Geometry of motion and nutation stability of free axisymmetric variable mass systems

In classical mechanics, the ‘geometry of motion’ refers to a development to visualize the motion of freely spinning bodies. In this paper, such an approach of studying the rotational motion of axisymmetric variable mass systems is developed. An analytic solution to the second Euler angle characterizing nutation naturally falls out of this method, without explicitly solving the nonlinear differential equations of motion. This is used to examine the coning motion of a free axisymmetric cylinder subject to three idealized models of mass loss and new insight into their rotational stability is presented. It is seen that the angular speeds for some configurations of these cylinders grow without bounds. In spite of this phenomenon, all configurations explored here are seen to exhibit nutational stability, a desirable property in solid rocket motors

Angular momentum of free variable mass systems is partially conserved

Variable mass systems are a classic example of open systems in classical mechanics with rockets being a standard practical example. Due to the changing mass, the angular momentum of these systems is not generally conserved. Here, we show that the angular momentum vector of a free variable mass system is fixed in inertial space and, thus, is a partially conserved quantity. It is well known that such conservation rules allow simpler approaches to solving the equations of motion. This is demonstrated by using a graphical technique to obtain an analytic solution for the second Euler angle that characterizes nutation in spinning bodies

Cinematic itineraries and identities: Studying Bollywood tourism among the Hindustanis in the Netherlands

For decades, the ‘make-believe’ world of Bollywood has created elaborate imaginaries of India. A sizable part of its audience consists of diasporic communities, who not only consume Bollywood movies for entertainment but also as a way to stay connected with their Indian heritage. This study closely looks at one such diasporic community, namely the Dutch Hindustanis, investigating how Bollywood cinema affects their image of India, and how influential Bollywood cinema is in influencing their travel decisions to India. In-depth interviews indicate that Bollywood is a dominant cultural source for defining the respondents’ relationship with India. Moreover, the repeated consumption of Bollywood cinema stirs the desire to actually travel to India, seldom in search of ‘home’, but to visit sites associated with multiple Bollywood movies. Bollywood cinema being from their ‘distant homeland’ also incentivizes their travels to India thereby making it a meaningful experience. This study contributes to film (and) tourism research by introducing the concept of ‘cinematic itinerary’ to refer to these comprehensive film tourism practices

Robotics and AI-Enabled On-Orbit Operations With Future Generation of Small Satellites

The low-cost and short-lead time of small satellites has led to their use in science-based missions, earth observation, and interplanetary missions. Today, they are also key instruments in orchestrating technological demonstrations for On-Orbit Operations (O 3 ) such as inspection and spacecraft servicing with planned roles in active debris removal and on-orbit assembly. This paper provides an overview of the robotics and autonomous systems (RASs) technologies that enable robotic O 3 on smallsat platforms. Major RAS topics such as sensing & perception, guidance, navigation & control (GN&C) microgravity mobility and mobile manipulation, and autonomy are discussed from the perspective of relevant past and planned missions

Novel Insights Into Breast Cancer Copy Number Genetic Heterogeneity Revealed by Single-Cell Genome Sequencing

Copy number alterations (CNAs) play an important role in molding the genomes of breast cancers and have been shown to be clinically useful for prognostic and therapeutic purposes. However, our knowledge of intra-tumoral genetic heterogeneity of this important class of somatic alterations is limited. Here, using single-cell sequencing, we comprehensively map out the facets of copy number alteration heterogeneity in a cohort of breast cancer tumors. Ou/var/www/html/elife/12-05-2020/backup/r analyses reveal: genetic heterogeneity of non-tumor cells (i.e. stroma) within the tumor mass; the extent to which copy number heterogeneity impacts breast cancer genomes and the importance of both the genomic location and dosage of sub-clonal events; the pervasive nature of genetic heterogeneity of chromosomal amplifications; and the association of copy number heterogeneity with clinical and biological parameters such as polyploidy and estrogen receptor negative status. Our data highlight the power of single-cell genomics in dissecting, in its many forms, intra-tumoral genetic heterogeneity of CNAs, the magnitude with which CNA heterogeneity affects the genomes of breast cancers, and the potential importance of CNA heterogeneity in phenomena such as therapeutic resistance and disease relapse

A classification model for distinguishing copy number variants from cancer-related alterations

<p>Abstract</p> <p>Background</p> <p>Both somatic copy number alterations (CNAs) and germline copy number variants (CNVs) that are prevalent in healthy individuals can appear as recurrent changes in comparative genomic hybridization (CGH) analyses of tumors. In order to identify important cancer genes CNAs and CNVs must be distinguished. Although the Database of Genomic Variants (DGV) contains a list of all known CNVs, there is no standard methodology to use the database effectively.</p> <p>Results</p> <p>We develop a prediction model that distinguishes CNVs from CNAs based on the information contained in the DGV and several other variables, including segment's length, height, closeness to a telomere or centromere and occurrence in other patients. The models are fitted on data from glioblastoma and their corresponding normal samples that were collected as part of The Cancer Genome Atlas project and hybridized to Agilent 244 K arrays.</p> <p>Conclusions</p> <p>Using the DGV alone CNVs in the test set can be correctly identified with about 85% accuracy if the outliers are removed before segmentation and with 72% accuracy if the outliers are included, and additional variables improve the prediction by about 2-3% and 12%, respectively. Final models applied to data from ovarian tumors have about 90% accuracy with all the variables and 86% accuracy with the DGV alone.</p

Chromosomal instability drives metastasis through a cytosolic DNA response

Chromosomal instability is a hallmark of cancer that results from ongoing errors in chromosome segregation during mitosis. Although chromosomal instability is a major driver of tumour evolution, its role in metastasis has not been established. Here we show that chromosomal instability promotes metastasis by sustaining a tumour cell-autonomous response to cytosolic DNA. Errors in chromosome segregation create a preponderance of micronuclei whose rupture spills genomic DNA into the cytosol. This leads to the activation of the cGAS–STING (cyclic GMP-AMP synthase–stimulator of interferon genes) cytosolic DNA-sensing pathway and downstream noncanonical NF-κB signalling. Genetic suppression of chromosomal instability markedly delays metastasis even in highly aneuploid tumour models, whereas continuous chromosome segregation errors promote cellular invasion and metastasis in a STING-dependent manner. By subverting lethal epithelial responses to cytosolic DNA, chromosomally unstable tumour cells co-opt chronic activation of innate immune pathways to spread to distant organs

Ordered and deterministic cancer genome evolution after p53 loss

Although p53 inactivation promotes genomic instability1 and presents a route to malignancy for more than half of all human cancers2,3, the patterns through which heterogenous TP53 (encoding human p53) mutant genomes emerge and influence tumorigenesis remain poorly understood. Here, in a mouse model of pancreatic ductal adenocarcinoma that reports sporadic p53 loss of heterozygosity before cancer onset, we find that malignant properties enabled by p53 inactivation are acquired through a predictable pattern of genome evolution. Single-cell sequencing and in situ genotyping of cells from the point of p53 inactivation through progression to frank cancer reveal that this deterministic behaviour involves four sequential phases-Trp53 (encoding mouse p53) loss of heterozygosity, accumulation of deletions, genome doubling, and the emergence of gains and amplifications-each associated with specific histological stages across the premalignant and malignant spectrum. Despite rampant heterogeneity, the deletion events that follow p53 inactivation target functionally relevant pathways that can shape genomic evolution and remain fixed as homogenous events in diverse malignant populations. Thus, loss of p53-the 'guardian of the genome'-is not merely a gateway to genetic chaos but, rather, can enable deterministic patterns of genome evolution that may point to new strategies for the treatment of TP53-mutant tumours

Mutant-IDH1-dependent chromatin state reprogramming, reversibility, and persistence

Mutations in IDH1 and IDH2 (encoding isocitrate dehydrogenase 1 and 2) drive the development of gliomas and other human malignancies. Mutant IDH1 induces epigenetic changes that promote tumorigenesis, but the scale and reversibility of these changes are unknown. Here, using human astrocyte and glioma tumorsphere systems, we generate a large-scale atlas of mutant-IDH1-induced epigenomic reprogramming. We characterize the reversibility of the alterations in DNA methylation, the histone landscape, and transcriptional reprogramming that occur following IDH1 mutation. We discover genome-wide coordinate changes in the localization and intensity of multiple histone marks and chromatin states. Mutant IDH1 establishes a CD24+ population with a proliferative advantage and stem-like transcriptional features. Strikingly, prolonged exposure to mutant IDH1 results in irreversible genomic and epigenetic alterations. Together, these observations provide unprecedented high-resolution molecular portraits of mutant-IDH1-dependent epigenomic reprogramming. These findings have substantial implications for understanding of mutant IDH function and for optimizing therapeutic approaches to targeting IDH-mutant tumors