Multi-Channel SQUID System for MEG and Ultra-Low-Field MRI

A seven-channel system capable of performing both magnetoencephalography (MEG) and ultra-low-field magnetic resonance imaging (ULF MRI) is described. The system consists of seven second-order SQUID gradiometers with 37 mm diameter and 60 mm baseline, having magnetic field resolution of 1.2-2.8 fT/rtHz. It also includes four sets of coils for 2-D Fourier imaging with pre-polarization. The system's MEG performance was demonstrated by measurements of auditory evoked response. The system was also used to obtain a multi-channel 2-D image of a whole human hand at the measurement field of 46 microtesla with 3 by 3 mm resolution.Comment: To appear in Proceedings of 2006 Applied Superconductivity Conferenc

Forward model for the superconducting imaging-surface meg system

We have recently completed a novel whole-head MEG system based on the Superconducting Imaging-Surface (SIS) concept originally proposed by van Hulsteyn, et al.[l]. The SIS concept is generally described as a source near a superconducting surface. The source field induces Meissner currents in the superconductor equivalent to a source image 'behind' the surface. A sensor (SQUIDS in our system) placed on the source-side of the SIS will measure the superposed fields from the real and image sources. A second consequence of the Meissner effect is to shield the SQUIDS sensors near the SIS from external or background fields. The shape of the SIS used in our MEG system is a hemisphere with two cut-outs at the nominal ear-locations. A brim is added around the entire periphery with a smooth 0.5 cm radius transition between brim and hemisphere. Benefits of the SIS concept over existing systems include significantly enhanced signal-to-noise as a consequence of the SIS shielding and inherently generating pseudo-first order gradient fields at the sensors. One of the most significant challenges in realizing this system has been to accurately describe how the SIS system impacts the forward physics of any source model. Two approaches have been examined. The first is a hybrid analytical and empirical model using the analytic formalism to describe the hemisphere [1] and a correction matrix derived from empirical measurements to correct for edge effects. This approach proved overly complex and difficult in practice to obtain sufficient empirical data to derive a well-conditioned correction matrix. The second approach, reported here, was to develop a boundary element model (BEM) description of the SIS using the exact as-built geometry. Each element is described by a uniform magnetization arising from a distribution of Meissner currents in the superconductor such that B{perpendicular} = 0 at the surface. B{sub i} at each element is a superposition of the source field and the fields resulting from currents in all other elements. A precision phantom was developed to test the model. Modeled and measured magnetic field distributions agreed with typically less than 1% (< 0.1% in most cases) discrepancy at all SQUID sensors for more than 60 phantom coil positions. The attached figure shows modeled and measured magnetic field distributions for 25 such phantom coils

Weld quality evaluation using a high temperature SQUID array

This paper presents preliminary data for evaluating weld quality using high temperature SQUIDS. The SQUIDS are integrated into an instrument known as the SQUID Array Microscope, or SAMi. The array consists of ll SQUIDs evenly distributed over an 8.25 mm baseline. Welds are detected using SAMi by using an on board coil to induce eddy currents in a conducting sample and measuring the resulting magnetic fields. The concept is that the induced magnetic fields will differ in parts of varying weld quality. The data presented here was collected from three stainless steel parts using SAMi. Each part was either solid, included a good weld, or included a bad weld. The induced magnetic field's magnitude and phase relative to the induction signal were measured. For each sample considered, both the magnitude and phase data were measurably different than the other two samples. These results indicate that it is possible to use SAMi to evaluate weld quality

The genomes of two key bumblebee species with primitive eusocial organization

Background: The shift from solitary to social behavior is one of the major evolutionary transitions. Primitively eusocial bumblebees are uniquely placed to illuminate the evolution of highly eusocial insect societies. Bumblebees are also invaluable natural and agricultural pollinators, and there is widespread concern over recent population declines in some species. High-quality genomic data will inform key aspects of bumblebee biology, including susceptibility to implicated population viability threats. Results: We report the high quality draft genome sequences of Bombus terrestris and Bombus impatiens, two ecologically dominant bumblebees and widely utilized study species. Comparing these new genomes to those of the highly eusocial honeybee Apis mellifera and other Hymenoptera, we identify deeply conserved similarities, as well as novelties key to the biology of these organisms. Some honeybee genome features thought to underpin advanced eusociality are also present in bumblebees, indicating an earlier evolution in the bee lineage. Xenobiotic detoxification and immune genes are similarly depauperate in bumblebees and honeybees, and multiple categories of genes linked to social organization, including development and behavior, show high conservation. Key differences identified include a bias in bumblebee chemoreception towards gustation from olfaction, and striking differences in microRNAs, potentially responsible for gene regulation underlying social and other traits. Conclusions: These two bumblebee genomes provide a foundation for post-genomic research on these key pollinators and insect societies. Overall, gene repertoires suggest that the route to advanced eusociality in bees was mediated by many small changes in many genes and processes, and not by notable expansion or depauperation

Synaptic Reorganization in the Adult Rat's Ventral Cochlear Nucleus following Its Total Sensory Deafferentation

Ablation of a cochlea causes total sensory deafferentation of the cochlear nucleus in the brainstem, providing a model to investigate nervous degeneration and formation of new synaptic contacts in the adult brain. In a quantitative electron microscopical study on the plasticity of the central auditory system of the Wistar rat, we first determined what fraction of the total number of synaptic contact zones (SCZs) in the anteroventral cochlear nucleus (AVCN) is attributable to primary sensory innervation and how many synapses remain after total unilateral cochlear ablation. Second, we attempted to identify the potential for a deafferentation-dependent synaptogenesis. SCZs were ultrastructurally identified before and after deafferentation in tissue treated for ethanolic phosphotungstic acid (EPTA) staining. This was combined with pre-embedding immunocytochemistry for gephyrin identifying inhibitory SCZs, the growth-associated protein GAP-43, glutamate, and choline acetyltransferase. A stereological analysis of EPTA stained sections revealed 1.11±0.09 (S.E.M.)×109 SCZs per mm3 of AVCN tissue. Within 7 days of deafferentation, this number was down by 46%. Excitatory and inhibitory synapses were differentially affected on the side of deafferentation. Excitatory synapses were quickly reduced and then began to increase in number again, necessarily being complemented from sources other than cochlear neurons, while inhibitory synapses were reduced more slowly and continuously. The result was a transient rise of the relative fraction of inhibitory synapses with a decline below original levels thereafter. Synaptogenesis was inferred by the emergence of morphologically immature SCZs that were consistently associated with GAP-43 immunoreactivity. SCZs of this type were estimated to make up a fraction of close to 30% of the total synaptic population present by ten weeks after sensory deafferentation. In conclusion, there appears to be a substantial potential for network reorganization and synaptogenesis in the auditory brainstem after loss of hearing, even in the adult brain

Over-Expression of DSCAM and COL6A2 Cooperatively Generates Congenital Heart Defects

A significant current challenge in human genetics is the identification of interacting genetic loci mediating complex polygenic disorders. One of the best characterized polygenic diseases is Down syndrome (DS), which results from an extra copy of part or all of chromosome 21. A short interval near the distal tip of chromosome 21 contributes to congenital heart defects (CHD), and a variety of indirect genetic evidence suggests that multiple candidate genes in this region may contribute to this phenotype. We devised a tiered genetic approach to identify interacting CHD candidate genes. We first used the well vetted Drosophila heart as an assay to identify interacting CHD candidate genes by expressing them alone and in all possible pairwise combinations and testing for effects on rhythmicity or heart failure following stress. This comprehensive analysis identified DSCAM and COL6A2 as the most strongly interacting pair of genes. We then over-expressed these two genes alone or in combination in the mouse heart. While over-expression of either gene alone did not affect viability and had little or no effect on heart physiology or morphology, co-expression of the two genes resulted in ≈50% mortality and severe physiological and morphological defects, including atrial septal defects and cardiac hypertrophy. Cooperative interactions between DSCAM and COL6A2 were also observed in the H9C2 cardiac cell line and transcriptional analysis of this interaction points to genes involved in adhesion and cardiac hypertrophy. Our success in defining a cooperative interaction between DSCAM and COL6A2 suggests that the multi-tiered genetic approach we have taken involving human mapping data, comprehensive combinatorial screening in Drosophila, and validation in vivo in mice and in mammalian cells lines should be applicable to identifying specific loci mediating a broad variety of other polygenic disorders

Holographic Calculations of Renyi Entropy

We extend the approach of Casini, Huerta and Myers to a new calculation of the Renyi entropy of a general CFT in d dimensions with a spherical entangling surface, in terms of certain thermal partition functions. We apply this approach to calculate the Renyi entropy in various holographic models. Our results indicate that in general, the Renyi entropy will be a complicated nonlinear function of the central charges and other parameters which characterize the CFT. We also exhibit the relation between this new thermal calculation and a conventional calculation of the Renyi entropy where a twist operator is inserted on the spherical entangling surface. The latter insight also allows us to calculate the scaling dimension of the twist operators in the holographic models.Comment: 71 pages, 6 figure

Lethal Antibody Enhancement of Dengue Disease in Mice Is Prevented by Fc Modification

Immunity to one of the four dengue virus (DV) serotypes can increase disease severity in humans upon subsequent infection with another DV serotype. Serotype cross-reactive antibodies facilitate DV infection of myeloid cells in vitro by promoting virus entry via Fcγ receptors (FcγR), a process known as antibody-dependent enhancement (ADE). However, despite decades of investigation, no in vivo model for antibody enhancement of dengue disease severity has been described. Analogous to human infants who receive anti-DV antibodies by transplacental transfer and develop severe dengue disease during primary infection, we show here that passive administration of anti-DV antibodies is sufficient to enhance DV infection and disease in mice using both mouse-adapted and clinical DV isolates. Antibody-enhanced lethal disease featured many of the hallmarks of severe dengue disease in humans, including thrombocytopenia, vascular leakage, elevated serum cytokine levels, and increased systemic viral burden in serum and tissue phagocytes. Passive transfer of a high dose of serotype-specific antibodies eliminated viremia, but lower doses of these antibodies or cross-reactive polyclonal or monoclonal antibodies all enhanced disease in vivo even when antibody levels were neutralizing in vitro. In contrast, a genetically engineered antibody variant (E60-N297Q) that cannot bind FcγR exhibited prophylactic and therapeutic efficacy against ADE-induced lethal challenge. These observations provide insight into the pathogenesis of antibody-enhanced dengue disease and identify a novel strategy for the design of therapeutic antibodies against dengue

Adult attention deficit hyperactivity disorder symptom profiles and concurrent problems with alcohol and cannabis: Sex differences in a representative, population survey

Background: Adult attention deficit hyperactivity disorder (ADHD) shows a robust association with alcohol and cannabis misuse, and these relationships are expressed differently in males and females. Manifestation of specific ADHD symptom profiles, even in the absence of the full disorder, may also be related to problems with alcohol and cannabis, although these relationships have not been investigated in epidemiological studies. To address this question, we studied the sex-specific associations of ADHD symptomatology with problematic alcohol and cannabis use in a representative sample of adults aged 18 years and older residing in Ontario, Canada. Methods: Data were obtained from the Centre for Addiction and Mental Health Monitor, an ongoing cross-sectional telephone survey, between January 2011 and December 2013. Respondents (n = 5080) reported on current ADHD symptomatology, measured using the Adult ADHD Self-Report Version 1.1 Screener (ASRS-V1.1) and four additional items, and alcohol and cannabis use, which were measured using the Alcohol Use Disorders Identification Test (AUDIT) and the Alcohol, Smoking and Substance Involvement Screening Test (ASSIST), respectively. Logistic regression analyses were conducted in men and women to test the association of each ADHD symptom cluster (hyperactivity, inattentiveness, impulsivity) with problematic alcohol and cannabis use. Results: After controlling for age, education, and comorbid internalizing and externalizing psychopathology, hyperactive symptoms were associated with problematic alcohol use in both men and women and with problematic cannabis use in men. Impulsive symptoms were independently associated with problematic cannabis use in men. By contrast, inattentive symptomatology predicted problems with alcohol and cannabis only in women. In all models, age was negatively associated with substance misuse and externalizing behavior was positively correlated and the strongest predictor of hazardous alcohol and cannabis use. Conclusions: ADHD symptom expression in adulthood is related to concurrent hazardous use of alcohol and cannabis. Distinctive ADHD symptom profiles may confer increased risk for substance misuse in a sex-specific manner