gebhart/patrepeval huggingface dataset:
TLR5-Mediated Phosphoinositide 3-Kinase Activation Negatively Regulates Flagellin-Induced Proinflammatory Gene Expression (2006)

Epithelial cells detect motile pathogens via TLR5 ligation of flagellin, resulting in rapid induction of antibacterial/proinflammatory gene expression. Although such flagellin-induced gene expression is quite transient, likely to avoid the negative consequences of inflammation, little is known regarding the molecular mechanisms that mediate its shutdown. We hypothesized that, analogous to the case for TLR4, phosphoinositide 3-kinase (PI3K) might negatively regulate TLR5 signaling. However, because PI3K is an essential positive mediator of some pathways of TLR-mediated gene expression, the opposite hypothesis was also considered. Herein, we observed that flagellin stimulation of epithelial cells indeed induced rapid (<30 min) PI3K activation, as evidenced by Akt phosphorylation, via a TLR5-mediated mechanism. Blockade of PI3K with wortmannin resulted in marked enhancement of flagellin-induced gene expression as assessed by measuring levels of inducible NO synthase, IL-6, and IL-8. Such enhancement of gene expression by PI3K inhibition correlated with prolonged activation of MAPK (p38 and ERK1/2) and was ablated under MAPK inhibition. Such effect of inhibiting PI3K with wortmannin was mimicked by the PI3K inhibitor LY294002, and, conversely, a constitutively active PI3K prevented p38 activation in response to flagellin. Last, to test the significance of these results in vivo, we measured flagellin-induced gene expression in PI3K knockout mice. PI3K-null mice displayed increased levels of flagellin-induced serum IL-6, KC (IL-8 homolog), and nitrite as compared with heterozygous littermates. Thus, TLR5's rapid activation of PI3K serves to limit MAPK signaling, thus limiting proinflammatory gene expression and reducing the potential negative consequences of proinflammatory gene expression.
An MRI Classification of Lesions Around Metal-on-Metal Hip Replacements (2012)

Introduction Metal Artefact Reduction Sequence (MARS) MRI is being increasingly used to detect soft tissue inflammatory reactions surrounding metal-on-metal hip replacements. The UK MHRA safety alert announced in April 2010 recommended cross-sectional imaging such as MRI for all patients with painful MOM hips. The terms used to describe the findings include bursae, cystic lesions and solid masses. A recently used term, pseudotumour, incorporates all of these lesions. We aimed to correlate the pattern of abnormalities on MRI with clinical symptoms. Method Following our experience with over 160 MARS MRI scans of patients with MOM hips we recognized patterns of lesions according to their: wall thickness, T1/T2 signal, shape, and location. We categorised the 79 lesions from 159 MARS MRI scans of into our novel classification scheme of 1, 2a, 2b and 3. There were two groups of patients: well functioning and painful. Results We found a surprisingly high prevalence of lesions on MRI scan in the well functioning group (11 out 23, 48%) when compared to the painful group (79 out of 137, 57%). However, there were a significantly greater number of grade 1 lesions in the well functioning group. We suggest that these are post-surgical changes and should not be confused with pathological, tissue destroying lesions. Discussion This is the largest ever study of patients with MARS MRI scans of MOM hips. It is the first to use a classification system and the first to compare well functioning with painful hips. We are now able to provide radiologists and surgeons with clinical interpretation of a lesion on MRI scan. Our classification system will provide useful information on both symptomatic and asymptomatic patients. Longitudinal follow up of these patients will provide the final validation.
Usefulness of Lower Infundibular Length-to-Diameter Ratio as a Predictor of Lower Pole Stone Clearance After Extracorporeal Shock Wave Lithotripsy: Clinical Research With Two Lithotriptors (2005)

No AccessJournal of UrologyAdult Urology: Urological Survey: Urolithiasis, Endourology And Laparoscopy1 Mar 2005Usefulness of Lower Infundibular Length-to-Diameter Ratio as a Predictor of Lower Pole Stone Clearance After Extracorporeal Shock Wave Lithotripsy: Clinical Research With Two Lithotriptors Ralph V. ClaymanM.D. Ralph V. ClaymanRalph V. Clayman More articles by this author View All Author Informationhttps://doi.org/10.1016/S0022-5347(05)60364-3AboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail "Usefulness of Lower Infundibular Length-to-Diameter Ratio as a Predictor of Lower Pole Stone Clearance After Extracorporeal Shock Wave Lithotripsy: Clinical Research With Two Lithotriptors." The Journal of Urology, 173(3), p. 868 © 2005 by American Urological Association, Inc.FiguresReferencesRelatedDetails Volume 173Issue 3March 2005Page: 868 Advertisement Copyright & Permissions© 2005 by American Urological Association, Inc.MetricsAuthor Information Ralph V. Clayman More articles by this author Expand All Advertisement PDF downloadLoading ...
Moving oncolytic viruses into the clinic: clinical-grade production, purification, and characterization of diverse oncolytic viruses (2016)

Oncolytic viruses (OVs) are unique anticancer agents based on their pleotropic modes of action, which include, besides viral tumor cell lysis, activation of antitumor immunity. A panel of diverse viruses, often genetically engineered, has advanced to clinical investigation, including phase 3 studies. This diversity of virotherapeutics not only offers interesting opportunities for the implementation of different therapeutic regimens but also poses challenges for clinical translation. Thus, manufacturing processes and regulatory approval paths need to be established for each OV individually. This review provides an overview of clinical-grade manufacturing procedures for OVs using six virus families as examples, and key challenges are discussed individually. For example, different virus features with respect to particle size, presence/absence of an envelope, and host species imply specific requirements for measures to ensure sterility, for handling, and for determination of appropriate animal models for toxicity testing, respectively. On the other hand, optimization of serum-free culture conditions, increasing virus yields, development of scalable purification strategies, and formulations guaranteeing long-term stability are challenges common to several if not all OVs. In light of the recent marketing approval of the first OV in the Western world, strategies for further upscaling OV manufacturing and optimizing product characterization will receive increasing attention.
Metabolic engineering of 2‐pentanone synthesis in Escherichia coli (2013)

Expanding the chemical diversity of microbial fermentation products enables green production of fuel, chemicals, and pharmaceuticals. In recent years, coenzyme A (CoA) dependent chain elongation, resembling the reversed β‐oxidation pathway, has attracted interest for its use in producing higher alcohols, fatty acids, and polyhydroxyalkanoate. To expand the chemical diversity of this pathway, we metabolically engineered Escherichia coli to produce 2‐pentanone, which is not a natural fermentation product of E. coli. We describe the first demonstration of 2‐pentanone synthesis in E. coli by coupling the CoA‐dependent chain elongation with the acetone production pathway. By bioprospecting for enzymes capable of efficient hydrolysis of 3‐keto‐hexanoyl‐CoA, production of 2‐pentanone increased 20 fold, reaching a titer of 240 mg/L. © 2013 American Institute of Chemical Engineers AIChE J , 59: 3167–3175, 2013
Chemically Responsive Elastomers Exhibiting Unity‐Order Refractive Index Modulation (2018)

Chameleons are masters of light, expertly changing their color, pattern, and reflectivity in response to their environment. Engineered materials that share this tunability can be transformative, enabling active camouflage, tunable holograms, and novel colorimetric medical sensors. While progress has been made in creating artificial chameleon skin, existing schemes often require external power, are not continuously tunable, and may prove too stiff or bulky for applications. Here, a chemically tunable, large-area metamaterial is demonstrated that accesses a wide range of colors and refractive indices. An ordered monolayer of nanoresonators is fabricated, then its optical response is dynamically tuned by infiltrating its polymer substrate with solvents. The material shows a strong magnetic response with a dependence on resonator spacing that leads to a highly tunable effective permittivity, permeability, and refractive index spanning negative and positive values. The unity-order index tuning exceeds that of traditional electro-optic and photochromic materials and is robust to cycling, providing a path toward programmable optical elements and responsive light routing.
Abstract 5835: Adipocyte-released agents induce resistance of breast cancer cells to lapatinib (2018)

Abstract Adipose tissue is often reduced to its role in fat storage and metabolic support for tumor cells. However, several studies have shown an adipocyte-mediated resistance effect to various anticancer therapies. However, the responsible agent(s), the mechanism(s) and the signaling pathway(s) involved in this resistance remain unclear. In the present study, we assessed the cytotoxic effect of lapatinib on several breast cancer cell lines in the presence or absence of adipocyte-conditioned medium. We performed different physical and chemical treatments on these conditioned media in order to separate and identify the different molecules and agents involved. In parallel, we investigated the changes that occurs in breast tumor cells following the contact with adipocyte-conditioned medium and the exposure to lapatinib both at transcriptional and protein level. In order to validate our hypothesis in vivo, we created a mouse model reproducing the contact between adipose tissue and tumors. Our results showed that tumor cells exposed to adipocyte-conditioned medium were less sensitive to lapatinib-mediated cytotoxic effects and cell cycle blockade than cells grown in standard culture medium. For example, we found that the IC50 was approximately seven-fold increased with lapatinib for tumor cells exposed to adipocyte-conditioned medium compared to the cells kept in control medium. This resistance was observed with the conditioned medium obtained both from human and murine adipocytes and confirmed on different breast tumor cell lines overexpressing HER2. Using a xenograft of normal human adipose tissue with implantation of tumor cells in contact to this adipose tissue, we also confirmed the protective effect against the antitumoral activity of lapatinib in vivo. The nature of the responsible agents of the resistance has been partly elucidated as well as the mechanisms. Indeed, it seems that the presence of soluble factors released from adipocytes such as lipolysis and metabolism products are required to limit the effect of lapatinib on tumor cells. The exposure of tumor cells to adipocyte-conditioned medium triggered changes on the lapatinib-mediated cell cycle blockade and on the expression of cell cycle regulation dependent proteins such as AKT, P27 and cyclins. In conclusion, compounds released from adipocytes reduced the lapatinib induced cytotoxicity on breast cancer cells overexpressing HER2 by interfering with the AKT signaling pathway. These results suggest possible strategies to counteract tumor cell resistance to lapatinib, by targeting adipocyte-released mediators. Citation Format: Aline Geneste, Minh Ngoc Duong, Aurore Cleret, Sabine Beaumel, Kamel Chettab, Emmanuel Delay, Philippe Valet, Lars Petter Jordheim, Charles Dumontet. Adipocyte-released agents induce resistance of breast cancer cells to lapatinib [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 5835.
Untersuchungen der Mesomerie in schwefelhaltigen Gruppierungen von Aroxylen durch Elektronenresonanz (1964)

Abstract Es werden durch schwefelhaltige Gruppen substituierte Aroxyle EPR‐spektroskopisch untersucht. Die durch Deuterierung interpretierbaren Hyperfeinstrukturen (HFS) lassen erkennen, daß geeignete Substituenten über den Schwefel an der Mesomerie unter Bildung hochmesomerer Radikale teilnehmen.
Chimerization of highly asynchronous murine blastomeres: Developmental alteration? (1988)

Previous studies have shown that early embryos contain information that can alter the developmental fate of adjacent cells and transferred nuclei. In this report we show that a specific combination of cells from early murine embryos, a single blastomere from an eight-cell embryo placed under the zona pellucida with a two-cell embryo, results in a difference in incorporation of 3H-uridine and expression of two protein bands between the chimeric treatment group and the nonchimeric controls, a single blastomere from an eight-cell embryo in a separate zona pellucida and a two-cell embryo. The incorporation of 3H-uridine in the chimeric group and nonchimeric control group was significantly different at 45 hours after chimerization (P less than .02). A stage-specific protein band (52k) on a polyacrylamide gel detected with fluorography was found to be qualitatively different (present more often; P less than .01) and another stage-specific protein band (48k) was found to be quantitatively different (more protein; P = .07) in the chimeric treatment vs. the nonchimeric controls at 45 hours after chimerization. These results suggest communication between the cells resulting in a change in their incorporation of uridine and protein synthetic profiles.
Melt pool and microstructure manipulation using diffractive holographic elements in high power conduction laser welding (2007)

A Doctoral Thesis. Submitted in partial fulfillment of the requirements for the award of Doctor of Philosophy of Loughborough University.
Pulsed Energy Storage System Design (1974)

A superconductive energy storage magnet which is connected to the three phase power system could be designed, constructed, and placed in operation at Fermilab which would essentially eliminate the large repetitive power pulses now required from the power system. In addition to the power pulses, voltage flicker is also caused due to the reactive power pulsation. Specifically, a one megawatt hour superconductive energy storage magnet and a 2.00 megawatt thyristorized converter can achieve nullification of these power pulses up to 400 GEV synchrotron operation. Above 400 GEV, operation should be possible up to 500 GEV with appreciable less power pulsing requirements from the system than are now considered permissible. Carried to successful completion, this project would serve to advance applied superconductivity to a highly significant degree. The effect would be of world wide importance to both high energy physics and to the electric power industry. The preliminary magnet design is a 1 MWh dipole composed of cryogenically stable composite conductors connected in parallel with aluminum shield windings. The shield windings carry impressed pulsed currents while eliminating pulsed currents from the dc superconductive windings. Without pulsed currents or pulsed magnetic fields there are no ac losses in standard helium. The major radius of the dipole is 8.85 m; the minor radius is 0.69m; there are 188 turns at 80,000 A and each turn is 4 conductors wound in parallel. The 20,000 A TiNb-copper composite conductor is l0x 1.12 cm in cross section similar to but larger than the FNAL bubble chamber conductor. The shield is 188 turns (equal number of turns is a shielding condition) of hollow aluminum conductor cooled via circulated cold helium gas at 40K. The turns are spaced around the minor circumference according to a cosine distribution which produces zero internal field. In use the shield loss converted to room temperature power is about .8MW when 0.1 MWh is used from a 1 MWh storage dipole. The 0.1 MWh is sufficient to provide complete load leveling for 400 GEV pulses, and operation at 500 GEV with lower power transients than are presently experienced.
Ethyl 1-benzoyl-4-chloro-2-phenylprolinate (2007)

The title compound, C20H20ClNO3, belongs to a family of non-nucleoside reverse transcriptase inhibitors (NNRTI). It crystallizes with two independent mol­ecules, A and B, in the asymmetric unit. In mol­ecule A, the pyrrolidine ring is disordered between two positions with occupancies of 0.650 (2) and 0.350 (2), corresponding to two isomers, viz. 2R,4R and 2R,4S, respectively. The disorder of the pyrrolidine ring in mol­ecule B [occupancies 0.512 (3) and 0.488 (3)] corresponds to the other two isomers, viz. 2S,4R and 2S,4S, respectively, showing that all four possible isomers are present in the crystal structure.
Completeness of HIV-1 Envelope Glycan Shield at Transmission Determines Neutralization Breadth (2018)

Densely arranged N-linked glycans shield the HIV-1 envelope (Env) trimer from antibody recognition. Strain-specific breaches in this shield (glycan holes) can be targets of vaccine-induced neutralizing antibodies that lack breadth. To understand the interplay between glycan holes and neutralization breadth in HIV-1 infection, we developed a sequence- and structure-based approach to identify glycan holes for individual Env sequences that are shielded in most M-group viruses. Applying this approach to 12 longitudinally followed individuals, we found that transmitted viruses with more intact glycan shields correlated with development of greater neutralization breadth. Within 2 years, glycan acquisition filled most glycan holes present at transmission, indicating escape from hole-targeting neutralizing antibodies. Glycan hole filling generally preceded the time to first detectable breadth, although time intervals varied across hosts. Thus, completely glycan-shielded viruses were associated with accelerated neutralization breadth development, suggesting that Env immunogens with intact glycan shields may be preferred components of AIDS vaccines.
A perturbation based fault modeling and simulation for mixed-signal circuits (2002)

The areas of analog circuit fault simulation and test generation have not witnessed the same degree of success as their digital counterparts. This is due mainly to the complexity of analog behavior and the lack of a fault mode. We present a new functional fault modeling technique called the perturbation fault model. The perturbation fault model is based on an estimation of the distance between the responses of the faulty and fault-free circuit and their distributions. The model allows fault abstraction of physical defects through structural fault modeling and perturbation estimation. The fault simulation technique uses a linear estimation of the faulty and fault-free output circuits. Techniques for fault observation and propagation are presented in order to build a hierarchical analog fault simulator.
Dust mitigation in the desert: Cleaning mechanisms for solar panels in arid regions (2014)

This review includes a comparative survey of cleaning mechanisms for solar power plants, with a focus on their application in arid regions. In these regions, dust accumulation can have a severe and detrimental effect on the productivity of solar arrays. The primary concern of this study is to address the need for a commercially viable cleaning solution and present candidate technologies that show promise in enabling solar technologies in the sun-rich, arid regions of the world. In addition to comparing the cleaning mechanisms categorically, specific examples from each category will be referenced to demonstrate the specific attributes of such tools. The survey will focus primarily on currently available product categories for the analysis, while developing technologies are reviewed for their potential strengths and weaknesses. The categories of cleaning solutions considered in this study include the following: manual cleaning, mechanized cleaning, hydraulic cleaning, installed robotic cleaning and deployable robotic cleaning.
Two Efficient Lattice Rescoring Methods Using Recurrent Neural Network Language Models (2016)

An important part of the language modelling problem for automatic speech recognition (ASR) systems, and many other related applications, is to appropriately model long-distance context dependencies in natural languages. Hence, statistical language models (LMs) that can model longer span history contexts, for example, recurrent neural network language models (RNNLMs), have become increasingly popular for state-of-the-art ASR systems. As RNNLMs use a vector representation of complete history contexts, they are normally used to rescore N-best lists. Motivated by their intrinsic characteristics, two efficient lattice rescoring methods for RNNLMs are proposed in this paper. The first method uses an n-gram style clustering of history contexts. The second approach directly exploits the distance measure between recurrent hidden history vectors. Both methods produced 1-best performance comparable to a 10 k-best rescoring baseline RNNLM system on two large vocabulary conversational telephone speech recognition tasks for US English and Mandarin Chinese. Consistent lattice size compression and recognition performance improvements after confusion network (CN) decoding were also obtained over the prefix tree structured N-best rescoring approach.
Reduction in Power Consumption in Multi-Core Amplifier (2019)

We report advances in low power consumption multi-core amplifiers. We namely show recent advances concerning core pumping, cladding pumping and hybrid pumping technologies for power efficient optical amplification with erbium doped multi-core fiber amplifiers.
ChemInform Abstract: SYNTHESIS AND REARRANGEMENTS OF ALKYL PHOSPHOROTHIOATES (1985)

Abstract Während die Umsetzung von Benzylalkohol (Ia) mit Triethylphosphat (II) zum S‐Benzylthioat (III) führt, entsteht aus Cyclohexanol (Ib) die entsprechende O‐alkylierte Verbindung (IVa).
Free-Electron Interactions with Designed van der Waals Materials: Novel Source of Lensed X-ray Radiation (2021)

We propose two novel X-ray generation schemes based on free electron interactions with van der Waals materials, in which the crystal geometry is shaped to create intrinsic lensing of the generated X-rays.
A structural dynamic explanation for observed escape of SARS-CoV-2 BA.2 variant mutation S371L/F (2022)

The SARS-CoV-2 Omicron sub-variants BA.1 and BA.2 have become the dominant variants worldwide due to enhanced transmissibility and immune evasion. In response to the rise of BA.1 and BA.2, two recent studies by Liu et al. and Iketani et al. provide a detailed analysis of loss of therapeutic antibody potency through evaluation of escape by pseudotyped viruses harboring BA.1 and BA.2 receptor binding domain (RBD) point mutations. Surprisingly, Liu et al. and Iketani et al. observed a profoundly broad escape effect for the individual mutations S371L and S371F. This result cannot be explained by known escape mechanisms of the SARS-CoV-2 RBD, and conflicts with existing computational and experimental escape measurements for S371 mutations performed on monomeric RBD. Through an examination of these conflicting datasets and a structural analysis of the antibodies assayed by Liu et al. and Iketani et al., we propose a mechanism to explain S371L/F escape according to a perturbation of spike trimer conformational dynamics that has not yet been described for any SARS-CoV-2 escape mutation. The proposed mechanism is relevant to Omicron and future variant surveillance as well as therapeutic antibody design.