Experimental study of coherent synchrotron radiation in the emittance exchange line at the A0-photoinjector

Next generation accelerators will require a high current, low emittance beam with a low energy spread. Such accelerators will employ advanced beam conditioning systems such as emittance exchangers to manipulate high brightness beams. One of the goals of the Fermilab A0 photoinjector is to investigate the transverse to longitudinal emittance exchange principle. Coherent synchrotron radiation could limit high current operation of the emittance exchanger. In this paper, we report on the preliminary experimental and simulation study of the coherent synchroton radiation (CSR) in the emittance exchange line at the A0 photoinjector.Comment: 4 pp. 14th Advanced Accelerator Concepts Workshop, 13-19 Jun 2010: Annapolis, Marylan

PHASE BEHAVIOUR OF SOME MIXED CHLORIDE SALT SYSTEMS

ABSTRACT Phase behaviours of two different series of chloride salt mixtures, viz (a) equimolecular (NaCI + KCI), MgCI,, BaCI, and (b) [NaCI + KCI], MgCI,, CaClz have been studied. The percentages of MgCI2 in the salt mixtures were kept fixed at four different valuesviz 10,20,30 and 40in these studies where other components vary. It has been found that the replacement of CaCI, with BaC12 in the four component salt mixtures d o e s not change the shape and the temperature of the liquidus curve significantly except in the cases when the percentage of BaCI, in the mixture is more than 50

Development and characterization of controlled release mucoadhesive tablets of captopril to increase the residence time in the gastrointestinal tract

The present investigation concerns the development of mucoadhesive tablets of captopril which were designed to prolong the gastric residence time after oral administration. Matrix tablets of captopril were formulated using different mucoadhesive polymers such as guar gum, xanthan gum, hydroxyl propyl methyl cellulose (HPMC) K4M and K15M in various ratios. The tablets were evaluated for physical properties, content uniformity, swelling index, bioadhesive strength and in vitro drug release. Swelling was increased as the concentration and viscosity of HPMC increases. Tablets formulated using guar gum and xanthan gum alone were eroded faster and dissolved completely within 5-7 h, while tablet containing HPMC remain intact and provided slow release up to 11-12 h. It was evident from the study that the formulation F10 containing HPMC K15M and xanthan gum (1:1) exhibited maximum bioadhesive strength of 31.59 ± 0.05 gm and in vitro drug release was found to be 91.85 % at the end of 12 h with non-fickian diffusion mechanism. The stability studies of optimized batch showed that there was no change in bioadhesive strength and in vitro release when stored at different temperature condition for 90 days. It was concluded that formulation F10 shows the better bioadhesive strength and drug release.Colegio de Farmacéuticos de la Provincia de Buenos Aire

Clinico-radiological features, molecular spectrum, and identification of prognostic factors in developmental and epileptic encephalopathy due to inosine triphosphate pyrophosphatase (ITPase) deficiency

Developmental and epileptic encephalopathy 35 (DEE 35) is a severe neurological condition caused by biallelic variants in ITPA, encoding inosine triphosphate pyrophosphatase, an essential enzyme in purine metabolism. We delineate the genotypic and phenotypic spectrum of DEE 35, analyzing possible predictors for adverse clinical outcomes. We investigated a cohort of 28 new patients and reviewed previously described cases, providing a comprehensive characterization of 40 subjects. Exome sequencing was performed to identify underlying ITPA pathogenic variants. Brain MRI (magnetic resonance imaging) scans were systematically analyzed to delineate the neuroradiological spectrum. Survival curves according to the Kaplan–Meier method and log-rank test were used to investigate outcome predictors in different subgroups of patients. We identified 18 distinct ITPA pathogenic variants, including 14 novel variants, and two deletions. All subjects showed profound developmental delay, microcephaly, and refractory epilepsy followed by neurodevelopmental regression. Brain MRI revision revealed a recurrent pattern of delayed myelination and restricted diffusion of early myelinating structures. Congenital microcephaly and cardiac involvement were statistically significant novel clinical predictors of adverse outcomes. We refined the molecular, clinical, and neuroradiological characterization of ITPase deficiency, and identified new clinical predictors which may have a potentially important impact on diagnosis, counseling, and follow-up of affected individuals

Short-term variations in response distribution to cortical stimulation

Patterns of responses in the cerebral cortex can vary, and are influenced by pre-existing cortical function, but it is not known how rapidly these variations can occur in humans. We investigated how rapidly response patterns to electrical stimulation can vary in intact human brain. We also investigated whether the type of functional change occurring at a given location with stimulation would help predict the distribution of responses elsewhere over the cortex to stimulation at that given location. We did this by studying cortical afterdischarges following electrical stimulation of the cortex in awake humans undergoing evaluations for brain surgery. Response occurrence and location could change within seconds, both nearby to and distant from stimulation sites. Responses might occur at a given location during one trial but not the next. They could occur at electrodes adjacent or not adjacent to those directly stimulated or to other electrodes showing afterdischarges. The likelihood of an afterdischarge at an individual site after stimulation was predicted by spontaneous electroencephalographic activity at that specific site just prior to stimulation, but not by overall cortical activity. When stimulation at a site interrupted motor, sensory or language function, afterdischarges were more likely to occur at other sites where stimulation interrupted similar functions. These results show that widespread dynamic changes in cortical responses can occur in intact cortex within short periods of time, and that the distribution of these responses depends on local brain states and functional brain architecture at the time of stimulation. Similar rapid variations may occur during normal intracortical communication and may underlie changes in the cortical organization of function. Possibly these variations, and the occurrence and distribution of responses to cortical stimulation, could be predicted. If so, interventions such as stimulation might be used to alter spread of epileptogenic activity, accelerate learning or enhance cortical reorganization after brain injury

Pathogenic <i>SPTBN1</i> variants cause an autosomal dominant neurodevelopmental syndrome

SPTBN1 encodes βII-spectrin, the ubiquitously expressed β-spectrin that forms micrometer-scale networks associated with plasma membranes. Mice deficient in neuronal βII-spectrin have defects in cortical organization, developmental delay and behavioral deficiencies. These phenotypes, while less severe, are observed in haploinsufficient animals, suggesting that individuals carrying heterozygous SPTBN1 variants may also show measurable compromise of neural development and function. Here we identify heterozygous SPTBN1 variants in 29 individuals with developmental, language and motor delays; mild to severe intellectual disability; autistic features; seizures; behavioral and movement abnormalities; hypotonia; and variable dysmorphic facial features. We show that these SPTBN1 variants lead to effects that affect βII-spectrin stability, disrupt binding to key molecular partners, and disturb cytoskeleton organization and dynamics. Our studies define SPTBN1 variants as the genetic basis of a neurodevelopmental syndrome, expand the set of spectrinopathies affecting the brain and underscore the critical role of βII-spectrin in the central nervous system

Vesicular Stomatitis Virus Infection Promotes Immune Evasion by Preventing NKG2D-Ligand Surface Expression

Vesicular stomatitis virus (VSV) has recently gained attention for its oncolytic ability in cancer treatment. Initially, we hypothesized that VSV infection could increase immune recognition of cancer cells through induction of the immune stimulatory NKG2D-ligands. Here we show that VSV infection leads to a robust induction of MICA mRNA expression, however the subsequent surface expression is potently hindered. Thus, VSV lines up with human cytomegalovirus (HCMV) and adenovirus, which actively subvert the immune system by negatively affecting NKG2D-ligand surface expression. VSV infection caused an active suppression of NKG2D-ligand surface expression, affecting both endogenous and histone deacetylase (HDAC)-inhibitor induced MICA, MICB and ULBP-2 expression. The classical immune escape mechanism of VSV (i.e., the M protein blockade of nucleocytoplasmic mRNA transport) was not involved, as the VSV mutant strain, VSVΔM51, which possess a defective M protein, prevented MICA surface expression similarly to wild-type VSV. The VSV mediated down modulation of NKG2D-ligand expression did not involve apoptosis. Constitutive expression of MICA bypassed the escape mechanism, suggesting that VSV affect NKG2D-ligand expression at an early post-transcriptional level. Our results show that VSV possess an escape mechanism, which could affect the immune recognition of VSV infected cancer cells. This may also have implications for immune recognition of cancer cells after combined treatment with VSV and chemotherapeutic drugs