The FIELDS Instrument Suite for Solar Probe Plus: Measuring the Coronal Plasma and Magnetic Field, Plasma Waves and Turbulence, and Radio Signatures of Solar Transients.

NASA's Solar Probe Plus (SPP) mission will make the first in situ measurements of the solar corona and the birthplace of the solar wind. The FIELDS instrument suite on SPP will make direct measurements of electric and magnetic fields, the properties of in situ plasma waves, electron density and temperature profiles, and interplanetary radio emissions, amongst other things. Here, we describe the scientific objectives targeted by the SPP/FIELDS instrument, the instrument design itself, and the instrument concept of operations and planned data products

Combination immunotherapy and active-specific tumor cell vaccination augments anti-cancer immunity in a mouse model of gastric cancer

<p>Abstract</p> <p>Background</p> <p>Active-specific immunotherapy used as an adjuvant therapeutic strategy is rather unexplored for cancers with poorly characterized tumor antigens like gastric cancer. The aim of this study was to augment a therapeutic immune response to a low immunogenic tumor cell line derived from a spontaneous gastric tumor of a CEA424-SV40 large T antigen (CEA424-SV40 TAg) transgenic mouse.</p> <p>Methods</p> <p>Mice were treated with a lymphodepleting dose of cyclophosphamide prior to reconstitution with syngeneic spleen cells and vaccination with a whole tumor cell vaccine combined with GM-CSF (a treatment strategy abbreviated as LRAST). Anti-tumor activity to subcutaneous tumor challenge was examined in a prophylactic as well as a therapeutic setting and compared to corresponding controls.</p> <p>Results</p> <p>LRAST enhances tumor-specific T cell responses and efficiently inhibits growth of subsequent transplanted tumor cells. In addition, LRAST tended to slow down growth of established tumors. The improved anti-tumor immune response was accompanied by a transient decrease in the frequency and absolute number of CD4⁺CD25⁺FoxP3⁺T cells (Tregs).</p> <p>Conclusions</p> <p>Our data support the concept that whole tumor cell vaccination in a lymphodepleted and reconstituted host in combination with GM-CSF induces therapeutic tumor-specific T cells. However, the long-term efficacy of the treatment may be dampened by the recurrence of Tregs. Strategies to counteract suppressive immune mechanisms are required to further evaluate this therapeutic vaccination protocol.</p

Highly structured slow solar wind emerging from an equatorial coronal hole

International audienceDuring the solar minimum, when the Sun is at its least active, the solar wind(1,2) is observed at high latitudes as a predominantly fast (more than 500 kilometres per second), highly Alfvenic rarefied stream of plasma originating from deep within coronal holes. Closer to the ecliptic plane, the solar wind is interspersed with a more variable slow wind(3) of less than 500 kilometres per second. The precise origins of the slow wind streams are less certain(4); theories and observations suggest that they may originate at the tips of helmet streamers(5,6), from interchange reconnection near coronal hole boundaries(7,8), or within coronal holes with highly diverging magnetic fields(9,10). The heating mechanism required to drive the solar wind is also unresolved, although candidate mechanisms include Alfven-wave turbulence(11,12), heating by reconnection in nanoflares(13), ion cyclotron wave heating(14) and acceleration by thermal gradients1. At a distance of one astronomical unit, the wind is mixed and evolved, and therefore much of the diagnostic structure of these sources and processes has been lost. Here we present observations from the Parker Solar Probe(15) at 36 to 54 solar radii that show evidence of slow Alfvenic solar wind emerging from a small equatorial coronal hole. The measured magnetic field exhibits patches of large, intermittent reversals that are associated with jets of plasma and enhanced Poynting flux and that are interspersed in a smoother and less turbulent flow with a near-radial magnetic field. Furthermore, plasma-wave measurements suggest the existence of electron and ion velocity-space micro-instabilities(10,16) that are associated with plasma heating and thermalization processes. Our measurements suggest that there is an impulsive mechanism associated with solar-wind energization and that micro-instabilities play a part in heating, and we provide evidence that low-latitude coronal holes are a key source of the slow solar wind

Is exercise a therapeutic tool for improvement of cardiovascular risk factors in adolescents with type 1 diabetes mellitus? A randomised controlled trial

<p>Abstract</p> <p>Background</p> <p>Type 1 diabetes mellitus (T1DM) is associated with a high risk for early atherosclerotic complications especially risk of coronary heart disease.</p> <p>Objective</p> <p>To evaluate the impact of six months exercise prgram on glycemic control, plasma lipids values, blood pressure, severity and frequency of hypoglycemia, anthropometric measurements and insulin dose in a sample of adolescents with T1DM.</p> <p>Research design and methods</p> <p>A total of 196 type 1 diabetic patients participated in the study. They were classified into three groups: Group (A) did not join the exercise program(n = 48), group (B) attended the exercise sessions once/week (n = 75), group (C) attended the exercise sessions three times/week (n = 73). Studied parameters were evaluated before and six months after exercise programe.</p> <p>Results</p> <p>Exercise improved glycemic control by reducing HbA1c values in exercise groups (P = 0.03, P = 0.01 respectively) and no change in those who were not physically active (P = 0.2). Higher levels of HbA1c were associated with higher levels of cholesterol, LDL-c, and triglycerides (P = 0.000 each). In both groups, B and C, frequent exercise improved dyslipidemia and reduced insulin requirements significantly (P = 0.00 both), as well as a reduction in BMI (P = 0.05, P = 0.00 respectively) and waist circumference(P = 0.02, P = 0.00 respectively). The frequency of hypoglycemic attacks were not statistically different between the control group and both intervention groups (4.7 ± 3.56 and 4.82 ± 4.23, P = 0.888 respectively). Reduction of blood pressure was statistically insignificant apart from the diastolic blood presure in group C (P = 0.04).</p> <p>Conclusion</p> <p>Exercise is an indispensable component in the medical treatment of patients with T1DM as it improves glycemic control and decreases cardiovascular risk factors among them.</p

Docosahexaenoic Acid-Derived Neuroprotectin D1 Induces Neuronal Survival via Secretase- and PPARγ-Mediated Mechanisms in Alzheimer's Disease Models

Neuroprotectin D1 (NPD1) is a stereoselective mediator derived from the omega-3 essential fatty acid docosahexaenoic acid (DHA) with potent inflammatory resolving and neuroprotective bioactivity. NPD1 reduces Aβ42 peptide release from aging human brain cells and is severely depleted in Alzheimer's disease (AD) brain. Here we further characterize the mechanism of NPD1's neurogenic actions using 3xTg-AD mouse models and human neuronal-glial (HNG) cells in primary culture, either challenged with Aβ42 oligomeric peptide, or transfected with beta amyloid precursor protein (βAPP)sw (Swedish double mutation APP695sw, K595N-M596L). We also show that NPD1 downregulates Aβ42-triggered expression of the pro-inflammatory enzyme cyclooxygenase-2 (COX-2) and of B-94 (a TNF-α-inducible pro-inflammatory element) and apoptosis in HNG cells. Moreover, NPD1 suppresses Aβ42 peptide shedding by down-regulating β-secretase-1 (BACE1) while activating the α-secretase ADAM10 and up-regulating sAPPα, thus shifting the cleavage of βAPP holoenzyme from an amyloidogenic into the non-amyloidogenic pathway. Use of the thiazolidinedione peroxisome proliferator-activated receptor gamma (PPARγ) agonist rosiglitazone, the irreversible PPARγ antagonist GW9662, and overexpressing PPARγ suggests that the NPD1-mediated down-regulation of BACE1 and Aβ42 peptide release is PPARγ-dependent. In conclusion, NPD1 bioactivity potently down regulates inflammatory signaling, amyloidogenic APP cleavage and apoptosis, underscoring the potential of this lipid mediator to rescue human brain cells in early stages of neurodegenerations

Nuclear versus mitochondrial DNA: evidence for hybridization in colobine monkeys

<p>Abstract</p> <p>Background</p> <p>Colobine monkeys constitute a diverse group of primates with major radiations in Africa and Asia. However, phylogenetic relationships among genera are under debate, and recent molecular studies with incomplete taxon-sampling revealed discordant gene trees. To solve the evolutionary history of colobine genera and to determine causes for possible gene tree incongruences, we combined presence/absence analysis of mobile elements with autosomal, X chromosomal, Y chromosomal and mitochondrial sequence data from all recognized colobine genera.</p> <p>Results</p> <p>Gene tree topologies and divergence age estimates derived from different markers were similar, but differed in placing <it>Piliocolobus/Procolobus </it>and langur genera among colobines. Although insufficient data, homoplasy and incomplete lineage sorting might all have contributed to the discordance among gene trees, hybridization is favored as the main cause of the observed discordance. We propose that African colobines are paraphyletic, but might later have experienced female introgression from <it>Piliocolobus</it>/<it>Procolobus </it>into <it>Colobus</it>. In the late Miocene, colobines invaded Eurasia and diversified into several lineages. Among Asian colobines, <it>Semnopithecus </it>diverged first, indicating langur paraphyly. However, unidirectional gene flow from <it>Semnopithecus </it>into <it>Trachypithecus </it>via male introgression followed by nuclear swamping might have occurred until the earliest Pleistocene.</p> <p>Conclusions</p> <p>Overall, our study provides the most comprehensive view on colobine evolution to date and emphasizes that analyses of various molecular markers, such as mobile elements and sequence data from multiple loci, are crucial to better understand evolutionary relationships and to trace hybridization events. Our results also suggest that sex-specific dispersal patterns, promoted by a respective social organization of the species involved, can result in different hybridization scenarios.</p

Defining the critical hurdles in cancer immunotherapy

Scientific discoveries that provide strong evidence of antitumor effects in preclinical models often encounter significant delays before being tested in patients with cancer. While some of these delays have a scientific basis, others do not. We need to do better. Innovative strategies need to move into early stage clinical trials as quickly as it is safe, and if successful, these therapies should efficiently obtain regulatory approval and widespread clinical application. In late 2009 and 2010 the Society for Immunotherapy of Cancer (SITC), convened an "Immunotherapy Summit" with representatives from immunotherapy organizations representing Europe, Japan, China and North America to discuss collaborations to improve development and delivery of cancer immunotherapy. One of the concepts raised by SITC and defined as critical by all parties was the need to identify hurdles that impede effective translation of cancer immunotherapy. With consensus on these hurdles, international working groups could be developed to make recommendations vetted by the participating organizations. These recommendations could then be considered by regulatory bodies, governmental and private funding agencies, pharmaceutical companies and academic institutions to facilitate changes necessary to accelerate clinical translation of novel immune-based cancer therapies. The critical hurdles identified by representatives of the collaborating organizations, now organized as the World Immunotherapy Council, are presented and discussed in this report. Some of the identified hurdles impede all investigators; others hinder investigators only in certain regions or institutions or are more relevant to specific types of immunotherapy or first-in-humans studies. Each of these hurdles can significantly delay clinical translation of promising advances in immunotherapy yet if overcome, have the potential to improve outcomes of patients with cancer