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This versatile and cost-effective microchip production method can be used to fabricate other types of microchips for in situ electron microscopy.Human leukocyte antigen (HLA) genes are among the most polymorphic of our genome, as a likely consequence of balancing selection related to their central role in adaptive immunity. HLA-A and HLA-B genes were recently suggested to evolve through a model of joint divergent asymmetric selection conferring all human populations, including those with severe loss of diversity, an equivalent immune potential. However, the mechanisms by which these two genes might undergo joint evolution while displaying very distinct allelic profiles in populations are still unknown. To address this issue, we carried out extensive data analyses (among which factorial correspondence analysis and linear modeling) on 2,909 common and rare HLA-A, HLA-B, and HLA-C alleles and 200,000 simulated pathogenic peptides by taking into account sequence variation, predicted peptide-binding affinity and HLA allele frequencies in 123 populations worldwide. Our results show that HLA-A and HLA-B (but not HLA-C) molecules maintain considerable functional divergence in almost all populations, which likely plays an instrumental role in their immune defense. We also provide robust evidence of functional complementarity between HLA-A and HLA-B molecules, which display asymmetric relationships in terms of amino acid diversity at both inter- and intraprotein levels and in terms of promiscuous or fastidious peptide-binding specificities. Like two wings of a flying bird, the functional complementarity of HLA-A and HLA-B is a perfect example, in our genome, of duplicated genes sharing their capacity of assuming common vital functions while being submitted to complex and sometimes distinct environmental pressures.In 1921, at the age of 65, 6 years after completing the final edition of his textbook, 22 years after first proposing the concept of dementia praecox (DP), and 1 year before retiring from clinical work, Emil Kraepelin completed the last edition of his "Introduction to Clinical Psychiatry," which contained a mini-textbook for students, 10 pages of which were devoted to DP. This work also included a series of new detailed case histories, 3 of which examined DP. This neglected text represents a distillation of what Kraepelin judged, near the end of his long career, to be the essential features of DP. The relevant text and case histories are translated into English for the first time. Kraepelin did not define DP solely by its chronic course and poor prognosis, acknowledging that remissions and even full recovery might be possible. His clinical description emphasized the frequency of bizarre delusions and passivity symptoms. He recognized the heterogeneity of the clinical presentations, outlining 6 subtypes of DP, including dementia simplex, depressive and stuporous dementia, and an agitated and circular DP. Kraepelin's original concept of DP was not impervious to change and expanded somewhat, especially with the inclusion of Diem's concept of simple DP. He also reviews several contributions of Bleuler, including his concept "latent schizophrenia." He writes poignantly of the psychological consequences of DP. His 3 DP cases, for advanced students, included simple DP, "periodic catatonic," and "speech confusion."Gamma-ray spectra were measured using a LaBr$_3$(Ce) spectrometer during the outage periods, aiming at quantifying the gamma source term of radiation workers' exposure, at the CANDU nuclear power reactors, for the purposes of eye lens dosimetry. The spectra were measured inside the boiler rooms, of the Bruce Power and Ontario Power Generation (OPG) CANDU nuclear power plants, where workers are exposed to relatively high dose rates radiation fields during the maintenance work. Prior to measurements at the CANDU reactors, the pulse shaping parameters of the gamma spectrometer were optimised for high rates gamma fields, up to an input rates of 120 kcps, in order to accomplish a high output rate with a reasonable energy resolution. In parallel, the response of the LaBr$_3$(Ce) detector was characterized by experiments and Monte Carlo simulations. The gamma spectra measured at the CANDU reactors were reported in terms of the gamma-ray fluence rate spectrum. In all measured data, $^60$Co and $^95$Nb were main contributors of the gamma fields. The measured spectra have been used to calculate the dosimetric quantities of interest personal dose equivalents H$_p$(10) and H$_p$(0.07) and eye lens absorbed dose. Enterovirus 71 (EV-A71), Coxsackievirus A16 (CV-A16) and Coxsackievirus A6 (CV-A6) are common serotypes causing hand, foot, and mouth disease (HFMD). Analyses on the basic reproduction number (R0) of common pathogens causing HFMD are limited and there are no related studies using field data from outbreaks in mainland China. We estimated the pathogen-specific basic reproduction number based on laboratory-confirmed HFMD outbreaks (clusters of ≥10 HFMD cases) reported to the national surveillance system between 2011 and 2018. The reproduction numbers were calculated using a mathematical model and the cumulative cases during the initial growth periods. This study included 539 outbreaks, of which 198 were caused by EV-A71, 316 by CV-A16, and 25 by CV-A6. All 10417 cases involved were children. Assuming the outbreaks occurred in closed systems and the incubation period is 5 days, the median R0s of EV-A71, CV-A16, and CV-A6 were 5.06 [2.81, 10.20], 4.84 [3.00, 9.00] and 5.94 [3.27, 10.00] (Median [IQR]). After adjusting for seroprevalences, the R0s for EV-A71, CV-A16 (optimistic and conservative scenarios), and CV-A6 were 12.60 [IQR 7.35, 25.40], 9.29 [IQR 6.01, 19.20], 15.50 [IQR 9.77, 30.40], and 25.80 [IQR 14.20, 43.50], respectively. GS-0976 manufacturer We did not observe changes in the R0s of EV-A71 after vaccine licensure (p-value = 0.67). HFMD is highly transmissible when caused by the three most common serotypes. In mainland China, it primarily affects young children. Although a vaccine became available in 2016, we have not yet observed any related changes in the disease dynamics.HFMD is highly transmissible when caused by the three most common serotypes. In mainland China, it primarily affects young children. Although a vaccine became available in 2016, we have not yet observed any related changes in the disease dynamics.