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High-dimensional data have provided vast amounts of information for scientific research and learning. However, in most cases, such information is buried in noise from noninformative features. Learning informative feature subspaces has become a necessary step for supervised learning tasks in high dimensions in order to improve accuracy and interpretability. The learning methods should also consider possible interactions among the features that may carry significant signals and reveal important scientific findings. In this paper, we develop a nonparametric measure of association between class label and continuous-valued feature subspaces using local point processes (LPP) patterns. A backward elimination algorithm based on random subspaces is used to identify informative feature subspaces according to this measure. Through simulations and real data applications, the proposed method demonstrates effectiveness in identifying patterns that are informative about the class difference not only marginally but also with higher-order interactions among features. As a result, the proposed method outperforms other popular feature selection methods with better generalizability and robustness. [ABSTRACT FROM AUTHOR]

Stochastic gradient descent (SGD) is commonly used for optimization in large-scale machine learning problems. Langford et al. (2009) introduce a sparse online learning method to induce sparsity via truncated gradient. With high-dimensional sparse data, however, this method suffers from slow convergence and high variance due to heterogeneity in feature sparsity. To mitigate this issue, we introduce a stabilized truncated stochastic gradient descent algorithm. We employ a soft-thresholding scheme on the weight vector where the imposed shrinkage is adaptive to the amount of information available in each feature. The variability in the resulted sparse weight vector is further controlled by stability selection integrated with the informative truncation. To facilitate better convergence, we adopt an annealing strategy on the truncation rate, which leads to a balanced trade-off between exploration and exploitation in learning a sparse weight vector. Numerical experiments show that our algorithm compares favorably with the original truncated gradient SGD in terms of prediction accuracy, achieving both better sparsity and stability. [ABSTRACT FROM AUTHOR]

A compact ultrasonic motor using sandwiching piezo-ceramic plates was developed, having advantages of low manufacturing costs, simple driving circuit, and high scalability. The stator is composed of two piezoelectric plates attached to a T-shaped steel body. Two orthogonal bending modes can be excited by driving one piezoelectric plate and the reversed motion of the rotor can be obtained by driving the piezoelectric plate on the opposite side. The prototype stator with a size of 15 mm × 2.44 mm × 2 mm, operated at 44.8 kHz, was experimentally characterized, and a maximum torque of 2 mN m was obtained. Maximum power of 2.3 mW and efficiency of 9% were produced with a load of 0.8 mN m at a rotation speed of 27 rpm. [ABSTRACT FROM AUTHOR]

Antitumor immunity driven by intratumoral dendritic cells contributes to the efficacy of anthracycline-based chemotherapy in cancer.We identified a loss-of-function allele of the gene coding for formyl peptide receptor 1 (FPR1) that was associated with poor metastasis-free and overall survival in breast and colorectal cancer patients receiving adjuvant chemotherapy. The therapeutic effects of anthracyclines were abrogated in tumor-bearing Fpr1-/- mice due to impaired antitumor immunity. Fpr1-deficient dendritic cells failed to approach dying cancer cells and, as a result, could not elicit antitumor T cell immunity. Experiments performed in a microfluidic device confirmed that FPR1 and its ligand, annexin-1, promoted stable interactions between dying cancer cells and human or murine leukocytes. Altogether, these results highlight the importance of FPR1 in chemotherapy-induced anticancer immune responses. [ABSTRACT FROM AUTHOR]

The therapeutic efficacy of anthracyclines relies, at least partially, on the induction of a dendritic cell- and T-lymphocyte--dependent anticancer immune response. Here, we show that anthracycline-based chemotherapy promotes the recruitment of functional CD11b+CD11c+Ly6ChighLy6G-MHCII+ dendritic cell--like antigenpresenting cells (APC) into the tumor bed, but not into lymphoid organs. Accordingly, draining lymph nodes turned out to be dispensable for the proliferation of tumor antigen--specific T cells within neoplastic lesions as induced by anthracyclines. In addition, we found that tumors treated with anthracyclines manifest increased expression levels of the chemokine Ccl2. Such a response is important as neoplasms growing in Ccl2-/- mice failed to accumulate dendritic cell--like APCs in response to chemotherapy. Moreover, cancers developing in mice lacking Ccl2 or its receptor (Ccr2) exhibited suboptimal therapeutic responses to anthracycline-based chemotherapy. Altogether, our results underscore the importance of the CCL2/CCR2 signaling axis for therapeutic anticancer immune responses as elicited by immunogenic chemotherapy. [ABSTRACT FROM AUTHOR]

The antineoplastic effects of anthracyclines have been shown to rely, at least in part, on a local immune response that involves dendritic cells (DCs) and several distinct subsets of T lymphocytes. Here, we show that the administration of anthracyclines to mice bearing established neoplasms stimulates the intratumoral secretion of tumor necrosis factor α (TNFα). However, blocking the TNFα/TNF receptor (TNFR) system by three different strategies—namely, (1) neutralizing antibodies, (2) etanercept, a recombinant protein in which TNFR is fused to the constant domain of an IgG1 molecule, and (3) gene knockout—failed to negatively affect the therapeutic efficacy of anthracyclines in three distinct tumor models. In particular, TNFα-blocking strategies did not influence the antineoplastic effects of doxorubicin (a prototypic anthracycline) against MCA 205 fibrosarcomas growing in C57BL/6 mice, F244 sarcomas developing in 129/Sv hosts and H2N100 mammary carcinomas arising in BALB/c mice. These findings imply that, in contrast to other cytokines (such as interleukin-1β, interleukin-17 and interferon γ), TNFα is not required for anthracyclines to elicit therapeutic anticancer immune responses. [ABSTRACT FROM AUTHOR]

Piezoelectric tubes with film electrodes on their outer and inner surfaces can be used to compose multitube actuators. The actuator of four piezoelectric tubes can substitute the traditional single-tube actuator with quartered electrodes which has been widely used in scanning probe microscopy and piezoelectric motors. In this article, the static deflection, static bending moment, resonant frequency, and dynamic deflection of the four-tube actuator are all studied in detail. The comparison between this actuator and the traditional single-tube actuator is also done and the results show that the four-tube actuator has better performances under certain conditions. The experiment results of a prototype actuator testified the validation of the analysis. [ABSTRACT FROM AUTHOR]

Tumor cells succumb to chemotherapy while releasing ATP. We have found that extracellular ATP attracts dendritic cell (DC) precursors into the tumor bed, facilitates their permanence in the proximity of dying cells and promotes their differentiation into mature DCs endowed with the capacity of presenting tumor-associated antigens. [ABSTRACT FROM AUTHOR]

• The non-uniform deformation and failure characteristics of siltstone under 1D, 2D, and 3D conditions were studied by various testing methods. • The multi-dimensional non-uniform deformation and failure characteristics of siltstone under uniaxial compression were quantitatively expressed. • The correlation between the evolution of characteristic stress, strain fields of siltstone, and the spatial distribution of fractures was revealed. Uniaxial compression tests monitored using linear variable differential transformers (LVDTs), digital image correlation (DIC), computed tomography (CT), acoustic emission (AE), and ultrasonic velocity were utilized to study the multi-dimensional non-uniform deformation and failure characteristics of siltstone. Under one-dimensional (1D) conditions, the characteristic stress of the siltstone was determined by the AE counts, ultrasonic velocity, and volumetric strain measured by the extensometer. Under two-dimensional (2D) conditions, zonal disintegration was observed on the apparent fracture of the siltstone specimen. The crack nucleation process, stress release characteristics, and crack type were analyzed in the "broken area," "penetrating crack area," and "non-penetrating crack area" under different characteristic stress states. Subsequently, the evolution of the non-uniformity coefficient of the 2D strain field with the 1D characteristic stress was established. Under three-dimensional (3D) conditions, the fracture size of the siltstone was divided according to the equivalent length of fracture volume, and the spatial distributions of macro-, meso -, and microfractures were analyzed. The siltstone 3D zonal disintegration phenomenon was further quantitatively described by calculating the fractal dimensions of fractures in different radius ranges. Finally, the AE source localization method was improved by modifying the wave velocity. The transformation of the primary and secondary bearing areas in different stress stages was revealed based on the spatio-temporal evolution of the AE sources with different energy levels. [ABSTRACT FROM AUTHOR]

Carbon-fiber-reinforced plastic (CFRP) composites are widely used in aerospace and concrete structure reinforcement due to their high strength and light weight. Terahertz (THz) time-domain spectroscopy is an attractive tool for defect inspection in CFRP composites. In order to improve THz nondestructive testing of CFRP composites, we have carried out systematic investigations of THz reflection and transmission properties of CFRP. Unidirectional CFRP composites with different thicknesses are measured with polarization directions 0 deg to 90 deg with respect to the fiber direction, in both reflection and transmission modes. As shown in the experiments, CFRP composites are electrically conducting and therefore exhibit a high THz reflectivity. In addition, CFRP composites have polarization-dependent reflectivity and transmissivity for THz radiation. The reflected THz power in the case of parallel polarization is nearly 1.8 times higher than for perpendicular polarization. At the same time, in the transmission of THz wave, a CFRP acts as a Fabry-Pérot cavity resulting from multiple internal reflections from the CFRP-air interfaces. Moreover, from the measured data, we extract the refractive index and absorption coefficient of CFRP composites in the THz frequency range. [ABSTRACT FROM AUTHOR]

Toll-like receptor-4-lipopolysaccharide (LPS)-mediated inflammation is used to delineate signals involved in cross-talk between antigen-presenting cells (APCs) and lymphocytes such as natural killer (NK) cells. Following APC stimulation and cytokine release, NK cells produce interferon (IFN)-γ. High levels of LPS induce endotoxicosis, a systemic inflammatory disease in which IFN-γ causes significant morbidity and mortality. Several studies have highlighted the role of interleukin (IL)-18, IL-1β, IL-17A and IFN-γ in the development of endotoxicosis, but whether these cytokines interact with each other is yet to be determined. Our data demonstrate that IL-18 and IL-17A have important roles in NK cell IFN-γ production during endotoxicosis. Importantly, we provide the first evidence that IL-18 also has a role in IL-17A production by T-cell receptor (TCR)-δ cells. Furthermore, we demonstrate that IL-18-deficient mice have a defect in γδ T-cell homeostasis and IL-1β production, both of which can contribute to the development of disease through induction of IL-17A. These results reveal novel requirements for IL-18 in innate immune cell homeostasis and activation, demonstrating that the role of IL-18 in innate immunity occurs at a level other than activation. [ABSTRACT FROM AUTHOR]

Terahertz (THz) time-domain spectroscopy (TDS) imaging is considered a nondestructive evaluation method for composite materials used for examining various defects of carbon fiber reinforced polymer (CFRP) composites and fire-retardant coatings in the reflective imaging modality. We demonstrate that hidden defects simulated by Teflon artificial inserts are imaged clearly in the perpendicular polarization mode. The THz TDS technique is also used to measure the thickness of thin fire-retardant coatings on CFRP composites with a typical accuracy of about 10 micrometers. In addition, coating debonding is successfully imaged based on the time-delay difference of the time-domain waveforms between closely adhered and debonded sample locations. [ABSTRACT FROM AUTHOR]

STAT3 is an oncogenic transcription factor with potent immunosuppressive functions. We found that pharmacologic inhibition of STAT3 or its selective knockout in cancer cells improved the tumor growth-inhibitory efficacy of anthracycline-based chemotherapies. This combined effect of STAT3 inhibition/depletion and anthracyclines was only found in tumors growing on immunocompetent (not in immunodeficient) mice. As compared with Stat3-sufficient control tumors, Stat3-/- cancer cells exhibited an increased infiltration by dendritic cells and cytotoxic T lymphocytes after chemotherapy. Anthracyclines are known to induce several stress pathways that enhance the immunogenicity of dying and dead cancer cells, thereby stimulating a dendritic cell--dependent and T lymphocyte--mediated anticancer immune response. Among these therapy-relevant stress pathways, Stat3-/- cancer cells manifested one significant improvement, namely an increase in the expression of multiple type-1 interferon-responsive genes, including that of the chemokines Cxcl9 and Cxcl10. This enhanced type-1 interferon response could be suppressed by reintroducing wild-type Stat3 (but not a transactivation-deficient mutant Stat3Y705F) into the tumor cells. This maneuver also abolished the improved chemotherapeutic response of Stat3-/- cancers. Finally, the neutralization of the common type-1 interferon receptor or that of the chemokine receptor CXCR3 (which binds CXCL9 and CXCL10) abolished the difference in the chemotherapeutic response between Stat3-/- and control tumors. Altogether, these results suggest that STAT3 inhibitors may improve the outcome of chemotherapy by enhancing the type-1 interferon response of cancer cells. [ABSTRACT FROM AUTHOR]

Solid tumors are constituted of a variety of cellular components, including bona fide malignant cells as well as endothelial, structural and immune cells. On one hand, the tumor stroma exerts major pro-tumorigenic and immunosuppressive functions, reflecting the capacity of cancer cells to shape the microenvironment to satisfy their own metabolic and immunological needs. On the other hand, there is a component of tumor-infiltrating leucocytes (TILs) that has been specifically recruited in the attempt to control tumor growth. Along with the recognition of the critical role played by the immune system in oncogenesis, tumor progression and response to therapy, increasing attention has been attracted by the potential prognostic and/or predictive role of the immune infiltrate in this setting. Data from large clinical studies demonstrate indeed that a robust infiltration of neoplastic lesions by specific immune cell populations, including (but not limited to) CD8+ cytotoxic T lymphocytes, Th1 and Th17 CD4+ T cells, natural killer cells, dendritic cells, and M1 macrophages constitutes an independent prognostic indicator in several types of cancer. Conversely, high levels of intratumoral CD4+CD25+FOXP3+ regulatory T cells, Th2 CD4+ T cells, myeloid-derived suppressor cells, M2 macrophages and neutrophils have frequently been associated with dismal prognosis. So far, only a few studies have addressed the true predictive potential of TILs in cancer patients, generally comforting the notion that-at least in some clinical settings- the immune infiltrate can reliably predict if a specific patient will respond to therapy or not. In this Trial Watch, we will summarize the results of clinical trials that have evaluated/are evaluating the prognostic and predictive value of the immune infiltrate in the context of solid malignancies. [ABSTRACT FROM AUTHOR]

Antineoplastic chemotherapies are particularly efficient when they elicit immunogenic cell death, thus provoking an anticancer immune response. Here we demonstrate that autophagy, which is often disabled in cancer, is dispensable for chemotherapy-induced cell death but required for its immunogenicity. In response to chemotherapy, autophagy-competent, but not autophagy-deficient, cancers attracted dendritic cells and T lymphocytes into the tumor bed. Suppression of autophagy inhibited the release of adenosine triphosphate (ATP) from dying tumor cells. Conversely, inhibition of extracellular ATP-degrading enzymes increased pericellular ATP in autophagy-deficient tumors, reestablished the recruitment of immune cells, and restored chemotherapeutic responses but only in immunocompetent hosts. Thus, autophagy is essential for the immunogenic release of ATP from dying cells, and increased extracellular ATP concentrations improve the efficacy of antineoplastic chemotherapies when autophagy is disabled. [ABSTRACT FROM AUTHOR]

Retrospective clinical data indicate that cardiac glycosides (CGs), notably digoxin, prolong the survival of carcinoma patients treated with conventional chemotherapy. CGs are known to influence the immune response at multiple levels. In addition, recent results suggest that CGs trigger the immunogenic demise of cancer cells, an effect that most likely contributes to their clinical anticancer activity. [ABSTRACT FROM AUTHOR]

Fully transparent inverted quantum dot light-emitting diodes (QLEDs) were fabricated by incorporating a Ag-nanowire-based anode. Aluminum-doped zinc oxide (ZnO:Al, AZO) was inserted by atomic layer deposition and reduced the sheet resistance by promoting adhesion of Ag nanowires (AgNWs) film and increasing its chemical stability towards oxygen. The performance of the QLEDs was optimal when the thickness of AZO was 20 nm. The current efficiency of the fully transparent inverted QLEDs integrated with the AgNWs/AZO anode reached 15.33 cd A−1. The main peak wavelength and optical transmittance of the inverted QLEDs were 530 nm and 75.66%, respectively. This discovery is expected to provide a basic method for the production of flexible displays with full transparency by AgNWs-based electrodes. [ABSTRACT FROM AUTHOR]