Yang-Mills instantons and dyons on homogeneous G_2-manifolds

We consider Lie G-valued Yang-Mills fields on the space R x G/H, where G/H is a compact nearly K"ahler six-dimensional homogeneous space, and the manifold R x G/H carries a G_2-structure. After imposing a general G-invariance condition, Yang-Mills theory with torsion on R x G/H is reduced to Newtonian mechanics of a particle moving in R^6, R^4 or R^2 under the influence of an inverted double-well-type potential for the cases G/H = SU(3)/U(1)xU(1), Sp(2)/Sp(1)xU(1) or G_2/SU(3), respectively. We analyze all critical points and present analytical and numerical kink- and bounce-type solutions, which yield G-invariant instanton configurations on those cosets. Periodic solutions on S^1 x G/H and dyons on iR x G/H are also given.Comment: 1+26 pages, 14 figures, 6 miniplot

Strings and branes are waves

We examine the equations of motion of double field theory and the duality manifest form of M-theory. We show the solutions of the equations of motion corresponding to null pp-waves correspond to strings or membranes from the usual spacetime perspective. A Goldstone mode analysis of the null wave solution in double field theory produces the equations of motion of the duality manifest string.Comment: 31 pages, LaTex, v2 some typos corrected and refs adde

In vivo regulation of interleukin 1β in patients with cryopyrin-associated periodic syndromes

The investigation of interleukin 1β (IL-1β) in human inflammatory diseases is hampered by the fact that it is virtually undetectable in human plasma. We demonstrate that by administering the anti–human IL-1β antibody canakinumab (ACZ885) to humans, the resulting formation of IL-1β–antibody complexes allowed the detection of in vivo–produced IL-1β. A two-compartment mathematical model was generated that predicted a constitutive production rate of 6 ng/d IL-1β in healthy subjects. In contrast, patients with cryopyrin-associated periodic syndromes (CAPS), a rare monogenetic disease driven by uncontrolled caspase-1 activity and IL-1 production, produced a mean of 31 ng/d. Treatment with canakinumab not only induced long-lasting complete clinical response but also reduced the production rate of IL-1β to normal levels within 8 wk of treatment, suggesting that IL-1β production in these patients was mainly IL-1β driven. The model further indicated that IL-1β is the only cytokine driving disease severity and duration of response to canakinumab. A correction for natural IL-1 antagonists was not required to fit the data. Together, the study allowed new insights into the production and regulation of IL-1β in man. It also indicated that CAPS is entirely mediated by IL-1β and that canakinumab treatment restores physiological IL-1β production

TLR expression profiles are a function of disease status in rheumatoid arthritis and experimental arthritis

The role of the innate immune system has been established in the initiation and perpetuation of inflammatory disease, but less attention has been paid to its role in the resolution of inflammation and return to homeostasis. Toll-like receptor (TLR) expression profiles were analysed in tissues with differing disease status in rheumatoid arthritis (RA), ankylosing spondylitis (AS), and in experimental arthritis. TLR gene expression was measured in whole blood and monocytes, before and after TNF blockade. In RA and osteoarthritis synovia, the expression of TLRs was quantified by standard curve qPCR. In addition, four distinct stages of disease were defined and validated in collagen-induced arthritis (CIA), the gold standard animal model for RA - pre-onset, early disease, late disease and immunised mice that were resistant to the development of disease. TLR expression was measured in spleens, lymph nodes, blood cells, liver and the paws (inflamed and unaffected). In RA whole blood, the expression of TLR1, 4 and 6 was significantly reduced by TNF blockade but the differences in TLR expression profiles between responders and non-responders were less pronounced than the differences between RA and AS patients. In RA non-responders, monocytes had greater TLR2 expression prior to therapy compared to responders. The expression of TLR1, 2, 4 and 8 was higher in RA synovium compared to control OA synovium. Circulating cytokine levels in CIA resistant mice were similar to naïve mice, but anti-collagen antibodies were similar to arthritic mice. Distinct profiles of inflammatory gene expression were mapped in paws and organs with differing disease status. TLR expression in arthritic paws tended to be similar in early and late disease, with TLR1 and 2 moderately higher in late disease. TLR expression in unaffected paws varied according to gene and disease status but was generally lower in resistant paws. Disease status-specific profiles of TLR expression were observed in spleens, lymph nodes, blood cells and the liver. Notably, TLR2 expression rose then fell in the transition from naïve to pre-onset to early arthritis. TLR gene expression profiles are strongly associated with disease status. In particular, increased expression in the blood precedes clinical manifestation

An action for F-theory: SL(2)R+ exceptional field theory

DSB is supported by the STFC grant ST/L000415/1 'String Theory, Gauge Theory and Duality'. CB is supported in part by the Belgian Federal Science Policy Office through the Interuniversity Attraction Pole P7/37 'Fundamental Interactions', and in part by the 'FWO-Vlaanderen' through the project G.0207.14N and by the Vrije Universiteit Brussel through the Strategic Research Program 'High-Energy Physics'. EM is supported by the ERC Advanced Grant "Strings and Gravity' (Grant No. 32004). FJR is supported by an STFC studentship

The JCMT BISTRO Survey: Studying the Complex Magnetic Field of L43

We present observations of polarized dust emission at 850 μm from the L43 molecular cloud, which sits in the Ophiuchus cloud complex. The data were taken using SCUBA-2/POL-2 on the James Clerk Maxwell Telescope as a part of the BISTRO large program. L43 is a dense (NH 10 22 2 ~ –1023 cm−2) complex molecular cloud with a submillimeter-bright starless core and two protostellar sources. There appears to be an evolutionary gradient along the isolated filament that L43 is embedded within, with the most evolved source closest to the Sco OB2 association. One of the protostars drives a CO outflow that has created a cavity to the southeast. We see a magnetic field that appears to be aligned with the cavity walls of the outflow, suggesting interaction with the outflow. We also find a magnetic field strength of up to ∼160 ± 30 μG in the main starless core and up to ∼90 ± 40 μG in the more diffuse, extended region. These field strengths give magnetically super- and subcritical values, respectively, and both are found to be roughly trans-Alfvénic. We also present a new method of data reduction for these denser but fainter objects like starless cores

Case Reports1. A Late Presentation of Loeys-Dietz Syndrome: Beware of TGFβ Receptor Mutations in Benign Joint Hypermobility

Background: Thoracic aortic aneurysms (TAA) and dissections are not uncommon causes of sudden death in young adults. Loeys-Dietz syndrome (LDS) is a rare, recently described, autosomal dominant, connective tissue disease characterized by aggressive arterial aneurysms, resulting from mutations in the transforming growth factor beta (TGFβ) receptor genes TGFBR1 and TGFBR2. Mean age at death is 26.1 years, most often due to aortic dissection. We report an unusually late presentation of LDS, diagnosed following elective surgery in a female with a long history of joint hypermobility. Methods: A 51-year-old Caucasian lady complained of chest pain and headache following a dural leak from spinal anaesthesia for an elective ankle arthroscopy. CT scan and echocardiography demonstrated a dilated aortic root and significant aortic regurgitation. MRA demonstrated aortic tortuosity, an infrarenal aortic aneurysm and aneurysms in the left renal and right internal mammary arteries. She underwent aortic root repair and aortic valve replacement. She had a background of long-standing joint pains secondary to hypermobility, easy bruising, unusual fracture susceptibility and mild bronchiectasis. She had one healthy child age 32, after which she suffered a uterine prolapse. Examination revealed mild Marfanoid features. Uvula, skin and ophthalmological examination was normal. Results: Fibrillin-1 testing for Marfan syndrome (MFS) was negative. Detection of a c.1270G > C (p.Gly424Arg) TGFBR2 mutation confirmed the diagnosis of LDS. Losartan was started for vascular protection. Conclusions: LDS is a severe inherited vasculopathy that usually presents in childhood. It is characterized by aortic root dilatation and ascending aneurysms. There is a higher risk of aortic dissection compared with MFS. Clinical features overlap with MFS and Ehlers Danlos syndrome Type IV, but differentiating dysmorphogenic features include ocular hypertelorism, bifid uvula and cleft palate. Echocardiography and MRA or CT scanning from head to pelvis is recommended to establish the extent of vascular involvement. Management involves early surgical intervention, including early valve-sparing aortic root replacement, genetic counselling and close monitoring in pregnancy. Despite being caused by loss of function mutations in either TGFβ receptor, paradoxical activation of TGFβ signalling is seen, suggesting that TGFβ antagonism may confer disease modifying effects similar to those observed in MFS. TGFβ antagonism can be achieved with angiotensin antagonists, such as Losartan, which is able to delay aortic aneurysm development in preclinical models and in patients with MFS. Our case emphasizes the importance of timely recognition of vasculopathy syndromes in patients with hypermobility and the need for early surgical intervention. It also highlights their heterogeneity and the potential for late presentation. Disclosures: The authors have declared no conflicts of interes

Integrative genomic analysis by interoperation of bioinformatics tools in GenomeSpace

Integrative analysis of multiple data types to address complex biomedical questions requires the use of multiple software tools in concert and remains an enormous challenge for most of the biomedical research community. Here we introduce GenomeSpace (http://www.genomespace.org), a cloud-based, cooperative community resource. Seeded as a collaboration of six of the most popular genomics analysis tools, GenomeSpace now supports the streamlined interaction of 20 bioinformatics tools and data resources. To facilitate the ability of non-programming users’ to leverage GenomeSpace in integrative analysis, it offers a growing set of ‘recipes’, short workflows involving a few tools and steps to guide investigators through high utility analysis tasks