Response of a ferrofluid to traveling-stripe forcing

We observe the dynamics of waves propagating on the surface of a ferrofluid under the influence of a spatially and temporarily modulated field. In particular, we excite plane waves by a travelling lamellar modulation of the magnetization. By this external driving both the wavelength and the propagation velocity of the waves can be controlled. The amplitude of the excited waves exhibits a resonance phenomenon similar to that of a forced harmonic oscillator. Its analysis reveals the dispersion relation of the free surface waves, from which the critical magnetic field for the onset of the Rosensweig instability can be extrapolated

Bi-allelic JAM2 Variants Lead to Early-Onset Recessive Primary Familial Brain Calcification.

Primary familial brain calcification (PFBC) is a rare neurodegenerative disorder characterized by a combination of neurological, psychiatric, and cognitive decline associated with calcium deposition on brain imaging. To date, mutations in five genes have been linked to PFBC. However, more than 50% of individuals affected by PFBC have no molecular diagnosis. We report four unrelated families presenting with initial learning difficulties and seizures and later psychiatric symptoms, cerebellar ataxia, extrapyramidal signs, and extensive calcifications on brain imaging. Through a combination of homozygosity mapping and exome sequencing, we mapped this phenotype to chromosome 21q21.3 and identified bi-allelic variants in JAM2. JAM2 encodes for the junctional-adhesion-molecule-2, a key tight-junction protein in blood-brain-barrier permeability. We show that JAM2 variants lead to reduction of JAM2 mRNA expression and absence of JAM2 protein in patient's fibroblasts, consistent with a loss-of-function mechanism. We show that the human phenotype is replicated in the jam2 complete knockout mouse (jam2 KO). Furthermore, neuropathology of jam2 KO mouse showed prominent vacuolation in the cerebral cortex, thalamus, and cerebellum and particularly widespread vacuolation in the midbrain with reactive astrogliosis and neuronal density reduction. The regions of the human brain affected on neuroimaging are similar to the affected brain areas in the myorg PFBC null mouse. Along with JAM3 and OCLN, JAM2 is the third tight-junction gene in which bi-allelic variants are associated with brain calcification, suggesting that defective cell-to-cell adhesion and dysfunction of the movement of solutes through the paracellular spaces in the neurovascular unit is a key mechanism in CNS calcification

ADAMTS19-associated heart valve defects: Novel genetic variants consolidating a recognizable cardiac phenotype

Recently, ADAMTS19 was identified as a novel causative gene for autosomal recessive heart valve disease (HVD), affecting mainly the aortic and pulmonary valves. Exome sequencing and data repository (CentoMD) analyses were performed to identify patients with ADAMTS19 variants (two families). A third family was recognized based on cardiac phenotypic similarities and SNP array homozygosity. Three novel loss of function (LoF) variants were identified in six patients from three families. Clinically, all patients presented anomalies of the aortic/pulmonary valves, which included thickening of valve leaflets, stenosis and insufficiency. Three patients had (recurrent) subaortic membrane, suggesting that ADAMTS19 is the first gene identified related to discrete subaortic stenosis. One case presented a bi-commissural pulmonary valve. All patients displayed some degree of atrioventricular valve insufficiency. Other cardiac anomalies included atrial/ventricular septal defects, persistent ductus arteriosus, and mild dilated ascending aorta. Our findings confirm that biallelic LoF variants in ADAMTS19 are causative of a specific and recognizable cardiac phenotype. We recommend considering ADAMTS19 genetic testing in all patients with multiple semilunar valve abnormalities, particularly in the presence of subaortic membrane. ADAMTS19 screening in patients with semilunar valve abnormalities is needed to estimate the frequency of the HVD related phenotype, which might be not so rare

Performance of the CMS Cathode Strip Chambers with Cosmic Rays

The Cathode Strip Chambers (CSCs) constitute the primary muon tracking device in the CMS endcaps. Their performance has been evaluated using data taken during a cosmic ray run in fall 2008. Measured noise levels are low, with the number of noisy channels well below 1%. Coordinate resolution was measured for all types of chambers, and fall in the range 47 microns to 243 microns. The efficiencies for local charged track triggers, for hit and for segments reconstruction were measured, and are above 99%. The timing resolution per layer is approximately 5 ns

The Detection of Magnetic Fields Toward M17 through the HI Zeeman Effect

We have carried out VLA Zeeman observations of HI absorption lines toward the HII region in the M17 giant molecular cloud complex. The HI absorption lines toward M17 show between 5 and 8 distinct velocity components which vary spatially in a complex manner across the source. We explore possible physical connections between these components and the M17 region based on calculations of HI column densities, line of sight magnetic field strengths, as well as comparisons with a wide array of previous optical, infrared, and radio observations. In particular, an HI component at the same velocity as the southwestern molecular cloud (M17 SW) ~20 km/s seems to originate from the edge-on interface between the HII region and M17 SW, in un-shocked PDR gas. We have detected a steep enhancement in the 20 km/s HI column density and line of sight magnetic field strengths (Blos) toward this boundary. A lower limit for the peak 20 km/s HI column density is N_{HI}/T_s > 5.6 x 10^{19} cm^{-2}/K while the peak Blos is ~ -450 muG. In addition, blended components at velocities of 11-17 km/s appear to originate from shocked gas in the PDR between the HII region and an extension of M17 SW, which partially obscures the southern bar of the HII region. The peak N_{HI}/T_s and Blos for this component are > 4.4 x 10^{19} cm^{-2}/K and +550 muG, respectively. Comparison of the peak magnetic fields detected toward M17 with virial equilibrium calculations suggest that ~1/3 of M17 SW's total support comes from its static magnetic field and the other 2/3 from its turbulent kinetic energy which includes support from Alfven waves.Comment: Contains 29 pages, 14 figures (Latex). Text and figures can be downloaded separately at http://www.pa.uky.edu/~brogan, submitted to Ap

Mutational spectrum of the SPG4 (SPAST) and SPG3A (ATL1) genes in Spanish patients with hereditary spastic paraplegia

<p>Abstract</p> <p>Background</p> <p>Hereditary Spastic Paraplegias (HSP) are characterized by progressive spasticity and weakness of the lower limbs. At least 45 loci have been identified in families with autosomal dominant (AD), autosomal recessive (AR), or X-linked hereditary patterns. Mutations in the <it>SPAST </it>(<it>SPG4</it>) and <it>ATL1 </it>(<it>SPG3A</it>) genes would account for about 50% of the ADHSP cases.</p> <p>Methods</p> <p>We defined the <it>SPAST </it>and <it>ATL1 </it>mutational spectrum in a total of 370 unrelated HSP index cases from Spain (83% with a pure phenotype).</p> <p>Results</p> <p>We found 50 <it>SPAST </it>mutations (including two large deletions) in 54 patients and 7 <it>ATL1 </it>mutations in 11 patients. A total of 33 of the <it>SPAST </it>and 3 of the <it>ATL1 </it>were new mutations. A total of 141 (31%) were familial cases, and we found a higher frequency of mutation carriers among these compared to apparently sporadic cases (38% vs. 5%). Five of the <it>SPAST </it>mutations were predicted to affect the pre-mRNA splicing, and in 4 of them we demonstrated this effect at the cDNA level. In addition to large deletions, splicing, frameshifting, and missense mutations, we also found a nucleotide change in the stop codon that would result in a larger ORF.</p> <p>Conclusions</p> <p>In a large cohort of Spanish patients with spastic paraplegia, <it>SPAST </it>and <it>ATL1 </it>mutations were found in 15% of the cases. These mutations were more frequent in familial cases (compared to sporadic), and were associated with heterogeneous clinical manifestations.</p

Infliximab Induces Clonal Expansion of γδ-T Cells in Crohn's Disease: A Predictor of Lymphoma Risk?

BACKGROUND: Concominant with the widespread use of combined immunotherapy in the management of Crohn's disease (CD), the incidence of hepato-splenic gamma-delta (γδ)-T cell lymphoma has increased sharply in CD patients. Malignant transformation of lymphocytes is believed to be a multistep process resulting in the selection of malignant γδ-T cell clones. We hypothesised that repeated infusion of anti-TNF-α agents may induce clonal selection and that concurrent treatment with immunomodulators further predisposes patients to γδ-T cell expansion. METHODOLOGY/PRINCIPAL FINDINGS: We investigated dynamic changes in the γδ-T cells of patient with CD following treatment with infliximab (Remicade®; n=20) or adalimumab (Humira®; n=26) using flow cytometry. In patients with a high γδ-T cell level, the γδ-T cells were assessed for clonality. Of these 46 CD patients, 35 had a γδ-T cells level (mean 1.6%) comparable to healthy individuals (mean 2.2%), and 11 CD patients (24%) exhibited an increased level of γδ-T cells (5-15%). In the 18 patients also receiving thiopurines or methotrexate, the average baseline γδ-T cell level was 4.4%. In three male CD patients with a high baseline value, the γδ-T cell population increased dramatically following infliximab therapy. A fourth male patient also on infliximab monotherapy presented with 20% γδ-T cells, which increased to 25% shortly after treatment and was 36% between infusions. Clonality studies revealed an oligoclonal γδ-T cell pattern with dominant γδ-T cell clones. In support of our clinical findings, in vitro experiments showed a dose-dependent proliferative effect of anti-TNF-α agents on γδ-T cells. CONCLUSION/SIGNIFICANCE: CD patients treated with immunomodulators had constitutively high levels of γδ-T cells. Infliximab exacerbated clonal γδ-T cell expansion in vivo and induced γδ-T cell proliferation in vitro. Overall, young, male CD patients with high baseline γδ-T cell levels may be at an increased risk of developing malignant γδ-T cell lymphomas following treatment with anti-TNF-α agents

Performance and Operation of the CMS Electromagnetic Calorimeter

The operation and general performance of the CMS electromagnetic calorimeter using cosmic-ray muons are described. These muons were recorded after the closure of the CMS detector in late 2008. The calorimeter is made of lead tungstate crystals and the overall status of the 75848 channels corresponding to the barrel and endcap detectors is reported. The stability of crucial operational parameters, such as high voltage, temperature and electronic noise, is summarised and the performance of the light monitoring system is presented

Truth after post-truth: for a Strong Programme in Discourse Studies

Contemporary post-truth discourses put the constructivist foundations of Discourse Studies to a test. According to critical observers, discourse analysts have been playing into the hands of Trump, Brexit and right-wing populists by politicising scientific knowledge and undermining the idea of scientific truth. In order to respond to these concerns, this article outlines a Strong Programme in Discourse Studies. While the Strong Programme insists on truths as discursive constructions, in no way does it claim that all ideas have the same truth value or that an idea can become true because somebody wants it to be true. The Strong Programme makes the case for discourse research that is constructivist (it asks how truths are constructed practically) without being relativist (all ideas do not have the same normative quality). Taking inspiration from debates in Science and Technology Studies of the 1970s, the Strong Programme formulates principles for discourse researchers dealing with conflicting truth claims. Discourse analytical explanations of truths of first-order participants and of second-order observers should be symmetrical, heterogeneous, multi-perspectival and reflexive. The Strong Programme discourse research is grounded in the founding traditions of ?French? and ?Critical? Discourse Studies, which have struggled over questions of truth and reality since the beginning. While critically interrogating the structuralist heritage of these strands, the Strong Programme insists on the practices of making and unmaking ideas through language use no matter whether they appear as true or false to participants and observers. Discourse Studies are encouraged to critically reflect on how hierarchies between knowledges are not only represented but, through their representation, also constituted through discursive practices