Suppression of stimulated Raman scattering by angularly incoherent light, towards a laser system of incoherence in all dimensions of time, space, and angle

Laser-plasma instability (LPI) is one of the main obstacles in laser-driven inertial confinement fusion (ICF) for achieving predictable and reproducible fusion at high gain. For the first time we have proved analytically and confirmed with three-dimensional particle-in-cell simulations that angular incoherence has additional and much stronger suppression of the instability growth rate than the well-known temporal incoherence and spatial incoherence usually used in ICF studies. For the model used in our calculations, the maximum field ratio between the stimulated Raman scattering and the driving pulses drops from 0.2 for the Laguerre-Gaussian pulse with a single non-zero topological charge to 0.05 for the super light spring with an angular momentum spread and random relative phases. In particular, angular incoherence does not introduce extra undesirable hot electrons. This opens a novel way to suppress LPI with the light of an angular momentum spread and paves the way towards a low LPI laser system with a super light spring of incoherence in all dimensions of time, space, and angle

TCF1 and LEF1 Control Treg Competitive Survival and Tfr Development to Prevent Autoimmune Diseases.

CD4+ Foxp3+ T regulatory (Treg) cells are key players in preventing lethal autoimmunity. Tregs undertake differentiation processes and acquire diverse functional properties. However, how Treg's differentiation and functional specification are regulated remains incompletely understood. Here, we report that gradient expression of TCF1 and LEF1 distinguishes Tregs into three distinct subpopulations, particularly highlighting a subset of activated Treg (aTreg) cells. Treg-specific ablation of TCF1 and LEF1 renders the mice susceptible to systemic autoimmunity. TCF1 and LEF1 are dispensable for Treg's suppressive capacity but essential for maintaining a normal aTreg pool and promoting Treg's competitive survival. As a consequence, the development of T follicular regulatory (Tfr) cells, which are a subset of aTreg, is abolished in TCF1/LEF1-conditional knockout mice, leading to unrestrained T follicular helper (Tfh) and germinal center B cell responses. Thus, TCF1 and LEF1 act redundantly to control the maintenance and functional specification of Treg subsets to prevent autoimmunity

Clinical Characteristics and Short-Term Prognosis of Autoimmune Encephalitis: A Single-Center Cohort Study in Changsha, China

Background and Purpose: The incidence and prevalence of autoimmune encephalitis is gradually increasing. This retrospective observational study primarily aimed to analyze the clinical characteristics of autoimmune encephalitis patients in the Second Xiangya Hospital and report patient prognoses after immunotherapy.Methods: The clinical data of 86 patients who were diagnosed with autoimmune encephalitis from October 2014 to September 2018 were collected, and their corresponding clinical characteristics, laboratory examination, treatment, and outcome data analyzed.Results: In our study, 72 patients (83.7%) were positive for anti-NMDAR (N-methyl-D-aspartate receptor) antibody; 5 patients (6%) for anti-GABABR (γ-aminobutyric acid receptor-A); 4 patients (4.7%) for anti-LGI1 (leucine-rich, glioma inactivated 1); 3 patients (3.5%) for anti-Caspr2 (contactin-associated protein-like 2) (1 patient was positive for both anti-LGI1 and anti-Caspr2 antibodies); and 3 patients (3.5%) for onconeural antibodies. Among the 86 patients diagnosed as having autoimmune encephalitis, 50% showed acute disease onset (≤2 weeks). The most common inducing factor was fever or cold (17/86, 19.8%). The main clinical symptoms included, among others, psychiatric disturbances (82.5%), epilepsy (60.5%), autonomic dysfunction (58.1%), sleep disorders (45.3%), consciousness disorders (45.3%), and speech disorders (46.5%). No significant correlation between ICU admission rates and CSF or serum antibody scores was observed. However, CSF antibody scores of (+ + +) and (++) were associated with longer lengths of hospitalization (p < 0.05) and a higher CSF WBC count when compared with CSF antibody scores of (+) in patients with anti-NMDAR encephalitis (p < 0.05). Additionally, there was no significant correlation between mRS score difference on admission and discharge (after immunotherapy) and age, sex, and choice of immune treatment, while immune therapy taken within 15 days from onset was more inclined to be associated with an mRS score difference ≥2 after immunotherapy in patients with anti-NMDAR encephalitis (p = 0.006).Conclusions: Autoimmune encephalitis has an acute or sub-acute onset and presents with psychotic symptoms, epilepsy, and autonomic dysfunction. The sex ratio in anti-NMDAR encephalitis was nearly balanced. Infection was a major factor inducing anti-NMDAR encephalitis, and the CSF antibody scores could be helpful in determining its prognosis since these scores showed associations with hospitalization duration and CSF WBC counts

Incentive compatible and anti-compounding of wealth in proof-of-stake

Geometric reward function is proposed as an alternative choice to circumvent the problem of compounding. However, it’s not so desirable since no parties have incentives to participate in the consensus mechanism. In this paper, we tailor a new bonus reward function by adding random salts to the geometric reward function. The new reward function is a tradeoff between equitablity and incentive compatibility. We conclude that the quitability of the new reward function is optimal compared with others. Beyond that, we present Gini coefficients to fine-evaluate euqitability of reward functions. We propose a new metric (aka. reward ratio) to quantify the level of incentive compatibility. Our simulation results show that the new reward function performs better than others in both incentive compatibility and anti-compounding

Pyrimido[4,5‐ d ]pyrimidin‐4(1 H )‐one Derivatives as Selective Inhibitors of EGFR Threonine 790 to Methionine 790 (T790M) Mutants

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/99681/1/8387_ftp.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/99681/2/anie_201302313_sm_miscellaneous_information.pd

Pyrimido[4,5‐ d ]pyrimidin‐4(1 H )‐one Derivatives as Selective Inhibitors of EGFR Threonine 790 to Methionine 790 (T790M) Mutants

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/99673/1/8545_ftp.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/99673/2/ange_201302313_sm_miscellaneous_information.pd

Research hotspots and trends of brain-computer interface technology in stroke: a bibliometric study and visualization analysis

BackgroundThe incidence and mortality rates of stroke are escalating due to the growing aging population, which presents a significant hazard to human health. In the realm of stroke, brain-computer interface (BCI) technology has gained considerable attention as a means to enhance treatment efficacy and improve quality of life. Consequently, a bibliometric visualization analysis was performed to investigate the research hotspots and trends of BCI technology in stroke, with the objective of furnishing reference and guidance for future research.MethodsThis study utilized the Science Citation Index Expanded (SCI-Expanded) within the Web of Science Core Collection (WoSCC) database as the data source, selecting relevant literature published between 2013 and 2022 as research sample. Through the application of VOSviewer 1.6.19 and CiteSpace 6.2.R2 visualization analysis software, as well as the bibliometric online analysis platform, the scientific knowledge maps were constructed and subjected to visualization display, and statistical analysis.ResultsThis study encompasses a total of 693 relevant literature, which were published by 2,556 scholars from 975 institutions across 53 countries/regions and have been collected by 185 journals. In the past decade, BCI technology in stroke research has exhibited an upward trend in both annual publications and citations. China and the United States are high productivity countries, while the University of Tubingen stands out as the most contributing institution. Birbaumer N and Pfurtscheller G are the authors with the highest publication and citation frequency in this field, respectively. Frontiers in Neuroscience has published the most literature, while Journal of Neural Engineering has the highest citation frequency. The research hotspots in this field cover keywords such as stroke, BCI, rehabilitation, motor imagery (MI), motor recovery, electroencephalogram (EEG), neurorehabilitation, neural plasticity, task analysis, functional electrical stimulation (FES), motor impairment, feature extraction, and induced movement therapy, which to a certain extent reflect the development trend and frontier research direction of this field.ConclusionThis study comprehensively and visually presents the extensive and in-depth literature resources of BCI technology in stroke research in the form of knowledge maps, which facilitates scholars to gain a more convenient understanding of the development and prospects in this field, thereby promoting further research work

High-fat diets enhance and delay ursodeoxycholic acid absorption but elevate circulating hydrophobic bile salts

Background: Ursodeoxycholic acid (UDCA) is a natural drug essential for the treatment of cholestatic liver diseases. The food effects on the absorption of UDCA and the disposition of circulating bile salts remain unclear despite its widespread global uses. This study aims to investigate the effects of high-fat (HF) diets on the pharmacokinetics of UDCA and disclose how the circulated bile salts were simultaneously perturbed.Methods: After an overnight fast, a cohort of 36 healthy subjects received a single oral dose (500 mg) of UDCA capsules, and another cohort of 31 healthy subjects received the same dose after consuming a 900 kcal HF meal. Blood samples were collected from 48 h pre-dose up to 72 h post-dose for pharmacokinetic assessment and bile acid profiling analysis.Results: The HF diets significantly delayed the absorption of UDCA, with the Tmax of UDCA and its major metabolite, glycoursodeoxycholic acid (GUDCA), changing from 3.3 h and 8.0 h in the fasting study to 4.5 h and 10.0 h in the fed study, respectively. The HF diets did not alter the Cmax of UDCA and GUDCA but immediately led to a sharp increase in the plasma levels of endogenous bile salts including those hydrophobic ones. The AUC0–72h of UDCA significantly increased from 25.4 μg h/mL in the fasting study to 30.8 μg h/mL in the fed study, while the AUC0–72h of GUDCA showed no difference in both studies. As a result, the Cmax of total UDCA (the sum of UDCA, GUDCA, and TUDCA) showed a significant elevation, while the AUC0–72h of total UDCA showed a slight increase without significance in the fed study compared to the fasting study.Conclusion: The HF diets delay UDCA absorption due to the extension of gastric empty time. Although UDCA absorption was slightly enhanced by the HF diets, the beneficial effect may be limited in consideration of the simultaneous elevation of circulating hydrophobic bile salts

Characterization of Full-Length Enterovirus 71 Strains from Severe and Mild Disease Patients in Northeastern China

Human enterovirus 71 (EV71)-associated hand, foot, and mouth disease (HFMD) has been a leading cause of childhood infection in China since 2008. Epidemic and molecular characteristics of HFMD have been examined in many areas of China, including the central and southern regions. However, clinical and genetic characterization of EV71 in the northeastern region of China is scarce. In this study, a series of analyses were performed on seven full-length EV71 sequences from HFMD patients who had either severe or mild disease. We have determined that these seven circulating EV71 viruses from Changchun, China are actually complex recombinant viruses involving multiple type A human enterovirus (HEV). Classified as EV71 subtype C4 (EV71 C4), these Changchun EV71 viruses contain genetic recombination events between the CA4, CA5, EV71B4 and EV71C1 strains. Most of the structural protein region (P1) of these viruses resembled that of the prototype EV71 C1 strains. The non-structural protein domains (P2 and P3) showed a high degree of similarity with CA4, CA5 and EV71 B4 in different regions. The 5′UTR had unclassified recombination,while partial 3D region of these viruses showed a high degree of similarity to CA16. Phylogenetic analysis of full-length or partial sequences of isolates from severe or mild disease patients in Changchun always formed a single cluster in various phylogenetic analyses of different genomic regions, suggesting that all seven strains originated from one single common ancestor. There was no correlation between viral genomic sequence and virulence. Thus, we found that circulating recombinant forms of EV71 are prevalent among HFMD patients in Northeastern China. The existence of a unique cluster of EV71 related viruses in Northeast China has important implications for vaccine development that would address the increasing prevalence of HFMD

Costs of treating patients with schizophrenia who have illness-related crisis events

<p>Abstract</p> <p>Background</p> <p>Relatively little is known about the relationship between psychosocial crises and treatment costs for persons with schizophrenia. This naturalistic prospective study assessed the association of recent crises with mental health treatment costs among persons receiving treatment for schizophrenia.</p> <p>Methods</p> <p>Data were drawn from a large multi-site, non-interventional study of schizophrenia patients in the United States, conducted between 1997 and 2003. Participants were treated at mental health treatment systems, including the Department of Veterans Affairs (VA) hospitals, community mental health centers, community and state hospitals, and university health care service systems. Total costs over a 1-year period for mental health services and component costs (psychiatric hospitalizations, antipsychotic medications, other psychotropic medications, day treatment, emergency psychiatric services, psychosocial/rehabilitation group therapy, individual therapy, medication management, and case management) were calculated for 1557 patients with complete medical information. Direct mental health treatment costs for patients who had experienced 1 or more of 5 recent crisis events were compared to propensity-matched samples of persons who had not experienced a crisis event. The 5 non-mutually exclusive crisis event subgroups were: suicide attempt in the past 4 weeks (n = 18), psychiatric hospitalization in the past 6 months (n = 240), arrest in the past 6 months (n = 56), violent behaviors in the past 4 weeks (n = 62), and diagnosis of a co-occurring substance use disorder (n = 413).</p> <p>Results</p> <p>Across all 5 categories of crisis events, patients who had a recent crisis had higher average annual mental health treatment costs than patients in propensity-score matched comparison samples. Average annual mental health treatment costs were significantly higher for persons who attempted suicide ($46,024), followed by persons with psychiatric hospitalization in the past 6 months ($37,329), persons with prior arrests ($31,081), and persons with violent behaviors ($18,778). Total cost was not significantly higher for those with co-occurring substance use disorder ($19,034).</p> <p>Conclusion</p> <p>Recent crises, particularly suicide attempts, psychiatric hospitalizations, and criminal arrests, are predictive of higher mental health treatment costs in schizophrenia patients.</p