Web-based product design review: Implementation perspective

Product design review is one of the typical scenarios of collaborative product development. We developed a web-based prototype framework for supporting the collaborative tele-product design review on the Internet. It provides a suite of tools to establishing and management the new product design review process. This paper discusses the issues related to the development and implementation of web application in prototype implication. The typical 3-tier architecture is explained to show how the CyberReview components work together to achieve the intended functionality. The VRML EAI and Java Applet-Servlet pair technology was included to support the implication.published_or_final_versio

Multi-seeded melt growth (MSMG) of bulk Y-Ba-Cu-O using thin-film seeds

Y-Ba-Cu-O (YBCO) and Sm-Ba-Cu-O (SmBCO) thin films have been used for the first time as heterogeneous seeds to multi-seed successfully the melt growth of bulk YBCO in a multi-seeded melt growth (MSMG) process. The use of thin film seeds, which may be prepared with highly controlled orientation (i.e. with a well-defined a-b plane and precisely known a-direction), is based on their superheating properties and reduces significantly contamination of the bulk sample by the seed material. A variety of grain boundaries were obtained by varying the angle between the seeds. Microstructural studies indicate that the extent of residual melt deposited at the grain boundary decreases with increasing grain boundary contact angle. It is established that the growth front proceeds continuously at the (110)/(110) grain boundary without trapping liquid, which leads to the formation of a clean grain boundary

A possible method for non-Hermitian and non-PTPT-symmetric Hamiltonian systems

A possible method to investigate non-Hermitian Hamiltonians is suggested through finding a Hermitian operator $\eta_+$ and defining the annihilation and creation operators to be $\eta_+$-pseudo-Hermitian adjoint to each other. The operator $\eta_+$ represents the $\eta_+$-pseudo-Hermiticity of Hamiltonians. As an example, a non-Hermitian and non-$PT$-symmetric Hamiltonian with imaginary linear coordinate and linear momentum terms is constructed and analyzed in detail. The operator $\eta_+$ is found, based on which, a real spectrum and a positive-definite inner product, together with the probability explanation of wave functions, the orthogonality of eigenstates, and the unitarity of time evolution, are obtained for the non-Hermitian and non-$PT$-symmetric Hamiltonian. Moreover, this Hamiltonian turns out to be coupled when it is extended to the canonical noncommutative space with noncommutative spatial coordinate operators and noncommutative momentum operators as well. Our method is applicable to the coupled Hamiltonian. Then the first and second order noncommutative corrections of energy levels are calculated, and in particular the reality of energy spectra, the positive-definiteness of inner products, and the related properties (the probability explanation of wave functions, the orthogonality of eigenstates, and the unitarity of time evolution) are found not to be altered by the noncommutativity.Comment: 15 pages, no figures; v2: clarifications added; v3: 16 pages, 1 figure, clarifications made clearer; v4: 19 pages, the main context is completely rewritten; v5: 25 pages, title slightly changed, clarifications added, the final version to appear in PLOS ON

Observation of long-lived interlayer excitons in monolayer MoSe2–WSe2 heterostructures

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Targeting adenosine monophosphate-activated protein kinase (AMPK) in preclinical models reveals a potential mechanism for the treatment of neuropathic pain

Neuropathic pain is a debilitating clinical condition with few efficacious treatments, warranting development of novel therapeutics. We hypothesized that dysregulated translation regulation pathways may underlie neuropathic pain. Peripheral nerve injury induced reorganization of translation machinery in the peripheral nervous system of rats and mice, including enhanced mTOR and ERK activity, increased phosphorylation of mTOR and ERK downstream targets, augmented eIF4F complex formation and enhanced nascent protein synthesis. The AMP activated protein kinase (AMPK) activators, metformin and A769662, inhibited translation regulation signaling pathways, eIF4F complex formation, nascent protein synthesis in injured nerves and sodium channel-dependent excitability of sensory neurons resulting in a resolution of neuropathic allodynia. Therefore, injury-induced dysregulation of translation control underlies pathology leading to neuropathic pain and reveals AMPK as a novel therapeutic target for the potential treatment of neuropathic pain

Comparative biomarker analysis of PALOMA-2/3 trials for palbociclib.

While cyclin-dependent kinase 4/6 (CDK4/6) inhibitors, including palbociclib, combined with endocrine therapy (ET), are becoming the standard-of-care for hormone receptor-positive/human epidermal growth factor receptor 2‒negative metastatic breast cancer, further mechanistic insights are needed to maximize benefit from the treatment regimen. Herein, we conducted a systematic comparative analysis of gene expression/progression-free survival relationship from two phase 3 trials (PALOMA-2 [first-line] and PALOMA-3 [≥second-line]). In the ET-only arm, there was no inter-therapy line correlation. However, adding palbociclib resulted in concordant biomarkers independent of initial ET responsiveness, with shared sensitivity genes enriched in estrogen response and resistance genes over-represented by mTORC1 signaling and G2/M checkpoint. Biomarker patterns from the combination arm resembled patterns observed in ET in advanced treatment-naive patients, especially patients likely to be endocrine-responsive. Our findings suggest palbociclib may recondition endocrine-resistant tumors to ET, and may guide optimal therapeutic sequencing by partnering CDK4/6 inhibitors with different ETs. Pfizer (NCT01740427; NCT01942135)

Combination of photothermal, prodrug and tumor cell camouflage technologies for triple-negative breast cancer treatment

Triple-negative breast cancer (TNBC) remains the most challenging breast cancer subtype. In the presented work, we have combined several emerging technologies to build up a nanoplatform for TNBC treatment: photothermal therapy, prodrug design and tumor cell camouflage formulation. First, we synthesized a paclitaxel (PTX) based prodrug PTX-SS, and then conjugated it to the surface of gold nanorod (Au NR) @ mesoporous silica (MSN) core-shell nanoparticles (Au@MSN-NH2 NPs). Subsequently, doxorubicin (DOX) was loaded into the Au@PTXSS-MSN NPs and further coated with cell membranes isolated from MDA-MB-231 cells to form cell camouflaged Au@PTXSS-MSN/DOX@CM NPs. The Au@PTXSS-MSN/DOX@CM NPs exhibited very good DOX loading capacity and the prodrug strategy enabled the precise adjustability of PTX-SS loading to achieve the optimized ratio between PTX and DOX to maximize the synergistic effect of these two drugs, as well as enabled GSH-responsive intracellular drug release. More interestingly, the cell membrane coating not only protected the drug from premature release, but also significantly improved the targeting ability of NPs to breast cancer MDA-MB-231 cells. The NPs also showed good photothermal responsiveness with clear improvement in inhibiting MDA-MB231 cell proliferation under laser irradiation. The in vivo studies further confirmed the effectiveness of Au@PTXSS-MSN/DOX@CM NPs on TNBC tumor inhibition in 4T1 cell grafted tumor mice model. (c) 2021 The Authors. Published by Elsevier Ltd. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/)

Self-assembly of DNA nanogels with endogenous microRNA toehold self-regulating switches for targeted gene regulation therapy

Herein, a smart nanohydrogel with endogenous microRNA-21 toehold is developed to encapsulate gemcitabine-loaded mesoporous silica nanoparticles for targeted pancreatic cancer therapy. This toehold mediated strand displacement method can simultaneously achieve specific drug release and miRNA-21 silencing, resulting in the up-regulation of the expression of tumor suppressor genes PTEN and PDCD4

Functional Mapping of Dynamic Traits with Robust t-Distribution

Functional mapping has been a powerful tool in mapping quantitative trait loci (QTL) underlying dynamic traits of agricultural or biomedical interest. In functional mapping, multivariate normality is often assumed for the underlying data distribution, partially due to the ease of parameter estimation. The normality assumption however could be easily violated in real applications due to various reasons such as heavy tails or extreme observations. Departure from normality has negative effect on testing power and inference for QTL identification. In this work, we relax the normality assumption and propose a robust multivariate -distribution mapping framework for QTL identification in functional mapping. Simulation studies show increased mapping power and precision with the distribution than that of a normal distribution. The utility of the method is demonstrated through a real data analysis