gebhart/patrepeval huggingface dataset:
PPARγ as a therapeutic target for tumor angiogenesis and metastasis (2005)

Peroxisome proliferator activated receptors (PPARs) are ligand-activated transcription factors with pleiotropic effects on cell fate and metabolism. Because of its anti-proliferative, pro-apoptotic and differentiation promoting activities, PPARgamma has been intensively evaluated as a target for anti-cancer therapy in preclinical models. However, PPARgamma has been reported to act both as a promoter and suppressor of neoplasia, and the role of PPARgamma activating ligands as well as antagonists in therapy remains controversial. In the past decade a new picture of tumors as a disease that involves changes in the non-cancerous tumor bed, including angiogenesis, inflammation and other stromal changes has emerged. PPARgamma has strong anti-inflammatory and anti-angiogenic effects, extending the repertoire of potential targets of PPARgamma ligands beyond cell autonomous mechanisms of cancer. The heterogeneous cellular targets and the biphasic effects of PPARgamma on various pro and anti-tumor processes may account for the apparent paradoxical effects of PPARgamma agonists. Here we review the action of PPARgamma agonists on angiogenesis and inflammation in the context of tumorigenesis as an integrated tissue process and discuss potential explanations for the conflicting effects of PPARgamma agonists on tumor progression and metastasis. Sorting out the various modes of action and defining their relative contribution in the context of tumor and host tissue as a heterogeneous target will therefore be crucial to understand the multi facetted effects of PPARgamma. This will be paramount if the potent biological activity of PPARgamma agonists are to be harnessed for cancer therapy.
Genetics and Physiology of the Myotonic Muscle Disorders (1993)

The myotonic muscle disorders represent a heterogeneous group of clinically similar diseases sharing the feature of myotonia: delayed relaxation of muscle after voluntary contraction (action myotonia) or mechanical stimulation (percussion myotonia). In classic myotonia the myotonia improves as muscles warm up, whereas in paradoxical myotonia (paramyotonia) it worsens with repeated muscle contractions. Electrophysiologically, myotonia is characterized by the repetitive electrical activity of muscle fibers. Two decades of work on the electrophysiology of myotonia focused attention on the muscle cell membrane as the site of the molecular defects of these diseases. Genetic-linkage studies have now pinpointed the lesions to chromosomal loci . . .
Diversity and signature of small RNA in different bodily fluids using next generation sequencing (2018)

This study shows the successful clustering and unique signatures of bodily fluids based on their miRNA, tRNA and piRNA content. With this information, cohorts may be differentiated based on multiple molecules from each small RNA class by a multidimensional assessment of the overall molecular signature.
Does virtual-reality training on orthopaedic simulators improve performance in the operating room? (2015)

This paper summarises recent validation studies and evidence demonstrating whether training on virtual reality (VR) simulators directly relates to improved performance in-vivo for orthopaedic surgical procedures. This research provides a summary of transfer validity on virtual reality orthopaedic simulators. This covers studies which have shown validation of simulators and have shown the transfer of simulator-acquired skill to the operating room. The findings of this study are that there are 6 studies showing transfer of skill for VR to in-vivo However more studies assessing efficacy and transfer validity are required to conclusively quantify the transfer validity of VR orthopaedic simulators. However there is a popular positive opinion for the ability of VR training to convert into better in-vivo performance.
Practical Issues in the Application of Direct Metal Laser Sintering (2006)

Direct Metal Laser Sintering (DMLS) was introduced to meet the objective of producing metal parts directly from CAD data. CRDM has accumulated six years of experience in applying this technique, mostly to prototyping parts for evaluation. For some applications, such as blow moulds, porosity generated in DMLS has proved to be beneficial, but for others a concession on tolerances or finish are necessary and/or complementary operations are required, which add to manufacturing time and cost. This paper examines such issues through some well chosen examples of parts to demonstrate both the strengths and weaknesses of the DMLS process.
ALK1 as an emerging target for antiangiogenic therapy of cancer (2011)

Members of the TGF-β family act on many, if not all, cell types within the body, producing diverse and complex cellular outcomes. Activation of the endothelial cell-restricted TGF-β type I receptor ALK1 results from the binding of several different ligands of the TGF-β family, including bone morphogenetic protein (BMP) 9, BMP10, and TGF-β. Mounting genetic, pharmacologic, and histopathologic evidence supports a critical role for ALK1 signaling in regulation of both developmental and pathologic blood vessel formation. However, the precise function of TGF-β family signaling in endothelial cells is difficult to predict and appears highly context dependent because of the multitude of ligands and receptors influencing the final outcome. Pharmacologic inhibitors of ALK1 have recently been developed and will allow for more accurate studies of ALK1 function in vivo, as well as for assessment of ALK1 as a target for suppression of angiogenesis during tumor development. Herein, we will summarize the current view of ALK1 regulation of endothelial cell phenotype in vitro and in vivo as well as provide an outlook for the ongoing clinical trials of ALK1 inhibitors in malignant disease.
Automated Detection of Activity Transitions for Prompting (2014)

Individuals with cognitive impairment can benefit from intervention strategies like recording important information in a memory notebook. However, training individuals to use the notebook on a regular basis requires a constant delivery of reminders. In this work, we design and evaluate machine learning-based methods for providing automated reminders using a digital memory notebook interface. Specifically, we identify transition periods between activities as times to issue prompts. We consider the problem of detecting activity transitions using supervised and unsupervised machine learning techniques, and find that both techniques show promising results for detecting transition periods. We test the techniques in a scripted setting with 15 individuals. Motion sensors data is recorded and annotated as participants perform a fixed set of activities. We also test the techniques in an unscripted setting with 8 individuals. Motion sensor data is recorded as participants go about their normal daily routine. In both the scripted and unscripted settings a true positive rate of greater than 80% can be achieved while maintaining a false positive rate of less than 15%. On average, this leads to transitions being detected within 1 minute of a true transition for the scripted data and within 2 minutes of a true transition on the unscripted data.
Large-scale spatial data processing on GPUs and GPU-accelerated clusters (2015)

The massive data parallel computing power provided by inexpensive commodity Graphics Processing Units(GPUs) makes large-scale spatial data processing on GPUs and GPU-accelerated clusters attractive from both a research and practical perspective. In this article, we report our works on data parallel designs of spatial indexing, spatial joins and several other spatial operations, including polygon rasterization, polygon decomposition and point interpolation. The data parallel designs are further scaled out to distributed computing nodes by integrating single-node GPU implementations with High-Performance Computing (HPC) toolset and the new generation in-memory Big Data systems such as Cloudera Impala. In addition to introducing GPGPU computing background and outlining data parallel designs for spatial operations, references to individual works are provided as a summary chart for interested readers to follow more details on designs, implementations and performance evaluations.
A multifunctional shape-morphing elastomer with liquid metal inclusions (2019)

Natural soft tissue achieves a rich variety of functionality through a hierarchy of molecular, microscale, and mesoscale structures and ordering. Inspired by such architectures, we introduce a soft, multifunctional composite capable of a unique combination of sensing, mechanically robust electronic connectivity, and active shape morphing. The material is composed of a compliant and deformable liquid crystal elastomer (LCE) matrix that can achieve macroscopic shape change through a liquid crystal phase transition. The matrix is dispersed with liquid metal (LM) microparticles that are used to tailor the thermal and electrical conductivity of the LCE without detrimentally altering its mechanical or shape-morphing properties. Demonstrations of this composite for sensing, actuation, circuitry, and soft robot locomotion suggest the potential for versatile, tissue-like multifunctionality.
Effects of p-coumaric acid on erythema and pigmentation of human skin exposed to ultraviolet radiation (2010)

These results suggest that PCA cream can reduce UV-induced erythema formation and subsequent pigmentation in human skin.
Chemopreventive effect of green tea (Camellia sinensis) against cigarette smoke-induced mutations (SCE) in humans (1997)

Green tea (Camellia sinensis) is consumed daily between the meals or after meals in Japan and other Asian countries. In recent years, green tea and its major polyphenolics have been demonstrated to prevent chemically induced tumors in a variety of experimental animal models system. The exact mechanism(s) of its anticarcinogenic activity remains to be elucidated, but green tea polyphenolics have demonstrated antimutagenic, anticarcinogenic, antioxidant, and antipromotional effects, including inhibition of Phase I and inducing Phase II enzymes. Enzyme activities of glutathione peroxidase, catalase, and quinone reductase, and glutathione S-transferase are also induced. However, a paucity of green tea effects in humans prompted us to investigate antimutagenic effects of green tea against smoke-induced mutation in humans. Chemopreventive effects of green tea and coffee among cigarette smokers were examined in 52 clinically healthy male subjects between 20–51 years of age. Blood specimens were obtained from non-smokers (Group I), smokers (II), smokers consuming green tea (III), and smoker/coffee drinkers (IV). The mean years of cigarette smoking ( > 10 cigarettes/day) of Groups II, III, and IV ranged from 13.4–14.7 years. Daily intake of green tea and coffee was 3 cups/day/6 months (III and IV). The frequencies of sister-chromatid exchange (SCE) in mitogen-stimulated peripheral lymphocytes from each experimental group were determined and statistically analyzed. SCE rates were significantly elevated in smokers (9.46 ± 0.46) vs. non-smokers (7.03 ± 0.33); however, the frequency of SCE in smokers who consumed green tea (7.94 ± 0.31) was comparable to that of non-smokers, implying that green tea can block the cigarette-induced increase in SCE frequency. Coffee, by contrast, did not exhibit a significant inhibitory effect on smoking-induced SCE. J. Cell. Biochem. Suppl. 27:68–75. © 1998 Wiley-Liss, Inc.
Studies on the syntheses of heterocyclic and natural compounds. 950. Asymmetric total synthesis of (+)-chenodeoxycholic acid. Stereoselectivity of intramolecular cycloaddition of olefinic o-quinodimethanes (1982)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTStudies on the syntheses of heterocyclic and natural compounds. 950. Asymmetric total synthesis of (+)-chenodeoxycholic acid. Stereoselectivity of intramolecular cycloaddition of olefinic o-quinodimethanesTetsuji Kametani, Koji Suzuki, and Hideo NemotoCite this: J. Org. Chem. 1982, 47, 12, 2331–2342Publication Date (Print):June 1, 1982Publication History Published online1 May 2002Published inissue 1 June 1982https://pubs.acs.org/doi/10.1021/jo00133a020https://doi.org/10.1021/jo00133a020research-articleACS PublicationsRequest reuse permissionsArticle Views506Altmetric-Citations26LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-Alertsclose Get e-Alerts
<title>Widely tunable hybrid semiconductor lasers</title> (1999)

A new hybrid design tunable semiconductor laser, with a wide tuning range, a narrow linewidth, simple tuning/control algorithms, low variations in output power across its tuning range and simple fabrication, is introduced. This hybrid laser consists of a large spot reflective amplifier (LS-RA) coupled to a Lithium Niobate Acousto-Optic Filter (AOF), giving wavelength selective feedback. The LS-RA waveguide is angled by 10 degrees to the coupling facet, but is normal to the other facet, giving reflectivities of 5 X 10<SUP>-5</SUP> and 3 X 10<SUP>-1</SUP> respectively. This amplifier structure allows maximum coupling to the AOF without stringent alignment tolerance. THe AOF consists of a 2-stage acoustic TE/TM converter with a high TE reflectivity coating at the end. A propagating surface acoustic wave is employed to phase-match the TE and TM modes of a specific wavelength, achieving a narrow-band feedback into the LS-RA. Output power and wavelength of the hybrid laser are controlled by the LS-RA current and RF drive frequency of the AOF respectively. Simulations using a Time-Domain Model and initial experiments have shown that the hybrid laser have a wide tuning range, narrow linewidth, SMSR >= 30 dB and low power variations across its tuning range.
Large‐scale synthesis of methyl <i>cis</i>‐9, <i>trans</i>‐11‐octadecadienoate from methyl ricinoleate (1997)

Abstract The conjugated linoleic acid methyl cis ‐9, trans ‐11‐octadecadienoate has been prepared on a large scale from methyl ricinoleate. Methyl ricinoleate was purified from castor esters by a partition method. It was converted to the mesylate, which was reacted with a base (1,8‐diazabicyclo[5,4,0]‐undec‐7‐ene) to give a product that contained 66% of the desired ester. Two urea crystallizations produced a product containing 83% methyl cis ‐9, trans ‐11‐octadecadienoate, the identity of which was confirmed by gas chromatography linked to mass spectrometry and by Fourier transform infrared spectroscopy. The remaining impurities were methyl cis ‐9, cis ‐11‐ and cis ‐9‐, trans ‐12‐octadecadienoate.
Discovery and Optimization of Selective Na <sub>v</sub> 1.8 Modulator Series That Demonstrate Efficacy in Preclinical Models of Pain (2015)

Voltage-gated sodium channels, in particular Nav1.8, can be targeted for the treatment of neuropathic and inflammatory pain. Herein, we described the optimization of Nav1.8 modulator series to deliver subtype selective, state, and use-dependent chemical matter that is efficacious in preclinical models of neuropathic and inflammatory pain.
Monosomy 1p36 ??? a recently delineated, clinically recognizable syndrome (2002)

Monosomy 1p36 is a recently delineated contiguous gene syndrome, which is now considered to be one of the most common subtelomeric microdeletion syndromes. We report four unrelated patients with subtle deletions within 1p36 confirmed by high resolution karyotyping and FISH. All exhibited severe psychomotor retardation. Microcephaly, seizures, and visual impairment occurred in three subjects. Results of a first routine karyotyping were unrevealing in three probands. The diagnosis was primarily suggested on the basis of a distinct pattern of facial anomalies in all except the first case. This report illustrates that monosomy 1p36 may be recognized clinically, at least in some patients, whereas the diagnosis is easily missed on routine karyotype.
1-O-alkyl-2-arachidonoyl-sn-glycero-3-phosphocholine. A common source of platelet-activating factor and arachidonate in human polymorphonuclear leukocytes. (1984)

1-O-[3H]Alkyl-2-lyso-sn-glycero-3-phosphocholine (1-O-[3H]alkyl-2-lyso-GPC) incubated with human polymorphonuclear leukocytes (PMN) for 30 min is metabolized to 1-O-alkyl-2-acyl-GPC containing greater than 80% arachidonate at the 2 position (Chilton, F. H., O'Flaherty, J. T., Ellis, J. M., Swendsen, C. L., and Wykle, R. L. (1983) J. Biol. Chem. 258, 7268-7271). PMN containing 1-O-[3H]alkyl-2-arachidonoyl-GPC incorporated into their cellular phospholipids in this manner were stimulated with Ca2+ ionophore (A23187). Within 5 min after stimulation, 14%, 7%, and 7% of the total 1-O-[3H]alkyl-2-arachidonoyl-GPC in the cells had been converted to 1-O-[3H]alkyl-2-acetyl-GPC (platelet-activating factor), 1-O-[3H]alkyl-2-lyso-GPC, and 3H-labeled neutral lipid, respectively. Stimulation by opsonized zymosan yielded similar results. In related studies, cells were labeled with 1-O-hexadecyl-2-arachidonoyl-GPC containing a [methyl-14C] choline moiety. The nature of the long-chain acyl residues in the sn-2 position of the labeled 1-O-hexadecyl-2-acyl-GPC remaining after stimulation with A23187 was examined. Analysis by high-performance liquid chromatography using synthetic 1-O-hexadecyl-2-acyl-GPC standards indicated there is a time-dependent loss of arachidonate from the 2 position of the labeled 1-O-hexadecyl-2-arachidonoyl-GPC followed by reacylation by other fatty acids (primarily linoleic and oleic). This shift in the acylation pattern exhibited after Ca2+ ionophore stimulation was further examined in PMN preincubated with A23187 and subsequently incubated with labeled 1-O-alkyl-2-lyso-GPC; the stimulated cells produced 1-O-[3H]alkyl-2-acetyl-GPC (greater than 15% of total label) and 1-O-[3H]alkyl-2-acyl-GPC containing linoleic acid and oleic acid, rather than arachidonic acid in the sn-2 position. The findings demonstrate that upon stimulation of PMN, 1-O-alkyl-2-arachidonoyl-GPC can yield arachidonate and 1-O-alkyl-2-lyso-GPC; the 1-O-alkyl-2-lyso-GPC formed may be acetylated producing platelet-activating factor or reacylated with fatty acyl residues other than arachidonate.
Maturing the software communications architecture for JTRS (2002)

This paper summarizes the status of the Joint Tactical Radio System (JTRS) software communications architecture (SCA). As the result of steps taken by the JTRS Joint Program Office (JPO) and the Modular Software-programmable Radio Consortium (MSRC), the SCA is at a level of maturity that ensures the goals of the JTRS program can be met. The SCA defines the framework for JTRS implementations in a manner that provides for communications interoperability, portability of application programs, and the ability to leverage commercial development and product availability into JTRS procurements. Key features of the SCA are the core software framework interfaces defined in a standard interface definition language (IDL), communication waveform application program interfaces (APIs) and API building blocks, and requirements for embedded INFOSEC and for INFOSEC APIs. The JTRS JPO has contracted with multiple vendors to implement these elements to validate the architecture. The results have shown that the architecture can be implemented in multiple products providing interoperable communications and that waveforms can be ported between different implementations with greatly reduced effort compared to that required in current radio designs. The SCA is designed and expected to grow as systems are procured and experience is gained with fielded equipment. The efforts to date show that the SCA meets or exceeds the goals and expectations of the JTRS JPO in defining the framework on which to base those equipment designs.
Abstract LB-005: Allosteric SHP2 phosphatase inhibition: Multiple mechanisms and chemotypes (2019)

Protein tyrosine phosphatase SHP2 is an oncoprotein associated with cancer as well as a potential immune modulator due to its role in the programmed cell death PD-L1/PD-1 pathway. Small molecule inhibition of SHP2 has been widely investigated including our previous reports describing SHP099, which binds to a tunnel-like allosteric binding site. To broaden our approach to allosteric inhibition of SHP2, we conducted additional hit finding, evaluation, and structure-based scaffold morphing. These studies led to the identification of multiple, potent inhibitor chemotypes, an additional and distinct allosteric binding site, and the identification of SHP394, an orally efficacious inhibitor of SHP2 with improved potency and enhanced pharmacokinetic properties. Overall, this work improves upon our previously described allosteric inhibitors, and exemplifies and extends the range of permissible chemical templates that inhibit SHP2 via the allosteric mechanism.Citation Format: Matthew J. LaMarche, Jeff Bagdanoff, Mike Acker, Ying-Nan Chen, Homan Chan, Michael Dore, Brant Firestone, Michelle Fodor, Jorge Garcia-Fortanet, Murphy Hentemann, Mitsunori Kato, Robert Koenig, Laura La Bonte, Shumei Liu, Movarid Mohseni, Rukundo Ntaganda, Patrick Sarver, Troy Smith, Martin Sendzik, Travis Stams, Stan Spence, Chris Towler, Hongyun Wang, Ping Wang, Sarah Williams, Zhouliang Chen, Huaixiang Hao, Gang Liu, Chen Liu, Eric McNeill, Bing Yu. Allosteric SHP2 phosphatase inhibition: Multiple mechanisms and chemotypes [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr LB-005.
HREM study of the chemical nature of twin planes in CuAlO<sub>2</sub> (1990)

Abstract High-resolution electron microscopy has been used to study the atomic structure of twins in the binary oxide CuAlO2. This compound is an occasional product of the bonding between pre-oxidized copper and alumina; its peculiarity is to exhibit a twinned microstructure, owing to the occurrence of two enantiomorphic right- and left-handed configurations. The microstructural examination at high resolution reveals that twin planes are located on copper basal planes rather than aluminium planes; this result is discussed on the basis of an analysis of the various possible stacking sequences which can reasonably be considered to occur at the twin interfaces.