gebhart/patrepeval huggingface dataset:
Allele‐specific, Hybridization‐based, Washing‐free Fluorescence Signal Production Platforms for Quantitation of Single‐Base Change (C → U) in RNA (2015)

A single nucleotide polymorphism ( SNP ) is a single base‐pair substitution that commonly constitutes the genetic variation in individuals. Because of its association with disease susceptibility and drug resistance, SNP detection is of great value in studying the variation in drug responses. Here we report four types of washing‐free ( i.e ., separation‐free or sequential addition of reagents) and polymerase chain reaction ( PCR )‐free fluorescence signal production platforms for quantitative detection of a single‐base mismatch in RNA and compare their analytical efficiency. The RNA ‐templated SNP detection methods in this study are based on the allele‐specific hybridization approach and/or on the allele‐specific oligonucleotide ligation approach, and have been successfully applied to the quantitation of single‐base mutation (C → U) in RNA of the BCR–ABL fusion gene, by endpoint measurements of fluorescence intensity. These methods have several advantages for practical applications, such as direct discrimination of single‐base mismatch of the RNA extracted from cells, no requirement of PCR amplification, performance of homogeneous detection, easy design of detection probes, and suitability for large‐scale genotyping.
Fuzzy State Machine Energy Management Strategy for Hybrid Electric UAVs with PV/Fuel Cell/Battery Power System (2018)

Energy management strategies are the key technology for hybrid electric UAVs. This paper proposes a fuzzy state machine (FSM) energy management strategy with an online potential to control the power flow for the hybrid electric UAV which includes the photovoltaic, fuel cell, and battery power sources. The FSM strategy couples the fuzzy logical strategy with a state machine strategy where the fuzzy logical strategy controls the power split between a fuel cell and a battery and the state machine deals with the power flow of photovoltaics and battery. To evaluate the FSM strategy, a simulation platform integrating the hybrid power system model and UAV model is developed with a Matlab/Simulink tool. An existed online thermostat control strategy for the same type of UAV is employed to compare with the proposed strategy based on the developed platform. The energy management process and the state of each power source are analyzed under a given mission scenario. The comparison of the two strategies about the power and energy contribution rates of each power source, the battery state of charge, and the hydrogen consumption is presented. The results indicate that the FSM strategy can satisfy the demand power effectively during the mission and performs better than the thermostat control strategy on power distribution and fuel consumption.
In vitro human cell‐based aneugen molecular mechanism assay (2022)

This laboratory previously described an in vitro human cell-based assay and data analysis scheme that discriminates common molecular targets responsible for chemical-induced in vitro aneugenicity: tubulin destabilization, tubulin stabilization, and inhibition of Aurora kinases (Bernacki et al., Toxicol. Sci. 170 [2019] 382-393). The current report describes updated procedures that simplify benchtop processing and data analysis methods. For these experiments, human lymphoblastoid TK6 cells were exposed to each of 25 aneugens over a range of concentrations in the presence of fluorescent paclitaxel (488 Taxol). After a 4 h treatment period, cells were lysed and nuclei were stained with a nucleic acid dye and labeled with fluorescent antibodies against phospho-histone H3 (p-H3). Flow cytometric analyses revealed several unique signatures: tubulin stabilizers caused increased frequencies of p-H3-positive events with concentration-dependent increases in 488 Taxol-associated fluorescence; tubulin destabilizers caused increased frequencies of p-H3-positive events with concomitant decreases in 488 Taxol-associated fluorescence; and Aurora kinase B inhibitors caused reduced frequencies of p-H3-positive events and lower median fluorescent intensities of p-H3-positive events. These results demonstrate a simple rubric based on 488 Taxol- and p-H3-associated metrics can reliably discriminate between several commonly encountered aneugenic molecular mechanisms.
Impact of Heat Shield Structure in the Growth Process of Czochralski Silicon Derived from Numerical Simulation (2014)

Further development of the photovoltaic industry is restricted by the productivity of mono-crystalline silicon technology due to its requirements of low cost and high efficient photocells.The heat shield is not only the important part of the thermal field in Czochralski(Cz)mono-crystalline silicon furnace,but also one of the most important factors influencing the silicon crystal growth.Large-diameter Cz-Si crystal growth process is taken as the study object.Based on FEM numerical simulation,different heat shield structures are analyzed to investigate the heater power,the melt-crystal interface shape,the argon flow field,and the oxygen concentration at the melt-crystal interface in the process of large Cz-Si crystal growth.The impact of these factors on the growth efficiency and crystal quality are analyzed.The results show that the oxygen concentration on the melt-crystal interface and the power consumption of the heater stay high due to the lack of a heat shield in the crystal growth system.Argon circumfluence is generated on the external side of the right angle heat shield.By the right-angle heat shield,the speed of gas flow is lowered on the melt free surface,and the temperature gradient of the free surface is increased around the melt-crystal interface.It is not conducive for the stable growth of crystal.The shape of the melt-crystal interface and the argon circulation above the melt free surface are improved by the inclined heat shield.Compared with the others,the system pulling rate is increased and the lowest oxygen concentration is achieved at the melt-crystal interface with the composite heat shield.By the adoption of the optimized composite heat shield in experiment,the real melt-crystal interface shapes and its deformation laws obtained by Quick Pull Separation Method at different pulling rates agree with the simulation results.The results show that the method of simulation is feasible.The proposed research provides the theoretical foundation for the thermal field design of the large diameter Cz-Si mon
Aging-aware compiler-directed VLIW assignment for GPGPU architectures (2013)

Negative bias temperature instability (NBTI) adversely affects the reliability of a processor by introducing new delay-induced faults. However, the effect of these delay variations is not uniformly spread across functional units and instructions: some are affected more (hence less reliable) than others. This paper proposes a NBTI-aware compiler-directed very long instruction word (VLIW) assignment scheme that uniformly distributes the stress of instructions with the aim of minimizing aging of GPGPU architecture without any performance penalty. The proposed solution is an entirely software technique based on static workload characterization and online execution with NBTI monitoring that equalizes the expected lifetime of each processing element by regenerating aging-aware healthy kernels that respond to the specific health state of GPGPU. We demonstrate our approach on AMD Evergreen architecture where iso-throughput executions of the healthy kernels reduce NBTI-induced voltage threshold shift up to 49% (11%) compared to naïve kernel executions, with (without) architectural support for power-gating. The kernel adaption flow takes average of 13 millisecond on a typical host machine thus making it suitable for practical implementation.
Adenosine 5′-Phosphosulfate Sulfotransferase and Adenosine 5′-Phosphosulfate Reductase Are Identical Enzymes (2000)

Adenosine 5'-phosphosulfate (APS) sulfotransferase and APS reductase have been described as key enzymes of assimilatory sulfate reduction of plants catalyzing the reduction of APS to bound and free sulfite, respectively. APS sulfotransferase was purified to homogeneity from Lemna minor and compared with APS reductase previously obtained by functional complementation of a mutant strain of Escherichia coli with an Arabidopsis thaliana cDNA library. APS sulfotransferase was a homodimer with a monomer M(r) of 43,000. Its amino acid sequence was 73% identical with APS reductase. APS sulfotransferase purified from Lemna as well as the recombinant enzyme were yellow proteins, indicating the presence of a cofactor. Like recombinant APS reductase, recombinant APS sulfotransferase used APS (K(m) = 6.5 microM) and not adenosine 3'-phosphate 5'-phosphosulfate as sulfonyl donor. The V(max) of recombinant Lemna APS sulfotransferase (40 micromol min(-1) mg protein(-1)) was about 10 times higher than the previously published V(max) of APS reductase. The product of APS sulfotransferase from APS and GSH was almost exclusively SO(3)(2-). Bound sulfite in the form of S-sulfoglutathione was only appreciably formed when oxidized glutathione was added to the incubation mixture. Because SO(3)(2-) was the first reaction product of APS sulfotransferase, this enzyme should be renamed APS reductase.
Role of the small Rho GTPases Rac1 and Cdc42 in host cell invasion of Campylobacter jejuni (2007)

Host cell invasion of the food-borne pathogen Campylobacter jejuni is one of the primary reasons of tissue damage in humans but molecular mechanisms are widely unclear. Here, we show that C. jejuni triggers membrane ruffling in the eukaryotic cell followed by invasion in a very specific manner first with its tip followed by the flagellar end. To pinpoint important signalling events involved in the C. jejuni invasion process, we examined the role of small Rho family GTPases. Using specific GTPase-modifying toxins, inhibitors and GTPase expression constructs we show that Rac1 and Cdc42, but not RhoA, are involved in C. jejuni invasion. In agreement with these observations, we found that internalization of C. jejuni is accompanied by a time-dependent activation of both Rac1 and Cdc42. Finally, we show that the activation of these GTPases involves different host cell kinases and the bacterial fibronectin-binding protein CadF. Thus, CadF is a bifunctional protein which triggers bacterial binding to host cells as well as signalling leading to GTPase activation. Collectively, our results suggest that C. jejuni invade host target cells by a unique mechanism and the activation of the Rho GTPase members Rac1 and Cdc42 plays a crucial role in this entry process.
Fas/Fas ligand and hematopoietic progenitor cells (1998)

Fas antigen is a receptor that crosslinks with a ligand or antibody initiating a signal transduction cascade that leads to apoptosis. During normal hematopoiesis, Fas antigen is not expressed on CD34+ cells, including premature hematopoietic progenitor cells. Functioning Fas antigen expression is induced by several hematopoietic regulators. These changes may appear not only in the process of differentiation of hematopoietic progenitor cells, but also as a negative feedback mechanism that controls chaotic proliferation of these cells. These findings suggest that the Fas/Fas ligand system is closely related to the maintenance of homeostasis during the process of normal hematopoiesis. Furthermore, increased Fas antigen expression is observed on CD34+ cells from patients with aplastic anemia, suggesting that it might cause bone marrow suppression. The use of Fas-mediated apoptosis of malignant cells as a tool for eliminating hematologic malignancies is promising. Increased Fas ligand expression is observed on natural killer lymphoma cells and may be associated with the pathogenesis of failure of several organs. The Fas/Fas ligand system plays an important role in the physiologic and pathologic processes of hematopoiesis. The development of treatments using this system are forthcoming.
Preclinical factors affecting the pharmacokinetic behaviour of tanshinone IIA, an investigational new drug isolated fromSalvia miltiorrhizafor the treatment of ischaemic heart diseases (2008)

Tanshinone IIA (TSIIA) is a major active triterpenoid isolated from Salvia miltiorrhiza. The purposes of this study were to investigate various preclinical factors that determined the pharmacokinetics of TSIIA. After oral dosing at 6.7, 20, and 60 mg kg(-1), TSIIA was detected mainly as glucuronidated conjugate (TSIIAG) with only small amounts of the unchanged in the plasma. TSIIA was predominantly excreted into the bile and faeces as TSIIAG, and urine to a minor extent. The C(max) and AUC(0-)(t) of TSIIAG after i.p. administration were significantly lower than those after intragastric administration. The plasma concentration-time profiles of TSIIA following oral dosing of TSIIA showed multiple peaks. The C(max) and AUC(0-)(t) of TSIIA and its glucuronides in rats with intact bile duct were significantly lower than those of rats with bile duct cannulation. Studies from the linked-rat model and intraduodenal injection of bile containing TSIIA and its metabolites indicate that TSIIA glucuronides underwent hydrolysis and the aglycone was reabsorbed from the gut and excreted into the bile as conjugates. TSIIA had a wide tissue distribution, with a very high accumulation in the lung, but very limited penetration into the brain and testes. TSIIA was metabolized by rat CYP2C, 3A and 2D, as ticlopidine, ketoconazole and quinidine all inhibited TSIIA metabolism in rat liver microsomes. Taken collectively, these findings indicate that multiple factors play important roles in determining the pharmacokinetics of TSIIA.
Immune microenvironment profiling of gastrointestinal stromal tumors (GIST) shows gene expression patterns associated to immune checkpoint inhibitors response (2019)

Few studies were conducted investigating the immunological profiles in gastrointestinal stromal tumors (GIST). Adaptive and innate immune cells are present in the tumor microenvironment, indicating GIST as inflamed tumors. In addition, murine models suggested a potential interaction between immune components and imatinib. In this retrospective study, the GIST immunological profile was investigated through <i>in silico</i> analysis and immunohistochemistry (IHC), exploring the basis for immunotherapy approaches. Gene expression profiles (GEP) from 31 KIT/PDGFRA-mutant GIST were analyzed to evaluate the tumor microenvironment and immunotherapy predictive signatures such as the expanded IFN-γ-induced immune signature (EIIS) and the T-cell-inflamed signature (TIS). GEP and IHC supported the presence of immune infiltrate in GIST, with dominance of CD4+ and CD8+ T cells and M2 macrophages showing a remarkable similarity with melanoma microenvironment. The EIIS genes were expressed in most of GIST samples and positively correlated with PD-L1 abundance (<i>p</i> < .0001). Co-expression was also found between PD-L1 and CD8A (<i>p</i> < .0001) or CD8B (<i>p</i> = .0003). Moreover, the median TIS score for GIST was between the 65th and 70th percentile of the Cancer Genome Atlas dataset, in the same range of tumors responding to anti-PD-1/PD-L1. Analysis of the Gene Expression Omnibus database GIST samples pre- and post-treatment confirmed that imatinib downregulates PD-L1 and IRF1 expression through the inhibition of KIT and PDGFRA, thus contributing to counteract the suppressed adaptive immune response against GIST. The presence of a rich immune infiltrate in GIST along with the presence of TIS and EIIS suggests that GIST may benefit from immunotherapy along with tyrosine kinase inhibitors.
A Micro-Machined Optical Fiber Cantilever as a Miniaturized pH Sensor (2015)

A micro-cantilever fabricated using a combination of picosecond-laser machining and focused ion beam milling directly onto the end of a standard telecommunications optical fiber is demonstrated as a liquid pH sensor. Conventional pH meters typically require relatively large reaction volumes up to ~50 mL, which is not always convenient. The micro-scale nature of this sensor offers the potential for pH measurement on a smaller sample volume down to micro-liter. The fiber end-tip cantilever is coated with a pH sensitive layer, and the pH-induced deflection is monitored interfermetically. A detectable pH range from 4.0 to 10.0 is demonstrated for the cantilevers coated with 16-mercapto-hexadecanoic-1-acid as the functional layer, and a detectable pH range from 4.0 to 9.0 is demonstrated for the cantilevers coated with Al2O3 as the functional layer.
Supplementary Figure Legend 1 from Phase II, Open-Label, Randomized Trial of the MEK1/2 Inhibitor Selumetinib as Monotherapy versus Temozolomide in Patients with Advanced Melanoma (2023)

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A Emergency Communication System based on WMN in underground mine (2010)

A Emergency Communication System based on Wireless Mesh Network (ECS-WMN) is proposed, which is easy to deploy and report the incidents and information such as personnel positions to the field rescue center and related members of rescue groups using different approaches, such as pop-ups on a computer or PDA screen, WiFi video terminals, WiFi cell phones and so on. A ECS-WMN consists of a WMN gateway, multiple WMN routers, a field rescue center and several mine rescue and emergency communication clients. Network architecture, application requirements and routing protocol are also analyzed. Finally the experiment results are shown such as throughput and latencies performance, i.e., multi-hop transmission throughputs decline while average delays increase with increased hops. Since ECS-WMN supports WiFi mesh and ZigBee mesh, it shows higher flexibility and reliability of applications than traditional WLAN and WSN, and therefore will be the preferred mine emergency communication systems in future.
Theoretical Analysis of Intra-Cavity Second-Harmonic Generation of Semiconductor Lasers by a Periodically Poled Nonlinear Crystal Waveguide (2011)

General time-domain traveling wave rate equations are employed for the simulation of the intra-cavity second harmonic generation (IC-SHG) of semiconductor lasers by a periodically poled nonlinear crystal waveguide. A 1060 nm high power, single-mode, ridge waveguide semiconductor laser is used in the simulation. The SHG crystal is a MgO-doped periodically poled lithium niobate with a single-mode ridge waveguide. Comparisons are made between the computed and experimental results of single-pass SHG for the purposes of model validation. The design of an IC-SHG green laser is further compared to the single-pass SHG laser in terms of the SHG output power, conversion efficiency, temperature tolerance, and high speed modulation capability. It is theoretically found that by using the IC-SHG configuration, SHG power and efficiency can be improved with a relatively short nonlinear crystal.
Structural Interpretation of Activity Cliffs Revealed by Systematic Analysis of Structure−Activity Relationships in Analog Series (2009)

Discontinuity in structure-activity relationships (SARs) is caused by so-called activity cliffs and represents one of the major caveats in SAR modeling and lead optimization. At activity cliffs, small structural modifications of compounds lead to substantial differences in potency that are essentially unpredictable using quantitative structure-activity relationship (QSAR) methods. In order to better understand SAR discontinuity at the molecular level of detail, we have analyzed different compound series in combinatorial analog graphs and determined substitution patterns that introduce activity cliffs of varying magnitude. So identified SAR determinants were then analyzed on the basis of complex crystal structures to enable a structural interpretation of SAR discontinuity and underlying activity cliffs. In some instances, SAR discontinuity detected within analog series could be well rationalized on the basis of structural data, whereas in others a structural explanation was not possible. This reflects the intrinsic complexity of small molecule SARs and suggests that the analysis of short-range receptor-ligand interactions seen in X-ray structures is insufficient to comprehensively account for SAR discontinuity. However, in other cases, SAR information extracted from ligands was incomplete but could be deduced taking X-ray data into account. Thus, taken together, these findings illustrate the complementarity of ligand-based SAR analysis and structural information.
Frontiers and Opportunities in Bioenergy Crop Microbiome Research Networks (2021)

Researchers from across the four United States Department of Energy Bioenergy Research Centers (BRCs) engaged in a microbiome workshop that focused on identifying challenges and collaboration opportunities to better understand bioenergy-relevant plant–microbe interactions. The virtual workshop included hands-on educational sessions and a keynote address on current best practices in microbiome science and community microbiome standards, as well as breakout sessions aimed at identifying microbiome-related data and measurements that should be prioritized, opportunities for and barriers to integrating plant metabolites to microbiome research, and strategies for more effectively integrating microbiome data and processes into existing models. Based on participant discussion, key findings of the workshop were the need to prioritize scaling data sharing across BRCs and the broader research community and securing collaborative infrastructure in the areas of microbiome-ecosystem modeling and molecular plant–microbe interactions. This workshop review highlights additional main findings from this event, to encourage cross-site and more holistic metaanalyses while promoting wide scientific community engagement across plant microbiome sciences.
Silicon Rectifier Locomotive Developments in Europe (1965)

After a short historical review of the use of semiconductor junctions as rectifiers, first in control circuits and then in the application to auxiliaries on locomotives and MU (multiple unit) cars, the use of silicon on main power rectifiers on these vehicles in place of ignitrons is examined, especially in France where 50-cycle single-phase electrical traction is now extensively used and is the only system applied on all new lines. After a survey of the new problems which appear in conjunction with the use of semiconductor rectifiers, some of the most recent applications in France are described briefly. Attention is called to the fact that 25 locomotives and MU cars are in service and 182 are in the process of being built. Future uses are diesel-electric locomotives with ac generators and rectifiers, substations for main lines, and silicon-controlled rectifiers (SCRs) for auxiliary functions and main circuits, with the voltage control and the possibility of inverter operation combined in the same equipment for a new prototype locomotive.