Asymptomatic members with SOD1 mutation in a large kindred with familial amyotrophic lateral sclerosis have abnormal water diffusion characterisitcs

DTI was carried out in FALS/SALS patients and familial members with SOD1 mutation (AFALS) who may be in a pre-symptomatic phase of ALS. The changes in FA and TT were investigated in CBT/CST and in whole brain. In FALS/SALS, diffusion pattern changes were found in cerebral peduncle, internal capsule, sub-cortical white matter, cerebellum and frontal lobe while in AFALS, abnormal pattern could also be detected in the cerebral peduncle, cerebellum and frontal lobe but with a smaller extent. Our study indicates that DTI can show early diffusion changes in members with SOD1 mutation in FALS prior to symptom-onset.published_or_final_versio

The Mechanical Behavior of a 25Cr Super Duplex Stainless Steel at Elevated Temperature

Peer reviewedPostprin

PIM-1 as a Multifunctional Framework to Enable High-Performance Solid-State Lithium-Sulfur Batteries

Poly(ethylene oxide) (PEO) is a promising solid electrolyte material for solid-state lithium–sulfur (Li–S) batteries, but low intrinsic ionic conductivity, poor mechanical properties, and failure to hinder the polysulfide shuttle effect limits its application. Herein, a polymer of intrinsic microporosity (PIM) is synthesized and applied as an organic framework to comprehensively enhance the performance of PEO by forming a composite electrolyte (PEO-PIM). The unique structure of PIM-1 not only enhances the mechanical strength and hardness over the PEO electrolyte by an order of magnitude, increasing stability toward the metallic lithium anode but also increases its ionic conductivity by lowering the degree of crystallinity. Furthermore, the PIM-1 is shown to effectively trap lithium polysulfide species to mitigate against the detrimental polysulfide shuttle effect, as electrophilic 1,4-dicyanooxanthrene functional groups possess higher binding energy to polysulfides. Benefiting from these properties, the use of PEO-PIM composite electrolyte has achieved greatly improved rate performance, long-cycling stability, and excellent safety features for solid-state Li-S batteries. This methodology offers a new direction for the optimization of solid polymer electrolytes

Respiratory and hemodynamic contributions to emotion-related pre-syncopal vasovagal symptoms

Vasovagal reactions are conventionally understood as resulting from systemic changes in cardiovascular activity; however, there exists a complementary perspective focused on specific changes in cerebral vasoconstriction associated with hyperventilation-induced hypocapnia. The present study investigated the role cardiovascular and respiratory activity in self-reported pre-syncopal vasovagal reactions to a surgery video in a sample of 49 healthy women. Participants who indicated more previous real-life episodes of dizziness reported experiencing significantly more symptoms in the laboratory consistent with a vasovagal response. They also showed lower total peripheral resistance and higher pre-ejection period in general, suggesting lower sympathetic nervous system activity. Significant decreases in end-tidal carbon dioxide (PETCO2) occurred during the surgery video among susceptible participants, without significant increases in respiration rate. Further, participants who experienced reductions from the neutral video in PETCO2, systolic blood pressure, or both, reported vasovagal symptoms during the surgery video. The results suggest that patterns of respiration associated with decreases in PETCO2 may contribute to vasovagal symptoms reported in non-clinical groups as well as those with blood-injection-injury phobia and are associated with susceptibility to dizziness.This research was supported by a grant from the Canadian Institutes of Health Research (#133459) (B.D.). Fellowship support for the first author and second authors was provided by Les Fonds de la recherche en santé du Quebec

Pine cone scale-inspired motile origami

Stimuli-sensitive hydrogels have received attention because of their potential applications in various fields. Stimuli-directed motion offers many practical applications, such as in drug delivery systems and actuators. Directed motion of asymmetric hydrogels has long been designed; however, few studies have investigated the motion control of symmetric hydrogels. We designed a pine cone scale-inspired movable temperature-sensitive symmetric hydrogel that contains Fe3O4. Alignment of Fe3O4 along the magnetic force is key in motion control in which Fe3O4 acts like fibers in a pine cone scale. Although a homogeneous temperature-sensitive hydrogel cannot respond to a temperature gradient, the Fe3O4-containing hydrogel demonstrates considerable bending motion. Varying degrees and directions of motion are easily facilitated by controlling the amount and alignment angle of the Fe3O4. The shape of the hydrogel layer also influences the morphological structure. This study introduced facile and low-cost methods to control various bending motions. These results can be applied to many fields of engineering, including industrial engineering.111Ysciescopu

New directions in cellular therapy of cancer: a summary of the summit on cellular therapy for cancer

A summit on cellular therapy for cancer discussed and presented advances related to the use of adoptive cellular therapy for melanoma and other cancers. The summit revealed that this field is advancing rapidly. Conventional cellular therapies, such as tumor infiltrating lymphocytes (TIL), are becoming more effective and more available. Gene therapy is becoming an important tool in adoptive cell therapy. Lymphocytes are being engineered to express high affinity T cell receptors (TCRs), chimeric antibody-T cell receptors (CARs) and cytokines. T cell subsets with more naïve and stem cell-like characteristics have been shown in pre-clinical models to be more effective than unselected populations and it is now possible to reprogram T cells and to produce T cells with stem cell characteristics. In the future, combinations of adoptive transfer of T cells and specific vaccination against the cognate antigen can be envisaged to further enhance the effectiveness of these therapies

Improved annotation of 3' untranslated regions and complex loci by combination of strand-specific direct RNA sequencing, RNA-seq and ESTs

The reference annotations made for a genome sequence provide the framework for all subsequent analyses of the genome. Correct annotation is particularly important when interpreting the results of RNA-seq experiments where short sequence reads are mapped against the genome and assigned to genes according to the annotation. Inconsistencies in annotations between the reference and the experimental system can lead to incorrect interpretation of the effect on RNA expression of an experimental treatment or mutation in the system under study. Until recently, the genome-wide annotation of 3-prime untranslated regions received less attention than coding regions and the delineation of intron/exon boundaries. In this paper, data produced for samples in Human, Chicken and A. thaliana by the novel single-molecule, strand-specific, Direct RNA Sequencing technology from Helicos Biosciences which locates 3-prime polyadenylation sites to within +/- 2 nt, were combined with archival EST and RNA-Seq data. Nine examples are illustrated where this combination of data allowed: (1) gene and 3-prime UTR re-annotation (including extension of one 3-prime UTR by 5.9 kb); (2) disentangling of gene expression in complex regions; (3) clearer interpretation of small RNA expression and (4) identification of novel genes. While the specific examples displayed here may become obsolete as genome sequences and their annotations are refined, the principles laid out in this paper will be of general use both to those annotating genomes and those seeking to interpret existing publically available annotations in the context of their own experimental dataComment: 44 pages, 9 figure

Timed inhibition of CDC7 increases CRISPR-Cas9 mediated templated repair.

Repair of double strand DNA breaks (DSBs) can result in gene disruption or gene modification via homology directed repair (HDR) from donor DNA. Altering cellular responses to DSBs may rebalance editing outcomes towards HDR and away from other repair outcomes. Here, we utilize a pooled CRISPR screen to define host cell involvement in HDR between a Cas9 DSB and a plasmid double stranded donor DNA (dsDonor). We find that the Fanconi Anemia (FA) pathway is required for dsDonor HDR and that other genes act to repress HDR. Small molecule inhibition of one of these repressors, CDC7, by XL413 and other inhibitors increases the efficiency of HDR by up to 3.5 fold in many contexts, including primary T cells. XL413 stimulates HDR during a reversible slowing of S-phase that is unexplored for Cas9-induced HDR. We anticipate that XL413 and other such rationally developed inhibitors will be useful tools for gene modification

Properties of Light Flavour Baryons in Hypercentral quark model

The light flavour baryons are studied within the quark model using the hyper central description of the three-body system. The confinement potential is assumed as hypercentral coulomb plus power potential ($hCPP_\nu$) with power index $\nu$. The masses and magnetic moments of light flavour baryons are computed for different power index, $\nu$ starting from 0.5 to 1.5. The predicted masses and magnetic moments are found to attain a saturated value with respect to variation in $\nu$ beyond the power index $\nu>$ 1.0. Further we computed transition magnetic moments and radiative decay width of light flavour baryons. The results are in good agreement with known experimental as well as other theoretical models.Comment: Accepted in Pramana J. of Physic