The c-Jun n-terminal kinase/stress-activated protein kinase (JNK/SAPK) pathway in paclitaxel-induced apoptosis of cancer cells

The essential cellular functions associated with microtubules have led to a wide use of microtubule-interfering agents in cancer chemotherapy with promising results. Although the most well studied effect of microtubule-interfering agents is an arrest of cells at the G2/M phase of the cell cycle,other effects may also exist. I have observed that paclitaxel (Taxol), docetaxel (Taxotere), vinblastine,vincristine, nocodazole and colchicine activate the c-Jun N-terminal kinase/stress-activated protein kinase(JNK/SAPK) signaling pathway in a variety of human cells. Activation of JNK/SAPK by microtubule interfering agents is dose-dependent and time-dependent and requires interactions with microtubules.Functional activation of the JNKK/SEKl-JNK/SAPK-c Jun cascade was demonstrated by cotransfection with a TPA-response element reporter construct and dominant negative (dn) signal transducers followed by chloramphenicol acetyl-transferase assays. Microtubule-interfering agents also activate both Ras and apoptosis signal-regulating kinase (ASKl), and coexpression of dn Ras and dn ASKl exerted individual and additive inhibition of JNK/SAPK activation by microtubule-interfering agents. These findings suggest that multiple signal transduction pathways are involved with cellular detection of microtubular disarray and subsequent activation of JNK/SAPK.To further examine the role of JNK/SAPK signaling cascades in apoptosis resulting from microtubule dysfunction induced by paclitaxel, I have coexpressed dn signaling proteins of theJNK/SAPK pathway (Ras, ASKl, Rac, JNKK, JNK) in human ovarian cancer cells with a selectable marker to analyze the apoptotic characteristics of cells expressing dn-vectors following exposure to paclitaxel. Expression of these dn signaling proteins had no effect on Bcl-2 phosphorylation, yet inhibited apoptotic changes induced by paclitaxel up to 16 h after treatment. Coexpression of these dna-signaling proteins had no protective effect after 48 h of paclitaxel treatment. These data indicate that: (i) activatedJNK/SAPK acts upstream of membrane changes and caspase-3 activation in paclitaxel-initiated apoptotic pathways, independently of cell cycle stage, (ii) activated JNK/SAPK is not responsible for paclitaxelinducedphosphorylation of Bcl-2, and (iii) apoptosis resulting from microtubule damage may comprise multiple mechanisms, including a JNK/SAPK-dependent early phase and a JNK/SAPK-independent latephase

The Feedwater Control System and Steam Dump Control System Responses During Large-Load Reduction Transient for Maanshan PWR Plant

AbstractIn this study, the development of TRACE (TRAC/RELAP Advanced Computational Engine) models for Maanshan nuclear power plant (NPP) important control systems, such as feedwater control system and steam dump control system, are performed in using SNAP (Symbolic Nuclear Analysis Program) / TRACE. The large-load reduction transient analysis of the Maanshan NPP control system TRACE models are also performed and the responses of the control systems of TRACE models compare with Maanshan NPP startup tests data to verify their accuracy. Analysis results of TRACE indicate that the responses of the Maanshan NPP control system TRACE models are consistent with the plant data for large-load reduction transient

Comfort-Centered Design of a Lightweight and Backdrivable Knee Exoskeleton

This paper presents design principles for comfort-centered wearable robots and their application in a lightweight and backdrivable knee exoskeleton. The mitigation of discomfort is treated as mechanical design and control issues and three solutions are proposed in this paper: 1) a new wearable structure optimizes the strap attachment configuration and suit layout to ameliorate excessive shear forces of conventional wearable structure design; 2) rolling knee joint and double-hinge mechanisms reduce the misalignment in the sagittal and frontal plane, without increasing the mechanical complexity and inertia, respectively; 3) a low impedance mechanical transmission reduces the reflected inertia and damping of the actuator to human, thus the exoskeleton is highly-backdrivable. Kinematic simulations demonstrate that misalignment between the robot joint and knee joint can be reduced by 74% at maximum knee flexion. In experiments, the exoskeleton in the unpowered mode exhibits 1.03 Nm root mean square (RMS) low resistive torque. The torque control experiments demonstrate 0.31 Nm RMS torque tracking error in three human subjects.Comment: 8 pages, 16figures, Journa

Developing the Ideal Profile of OCAs and IT Usage in the Foodservice Chain

In recent years, the number of the branches of the foodservice chain rapidly increases, and every branch wants to be successful. Thus, how to use information technology to support Organizational Critical Activities (OCAs) has become an important issue. This research found out ten Organizational Critical Activities (OCAs) of the foodservice chain and three types of information technology usage, Defender Type, Follower Type, and Innovator Type. Furthermore, after the revision of two experts, the ten Organizational Critical Activities (OCAs) are divided into three categories, Internal Management, External Management, and Product Service. The analytical result found out that Defender Type matches Internal Management, External Management matches Innovator Type, and Product Service matches Follower Type. Finally, this study hopes that companies in the foodservice chain can develop appropriate IT strategies according to this research result to enhance their core competitiveness

Quantum correlation generation capability of experimental processes

Einstein-Podolsky-Rosen (EPR) steering and Bell nonlocality illustrate two different kinds of correlations predicted by quantum mechanics. They not only motivate the exploration of the foundation of quantum mechanics, but also serve as important resources for quantum-information processing in the presence of untrusted measurement apparatuses. Herein, we introduce a method for characterizing the creation of EPR steering and Bell nonlocality for dynamical processes in experiments. We show that the capability of an experimental process to create quantum correlations can be quantified and identified simply by preparing separable states as test inputs of the process and then performing local measurements on single qubits of the corresponding outputs. This finding enables the construction of objective benchmarks for the two-qubit controlled operations used to perform universal quantum computation. We demonstrate this utility by examining the experimental capability of creating quantum correlations with the controlled-phase operations on the IBM Quantum Experience and Amazon Braket Rigetti superconducting quantum computers. The results show that our method provides a useful diagnostic tool for evaluating the primitive operations of nonclassical correlation creation in noisy intermediate scale quantum devices.Comment: 5 figures, 3 appendice

Trojan Horse nanotheranostics with dual transformability and multifunctionality for highly effective cancer treatment.

Nanotheranostics with integrated diagnostic and therapeutic functions show exciting potentials towards precision nanomedicine. However, targeted delivery of nanotheranostics is hindered by several biological barriers. Here, we report the development of a dual size/charge- transformable, Trojan-Horse nanoparticle (pPhD NP) for delivery of ultra-small, full active pharmaceutical ingredients (API) nanotheranostics with integrated dual-modal imaging and trimodal therapeutic functions. pPhD NPs exhibit ideal size and charge for drug transportation. In tumour microenvironment, pPhD NPs responsively transform to full API nanotheranostics with ultra-small size and higher surface charge, which dramatically facilitate the tumour penetration and cell internalisation. pPhD NPs enable visualisation of biodistribution by near-infrared fluorescence imaging, tumour accumulation and therapeutic effect by magnetic resonance imaging. Moreover, the synergistic photothermal-, photodynamic- and chemo-therapies achieve a 100% complete cure rate on both subcutaneous and orthotopic oral cancer models. This nanoplatform with powerful delivery efficiency and versatile theranostic functions shows enormous potentials to improve cancer treatment

dbPTM: an information repository of protein post-translational modification

dbPTM is a database that compiles information on protein post-translational modifications (PTMs), such as the catalytic sites, solvent accessibility of amino acid residues, protein secondary and tertiary structures, protein domains and protein variations. The database includes all of the experimentally validated PTM sites from Swiss-Prot, PhosphoELM and O-GLYCBASE. Only a small fraction of Swiss-Prot proteins are annotated with experimentally verified PTM. Although the Swiss-Prot provides rich information about the PTM, other structural properties and functional information of proteins are also essential for elucidating protein mechanisms. The dbPTM systematically identifies three major types of protein PTM (phosphorylation, glycosylation and sulfation) sites against Swiss-Prot proteins by refining our previously developed prediction tool, KinasePhos (). Solvent accessibility and secondary structure of residues are also computationally predicted and are mapped to the PTM sites. The resource is now freely available at

Relationships among Constitution, Stress, and Discomfort in the First Trimester

The purpose of this study was to explore correlations among constitution, stress, and discomfort symptoms during the first trimester of pregnancy. We adopted a descriptive and correlational research design and collected data from 261 pregnant women during their first trimester in southern Taiwan using structured questionnaires. Results showed that (1) stress was significantly and positively correlated with Yang-Xu, Yin-Xu, and Tan-Shi-Yu-Zhi constitutions, respectively; (2) Yin-Xu and Tan-Shi-Yu-Zhi constitutions had significant correlations with all symptoms of discomfort, while Yang-Xu had significant correlations with all symptoms of discomfort except for “running nose”; (3) Tan-Shi-Yu-Zhi constitution and stress were two indicators for “fatigue”; Tan-Shi-Yu-Zhi was the indicator for “nausea”; Yang-Xu and Yin-Xu were indicators for “frequent urination.” Our findings also indicate that stress level affects constitutional changes and that stress and constitutional change affect the incidence of discomfort. This research can help healthcare professionals observe these discomforts and provide individualized care for pregnant women, to nurture pregnant women into neutral-type constitution, minimize their levels of discomfort, and promote the health of the fetus and the mother