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We present a review of Anomalous Cosmic Rays (ACRs), including the history of their discovery and recent insights into their acceleration and transport in the heliosphere. We focus on a few selected topics including a discussion of mechanisms of their acceleration, escape from the heliosphere, their effects on the dynamics of the heliosheath, transport in the inner heliosphere, and their solar cycle dependence. A discussion concerning their name is also presented towards the end of the review. We note that much is known about ACRs and perhaps the term Anomalous Cosmic Ray is not particularly descriptive to a non specialist. We suggest that the more-general term: “Heliospheric Energetic Particles”, which is more descriptive, for which ACRs and other energetic particle species of heliospheric origin are subsets, might be more appropriate.

Issue Title: Special Issue: Coronal Mass Ejections This chapter provides an overview of current efforts in the theory and modeling of CMEs. Five key areas are discussed: (1) CME initiation; (2) CME evolution and propagation; (3) the structure of interplanetary CMEs derived from flux rope modeling; (4) CME shock formation in the inner corona; and (5) particle acceleration and transport at CME driven shocks. In the section on CME initiation three contemporary models are highlighted. Two of these focus on how energy stored in the coronal magnetic field can be released violently to drive CMEs. The third model assumes that CMEs can be directly driven by currents from below the photosphere. CMEs evolve considerably as they expand from the magnetically dominated lower corona into the advectively dominated solar wind. The section on evolution and propagation presents two approaches to the problem. One is primarily analytical and focuses on the key physical processes involved. The other is primarily numerical and illustrates the complexity of possible interactions between the CME and the ambient medium. The section on flux rope fitting reviews the accuracy and reliability of various methods. The section on shock formation considers the effect of the rapid decrease in the magnetic field and plasma density with height. Finally, in the section on particle acceleration and transport, some recent developments in the theory of diffusive particle acceleration at CME shocks are discussed. These include efforts to combine self-consistently the process of particle acceleration in the vicinity of the shock with the subsequent escape and transport of particles to distant regions.[PUBLICATION ABSTRACT]

Genetic and immunological screening for type 1 diabetes has led to the possibility of preventing disease in susceptible individuals. Here, we show that human mesenchymal stem/stromal cells (hMSCs) and tumor necrosis factor-α–stimulated gene 6 (TSG-6), a protein produced by hMSCs in response to signals from injured tissues, delayed the onset of spontaneous autoimmune diabetes in NOD mice by inhibiting insulitis and augmenting regulatory T cells (Tregs) within the pancreas. Importantly, hMSCs with a knockdown of tsg-6 were ineffective at delaying insulitis and the onset of diabetes in mice. TSG-6 inhibited the activation of both T cells and antigen-presenting cells (APCs) in a CD44-dependent manner. Moreover, multiple treatments of TSG-6 rendered APCs more tolerogenic, capable of enhancing Treg generation and delaying diabetes in an adoptive transfer model. Therefore, these results could provide the basis for a novel therapy for the prevention of type 1 diabetes.

•  Paradigm I: the haematopoietic niche •  Paradigm II: engraftment/differentiation ‐  Early observations on engraftment and differentiation ‐  Technical challenges in testing paradigm II ‐  The impetus to test the paradigm II in clinical trials ‐  Tests of the paradigm II with local administrations ‐  Tests of paradigm II with systemic infusion •  Paradigm III: transient ‘quasi‐niches’ ‐  Unusual features of MSCs in culture ‐  Cross‐talk with injured tissues ‐  Modulation of inflammation in paradigm III ‐  Modulation of apoptosis in paradigm III ‐  Modulation of immune reactions ‐  Paradigm III and the similarities to paradigm I •  Conclusions/perspectives ‐  Why is administration of MSCs beneficial? ‐  Better assays for the potency of MSCs? ‐  Are MSCs pericytes? ‐  Therapies with recombinant proteins? ‐  Additional questions in developing therapies with MSCs In this review, we focus on the adult stem/progenitor cells that were initially isolated from bone marrow and first referred to as colony forming units‐fibroblastic, then as marrow stromal cells and subsequently as either mesenchymal stem cells or multipotent mesenchymal stromal cells (MSCs). The current interest in MSCs and similar cells from other tissues is reflected in over 10,000 citations in PubMed at the time of this writing with 5 to 10 new publications per day. It is also reflected in over 100 registered clinical trials with MSCs or related cells (http//www.clinicaltrials.gov). As a guide to the vast literature, this review will attempt to summarize many of the publications in terms of three paradigms that have directed much of the work: an initial paradigm that the primary role of the cells was to form niches for haematopoietic stem cells (paradigm I); a second paradigm that the cells repaired tissues by engraftment and differentiation to replace injured cells (paradigm II); and the more recent paradigm that MSCs engage in cross‐talk with injured tissues and thereby generate microenvironments or ‘quasi‐niches’ that enhance the repair tissues (paradigm III).

Due to their capacity to self‐renew, proliferate and generate multi‐lineage cells, adult‐derived stem cells offer great potential for use in regenerative therapies to stop and/or reverse degenerative diseases such as diabetes, heart failure, Alzheimer's disease and others. However, these subsets of cells can be isolated from different niches, each with differing potential for therapeutic applications. The stromal vascular fraction (SVF), a stem cell enriched and adipose‐derived cell population, has garnered interest as a therapeutic in regenerative medicine due to its ability to secrete paracrine factors that accelerate endogenous repair, ease of accessibility and lack of identified major adverse effects. Thus, one can easily understand the rush to employ adipose‐derived SVF to treat human disease. Perhaps faster than any other cell preparation, SVF is making its way to clinics worldwide, while critical preclinical research needed to establish SVF safety, efficacy and optimal, standardized clinical procedures are underway. Here, we will provide an overview of the current knowledge driving this phenomenon, its regulatory issues and existing studies, and propose potential unmapped applications. Stem Cells Translational Medicine 2017;6:1096–1108

In this study, an animal model of moderate‐severe traumatic brain injury (TBI) was treated with an acute dose of propranolol followed by a delayed dose of human mesenchymal stem cells (MSCs), resulting in improved short‐ and long‐term measurements. These results reinforce the inevitable clinical trial of MSCs to treat TBI by demonstrating, among other benefits, a notable decrease in chronic neuroinflammation and demonstrating that MSCs and propranolol are compatible treatments that improve overall outcome. More than 6.5 million patients are burdened by the physical, cognitive, and psychosocial deficits associated with traumatic brain injury (TBI) in the U.S. Despite extensive efforts to develop neuroprotective therapies for this devastating disorder, there have been no successful outcomes in human clinical trials to date. Retrospective studies have shown that β‐adrenergic receptor blockers, specifically propranolol, significantly decrease mortality of TBI through mechanisms not yet fully elucidated but are thought to counterbalance a hyperadrenergic state resulting from a TBI. Conversely, cellular therapies have been shown to improve long‐term behavior following TBI, likely by reducing inflammation. Given the nonredundancy in their therapeutic mechanisms, we hypothesized that a combination of acute propranolol followed by mesenchymal stem cells (MSCs) isolated from human bone marrow would have additive effects in treating a rodent model of TBI. We have found that the treatments are well‐tolerated individually and in combination with no adverse events. MSCs decrease BBB permeability at 96 hours after injury, inhibit a significant accumulation of activated microglia/macrophage in the thalamic region of the brain both short and long term, and enhance neurogenesis short term. Propranolol decreases edema and reduces the number of fully activated microglia at 7 days and the number of semiactivated microglia at 120 days. Combinatory treatment improved cognitive and memory functions 120 days following TBI. Therefore, the results here suggest a new, efficacious sequential treatment for TBI may be achieved using the β‐blocker propranolol followed by MSC treatment. Significance Despite continuous efforts, traumatic brain injury (TBI) remains the leading cause of death and disability worldwide in patients under the age of 44. In this study, an animal model of moderate‐severe TBI was treated with an acute dose of propranolol followed by a delayed dose of human mesenchymal stem cells (MSCs), resulting in improved short‐ and long‐term measurements. These results have direct translational application. They reinforce the inevitable clinical trial of MSCs to treat TBI by demonstrating, among other benefits, a notable decrease in chronic neuroinflammation. More importantly, these results demonstrate that MSCs and propranolol, which is increasingly being used clinically for TBI, are compatible treatments that improve overall outcome.

We present a brief review of the modeling of corotating 3-dimensional features in heliospheric cosmic rays. The model heliosphere incorporates a wavy current sheet and Corotating Interaction Regions (CIRs). We find that present models can qualitatively account for the observed extension of recurrent 26-day cosmic-ray variations to high heliospheric latitudes if perpendicular diffusion is significant. The recurrent enhancement of low-energy (MeV) particles accelerated at CIR-s is also shown to fit into this same picture.

The BCR-ABL-negative myeloproliferative neoplasms (MPNs), polycythemia vera (PV), essential thrombocythemia (ET) and primary myelofibrosis (PMF), entered the spotlight in 2005 when the unique somatic acquired JAK2 V617F mutation was described in >95% of PV and in 50% of ET and PMF patients. For the very rare PV patients who do not harbor the JAK2 V617F mutation, exon 12 JAK2 mutants were discovered also to result in activated forms of JAK2. A minority of ET and PMF patients harbor mutations that constitutively activate the thrombopoietin receptor (TpoR). In bone marrow reconstitution models based on retroviral transduction, the phenotype induced by JAK2 V617F is less severe and different from the rapid fatal myelofibrosis induced by TpoR W515L. The reasons for these differences are unknown. Exactly by which mechanism(s) one acquired somatic mutation, JAK2 V617F, can promote three different diseases remains a mystery, although gene dosage and host genetic variation might have important functions. We review the recent progress made in deciphering signaling anomalies in PV, ET and PMF, with an emphasis on the relationship between JAK2 V617F and cytokine receptor signaling and on cross-talk with several other signaling pathways.

INTRODUCTION South Asian (SA) and East Asian (EA) older adults represent the fastest‐growing racial/ethnic groups of Americans at risk for dementia. While recruiting older SA adults into a brain health study, we encountered unexpected hesitancy toward structural brain magnetic resonance imaging (MRI) analysis and stigmatizing attitudes related to internal locus of control (LoC) for future dementia risks. We hypothesized that support for MRI‐related research was influenced by these attitudes as well as personal MRI experience, perceived MRI safety, and concerns for personal risk for future dementia/stroke. METHODS We developed a brief cross‐sectional survey to assess older adults’ MRI experiences and perceptions, desire to learn of six incidental findings of increasing impact on health, and attitudes related to dementia (including LoC) and research participation. We recruited a convenience sample of 256 respondents (74% reporting as 50+) from the New Jersey/New York City area to complete the survey (offered in English, Chinese, Korean, and Spanish) and modeled the proportional odds (PO) for favorable attitudes toward research activities. RESULTS Seventy‐seven SA and 84 EA respondents were analyzed alongside 95 White, Black, or Hispanic adults. White (PO = 2.54, p = 0.013) and EA (PO = 2.14, p = 0.019) respondents were both more likely than SA respondents to endorse healthy volunteers’ participation in research, and the difference between White and SA respondents was mediated by the latter's greater internal LoC for dementia risks. EA respondents had more worries for future dementia/stroke than SA respondents (p = 0.006) but still shared SA respondents’ lower wish (measured by proportion of total) to learn of incidental MRI findings. DISCUSSION SA—and EA compared to SA—older adults had low desire to learn of incidental MRI findings but had different attitudes toward future dementia/stroke risks. A culturally appropriate protocol to disclose incidental MRI findings may improve SA and EA participation in brain health research. Highlights Older Asian Americans have limited interest in incidental findings on research MRI South Asians are most likely to attribute dementia to people's own behaviors South Asians’ attitudes mediate lower support for healthy volunteers in research South and East Asians differ in dementia worries and research‐related attitudes