Anti-CD20 therapy depletes activated myelin-specific CD8+ T cells in multiple sclerosis.

CD8+ T cells are believed to play an important role in multiple sclerosis (MS), yet their role in MS pathogenesis remains poorly defined. Although myelin proteins are considered potential autoantigenic targets, prior studies of myelin-reactive CD8+ T cells in MS have relied on in vitro stimulation, thereby limiting accurate measurement of their ex vivo precursor frequencies and phenotypes. Peptide:MHC I tetramers were used to identify and validate 5 myelin CD8+ T cell epitopes, including 2 newly described determinants in humans. The validated tetramers were used to measure the ex vivo precursor frequencies and phenotypes of myelin-specific CD8+ T cells in the peripheral blood of untreated MS patients and HLA allele-matched healthy controls. In parallel, CD8+ T cell responses against immunodominant influenza epitopes were also measured. There were no differences in ex vivo frequencies of tetramer-positive myelin-specific CD8+ T cells between MS patients and control subjects. An increased proportion of myelin-specific CD8+ T cells in MS patients exhibited a memory phenotype and expressed CD20 compared to control subjects, while there were no phenotypic differences observed among influenza-specific CD8+ T cells. Longitudinal assessments were also measured in a subset of MS patients subsequently treated with anti-CD20 monoclonal antibody therapy. The proportion of memory and CD20+ CD8+ T cells specific for certain myelin but not influenza epitopes was significantly reduced following anti-CD20 treatment. This study, representing a characterization of unmanipulated myelin-reactive CD8+ T cells in MS, indicates these cells may be attractive targets in MS therapy

Dark matter effective field theory scattering in direct detection experiments

Artículo escrito por un elevado número de autores, solo se referencian el que aparece en primer lugar, el nombre del grupo de colaboración, si le hubiere, y los autores pertenecientes a la UAMWe examine the consequences of the effective field theory (EFT) of dark matter-nucleon scattering for current and proposed direct detection experiments. Exclusion limits on EFT coupling constants computed using the optimum interval method are presented for SuperCDMS Soudan, CDMS II, and LUX, and the necessity of combining results from multiple experiments in order to determine dark matter parameters is discussed. We demonstrate that spectral differences between the standard dark matter model and a general EFT interaction can produce a bias when calculating exclusion limits and when developing signal models for likelihood and machine learning techniques. We also discuss the implications of the EFT for the next-generation (G2) direct detection experiments and point out regions of complementarity in the EFT parameter spaceThe authors gratefully acknowledge Liam Fitzpatrick, Wick Haxton, and Tim Tait for helpful conversations. This work is supported in part by the National Science Foundation, by the United States Department of Energy, by NSERC Canada, and by MultiDark (Spanish MINECO). Fermilab is operated by the Fermi Research Alliance, LLC under Contract No. De-AC02-07CH11359. SLAC is operated under Contract No. DE-AC02- 76SF00515 with the United States Department of Energ

Reducing the positional modulation of NbO6-octahedra in SrxBa1-xNb2O6 by increasing the Barium content: A single crystal neutron diffraction study at ambient temperature for x=0.61 and x=0.34

We report on the influence of the Barium content on the modulation amplitude in SrxBa1-xNb2O6 compounds by comparing Sr0.61Ba0.39Nb2O6 (SBN61) and Sr0.34Ba0.66Nb2O6 (SBN34). Our single crystal neutron diffraction results demonstrate that the amplitude of the positional modulation of the NbO6 octahedra is reduced with increasing barium content, indicating that the origin of the modulation is the partial occupation of the pentagonal channels by Sr and Ba atoms. By increasing the Sr content the bigger Ba atoms are replaced by the smaller Sr atoms, which leads to a larger deformation of the surrounding lattice and hence to a larger modulation amplitude. The more homogeneous the filling of these channels with one atomic type (Ba) the lower the modulation amplitude. Our results also show that the structure can be described with a two-dimensional incommensurate harmonic modulation. No second order modulation has been observed, both by single crystal diffraction measurements and q-scans. The positional modulation of the Nb atoms is much smaller than that of the oxygen atoms, such that the modulation can be seen as a rotational modulation of almost rigid NbO6-octahedra

Sampling effort and information quality provided by rare and common species in estimating assemblage structure

Reliable biological assessments are essential to answer ecological and management questions but require well-designed studies and representative sample sizes. However, large sampling effort is rarely possible, because it demands large financial resources and time, restricting the number of sites sampled, the duration of the study and the sampling effort at each site. In this context, we need methods and protocols allowing cost-effective surveys that would, consequently, increase the knowledge about how biodiversity is distributed in space and time. Here, we assessed the minimal sampling effort required to correctly estimate the assemblage structure of stream insects sampled in near-pristine boreal and subtropical regions. We used five methods grouped into two different approaches. The first approach consisted of the removal of individuals 1) randomly or 2) based on a count threshold. The second approach consisted of simplification in terms of 1) sequential removal from rare to common species; 2) sequential removal from common to rare species; and 3) random species removal. The reliability of the methods was assessed using Procrustes analysis, which indicated the correlation between a reduced matrix (after removal of individuals or species) and the complete matrix. In many cases, we found a strong relationship between ordination patterns derived from presence/absence data (the extreme count threshold of a single individual) and those patterns derived from abundance data. Also, major multivariate patterns derived from the complete data matrices were retained even after the random removal of more than half of the individuals. Procrustes correlation was generally high ( > 0.8), even with the removal of 50% of the species. Removal of common species produced lower correlation than removal of rare species, indicating higher importance of the former to estimate resemblance between assemblages. Thus, we conclude that sampling designs can be optimized by reducing the sampling effort at a site. We recommend that such efforts saved should be redirected to increase the number of sites studied and the duration of the studies, which is essential to encompass larger spatial, temporal and environmental extents, and increase our knowledge of biodiversity.peerReviewe

Impact of forward bias injection on minority carrier transport in p-type ZnO nanowires

Minority carrier diffusion length in p-type Sb-doped ZnO nanowires was measured as a function of temperature and forward bias injection duration. The minority carrier diffusion length displays a thermally activated length increase with the energy of 144 +/- 5 meV. The forward bias injection exhibits an increase in diffusion length with the activation energy of 217 +/- 20 meV, indicating the possible involvement of a Sb(Zn)-2V(Zn) acceptor complex

T-Cell Memory Responses Elicited by Yellow Fever Vaccine are Targeted to Overlapping Epitopes Containing Multiple HLA-I and -II Binding Motifs

The yellow fever vaccines (YF-17D-204 and 17DD) are considered to be among the safest vaccines and the presence of neutralizing antibodies is correlated with protection, although other immune effector mechanisms are known to be involved. T-cell responses are known to play an important role modulating antibody production and the killing of infected cells. However, little is known about the repertoire of T-cell responses elicited by the YF-17DD vaccine in humans. In this report, a library of 653 partially overlapping 15-mer peptides covering the envelope (Env) and nonstructural (NS) proteins 1 to 5 of the vaccine was utilized to perform a comprehensive analysis of the virus-specific CD4+ and CD8+ T-cell responses. The T-cell responses were screened ex-vivo by IFN-γ ELISPOT assays using blood samples from 220 YF-17DD vaccinees collected two months to four years after immunization. Each peptide was tested in 75 to 208 separate individuals of the cohort. The screening identified sixteen immunodominant antigens that elicited activation of circulating memory T-cells in 10% to 33% of the individuals. Biochemical in-vitro binding assays and immunogenetic and immunogenicity studies indicated that each of the sixteen immunogenic 15-mer peptides contained two or more partially overlapping epitopes that could bind with high affinity to molecules of different HLAs. The prevalence of the immunogenicity of a peptide in the cohort was correlated with the diversity of HLA-II alleles that they could bind. These findings suggest that overlapping of HLA binding motifs within a peptide enhances its T-cell immunogenicity and the prevalence of the response in the population. In summary, the results suggests that in addition to factors of the innate immunity, "promiscuous" T-cell antigens might contribute to the high efficacy of the yellow fever vaccines. © 2013 de Melo et al

CDMSlite: A Search for Low-Mass WIMPs using Voltage-Assisted Calorimetric Ionization Detection in the SuperCDMS Experiment

SuperCDMS is an experiment designed to directly detect Weakly Interacting Massive Particles (WIMPs), a favored candidate for dark matter ubiquitous in the Universe. In this paper, we present WIMP-search results using a calorimetric technique we call CDMSlite, which relies on voltage- assisted Luke-Neganov amplification of the ionization energy deposited by particle interactions. The data were collected with a single 0.6 kg germanium detector running for 10 live days at the Soudan Underground Laboratory. A low energy threshold of 170 eVee (electron equivalent) was obtained, which allows us to constrain new WIMP-nucleon spin-independent parameter space for WIMP masses below 6 GeV/c2.Comment: 7 pages, 4 figure

The reliability of two visual motor integration tests used with children

Occupational therapists often assess the visual motor integration (VMI) skills of children and young people. It is important that therapists use tools with strong psychometric properties. This study aims to examine the reliability of 2 VMI tests. Ninety-two children between the ages of 5 and 17 years (response rate of 31%) completed 2 VMI tests: the Developmental Test of Visual Motor Integration (DTVMI) and the Full Range Test of Visual Motor Integration (FRTVMI). Cronbach\u27s alpha coefficient was used to examine the internal consistency of the 2 VMI tests whereas Spearman\u27s rho correlation was used to evaluate the test&ndash;retest reliability, intrarater reliability, and interrater reliability of the 2 VMI tests. The Cronbach\u27s alpha coefficient for the DTVMI was .82 and .72 for the FRTVMI. The test&ndash;retest reliability coefficient was .73 (p = .000) for the DTVMI and .49 (p = .05) for the FRTVMI. The interrater correlation was significant for both the DTVMI at .94 (p = .000) and FRTVMI at .68 (p = .001). The DTVMI intrarater reliability correlation result was .90 (p = .000) and the FRTVMI at .85 (p = .000). Overall, the DTVMI exhibited a higher level of reliability than the FRTVMI. Both VMI tests appear to exhibit reasonable levels of reliability and are recommended for use with children and young people.<br /

Critical behavior of certain antiferromagnets with complicated ordering: Four-loop \ve-expansion analysis

The critical behavior of a complex N-component order parameter Ginzburg-Landau model with isotropic and cubic interactions describing antiferromagnetic and structural phase transitions in certain crystals with complicated ordering is studied in the framework of the four-loop renormalization group (RG) approach in (4-\ve) dimensions. By using dimensional regularization and the minimal subtraction scheme, the perturbative expansions for RG functions are deduced and resummed by the Borel-Leroy transformation combined with a conformal mapping. Investigation of the global structure of RG flows for the physically significant cases N=2 and N=3 shows that the model has an anisotropic stable fixed point governing the continuous phase transitions with new critical exponents. This is supported by the estimate of the critical dimensionality $N_c=1.445(20)$ obtained from six loops via the exact relation $N_c={1/2} n_c$ established for the complex and real hypercubic models.Comment: LaTeX, 16 pages, no figures. Expands on cond-mat/0109338 and includes detailed formula