gebhart/patrepeval huggingface dataset:
Abstract 3967: BET protein inhibitor OTX015 has selective anti-tumoral activity in preclinical models of MYCN- amplified neuroblastoma (2014)

Abstract Neuroblastomas harboring MYCN amplifications are highly lethal tumors. They are often resistant to standard chemotherapy, yet the development of targeted therapies has been hampered by a lack of compounds targeting MYCN. We and others have recently discovered that targeting BET bromodomain proteins, especially BRD4, disrupts epigenetic regulation of MYCN and its targets in neuroblastoma. OTX015, a new BET protein inhibitor, is the first lead into clinical phase I/II trials and has shown promising pharmacological properties in adults. Here, we investigate the preclinical efficacy of OTX015 in MYCN-amplified neuroblastoma. We tested in vitro OTX015 efficacy in 6 established neuroblastoma (NB) cell lines. We performed cell cycle profiling and analyzed markers for apoptosis and proliferation after 72h-treatment at 500 nM OTX015. The effect of OTX015 on MYCN expression and global MYCN-associated transcriptional activity was assessed by quantitative real time PCR and gene expression microarray profiling, respectively. In vivo efficacy of orally OTX015 was assessed in IMR5 xenografts, a N-MYC driven NB model, using diffent treatment schedules (50mg/kg/day, 100mg/kg/day and 50mg/kg/bidaily). Treatment of MYCN-amplified neuroblastoma cells with OTX015 resulted in decreased cell viability, induction of apoptosis and reduced proliferation. Concentrations of 50% inhibition (IC50) ranged between 50nM and 500nM. OTX015 treatment also resulted in an increase in the percentage of cells in G1 phase. This corresponded with the downregulation of MYCN mRNA and protein levels and MYCN-associated transcriptional activity. Interestigly, MYCN amplified cell lines were most sensitive to OTX015 treatment. In contrast, no effect was observed with OTX15 on normal cells. In vivo treatment with OTX015, significantly decreased tumor burden after 4 weeks and prolonged survival as compared to vehicle-treated mice. These preclinical findings highlight the promise of BET bromodomain inhibitors as novel agents for MYCN-driven neuroblastomas and serve as rationale to move forward with early phase clinical trials for children with these highly lethal tumors. Citation Format: Johannes H. Schulte, Kristina Althoff, Emma Bell, Andrea Odersky, Anneleen Beckers, Frank Speleman, Simon Schäfers, Alexander Schramm, Angelika Eggert, Frank Westermann, Eugenia Riveiro, Esteban Cvitkovic, Anton Henssen. BET protein inhibitor OTX015 has selective anti-tumoral activity in preclinical models of MYCN- amplified neuroblastoma. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 3967. doi:10.1158/1538-7445.AM2014-3967
RELATIONSHIP OF GENE EXPRESSION AND SEX HORMONE RECEPTORS IN PRIMARY BREAST CARCINOMA AND METASTASES FROM THE SAME PATIENT (2012)

Using microarray results and published reports, 32 genes were selected whose expression appears related to clinical outcome of breast cancer. Candidate gene expression and estrogen (ER) and progestin receptor (PR), determined by ligand binding or EIA, were evaluated to ascertain their relationship during lymph node invasion. RNA was isolated from tissue sections of de‐identified frozen carcinoma biopsies. cDNA was prepared with Superscript RT III reagents (Invitrogen) and qPCR reactions were performed using Power Sybr Green PCR Master Mix (Applied Biosystems). Although levels of ER and PR protein varied between the primary and the metastasis, no primary lesion that was ER− or PR−exhibited a positive ER/PR result in the metastasis. Only 7 patients with either ER+ or PR+ primaries exhibited loss of receptor expression in the metastasis. ESR1 and PGR gene expression correlated highly with protein levels of ER and PR. Expression of 6 of 32 genes (TBC1D9, TRIM29, SCUBE2, IL6ST, SLC39A6, LRBA) was discordant in at least half of the primary lesion‐lymph node pairs, while expression of 6 genes (TRIM29, SCUBE2, SLC39A6, TCEAL1, PFKP, XBP1) was discordant in at least half of the primary‐distant metastasis pairs. These results address the molecular basis for progression of a primary lesion to a metastatic phenotype. Supported in part by grants from Phi Beta Psi Charity Trust and a CTSP Grant from the Commonwealth of Kentucky.
The PD-L1 metabolic interactome intersects with choline metabolism and inflammation (2021)

Abstract Background: Harnessing the power of the immune system by using immune checkpoint inhibitors has resulted in some of the most exciting advances in cancer treatment. The full potential of this approach has, however, not been fully realized for treating many cancers such as pancreatic and breast cancer. Cancer metabolism influences many aspects of cancer progression including immune surveillance. An expanded understanding of how cancer metabolism can directly impact immune checkpoints may allow further optimization of immunotherapy. We therefore investigated, for the first time, the relationship between the overexpression of choline kinase-α (Chk-α), an enzyme observed in most cancers, and expression of the immune checkpoint PD-L1. Methods: We used small interfering RNA to downregulate Chk-a, PD-L1 or both in two triple negative human breast cancer cell lines (MDA-MB-231 and SUM-149) and two human pancreatic ductal adenocarcinoma cell lines (Pa09C and Pa20C). The effects of the downregulation were studied at the genomic, proteomic and metabolomic levels. The findings were compared with results obtained by analysis of public data from The Cancer Genome Atlas Program. Results: We identified an inverse dependence between Chk-α and PD-L1 at the genomic, proteomic and metabolomic levels. We also found that prostaglandin-endoperoxide synthase 2 (COX-2) and transforming growth factor beta (TGF-β) play an important role in this relationship. We independently confirmed this relationship in human cancers by analyzing data from The Cancer Genome Atlas Program. Conclusions: Our data identified previously unknown roles of PD-L1 in cancer cell metabolic reprogramming, and revealed the immunosuppressive increased PD-L1 effect of Chk-α downregulation. These data suggest that PD-L1 regulation of metabolism may be mediated through Chk-α, COX-2 and TGF-β. The observations provide new insights that can be applied to the rational design of combinatorial therapies targeting immune checkpoints and cancer metabolism.
Automatic Annotation of Unlabeled Data from Smartphone-Based Motion and Location Sensors (2018)

Automatic data annotation eliminates most of the challenges we faced due to the manual methods of annotating sensor data. It significantly improves users&rsquo; experience during sensing activities since their active involvement in the labeling process is reduced. An unsupervised learning technique such as clustering can be used to automatically annotate sensor data. However, the lingering issue with clustering is the validation of generated clusters. In this paper, we adopted the <i>k</i>-means clustering algorithm for annotating unlabeled sensor data for the purpose of detecting sensitive location information of mobile crowd sensing users. Furthermore, we proposed a cluster validation index for the <i>k</i>-means algorithm, which is based on Multiple Pair-Frequency. Thereafter, we trained three classifiers (Support Vector Machine, <i>K</i>-Nearest Neighbor, and Na&iuml;ve Bayes) using cluster labels generated from the <i>k</i>-means clustering algorithm. The accuracy, precision, and recall of these classifiers were evaluated during the classification of &ldquo;non-sensitive&rdquo; and &ldquo;sensitive&rdquo; data from motion and location sensors. Very high accuracy scores were recorded from Support Vector Machine and <i>K</i>-Nearest Neighbor classifiers while a fairly high accuracy score was recorded from the Na&iuml;ve Bayes classifier. With the hybridized machine learning (unsupervised and supervised) technique presented in this paper, unlabeled sensor data was automatically annotated and then classified.
Informative narrowcasting with consumer search (2003)

Improved consumer addressability in electronic markets allows vendors to send focused promotional messages to specific customers, facilitating a targeted advertising approach that we call "narrowcasting". We characterize a rational consumer's market participation decision and identify a narrowcasting firm's optimal targeting decision when buyers face nontrivial search costs. In the special case where consumer reservation utility is relatively low and search cost is relatively high, consumers will neither search nor purchase blindly without search, and the market breaks down. Our main contribution here is to show that narrowcasting can help a seller revitalize this market by replacing learning by consumers with learning and targeting by the seller.
Synthesis of 2-substituted adenine-arabinosides and related compounds from 5-amino-4-cyano-1-(.BETA.-d-ribofuranosyl)imidazole. (1989)

Triflation of the N5-benzylidene-3', 5'-O-silyl protected 5-amino-4-cyano-1-(β-D-ribofuranosyl)imidazole (AICN-riboside) (IIb), followed by nucleophilic displacement with OAc- and N3-provided the corresponding 2'(S)-substituted derivatives (VIIa, VIIb). Deprotection of the silyl and benzylidene groups of VIIa, followed by hydrolysis of the acetyl group gave AICN-arabinoside (IXc). Reaction of IXc with alkyl, aryl and aralkyl nitriles afforded the corresponding 2-substituted adenine-arabinosides (XIa-e). The 2'-azido (Xa) and 2'-amino (Xb) analogs of XIa were similarly prepared.
Continuous Particle Filtration and Concentration by Multigradient Dielectrophoresis (2004)

A novel methodology for designing selective particle concentrators in electrokinetic flows is presented. The technique is based on two-level etching of channels to produce ridges along which field gradients are patterned. The field gradients are then used to deflect particles using dielectrophoresis. Using uniform-field designs as a basis, fields in the vicinity of a single ridge are examined both experimentally and numerically. Although isotropic etching causes local deviations from piecewise continuous fields, ridges are found to serve as selective particle deflectors in experiments with both polystyrene beads and Bacillus subtilis. Sequences of parallel ridges are also tested, illustrating the efficacy of corrugated ridge structures for selective particle concentration.
In vitro immunization of human B lymphocytes with cultured melanoma cells (SK-MEL 28) (1990)

Human peripheral blood lymphocytes (PBL) from 10 healthy donors were in vitro immunized using the human melanoma cell line SK-MEL 28 as an immunogen. The parameters necessary to obtain an optimal immune response against the tumor cells in vitro were determined. Different ratios of PBL and SK-MEL 28 were tested during the in vitro immunization period, and their effect on cell viability, specific antibody secretion, and yield of antigen-specific EBV clones was determined. A statistically significant positive dose-response relation was shown to exist between the immunogenic dose present during in vitro immunization and the number of antigen-specific EBV clones that was obtained. A ratio of PBL:SK-MEL 28 cells of 1:1 was found to be optimal and gave 2.6% positive clones from which human monoclonal antibodies specific for the melanoma cells were detected.
NMR-Derived Models of Amidopyrine and Its Metabolites in Complexes with Rabbit Cytochrome P450 2B4 Reveal a Structural Mechanism of Sequential N-Dealkylation (2011)

To understand the molecular basis of sequential N-dealkylation by cytochrome P450 2B enzymes, we studied the binding of amidopyrine (AP) as well as the metabolites of this reaction, desmethylamidopyrine (DMAP) and aminoantipyrine (AAP), using the X-ray crystal structure of rabbit P450 2B4 and two nuclear magnetic resonance (NMR) techniques: saturation transfer difference (STD) spectroscopy and longitudinal (T(1)) relaxation NMR. Results of STD NMR of AP and its metabolites bound to P450 2B4 were similar, suggesting that they occupy similar niches within the enzyme's active site. The model-dependent relaxation rates (R(M)) determined from T(1) relaxation NMR of AP and DMAP suggest that the N-linked methyl is closest to the heme. To determine the orientation(s) of AP and its metabolites within the P450 2B4 active site, we used distances calculated from the relaxation rates to constrain the metabolites to the X-ray crystal structure of P450 2B4. Simulated annealing of the complex revealed that the metabolites do indeed occupy similar hydrophobic pockets within the active site, while the N-linked methyls are free to rotate between two binding modes. From these bound structures, a model of N-demethylation in which the N-linked methyl functional groups rotate between catalytic and noncatalytic positions was developed. This study is the first to provide a structural model of a drug and its metabolites complexed to a cytochrome P450 based on NMR and to provide a structural mechanism for how a drug can undergo sequential oxidations without unbinding. The rotation of the amide functional group might represent a common structural mechanism for N-dealkylation reactions for other drugs such as the local anesthetic lidocaine.
Separation of acid and sugar by ion exclusion chromatography. An application in the conversion of cellulose to ethanol (1993)

The production of fuel grade alcohol by fermentation from sugars obtained by the acid hydrolysis of cellulose has been hindered by costly methods of cleansing the acid in the sugar stream. An economical and environmentally acceptable acid-sugar separation process based on ion exclusion chromatography has been developed and analyzed. This process recovers the acid for reuse in hydrolysis without producing landfill waste allowing a concentrated acid hydrolysis process to be commercially feasible.
Safety and Efficacy of Epicardial Ablation of Ventricular Tachyarrhythmias: Experience from a Tertiary Referral Center in Taiwan. (2018)

In this tertiary referral center's experience, the complication rate of an epicardial approach was acceptable. Patients with NICM displayed a growing trend for a referral for epicardial ablation. The long-term follow-up demonstrated that an epicardial ablation for idiopathic VAs and BrS was associated with a better prognosis than that for the other etiologies.
DECA: Density-aware reliable broadcasting in vehicular ad hoc networks (2010)

Reliable broadcasting in vehicular ad hoc networks is challenging due to its unique characteristics including intermittent connectivity and various vehicular scenarios (car traffic is possibly very dense in urban areas or very sparse on highways). In this paper, we propose a new reliable broadcast protocol which is suitable for such characteristics. To address the issue of various vehicular scenarios, our protocol performs periodic beaconing to gather local density information of 1-hop neighbors and uses such information to adapt its broadcast decision dynamically. Specifically, before broadcasting each message, a node selects a neighbor with the highest density. Upon the reception of the broadcast message, each node checks if it is the selected neighbor. If so, it is responsible for rebroadcasting the message immediately. Otherwise, it stores the message for possible rebroadcasting. To address the issue of intermittent connectivity, message information in beacons is used to discover new neighbors, which have not yet received the message. Simulation results show that, in both highway and urban scenarios, our proposed protocol outperforms other competing solutions in terms of reliability, overhead and speed of data dissemination.
Hypoglycemia-associated Hyperammonemia Caused by Impaired Expression of Ornithine Cycle Enzyme Genes in C/EBPα Knockout Mice (1998)

Ammonia produced by amino acid metabolism is detoxified through conversion into urea by the ornithine cycle in the liver, whereas carbon skeletons of amino acids are converted to glucose by gluconeogenic enzymes. Promoter and enhancer sequences of several genes for ornithine cycle enzymes interact with members of the CCAAT/enhancer-binding protein (C/EBP) transcription factor family. Disruption of the C/EBPalpha gene in mice causes hypoglycemia associated with the impaired expression of gluconeogenic enzymes. Here we examined the expression of ornithine cycle enzyme genes in the livers of C/EBPalpha-deficient mice. mRNA levels for the first, third, fourth, and fifth enzymes of five enzymes in the cycle were decreased in C/EBPalpha-deficient mice. Protein levels for the first, second, fourth, and fifth enzymes were also decreased. In situ hybridization analysis revealed that the enzyme mRNAs were distributed normally in the periportal region but were disordered in C/EBPalpha-deficient mice with relatively higher mRNA levels in the midlobular region. Blood ammonia concentrations in the mutant mice were severalfold higher than in wild-type mice. Thus, C/EBPalpha is crucial for ammonia detoxification by ornithine cycle enzymes and for coordination of gluconeogenesis and urea synthesis.
Synthesis of Ni–Ag–ZnO solid solution nanoparticles for photoreduction and antimicrobial applications (2022)

ZnO is one of the most promising and efficient semiconductor materials for various light-harvesting applications. Herein, we reported the tuning of optical properties of ZnO nanoparticles (NPs) by co-incorporation of Ni and Ag ions in the ZnO lattice. A sonochemical approach was used to synthesize pure ZnO NPs, Ni-ZnO, Ag-ZnO and Ag/Ni-ZnO with different concentrations of Ni and Ag (0.5%, 2%, 4%, 8%, and 15%) and Ni doped Ag-ZnO solid solutions with 0.25%, 0.5%, and 5% Ni ions. The as-synthesized Ni-Ag-ZnO solid solution NPs were characterized by powdered X-ray diffraction (pXRD), FT-IR spectroscopy, scanning electron microscopy (SEM), energy dispersive spectroscopy (EDS), UV-vis (UV) spectroscopy, and photoluminescence (PL) spectroscopy. Ni-Ag co-incorporation into a ZnO lattice reduces charge recombination by inducing charge trap states between the valence and conduction bands of ZnO and interfacial transfer of electrons. The Ni doped Ag-ZnO solid solution NPs have shown superior 4-nitrophenol reduction compared to pure ZnO NPs which do not show this reaction. Furthermore, a methylene blue (MB) clock reaction was also performed. Antibacterial activity against <i>E. coli</i> and <i>S. aureus</i> has inhibited the growth pattern of both strains depending on the concentration of catalysts.
Common haplotype in the annexin A5 gene promoter associated with recurrent pregnancy loss (2008)

N. Bogdanova1, J. Horst1, M. Chlystun2, P. J. P. Croucher3, A. Nebel4, A. Bohring1, A. Todorova5, S. Schreiber4, V. Gerke2, M. Krawczak3, A. Markoff2 Institutes of 1Human Genetics, 2Medical Biochemistry, ZMBE, Westfalian Wilhelms-University and University Clinics, Munster, 3Medical Informatics and Statistics, 4Clinical Molecular Biology, ChristianAlbrechts University and University Clinics Schleswig-Holstein, Kiel, Germany, 5Laboratory of Molecular Pathology, University Hospital of Obstetrics and Gynecology, Medical University of Sofia, Bulgaria
The one-sided mean kernel: a positive definite kernel for time series (2015)

Abstract. We propose in this paper a new kernel for time series on structured data in the dynamic time warping family. We demonstrate using the theory of infinitely divisible kernels that this kernel is positive definite, that it is a radial basis kernel and that it reduces to a product kernel when comparing two sequences of the same length. Finally we compare this kernel with the global alignment kernel in a classification task using support vector machines. 1
Ambient molecular imaging by laser ablation atmospheric pressure chemical ionization mass spectrometry (2013)

LA-APCI-MS is introduced as an ambient molecular mass spectral imaging method for molecules with high resolution in space and mass. The combination of two independent instruments offers flexible ion source and mass analyzer exchange and therefore LA-APCI-MS opens up new possibilities for molecular imaging under ambient conditions.
Compressed sensing snapshot spectral imaging by a regular digital camera with an added optical diffuser (2016)

We propose a spectral imaging method that allows a regular digital camera to be converted into a snapshot spectral imager by equipping the camera with a dispersive diffuser and with a compressed sensing-based algorithm for digital processing. Results of optical experiments are reported.
Correction: Common Key Genes in Differentiating Parathyroid Adenoma From Thyroid Adenoma (2023)

Department of Nephrology, Zhongshan Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, China
External cavity quantum-cascade laser tunable from 8.2to10.4μm using a gain element with a heterogeneous cascade (2006)

A heterogeneous quantum-cascade structure based on two bound-to-continuum designs emitting at 9.6 and 8.4μm is presented. Its spontaneous emission spectrum at room temperature has a full width at half maximum of 350cm−1 and shows a variation of intensity of less than 20% over more than 200cm−1. External cavity lasers using a grating in Littrow configuration and antireflection coated chips with this active region could be tuned over 265cm−1 from 8.2to10.4μm, that is, over 24% of the center wavelength.
Successful risk assessment may not always lead to successful risk control: A systematic literature review of risk control after root cause analysis (2012)

Root cause analysis is perhaps the most widely used tool in healthcare risk management, but does it actually lead to successful risk control? Are there categories of risk control that are more likely to be effective? And do healthcare risk managers have the tools they need to support the risk control process? This systematic review examines how the healthcare sector translates risk analysis to risk control action plans and examines how to do better. It suggests that the hierarchy of risk controls should inform risk control action planning and that new tools should be developed to improve the risk control process.
Self-reported music perception is related to quality of life and self-reported hearing abilities in cochlear implant users (2021)

The findings suggest some relationship between CI users' self-reported music perception ability and QoL and self-reported hearing ability. While the causal relationship is not currently evaluated, the findings may imply that music training programs and/or device improvements that improve music perception may improve QoL and hearing ability.