gebhart/patrepeval huggingface dataset:
Abstract IA26: Clinical development of PI3K/AKT pathway inhibitors in breast cancer (2018)

Abstract Targeting the PI3K/AKT/mTOR pathway has been a focus for drug development since the discovery of PI3K-activating mutations in p110α over 10 years ago. Breast cancer has been a primary indication for development of this class of drugs because of the high prevalence of these mutations, up to 45% in hormone receptor-positive breast cancer, and the synergy observed in combinations with endocrine therapies. An mTOR inhibitor, everolimus, was approved in breast cancer in combination with exemestane in 2012, indicating the synergy between ER and PI3K pathway translates to the clinic. Apitolisib, a dual PI3K pan-isoform and mTOR inhibitor, has discontinued development due to toxicities, despite compelling preclinical activity across multiple tumor types regardless of PI3K and PTEN status. Pictilisib, a pan-isoform PI3K inhibitor, has shown some evidence of activity, but in phase II studies has demonstrated that the activity is limited by dose intensity. Buparlisib, a pan-isoform PI3K inhibitor, has demonstrated efficacy in a large phase III study, but was not deemed sufficiently active relative to the toxicity in HR+ breast cancer to be submitted for regulatory approval. Second-generation PI3K and AKT inhibitors with higher selectivity and mutant specificity are in clinical development and hope to thread a better therapeutic index by dosing higher for more profound inhibition, and/or selectively inhibiting mutated forms of PI3K. Taselisib (GDC-0032) is a beta-sparing and PI3K-mutant selective inhibitor that leads to degradation of only the mutant form of PI3K and is currently in phase III. More recently, taselisib met the primary endpoint of improved response rates in a randomized, neoadjuvant phase II trial, LORELEI. Alpelisib is an alpha-selective PI3K inhibitor that is also in phase III. Recent data with ipatasertib, an AKT inhibitor, has demonstrated better tolerability and efficacy in randomized phase II trials of both prostate cancer and triple-negative breast cancer, where the PI3K/AKT signaling pathway is activated by either loss of PTEN or PI3K mutations, and may offer a better therapeutic index given its unique mechanism of action and place in the PI3K signaling pathway. Overall, the PI3K/AKT pathway is still considered an important pathway to target for certain cancers; however, target selectivity, dosing, and the right combination are critical to find a therapeutic index to provide a good option for patients. Citation Format: Mika Derynck. Clinical development of PI3K/AKT pathway inhibitors in breast cancer [abstract]. In: Proceedings of the AACR Special Conference: Advances in Breast Cancer Research; 2017 Oct 7-10; Hollywood, CA. Philadelphia (PA): AACR; Mol Cancer Res 2018;16(8_Suppl):Abstract nr IA26.
Hydrophilic Poly(vinylidene Fluoride) Film with Enhanced Inner Channels for Both Water- and Ionic Liquid-Driven Ion-Exchange Polymer Metal Composite Actuators (2019)

This study presents a novel and facile strategy to fabricate a hydrophilic poly(vinylidene fluoride) (PVDF) electrolyte film with enhanced inner channels for a high-performance and cost-effective ion-exchange polymer metal composite (IPMC) actuator. The resultant PVDF composite film is composed of hierarchical micro/nanoscale structures: well-defined polymer grains with a diameter of ∼20 μm and much finer particles with a diameter of ∼390 nm, producing three-dimensional interconnected, hierarchical inner channels to facilitate ion migration of IPMC. Interestingly, the electrolyte matrix film has a high porosity of 15.8% and yields a high water uptake of 44.2% and an ionic liquid (IL, [EMIm]·[BF<sub>4</sub>]) uptake of 38.1% to make both water-driven and IL-driven IPMC actuators because of the introduction of polar polyvinyl pyrrolidone. Compared to the conventional PVDF/IL-based IPMC, both water-driven and IL-driven PVDF-based IPMCs exhibit high ion migration rates, thus effectively improving the actuation frequency and producing remarkably higher levels of actuation force and displacement. Specifically, the force outputs are increased by 13.4 and 3.0 folds, and the displacement outputs are increased by 2.2 and 1.9 folds. Using an identical electrolyte matrix, water-driven IPMC exhibits stronger electromechanical performance, benefiting to make IPMC actuator with high levels of force and power outputs, whereas IL-driven IPMC exhibits a more stable electromechanical performance, benefiting to make long lifetime IPMC actuator in air. Thus, the resultant IPMCs are promising in the design of artificial muscles with tunable electromechanical performance for flexible actuators or displacement/vibration sensors at low cost.
Data from Comparative Microbiomics Analysis of Antimicrobial Antibody Response between Patients with Lung Cancer and Control Subjects with Benign Pulmonary Nodules (2023)

&lt;div&gt;AbstractBackground:&lt;p&gt;CT screening can detect lung cancer early but suffers a high false-positive rate. There is a need for molecular biomarkers that can distinguish malignant and benign indeterminate pulmonary nodules (IPN) detected by CT scan.&lt;/p&gt;Methods:&lt;p&gt;We profiled antibodies against 901 individual microbial antigens from 27 bacteria and 29 viruses in sera from 127 lung adenocarcinoma (ADC), 123 smoker controls (SMC), 170 benign nodule controls (BNC) individuals using protein microarrays to identify ADC and BNC specific antimicrobial antibodies.&lt;/p&gt;Results:&lt;p&gt;Analyzing fourth quartile ORs, we found more antibodies with higher prevalence in the three BNC subgroups than in ADC or SMC. We demonstrated that significantly more anti-&lt;i&gt;Helicobacter pylori&lt;/i&gt; antibodies showed higher prevalence in ADC relative to SMC. We performed subgroup analysis and found that more antibodies with higher prevalence in light smokers (≤20 pack-years) compared with heavy smokers (&gt;20 pack-years), in BNC with nodule size &gt;1 cm than in those with ≤1 cm nodules, and in stage I ADC than in stage II and III ADC. We performed multivariate analysis and constructed antibody panels that can distinguish ADC versus SMC and ADC versus BNC with area under the ROC curve (AUC) of 0.88 and 0.80, respectively.&lt;/p&gt;Conclusions:&lt;p&gt;Antimicrobial antibodies have the potential to reduce the false positive rate of CT screening and provide interesting insight in lung cancer development.&lt;/p&gt;Impact:&lt;p&gt;Microbial infection plays an important role in lung cancer development and the formation of benign pulmonary nodules.&lt;/p&gt;&lt;/div&gt;
Distributed Controller Design for Vehicle Platooning under Packet Drop Scenario (2020)

This paper proposes a distributed control strategy for homogeneous platoon systems with external disturbances under random packet drop scenario which can occur due to underlying communication network among the vehicles in a platoon. A linear matrix inequality (LMI) based approach is used to obtain the controller gains for ensuring the stability with a bounded H <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">∞</sub> norm. The effectiveness of the proposed method is demonstrated through numerical results considering different network topologies in a platoon under single packet drop. The H <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">∞</sub> norm bound has been studied for different number of platoon members under the different structure of network topologies and the packet drop.
Supramolecular nanocarriers with photoresponsive cargo (2016)

The covalent integration of fluorescent and photoswitchable components within the same molecular skeleton can be exploited to activate fluorescence under optical control. Specifically, a photoswitchable oxazine heterocycle can be connected to either a coumarin or a borondipyrromethene fluorophore. Illumination of the resulting molecular dyads at an appropriate activation wavelength either opens the heterocycle reversibly or cleaves it irreversibly, depending on the relative positions of its methylene and nitro substituents. These photochemical transformations shift bathochromically the main absorption band of the fluorophore and allow its selective excitation at a given wavelength. These hydrophobic molecular dyads can be entrapped within the hydrophobic interior of self-assembling nanoparticles of amphiphilic polymer. The supramolecular envelope around the switchable compounds enables their transfer into aqueous environments and their operation under these conditions with minimal influence on their photochemical and photophysical properties. The reversible fluorescence activation, possible in one instance, imposes intermittence on the detected emission and offers the opportunity to resolve closely-spaced nanocarriers in time to reconstruct images with subdiffraction resolution. The irreversible fluorescence activation, possible in the other, maintains emission on after the activation event and permits the monitoring of the diffusion of the activated nanocarriers in real time with the sequential acquisition of images. Thus, these operating principles to solubilize and operate photoswitchable fluorophores in aqueous environments with the aid of supramolecular nanocarriers can lead to valuable protocols to image specimens with subdiffraction resolution and to monitor dynamic events noninvasively.
Homologous recombination inquiry through ovarian malignancy investigations: JGOG3025 Study (2023)

The Cancer Genome Atlas (TCGA) network has clarified that ~50% of high-grade serous ovarian cancers show homologous recombination deficiency (HRD). However, the frequency of HRD in Japanese patients with ovarian cancer remains unclear. We aimed to identify the frequency of HR-associated gene mutations in Japanese patients with ovarian cancer. The JGOG3025 study is a multicenter collaborative prospective observational study involving 65 study sites throughout Japan. We recruited 996 patients who were clinically diagnosed with ovarian cancer before surgery from March 2017 to March 2019, and 701 patients were eligible according to the criteria. We used frozen tumor tissues to extract DNA and performed next-generation sequencing for 51 targeted genes (including 29 HR-associated genes) in 701 ovarian cancers (298 high-grade serous cases, 189 clear cell cases, 135 endometrioid cases, 12 mucinous cases, 3 low-grade serous cases, and 64 others). HRD was defined as positive when at least one HR-associated gene was mutated. The frequencies of HRD and tumor BRCA1/2 mutations were 45.2% (317/701) and 18.5% (130/701), respectively, in the full analysis set. Next, we performed multivariate Cox proportional hazards regression analysis for progression-free survival (PFS) and overall survival (OS). Advanced-stage ovarian cancer patients with HRD had adjusted hazard ratios of 0.72 (95% CI, 0.55-0.94) and 0.57 (95% CI, 0.38-0.86) for PFS and OS, respectively, compared with those without HRD (p = 0.016 and 0.007). Our study demonstrated that mutations in HR-associated genes were associated with prognosis. Further studies are needed to investigate the prognostic impact of each HR-associated gene in ovarian cancer.
EXCITING NEW TECHNOLOGIES FOR CREATING ACCURATE IVHS DATABASES (1993)

An exciting new program is underway in the U.S. in which Global Positioning Systems (GPS) and Geographic Information Systems (GIS) are being combined with advanced video technology to create GeoVISTA (TM) databases of street and attribute data for all urban streets in the U.S. This paper describes the new methods, compares them to classical methods and explores how the new methods can improve IVHS database effectiveness. Considered are: Database contents and requirements, factors affecting database quality, positional and attribute accuracies, updating and digitizing existing maps, commonly used map sources, methods of collecting and extracting attributes (such as speed limits and turn restrictions) field inventory methods, accuracy, completeness and reliability of attributes and methods of validating accuracy and completeness.
Postharvest Heat Treatment of Apples to Control San Jose Scale (Quadraspidiotus perniciosus Comstock) and Blue Mold (Penicillium expansum Link) and Maintain Fruit Firmness (1998)

Postharvest heat treatments were applied to three apple ( Malus domestica Borkh.) cultivars: `Anna', `Golden Delicious', and `Jonathan'. The temperatures ranged from 38 to 50 °C and from 5 to 96 hours. The temperatures of 50 °C for 5 or 10 hours and 46 °C for 10 hours controlled all developmental stages of San Jose scale on `Golden Delicious' and `Jonathan' fruit. Blue mold germination was prevented by 46, 42, and 38 °C after 28, 34, and 42 hours, respectively. The time needed to control the fungus was longer than that required to kill the insect. Apples were damaged by a 50 °C treatment but could withstand at least 12 hours at 46 °C and at least 24 hours at 42 °C. At 38 °C no damage was found on preclimacteric apples even after 96 hours, but if postclimacteric fruit were heated at 38 °C heat damage occurred. The treatments that did not cause damage maintained the fruit firmness during post storage ripening. The results are discussed in the context of developing integrated postharvest heat treatments.
Structural health monitoring (vibration) as a tool for identifying structural alterations of the lumbar spine: a twin control study (2016)

Structural health monitoring (SHM) is an engineering technique used to identify mechanical abnormalities not readily apparent through other means. Recently, SHM has been adapted for use in biological systems, but its invasive nature limits its clinical application. As such, the purpose of this project was to determine if a non-invasive form of SHM could identify structural alterations in the spines of living human subjects. Lumbar spines of 10 twin pairs were visualized by magnetic resonance imaging then assessed by a blinded radiologist to determine whether twin pairs were structurally concordant or discordant. Vibration was then applied to each subject's spine and the resulting response recorded from sensors overlying lumbar spinous processes. The peak frequency, area under the curve and the root mean square were computed from the frequency response function of each sensor. Statistical analysis demonstrated that in twins whose structural appearance was discordant, peak frequency was significantly different between twin pairs while in concordant twins, no outcomes were significantly different. From these results, we conclude that structural changes within the spine can alter its vibration response. As such, further investigation of SHM to identify spinal abnormalities in larger human populations is warranted.
Optogénétique et douleur chronique : une stratégie applicable chez l’humain ? (2016)

Les traitements actuels contre la douleur chronique procurent peu d’analgésie mais d’importants effets secondaires. Une alternative serait de moduler l’activité neuronale directement à l’aide de l’optogénétique, une thérapie génique impliquant l’utilisation de protéines photo-activables. Dans les modèles animaux, cette approche diminue les douleurs inflammatoire et neuropathique. Des avancées spectaculaires permettent d’envisager son application clinique dans les prochaines décennies.
Graph Constrained Discriminant Analysis: A New Method for the Integration of a Graph into a Classification Process (2011)

Integrating gene regulatory networks (GRNs) into the classification process of DNA microarrays is an important issue in bioinformatics, both because this information has a true biological interest and because it helps in the interpretation of the final classifier. We present a method called graph-constrained discriminant analysis (gCDA), which aims to integrate the information contained in one or several GRNs into a classification procedure. We show that when the integrated graph includes erroneous information, gCDA's performance is only slightly worse, thus showing robustness to misspecifications in the given GRNs. The gCDA framework also allows the classification process to take into account as many a priori graphs as there are classes in the dataset. The gCDA procedure was applied to simulated data and to three publicly available microarray datasets. gCDA shows very interesting performance when compared to state-of-the-art classification methods. The software package gcda, along with the real datasets that were used in this study, are available online: http://biodev.cea.fr/gcda/.
Fighter aircraft lateral axis full envelope control law design (2002)

A decoupled wide envelope lateral/directional axes control design is presented for a supermaneuverable version of an F-18 aircraft. A control structure is developed that separates gain-scheduling issues from aircraft performance issues. Flight condition dependent state and control effectiveness variations are accounted for by an inner loop controller designed using eigenstructure assignment. Structured singular value synthesis is used to design an implicit model following outer loop controller that addresses flying qualities performance specifications. A control selector is designed that generates lateral/directional aerodynamic and thrust vectoring commands from generalized control inputs of roll and yaw acceleration. Robustness analysis show that the control system performs well despite neglected dynamics and system uncertainties. Nonlinear simulations are presented showing excellent decoupling of roll and yaw responses.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Investigating Tissue-Specific Abnormalities in Alzheimer’s Disease with Multi-Shell Diffusion MRI (2022)

This analysis framework constitutes a comprehensive approach allowing simultaneous macro and microscopic assessment of WM, GM, and CSF, from a single DW-MRI dataset.
Traiter la traite : quand la prostituée navigue dans les eaux troubles de la dignité humaine (2012)

info:eu-repo/semantics/published
ChemInform Abstract: “Salted” Iron Pentacarbonyl: Molecular Isolation in Alkali Halide Solids. (1990)

Abstract The conditions for single‐molecule isolation of iron pentacarbonyl by codeposition from vapor phase onto a cold substrate with excess alkali halide vapor are established.
SPE hydrogen/oxygen fuel cells for rigorous naval applications (2002)

The sheet metal design approach currently used in production SPE water electrolyzers for nuclear submarines has been converted into SPE fuel cells for rigorous naval applications. A review of the capabilities of the naval SPE water electrolyzer is provided. This includes lifetime testing, severe environmental testing and accumulated experience of the naval SPE water electrolyzer system. A comparison of the sheet metal SPE fuel cell is made with the sheet metal SPE electrolyzer. Similarities and differences are identified. A comparison of sheet metal hardware with carbon/graphite type hardware is also provided. The performance of the SPE fuel cell is presented. This includes voltage/current relationships for various applications. Weight and volume projections for complete systems are provided for several mission scenarios.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Revisiting Staggered Wages to Consider Discounting (2011)

In the literature of staggered wages [2, 3, 6, 7], the discount factor is neglected in the workers ’ loss function. Yet, discounting is to be viewed as an extra piece of microfoundation with implications for discretionary monetary policy. We revisit the issue and show that discounting in the model of staggered wages actually lowers the time-consistent steady inflation.
Viscoelastic and dynamic properties of polymer grafted nanocomposites with high glass transition temperature graft chains (2019)

The viscoelastic and dynamic properties of dynamically asymmetric polymer-grafted nanocomposites (PGNs) are studied via molecular dynamics simulations. The model PGN is made up of two chains having a large glass transition temperature (Tg) difference, where the grafted chains have the higher Tg. The viscoelastic and dynamic properties were studied at temperatures between the Tgs of the graft and matrix polymers as a function of the average brush height. Simulation results showed that the static and dynamic properties of the glassy brush played an important role in reinforcing the overall nanocomposite. Although the bare nanofiller containing nanocomposite showed increased shear storage moduli compared to the neat low-Tg polymer, PGNs presented the greatest increases in the shear storage modulus. In addition, the shear storage modulus increased with increasing average brush height, reaching a maximum value at the brush height limit. Analysis of the simulation results revealed that the reinforcement of the shear storage modulus was mainly related to the slowing down of the dynamics of matrix polymer chains. The following mechanisms were identified that were responsible for this effect: (i) High-Tg grafted chains act as obstacles for matrix polymer chains. (ii) With increasing average brush height, grafted and matrix chains form a well-mixed morphology at the nanofiller interface, which leads to further slowing down of the matrix chain dynamics. (iii) Finally, at the brush height limit, grafted chains form a stiff and immobile percolated network, which leads to the observed maximum in the shear storage modulus.
Spatial transcriptome of a germinal center plasmablastic burst hints at MYD88 / CD79B mutants‐enriched diffuse large B‐cell lymphomas (2022)

The GC reaction results in the selection of B cells acquiring effector Ig secreting ability by progressing toward plasmablastic differentiation. This transition is associated with exclusion from the GC microenvironment. The aberrant expansion of plasmablastic elements within the GC fringes configures an atypical condition, the biological characteristics of which have not been defined yet. We investigated the in situ immunophenotypical and transcriptional characteristics of a nonclonal germinotropic expansion of plasmablastic elements (GEx) occurring in the tonsil of a young patient. Compared to neighboring GC and perifollicular regions, the GEx showed a distinctive signature featuring key regulators of plasmacytic differentiation, cytokine signaling, and cell metabolism. The GEx signature was tested in the setting of diffuse large B-cell lymphoma (DLBCL) as a prototypical model of lymphomagenesis encompassing transformation at different stages of GC and post-GC functional differentiation. The signature outlined DLBCL clusters with different immune microenvironment composition and enrichment in genetic subtypes. This report represents the first insight into the transcriptional features of a germinotropic plasmablastic burst, shedding light into the molecular hallmarks of B cells undergoing plasmablastic differentiation and aberrant expansion within the noncanonical setting of the GC microenvironment.