(S)-tert-Butyl 3-(3-phenyl-1,2,4-oxa­diazol-5-yl)piperidine-1-carboxyl­ate

The title compound, C18H23N3O3, crystallized with two independent mol­ecules (A and B) in the asymmetric unit. The phenyl ring and the 1,2,4-oxadiazole ring are inclined to one another by 19.9 (3)° in mol­ecule A and 7.3 (3)° in mol­ecule B. The absolute structure of the title compound was referred to the transfered chiral center (S) of one of the starting reacta­nts. In the crystal, A mol­ecules are linked by C—H⋯N inter­actions involving the two oxadiazole N atoms

Simplified HIV Testing and Treatment in China: Analysis of Mortality Rates Before and After a Structural Intervention.

BackgroundMultistage stepwise HIV testing and treatment initiation procedures can result in lost opportunities to provide timely antiretroviral therapy (ART). Incomplete patient engagement along the continuum of HIV care translates into high levels of preventable mortality. We aimed to evaluate the ability of a simplified test and treat structural intervention to reduce mortality.Methods and findingsIn the "pre-intervention 2010" (from January 2010 to December 2010) and "pre-intervention 2011" (from January 2011 to December 2011) phases, patients who screened HIV-positive at health care facilities in Zhongshan and Pubei counties in Guangxi, China, followed the standard-of-care process. In the "post-intervention 2012" (from July 2012 to June 2013) and "post-intervention 2013" (from July 2013 to June 2014) phases, patients who screened HIV-positive at the same facilities were offered a simplified test and treat intervention, i.e., concurrent HIV confirmatory and CD4 testing and immediate initiation of ART, irrespective of CD4 count. Participants were followed for 6-18 mo until the end of their study phase period. Mortality rates in the pre-intervention and post-intervention phases were compared for all HIV cases and for treatment-eligible HIV cases. A total of 1,034 HIV-positive participants (281 and 339 in the two pre-intervention phases respectively, and 215 and 199 in the two post-intervention phases respectively) were enrolled. Following the structural intervention, receipt of baseline CD4 testing within 30 d of HIV confirmation increased from 67%/61% (pre-intervention 2010/pre-intervention 2011) to 98%/97% (post-intervention 2012/post-intervention 2013) (all p < 0.001 [i.e., for all comparisons between a pre- and post-intervention phase]), and the time from HIV confirmation to ART initiation decreased from 53 d (interquartile range [IQR] 27-141)/43 d (IQR 15-113) to 5 d (IQR 2-12)/5 d (IQR 2-13) (all p < 0.001). Initiation of ART increased from 27%/49% to 91%/89% among all cases (all p < 0.001) and from 39%/62% to 94%/90% among individuals with CD4 count ≤ 350 cells/mm3 or AIDS (all p < 0.001). Mortality decreased from 27%/27% to 10%/10% for all cases (all p < 0.001) and from 40%/35% to 13%/13% for cases with CD4 count ≤ 350 cells/mm3 or AIDS (all p < 0.001). The simplified test and treat intervention was significantly associated with decreased mortality rates compared to pre-intervention 2011 (adjusted hazard ratio [aHR] 0.385 [95% CI 0.239-0.620] and 0.380 [95% CI 0.233-0.618] for the two post-intervention phases, respectively, for all newly diagnosed HIV cases [both p < 0.001], and aHR 0.369 [95% CI 0.226-0.603] and 0.361 [95% CI 0.221-0.590] for newly diagnosed treatment-eligible HIV cases [both p < 0.001]). The unit cost of an additional patient receiving ART attributable to the intervention was US$83.80. The unit cost of a death prevented because of the intervention was US$234.52.ConclusionsOur results demonstrate that the simplified HIV test and treat intervention promoted successful engagement in care and was associated with a 62% reduction in mortality. Our findings support the implementation of integrated HIV testing and immediate access to ART irrespective of CD4 count, in order to optimize the impact of ART

Novel Ionic Liquid with Both Lewis and Brønsted Acid Sites for Michael Addition

Ionic liquid with both Lewis and Brønsted acid sites has been synthesized and its catalytic activities for Michael addition were carefully studied. The novel ionic liquid was stable to water and could be used in aqueous solution. The molar ratio of the Lewis and Brønsted acid sites could be adjusted to match different reactions. The results showed that the novel ionic liquid was very efficient for Michael addition with good to excellent yields within several min. Operational simplicity, high stability to water and air, small amount used, low cost of the catalyst used, high yields, chemoselectivity, applicability to large-scale reactions and reusability are the key features of this methodology, which indicated that this novel ionic liquid also holds great potential for environmentally friendly processes

The Tianlin Mission: a 6m UV/Opt/IR space telescope to explore the habitable worlds and the universe

[Abridged] It is expected that the ongoing and future space-borne planet survey missions including TESS, PLATO, and Earth 2.0 will detect thousands of small to medium-sized planets via the transit technique, including over a hundred habitable terrestrial rocky planets. To conduct a detailed study of these terrestrial planets, particularly the cool ones with wide orbits, the exoplanet community has proposed various follow-up missions. The currently proposed ESA mission ARIEL is capable of characterization of planets down to warm super-Earths mainly using transmission spectroscopy. The NASA 6m UV/Opt/NIR mission proposed in the Astro2020 Decadal Survey may further tackle down to habitable rocky planets, and is expected to launch around 2045. In the meanwhile, China is funding a concept study of a 6-m class space telescope named Tianlin (A UV/Opt/NIR Large Aperture Space Telescope) that aims to start its operation within the next 10-15 years and last for 5+ years. Tianlin will be primarily aimed to the discovery and characterization of rocky planets in the habitable zones (HZ) around nearby stars and to search for potential biosignatures mainly using the direct imaging method. Transmission and emission spectroscopy at moderate to high resolution will be carried out as well on a population of exoplanets to strengthen the understanding of the formation and evolution of exoplanets. It will also carry out in-depth studies of the cosmic web and early galaxies, and constrain the nature of the dark matter and dark energy. We describe briefly the primary scientific motivations and main technical considerations based on our preliminary simulation results. We find that a monolithic off-axis space telescope with a primary mirror diameter larger than 6m equipped with a high contrast chronograph can identify water in the atmosphere of a habitable-zone Earth-like planet around a Sun-like star.Comment: 15 pages, 5 figures, accepted for publication in RAA and is available onlin

Study on crustal deformation of the Ms6. 6 Damxung earthquake in 2008 by InSAR measurements

Abstract:Three Envisat images from ESA were used to derive the pre – and co-seismic deformation interfereograms caused by the Damxung Ms6. 6 earthquake of Oct. 6, 2008, by using InSAR. The result shows no significant crustal motion more than 4 months before the earthquake, but a maximum co-seismic displacement of about 0.3m in an epicentral area of 20km × 20km. The deformation field was symmetrically distributed about a NS axis, where the west side subsided and the east side uplifted. We used a linear elastic dislocation model in half space and a nonlinear constraint optimized algorithm to estimate the slip distribution along the fault. The results indicates that the epicenter is located at 90.374°E, 29.745°N with a moment magnitude of Mw6. 35. The earthquake is dominated by normal faulting with a maximum slip of 3m on a 12km × 11km fault plane striking S189°W, dipping 60° to NW at a depth of 9.5km, and is located at a sub-fault of the southeastern Piedmont of the Nyainqentanglha mountains. The relatively shallow depth of earthquake is related to relatively high heat flow in the area

Multiplex LNA probe-based RAP assay for rapid and highly sensitive detection of rifampicin-resistant Mycobacterium tuberculosis

ObjectivesThe World Health Organization (WHO) Global tuberculosis Report 2021 stated that rifampicin-resistant tuberculosis (RR-TB) remains a major public health threat. However, the in-practice diagnostic techniques for RR-TB have a variety of limitations including longer time, lack of sensitivity, and undetectable low proportion of heterogeneous drug resistance.MethodsHere we developed a multiplex LNA probe-based RAP method (MLP-RAP) for more sensitive detection of multiple point mutations of the RR-TB and its heteroresistance. A total of 126 clinical isolates and 78 sputum samples collected from the National Tuberculosis Reference Laboratory, China CDC, were tested by MLP-RAP assay. In parallel, qPCR and Sanger sequencing of nested PCR product assay were also performed for comparison.ResultsThe sensitivity of the MLP-RAP assay could reach 5 copies/μl using recombinant plasmids, which is 20 times more sensitive than qPCR (100 copies/μl). In addition, the detection ability of rifampicin heteroresistance was 5%. The MLP-RAP assay had low requirements (boiling method) for nucleic acid extraction and the reaction could be completed within 1 h when placed in a fluorescent qPCR instrument. The result of the clinical evaluation showed that the MLP-RAP method could cover codons 516, 526, 531, and 533 with good specificity. 41 out of 78 boiled sputum samples were detected positive by MLP-RAP assay, which was further confirmed by Sanger sequencing of nested PCR product assay, on the contrary, qPCR was able to detect 32 samples only. Compared with Sanger sequencing of nested PCR product assay, both the specificity and sensitivity of the MLP-RAP assay were 100%.ConclusionMLP-RAP assay can detect RR-TB infection with high sensitivity and specificity, indicating that this assay has the prospect of being applied for rapid and sensitive RR-TB detection in general laboratories where fluorescent qPCR instrument is available

Several Critical Cell Types, Tissues, and Pathways Are Implicated in Genome-Wide Association Studies for Systemic Lupus Erythematosus

We aimed to elucidate the cell types, tissues, and pathways influenced by common variants in systemic lupus erythematosus (SLE). We applied a nonparameter enrichment statistical approach, termed SNPsea, in 181 single nucleotide polymorphisms (SNPs) that have been identified to be associated with the risk of SLE through genome-wide association studies (GWAS) in Eastern Asian and Caucasian populations, to manipulate the critical cell types, tissues, and pathways. In the two most significant cells’ findings (B lymphocytes and CD14+ monocytes), we subjected the GWAS association evidence in the Han Chinese population to an enrichment test of expression quantitative trait locus (QTL) sites and DNase I hypersensitivity, respectively. In both Eastern Asian and Caucasian populations, we observed that the expression level of SLE GWAS implicated genes was significantly elevated in xeroderma pigentosum B cells (P ≤ 1.00 × 10−6), CD14+ monocytes (P ≤ 2.74 × 10−4) and CD19+ B cells (P ≤ 2.00 × 10−6), and plasmacytoid dendritic cells (pDCs) (P ≤ 9.00 × 10−6). We revealed that the SLE GWAS-associated variants were more likely to reside in expression QTL in B lymphocytes (q1/q0 = 2.15, P = 1.23 × 10−44) and DNase I hypersensitivity sites (DHSs) in CD14+ monocytes (q1/q0 = 1.41, P = 0.08). We observed the common variants affected the risk of SLE mostly through by regulating multiple immune system processes and immune response signaling. This study sheds light on several immune cells and responses, as well as the regulatory effect of common variants in the pathogenesis of SLE