WitchTok describes a sub-section of the social media platform TikTok, which caters to Contemporary Pagans and other practitioners of modern Witchcraft. Through short micro-videos, users share ...snapshots of their lives, providing a window into their religious identities and practices. Through a qualitative analysis of videos and comments, this exploratory study examines how modern Witches engage with religion through this digital space. Although this platform is wholly virtual, WitchTok is also eminently material. Through sharing and commenting on videos of spells, potions, altars, and other practices, users engage with a range of material objects. By announcing the magical properties of materials, instructing how to use certain objects, and advising where items can be found, WitchTok reveals how Witches conceptualize materiality and magic. The promotion of products, businesses, and personal brands in this space also reveals how Witchcraft is shaped by consumerism. In contrast to scholars who distinguish between “traditional” Witchcraft and “consumerist” Witches, I argue that WitchTok highlights the complex entanglements of Witchcraft with consumer capitalism.
When Vladimir Putin first took power in 1999, he was a little-known figure ruling a country that was reeling from a decade and a half of crisis. In the years since, he has reestablished Russia as a ...great power. How did he do it? What principles have guided Putin's economic policies? What patterns can be discerned? In this new analysis of Putin's Russia, Chris Miller examines its economic policy and the tools Russia's elite have used to achieve its goals. Miller argues that despite Russia's corruption, cronyism, and overdependence on oil as an economic driver, Putin's economic strategy has been surprisingly successful.Explaining the economic policies that underwrote Putin's two-decades-long rule, Miller shows how, at every juncture, Putinomics has served Putin's needs by guaranteeing economic stability and supporting his accumulation of power. Even in the face of Western financial sanctions and low oil prices, Putin has never been more relevant on the world stage.
Generations of Russians have pursued wealth and power in the East, colonizing Pacific regions and spreading political influence into Asia. Why have these efforts largely failed? Chris Miller argues ...that Russian citizens and leaders, concentrated in the European borderlands, have always struggled to maintain faith and interest in eastward expansion.
Tractable human tissue-engineered 3D models of cancer that enable fine control of tumor growth, metabolism, and reciprocal interactions between different cell types in the tumor microenvironment ...promise to accelerate cancer research and pharmacologic testing. Progress to date mostly reflects the use of immortalized cancer cell lines, and progression to primary patient-derived tumor cells is needed to realize the full potential of these platforms. For the first time, we report endothelial sprouting induced by primary patient tumor cells in a 3D microfluidic system. Specifically, we have combined primary human clear cell renal cell carcinoma (ccRCC) cells from six independent donors with human endothelial cells in a vascularized, flow-directed, 3D culture system (“ccRCC-on-a-chip”). The upregulation of key angiogenic factors in primary human ccRCC cells, which exhibited unique patterns of donor variation, was further enhanced when they were cultured in 3D clusters. When embedded in the matrix surrounding engineered human vessels, these ccRCC tumor clusters drove potent endothelial cell sprouting under continuous flow, thus recapitulating the critical angiogenic signaling axis between human ccRCC cells and endothelial cells. Importantly, this phenotype was driven by a primary tumor cell–derived biochemical gradient of angiogenic growth factor accumulation that was subject to pharmacological blockade. Our novel 3D system represents a vascularized tumor model that is easy to image and quantify and is fully tunable in terms of input cells, perfusate, and matrices. We envision that this ccRCC-on-a-chip will be valuable for mechanistic studies, for studying tumor-vascular cell interactions, and for developing novel and personalized antitumor therapies.
IMPORTANCE: Despite its high prevalence and morbidity, the underlying neural basis of major depressive disorder (MDD) in youth is not well understood. OBJECTIVES: To identify in youth diagnosed as ...having MDD the most reliable neural abnormalities reported in existing functional neuroimaging studies and characterize their relations with specific psychological dysfunctions. DATA SOURCES: Searches were conducted in PubMed and Web of Science to identify relevant studies published from November 2006 through February 2015. The current analysis took place from August 21, 2014, to March 28, 2015. STUDY SELECTION: We retained articles that conducted a comparison of youth aged 4 to 24 years diagnosed as having MDD and age-matched healthy controls using task-based functional magnetic resonance imaging and a voxelwise whole-brain approach. DATA EXTRACTION AND SYNTHESIS: We extracted coordinates of brain regions exhibiting differential activity in youth with MDD compared with healthy control participants. Multilevel kernel density analysis was used to examine voxelwise between-group differences throughout the whole brain. Correction for multiple comparisons was performed by computing null hypothesis distributions from 10 000 Monte Carlo simulations and calculating the cluster size necessary to obtain the familywise error rate control at P < .05. MAIN OUTCOMES AND MEASURES: Abnormal levels of activation in youth diagnosed as having MDD compared with control participants during a variety of affective processing and executive functioning tasks. RESULTS: Compared with age-matched healthy control participants (n = 274), youth with MDD (n = 246) showed reliable patterns of abnormal activation, including the following task-general and task-specific effects: hyperactivation in subgenual anterior cingulate cortex (P < .05) and ventrolateral prefrontal cortex (P < .05) and hypoactivation in caudate (P < .01) across aggregated tasks; hyperactivation in thalamus (P < .03) and parahippocampal gyrus (P < .003) during affective processing tasks; hypoactivation in cuneus (P < .001), dorsal cingulate cortex (P < .05), and dorsal anterior insula (P < .05) during executive functioning tasks; hypoactivity in posterior insula (P < .005) during positive valence tasks; and hyperactivity in dorsolateral prefrontal cortex (P < .001) and superior temporal cortex (P < .003) during negative valence tasks. CONCLUSIONS AND RELEVANCE: Altered activations in several distributed brain networks may help explain the following seemingly disparate symptoms of MDD in youth: hypervigilance toward emotional stimuli from the overactivation of central hubs in the subgenual anterior cingulate cortex and thalamus that lead to a cascade of other symptoms; ineffective emotion regulation despite increased activation of the dorsolateral prefrontal cortex and ventrolateral prefrontal cortex during affective processing, which may reverse across development or the clinical course; maladaptive rumination and poor executive control from difficulties shifting from default mode network activity to task-positive network activity during cognitively demanding tasks; and anhedonia from hypoactivation of the cuneus and posterior insula during reward processing.
The sexual abuse crisis that has rocked the Catholic Church in recent decades has resulted in one major unintended casualty: creating a skeptical distance in the relationship between adult leaders ...and youth. This article provides a short history of the abuse scandal in the US and discusses the reforms and repercussions of the Dallas Charter, in conjunction with the relationships between adult leaders and youth. By incorporating the five aspects of the Developmental Relationships Framework into youth programs, ministers and volunteers will have the means to provide tangible action items for developing positive relationships with young people. These five items include expressing care, challenging growth, providing support, sharing power, and expanding possibilities.
Cancers that appear pathologically similar often respond differently to the same drug regimens. Methods to better match patients to drugs are in high demand. We demonstrate a promising approach to ...identify robust molecular markers for targeted treatment of acute myeloid leukemia (AML) by introducing: data from 30 AML patients including genome-wide gene expression profiles and in vitro sensitivity to 160 chemotherapy drugs, a computational method to identify reliable gene expression markers for drug sensitivity by incorporating multi-omic prior information relevant to each gene's potential to drive cancer. We show that our method outperforms several state-of-the-art approaches in identifying molecular markers replicated in validation data and predicting drug sensitivity accurately. Finally, we identify SMARCA4 as a marker and driver of sensitivity to topoisomerase II inhibitors, mitoxantrone, and etoposide, in AML by showing that cell lines transduced to have high SMARCA4 expression reveal dramatically increased sensitivity to these agents.
Triple-negative breast cancer is a heterogeneous disease characterized by poor clinical outcomes and a shortage of targeted treatment options. To discover molecular features of triple-negative breast ...cancer, we performed quantitative proteomics analysis of twenty human-derived breast cell lines and four primary breast tumors to a depth of more than 12,000 distinct proteins. We used this data to identify breast cancer subtypes at the protein level and demonstrate the precise quantification of biomarkers, signaling proteins, and biological pathways by mass spectrometry. We integrated proteomics data with exome sequence resources to identify genomic aberrations that affect protein expression. We performed a high-throughput drug screen to identify protein markers of drug sensitivity and understand the mechanisms of drug resistance. The genome and proteome provide complementary information that, when combined, yield a powerful engine for therapeutic discovery. This resource is available to the cancer research community to catalyze further analysis and investigation.
An illuminating account of Russia's attempts-and
failures-to achieve great power status in Asia. Since
Peter the Great, Russian leaders have been lured by opportunity to
the East. Under the tsars, ...Russians colonized Alaska, California,
and Hawaii. The Trans-Siberian Railway linked Moscow to
Vladivostok. And Stalin looked to Asia as a sphere of influence,
hospitable to the spread of Soviet Communism. In Asia and the
Pacific lay territory, markets, security, and glory. But all these
expansionist dreams amounted to little. In We Shall Be
Masters , Chris Miller explores why, arguing that Russia's
ambitions have repeatedly outstripped its capacity. With the core
of the nation concentrated thousands of miles away in the European
borderlands, Russia's would-be pioneers have always struggled to
project power into Asia and to maintain public and elite interest
in their far-flung pursuits. Even when the wider population
professed faith in Asia's promise, few Russians were willing to pay
the steep price. Among leaders, too, dreams of empire have always
been tempered by fears of cost. Most of Russia's pivots to Asia
have therefore been halfhearted and fleeting. Today the Kremlin
talks up the importance of "strategic partnership" with Xi
Jinping's China, and Vladimir Putin's government is at pains to
emphasize Russian activities across Eurasia. But while distance is
covered with relative ease in the age of air travel and digital
communication, the East remains far off in the ways that matter
most. Miller finds that Russia's Asian dreams are still restrained
by the country's firm rooting in Europe.
Tissues- and organs-on-chips are microphysiological systems (MPSs) that model the architectural and functional complexity of human tissues and organs that is lacking in conventional cell monolayer ...cultures. While substantial progress has been made in a variety of tissues and organs, chips recapitulating immune responses have not advanced as rapidly. This review discusses recent progress in MPSs for the investigation of immune responses. To illustrate recent developments, we focus on two cases in point: immunocompetent tumor microenvironment-on-a-chip devices that incorporate stromal and immune cell components and pathomimetic modeling of human mucosal immunity and inflammatory crosstalk. More broadly, we discuss the development of systems immunology-on-a-chip devices that integrate microfluidic engineering approaches with high-throughput omics measurements and emerging immunological applications of MPSs.
Human tumor immune microenvironment-on-a-chip models have been developed to emulate cell-type-dependent interactions, physical and chemical perturbations, and the infiltration and cytotoxicity of therapeutic antitumor lymphocytes and clinically relevant immunomodulatory agents.Intestinal inflammation-on-a-chip models recapitulating the 3D intestinal transmural interface have been developed to discover how pathophysiological factors impair the intercellular crosstalk in the epithelium-microbiome-immune axis and trigger chronic inflammatory immune responses.Combining engineered microphysiological immune system responses with high-throughput multiomics measurements at the single-cell level facilitates a systems immunology-on-a-chip approach to gain novel insights into immune disorders.Immune cells are being incorporated in tissues- and organs-on-chips modeling a variety of diseases.
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