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We describe the scientific goals and survey design of the First Large Absorption Survey in H i (FLASH), a wide field survey for 21-cm line absorption in neutral atomic hydrogen (H i) at intermediate cosmological redshifts. FLASH will be carried out with the Australian Square Kilometre Array Pathfinder (ASKAP) radio telescope and is planned to cover the sky south of
$\delta \approx +40\,\deg$
at frequencies between 711.5 and 999.5 MHz. At redshifts between
$z = 0.4$
(look-back times of 4 – 8 Gyr), the H i content of the Universe has been poorly explored due to the difficulty of carrying out radio surveys for faint 21-cm line emission and, at ultra-violet wavelengths, space-borne searches for Damped Lyman-
absorption in quasar spectra. The ASKAP wide field of view and large spectral bandwidth, in combination with a radio-quiet site, will enable a search for absorption lines in the radio spectra of bright continuum sources over 80% of the sky. This survey is expected to detect at least several hundred intervening 21-cm absorbers and will produce an H i-absorption-selected catalogue of galaxies rich in cool, star-forming gas, some of which may be concealed from optical surveys. Likewise, at least several hundred associated 21-cm absorbers are expected to be detected within the host galaxies of radio sources at
$0.4 < z < 1.0$
, providing valuable kinematical information for models of gas accretion and jet-driven feedback in radio-loud active galactic nuclei. FLASH will also detect OH 18-cm absorbers in diffuse molecular gas, megamaser OH emission, radio recombination lines, and stacked H i emission.
In this article, we reviewed the current literature studies and our understanding of the parameters that affect the chimeric antigen receptor T cells (CAR-T's) activation, effector function, in vivo persistence, and antitumour effects. These factors include T cell subsets and their differentiation stages, the components of chimeric antigen receptors (CAR) design, the expression promoters and delivery vectors, and the CAR-T production process. The CAR signalling and CAR-T activation were also studied in comparison to TCR. The last section of the review gave special consideration of CAR design for solid tumours, focusing on strategies to improve CAR-T tumour infiltration and survival in the hostile tumour microenvironment. With several hundred clinical trials undergoing worldwide, the pace of CAR-T immunotherapy moves from bench to bedside is unprecedented. We hope that the article will provide readers a clear and comprehensive view of this rapidly evolving field and will help scientists and physician to design effective CAR-Ts immunotherapy for solid tumours.
Bioarchaeological research provides unique insights on human adaptation, diet, lifestyle and epidemiology. The Mogou Bioarchaeology Project explores how health was affected by the Bronze Age transition in north-west China. Preliminary results reveal that the inhabitants experienced substantial physiological stress, infectious disease and lethal trauma.
ABSTRACT IMPACT: Better understanding of the factors impacting disease severity and immunological response of MS patients on disease modifying therapy will enable better recommendations for vaccination options and risk mitigation strategies OBJECTIVES/GOALS: The Coronavirus Disease 2019 (COVID-19) and global health crisis has raised health concerns for patients with multiple sclerosis (MS). We aim to study the clinical characteristics, immunological laboratory data, and immunoglobulin response in patients with MS and COVID-19, to identify factors impacting disease severity and immune response. METHODS/STUDY POPULATION: Database search was done using DataDirect to search for MS patients who had tested positive for COVID-19 at the University of Michigan hospital. Patients with a positive nasopharyngeal swab polymerase chain reaction (PCR) for COVID-19 between March 1 and September 2020 were included. The primary outcome was the immunological laboratory data and immunoglobulin levels and the secondary outcome was their disease severity. We collected demographics, neurological history, MS treatment, Expanded Disability Scale Score (EDSS), comorbidities, and COVID-19 characteristics. A 7-point ordinal scale previously used to assess disease severity was used. Univariate and multivariate analyses will be performed to assess relationships between the collected variables. RESULTS/ANTICIPATED RESULTS: A total of 17 patients, mean age 53 (SD 11.6) years, mean disease duration, 6.2(SD 4.1) years were analyzed. 41% of patients had relapsing remitting multiple sclerosis, 17% had primary progressive MS. (88%) patients were on Disease Modifying Therapy (DMT) at the time of COVID-19 diagnosis. 2 patients died from COVID-19 complications. There was a higher proportion of patients with higher disease severity receiving Ocrelizumab. Only one patient showed positive IgG to SARS-CoV-2 after the resolution of infection. CBC with differential was obtained and a longitudinal follow-up of labs will be done. Regression analysis will be done to check the association between the use of DMT, immunological response, and COVID disease severity in them. The impact of COVID-19 on MS relapse, EDSS, and MRI activities will also be studied. DISCUSSION/SIGNIFICANCE OF FINDINGS: Recommendations to continue current DMT have been made, however, the immune response has not been correlated with the individual’s risk profile. Certain therapies may interfere with mounting a protective immune response of COVID-19 and this knowledge is crucial when advising patients regarding the choice of vaccine and risk mitigation strategies.
A disruption database characterizing the current quench of disruptions with ITER-like tungsten divertor has been developed on EAST. It provides a large number of plasma parameters describing the predisruptive plasma, current quench time, eddy current, and mitigation by massive impurity injection, which shows that the current quench time strongly depends on magnetic energy and post-disruption electron temperature. Further, the energy balance and magnetic energy dissipation during the current quench phase has been well analysed. Magnetic energy is also demonstrated to be dissipated mainly by ohmic reheating and inductive coupling, and both of the two channels have great effects on current quench time. Also, massive gas injection is an efficient method to speed up the current quench and increase the fraction of impurity radiation.
Localized deformation, including that by the deformation-induced shearing martensitic phase transformation, is responsible for hardening and embrittlement in irradiated face-centered cubic alloys. These localized deformation processes can have profound consequences on the mechanical integrity of common structural metals used in extreme radiation environments such as nuclear reactors. This article aims to review and understand exactly how irradiation affects the martensitic phase transformation in face-centered cubic alloys, with an emphasis on austenitic stainless steel, given its ubiquity in the archival literature. The influence of irradiation on stacking fault energy and subsequent implications on the phase transformation are discussed. Mechanisms by which irradiation-induced microstructures enhance the phase transformation are also described, including the surface energy contribution of irradiation-induced cavities (i.e., voids and bubbles) toward the critical martensite nucleation energy, and partial dislocation–cavity interactions. A deformation mechanism map illustrates how irradiation-induced cavities can modulate the martensitic transformation pathway.
The risk factors of criminal behavior in patients with schizophrenia are not well explored. This study is to explore the risk factors for criminal behavior in patients with schizophrenia in rural China.
We used data from a 14-year prospective follow-up study (1994-2008) of criminal behavior among a cohort (n=510) of patients with schizophrenia in Xinjin County, Chengdu, China.
There were 489 patients (95.9%) who were followed up from 1994 to 2008. The rate of criminal behavior was 13.5% among these patients with schizophrenia during the follow-up period. Compared with female subjects (6 cases, 20.0%), male patients had significantly higher rate of violent criminal behavior (e.g., arson, sexual assault, physical assault, and murder) (24 cases, 80.0%) (p< 0.001). Bivariate analyses showed that the risk of criminal behavior was significantly associated with being unmarried, of younger age, previous violent behavior, homelessness, lower family economic status, no family caregivers, and higher scores on measures (PANSS) of positive, negative, and total symptoms of illness. In multiple logistic regression analyses being unmarried and previous violent behavior were identified as independent predictors of increased criminal behavior in persons with schizophrenia.
The risk factors for criminal behavior among patients with schizophrenia should be understood within a particular social context. Criminal behavior may be predicted by specific characteristics of patients with schizophrenia in rural community. The findings of risk factors for criminal behavior should be considered in planning community mental health care and interventions for high-risk patients and their families.
Un échec de traitement peut entraîner diverses conséquences à la fois pour le patient souffrant de schizophrénie mais aussi en terme de santé publique (arrêt du traitement, hospitalisation, addiction, arrestation/incarcération) [1–3]. Cette étude a comparé en vraie vie, les délais avant échec au traitement des patients souffrant de schizophrénie ayant des antécédents d’incarcération, traités soit par palmitate de paliperidone (PP) ou par des antipsychotiques oraux (APO).
Paliperidone Research In Demonstrating Effectiveness (PRIDE) est une étude en ouvert, prospective, randomisée, d’une durée de 15 mois, comparant le PP une fois par mois aux APO chez des sujets atteints de schizophrénie, avec des antécédents d’incarcération (NCT01157351). Les sujets ont été randomisés (1:1) en deux groupes :
– PP à doses flexibles (78–234 mg) administrées une fois par mois ou à ;
– l’un des 7 APO couramment prescrits par l’investigateur.
Le critère de jugement principal était le délai avant échec du traitement (défini comme arrestation/incarcération, hospitalisation, suicide, arrêt du traitement ou supplémentation par manque d’efficacité ou mauvaise tolérance et/ou besoin d’intensifier les soins psychiatriques) évalué par la méthode de Kaplan-Meier.
Un total de 450 sujets ont été inclus (sexe masculin = 86,3 %). Le délai avant échec du traitement était significativement plus long avec le PP par rapport aux APO (médiane = 416 vs 226 jours avant arrêt du traitement ou supplémentation ; Rapport de risque [IC95 %] = 1,43 [1,09, 1,88] ; p = 0,011). Les taux d’échecs du traitement étaient de 39,8 % avec le PP et de 53,7 % avec les APO. Des résultats similaires ont été observés pour le délai avant hospitalisation ou arrestation/incarcération (médiane ≥ 450 vs 274 jours ; rapport de risque [IC95 %] = 1,43 [1,06, 1,93] ; p = 0,019). Les événements indésirables les plus fréquents (PP vs APO, ≥ 10 %) étaient : douleur au site d’injection (18,6 % vs 0 %) ; insomnie (16,8 % vs 11,5 %) ; prise de poids (11,9 % vs 6,0 %) ; akathisie (11,1 % vs 6,9 %) ; anxiété (10,6 % vs 7,3 %).
Le traitement mensuel par PP injectable retarde significativement le délai de survenue d’un large éventail de conséquences négatives de la schizophrénie en vie réelle.
Mounting evidence has implicated oxidative stress in severe psychiatric disorders, including major depressive disorder (MDD). Glutathione (GSH) is the major intracellular antioxidant that protects cells against oxidative stress.
To test the hypothesis that oxidative stress is implicated MDD by measuring cortical GSH in MDD patients and in matched healthy controls in vivo, using magnetic resonance spectroscopy (MRS).
Fifteen psychotropic medication-free patients with MDD diagnosed according DSM-IV-TR criteria and 13 healthy volunteers (HV) participated in the study. A history of other axis I diagnoses or substance/alcohol abuse was exclusionary for all subjects. In vivo brain GSH levels, expressed in institutional units, were obtained from a single 3 × 3 × 2-cm3 occipital lobe voxel at 3.0 Tesla using MRS spectral editing.
Statistical comparisons revealed a 20.6% mean cortical GSH decrease (p< .003) in MDD (2.3 ± 0.4) compared to HV (2.9 ± 0.6), which remained significant after adjusting for age, sex, bmi, and smoking status. In addition, we found GSH levels to correlate negatively with depressive symptoms and with indices of emotional and functional disability across all participants.
To our knowledge, this is the first study to report a significant cortical GSH deficit in vivo in MDD, a finding that supports a role for oxidative stress in the pathophysiology of the disorder, and suggests the viability of treatment strategies based on using synthetic GSH precursors, such as N-acetylcysteine, to spur in situ synthesis and elevation of the antioxidant and mitigate the pathogenic effects of oxidative stress.
Space Infrared Telescope for Cosmology and Astrophysics (SPICA), the cryogenic infrared space telescope recently pre-selected for a ‘Phase A’ concept study as one of the three remaining candidates for European Space Agency (ESA's) fifth medium class (M5) mission, is foreseen to include a far-infrared polarimetric imager [SPICA-POL, now called B-fields with BOlometers and Polarizers (B-BOP)], which would offer a unique opportunity to resolve major issues in our understanding of the nearby, cold magnetised Universe. This paper presents an overview of the main science drivers for B-BOP, including high dynamic range polarimetric imaging of the cold interstellar medium (ISM) in both our Milky Way and nearby galaxies. Thanks to a cooled telescope, B-BOP will deliver wide-field 100–350 $\mu$m images of linearly polarised dust emission in Stokes Q and U with a resolution, signal-to-noise ratio, and both intensity and spatial dynamic ranges comparable to those achieved by Herschel images of the cold ISM in total intensity (Stokes I). The B-BOP 200 $\mu$m images will also have a factor $\sim $30 higher resolution than Planck polarisation data. This will make B-BOP a unique tool for characterising the statistical properties of the magnetised ISM and probing the role of magnetic fields in the formation and evolution of the interstellar web of dusty molecular filaments giving birth to most stars in our Galaxy. B-BOP will also be a powerful instrument for studying the magnetism of nearby galaxies and testing Galactic dynamo models, constraining the physics of dust grain alignment, informing the problem of the interaction of cosmic rays with molecular clouds, tracing magnetic fields in the inner layers of protoplanetary disks, and monitoring accretion bursts in embedded protostars.
Latrophilin (LPH) is known as an adhesion G-protein-coupled receptor which involved in multiple physiological processes in organisms. Previous studies showed that lph not only involved the susceptibility to anticholinesterase insecticides but also affected fecundity in Tribolium castaneum. However, its regulatory mechanisms in these biological processes are still not clear. Here, we identified two potential downstream carboxylesterase (cce) genes of Tclph, esterase4 and esterase6, and further characterized their interactions with Tclph. After treatment of T. castaneum larvae with carbofuran or dichlorvos insecticides, the transcript levels of Tcest4 and Tcest6 were significantly induced from 12 to 72 h. RNAi against Tcest4 or Tcest6 led to the higher mortality compared with the controls after the insecticides treatment, suggesting that these two genes play a vital role in detoxification of insecticides in T. castaneum. Furthermore, with insecticides exposure to Tclph knockdown beetles, the expression of Tcest4 was upregulated but Tcest6 was downregulated, indicating that beetles existed a compensatory response against the insecticides. Additionally, RNAi of Tcest6 resulted in 43% reductions in female egg laying and completely inhibited egg hatching, which showed the similar phenotype as that of Tclph knockdown. These results indicated that Tclph affected fecundity by positively regulating Tcest6 expression. Our findings will provide a new insight into the molecular mechanisms of Tclph involved in physiological functions in T. castaneum.
Feeding ruminants a high-grain (HG) diet is a widely used strategy to improve milk yield and cost efficiency. However, it may cause certain metabolic disorders. At present, information about the effects of HG diets on the systemic metabolic profile of goats and the correlation of such diets with rumen bacteria is limited. In the present study, goats were randomly divided into two groups: one was fed the hay diet (hay; n = 5), while the other was fed HG diets (HG; n = 5). On day 50, samples of rumen contents, peripheral blood serum and liver tissues were collected to determine the metabolic profiles in the rumen fluid, liver and serum and the microbial composition in rumen. The results revealed that HG diets reduced (P < 0.05) the community richness and diversity of rumen microbiota, with an increase in the Chao 1 and Shannon index and a decrease in the Simpson index. HG diets also altered the composition of rumen microbiota, with 30 genera affected (P < 0.05). Data on the metabolome showed that the metabolites in the rumen fluid, liver and serum were affected (variable importance projection > 1, P <0.05) by dietary treatment, with 47, 10 and 27 metabolites identified as differentially metabolites. Pathway analysis showed that the common metabolites in the shared key pathway (aminoacyl-transfer RNA biosynthesis) in the rumen fluid, liver and serum were glycine, lysine and valine. These findings suggested that HG diets changed the composition of the rumen microbiota and metabolites in the rumen fluid, liver and serum, mainly involved in amino acid metabolism. Our findings provide new insights into the understanding of diet-related systemic metabolism and the effects of HG diets on the overall health of goats.
The rapid shift to high-grain (HG) diets in ruminants can affect the function of the rumen epithelium, but the dynamic changes in the composition of the epithelium-associated (epimural) bacterial community in sheep still needs further investigation. Twenty male lambs were randomly allocated to four groups (n = 5). Animals of the first group received hay diet and represented a control group (CON). Simultaneously, animals in the other three groups (HG groups) were rapidly shifted to an HG diet (60% concentrate)which continued for 7 (HG7), 14 (HG14) and 28 (HG28) days, correspondingly. Results showed that ruminal pH dramatically decreased due to the rapid shift to the HG diet (P <0.001), while, the concentrations of butyrate (P <0.001), lactate (P = 0.001), valerate (P = 0.008) and total volatile fatty acids (P = 0.001) increased. Diversity estimators showed a dramatic decrease after the shift without recovering as the HG feeding continued. The principal coordinates analysis showed that CON group clustered separately from all HG groups with the presence of significant difference only between HG7 and HG28 (P = 0.034). The non-parametric multivariate analysis (npmv R-package) deduced that the primary significant differences in phyla and phylogenetic investigation of communities by reconstruction of unobserved states (PICRUSt)-predicted Kyoto Encyclopedia of Genes and Genomes (KEGGs) was attributed mainly to the diet composition (P <0.001, P = 0.001) compared to its application period (P = 0.140, 0.545) which showed a significant effect only on the genus (P = 0.001) and the operational taxonomic units (OTUs) level (P = 0.011). The Kruskal–Wallis test deduced that six phyla showed a significant effect due to the shift in diet composition. At the genus level, HG feeding altered the abundance of 12 taxa, four of which showed a significant variation due to the duration of the HG diet application. Similarly, we found that 21 OTUs showed significant variations due to the duration of the HG diet application. Furthermore, the genes abundance predicted by PICRUSt revealed that the HG feeding significantly affected seven metabolic pathways identified in the KEGG. Particularly, the abundance of gene families associated with carbohydrates metabolism were significantly higher in HG feeding groups (P = 0.027). Collectively, these results revealed that the rapid transition to an HG diet causes dramatic alterations in ruminal fermentation and the composition and function of ruminal epithelium-associated microbiome in sheep, while, the duration of the HG diet application causes drastic alterations to the abundance of some species.
Lentil (Lens culinaris Medik.) is an important and expanding crop in southern Australia and a significant crop in western Canada. Currently, production in both countries is limited by an inability to effectively control weeds, due in part to a lack of registered safe and effective herbicides. Metribuzin is a broad-spectrum herbicide providing an alternative weed control option to the imidazolinones, but it has low crop safety in lentil. Two methods, germplasm screening using a hydroponic sand assay and field screening of a large mutated population of the Australian cultivar ‘PBA Flash’ were initially used to identify lines with putative metribuzin tolerance over current cultivars. Dose–response experiments showed the germplasm line SP1333 had GR50 (the rate required to reduce dry weight 50%) values up to four times higher than PBA Flash. However, the mutation selections M043 and M009 had GR50 values more than 25 times higher than PBA Flash. A field study in Canada, under conditions of induced shade and no shade 72 h before POST application of metribuzin, confirmed the intermediate level of tolerance in SP1333 and the high level in the two mutant lines compared with 20 Canadian and Australian genotypes. This relative increase in metribuzin tolerance of the two mutant lines over the parent cultivar is higher than all previous reports in a range of crop species. The development of large mutant populations combined with large M2 field screens was a successful method for developing high levels of metribuzin tolerance in lentil. The estimated mutation rate of the mutant lines was 9.4×10−8. All three lines are currently being used as parents in lentil breeding programs.
Pathogenesis of pregnancy toxemia (PT) is believed to be associated with the disruption of lipid metabolism. The present study aimed to explore the underlying mechanisms of lipid metabolism disorder in the livers of ewes with PT. In total, 10 pregnant ewes were fed normally (control group) whereas another 10 were subjected to 70% level feed restriction for 15 days to establish a pathological model of PT. Results showed that, as compared with the controls, the levels of blood β-hydroxybutyrate (BHBA), non-esterified fatty acids (NEFAs) and cholesterol were greater (P<0.05) and blood glucose level was lower (P<0.05) in PT ewes. The contents of NEFAs, BHBA, cholesterol and triglyceride were higher (P<0.05) and glycerol content was lower (P<0.05) in hepatic tissues of PT ewes than those of the controls. For ewes with PT, excessive fat vacuoles were observed in liver sections stained with hematoxylin–eosin; furthermore, inner structures of hepatocytes including nuclei, mitochondria and endoplasmic reticulum were damaged seriously according to the results of transmission electron microscope. Real-time PCR data showed that compared with the controls, the expression of hepatic genes involved in fatty acid oxidation (FAO) and triglyceride synthesis (TGS) was enhanced (P<0.05) whereas that related to acetyl-CoA metabolism (ACM) was repressed (P<0.05) in PT ewes. Generally, our results showed that negative energy balance altered the expression of genes involved in FAO, ACM and TGS, further caused lipid metabolism disorder in livers, resulting in PT of ewes. Our findings may provide the molecular basis for novel therapeutic strategies against this systemic metabolic disease in sheep.
The unprecedented sensitivity, angular resolution and broad bandwidth coverage of Square Kilometre Array (SKA) radio polarimetric observations will allow us to address many long-standing mysteries in cosmic magnetism science. I will highlight the unique capabilities of the SKA to map the warm hot intergalactic medium, reveal detailed 3-dimensional structures of magnetic fields in local galaxies and trace the redshift evolution of galactic magnetic fields.
An excellent laboratory for studying large scale magnetic fields is the grand design face-on spiral galaxy M51. Due to wavelength-dependent Faraday depolarization, linearly polarized synchrotron emission at different radio frequencies gives a picture of the galaxy at different depths: Observations at L-band (1 – 2 GHz) probe the halo region while at C- and X-band (4 – 8 GHz) the linearly polarized emission probe the disk region of M51. We present new observations of M51 using the Karl G. Jansky Very Large Array (VLA) at S-band (2 – 4 GHz), where previously no polarization observations existed, to shed new light on the transition region between the disk and the halo. We discuss a model of the depolarization of synchrotron radiation in a multilayer magneto-ionic medium and compare the model predictions to the multi-frequency polarization data of M51 between 1 – 8 GHz. The new S-band data are essential to distinguish between different models. Our study shows that the initial model parameters, i.e. the total regular and turbulent magnetic field strengths in the disk and halo of M51, need to be adjusted to successfully fit the models to the data.
In the current intensive production system, ruminants are often fed high-grain (HG) diets. However, this feeding pattern often causes rumen metabolic disorders and may further trigger laminitis, the exact mechanism is not clear. This study investigated the effect of HG diet feeding on fermentative and microbial changes in the rumen and on the expression of pro-inflammatory cytokines and matrix metalloproteinases (MMPs) in the lamellar tissue. In all, 12 male goats were fed a hay diet (0% grain; n=6) or an HG diet (56.5% grain; n=6). On day 50 of treatment, samples of blood, rumen content, and lamellar tissue of hooves of goats were collected. The data showed that compared with the hay group, HG-fed goats had lower (P<0.05) rumen pH but higher (P<0.05) total volatile fatty acids and lactate in the rumen and higher (P<0.05) lipopolysaccharide (LPS) levels in the rumen and blood. HG diet feeding altered the composition of rumen bacterial community, and correspondingly, the results suggested that their functions in the HG group were also altered. HG diet feeding increased (P<0.05) the expression of interleukin-1β, interleukin-6, tumour necrosis factor-α and MMP-2 mRNA in the lamellar tissues compared with the hay group. Correlation analysis indicated that the expression of pro-inflammatory cytokines were positively correlated with MMP-2 expression in lamellar tissues. Overall, these results revealed that HG feeding altered the patterns of rumen fermentation and the composition and functions of rumen bacterial community, and lead to higher levels of LPS in the peripheral blood, and further activated the inflammatory response in lamellar tissues, which may progress to the level of laminar damage.
The triplite LiFeSO4F displays both the highest potential ever reported for an Fe-based compound, as well as a comparable specific energy with that of popular LiFePO4. The synthesis is still a challenge because the present approaches are connected with long time, special equipments or organic reagents, etc. In this work, the triplite LiFeSO4F powder was synthesized through an ambient two-step solid-state route. The reaction process and phase purity were analyzed, coupled with structure refinement and electrochemical test.