3DICE coding matrix multidirectional macro-architecture modulates cell organization, shape, and co-cultures endothelization network

Natural extracellular matrix governs cells providing biomechanical and biofunctional outstanding properties, despite being porous and mostly made of soft materials. Among organs, specific tissues present specialized macro-architectures. For instance, hepatic lobules present radial organization, while vascular sinusoids are branched from vertical veins, providing specific biofunctional features. Therefore, it is imperative to mimic such structures while modeling tissues. So far, there is limited capability of coupling oriented macro-structures with interconnected micro-channels in programmable long-range vertical and radial sequential orientations. Herein, a three-directional ice crystal elongation (3DICE) system is presented to code geometries in cryogels. Using 3DICE, guided ice crystals growth templates vertical and radial pores through bulky cryogels. Translucent isotropic and anisotropic architectures of radial or vertical pores are fabricated with tunable mechanical response. Furthermore, 3D combinations of vertical and radial pore orientations are coded at the centimeter scale. Cell morphological response to macro-architectures is demonstrated. The formation of endothelial segments, CYP450 activity, and osteopontin expression, as liver fibrosis biomarkers, present direct response and specific cellular organization within radial, linear, and random architectures. These results unlock the potential of ice-templating demonstrating the relevance of macro-architectures to model tissues, and broad possibilities for drug testing, tissue engineering, and regenerative medicine.The authors are grateful for the Portuguese Foundation for Science and Technology (FCT) distinction attributed to R. F. Canadas (SFRH/ BD/92565/2013), and to J. M. Oliveira (IF/00423/2012, IF/01285/ 2015). R. F. Canadas is also thankful to FCT, Fundo Europeu de Desenvolvimento Regional (FEDER), and Programa Operacional Competitividade e Internacionalizaç˜ao (POCI) for funding the B-Liver Project (PTDC/EMD-EMD/29139/2017). The authors are also thankful to FCT for supporting the project Hierarchitech (M-ERA-NET/0001/2014) and for the funds provided under the 3 BioMeD project (JICAM/0001/2017). The authors acknowledge that this material and collaboration is based in part upon work supported by Luso-American Development Foundation (FLAD), 2016/CON15/CAN6). U. Demirci is also grateful for the Canary Center at Stanford for Cancer Early Detection Seed Award. The authors are also grateful for the support provided by Diana Bicho and Nicolas Cristini on scaffold characterization and cell culture, respectively

Well-Posedness of Nematic Liquid Crystal Flow in Luloc3(R3)L^3_{\hbox{uloc}}(\R^3)

In this paper, we establish the local well-posedness for the Cauchy problem of the simplified version of hydrodynamic flow of nematic liquid crystals (\ref{LLF}) in $\mathbb R^3$ for any initial data $(u_0,d_0)$ having small $L^3_{\hbox{uloc}}$-norm of $(u_0,\nabla d_0)$. Here $L^3_{\hbox{uloc}}(\mathbb R^3)$ is the space of uniformly locally $L^3$-integrable functions. For any initial data $(u_0, d_0)$ with small $\displaystyle |(u_0,\nabla d_0)|_{L^3(\mathbb R^3)}$, we show that there exists a unique, global solution to (\ref{LLF}) which is smooth for $t>0$ and has monotone deceasing $L^3$-energy for $t\ge 0$.Comment: 29 page

Identification of Mycobacterium tuberculosis-Specific Th1, Th17 and Th22 Cells Using the Expression of CD40L in Tuberculous Pleurisy

Important advances have been made in the immunodiagnosis of tuberculosis (TB) based on the detection of Mycobacterium tuberculosis (MTB)-specific T cells. However, the sensitivity and specificity of the immunological approach are relatively low because there are no specific markers for antigen-specific Th cells, and some of the Th cells that do not produce cytokines can be overlooked using this approach. In this study, we found that MTB-specific peptides of ESAT-6/CFP-10 can stimulate the expression of CD40L specifically in CD4+ T cells but not other cells from pleural fluid cells (PFCs) in patients with tuberculous pleurisy (TBP). CD4+CD40L+ but not CD4+CD40L− T cells express IFN-γ, IL-2, TNF-α, IL-17 or IL-22 after stimulation with MTB-specific peptides. In addition, CD4+CD40L+ T cells were found to be mostly polyfunctional T cells that simultaneously produce IFN-γ, IL-2 and TNF-α and display an effector or effector memory phenotype (CD45RA−CD45RO+CCR7−CD62L−ICOS−). To determine the specificity of CD4+CD40L+ T cells, we incubated PFCs with ESTA-6/CFP-10 peptides and sorted live CD4+CD40L+ and CD4+CD40L− T cells by flow cytometry. We further demonstrated that sorted CD4+CD40L+, but not CD4+CD40L− fractions, principally produced IFN-γ, IL-2, TNF-α, IL-17 and IL-22 following restimulation with ESTA-6/CFP-10 peptides. Taken together, our data indicate that the expression of CD40L on MTB-specific CD4+ T cells could be a good marker for the evaluation and isolation of MTB-specific Th cells and might also be useful in the diagnosis of TB

Analysis of Import Demand for Wooden Beds in the U.S.

The market of wooden beds in the U.S. has been flooded with imports from China and Vietnam in recent years. Static and dynamic Almost Ideal Demand System models are used to assess the import demand for wooden beds from the top seven supplying countries. The analyses reveal that the antidumping investigation on China has some temporary trade depression effect on China, but trade diversion occur to Vietnam, Indonesia, Canada, and Brazil. The formal implementation of antidumping duties since 2005 has not shown any significant effect on the trade pattern. U.S. consumers spend more on beds from newly industrialized countries and there are moderate degrees of substitution among wooden beds from most countries

Analiza wrażliwości wskaźnika niezawodności w zakresie dokładności indeksowania głowicy narzędziowej z napędzanymi narzędziami

Power tool turret (PTT) is one of the most key parts of CNC (Computer Numerical Control) turning center and CNC turning and milling machining center. Therefore, it is very important for improving these two types of machine tools’ reliability to explore the indexing accuracy reliability of PTT and its sensitivity. To analyze the indexing accuracy reliability sensitivity of PTT, the angular displacement error of the rotating gear disc is discussed based on the measurement uncertainty theory. The tooth thickness wear process of the fixed gear disc, the rotating gear disc and the lock gear disc are modeled using Gamma process of which the parameters are estimated. The indexing error of PTT is formulated by employing the BP neural network and validated by the experiment data. Then, the indexing accuracy reliability equation of PTT is derived and its sensitivity to the mean and the standard deviation of random variables or wear stochastic processes is analyzed. The results show that the presented indexing accuracy reliability and its sensitivity of PTT are effective.Głowica narzędziowa z napędzanymi narzędziami (ang. power tool turret, PTT) stanowi jedną z kluczowych części sterowanych komputerowo tokarskich i tokarsko-frezarskich centrów obróbczych CNC. Dlatego też dla poprawy niezawodności tych dwóch rodzajów obrabiarek istotne jest badanie niezawodności w zakresie dokładności indeksowania głowicy PTT oraz wrażliwości wskaźnika niezawodności. Dla celów analizy wrażliwości wskaźnika niezawodności w zakresie dokładności indeksowania głowicy PTT, omówiono błąd przesunięcia kątowego obrotowej tarczy narzędziowej w oparciu o teorię niepewności pomiaru. Proces zużycia ściernego zębów tarcz narzędziowych: stałej, obrotowej oraz uchwytowej, zamodelowano przy użyciu procesu Gamma o szacunkowych parametrach. Błąd indeksowania PTT obliczono przy zastosowaniu sieci neuronowej BP i zweryfikowano na podstawie danych doświadczalnych. Następnie wyprowadzono równanie niezawodności w zakresie dokładności indeksowania PTT oraz przeprowadzono analizę wrażliwości wskaźnika niezawodności na średnią i odchylenie standardowe zmiennych losowych lub procesów stochastycznych zużycia. Wyniki pokazały skuteczność omawianej analizy niezawodności w zakresie dokładności indeksowania PTT oraz wrażliwości wskaźnika niezawodności

Systemic administration of a cyclic signal transducer and activator of transcription 3 (STAT3) decoy oligonucleotide inhibits tumor growth without inducing toxicological effects.

Hyperactivation of signal transducer and activator of transcription 3 (STAT3) has been linked to tumorigenesis in most malignancies, including head and neck squamous cell carcinoma. Intravenous delivery of a chemically modified cyclic STAT3 decoy oligonucleotide with improved serum and thermal stability demonstrated antitumor efficacy in conjunction with downmodulation of STAT3 target gene expression such as cyclin D1 and Bcl-X(L) in a mouse model of head and neck squamous cell carcinoma. The purpose of the present study was to determine the toxicity and dose-dependent antitumor efficacy of the cyclic STAT3 decoy after multiple intravenous doses in Foxn1 nu mice in anticipation of clinical translation. The two doses (5 and 10 mg/kg) of cyclic STAT3 decoy demonstrated a significant decrease in tumor volume compared with the control groups (mutant cyclic STAT3 decoy or saline) in conjunction with downmodulation of STAT3 target gene expression. There was no dose-dependent effect of cyclic STAT3 decoy on tumor volume or STAT3 target gene expression. There were no significant changes in body weights between the groups during the dosing period, after the dosing interval or on the day of euthanasia. No hematology or clinical chemistry parameters suggested toxicity of the cyclic STAT3 decoy compared with saline control. No gross or histological pathological abnormalities were noted at necropsy in any of the animals. These findings suggest a lack of toxicity of intravenous administration of a cyclic STAT3 decoy oligonucleotide. In addition, comparable antitumor effects indicate a lack of dose response at the two dose levels investigated