People with schizophrenia have difficulty with emotion perception. Functional imaging studies indicate regional brain activation abnormalities in patients with schizophrenia when processing facial ...emotion. However, findings have not been entirely consistent across different studies.
Activation likelihood estimation (ALE) meta-analyses were conducted to examine brain activation during facial emotion processing in patients with schizophrenia, controls, and patients compared with controls. Secondary meta-analyses were performed to assess the contribution of task design and illness chronicity to the results reported.
When processing facial expressions of emotions, both patients with schizophrenia and healthy controls activated the bilateral amygdala and right fusiform gyri. However, the extent of activation in these regions was generally much more limited in the schizophrenia samples. When directly compared with controls, the extent of activation in bilateral amygdala, parahippocampal gyrus and fusiform gyrus, right superior frontal gyrus, and lentiform nucleus was significantly less in patients. Patients with schizophrenia, but not controls, activated the left insula. A relative failure to recruit the amygdala in patients occurred regardless of whether the task design was explicit or implicit, while differences in fusiform activation were evident in explicit, not implicit, tasks. Restricting the analysis to patients with chronic illness did not substantially change the results.
A marked underrecruitment of the amygdala, accompanied by a substantial limitation in activation throughout a ventral temporal-basal ganglia-prefrontal cortex "social brain" system may be central to the difficulties patients experience when processing facial emotion.
•Biomass chars reactivities significantly greater than that of coal char.•Biomass- and coal-char reactivities correlate well with some char properties.•10% biomass char addition did not influence ...coal char gasification rate.•20 and 30% addition of biomass impacted coal char gasification behaviour.•SF < 1 for all biomass-coal char co-gasification.
The carbon dioxide gasification characteristics of three biomass char samples and bituminous coal char were investigated in a thermogravimetric analyser in the temperature range of 850–950 °C. Char SB exhibited higher reactivities (Ri, Rs, Rf) than chars SW and HW. Coal char gasification reactivities were observed to be lower than those of the three biomass chars. Correlations between the char reactivities and char characteristics were highlighted. The addition of 10% biomass had no significant impact on the coal char gasification reactivity. However, 20 and 30% biomass additions resulted in increased coal char gasification rate. During co-gasification, chars HW and SW caused increased coal char gasification reactivity at lower conversions, while char SB resulted in increased gasification rates throughout the entire conversion range. Experimental data from biomass char gasification and biomass-coal char co-gasification were well described by the MRPM, while coal char gasification was better described by the RPM.
•Sabatier reaction is successfully demonstrated in a microchannel reactor.•A combined approach with experiments and computational fluid dynamics is presented.•Microchannel reactor showed high CO2 ...conversion and CH4 productivity.•Global methanation kinetic rate law to predict experimental data is developed.•CFD model identified operational limits and reaction-coupled transport phenomena.
The methanation of carbon dioxide (CO2) via the Sabatier process is increasingly gaining interest for power-to-gas application. In this investigation, a microchannel reactor was evaluated for CO2 methanation at different operational pressures (atmospheric, 5bar, and 10bar), reaction temperatures (250–400°C) and space velocities (32.6–97.8L.gcat−1.h−1). The recommended operation point was identified at reactor conditions corresponding to 5bar, 400°C, and 97.8L.gcat−1.h−1. At this condition, the microchannel reactor yielded good CO2 conversion (83.4%) and high methane (CH4) productivity (16.9L.gcat−1.h−1). The microchannel reactor also demonstrated good long-term performance at demanding operation conditions relating to high space velocity and high temperature. Subsequently, a CFD model was developed to describe the reaction-coupled transport phenomena within the microchannel reactor. Kinetic rate expressions were developed and validated for all reaction conditions to provide reaction source terms for the CFD modelling. Velocity and concentration profiles were discussed at different reaction conditions to interpret experimental results and provide insight into reactor operation. Overall, the results reported in this paper could give fundamental design and operational insight to the further development of microchannel reactors for CO2 methanation in power-to-gas applications.
The geologic context of red organic‐rich materials (ROR) found across an elongated 200 km region on Ceres is evaluated with spectral information from the multispectral framing camera (FC) and the ...visible and near‐infrared mapping spectrometer (VIR) of Dawn. Discrete areas of ROR materials are found to be associated with small fresh craters less than a few hundred meters in diameter. Regions with the highest concentration of discrete ROR areas exhibit a weaker diffuse background of ROR materials. The observed pattern could be consistent with a field of secondary impacts, but no appropriate primary crater has been found. Both endogenic and exogenic sources are being considered for these distinctive organic materials.
Alexithymia has been a familiar conception of psychosomatic phenomenon. The aim of this study was to investigate whether there were subtypes of alexithymia associating with different traits of ...emotional expression and regulation among a group of healthy college students.
1788 healthy college students were administered with the Chinese version of the 20-item Toronto Alexithymia Scale (TAS-20) and another set of questionnaires assessing emotion status and regulation. A hierarchical cluster analysis was conducted on the three factor scores of the TAS-20. The cluster solution was cross-validated by the corresponding emotional regulation.
The results indicated there were four subtypes of alexithymia, namely extrovert-high alexithymia (EHA), general-high alexithymia (GHA), introvert-high alexithymia (IHA) and non-alexithymia (NA). The GHA was characterized by general high scores on all three factors, the IHA was characterized by high scores on difficulty identifying feelings and difficulty describing feelings but low score on externally oriented cognitive style of thinking, the EHA was characterized by high score on externally oriented cognitive style of thinking but normal score on the others, and the NA got low score on all factors. The GHA and IHA were dominant by suppressive character of emotional regulation and expression with worse emotion status as compared to the EHA and NA.
The current findings suggest there were four subtypes of alexithymia characterized by different emotional regulation manifestations.
Despite significant efforts, obesity continues to be a major public health problem, and there are surprisingly few effective strategies for its prevention and treatment. We now realize that healthy ...diet and activity patterns are difficult to maintain in the current physical environment. Recently, it was suggested that the social environment also contributes to obesity. Therefore, using network‐based interaction models, we simulate how obesity spreads along social networks and predict the effectiveness of large‐scale weight management interventions. For a wide variety of conditions and networks, we show that individuals with similar BMIs will cluster together into groups, and if left unchecked, current social forces will drive these groups toward increasing obesity. Our simulations show that many traditional weight management interventions fail because they target overweight and obese individuals without consideration of their surrounding cluster and wider social network. The popular strategy for dieting with friends is shown to be an ineffective long‐term weight loss strategy, whereas dieting with friends of friends can be somewhat more effective by forcing a shift in cluster boundaries. Fortunately, our simulations also show that interventions targeting well‐connected and/or normal weight individuals at the edges of a cluster may quickly halt the spread of obesity. Furthermore, by changing social forces and altering the behavior of a small but random assortment of both obese and normal weight individuals, highly effective network‐driven strategies can reverse current trends and return large segments of the population to a healthier weight.
BackgroundCheckpoint inhibitors can induce profound anticancer responses, but programmed cell death protein-1 (PD-1) inhibition monotherapy has shown minimal activity in prostate cancer. A published ...report showed that men with prostate cancer who were resistant to the second-generation androgen receptor inhibitor enzalutamide had increased programmed death-ligand 1 (PD-L1) expression on circulating antigen-presenting cells. We hypothesized that the addition of PD-1 inhibition in these patients could induce a meaningful cancer response.MethodsWe evaluated enzalutamide plus the PD-1 inhibitor pembrolizumab in a single-arm phase II study of 28 men with metastatic castration-resistant prostate cancer (mprogressing on enzalutamide alone. Pembrolizumab 200 mg intravenous was given every 3 weeks for four doses with enzalutamide. The primary endpoint was prostate-specific antigen (PSA) decline of ≥50%. Secondary endpoints were objective response, PSA progression-free survival (PFS), time to subsequent treatment, and time to death. Baseline tumor biopsies were obtained when feasible, and samples were sequenced and evaluated for the expression of PD-L1, microsatellite instability (MSI), mutational and neoepitope burdens.ResultsFive (18%) of 28 patients had a PSA decline of ≥50%. Three (25%) of 12 patients with measurable disease at baseline achieved an objective response. Of the five responders, two continue with PSA and radiographic response after 39.3 and 37.8 months. For the entire cohort, median follow-up was 37 months, and median PSA PFS time was 3.8 months (95% CI: 2.8 to 9.9 months). Time to subsequent treatment was 7.21 months (95% CI: 5.1 to 11.1 months). Median overall survival for all patients was 21.9 months (95% CI: 14.7 to 28 .4 months), versus 41.7 months (95% CI: 22.16 to not reached (NR)) in the responders. Of the three responders with baseline biopsies, one had MSI high disease with mutations consistent with DNA-repair defects. None had detectable PD-L1 expression.ConclusionsPembrolizumab has activity in mCRPC when added to enzalutamide. Responses were deep and durable and did not require tumor PD-L1 expression or DNA-repair defects.Trial registration numberclinicaltrials.gov (NCT02312557).
Adrenergic receptors are highly homologous while at the same time display a wide diversity of ligand and G-protein binding, and understanding this diversity is key for designing selective or biased ...drugs for them. Here, we determine two crystal structures of the α2A adrenergic receptor (α2AAR) in complex with a partial agonist and an antagonist. Key non-conserved residues from the ligand-binding pocket (Phe7.39 and Tyr6.55) to G-protein coupling region (Ile34.51 and Lys34.56) are discovered to play a key role in the interplay between partial agonism and biased signaling of α2AAR, which provides insights into the diversity of ligand binding and G-protein coupling preference of adrenergic receptors and lays the foundation for the discovery of next-generation drugs targeting these receptors.
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•Partial agonist and antagonist-bound α2AAR crystal structures are determined•F4127.39 is essential for α2AAR agonist binding, sterically and energetically•Full agonists but not partial agonists of α2AAR form hbonds with Y3946.55•ICL2 plays key role in Gs coupling of α2AAR for partial agonists
Crystal structures of α2A adrenergic receptor (α2AAR) reveal the molecular basis for the diversity in adrenergic receptors. Qu et al. define compelling roles for key amino acids in ligand binding, partial agonism, and biased signaling of α2AAR.
The clinical presentation of common symptoms during depressive episodes in bipolar disorder (BD) and major depressive disorder (MDD) poses challenges for accurate diagnosis. Disorder-specific ...neuroanatomical features may aid the development of reliable discrimination between these two clinical conditions.
For our sample of 16 BD patients, 19 MDD patients and 29 healthy volunteers, we adopted vertex-wise cortical based brain imaging techniques to examine cortical thickness and surface area, two components of cortical volume with distinct genetic determinants. Based on specific characteristics of neuroanatomical features, we then used support vector machine (SVM) algorithm to discriminate between patients with BD and MDD.
Compared to MDD patients, BD patients showed significantly larger cortical surface area in the left bankssts, precuneus, precentral, inferior parietal, superior parietal and the right middle temporal gyri. In addition, larger volumes of subcortical regions were found in BD patients. In SVM discriminative analyses, the overall accuracy was 74.3 %, with a sensitivity of 62.5 % and a specificity of 84.2 % (p = 0.028). Compared to controls, larger surface area in the temporo-parietal regions were observed in BD patients, and thinner cortices in fronto-temporal regions were observed in MDD patients, especially in the medial orbito-frontal area.
These findings have demonstrated distinct spatially distributed variations in cortical thickness and surface area in patients with BD and MDD, suggesting potentially varying etiological and neuropathological processes in these two conditions. The employment of multimodal classification on disorder-specific biological features has shed light to the development of potential classification tools that could aid diagnostic decisions.
Cassiopeia A (Cas A) is one of the best studied young Galactic supernova remnants. While it provides a rare opportunity to study in detail the remnant of a supernova (SN) type IIb, questions remain ...regarding the nature of its progenitor, its mass-loss history, and its pre-SN evolution. Here we present an optical investigation of the circumstellar environment around Cas A and find clumpy and filamentary H emission nebulosities concentrated 10-15 pc (10′-15′) to the north and east. First reported by Minkowski as a faint H ii region, these nebulosities exhibit distinct morphological and spectroscopic properties relative to the surrounding diffuse emissions. Compared to neighboring H ii regions, these nebulae show stronger N ii 6548, 6583 and S ii 6716, 6731 emissions relative to H . We show that Cas A's highest-velocity ejecta knots are interacting with some of the closest projected emission nebulae, thus providing strong evidence that these nebulae lie at the same distance as the remnant. We interpret these surrounding nebulosities to be the remains of the progenitor's red supergiant wind, which accumulated against the southern edge of a large extended H ii region located north of Cas A. Our findings are consistent with the view that Cas A's progenitor underwent considerable mass loss, first from a fast main-sequence wind, then from a slower, clumpy red supergiant wind, and finally from a brief high-velocity wind, like that from a yellow supergiant.
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