gebhart/patrepeval huggingface dataset:
Abstract 390: A comparison of the activity of the quadruplex-targeting experimental drugs QN-302 and CX-5461 (pidnarulex) in wild-type and gemcitabine-resistant pancreatic cancer cell lines (2023)

Abstract The compound QN-302, a tetra-substituted naphthalene diimide (ND) derivative has been designed as a potent compound for targeting quadruplex sequences in cancer genes. It has single-digit nM anti-proliferative activity in a panel of human pancreatic cancer (PDAC) cell lines (Ahmed et al., ACS Med Chem Lett, 2020, 11, 1634-1644). It also has significant anti-tumor activity in xenograft, orthotopic and genetic (KPC) models for PDAC. Its mode of action involves the targeting of quadruplex (G4)-forming sites in promoter regions of cancer-associated genes, where their prevalence is over-represented compared to other genes. The structurally unrelated compound CX-5461 has also been reported to be a G4-binding agent, with selective activity in BRCA1/2 deficient cells and tumors (Xu and Hurley, Bioorg Med Chem Lett. 2022; Xu et al., Nat Commun, 2017). It is currently in early-stage clinical trials in breast and other solid cancers with deficiencies in DNA repair (Hilton et al., Nat Commun. 2022). We have previously reported that a precursor to QN-302, the tri-substituted naphthalene diimide compound CM03, is highly active in both wild-type and gemcitabine-resistant PDAC cell lines (Ahmed et al, Sci Rep, 2020). This is explained by the finding using whole-genome transcriptome analysis that the CM03-sensitive genes are largely unaffected in the resistant lines. We now report that the clinical candidate compound QN-302, which is 10-fold more potent than CM03, retains its potency in both MIA-PACA2 and PANC-1 PDAC cell lines with &amp;gt;1000-fold increase in gemcitabine resistance. This is also the case for CX-5461, although this compound is 50-100 times less potent, with GI50 values of 83-95 nM in cell proliferation assays treated for 96 h. Gemcitabine either alone or in combination is still a mainstay of current PDAC treatment. Resistance to gemcitabine is common and is a major contributor to the poor outcomes for most PDAC patients. The ability of QN-302 to retain activity in chemo-resistant PDAC cell lines suggests that it will offer significant advantage in the clinic over gemcitabine-based therapies. QN-302 is bio-available at therapeutic doses and is well tolerated at these levels in animal models. It is being developed for clinical evaluation by Qualigen Therapeutics Inc and is currently at the pre-IND stage. Citation Format: Ahmed Ahmed, Tariq Arshad, Stephen Neidle. A comparison of the activity of the quadruplex-targeting experimental drugs QN-302 and CX-5461 (pidnarulex) in wild-type and gemcitabine-resistant pancreatic cancer cell lines [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 390.
SOD activity, NOx, SH level in wobbler mice (1999)

We measured SOD activity, NOx, and free SH level in wobbler mice. Their NOx levels in both brain and spinal cord were significantly higher than those in healthy littermates. In addition, the SOD activity in both brain and spinal cord was lower with a significant difference. Furthermore, it was found that the free SH level in their brain was also lower. These results suggest that free radical might play some role of the motoneuron degeneration in wobbler mice.
Chiral Separation through Capillary Electromigration Methods (1994)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTChiral Separation through Capillary Electromigration MethodsMilos Novotny, Helena Soini, and Morgan StefanssonCite this: Anal. Chem. 1994, 66, 11, 646A–655APublication Date (Print):June 1, 1994Publication History Published online6 June 2012Published inissue 1 June 1994https://pubs.acs.org/doi/10.1021/ac00083a728https://doi.org/10.1021/ac00083a728research-articleACS PublicationsRequest reuse permissionsArticle Views169Altmetric-Citations9LEARN 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
Four-directional pixel-wise polarization CMOS image sensor using air-gap wire grid on 2.5-μm back-illuminated pixels (2016)

Polarization information is useful in highly functional imaging. This paper presents a four-directional pixel-wise polarization CMOS image sensor using an air-gap wire grid on 2.5-μm back-illuminated pixels. The fabricated air-gap wire grid polarizer achieved a transmittance of 63.3 % and an extinction ratio of 85 at 550 nm, outperforming conventional polarization sensors. The pixel-wise polarizers fabricated with the wafer process on back-illuminated image sensors exhibit good oblique-incidence characteristics, even with small polarization pixels of 2.5 μm. The proposed image sensor realizes mega-pixel various fusion-imaging applications, such as surface reflection reduction, highly accurate depth mapping, and condition-robust surveillance.
Effect of Intraperitoneal 224 Radium-Labelled Microparticles on Compartmentalized Inflammation After Cytoreductive Surgery and Hypertherm Intraperitoneal Chemotherapy (2023)

Despite extensive treatment with surgery and chemotherapy many patients with peritoneal metastases from colorectal cancer experience intraperitoneal disease relapse. The α-emitting <sup>224</sup>radium-labelled microparticle radionuclide therapeutic Radspherin® is being explored as a novel treatment option for these patients. Radspherin® is specially designed to give local radiation to the surface of the peritoneal cavity and potentially kill remaining attached micrometastases as well as free-floating cancer cells, thus preventing future relapse. The effect of Radspherin® on the immune system is not known. Systemic and local inflammatory responses were analyzed in plasma, intraperitoneal fluid and urine collected prospectively as part of a phase 1 dose-escalation study of intraperitoneal instillation of the α-emitting therapeutic radiopharmaceutical Radspherin®, at baseline and the first 7 postoperative days from nine patients undergoing cytoreductive surgery and hyperthermic intraperitoneal chemotherapy. All patients additionally received intraperitoneal instillation of Radspherin® on postoperative day 2. Complement activation products C3bc and the terminal complement complex were analyzed using enzyme-linked immunosorbent assay. Cytokines (<i>n</i> = 27), including interleukins, chemokines, interferons and growth factors, were analyzed using multiplex technique. The time course and magnitude of the postoperative cytokine response after cytoreductive surgery and hyperthermic intraperitoneal chemotherapy displayed a modest systemic response in plasma, in contrast to a substantial local intraperitoneal response. After administration of Radspherin®, a significant increase (<i>P</i> < 0.05) in TNF and MIP-1β was observed in both plasma and peritoneal fluid, whereas IL-9 increased only in plasma and IFNγ and IL1-RA only in peritoneal fluid. Only minor changes were seen for the majority of the inflammatory markers after Radspherin® administration. Our study showed a predominately local rather than systemic inflammatory response to cytoreductive surgery and hyperthermic intraperitoneal chemotherapy. Radspherin® had overall modest impact on the inflammation.
VMOS: high speed TTL compatible MOS logic (1974)

VMOS is a new v-groove n-channel MOS logic structure well suited for 5-V high-speed random logic. Compared to a typical gold-doped TTL medium-scale integrated (MSI) circuit, an experimental pin for pin equivalent VMOS circuit is 20 percent faster, four times smaller in area, and six times lower in power dissipation. On-chip VMOS delays are in the 2-3 ns range; off-chip drive capability exceeds 50 MHz with 6 TTL unit loads.
Key insights in the AIDA community policy on sharing of clinical imaging data for research in Sweden (2020)

Development of world-class artificial intelligence (AI) for medical imaging requires access to massive amounts of training data from clinical sources, but effective data sharing is often hindered by uncertainty regarding data protection. We describe an initiative to reduce this uncertainty through a policy describing a national community consensus on sound data sharing practices.
Expression of Zonula Occludens and Adherens Junctional Proteins in Human Venous and Arterial Endothelian Cells: Role of Occludin in Endothelial Solute Barriers (1998)

Objective: The purpose of this study was to correlate the expression of occludin and VE-cadherin with the solute barrier properties of arterial and venous endothelial monolayers. Methods: Immunofluorescent confocal and traditional microscopy were used to determine junctional protein localization in endothelium in vivo and in vitro respectively, and western and northern analysis used to determine protein and gene expression levels. Permeability of endothelial monolayers was examined under normal, low calcium, and cytochalasin-D treatment conditions. Antisense oligonucleotide experiments for occludin were performed to determine the contribution of occluding to solute barrier. Results: Occludin protein in endothelial monolayers in more concentrated in arterial junctions than in venous junctions both in vivo and in vitro. Arterial endothelial cells express 18-fold more occluding protein and nine times more occluding mRNA compared to venous endothelial cells. In vivo, both endothelial cells demonstrate VE-cadherin staining; in vitro, only venous endothelial cells express VE-cadherin protein and mRNA. Occludin antisense experiments suggest that both arterial and venous barrier properties are due to these different amounts of occluding expression. Venous barrier was remarkably sensitive to low extracellular calcium, while arterial barrier was more sensitive to cytochalasin-D. Conclusions: These findings suggest strongly that arterial and venous endothelial barrier reflects the level of expression of different adhesion molecules and that modulation of these proteins, especially occluding, may regulate the level of endothelial solute barrier.
LC/ESI-MS/MS detection of FAs by charge reversal derivatization with more than four orders of magnitude improvement in sensitivity (2013)

Quantitative analysis of fatty acids (FAs) is an important area of analytical biochemistry. Ultra high sensitivity FA analysis usually is done with gas chromatography of pentafluorobenzyl esters coupled to an electron-capture detector. With the popularity of electrospray ionization (ESI) mass spectrometers coupled to liquid chromatography, it would be convenient to develop a method for ultra high sensitivity FA detection using this equipment. Although FAs can be analyzed by ESI in negative ion mode, this method is not very sensitive. In this study, we demonstrate a new method of FA analysis based on conversion of the carboxylic acid to an amide bearing a permanent positive charge, N-(4-aminomethylphenyl)pyridinium (AMPP) combined with analysis on a reverse-phase liquid chromatography column coupled to an ESI mass spectrometer operating in positive ion mode. This leads to an ∼60,000-fold increase in sensitivity compared with the same method carried out with underivatized FAs. The new method is about 10-fold more sensitive than the existing method of gas chromatography/electron-capture mass spectrometry of FA pentafluorobenzyl esters. Furthermore, significant fragmentation of the precursor ions in the nontag portion improves analytical specificity. We show that a large number of FA molecular species can be analyzed with this method in complex biological samples such as mouse serum.
An implicit velocity decoupling procedure for the incompressible Navier–Stokes equations (2001)

Abstract An efficient numerical method to solve the unsteady incompressible Navier–Stokes equations is developed. A fully implicit time advancement is employed to avoid the Courant–Friedrichs–Lewy restriction, where the Crank–Nicolson discretization is used for both the diffusion and convection terms. Based on a block LU decomposition, velocity–pressure decoupling is achieved in conjunction with the approximate factorization. The main emphasis is placed on the additional decoupling of the intermediate velocity components with only nth time step velocity. The temporal second‐order accuracy is preserved with the approximate factorization without any modification of boundary conditions. Since the decoupled momentum equations are solved without iteration, the computational time is reduced significantly. The present decoupling method is validated by solving several test cases, in particular, the turbulent minimal channel flow unit. Copyright © 2002 John Wiley &amp; Sons, Ltd.
Minimizing User Involvement for Accurate Ontology Matching Problems (2015)

Many various types of sensors coming from different complex devices collect data from a city. Their underlying data representation follows specific manufacturer specifications that have possibly incomplete descriptions (in ontology) alignments. This paper addresses the problem of determining accurate and complete matching of ontologies given some common descriptions and their pre-determined high level alignments. In this context the problem of ontology matching consists of automatically determining all matching given the latter alignments, and manually verifying the matching results. Especially for applications where it is crucial that ontologies are matched correctly the latter can turn into a very time-consuming task for the user. This paper tackles this challenge and addresses the problem of computing the minimum number of user inputs needed to verify all matchings. We show how to represent this problem as a reasoning problem over a bipartite graph and how to encode it over pseudo Boolean constraints. Experiments show that our approach can be successfully applied to real-world data sets.
Privacy Protection by Anonymizing Based on Status of Provider and Community (2011)

When a user receives personal services from a service provider, the service can be of a higher quality if the user provides more personal information.However, the risk of privacy violation could increase.Therefore, this paper proposes a privacy protection method that realizes avoidance of unwanted information disclosure by controlling disclosable attributes according to the results from monitoring two elements: user background information of the provider and user community status.This is done before disclosing individual attributes corresponding to the privacy policy (i.e., the required anonymity level) by each user.The system architecture based on the aforementioned is also proposed.The validity of the proposed methods was confirmed by a desk model.
An 80% effeciency and highly adaptable PV energy harvest circuitry with MPPT for IOT devices (2017)

An on-chip DC-DC converter for energy harvesting is proposed for a new battery-less solar cell tag applied to the Internet of Things (IoTs) devices. The main purpose of this design is to maximize the transfer efficiency and to stably provide a high enough supply voltage to the back-end loads. The overall circuit consists of a cross-coupled charge pump, a maximum power point tracking (MPPT) circuit, a timing control circuit and regulator. The input voltage range is from 0.45V to 3V. The output voltage can be boosted to the required level, in the range of 1V to 3.3V, with more than 60% power conversion efficiency. The throughput power is at least 500pW. A gated clock frequency modulation circuit is designed and adopted in the MPPT unit to lock the input resistance of the charge pump. In addition, a low-dropout (LDO) regulator circuit is used to provide a stable voltage to the load. The experimental results of chip show that the maximum power conversion efficiency (PCE) is 80% at 33pW input power condition.
Comparison of the 1-year surgical outcomes of ab interno trabeculotomy using three types of microhooks (2023)

The 1-year surgical outcomes and complications after μLOT did not differ significantly among the three microhooks. The differences in the microhook tips might be associated with postoperative transient IOP spikes.
076 Growth of the Vulvar Vaginal Atrophy (VVA) Therapy Market (2020)

Up to about 70% of postmenopausal women representing an estimated 32 million women in the United States have VVA symptoms.1-3 Surveys published in 20134 and 20172 found that only 7% of women with VVA symptoms currently use prescription therapy, indicating a significant unmet need. Some newer products that have expanded the treatment armamentarium, have been approved for moderate to severe dyspareunia over the past few years. In addition, the North American Menopause Society, the International Society for the Study of Women’s Sexual Health, and other medical societies focused on women’s health have developed several initiatives to increase awareness of VVA and the genitourinary syndrome of menopause (GSM), which may include genital symptoms of dryness, burning, and irritation; lack of lubrication and/or discomfort or pain during sexual activity; and urinary symptoms. Newer product approvals, which included innovation, as well as awareness initiatives, may have impacted the size of the VVA treatment market. The objective of this study was to analyze growth of the market for VVA treatment using a large prescription database.
Surface properties of spider silk particles in solution (2013)

Recombinant spider silk proteins, such as eADF4(C16), can be used for various applications. Colloidal particles of eADF4(C16) show potential as drug delivery systems. Tuning the colloidal properties of suspensions of eADF4(C16) particles represents a major prerequisite for their use in pharmaceutical formulations. In this study we determined the surface properties concerning inter-particle interactions by means of electrophoretic mobility and direct force measurements. The surface charge of eADF4(C16) spider silk particles was determined as a function of ionic strength and pH, respectively. The resulting electrophoretic mobility can be described using the O'Brien and White theory and is directly related to the amino acid sequence of the protein. We determined the extension of a fuzzy protein layer protruding into the solution by direct force measurements using a colloidal probe technique. This soft layer leads to deviations in the electrophoretic mobility and is responsible for additional repulsive forces at small separation distances. These steric forces lead to a stabilization of the particle suspension at high ionic strength.
Simultaneous Determination of the Conformation and Relative Configuration of Archazolide A by Using Nuclear Overhauser Effects, J Couplings, and Residual Dipolar Couplings (2008)

Kombiniere: Die Zuordnung der Konfiguration entfernter Stereozentren in dem komplexen Polyketidmakrolid Archazolid A (siehe Struktur; rot O, blau N, gelb S) gelang mithilfe eines ausschließlich auf NMR-Spektroskopie basierenden Ansatzes, der sich eine Kombination von Kern-Overhauser-Effekten, J-Kopplungen und dipolaren Restkopplungen (RDCs) zunutze macht. Supporting information for this article is available on the WWW under http://www.wiley-vch.de/contents/jc_2001/2008/z800225_s.pdf or from the author. 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.
Assessment of in vitro growth potential of hepatocytes expressing hepatocyte growth factor in an autocrine fashion. (1994)

We recently developed transgenic mice expressing hepatocyte growth factor (HGF) specific to hepatocytes. Hepatocytes of HGF transgenic mice showed a 2-fold increase of DNA labeling indices in vivo compared with those of wild type mice. To assess in vitro growth potential of hepatocytes from HGF transgenic mice, we studied the effects of epidermal growth factor (EGF), insulin or transforming growth factor beta (TGF beta) on DNA synthesis of hepatocytes derived from HGF transgenic or wild type mice, respectively. We found that DNA synthesis of hepatocytes from HGF transgenic mice was significantly enhanced, compared with that from wild type mice, respectively, and that its effect was additive with EGF or insulin. Further, growth-inhibitory effects of TGF beta on hepatocytes was greatly depressed in transgenic mice-derived hepatocytes, compared with that in wild type hepatocytes. These data suggest that the autocrine action of HGF is a potent stimulus for hepatocyte growth, and stress its importance as regulator of liver regeneration.
Glutamate pathway implication in amyotrophic lateral sclerosis: what is the signal in the noise? (2010)

Abstract: The cause of the fatal motor neuron disease, amyotrophic lateral sclerosis (ALS), remains largely unknown. Most cases of ALS are sporadic and, for ~20% of familial ALS patients, mutations in the superoxide dismutase-1 ( SOD1 ) gene have been identified. Transgenic rodents overexpressing mutant SOD1 emulate the disease and constitute the best ALS animal model so far. Several lines of evidence suggest that ALS is a multifactorial condition. In this review, we discuss the question of the involvement of the glutamate pathways in ALS-induced motor neuron death. As such, we review the data implicating glutamate metabolism alterations, glutamatergic environmental toxins, glutamate transporter/receptor defects, and Ca 2+ -mediated glutamate toxicity in the etiopathogenesis of ALS. Given the published data, we contend that glutamate-induced neurotoxicity more likely precipitates motor neuron degeneration rather than being the initiating factor of ALS. Furthermore, we propose that glutamate-induced neurotoxicity participates in the ALS deadly molecular cascade only as an executioner to put an end to a series of molecular perturbations that have irreversibly compromised motor neuron function. This could provide an explanation for the modest effect of therapeutic strategies targeting the glutamatergic system, including the only currently FDA-approved ALS treatment, riluzole. As in diseased motor neurons, overwhelming Ca 2+ overload may be the converging point for glutamate, endoplasmic reticulum stress, and mitochondrial dysfunctional pathways, and only therapies targeting these simultaneously or targeting the earliest alterations initiating this deleterious cascade may have a real impact on halting ALS progression. Keywords: glutamate, excitotoxicity, amyotrophic lateral sclerosis, glutamate receptors, glutamate transporters, calcium