An assessment of the resolution limitation due to radiation-damage in x-ray diffraction microscopy

X-ray diffraction microscopy (XDM) is a new form of x-ray imaging that is being practiced at several third-generation synchrotron-radiation x-ray facilities. Although only five years have elapsed since the technique was first introduced, it has made rapid progress in demonstrating high-resolution threedimensional imaging and promises few-nm resolution with much larger samples than can be imaged in the transmission electron microscope. Both life- and materials-science applications of XDM are intended, and it is expected that the principal limitation to resolution will be radiation damage for life science and the coherent power of available x-ray sources for material science. In this paper we address the question of the role of radiation damage. We use a statistical analysis based on the so-called "dose fractionation theorem" of Hegerl and Hoppe to calculate the dose needed to make an image of a lifescience sample by XDM with a given resolution. We conclude that the needed dose scales with the inverse fourth power of the resolution and present experimental evidence to support this finding. To determine the maximum tolerable dose we have assembled a number of data taken from the literature plus some measurements of our own which cover ranges of resolution that are not well covered by reports in the literature. The tentative conclusion of this study is that XDM should be able to image frozen-hydrated protein samples at a resolution of about 10 nm with "Rose-criterion" image quality.Comment: 9 pages, 4 figure

Major depressive disorder and alterations in insular cortical activity: A review of current functional magnetic imaging (fMRI) research

Major depressive disorder (MDD) is characterized by a dysregulated fronto-limbic network. The hyperactivation of limbic regions leads to increased attention and processing of emotional information, with a bias toward negative stimuli. Pathological ruminative behavior is a common symptom of depressive disorder whereby the individual is unable to disengage from internal mental processing of emotionally-salient events. In fact, lower deactivations of the neural baseline resting state may account for the increased internal self-focus. The insular cortex, with its extensive connections to fronto-limbic and association areas has recently also been implicated to be a part of this network. Given its wide-reaching connectivity, it has been putatively implicated as an integration center of autonomic, visceromotor, emotional and interoceptive information. The following paper will review recent imaging findings of altered insular function and connectivity in depressive pathology

Preparation and characterization of binary Mg-silicate glasses via Sol-Gel route

AbstractSol-gel processing allows synthesis of low-energy glasses. In this work, binary magnesium silicate glasses with various MgO contents are synthesized using a modified sol-gel route. TGA and XRD analyses indicate that amorphous glasses with up to 50 mol% MgO can be obtained at 500°C. The reactivity of the glasses is evaluated to assess the use of the sol-gel technique in the large-scale synthesis of alternative cementitious materials. Reactivity tests show that, as MgO content increases, reactivity of glasses increases, reaches an optimum and then declines. This trend doesn’t agree with the theoretical one estimated by NBO/T value, which is generally used for the evaluation of glass reactivity. Mg²⁺ ions play a role as the network modifier when first introduced to silicate glasses. This leads to the depolymerization of the networks, causing an increase in reactivity. Then the magnesium partly behaves as a network former, bonding with oxygens to form MgOₓ polyhedron when there are insufficient primary glass-forming oxide SiO₂, resulting in the polymerization of networks, hence the decrease in reactivity.Abstract Sol-gel processing allows synthesis of low-energy glasses. In this work, binary magnesium silicate glasses with various MgO contents are synthesized using a modified sol-gel route. TGA and XRD analyses indicate that amorphous glasses with up to 50 mol% MgO can be obtained at 500°C. The reactivity of the glasses is evaluated to assess the use of the sol-gel technique in the large-scale synthesis of alternative cementitious materials. Reactivity tests show that, as MgO content increases, reactivity of glasses increases, reaches an optimum and then declines. This trend doesn’t agree with the theoretical one estimated by NBO/T value, which is generally used for the evaluation of glass reactivity. Mg²⁺ ions play a role as the network modifier when first introduced to silicate glasses. This leads to the depolymerization of the networks, causing an increase in reactivity. Then the magnesium partly behaves as a network former, bonding with oxygens to form MgOₓ polyhedron when there are insufficient primary glass-forming oxide SiO₂, resulting in the polymerization of networks, hence the decrease in reactivity

Screen-Printed Composite LiFePO4-LLZO Cathodes Towards Solid-State Li-ion Batteries

LiFePO4(LFP) is widely used as cathode material for its low cost, high safety, and good thermal properties. It is one of the most exploited cathode materials for commercial Li-ion batteries (LIBs). Herein, we present a screen-printing method to prepare a LFP composite cathode, and a rational combination of the typical composite solid electrolytes (CSE) consisting of polyethylene oxide (PEO)/Li-salt (LiTFSi) electrolyte with ceramic filler (LLZO or Li6.4La3Zr1.4Ta0.6O12 (LLZTO)) has been successfully demonstrated for SSB. The prepared CSE offers: i) a promising ionic conductivity (0.425 mS cm(-1) at 60(degrees)C), ii) a wide electrochemical window (>4.6 V), iii) a high Li-ion transference number (tLi(+)=0.44), iv) a good interfacial compatibility with the electrode, v) a good thermal stability, and vi) a high chemical stability toward Li metal anode. The Li/CSE/Li symmetric cells can be cycled for more than 1000 h without Li-dendrites growth at a current density of 0.2 mA cm(-2). The final cell screen-printed LFP composite cathode (LFP+LLZO)//Li metal displays a high reversible specific capacity of 140 mAh g(-1) (0.1 C) and 50 mAh g(-1) (0.5 C) after 1(st) and 500th cycles

Massage-like stroking boosts the immune system in mice

Recent clinical evidence suggests that the therapeutic effect of massage involves the immune system and that this can be exploited as an adjunct therapy together with standard drug-based approaches. In this study, we investigated the mechanisms behind these effects exploring the immunomodulatory function of stroking as a surrogate of massage-like therapy in mice. C57/BL6 mice were stroked daily for 8 days either with a soft brush or directly with a gloved hand and then analysed for differences in their immune repertoire compared to control non-stroked mice. Our results show that hand-but not brush-stroked mice demonstrated a significant increase in thymic and splenic T cell number (p lt 0.05; p lt 0.01). These effects were not associated with significant changes in CD4/CD8 lineage commitment or activation profile. The boosting effects on T cell repertoire of massage-like therapy were associated with a decreased noradrenergic innervation of lymphoid organs and counteracted the immunosuppressive effect of hydrocortisone in vivo. Together our results in mice support the hypothesis that massage-like therapies might be of therapeutic value in the treatment of immunodeficiencies and related disorders and suggest a reduction of the inhibitory noradrenergic tone in lymphoid organs as one of the possible explanations for their immunomodulatory function

Development of the Precision Link Biobank at Boston Children’s Hospital: Challenges and Opportunities

Increasingly, biobanks are being developed to support organized collections of biological specimens and associated clinical information on broadly consented, diverse patient populations. We describe the implementation of a pediatric biobank, comprised of a fully-informed patient cohort linking specimens to phenotypic data derived from electronic health records (EHR). The Biobank was launched after multiple stakeholders’ input and implemented initially in a pilot phase before hospital-wide expansion in 2016. In-person informed consent is obtained from all participants enrolling in the Biobank and provides permission to: (1) access EHR data for research; (2) collect and use residual specimens produced as by-products of routine care; and (3) share de-identified data and specimens outside of the institution. Participants are recruited throughout the hospital, across diverse clinical settings. We have enrolled 4900 patients to date, and 41% of these have an associated blood sample for DNA processing. Current efforts are focused on aligning the Biobank with other ongoing research efforts at our institution and extending our electronic consenting system to support remote enrollment. A number of pediatric-specific challenges and opportunities is reviewed, including the need to re-consent patients when they reach 18 years of age, the ability to enroll family members accompanying patients and alignment with disease-specific research efforts at our institution and other pediatric centers to increase cohort sizes, particularly for rare diseases

Genome-wide association study of susceptibility to hospitalised respiratory infections

Background: Globally, respiratory infections contribute to significant morbidity and mortality. However, genetic determinants of respiratory infections are understudied and remain poorly understood. Methods: We conducted a genome-wide association study in 19,459 hospitalised respiratory infection cases and 101,438 controls from UK Biobank (Stage 1). We followed-up well-imputed top signals from our Stage 1 analysis in 50,912 respiratory infection cases and 150,442 controls from 11 cohorts (Stage 2). We aggregated effect estimates across studies using inverse variance-weighted meta-analyses. Additionally, we investigated the function of the top signals in order to gain understanding of the underlying biological mechanisms. Results: From our Stage 1 analysis, we report 56 signals at P&lt;5×10 -6, one of which was genome-wide significant ( P&lt;5×10 -8). The genome-wide significant signal was in an intron of PBX3, a gene that encodes pre-B-cell leukaemia transcription factor 3, a homeodomain-containing transcription factor. Further, the genome-wide significant signal was found to colocalise with gene-specific expression quantitative trait loci (eQTLs) affecting expression of PBX3 in lung tissue, where the respiratory infection risk alleles were associated with decreased PBX3 expression in lung tissue, highlighting a possible biological mechanism. Of the 56 signals, 40 were well-imputed in UK Biobank and were investigated in Stage 2. None of the 40 signals replicated, with effect estimates attenuated. Conclusions: Our Stage 1 analysis implicated PBX3 as a candidate causal gene and suggests a possible role of transcription factor binding activity in respiratory infection susceptibility. However, the PBX3 signal, and the other well-imputed signals, did not replicate in the meta-analysis of Stages 1 and 2. Significant phenotypic heterogeneity and differences in study ascertainment may have contributed to this lack of statistical replication. Overall, our study highlighted putative associations and possible biological mechanisms that may provide insight into respiratory infection susceptibility.</p

Could vitamin D reduce obesity-associated inflammation? Observational and Mendelian randomization study.

BACKGROUND: Obesity is associated with inflammation but the role of vitamin D in this process is not clear. OBJECTIVES: We aimed to assess the associations between serum 25-hydroxyvitamin D [25(OH)D], BMI, and 16 inflammatory biomarkers, and to assess the role of vitamin D as a potential mediator in the association between higher BMI and inflammation. METHODS: Northern Finland Birth Cohort 1966 (NFBC1966) 31-y data on 3586 individuals were analyzed to examine the observational associations between BMI, 25(OH)D, and 16 inflammatory biomarkers. Multivariable regression analyses and 2-sample regression-based Mendelian randomization (MR) mediation analysis were performed to assess any role of vitamin D in mediating a causal effect of BMI on inflammatory biomarkers [soluble intercellular adhesion molecule 1 (sICAM-1), high sensitivity C-reactive protein (hs-CRP), and α1-acid glycoprotein (AGP)] for which observational associations were detected. For MR, genome-wide association study summary results ranging from 5163 to 806,834 individuals were used for biomarkers, 25(OH)D, and BMI. Findings were triangulated with a literature review of vitamin D supplementation trials. RESULTS: In NFBC1966, mean BMI (kg/m2) was 24.8 (95% CI: 24.7, 25.0) and mean 25(OH)D was 50.3 nmol/L (95% CI: 49.8, 50.7 nmol/L). Inflammatory biomarkers correlated as 4 independent clusters: interleukins, adhesion molecules, acute-phase proteins, and chemokines. BMI was positively associated with 9 inflammatory biomarkers and inversely with 25(OH)D (false discovery rate < 0.05). 25(OH)D was inversely associated with sICAM-1, hs-CRP, and AGP, which were positively associated with BMI. The MR analyses showed causal association of BMI on these 3 inflammatory biomarkers. There was no observational or MR evidence that circulating 25(OH)D concentrations mediated the association between BMI and these 3 inflammatory markers. Review of randomized controlled trials (RCTs) supported our findings showing no impact of vitamin D supplementation on inflammatory biomarkers. CONCLUSIONS: The findings from our observational study and causal MR analyses, together with data from RCTs, do not support a beneficial role of vitamin D supplementation on obesity-related inflammation

Neural correlates of a single-session massage treatment

The current study investigated the immediate neurophysiological effects of different types of massage in healthy adults using functional magnetic resonance imaging (fMRI). Much attention has been given to the default mode network, a set of brain regions showing greater activity in the resting state. These regions (i.e. insula, posterior and anterior cingulate, inferior parietal and medial prefrontal cortices) have been postulated to be involved in the neural correlates of consciousness, specifically in arousal and awareness. We posit that massage would modulate these same regions given the benefits and pleasant affective properties of touch. To this end, healthy participants were randomly assigned to one of four conditions: 1. Swedish massage, 2. reflexology, 3. massage with an object or 4. a resting control condition. The right foot was massaged while each participant performed a cognitive association task in the scanner. We found that the Swedish massage treatment activated the subgenual anterior and retrosplenial/posterior cingulate cortices. This increased blood oxygen level dependent (BOLD) signal was maintained only in the former brain region during performance of the cognitive task. Interestingly, the reflexology massage condition selectively affected the retrosplenial/posterior cingulate in the resting state, whereas massage with the object augmented the BOLD response in this region during the cognitive task performance. These findings should have implications for better understanding how alternative treatments might affect resting state neural activity and could ultimately be important for devising new targets in the management of mood disorders

Data publication with the structural biology data grid supports live analysis

Access to experimental X-ray diffraction image data is fundamental for validation and reproduction of macromolecular models and indispensable for development of structural biology processing methods. Here, we established a diffraction data publication and dissemination system, Structural Biology Data Grid (SBDG; data. sbgrid. org), to preserve primary experimental data sets that support scientific publications. Data sets are accessible to researchers through a community driven data grid, which facilitates global data access. Our analysis of a pilot collection of crystallographic data sets demonstrates that the information archived by SBDG is sufficient to reprocess data to statistics that meet or exceed the quality of the original published structures. SBDG has extended its services to the entire community and is used to develop support for other types of biomedical data sets. It is anticipated that access to the experimental data sets will enhance the paradigm shift in the community towards a much more dynamic body of continuously improving data analysis