Alignment of spatial genomics and histology data using deep Gaussian processes

Spatially-resolved genomic technologies have allowed us to study the physical organization of cells and tissues, and promise an understanding of the local interactions between cells. However, it remains difficult to precisely align spatial observations across slices, samples, scales, individuals, and technologies. Here, we propose a probabilistic model that aligns a set of spatially-resolved genomics and histology slices onto a known or unknown common coordinate system into which the samples are aligned both spatially and in terms of the phenotypic readouts (e.g., gene or protein expression levels, cell density, open chromatin regions). Our method consists of a two-layer Gaussian process: the first layer maps the observed samples' spatial locations into a common coordinate system, and the second layer maps from the common coordinate system to the observed readouts. Our approach also allows for slices to be mapped to a known template coordinate space if one exists. We show that our registration approach enables complex downstream spatially-aware analyses of spatial genomics data at multiple resolutions that are impossible or inaccurate with unaligned data, including an analysis of variance, differential expression across the z-axis, and association tests across multiple data modalities.

The (Un)governable City: Productive Failure in the Making of Colonial Delhi, 1858-1911 by Raghav Kishore

Delhi has always been a crucible of political disquiet, and the seat of manifold state and aesthetic desires to order, control and design the city. Even at this moment, we find ourselves before a ubiquitous impulse to change the appearance of the city through the Central Vista Project which proposes to cater to needs of increase in government office space. There are layers to the city and obvious enough, it is not monolithic. The vestiges and architectural remnants of subsequent ages narrate the relentless saga of power, domination and settlement. A historical analysis of the spatial structures reflects the reasons behind its physical organization. To talk about colonial designs within this very broad spectrum is but, only a brief moment in a longue duree of human settlement in this region. Yet, it is necessary to understand the spatial synchrony, for much of it is what we have inherited today and this is what shapes our experiences of this city even at present. Raghav Kishore’s The (Un)governable City (2020), makes an intervention in this corpus of historical analysis with his impeccable research and endless forays into the archives. This is a welcome addition to studies in the field of urban development of Delhi, with Pilar Maria Guerrieri’s Maps of Delhi (2017) being one precursor, which painstakingly curates maps of Delhi from the precolonial times, to the modern municipal Master Plans to contemporary digital mappings. Kishore unearths curious details from local sources and twines those with debates among colonial policy makers and personnel to highlight issues of political ideology, statecraft and governmentality. This volume juxtaposes notions of policing, control and accessibility with debates and discussions on sanitation, traffic, communication, railways and the building of military cantonments, which are significant if we think of the British rule in India as a garrison state, heavily dependent on the easy mobility of its military forces. The success of the control was conditional on the ability to gather up huge military forces to curb parallel sporadic outbursts at their very onset. The broadening of roads, regulation of quarters and delimiting encroachments and concerns over connectivity, were carefully thought out strategisations towards the goal of containment and territorialisation.

Nuclear morphogenesis: forming a heterogeneous nucleus during embryogenesis

An embryo experiences progressively complex spatial and temporal patterns of gene expression that guide the morphogenesis of its body plan as it matures. Using super-resolution fluorescence microscopy in Drosophila melanogaster embryos, we observed a similar increase in complexity in the nucleus: the spatial distributions of transcription factors became increasingly heterogeneous as the embryo matured. We also observed a similar trend in chromatin conformation with the establishment of specific histone modification patterns. However, transcription sites of specific genes had distinct local preferences for histone marks separate from the average nuclear trend, depending on the time and location of their expression. These results suggest that reconfiguring the nuclear environment is an integral part of embryogenesis and that the physical organization of the nucleus a key element in developmental gene regulation.

To the Prerequisites for the Formation of an Egocentric Picture of the World: at the Intersection of Physics and Metaphysics

The article considers the most general prerequisites for creating a new model of the ecological picture of the world, which is characterized by the comprehensiveness and completeness of coverage of various aspects of the study of the relationships between man and nature. For its formation, it is proposed to use an ecological version of the worldview-methodological platform, called ‘postholism’ by the author, which is able to coordinate the one, whole, many and singular, unique in (among others) the environmental relations of man, society and nature. This allows us to eliminate the methodological shortcomings of the reduction to the individual (merism), to the whole (holism), to the one (onecentrism) of human worldview orientations in the nature of naturcentrism, anthropo(socio)centrism, technocentrism, theocentrism. Such categories of philosophy as ‘reality’, ‘being’, ‘otherness’, ‘non-existence’, ‘being’, ‘nature’, ‘matter’, ‘physical’, ‘metaphysical’, and ‘spiritual’ were important tools for constructing a picture of the world of ecocentrism. They were refined and correlated with the latest achievements in quantum physics, astrophysics, cosmology, as well as reflexed based on extra-scientific representations of ancient cultures and religions. Physical, as well as metaphysical features of nature and man are briefly discussed. Nature is represented at various levels of physical organization (micro-world, macro-world and mega-world) and outside of physical dimensions. These dimensions presumably contain the ‘metaphysical’ content of nature. In them, the objective ‘spiritual’ of the universe, deified by man, is allowed. This does not exclude the pantheistic presence of metaphysical transcendence, estimated as ‘nonexistence’, ‘nothing’ for the reality of man within nature. Man himself is positioned as one whole of physical and spiritual existence, serving as a semblance of a Single Whole of nature. In conclusion, a list of the main environmental invariants of the world picture is given in comparison with the proposed picture of the world of ecologized postholism − ecocentrism, the advantages of which are emphasized. The Universe and quantum-field reality, along with the Earth, become components of the All-unified Whole authentic home of the ‘ecos’ of man. Further conditions and prospects for the direct development of this model are discussed.

A high-quality genome assembly highlights rye genomic characteristics and agronomically important genes

Rye is a valuable food and forage crop, an important genetic resource for wheat and triticale improvement and an indispensable material for efficient comparative genomic studies in grasses. Here, we sequenced the genome of Weining rye, an elite Chinese rye variety. The assembled contigs (7.74 Gb) accounted for 98.47% of the estimated genome size (7.86 Gb), with 93.67% of the contigs (7.25 Gb) assigned to seven chromosomes. Repetitive elements constituted 90.31% of the assembled genome. Compared to previously sequenced Triticeae genomes, Daniela, Sumaya and Sumana retrotransposons showed strong expansion in rye. Further analyses of the Weining assembly shed new light on genome-wide gene duplications and their impact on starch biosynthesis genes, physical organization of complex prolamin loci, gene expression features underlying early heading trait and putative domestication-associated chromosomal regions and loci in rye. This genome sequence promises to accelerate genomic and breeding studies in rye and related cereal crops.

Deafness mutation D572N of TMC1 destabilizes TMC1 expression by disrupting LHFPL5 binding

Transmembrane channel-like protein 1 (TMC1) and lipoma HMGIC fusion partner-like 5 (LHFPL5) are recognized as two critical components of the mechanotransduction complex in inner-ear hair cells. However, the physical and functional interactions of TMC1 and LHFPL5 remain largely unexplored. We examined the interaction between TMC1 and LHFPL5 by using multiple approaches, including our recently developed ultrasensitive microbead-based single-molecule pulldown (SiMPull) assay. We demonstrate that LHFPL5 physically interacts with and stabilizes TMC1 in both heterologous expression systems and in the soma and hair bundle of hair cells. Moreover, the semidominant deafness mutation D572N in human TMC1 (D569N in mouse TMC1) severely disrupted LHFPL5 binding and destabilized TMC1 expression. Thus, our findings reveal previously unrecognized physical and functional interactions of TMC1 and LHFPL5 and provide insights into the molecular mechanism by which the D572N mutation causes deafness. Notably, these findings identify a missing link in the currently known physical organization of the mechanotransduction macromolecular complex. Furthermore, this study has demonstrated the power of the microbead-based SiMPull assay for biochemical investigation of rare cells such as hair cells.

One Hundred Years of Instability: Sex, Law, and Transgender Rights

Five years before the famous Seneca Falls Meeting in which a gathering of women demanded suffrage, Levi Suydam already had encountered the problem that sex posed for suffrage. Suydam, a 23-year-old man who supported the Whigs, petitioned to vote in 1843. The opposing party challenged his petition “on the grounds that ‘he was more a female than a male, and that, in his physical organization, he partook of both sexes’” (Reis 2009, 34). Because the Whigs won by one vote, Suydam’s status was central to the election outcome. After several medical exams in which different doctors reached different conclusions about Suydam’s true sex, Suydam was determined to be “more female than male” (Reis 2009, 35). Suydam’s case presents an important corollary to a more famous case of voting “fraud” after Susan B. Anthony voted in the 1872 presidential election. The 1873 trial and conviction of Anthony was straightforward: as a woman, she could not vote. Suydam posed a greater challenge to political order insofar as neither law nor medicine could pin down Suydam’s sex within a framework of binary sex. The Nineteenth Amendment, which prohibited the denial of the vote “on account of sex,” might have rendered the uncertainty of sex politically and legally moot. It did not.

Pengaruh Human Relation, Kondisi Fisik Lingkungan dan Organization Based Self-Esteem Terhadap Etos Kerja Serta Dampaknya Pada Kinerja Karyawan BPR Kedung Arto Semarang

This research intent to test Subjective implement effectiveness Human Relation, Condition of Environment Physical, Organization Based Self Esteem to job and Performance Ethos. Base former observational result, condition of environment physical constitute molded environment of implemented subjective human squire. Relationship among human contain mean a communication since its character that orientation on behavioral. Therefore, organization righteously has give freedom to fire an employee to get that communication they can collaborate properly in their work. This research is done on BPR Kedung Arto at Semarang. Method that is utilized as method of census via pervading questionnaire of population a number 102 person. Two phase regression analysis is utilized as quantitative analysis. Coefficients arithmetic result determinant totaled point out that 72% changing variable dependent can be worded by independent variables. Meanwhile its rest as big as 28% worded by outdoor other variables model observational. Hypthothesis testing result partially of each step points out to mark sense influence positively and significant of job Ethos to Performance. Hereafter, Human Relation, Condition of Environment Physical and OBSE each have influence positively and significant to job Ethos.