gebhart/patrepeval huggingface dataset:
Variations in mRNA Content Have No Effect on the Potency of Antisense Oligonucleotides (2000)

A fundamental question with regard to antisense pharmacology is the extent to which RNA content or transcription rate or both affect the potency of antisense drugs. We have addressed this by controlling RNA content and transcription rate using either an exogenous gene expressed after transfection or an endogenous gene induced with a cytokine. We have demonstrated that in both A549 and HeLa cells, varying RNA copy numbers from <1 to >100 copies per cell has no effect on the potency of RNase H-active antisense drugs transfected into cells, nor did variation in transcription rate have an effect on potency. We demonstrate that this is because the number of oligonucleotide molecules per cell is vastly in excess of the RNA copy number. These data further suggest that a significant fraction of cell-associated antisense drug molecules may be unavailable to interact with the target RNA, an observation that is not surprising, as phosphorothioate oligonucleotides interact with many cellular proteins. We suggest that these data may extrapolate to in vivo results.
Development and Validation of a Clinical Polygenic Risk Score to Predict Breast Cancer Risk (2020)

The validation and implementation of a PRS for women without pathogenic variants in known breast cancer susceptibility genes offers potential for risk stratification to guide surveillance recommendations.
Is the Association Between Smoking and the Retinal Venular Diameter Reversible Following Smoking Cessation? (2013)

Purpose.: Wider retinal venular caliber is shown to be associated with an increased risk of stroke, and smoking is associated with a wider retinal venular caliber. However, the impact of smoking cessation on the retinal vessels has not been previously reported. We examined this issue in an adult cohort of atomic bomb survivors. Methods.: In the Adult Health Study of Japanese atomic bomb survivors, 1664 subjects had retinal photographs taken from 2006 to 2008. The central retinal artery and vein equivalents (CRAE and CRVE) were calculated using a semiautomated software program. Multiple surveys have assessed the effects of smoking since 1963. The associations between smoking, the time since cessation, and the retinal vessel caliber were determined using linear mixed effects models. Results.: The CRVE was associated with an increased number of cigarettes smoked per day among women after adjusting for potential confounding factors (age, sex, blood pressure, hypertensive medications, white blood cell count, diabetes, body mass index, lipids, and radiation dose). Females who smoked 10 cigarettes per day had a 6.9-μm wider mean CRVE (P = 0.001) than nonsmokers. Females who had stopped smoking for 10 or more years had a mean CRVE similar to those who had never smoked (191.8 vs. 194.4 μm; P = 0.23). These associations were not observed in males or for CRAE. Conclusions.: Wider retinal venular caliber is associated with smoking in Japanese females; however, this association becomes nonsignificant after 10 or more years of smoking cessation, suggesting that the impact of smoking on retinal venular dilation is reversible following long-term smoking cessation.
Distributed channel assignment in large-scale wireless mesh networks: A performance analysis (2013)

In this paper we present a performance evaluation of two distributed channel assignment algorithms in a large-scale wireless multi-radio testbed. We compare the performance of a link-based approach, in which channels are assigned to existing links in the network, with an interface-based approach, in which channels are assigned to the network interfaces. Both algorithms have significantly increased the network capacity in small wireless testbeds with less than 15 nodes. In this study, we investigate if the performance gain scales to large-scale wireless mesh networks. We evaluate the performance of the algorithms in the DES-Testbed, a multi-radio wireless mesh network with 126 nodes at Freie Universität Berlin. We compare the results to a single channel network and a randomized strategy. Additionally, we analyze the impact of the algorithms on the network connectivity and the spectral diversity. The results show, that compared to the single channel network, both algorithms increase the network capacity by a factor of three.
Radiopure ZnMoO4 scintillating bolometers for the LUMINEU double-beta experiment (2015)

The results of R&amp;D of radiopure zinc molybdate (ZnMoO4) based scintillating bolometers for the LUMINEU (Luminescent Underground Molybdenum Investigation for NEUtrino mass and nature) double-beta decay experiment are presented. A dedicated two-stage molybdenum purification technique (sublimation in vacuum and recrystallization from aqueous solutions) and an advanced directional solidification method (the low-thermal-gradient Czochralski technique) were utilized to produce high optical quality large mass (∼1 kg) ZnMoO4 crystal boules and first 100Mo (99.5%) enriched Zn100MoO4 crystal scintillator (mass of ∼0.2 kg). Scintillating bolometers based on ZnMoO4 (≈ 0.33 kg) and Zn100MoO4 (≈ 0.06 kg) scintillation elements and high purity Ge wafers were tested in the EDELWEISS set-up at the Modane Underground Laboratory (France). Long term low temperature tests demonstrate excellent detectors’ performance and effectiveness of the purification and solidification procedures for the achievement of high radiopurity of the material, in particular with a bulk activity of 228Th and 226Ra below 4 µBq/kg. The adopted protocol was used to produce for the first time a large volume Zn100MoO4 crystal scintillator (mass of ∼1.4 kg, 100Mo enrichment is 99.5%) to search for neutrinoless double-beta decay of 100Mo in the framework of the LUMINEU project.
Automated Engineering Application By Internet (2003)

In the modem product development process, engineering analysis of components and assemblies is completed through the use of tools that do FEA, CFD, kinematicsldynamics, crash simulation, etc. The skills necessary to build these types of models are still limited to a few experienced analytical engineers in an organization. Those engineers should be able to fully identify and understand load paths, boundary conditions, and the intricacies of the modeling software. To empower the non-expert engineer to perfonn the analysis, a web-based approach is proposed to encapsulate the knowledge and skill of the analytical engineer in tool familiar to all engineers. Currently, ArvinMeritor is using custom websites on the corporate intranet as interfaces between automated analysis scripts and users with no specialized analysis tools or training. The following advantages are realized by using the web to automate repetitive analyses: Cycle time and expense is reduced, consistency of approach is maintained, and personnel with analysis expertise are freed fiom repetitive tasks. Not all the commercial software and product design are suitable for engineering web tool development. Many technical restrictions may prevent the web tool application. First, the designed product should be conceptualized and simplified to the problem that can be described by definite design parameters and geometry inputs. Thus the web can handle the inputs and transfer them to the user-coded program and commercial software. Secondly, commercial software should have the basic inputloutput channel with the external program. This paper will address the development procedure for commercial software based web tool, from the perspective of web, software and product characteristics. This paper will also illustrate two existing examples of web-based tools used for product design and development. The first uses ANSYS for Finite Element Analysis of automotive stabilizer bars. The second uses ADAMS for simulating automotive Gas-Spring assisted mechanisms. Transactions on the Built Environment vol 67, © 2003 WIT Press, www.witpress.com, ISSN 1743-3509
Figure S3 from The PET-Tracer <sup>89</sup>Zr-Df-IAB22M2C Enables Monitoring of Intratumoral CD8 T-cell Infiltrates in Tumor-Bearing Humanized Mice after T-cell Bispecific Antibody Treatment (2023)

&lt;p&gt;Figure S3 shows autoradiography slides after CEA-4-1BBL/CEA-TCB single or combo treatment.&lt;/p&gt;
Current Induced Tilting of Domain Walls in High Velocity Motion along Perpendicularly Magnetized Micron-Sized Co/Ni/Co Racetracks (2012)

Kerr microscopy is used to investigate domain wall motion in response to nanosecond-long current pulses in perpendicularly magnetized micron-sized Co/Ni/Co racetracks. Domain wall velocities greater than 300 m/s are observed. The velocity is independent of the pulse length for a wide range of current densities. However, the domain wall dynamics depends on the pulse length just above the threshold current for motion, where slow creep motion occurs, and at very high current densities, where domain nucleation takes place. We also observe a tilting of the domain wall that cannot be accounted for by the Oersted field from the driving current.
A Drawing-Based Digital Music Instrument (2013)

This paper presents an innovative digital musical instrument, the Illusio, based on an augmented multi-touch interface that combines a traditional multi-touch surface and a device similar to a guitar pedal. Illusio allows users to perform by drawing and by associating the sketches with live loops. These loops are manipulated based on a concept called hierarchical live looping, which extends traditional live looping through the use of a musical tree, in which any music operation applied to a given node affects all its children nodes. Finally, we evaluate the instrument considering the performer and the audience, which are two of the most important stakeholders involved in the use, conception, and perception of a musical device. The results achieved are encouraging and led to useful insights about how to improve instrument features, performance and usability.
Polyfluorenes as organic semiconductors for polymeric field effect transistors (2003)

Well-characterized F8T2 polyfluorene (Dow Chemical) has been prepared with weight average molecular weights (Mw) ranging from about 20,000 to 120,000. This semiconducting polymer has been used by Plastic Logic to fabricate arrays of 4,800 thin film transistors (TFTs) with 50 dpi, to be used as backplanes for active matrix displays. In this paper, the effects that molecular weight and thermal treatment have on the electrical characteristics of F8T2-based TFTs are reported. First, transistor performance improves with increasing molecular weight, with maximum values of TFT mobility approaching 1x 10<sup>-2</sup> cm<sup>2</sup> /V-s. Consistently higher mobilities are obtained when the F8T2 semiconductor makes contact with PEDOT/PSS versus gold electrodes. Alignment of F8T2 on a rubbed polyimide substrate is maintained after quenching, as determined by measurement of the dichroic ratios. Early-stage results on the development of inks based on F8T2 polyfluorene are also reported.
World's First Cement Replacement with Metal Expandable Annular Sealing on a Highly Laminated, Deep Water Injector in West Africa (2020)

Abstract The field is developed within a complex environment, located within deep water and operated from a TLP / FPU facility. The wells are targeting 2 reservoir structures at 4000m TVD, requiring long and deviated wells to achieve field coverage. The reservoir is highly laminated with complex lithology requiring approximately 3:2 producers to injectors. Existing lower completion design utilizes a combination of cement and metal expandable annular sealing technology, to ensure zonal isolation and annular sealing (liner to formation) during the high-pressure stimulation and to ensure sealing over the life of well for zonal water shut off requirements. The oil reservoir is located approximately 20m TVD above a highly-pressurized water zone, making the oil producers challenging to drill and cement. Existing wells were drilled with a long shoe track into the water zone creating a possible flow path for the water to migrate along the annulus if annular sealing is not achieved. As part of a global efficiency drive, the operator issued a challenge to the service industry, to reduce the DRILLEX of these wells whilst maintaining the beneficial productivity index that has been achieved within the highly heterogeneous carbonate field, being prone to asphaltenes. One of the implemented solutions was cement replacement across the reservoir. The benefits of this solution impacted several areas; it removed the need for drilling 100m of rat hole, under reaming of the 6 ½″ hole, clean out of the 6 ½″ hole and most significantly, eliminating cementing of the 4 ½″ liner. This led to a substantial cost savings and reduction of rig time and because it simplified the operations, the operational risks were also reduced. The scope of work to deliver the solution included the design, development and qualification of the metal expandable annular sealing system. The project included validation of both sealing and anchoring of the cement-less liner within the open hole. The solution was also required to maintain the synergies with the perforation, acid stimulation and diversion techniques to achieve the required Productivity Index (PI) and Injectivity Index (II). The first deployment was within a well that was converted from producer to water injector. This would help validate the technology for further deployment on oil producers. The lower liner with the metal expandable annular sealing system was deployed from the rig whilst the activation (expansion) and subsequent acid stimulation were completed offline. Production and injectivity data were analysed and compared to the PI / II to the prior cemented and perforated well designs. This paper will discuss the project scope of work, first deployment of the metal expandable sealing system, data analysis and an estimate of the risk and cost reduction delivered.
Serum Lipid and Protein Changes in Healthy Dyslipidemic Subjects Given a Selective Inhibitor of p70 S6 Kinase‐1 (2017)

The safety, pharmacokinetic, and pharmacodynamic effects of LY2584702, a selective inhibitor for p70 S6 serine/threonine protein kinase-1, were evaluated in healthy dyslipidemic volunteers. LY2584702 was tolerated well as a monotherapy and dose-dependently reduced low-density lipoprotein cholesterol and triglycerides by up to 60% and 50%, respectively, without significantly changing high-density lipoprotein cholesterol levels in plasma. LY2584702 also dose-dependently decreased factor V activity. Alanine aminotransferase elevations were noted in 2 subjects when LY2584702 was given with atorvastatin. We suspect that the formation of 4-aminopyrazolo[3,4-d]pyrimidine (4-APP) during metabolism may have contributed to some of the adverse effects of LY2584702, and the contribution of 4-APP to the pharmacology merits further investigation. Although clinical investigation of LY2584702 has been terminated because of hepatotoxicity risk, we suggest that a selective inhibitor of p70 S6 serine/threonine protein kinase-1 with a larger margin of safety and without the possibility of being metabolized to 4-APP may be useful in the treatment of dyslipidemia.
Downlink beamforming and resource allocation in multicell MISO‐OFDMA systems (2012)

ABSTRACT We study the downlink beamforming (DLBF) and resource optimisation problem in multicell multi‐input single‐output orthogonal frequency division multiple access (MISO‐OFDMA) systems. This is a mixed combinatorial, nonlinear and nonconvex optimisation problem. By using uplink downlink duality, we propose an efficient suboptimal algorithm. This algorithm provides beamformers and allocates subcarriers and power to different users in the network with minimum message passing between the transmitting base stations. DLBF and resource optimisation algorithm for single‐cell MISO‐OFDMA systems can be obtained as a special case of the multicell algorithm. Simulation results reveal the performance gains provided by the proposed algorithm. Copyright © 2012 John Wiley &amp; Sons, Ltd.
Data from Targeting the PI3K Pathway in the Brain—Efficacy of a PI3K Inhibitor Optimized to Cross the Blood–Brain Barrier (2023)

&lt;div&gt;Abstract&lt;p&gt;&lt;b&gt;Purpose:&lt;/b&gt; Glioblastoma (GBM), the most common primary brain tumor in adults, presents a high frequency of alteration in the PI3K pathway. Our objectives were to identify a dual PI3K/mTOR inhibitor optimized to cross the blood–brain barrier (BBB) and characterize its brain penetration, pathway modulation in the brain and efficacy in orthotopic xenograft models of GBM.&lt;/p&gt;&lt;p&gt;&lt;b&gt;Experimental Design:&lt;/b&gt; Physicochemical properties of PI3K inhibitors were optimized using in silico tools, leading to the identification of GNE-317. This compound was tested in cells overexpressing P-glycoprotein (P-gp) or breast cancer resistance protein (BCRP). Following administration to mice, GNE-317 plasma and brain concentrations were determined, and phosphorylated biomarkers (pAkt, p4EBP1, and pS6) were measured to assess PI3K pathway suppression in the brain. GNE-317 efficacy was evaluated in the U87, GS2, and GBM10 orthotopic models of GBM.&lt;/p&gt;&lt;p&gt;&lt;b&gt;Results:&lt;/b&gt; GNE-317 was identified as having physicochemical properties predictive of low efflux by P-gp and BCRP. Studies in transfected MDCK cells showed that GNE-317 was not a substrate of either transporter. GNE-317 markedly inhibited the PI3K pathway in mouse brain, causing 40% to 90% suppression of the pAkt and pS6 signals up to 6-hour postdose. GNE-317 was efficacious in the U87, GS2, and GBM10 orthotopic models, achieving tumor growth inhibition of 90% and 50%, and survival benefit, respectively.&lt;/p&gt;&lt;p&gt;&lt;b&gt;Conclusions:&lt;/b&gt; These results indicated that specific optimization of PI3K inhibitors to cross the BBB led to potent suppression of the PI3K pathway in healthy brain. The efficacy of GNE-317 in 3 intracranial models of GBM suggested that this compound could be effective in the treatment of GBM. &lt;i&gt;Clin Cancer Res; 18(22); 6239–48. ©2012 AACR&lt;/i&gt;.&lt;/p&gt;&lt;/div&gt;
MANAGEMENT, AUTOMATION, AND PEOPLE (1965)

MANAGEMENT, AUTOMATION, AND PEOPLE Robert G. Webster CopyRight https://doi.org/10.2105/AJPH.55.10.1666-a Published Online: August 29, 2011
Elemental Fluorine. Part 21.1 Direct Fluorination of Benzaldehyde Derivatives (2008)

Direct fluorination of a range of benzaldehyde derivatives gives mixtures of fluorobenzaldehyde and benzoyl fluoride products in ratios that depend upon the nature of the ring substituent. Electron-withdrawing substituents give predominantly benzoyl fluoride derivatives, whereas electron-donating substituents lead to fluoroarene systems. Separation of ring-fluorinated products can be easily accomplished by esterification of the benzoyl fluoride side products. Scale-up of these processes to provide significant quantities of appropriate fluorobenzaldehyde systems has also been achieved using continuous flow techniques.
Topotactic Kinetics in Zeolite Nanoreaction Chambers (1992)

The first kinetic study is reported for archetypical substitution reactions of PMe3 and 13CO with the well defined intrazeolite system Mo(12CO)6-M56Y where M = Li, Na, K, Rb and Cs. Excellent isosbestic points and first-order dissociative behaviour are obtained, the activation parameters indicating a highly ordered supramolecular transition-state consisting of activated Mo(12CO)6 and PMe3 or 13CO anchored to M+ ions and/or oxygen-framework sites in the α-cage of the host lattice. Generally, an increase in reactant loading produces a decrease in the activating ability of the host lattice but, for reaction with PMe3, reactivity is enhanced at higher loading and associative attack on Mo(12CO)6 by PMe3 may be important under some conditions. The global picture that emerges from this investigation is that the α-cages of zeolite Y behave as rigid macrospheroidal multidentate anionic ligands (called zeolates or cavitates) towards extraframework charge-balancing cations to which organometallic and ligand guests can become attached. An approach of this kind can assist with the design of experiments and the understanding of cation and framework anchoring and guest loading effects on the activation parameters and reaction mechanisms compared to gas, solution, surface, and matrix phases where such data are available.
Flexible Optical Cross-Connects for High Bit Rate Elastic Photonic Transport Networks [Invited] (2016)

We present here the work performed in the EU-funded flexible optical cross-connect (FOX-C) project, which investigates and develops new flexible optical switching solutions with ultra-fine spectral granularity. Thanks to high spectral resolution filtering elements, the sub-channel content can be dropped from or added to a super-channel, offering high flexibility to optical transport networks through the fine adaptability of the network resources to the traffic demands. For the first time, the FOX-C solutions developed in the project are investigated here and evaluated experimentally. Their efficiency is demonstrated over two high spectral efficiency modulation schemes, namely multi-band orthogonal frequency division multiplexing (MB-OFDM) and Nyquist WDM (N-WDM) formats. Finally, in order to demonstrate the relevance of the FOX-C node concepts, a networking study comparing the economic advantages of the FOX-C optical aggregation solution versus the electronic one is performed.
OA02-06 LB. Recombinant modified Vaccinia virus ankara expressing HIV-1 genes activates NK subset capable of controlling HIN infection in vitro (2009)

Background Primate innate immune mechanisms are critical for the normal development of adaptive immune responses to antigen. Part of the modern effort to design and distribute vaccines against pathogens must involve detailed descriptions of innate responses resulting from vaccine challenges. Particularly, the interaction between Natural Killer (NK) and Dendritic cells is expected to greatly impact the establishment of both innate and adaptive immune responses to vaccine. In this study, we describe responses of Natural Killer cells to recombinant Modified Vaccinia Virus Ankara expressing HIV-1 genes (rMVA) compared to wild type MVA (MVAwt).
Integrating Terrestrial and Non-terrestrial Networks: 3D Opportunities and Challenges (2022)

Integrating terrestrial and non-terrestrial networks has the potential of connecting the unconnected and enhancing the user experience for the already-connected, with technological and societal implications of the greatest long-term significance. A convergence of ground, air, and space wireless communications also represents a formidable endeavor for the mobile and satellite communications industries alike, as it entails defining and intelligently orchestrating a new 3D wireless network architecture. In this article, we present the key opportunities and challenges arising from this (r)evolution by presenting some of its disruptive use-cases and key building blocks, reviewing the relevant standardization activities, and pointing to open research problems. By considering two multi-operator paradigms, we also showcase how terrestrial networks could be efficiently re-engineered to cater for aerial services, or opportunistically complemented by non-terrestrial infrastructure to augment their current capabilities.
Triple-Mode True Elliptic Function Filter Realization for Satellite Transponders (2005)

A six-pole, triple mode filter with true elliptic-function response has been synthesized and experimentally realized, This was done by using a new intercavity iris structure that can control three intercavity mode couplings simultaneously.