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The expansion of three-dimensional protein structures and enhanced computing power have significantly facilitated our understanding of protein sequence/structure/function relationships. A challenge in structural genomics is to predict the function of uncharacterized proteins. Protein function deconvolution based on global sequence or structural homology is impracticable when a protein relates to no other proteins with known function, and in such cases, functional relationships can be established by detecting their local ligand binding site similarity. Here, we introduce a sequence order-independent comparison algorithm, PocketShape, for structural proteome-wide exploration of protein functional site by fully considering the geometry of the backbones, orientation of the sidechains, and physiochemical properties of the pocket-lining residues. PocketShape is efficient in distinguishing similar from dissimilar ligand binding site pairs by retrieving 99.3% of the similar pairs while rejecting 100% of the dissimilar pairs on a dataset containing 1538 binding site pairs. This method successfully classifies 83 enzyme structures with diverse functions into 12 clusters, which is highly in accordance with the actual structural classification of proteins classification. PocketShape also achieves superior performances than other methods in protein profiling based on experimental data. Potential new applications for representative SARS-CoV-2 drugs Remdesivir and 11a are predicted. The high accuracy and time-efficient characteristics of PocketShape will undoubtedly make it a promising complementary tool for proteome-wide protein function inference and drug repurposing study.Post-transcriptional regulatory networks in Gammaproteobacteria are to a large extent built around the two globally acting RNA-binding proteins (RBPs) CsrA and Hfq. Both RBPs interact with small regulatory RNAs (sRNAs), but the functional outcomes of these interactions are generally distinct. Whereas Hfq both stabilizes sRNAs and promotes their base-pairing to target mRNAs, the sRNAs bound by CsrA act as sequestering molecules that titrate the RBP away from its mRNA targets. In this issue of Molecular Microbiology, Lai et al. reveal that CsrA interacts with the Hfq-associated and base-pairing sRNA Spot 42. Evofosfamide manufacturer In this case, CsrA increases Spot 42 stability by masking a cleavage site for endoribonuclease RNase E, thereby promoting Spot 42-dependent regulation of srlA mRNA. Interestingly, the effect of CsrA on srlA expression is two-fold. In addition to affecting Spot 42-dependent regulation, CsrA directly inhibits translation of SrlM, an activator of srlA transcription. Together, this study reveals a new function for CsrA and indicates more intricate connections between the CsrA and Hfq networks than previously anticipated. Several recent studies have identified additional RBPs that interact with sRNAs. With new RBP identification methods at hand, it will be intriguing to see how many more sRNA-binding proteins will be uncovered.The ternary strategy, introducing a third component into a binary blend, opens a simple and promising avenue to improve the power conversion efficiency (PCE) of organic solar cells (OSCs). The judicious selection of an appropriate third component, without sacrificing the photocurrent and voltage output of the OSC, is of significant importance in ternary devices. Herein, highly efficient OSCs fabricated using a ternary approach are demonstrated, wherein a novel non-fullerene acceptor L8-BO-F is designed and incorporated into the PM6BTP-eC9 blend. The three components show complementary absorption spectra and cascade energy alignment. L8-BO-F and BTP-eC9 are found to form a homogeneous mixed phase, which improves the molecular packing of both the donor and acceptor materials, and optimizes the ternary blend morphology. Moreover, the addition of L8-BO-F into the binary blend suppresses the non-radiative recombination, thus leading to a reduced voltage loss. Consequently, concurrent increases in open-circuit voltage, short-circuit current, and fill factor are realized, resulting in an unprecedented PCE of 18.66% (certified value of 18.2%), which represents the highest efficiency values reported for both single-junction and tandem OSCs so far.Phosphorescent molecular aggregates show promise in realizing efficient and stable organic light-emitting diodes (OLEDs) operating at high brightness level, which is highly desired for future lighting and display applications. Herein, four tetradentate Pd(II) complexes are prepared with judicious ligand design, and their electrochemical and photophysical properties are thoroughly examined. The studies indicate that slight structural changes of ligands can modify the hole and electron transporting capabilities, and alter the horizontal emitting dipole ratios of aggregates in amorphous film, the latter of which are sensitive to the thin-film deposition conditions including the deposition rate and the choice of the templating layer. An optimized OLED device using Pd3O8-Py5 aggregates exhibits a peak external quantum efficiency (EQE) of 37.3% and a reduced efficiency roll-off with high EQEs of 36.0% and 32.5% at 1000 and 10 000 cd m-2 , respectively. Moreover, such an efficient device demonstrates a long measured LT95 (time to 95% of the initial luminance) lifetime of over 500 h with an initial brightness of 17 304 cd m-2 corresponding to an estimated LT95 lifetime of 48 246 h at 1000 cd m-2 .
To examine the association of the timing and consistency of parent bedtime routines with infant night-time sleep duration and variability.
This was a prospective observational study conducted between November 2012 and November 2016.
Three hundred and twenty healthy 6-month-old infants were recruited from the well-child clinics of a university-affiliated hospital in northern Taiwan. Participating families provided sociodemographic, health and bedtime routine information. Infants wore an actigraph on the ankle for a week. General linear model analysis was performed with the frequency and timing of bedtime routines treated as the primary predictor variables of interest.
One hundred and ninety-seven (61.6%) parents started the bedtime routine for infants after 9 PM, with 162 (50.6%) not having the exact same bedtime routine every night. In both crude and adjusted analyses, starting a bedtime routine after 9 PM was associated with shorter infant night-time sleep duration (b=-23.55, p<0.01). Infants withd as part of anticipatory guidance in the well-child clinics. Future studies should include infant sleep variability as an outcome in addition to the conventional mean-level sleep variable analyses to more thoroughly characterize bedtime routine effects.This guideline on mucous membrane pemphigoid (MMP) has been elaborated by the Task Force for Autoimmune Blistering Diseases of the European Academy of Dermatology and Venereology (EADV) with a contribution of physicians from all relevant disciplines and patient organizations. It is a S3 consensus-based guideline encompassing a systematic review of the literature until June 2019 in the MEDLINE and EMBASE databases. This first part covers methodology, the clinical definition of MMP, epidemiology, MMP subtypes, immunopathological characteristics, disease assessment and outcome scores. MMP describes a group of autoimmune skin and mucous membrane blistering diseases, characterized by a chronic course and by predominant involvement of the mucous membranes, such as the oral, ocular, nasal, nasopharyngeal, anogenital, laryngeal and oesophageal mucosa. MMP patients may present with mono- or multisite involvement. Patients' autoantibodies have been shown to be predominantly directed against BP180 (also called BPAG2, type XVII collagen), BP230, laminin 332 and type VII collagen, components of junctional adhesion complexes promoting epithelial stromal attachment in stratified epithelia. Various disease assessment scores are available, including the Mucous Membrane Pemphigoid Disease Area Index (MMPDAI), the Autoimmune Bullous Skin disorder Intensity Score (ABSIS), the 'Cicatrising Conjunctivitis Assessment Tool' and the Oral Disease Severity Score (ODSS). Patient-reported outcome measurements (PROMs), including DLQI, ABQOL and TABQOL, can be used for assessment of quality of life to evaluate the effectiveness of therapeutic interventions and monitor disease course.Neurological disorders are a leading cause of disease burden worldwide, placing a heavy demand on health systems. This study evaluated the impacts and cost savings of a community-based nursing service providing supported discharge for neurological patients deemed high-risk for unplanned emergency department presentations and/or hospital readmissions. It focused on adult patients with stroke, epilepsy, migraine/headache or functional neurological disorders discharged from a Western Australian tertiary hospital. An observational design was used comprising prospective enrolment of patients receiving nurse-led supported discharge and follow-up (Neurocare), 21 August 2018 to 6 December 2019 (N = 81), and hospital administrative data, 1 February 2016 to 31 January 2018, for patients in previous care model (N = 740). Healthcare utilisation and annualised cost savings from reduced rehospitalisation and/or emergency department presentations within 28 days post discharge were compared. Neurocare patients' postdischarge quality of life may positively impact healthcare utilisation. Future research should include larger patient samples and multiple sites.Charge carrier transport in colloidal quantum dot (CQD) solids is strongly influenced by coupling among CQDs. The shape of as-synthesized CQDs results in random orientational relationships among facets in CQD solids, and this limits the CQD coupling strength and the resultant performance of optoelectronic devices. Here, colloidal-phase reconstruction of CQD surfaces, which improves facet alignment in CQD solids, is reported. This strategy enables control over CQD faceting and allows demonstration of enhanced coupling in CQD solids. The approach utilizes post-synthetic resurfacing and unites surface passivation and colloidal stability with a propensity for dots to couple via (100)(100) facets, enabling increased hole mobility. Experimentally, the CQD solids exhibit a 10× increase in measured hole mobility compared to control CQD solids, and enable photodiodes (PDs) exhibiting 70% external quantum efficiency (vs 45% for control devices) and specific detectivity, D* > 1012 Jones, each at 1550 nm. The photodetectors feature a 7 ns response time for a 0.01 mm2 area-the fastest reported for solution-processed short-wavelength infrared PDs.The impact of sex on immune composition in the setting of solid organ transplantation is unknown. Immunocompetent men and women have quantitative differences in multiple markers of immunity, including lymphocyte subsets. Lymphocytes are of particular interest given the routine use of medications targeted at cell-mediated immunity. The objective of this retrospective cohort study was to compare absolute lymphocyte count (ALC) measurements of male and female heart recipients immediately before, and 1 month after, transplantation. Data was collected on 375 adult recipients (104 female and 271 male) from 2000 to 2018 at a single center. Mean ALC was compared using Student's t-test. Women had higher mean ALC both at baseline (female 1.6 × 103 cells/μl vs. male 1.3 × 103 cells/μl; P less then .001) and at 1 month post-transplantation (mean 1.2 × 103 cells/μl vs. .8 × 103 cells/μl; P less then .001). This finding could have important implications for sex-based differences in predisposition to rejection or response to infection or vaccination.
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