromal cell line, ST2, in response to 1,25-dihydroxyvitamin D3. An anti-OPG/OCIF antibody that blocks the binding abolishes the biological activity of OPG/OCIF. When the sites are blocked with OPG/OCIF, ST2 cells fail to support osteoclastogenesis. These results suggest that the sites are involved in cell-to-cell signaling between stromal cells and osteoclast progenitors and that OPG/OCIF inhibits osteoclastogenesis by interrupting the signaling through the sites.
2019년 유럽의회선거의 함의: 극우 포퓰리즘과 중도자유주의의 부상 (2019)

본 연구는 2019년 유럽의회선거 결과의 함의를 분석하는 것을 목표로 한다. 기존 연구는 유럽의회선거가 국내 이슈에 의해 좌우되는 부차적인 선거로 기능한다고 분석해왔으나, 이번 선거는 브렉시트 협상과 극우 포퓰리즘 부상이라는 유럽 쟁점이 부각됐으며, 투표율도 크게 상승하여 2000년대 이후 최고 수치인 50.62%를 기록했다. 각 정치그룹별 의석수에도 큰 변화가 있었다. 첫째, 유럽의회를 이끌어 오던 유럽인민당그룹(EPP)과 유럽사회민주그룹(S&D)은 과반 의석을 달성하는 데에 실패했다. 둘째, 중도자유주의그룹인 리뉴유럽(Renew Europe)의 의석수가 크게 증가했다. 셋째, 극우 정치그룹은 정체성과민주주의그룹(ID)을 중심으로 결집하여 본격적인 정치세력화를 시도했다. 중도자유주의의 부상은 반-유럽 포퓰리즘 인기에 대한 반작용으로 볼 수 있다. 특히 중도우파와 중도좌파 그룹이 이민통제와 안보, 고용과 복지를 위한 국가개입 필요성을 강조했기 때문에 리뉴유럽그룹의 개방시장경쟁에 대한 강조는 차별화되는 쟁점을 형성했다. 극우 포퓰리즘과 함께 중도자유주의가 유럽의 정치 균열을 새롭게 재편했으며, 유럽의회에서 ‘자유주의’ 대 ‘보호주의’의 대립구도가 보다 선명해졌다.
Genetic stability of RSV-F expression and the restricted growth phenotype of a live attenuated PIV3 vectored RSV vaccine candidate (MEDI-534) following restrictive growth in human lung cells (2013)

MEDI-534 is the first live, attenuated and vectored respiratory syncytial virus (RSV) vaccine to be evaluated in seronegative children. It consists of a bovine/human parainfluenza virus type 3 (PIV3) backbone with the RSV fusion glycoprotein (RSV-F) expressed from the second position. The PIV3 fusion and hemaglutinin-neuraminidase proteins are human-derived. No small animal appropriately replicates the restrictive growth of bovine PIV3 (bPIV3) based viruses relative to human PIV3 (hPIV3) observed in the respiratory tract of rhesus monkeys and humans, making analysis of the genetic stability of the attenuation phenotype and maintenance of RSV-F expression difficult. Screening of multiple cell-lines identified MRC-5 cells as supporting permissive growth of hPIV3 while restricting bPIV3 and MEDI-534 growth. In MRC-5 cells, the peak titers of MEDI-534 were more than 20-fold lower compared to hPIV3 peak titers. After more than 10 multicycle passages in MRC-5 cells, genetic alterations were detected in MEDI-534 that contributed to a partial loss in restricted growth in MRC-5 cells and a decrease in RSV-F expression. These adaptive mutations did not occur in the RSV-F gene but were found in the polyA sequence upstream of the transgene. MRC-5 adapted MEDI-534 viruses (1) lost some attenuation but did not replicate to the level of hPIV3 in this cell line, (2) did not completely lose RSV-F expression and (3) were able to elicit a protective anti-RSV immune response in hamsters despite lower levels of RSV-F expression. Interestingly analysis of shed MEDI-534 from a recent clinical trial indicates that in some recipients similar mutations arise by day 7 or day 12 post immunization (in press) suggesting that these mutations can arise rapidly in the human host. The utility and limits of MRC-5 cells for characterizing the attenuation and RSV-F expression of MEDI-534 is discussed.
Visualization of Newly Deposited tau in Neurofibrillary Tangles and Neuropil Threads (2005)

Neurofibrillary tangles (NFTs) and neuropil threads (NTs), the major hallmark of Alzheimer disease (AD), are composed of the microtubule-associated protein tau that has undergone posttranslational modifications, including deamidation and isomerization on asparaginyl or aspartyl residues. Because such modifications represent protein aging, we generated 2 antibodies, TM4, specific for Asp-387 of tau, and iD387, specific for isoAsp-387 of tau, to investigate the evolution of NFTs and NTs. On Western blots of Sarkosyl-insoluble fractions, TM4 strongly labeled paired helical filament-tau (PHF-tau), whereas iD387 preferentially labeled PHF smear. Thus, it is reasonable to postulate that TM4-labeled tau (unmodified tau species) represents more recent deposition, and iD387-labeled tau (modified tau species) represents earlier deposition. Unexpectedly, TM4 immunostained even highly evolved NFTs, suggesting that deposition of newly produced tau continues until neuronal death. iD387 labeled the whole profile of NFTs up to distal dendritic branches, whereas TM4 staining was localized to particular portions of NFTs in proximal dendrites and neuronal perikarya. In NTs, TM4 preferentially labeled the outer portion, whereas iD387 intensely labeled the core portion. Based on TM4-positive NFT counts and total NFT counts, we speculate that NFTs in the human hippocampus are produced at a constant rate irrespective of the disease stage.
Micromachined pixel arrays integrated with CMOS for infrared applications (2002)

Large arrays of small micromachined structures with low thermal mass and low thermal-conductance above silicon CMOS substrates and operate as (1) sensitive uncooled IR cameras or (2) high-temperature IR projectors. Arrays of small thin micromachined structures with high thermal masses, are suspended above the underlying silicon substrate by supports that are extremely well thermally isolated from the substrate with a high thermal conductance. This high thermal isolation allows for efficient heating of the microstructure with small currents (the case for microemitters), or small amounts of infrared (IR) incident flux (for microbolometers). The low mass ensures that despite the low conductance, the thermal time constants are in the millisecond range. We show the basic microstructure design common to both microbolometers and microemitters.
Synchronization in ad hoc networks based on UTRA TDD (2003)

Within the FleetNet project an ad hoc radio network for intervehicle communications (IVC) and road telematics is being developed. For the air interface, the framework of the UMTS Terrestrial Radio Access time division duplex (UTRA TDD) standard has been selected as the most promising candidate. The requirements and challenges for synchronization in an ad hoc network with rapidly changing topology and high velocities are discussed. Solutions for synchronization in ad hoc networks based on UTRA TDD are proposed and evaluated by means of link-level simulations. The results indicate promising performance with only minor changes to the UTRA TDD standard specifications.
Alterations in potential sites for glycosylation predominate during evolution of the simian immunodeficiency virus envelope gene in macaques (1992)

Genetic diversity is a hallmark of the human immunodeficiency virus (HIV) genome, but the role of distinct HIV variants in the development of AIDS is unclear. Envelope (env) is the most highly variable gene in HIV as well as in other retroviruses. We have previously demonstrated that variation in simian immunodeficiency virus (SIV) env is primarily localized in two regions (V1 and V4) during progression to simian AIDS. To determine whether there is a common genotype that evolves as AIDS develops, a total of 160 SIV env genes isolated directly from the tissue DNAs of four macaques infected with cloned virus were compared. Common amino acid sequence changes were identified within V1, V4, and, in the late stages of disease, near V3. At several positions, the same amino acid change was seen frequently in the variant genomes from all four animals. As AIDS developed, the majority of viruses evolved an extended sequence in V1 that was rich in serine and threonine residues and shared similarity with proteins modified by O-linked glycosylation. Several of the predominant common sequence changes in V1 and V4 created new sites for N-linked glycosylation. Thus, common features of the SIV variants that evolve during progression to AIDS are motifs that potentially allow for structural and functional changes in the env protein as a result of carbohydrate addition.
Multiple myeloma – an update on diagnosis and treatment (2008)

Multiple myeloma is a plasma cell (PC) malignancy characterized by the accumulation of monoclonal PCs in the bone marrow and the production of large amounts of a monoclonal immunoglobulin or paraprotein. In the past years, new approaches in the diagnosis and treatment were introduced aiming to identify high-risk patients who need proper anti-myeloma treatment. Intensive therapy including autologous hematopoietic stem cell transplantation and the new agents bortezomib, thalidomide, and lenalidomide have improved patients' responses. Further optimalization of the different treatment schedules in well-defined patient groups may prolong their survival. Patient stratification is currently based on patient characteristics, extent of myeloma disease, and associated cytogenetic and laboratory anomalies. More and more gene expression studies are introduced to stratify patients and to individualize therapy.
High Bone Density Due to a Mutation in LDL-Receptor–Related Protein 5 (2002)

The LRP5V171 mutation causes high bone density, with a thickened mandible and torus palatinus, by impairing the action of a normal antagonist of the Wnt pathway and thus increasing Wnt signaling. These findings demonstrate the role of altered LRP5 function in high bone mass and point to Dkk as a potential target for the prevention or treatment of osteoporosis.
GONAD: Genome-editing via Oviductal Nucleic Acids Delivery system: a novel microinjection independent genome engineering method in mice (2015)

Microinjection is considered the gold standard technique for delivery of nucleic acids (NAs; transgenes or genome editing tools such as CRISPR/Cas9 systems) into embryos, for creating genetically modified organisms. It requires sophisticated equipment as well as well-trained and highly skilled personnel to perform the micro-injection technique. Here, we describe a novel and simple microinjection-independent technique, called Genome-editing via Oviductal Nucleic Acids Delivery (GONAD). Using GONAD, we show that NAs (e.g., eGFP mRNA or Cas9 mRNA/sgRNAs) can be effectively delivered to pre-implantation embryos within the intact mouse oviduct by a simple electroporation method, and result in the desired genetic modification in the embryos. Thus GONAD can bypass many complex steps in transgenic technology such as isolation of zygotes, microinjection of NAs into them, and their subsequent transfer to pseudo-pregnant animals. Furthermore, this method can potentially be used for genome editing in species other than mice.
Regulation of the Complement Membrane Attack Pathway (1999)

Complement activation, triggered through classic, alternative, or lectin pathways of activation, leads to activation of a final common reaction sequence, the membrane attack pathway, in which five soluble plasma proteins assemble into a multimolecular complex that inserts into and through the membrane, creating a functional pore, the membrane attack complex. The active products of membrane attack are the anaphylactic and chemotactic fragment C5a and the membrane attack complex itself. These active products are important in immune defense but also carry the potential to damage host cells. Regulation of the membrane attack pathway is essential to protect host cells from damage at sites of C activation, and several protective systems have evolved to achieve this in vivo. Nevertheless, in disease these protective systems may be overwhelmed, and the availability of agents that specifically inhibit the membrane attack pathway might be of considerable therapeutic benefit. In this article I first describe the membrane attack pathway, its active products, and its role in disease. Second, I discuss systems operating to prevent damage to host cells by membrane attack, the regulatory proteins and activities that form the core of the article. Finally, I describe recent developments in the production of therapeutic agents with the capacity to inhibit membrane attack pathway.
Novel Wearable Energy Devices Based on Aligned Carbon Nanotube Fiber Textiles (2014)

A novel wearable supercapacitor textile with the desired and combined properties of being thin, lightweight, transparent, and flexible is developed by stacking two aligned carbon nanotube fiber-based textile electrodes. The supercapacitor textile is further integrated to create a new energy textile that can convert solar energy to electric energy, in addition to storing it with a high entire photoelectric conversion and storage efficiency. As a service to our authors and readers, this journal provides supporting information supplied by the authors. Such materials are peer reviewed and may be re-organized for online delivery, but are not copy-edited or typeset. Technical support issues arising from supporting information (other than missing files) should be addressed to the authors. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
Effects of Pomegranate Juice and Extract Polyphenols on Platelet Function (2009)

Several studies have shown that polyphenols reduce cardiovascular accidents in high-risk patients; in particular, the inhibition of platelet function may be responsible for part of this benefit. This research studied the antiplatelet effect of Wonderful variety pomegranate (Punica granatum) products, which contain primarily hydrolyzed tannins such as ellagitannins. We have investigated in vitro the effects of treatment with either pomegranate juice (PJ) or the polyphenol-rich extract from pomegranate fruit (POMx) on platelet aggregation, calcium mobilization, thromboxane A(2) production, and hydrogen peroxide formation, induced by collagen and arachidonic acid. PJ and POMx reduce all the platelet responses studied. POMx showed a stronger action in reducing platelet activation; moreover, POMx is active at the concentration that it is possible to obtain after polyphenol-rich food intake (2 microM). These results demonstrated that the cardiovascular health benefits of pomegranate may in part be related to the ability of polyphenols to inhibit platelet function. In fact, PJ and pomegranate extract have similar effects at concentrations expected for normal intake.
Mechanisms of Hepatotoxicity (2002)

This review addresses recent advances in specific mechanisms of hepatotoxicity. Because of its unique metabolism and relationship to the gastrointestinal tract, the liver is an important target of the toxicity of drugs, xenobiotics, and oxidative stress. In cholestatic disease, endogenously generated bile acids produce hepatocellular apoptosis by stimulating Fas translocation from the cytoplasm to the plasma membrane where self-aggregation occurs to trigger apoptosis. Kupffer cell activation and neutrophil infiltration extend toxic injury. Kupffer cells release reactive oxygen species (ROS), cytokines, and chemokines, which induce neutrophil extravasation and activation. The liver expresses many cytochrome P450 isoforms, including ethanol-induced CYP2E1. CYP2E1 generates ROS, activates many toxicologically important substrates, and may be the central pathway by which ethanol causes oxidative stress. In acetaminophen toxicity, nitric oxide (NO) scavenges superoxide to produce peroxynitrite, which then causes protein nitration and tissue injury. In inducible nitric oxide synthase (iNOS) knockout mice, nitration is prevented, but unscavenged superoxide production then causes toxic lipid peroxidation to occur instead. Microvesicular steatosis, nonalcoholic steatohepatitis (NASH), and cytolytic hepatitis involve mitochondrial dysfunction, including impairment of mitochondrial fatty acid beta-oxidation, inhibition of mitochondrial respiration, and damage to mitochondrial DNA. Induction of the mitochondrial permeability transition (MPT) is another mechanism causing mitochondrial failure, which can lead to necrosis from ATP depletion or caspase-dependent apoptosis if ATP depletion does not occur fully. Because of such diverse mechanisms, hepatotoxicity remains a major reason for drug withdrawal from pharmaceutical development and clinical use.
Testosterone Secretion and Metabolism in Male Senescence (1972)

The influence of aging on plasma testosterone levels and testosterone metabolism in males was studied. It was observed that plasma testosterone levels and the apparent free plasma testosterone concentration (AFTC) remain within the same range from adolescence until the age of 50 yr, but that from the 6th decade on, the mean plasma levels decrease rather rapidly, with however a wide range of individual values. As the metabolic clearance rate (MCR) decreases in male senescence, the net result is an important decrease in the testosterone blood production rate. Within the group of subjects studied, a statistically significant correlation between the free testosterone fraction and the MCR was found. It was observed that testosterone metabolism in male senescence is characterized by a relative decrease of the formation of androstanediols, with a relative increase of 5β over 5α metabolites;moreover a statistically significant correlation between the formation of 5α-androstane-3α,17β-diol and the free testosterone fraction was found. As the latter metabolite is largely formed in peripheral target tissues, this suggests that testosterone metabolism by target tissues becomes more important with increasing free T fraction and indirectly, that only free testosterone can be taken up by target tissues.