gebhart/patrepeval huggingface dataset:
mTOR inhibition leads to increased sensitivity to methotrexate (2005)

3303 The mammalian target of rapamycin (mTOR) is an important player in the regulation of cell proliferation, growth, differentiation and survival. mTOR regulates both the activity of the 40S ribosomal protein S6 kinase and the eukaryotic initiation factor 4E-binding protein 1 (4E-BP1). This pathway also regulates the translation of mRNAs (e.g. cyclin D1) that are important for the G1/S transition. Inhibition of mTOR pathway increases the rate of turnover of cyclin D1. The cyclin D/CDKs phosphorylate pRb and release the E2Fs which mediate the transcription of proteins required for DNA synthesis, such as dihydrofolate reductase (DHFR). In a variety of cancers, including leukemia and lymphomas the Cyclin D-Cdk4,6/INK4/Rb/E2F pathway is deregulated and contributes to tumor development and also drug resistance towards antifolates. For example, inactivation of p16 and p15 genes, one of the most common genetic events in acute leukemia, is associated with increased DHFR expression and plays an important role in the pathogenesis of acute leukemia. Moreover, the PI3K/Akt/PTEN, the upstream regulators of mTOR pathway are also deregulated in leukemia and lymphomas. Mutations and hemizygous deletions of PTEN have been shown in some primary acute leukemia and non-Hodgkin’s lymphomas, and many hematopoietic cell lines. Akt1 is also frequently translocated in leukemia and lymphoma. Expression of DHFR is regulated both at the transcriptional through the Rb pathway and at the translational levels. We therefore hypothesized that by inhibiting mTOR pathway DHFR levels would be downregulated due to accelerating cyclin D1 degradation or by reducing the levels of DHFR translation through attenuation of 4E-BP1 phosphorylation. To test our hypothesis, four leukemic cell lines were used; namely CEM-S, K562, SKI-DLCL and HL60. The sensitivity of these cell lines against MTX and rapamycin was measured using the XTT assay. Briefly, in each well of a 96-well plate 4000 cells were plated in 300μL of medium containing the desired concentration of drug, and after 5 days, the XTT assay was performed according to standard protocols. After determining the IC50 values of each drug, the sensitivity of these leukemic cells against MTX in the presence of rapamycin at a concentration that corresponds to IC20 of these cell lines with rapamycin alone were determined. The addition of rapamycin sensitized the cells with lymphoblastic origin to MTX approximately 100-fold. We are currently measuring the levels of the proteins involved in the Rb pathway and the mTOR pathway to determine the mechanism of the observed sensitization. Our studies are also underway with combination studies using RAD001, which is a rapamycin analog that is being developed as an antiproliferative agent and other antifolates targeting DHFR and thymidylate synthase.
Embodied Social Proxy: Connecting Hub-and-Satellite Teams (2010)

Current business conditions have given rise to a particular kind of distributed team that is mostly collocated except for one remote member. These “hub-and-satellite ” teams face the challenge of leaving the satellite colleague out-of-sight and out-of-mind. We developed a telepresence device, called an Embodied Social Proxy (ESP), which represents the satellite worker in collaborations with hub colleagues. ESP serves as a consistent video conferencing terminal for the satellite that can be moved to wherever meetings occur. Our studies of teams using ESP in their daily work show that its continuous physical presence improved the interpersonal connections between hub and satellite colleagues.
Assessing the lithological composition of carbonate rocks of the Permian age in order to clarify calculated parameters (2021)

The article deals with the determination of the reservoir properties of Permian-age carbonate rocks. There is a section dissection technique, taking into account the fossil organisms prevailing for a particular geological age. It was noted a high content of silica in the lower Artinskian deposits of Toravey and Varandey fields of the Komi Republic. The presence of silicon is associated with an increase in the population of siliceous sponges during this period of sedimentation; this fact caused the maximum values of porosity and permeability in the corresponding intervals. However, this was also the reason for the high values of the residual water saturation factor and, as a result, low oil flow rates from the lower Artinskian stage. The need for detailed correlation and accounting for the content of fossils in the rocks when dissecting the well section made it necessary to systematize the available actual material on core and well testing. It became obvious that the separation of reservoirs and stages at the qualitative level isn't possible, so quantitative estimates of the parameters that are significantly different for the upper and lower Artinskian deposits and allow you to dissect the well section were proposed.
Deep-Learning for phase unwrapping in Lens-Free imaging (2019)

International audience
Amplifier Considerations in ROADM–free Space–Switched Nonlinear Optical Links (2020)

Power fluctuations accumulate in ROADM–free space–switched networks. Thousands of randomized nonlinear transmissions demonstrate that capacity with an inventory of {5,10,15,20} dB gain amplifiers is within 10 % of optimal and triple that with {10,20} dB amplifiers over 1,000 km.
Staphylococcus aureus Decolonization of Mice With Monoclonal Antibody Neutralizing Protein A (2018)

Staphylococcus aureus persistently colonizes the nasopharynx of about one-third of the human population, a key risk factor for community- and hospital-acquired invasive infections. Current strategies for S. aureus decolonization include topical and systemic administration of antibiotics, which is associated with selection for antibiotic resistance and posttreatment recolonization. Using a mouse model for S. aureus colonization, we show here that systemic administration of a recombinant monoclonal antibody neutralizing staphylococcal protein A (SpA) can stimulate antibacterial immunoglobulin G and immunoglobulin A responses and promote S. aureus decolonization. These results suggest that antibody neutralizing SpA, a B-cell superantigen, may also be useful for S. aureus decolonization in humans.
Rapid and direct detection of early-stage cancer biomarkers using screen printed electrode with portable electrochemical biosensor detector (2023)

• SPE based enzymatic biosensor for early-stage I cancer detection. • Point-of-care device for rapid cancer diagnostics. • Determination of a specific cancer biomarker using a smartphone. • Portable electrochemical biosensor for cancer detection.
Application Map in the Noise Suppression Filter for Video Compression (2020)

This paper considers an application map method usage together with the Nose Suppression Filter (NSF) in-loop filter for video compression. The application map method is described in details and simulations results of basic NSF are provided as well as simulation results of NSF powered with the application map method. It is demonstrated that the application map method allows to significantly improve objective performance results of basic NSF and additionally decrease decoder average complexity. As a result, an average bd-rate saving of NSF with the application map reaches 2.6% for luma component in Low Delay P coding configuration in comparing to Versatile Video Coding reference implementation (VTM) version 1.0.
An Adaptive Hybrid Multiprocessor technique for bioinformatics sequence alignment (2010)

Sequence alignment algorithms such as the Smith-Waterman algorithm are among the most important applications in the development of bioinformatics. Sequence alignment algorithms must process large amounts of data which may take a long time. Here, we introduce our Adaptive Hybrid Multiprocessor technique to accelerate the implementation of the Smith-Waterman algorithm. Our technique utilizes both the graphics processing unit (GPU) and the central processing unit (CPU). It adapts to the implementation according to the number of CPUs given as input by efficiently distributing the workload between the processing units. Using existing resources (GPU and CPU) in an efficient way is a novel approach. The peak performance achieved for the platforms GPU + CPU, GPU + 2CPUs, and GPU + 3CPUs is 10.4 GCUPS, 13.7 GCUPS, and 18.6 GCUPS, respectively (with the query length of 511 amino acid).
ChemInform Abstract: Rational Design of Lower‐Temperature Solid Oxide Fuel Cell Cathodes via Nanotailoring of Co‐Assembled Composite Structures. (2015)

Abstract The nanocomposite La 0.8 Sr 0.2 MnO 3 /Bi 1.6 Er 0.4 O 3 cathode is obtained by an in situ co‐assembly process through uniquely conjugated reverse‐strike coprecipitation and glycine‐nitrate combustion at extremely low temperature (&lt;300 °C).
Plasmonically Enhanced CRISPR/Cas13a‐Based Bioassay for Amplification‐Free Detection of Cancer‐Associated RNA (2021)

Novel methods that enable sensitive, accurate and rapid detection of RNA would not only benefit fundamental biological studies but also serve as diagnostic tools for various pathological conditions, including bacterial and viral infections and cancer. Although highly sensitive, existing methods for RNA detection involve long turn-around time and extensive capital equipment. Here, an ultrasensitive and amplification-free RNA quantification method is demonstrated by integrating CRISPR-Cas13a system with an ultrabright fluorescent nanolabel, plasmonic fluor. This plasmonically enhanced CRISPR-powered assay exhibits nearly 1000-fold lower limit-of-detection compared to conventional assay relying on enzymatic reporters. Using a xenograft tumor mouse model, it is demonstrated that this novel bioassay can be used for ultrasensitive and quantitative monitoring of cancer biomarker (lncRNA H19). The novel biodetection approach described here provides a rapid, ultrasensitive, and amplification-free strategy that can be broadly employed for detection of various RNA biomarkers, even in resource-limited settings.
Colloidally Confined Crystallization of Highly Efficient Ammonium Phosphomolybdate Catalysts (2018)

Nanodroplets in inverse miniemulsions provide a colloidal confinement for the crystallization of ammonium phosphomolybdate (APM), influencing the resulting particle size. The effects of the space confinement are investigated by comparing the crystallization of analogous materials both in miniemulsion and in bulk solution. Both routes result in particles with a rhombododecahedral morphology, but the ones produced in miniemulsion have sizes between 40 and 90 nm, 3 orders of magnitude smaller than the ones obtained in bulk solution. The catalytic activity of the materials is studied by taking the epoxidation of cis-cyclooctene as a model reaction. The miniemulsion route yields APM particles catalytically much more active than analogous samples produced in bulk solution, which can be explained by their higher dispersibility in organic solvents, their higher surface area, and their higher porosity. Inorganic phosphate salt precursors are compared with organic phosphate sources. APM nanoparticles prepared in miniemulsion from d-glucose-6-phosphate and O-phospho-dl-serine yield a conversion in the epoxidation reaction of more than 90% after only 1 h, compared to 30% for materials prepared in bulk solution. In addition, the catalysts prepared in miniemulsion display a promising recyclability.
Influence of Oxygen and Calcium in Titanium Welding Wire Surface on Arc Stability and Droplet Transfer in Pulsed MIG (Metal Inert Gas) Welding Process (2004)

The influence of oxygen and calcium in the surface layer of titanium welding wire on arc stability and droplet transfer in pulsed metal inert gas (MIG) welding was investigated. Outbreak phenomenon of the arc was classified into two types, a concentrated arc and a sprayed arc. In both types, cathode spots were generated stable position on base metal by the effect of oxygen in welding wire surface. With regard to droplet transfer, droplets were formed and transferred into molten pool stably in case of the concentrated arc, whereas droplets were not formed often or their travel times into molten pool were enlarged in case of the sprayed arc. The results of the investigation are concluded that the calcium in the surface layer of welding wire makes the arc stable and the oxygen in it assists the droplet transfer.
Covalent disruptor of YAP-TEAD association suppresses defective Hippo signaling (2022)

The transcription factor TEAD, together with its coactivator YAP/TAZ, is a key transcriptional modulator of the Hippo pathway. Activation of TEAD transcription by YAP has been implicated in a number of malignancies, and this complex represents a promising target for drug discovery. However, both YAP and its extensive binding interfaces to TEAD have been difficult to address using small molecules, mainly due to a lack of druggable pockets. TEAD is post-translationally modified by palmitoylation that targets a conserved cysteine at a central pocket, which provides an opportunity to develop cysteine-directed covalent small molecules for TEAD inhibition. Here, we employed covalent fragment screening approach followed by structure-based design to develop an irreversible TEAD inhibitor MYF-03-69. Using a range of in vitro and cell-based assays we demonstrated that through a covalent binding with TEAD palmitate pocket, MYF-03-69 disrupts YAP-TEAD association, suppresses TEAD transcriptional activity and inhibits cell growth of Hippo signaling defective malignant pleural mesothelioma (MPM). Further, a cell viability screening with a panel of 903 cancer cell lines indicated a high correlation between TEAD-YAP dependency and the sensitivity to MYF-03-69. Transcription profiling identified the upregulation of proapoptotic <i>BMF</i> gene in cancer cells that are sensitive to TEAD inhibition. Further optimization of MYF-03-69 led to an in vivo compatible compound MYF-03-176, which shows strong antitumor efficacy in MPM mouse xenograft model via oral administration. Taken together, we disclosed a story of the development of covalent TEAD inhibitors and its high therapeutic potential for clinic treatment for the cancers that are driven by TEAD-YAP alteration.
Characterization of field-effect transistors with La2Hf2O7 and HfO2 gate dielectric layers deposited by molecular-beam epitaxy (2006)

The electrical properties of La2Hf2O7 (LHO) and HfO2 (HO) high-k dielectric layers deposited by molecular-beam epitaxy are reported. Capacitors and transistors with LHO and HO gate dielectric layers and TaN metal gate electrodes deposited using physical vapor deposition were fabricated. The (SiO2) equivalent oxide thickness (EOT), the electrical oxide thickness in inversion toxinv, and the gate leakage current density (Jg) were determined on large area metal-oxide-semiconductor capacitors and metal-oxide-semiconductor field-effect transistors. HO layers with a physical thickness tph=30Å showed an EOT (toxinv) of 15.1Å (19.3Å) with Jg=8.1×10−6A∕cm2 at Vg=Vfb−1V. LHO layers deposited on SiON showed a minimum EOT (toxinv) of 18.7Å (25Å) with Jg=4×10−8A∕cm2 at Vg=Vfb−1V. The (effective) electron mobility at high E field for LHO layers was observed for a 40-Å-thick LHO layer deposited on Si with μeff=147cm2∕Vs at E=1MV∕cm. For a 30-Å-thick HO layer at identical field, μeff=170cm2∕Vs was found. LHO layers deposited on SiON interface exhibited 5%–10% higher electron mobility at high E field than identical layers deposited on Si. Further, both low E field and high E field mobilities decreased for thicker high-k layers, indicating remote charge scattering from both the interface and the bulk of the high-k dielectric. It was observed that LHO layers showed strongly reduced electron trapping in preexisting bulk defects as compared to HO layers. At E=1MV∕cm (corresponding to Vg=VT+0.6V), the trapped charges per area Ntr were Ntr&amp;lt;5×1010∕cm2 for the LHO layers and Ntr&amp;gt;5×1011∕cm2 for the HO layers. These results show that low-leakage Hf-based gate dielectric layers with low defect density can be obtained by alloying with La.
[Thyroid dysfunction: interactions between genetic and environmental conditions]. (2012)

Thyroid dysfunction (TD) is a very common entity in clinical practice nowadays. Prevalence may be underestimated because of the limitations of epidemiological studies. There are mainly genetic and environmental factors that interact on thyroid function. Genetic factors are extensively described in literature but molecular advance on the field may change older classifications based on B-cell or T-cell mediated disorders. The dominant pattern of inheritance makes family predisposition a relevant question in patient medical history but clinical research show that immune system is not enough to cause overt dysfunction. The role of environmental factors generates debate on medical literature. Some classic factors as iodine intake are well characterized but others as fetal microhimerism or new antineoplastic agents are less known. A review of medical literature on thyroid dysfunction has been performed and genetic and environmental factors are described in this article.
Wood from Angiosperms and Gymnosperms Shows Distinctive Lignin Peaks in Direct Analysis in Real Time (DART) Mass Spectra (2022)

A data set was constructed consisting of 3021 mass spectra randomly selected from the ForeST© (Forensic Spectra of Trees) database of mass spectra for wood analyzed by Direct Analysis in Real Time ionization coupled with time-of-flight mass spectrometry (DART-TOFMS). Clear and reproducible differences were observed between the lignin peaks for angiosperms and gymnosperms, with DART-TOFMS spectra of angiosperms showing significantly higher abundances for peaks associated with syringyl subunits. These differences can be used to provide support for enforcing trade laws by accurately identifying the source of finished wood products when anatomical differences are not present.
Discovery of Orally Efficacious Melanin-Concentrating Hormone Receptor-1 Antagonists as Antiobesity Agents. Synthesis, SAR, and Biological Evaluation of Bicyclo[3.1.0]hexyl Ureas (2006)

Melanin-concentrating hormone (MCH) is a cyclic, nonadecapeptide expressed in the CNS of all vertebrates that regulates feeding behavior and energy homeostasis via interaction with the central melanocortin system. Regulation of this interaction results in modulation of food intake and body weight gain, demonstrating significant therapeutic potential for the treatment of obesity. The MCH-1 receptor (MCH-R1) has been identified as a key target in MCH regulation, as small molecule antagonists of MCH-R1 have demonstrated activity in vivo. Herein, we document our research in a bicyclo[3.1.0]hexyl urea series with particular emphasis on structure-activity relationships and optimization of receptor occupancy, measured both in vitro and via an ex vivo binding assay following an oral dosing regimen. Several compounds have been tested in vivo and exhibit oral efficacy in relevant acute rodent feeding models. In particular, 24u has proven efficacious in chronic rodent models of obesity, showing a statistically significant reduction in food intake and body weight over a 28 day study.
A new method to suppress ghosting artifacts arising from long-T1 species in segmented inversion recovery (IR) sequences (2011)

To evaluate a new long-T1 artifact suppression method and compare its effectiveness with previously reported techniques.
Latissimus Dorsi Tendon Transfer for Irreparable Posterosuperior Rotator Cuff Tears (2007)

BACKGROUND: The purpose of this study was to evaluate the clinical results of latissimus dorsi tendon transfer in patients with an irreparable posterosuperior rotator cuff tear to help determine which patient and anatomic factors affect clinical outcome. METHODS: Fourteen patients with a latissimus dorsi tendon transfer were clinically evaluated with use of the PENN (University of Pennsylvania) shoulder score as well as with quantitative measurement of isometric muscle strength and the range of motion of both shoulders at a minimum of twenty-four months postoperatively. The anatomic results were evaluated with postoperative magnetic resonance imaging and electromyography. RESULTS: Nine patients were satisfied with the outcome, had significant clinical improvement, and reported that they would have the operation again under similar circumstances. The other five patients were dissatisfied with the result and had significantly worse PENN scores, active elevation, and objective measures of strength. Eight of the nine patients with a good clinical result were male, and four of the five with a poor result were female. Patients with a good clinical result had had significantly better preoperative function in active forward flexion and active external rotation compared with the patients with a poor result. The magnetic resonance imaging demonstrated healing of the tendon to the greater tuberosity in twelve patients and equivocal healing in two. There was no significant atrophy of any of the transferred muscles. Electromyography demonstrated clear activity in the transferred latissimus muscle during humeral adduction in all fourteen patients, some electrical activity with active forward elevation in only one patient, and some electrical activity with active external rotation in six of the nine patients with a good clinical result. None of the patients with a poor clinical result demonstrated electrical activity of the transferred muscle with active forward flexion or external rotation. CONCLUSIONS: Synchronous in-phase contraction of the transferred latissimus dorsi is a variable finding following the surgical treatment of irreparable posterosuperior rotator cuff tears, but when it is present it is associated with a better clinical result. Preoperative shoulder function and general strength influence the clinical result. Female patients with poor shoulder function and generalized muscle weakness prior to surgery have a greater likelihood of having a poor clinical result.
Visualizing three‐dimensional flow with simulated streamlines and three‐dimensional phase‐contrast MR imaging (1992)

Three-dimensional (3D) velocity maps acquired with 3D phase-contrast magnetic resonance (MR) imaging contain information regarding complex motions that occur during imaging. A technique called simulated streamlines, which facilitates the display and comprehension of these velocity data, is presented. Single or multiple seed points may be identified within blood vessels of interest and tracked through the velocity field. The resulting trajectories are combined with a 3D MR angiogram and displayed with 3D volume visualization software. Mathematical analysis highlights potential applications and pitfalls of the technique, which was implemented both in phantoms and in vivo with excellent results. For example, single streamlines reveal helical flow patterns in aneurysms, and multiple streamlines seeded in the common carotid artery reveal branch filling-time relationships and slow filling of the carotid bulb. The technique is helpful in understanding these complex flow patterns.