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Have you ever heard of a Hype-Cycle? It is a description that was put forward by an IT consultancy firm to describe certain phenomena that happen within the life cycle of new technology products. As Fenn and Raskino stated in their book (Fenn and Raskino 2008), a novel technology - a - “Technology Trigger” - gives rise to a steep increase in interest, leading to the “Peak of Inflated Expectations”. Following an accumulation of more detailed knowledge on the technology and its short-comings, the stake holders may need to traverse a “Trough of Disillusionment”, which is followed by a shallower “Slope of Enlightenment”, before finally reaching the “Plateau of Productivity”. In spite of the limitations and criticisms levied on this over-simplified description of a technology’s life-cycle, it is nonetheless able to describe well the situation we are all experiencing within the brain-machine-interfacing community. Our technology trigger was the development of batch-processed multisite neuronal interfaces based on silicon during the 1980s and 1990s (Sangler and Wise 1990, Campbell, Jones et al. 1991, Wise and Najafi 1991, Rousche and Normann 1992, Nordhausen, Maynard et al. 1996). This gave rise to a seemingly exponential growth of knowledge within the neurosciences, leading to the expectation of thought-controlled devices and prostheses for handicapped people in the very near future (Chapin, Moxon et al. 1999, Wessberg, Stambaugh et al. 2000, Chapin and Moxon 2001, Serruya, Hatsopoulos et al. 2002). Unfortunately, whereas significant steps towards artificial robotic limbs could have been implemented during the last decade (Johannes, Bigelow et al. 2011, Oung, Pohl et al. 2012, Belter, Segil et al. 2013), direct invasive intracortical interfacing was not quite able to keep up with these expectations. Insofar, we are currently facing the challenging, but tedious walk through the Trough of Disillusionment. Undoubtedly, more than two decades of intense research on brain-machine-interfaces (BMI’s) have produced a tremendous wealth of information towards the ultimate goal: a clinically useful cortical prosthesis. Unfortunately even today - after huge fiscal efforts - the goal seems almost to be as far away as it was when it was originally put forward. At the very least, we have to state that one of the main challenges towards a clinical useful BMI has not been sufficiently answered yet: regarding the long term – or even truly chronic – stability of the neural cortical interface, as well as the signals it has to provide over a significant fraction of a human’s lifespan. Even the recently demonstrated advances in BMI’s in both humans and non-human primates have to deal with a severe decay of spiking activity that occurs over weeks and months (Chestek, Gilja et al. 2011, Hochberg, Bacher et al. 2012, Collinger, Kryger et al. 2014, Nuyujukian, Kao et al. 2014, Stavisky, Kao et al. 2014, Wodlinger, Downey et al. 2014) and resolve to simplified features to keep a brain-derived communication channel open (Christie, Tat et al. 2014).

Hydrogel coating --- Gliosis --- Optical Coherence Tomography --- foreign body reaction --- indwelling implants --- Multisite neuronal recording --- immuno labeling --- flexible microprobes --- compliance match hypothesis

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Improved understanding of the cellular and molecular makeup of tumors in the last 30 years has unraveled a previously unexpected level of heterogeneity among tumor cells as well as within the tumor microenvironment. The concept of tumor heterogeneity underlines the realization that different tumors can display significant differences in their genomic content as well as in their overall behavior. Our capacity to better understand the heterogeneous make up of tumors has very important consequences on our ability to design efficient therapeutic strategies to improve patient survival. This book highlights several aspects of tumor heterogeneity in the context of metastatic development and summarize some of the challenges posed by heterogeneity for tumor diagnostics and therapeutic management of tumors.

clear cell renal cell carcinoma --- tumor evolution --- tumor ecology --- intratumor heterogeneity --- multisite tumor sampling --- targeted therapy --- uterine carcinosarcoma --- endometrial carcinoma --- metaplastic carcinoma --- epithelial-to-mesenchymal transition --- clonality --- mutation --- TP53 --- PI3K/AKT pathway --- gene expression --- miRNA expression --- tumor microenvironment --- interstitial pH --- acidosis --- tumor heterogeneity --- magnetic resonance imaging --- hyperpolarized 13C MRI --- carbonic anhydrase --- lactic acid --- positron emission tomography --- esophageal squamous cell carcinoma --- precision medicine --- natural killer cells --- tumor mutation burden --- immunotherapy --- PET --- heterogeneity --- radiomics --- radiopharmaceuticals --- SUV --- nuclear medicine --- colon cancer --- Wnt signaling --- phenotypic plasticity --- EMT --- hybrid E/M --- collective and single-cell migration --- beta-catenin paradox --- breast cancer --- immune microenvironment --- DCIS --- ADH --- mammary gland --- cell fate --- 3D cultures --- organoids --- signaling --- single-cell RNAseq --- tumor endothelial cell --- metastasis --- angiocrine factor --- microsatellite instability --- colorectal cancer --- immune checkpoints --- deficient mismatch repair --- plasticity --- biomechanics --- circulating tumor cells (CTCs) --- extracellular vesicles --- metastatic niche --- epigenetics --- CTC-clusters --- single-cell analysis --- cellular heterogeneity --- circulating tumor cells --- pancreatic cancer --- epithelial mesenchymal plasticity --- target discovery --- review --- genomics --- intra-tumour heterogeneity --- subclonal diversity --- treatment resistance

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Forest tree improvement has mainly been implemented to enhance the productivity of artificial forests. However, given the drastically changing global environment, improvement of various traits related to environmental adaptability is more essential than ever. This book focuses on genetic information, including trait heritability and the physiological mechanisms thereof, which facilitate tree improvement. Nineteen papers are included, reporting genetic approaches to improving various species, including conifers, broad-leaf trees, and bamboo. All of the papers in this book provide cutting-edge genetic information on tree genetics and suggest research directions for future tree improvement.

Research & information: general --- early selection --- stomatal characteristics --- water stress --- water relations --- specific leaf area --- Eucalyptus clones --- LTR-retrotransposon --- Ty3-gypsy --- Ty1-copia --- IRAP --- molecular markers --- bamboo --- Phyllostachys --- genetic diversity --- populations structure --- AMOVA --- central-marginal hypothesis --- cline --- Pinaceae --- trailing edge population --- Sakhalin fir --- sub-boreal forest --- gibberellin --- male strobilus induction --- transcriptome --- conifer --- Cryptomeria japonica --- linkage map --- male sterility --- marker-assisted selection --- C. fortunei --- differentially expressed genes --- phenylpropanoid metabolism --- candidate genes --- Camellia oleifera --- leaf senescence --- transcriptome analysis --- senescence-associated genes --- physiological characterization --- cpDNA --- next generation sequencing --- northern limit --- nucleotide diversity --- phylogeny --- In/Del --- SNP --- SSR --- Chinese fir --- heartwood --- secondary metabolites --- widely targeted metabolomics --- flavonoids --- amplicon sequencing --- AmpliSeq --- genomic selection --- Japanese cedar (Cryptomeria japonica) --- multiplexed SNP genotyping --- spatial autocorrelation error --- pine wood disease --- resistance to pine wood nematode --- inoculation test --- multisite --- cumulative temperature --- Pinus thunbergii --- Thujopsis dolabrata --- EST-SSR markers --- varieties --- population structure --- pine wilt disease --- Bursaphelenchus xylophilus --- genotype by environment interaction --- Japanese black pine --- variance component --- local adaptation --- silviculture --- seed zone --- tree improvement program --- breeding --- genotype × environment interaction --- mast seeding --- seed production --- thinning --- forest tree breeding --- high-throughput phenotyping --- epigenetics --- genotyping --- genomic prediction models --- quantitative trait locus --- breeding cycle --- Cryptomeria japonica var. sinensis --- demographic history --- RAD-seq --- ancient tree --- conservation --- infrared thermography --- chlorophyll fluorescence --- cumulative drought stress --- genetic conservation --- genetic management --- pine wood nematode --- pine wood nematode-Pinus thunbergii resistant trees --- early selection --- stomatal characteristics --- water stress --- water relations --- specific leaf area --- Eucalyptus clones --- LTR-retrotransposon --- Ty3-gypsy --- Ty1-copia --- IRAP --- molecular markers --- bamboo --- Phyllostachys --- genetic diversity --- populations structure --- AMOVA --- central-marginal hypothesis --- cline --- Pinaceae --- trailing edge population --- Sakhalin fir --- sub-boreal forest --- gibberellin --- male strobilus induction --- transcriptome --- conifer --- Cryptomeria japonica --- linkage map --- male sterility --- marker-assisted selection --- C. fortunei --- differentially expressed genes --- phenylpropanoid metabolism --- candidate genes --- Camellia oleifera --- leaf senescence --- transcriptome analysis --- senescence-associated genes --- physiological characterization --- cpDNA --- next generation sequencing --- northern limit --- nucleotide diversity --- phylogeny --- In/Del --- SNP --- SSR --- Chinese fir --- heartwood --- secondary metabolites --- widely targeted metabolomics --- flavonoids --- amplicon sequencing --- AmpliSeq --- genomic selection --- Japanese cedar (Cryptomeria japonica) --- multiplexed SNP genotyping --- spatial autocorrelation error --- pine wood disease --- resistance to pine wood nematode --- inoculation test --- multisite --- cumulative temperature --- Pinus thunbergii --- Thujopsis dolabrata --- EST-SSR markers --- varieties --- population structure --- pine wilt disease --- Bursaphelenchus xylophilus --- genotype by environment interaction --- Japanese black pine --- variance component --- local adaptation --- silviculture --- seed zone --- tree improvement program --- breeding --- genotype × environment interaction --- mast seeding --- seed production --- thinning --- forest tree breeding --- high-throughput phenotyping --- epigenetics --- genotyping --- genomic prediction models --- quantitative trait locus --- breeding cycle --- Cryptomeria japonica var. sinensis --- demographic history --- RAD-seq --- ancient tree --- conservation --- infrared thermography --- chlorophyll fluorescence --- cumulative drought stress --- genetic conservation --- genetic management --- pine wood nematode --- pine wood nematode-Pinus thunbergii resistant trees

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Forest tree improvement has mainly been implemented to enhance the productivity of artificial forests. However, given the drastically changing global environment, improvement of various traits related to environmental adaptability is more essential than ever. This book focuses on genetic information, including trait heritability and the physiological mechanisms thereof, which facilitate tree improvement. Nineteen papers are included, reporting genetic approaches to improving various species, including conifers, broad-leaf trees, and bamboo. All of the papers in this book provide cutting-edge genetic information on tree genetics and suggest research directions for future tree improvement.

early selection --- stomatal characteristics --- water stress --- water relations --- specific leaf area --- Eucalyptus clones --- LTR-retrotransposon --- Ty3-gypsy --- Ty1-copia --- IRAP --- molecular markers --- bamboo --- Phyllostachys --- genetic diversity --- populations structure --- AMOVA --- central-marginal hypothesis --- cline --- Pinaceae --- trailing edge population --- Sakhalin fir --- sub-boreal forest --- gibberellin --- male strobilus induction --- transcriptome --- conifer --- Cryptomeria japonica --- linkage map --- male sterility --- marker-assisted selection --- C. fortunei --- differentially expressed genes --- phenylpropanoid metabolism --- candidate genes --- Camellia oleifera --- leaf senescence --- transcriptome analysis --- senescence-associated genes --- physiological characterization --- cpDNA --- next generation sequencing --- northern limit --- nucleotide diversity --- phylogeny --- In/Del --- SNP --- SSR --- Chinese fir --- heartwood --- secondary metabolites --- widely targeted metabolomics --- flavonoids --- amplicon sequencing --- AmpliSeq --- genomic selection --- Japanese cedar (Cryptomeria japonica) --- multiplexed SNP genotyping --- spatial autocorrelation error --- pine wood disease --- resistance to pine wood nematode --- inoculation test --- multisite --- cumulative temperature --- Pinus thunbergii --- Thujopsis dolabrata --- EST-SSR markers --- varieties --- population structure --- pine wilt disease --- Bursaphelenchus xylophilus --- genotype by environment interaction --- Japanese black pine --- variance component --- local adaptation --- silviculture --- seed zone --- tree improvement program --- breeding --- genotype × environment interaction --- mast seeding --- seed production --- thinning --- forest tree breeding --- high-throughput phenotyping --- epigenetics --- genotyping --- genomic prediction models --- quantitative trait locus --- breeding cycle --- Cryptomeria japonica var. sinensis --- demographic history --- RAD-seq --- ancient tree --- conservation --- infrared thermography --- chlorophyll fluorescence --- cumulative drought stress --- genetic conservation --- genetic management --- pine wood nematode --- pine wood nematode-Pinus thunbergii resistant trees --- n/a