Intrinsic flat stability of the positive mass theorem for graphical hypersurfaces of Euclidean space

The rigidity of the Positive Mass Theorem states that the only complete asymptotically flat manifold of nonnegative scalar curvature and zero mass is Euclidean space. We study the stability of this statement for spaces that can be realized as graphical hypersurfaces in Euclidean space. We prove (under certain technical hypotheses) that if a sequence of complete asymptotically flat graphs of nonnegative scalar curvature has mass approaching zero, then the sequence must converge to Euclidean space in the pointed intrinsic flat sense. The appendix includes a new Gromov-Hausdorff and intrinsic flat compactness theorem for sequences of metric spaces with uniform Lipschitz bounds on their metrics.Comment: 31 pages, 2 figures, v2: to appear in Crelle's Journal, many minor changes, one new exampl

Prickle1 is required for EMT and migration of zebrafish cranial neural crest

The neural crest—a key innovation of the vertebrates—gives rise to diverse cell types including melanocytes, neurons and glia of the peripheral nervous system, and chondrocytes of the jaw and skull. Proper development of the cephalic region is dependent on the tightly-regulated specification and migration of cranial neural crest cells (NCCs). The core PCP proteins Frizzled and Disheveled have previously been implicated in NCC migration. Here we investigate the functions of the core PCP proteins Prickle1a and Prickle1b in zebrafish cranial NCC development. Using analysis of pk1a and pk1b mutant embryos, we uncover similar roles for both genes in facilitating cranial NCC migration. Disruption of either gene causes pre-migratory NCCs to cluster together at the dorsal aspect of the neural tube, where they adopt aberrant polarity and movement. Critically, in investigating Pk1-deficient cells that fail to migrate ventrolaterally, we have also uncovered roles for pk1a and pk1b in the epithelial-to-mesenchymal transition (EMT) of pre-migratory NCCs that precedes their collective migration to the periphery. Normally, during EMT, pre-migratory NCCs transition from a neuroepithelial to a bleb-based and subsequently, mesenchymal morphology capable of directed migration. When either Pk1a or Pk1b is disrupted, NCCs continue to perform blebbing behaviors characteristic of pre-migratory cells over extended time periods, indicating a block in a key transition during EMT. Although some Pk1-deficient NCCs transition successfully to mesenchymal, migratory morphologies, they fail to separate from neighboring NCCs. Additionally, Pk1b-deficient NCCs show elevated levels of E-Cadherin and reduced levels of N-Cadherin, suggesting that Prickle1 molecules regulate Cadherin levels to ensure the completion of EMT and the commencement of cranial NCC migration. We conclude that Pk1 plays crucial roles in cranial NCCs both during EMT and migration. These roles are dependent on the regulation of E-Cad and N-Cad

Gene Co-expression Network and Copy Number Variation Analyses Identify Transcription Factors Associated With Multiple Myeloma Progression

Multiple myeloma (MM) has two clinical precursor stages of disease: monoclonal gammopathy of undetermined significance (MGUS) and smoldering multiple myeloma (SMM). However, the mechanism of progression is not well understood. Because gene co-expression network analysis is a well-known method for discovering new gene functions and regulatory relationships, we utilized this framework to conduct differential co-expression analysis to identify interesting transcription factors (TFs) in two publicly available datasets. We then used copy number variation (CNV) data from a third public dataset to validate these TFs. First, we identified co-expressed gene modules in two publicly available datasets each containing three conditions: normal, MGUS, and SMM. These modules were assessed for condition-specific gene expression, and then enrichment analysis was conducted on condition-specific modules to identify their biological function and upstream TFs. TFs were assessed for differential gene expression between normal and MM precursors, then validated with CNV analysis to identify candidate genes. Functional enrichment analysis reaffirmed known functional categories in MM pathology, the main one relating to immune function. Enrichment analysis revealed a handful of differentially expressed TFs between normal and either MGUS or SMM in gene expression and/or CNV. Overall, we identified four genes of interest (MAX, TCF4, ZNF148, and ZNF281) that aid in our understanding of MM initiation and progression

Modeling Turbidity Currents Using the Multiple-state Discrete-time Markov Chain Approach

Source: ICHE Conference Archive - https://mdi-de.baw.de/icheArchive

Strategic and Operational Benefits of IOS-Enabled Interorganizational Integration

In this study, we employ the lens of the resource-based view of the firm to examine the strategic value of IOS- enabled interorganizational integration. We first develop the key construct of IOS-enabled interorganizational integration, identifying and defining its two dimensions: interorganizational system integration and business integration. Next, we propose that while the two dimensions have positive impacts on operational performance, only interorganizational business integration has strategic value. The data for this study were collected through a survey of firms in mainland China. The results provide empirical support for our propositions. The study contributes to research by providing a clear conceptualization of IOS-enabled interorganizational integration, establishing the theoretical link between its two dimensions and operational and strategic performance, developing scales for interorganizational system integration and business integration, as well as providing data on the IOS experience of Chinese firms

Spinal cord stimulation in chronic pain: evidence and theory for mechanisms of action.

Well-established in the field of bioelectronic medicine, Spinal Cord Stimulation (SCS) offers an implantable, non-pharmacologic treatment for patients with intractable chronic pain conditions. Chronic pain is a widely heterogenous syndrome with regard to both pathophysiology and the resultant phenotype. Despite advances in our understanding of SCS-mediated antinociception, there still exists limited evidence clarifying the pathways recruited when patterned electric pulses are applied to the epidural space. The rapid clinical implementation of novel SCS methods including burst, high frequency and dorsal root ganglion SCS has provided the clinician with multiple options to treat refractory chronic pain. While compelling evidence for safety and efficacy exists in support of these novel paradigms, our understanding of their mechanisms of action (MOA) dramatically lags behind clinical data. In this review, we reconstruct the available basic science and clinical literature that offers support for mechanisms of both paresthesia spinal cord stimulation (P-SCS) and paresthesia-free spinal cord stimulation (PF-SCS). While P-SCS has been heavily examined since its inception, PF-SCS paradigms have recently been clinically approved with the support of limited preclinical research. Thus, wide knowledge gaps exist between their clinical efficacy and MOA. To close this gap, many rich investigative avenues for both P-SCS and PF-SCS are underway, which will further open the door for paradigm optimization, adjunctive therapies and new indications for SCS. As our understanding of these mechanisms evolves, clinicians will be empowered with the possibility of improving patient care using SCS to selectively target specific pathophysiological processes in chronic pain

How Do You Perpetuate IT-Enabled Change When Top Management Participation and Involvement Diminish?

Background: Research has demonstrated that sustained top management participation and involvement are important for IT-enabled change. However, this is not always possible. How IT-enabled change can succeed when top management participation and involvement diminish is an unsolved, but important research question. Method: We perform a 5-year exploratory longitudinal case study. Results: Our data is presented in two parts. We first present the contextual elements (goals, people, structures/processes, and artifacts) during the two years top management was actively participating and involved. For the three-year period where top management participation and involvement diminished, we present the contextual elements, and middle management’s enactment of traditional middle management roles (information broker, mediator, facilitator, change agent) on three kinds of threats to the change (deviations from change vision, emergent issues, involving new stakeholders). Conclusions: We find IT-enabled change can succeed when top management participation and involvement diminish if middle management engages in joint action, i.e., intentional collective activity where members consciously choose to coordinate to achieve a goal. We identify three kinds of joint action: Constraining, where actions of the group limit the ability of individual middle managers to deviate from shared goals, Enabling, whereby a group of middle managers adapt the project to changing circumstances, and Extending, where groups of middle managers engage with others not in their functional areas. Joint action emerges when top management embeds, in the project context, (1) key influential stakeholders who are involved in the change, (2) a common goal, (3) structures and processes that promote collective work, and (4) artifacts inscribed with the common goal and collective work. Available at: https://aisel.aisnet.org/pajais/vol11/iss4/2