Long-range elastic guidance mechanisms for electrostatic comb-drive actuators

The range of motion and output force of the often used electrostatic comb-drive with folded flexure straight guidance, as shown in Figure 1, is limited by sideways instability due to poor sideways stiffness of the folded flexure at relatively large deflections [1]

Fluorescence-Activated Cell Sorting and Quantitative Real-Time PCR to Reveal VEGF-Expressing Macrophage Populations in the Zebrafish Larvae

The transparent, genetically tractable zebrafish is increasingly recognized as a useful model to both live image and uncover mechanistic insight into cell interactions governing tissue homeostasis, pathology, and regeneration. Here, we describe a protocol for the isolation of macrophages from zebrafish wounds using fluorescence-activated cell sorting (FACS), and the identification of specific pro-angiogenic macrophage populations that express high levels of vascular endothelial growth factor (vegf) using quantitative real-time PCR (qPCR). The cell dissociation and FACS sorting techniques have been optimized for immune cells and successfully used to isolate other fluorescently marked populations within the wound such as neutrophils and endothelial cells. More broadly, this protocol can be easily adapted to other contexts where identification of pro-angiogenic immune cells is transformative for understanding, from development to pathologies such as infection, cancer, and diabetes.</p

A Quantitative Theory of Solid Tumor Growth, Metabolic Rate and Vascularization

The relationships between cellular, structural and dynamical properties of tumors have traditionally been studied separately. Here, we construct a quantitative, predictive theory of solid tumor growth, metabolic rate, vascularization and necrosis that integrates the relationships between these properties. To accomplish this, we develop a comprehensive theory that describes the interface and integration of the tumor vascular network and resource supply with the cardiovascular system of the host. Our theory enables a quantitative understanding of how cells, tissues, and vascular networks act together across multiple scales by building on recent theoretical advances in modeling both healthy vasculature and the detailed processes of angiogenesis and tumor growth. The theory explicitly relates tumor vascularization and growth to metabolic rate, and yields extensive predictions for tumor properties, including growth rates, metabolic rates, degree of necrosis, blood flow rates and vessel sizes. Besides these quantitative predictions, we explain how growth rates depend on capillary density and metabolic rate, and why similar tumors grow slower and occur less frequently in larger animals, shedding light on Peto's paradox. Various implications for potential therapeutic strategies and further research are discussed

Penggunaan Informasi Akuntansi Diferensial dalam Pengambilan Keputusan Menerima Atau Menolak Pesanan Khusus pada Ud. Nabilah

Manajemen Perusahaan dihadapkan pada pengambilan keputusan untuk memilih satu pilihan yang terbaik dari beberapa alternatif pilihan. Manajemen memerlukan informasi yang dapat mengurangi ketidakpastian, sehingga mereka dapat menentukan pilihan yang terbaik bagi Perusahan. Salah satu jenis informasi yang diperlukan manajemen sebagai dasar perencanaan dalam pengambilan keputusan menerima atau menolak pesanan khusus adalah informasi akuntansi diferensial. Keputusan menerima atau menolak pesanan khusus sangat berpengaruh bagi Perusahaan, baik itu untuk keputusan jangkah pendek maupun jangkah panjang. Tujuan dari penelitian ini adalah untuk mengetahui penggunaan informasi akuntansi diferensial yang digunakan dalam pengambilan keputusan manajemen untuk menerima atau menolak pesanan khusus. Penelitian ini dilakukan di UD. Nabilah. Hasil penelitian menunjukkan pada bulan Januari 2014, Perusahaan menerima pesanan khusus di bawah harga jual. Meskipun pesanan khusus dibawah harga jual Perusahaan masih dapat menerima pesanan khusus tersebut, karena harga jual pesanan khusus masih dapat menutupi biaya diferensial. Bagi manajemen Perusahaan sebaiknya mampu untuk menerima pesanan khusus, dan menggunakan analisis akuntansi diferensial untuk memperkirakan biaya diferensial yang akan muncul dengan tujuan untuk mempertahankan laba usaha. Kata kunci : akuntansi diferensial, pengambilan keputusan,pesanan khusu

Therapeutic limitations in tumor-specific CD8+ memory T cell engraftment

BACKGROUND: Adoptive immunotherapy with cytotoxic T lymphocytes (CTL) represents an alternative approach to treating solid tumors. Ideally, this would confer long-term protection against tumor. We previously demonstrated that in vitro-generated tumor-specific CTL from the ovalbumin (OVA)-specific OT-I T cell receptor transgenic mouse persisted long after adoptive transfer as memory T cells. When recipient mice were challenged with the OVA-expressing E.G7 thymoma, tumor growth was delayed and sometimes prevented. The reasons for therapeutic failures were not clear. METHODS: OT-I CTL were adoptively transferred to C57BL/6 mice 21 – 28 days prior to tumor challenge. At this time, the donor cells had the phenotypical and functional characteristics of memory CD8+ T cells. Recipients which developed tumor despite adoptive immunotherapy were analyzed to evaluate the reason(s) for therapeutic failure. RESULTS: Dose-response studies demonstrated that the degree of tumor protection was directly proportional to the number of OT-I CTL adoptively transferred. At a low dose of OT-I CTL, therapeutic failure was attributed to insufficient numbers of OT-I T cells that persisted in vivo, rather than mechanisms that actively suppressed or anergized the OT-I T cells. In recipients of high numbers of OT-I CTL, the E.G7 tumor that developed was shown to be resistant to fresh OT-I CTL when examined ex vivo. Furthermore, these same tumor cells no longer secreted a detectable level of OVA. In this case, resistance to immunotherapy was secondary to selection of clones of E.G7 that expressed a lower level of tumor antigen. CONCLUSIONS: Memory engraftment with tumor-specific CTL provides long-term protection against tumor. However, there are several limitations to this immunotherapeutic strategy, especially when targeting a single antigen. This study illustrates the importance of administering large numbers of effectors to engraft sufficiently efficacious immunologic memory. It also demonstrates the importance of targeting several antigens when developing vaccine strategies for cancer

The Northern Eurasia Earth Science Partnership: An Example of Science Applied to Societal Needs

Northern Eurasia, the largest landmass in the northern extratropics, accounts for ~20% of the global land area. However, little is known about how the biogeochemical cycles, energy and water cycles, and human activities specific to this carbon-rich, cold region interact with global climate. A major concern is that changes in the distribution of land-based life, as well as its interactions with the environment, may lead to a self-reinforcing cycle of accelerated regional and global warming. With this as its motivation, the Northern Eurasian Earth Science Partnership Initiative (NEESPI) was formed in 2004 to better understand and quantify feedbacks between northern Eurasian and global climates. The first group of NEESPI projects has mostly focused on assembling regional databases, organizing improved environmental monitoring of the region, and studying individual environmental processes. That was a starting point to addressing emerging challenges in the region related to rapidly and simultaneously changing climate, environmental, and societal systems. More recently, the NEESPI research focus has been moving toward integrative studies, including the development of modeling capabilities to project the future state of climate, environment, and societies in the NEESPI domain. This effort will require a high level of integration of observation programs, process studies, and modeling across disciplines

Burden of Rare Sarcomere Gene Variants in the Framingham and Jackson Heart Study Cohorts

Rare sarcomere protein variants cause dominant hypertrophic and dilated cardiomyopathies. To evaluate whether allelic variants in eight sarcomere genes are associated with cardiac morphology and function in the community, we sequenced 3,600 individuals from the Framingham Heart Study (FHS) and Jackson Heart Study (JHS) cohorts. Out of the total, 11.2% of individuals had one or more rare nonsynonymous sarcomere variants. The prevalence of likely pathogenic sarcomere variants was 0.6%, twice the previous estimates; however, only four of the 22 individuals had clinical manifestations of hypertrophic cardiomyopathy. Rare sarcomere variants were associated with an increased risk for adverse cardiovascular events (hazard ratio: 2.3) in the FHS cohort, suggesting that cardiovascular risk assessment in the general population can benefit from rare variant analysis

The erythropoietin receptor expressed in skeletal muscle is essential for mitochondrial biogenesis and physiological exercise

Erythropoietin (EPO) is a haematopoietic hormone that regulates erythropoiesis, but the EPO-receptor (EpoR) is also expressed in non-haematopoietic tissues. Stimulation of the EpoR in cardiac and skeletal muscle provides protection from various forms of pathological stress, but its relevance for normal muscle physiology remains unclear. We aimed to determine the contribution of the tissue-specific EpoR to exercise-induced remodelling of cardiac and skeletal muscle. Baseline phenotyping was performed on left ventricle and m. gastrocnemius of mice that only express the EpoR in haematopoietic tissues (EpoR-tKO). Subsequently, mice were caged in the presence or absence of a running wheel for 4 weeks and exercise performance, cardiac function and histological and molecular markers for physiological adaptation were assessed. While gross morphology of both muscles was normal in EpoR-tKO mice, mitochondrial content in skeletal muscle was decreased by 50%, associated with similar reductions in mitochondrial biogenesis, while mitophagy was unaltered. When subjected to exercise, EpoR-tKO mice ran slower and covered less distance than wild-type (WT) mice (5.5 ± 0.6 vs. 8.0 ± 0.4 km/day, p < 0.01). The impaired exercise performance was paralleled by reductions in myocyte growth and angiogenesis in both muscle types. Our findings indicate that the endogenous EPO-EpoR system controls mitochondrial biogenesis in skeletal muscle. The reductions in mitochondrial content were associated with reduced exercise capacity in response to voluntary exercise, supporting a critical role for the extra-haematopoietic EpoR in exercise performance. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s00424-021-02577-4