NONLINEAR POLARIZATION SPECTROSCOPY (FREQUENCY DOMAIN) STUDIES OF EXCITED STATE PROCESSES: THE B800–850ANTENNA OF RHODOBACTER SPHAEROIDES

Nonlinear polarization spectroscopy in the frequency domain allows rate constant determinations of fast electronic energy and phase relaxations together with characterization of the type of line broadening. Application of this method to the B850 component of the isolated B800–850antenna ofRhodobacter sphaeroides at room temperature shows that B850 is inhomogeneously broadened, with homogeneous widths between 30 and 200 cm−1, depending on the spectral position of the subforms. The corresponding phase relaxation times are clearly in the subpicosecond range. There is also indication of an up-to-now unspecified1–5 ps energy relaxation channel per subunit

REACTIVITY OF CHLOROPHYLL a/b-PROTEINS AND MICELLAR TRITON X-100 COMPLEXES OF CHLOROPHYLLS a OR b WITH BOROHYDRIDE

The reaction of several plant chlorophyll-protein complexes with NaBH4 has been studied by absorption spectroscopy. In all the complexes studied, chlorophyll b is more reactive than Chi a, due to preferential reaction of its formyl substituent at C-7. The complexes also show large variations in reactivity towards NaBH4 and the order of reactivity is: LHCI > PSII complex > LHCII > PSI > P700 (investigated as a component of PSI). Differential pools of the same type of chlorophyll have been observed in several complexes. Parallel work was undertaken on the reactivity of micellar complexes of chlorophyll a and of chlorophyll b with NaBH4 to study the effect of aggregation state on this reactivity. In these complexes, both chlorophyll a and b show large variations in reactivity in the order monomer > oligomer > polymer with chlorophyll b generally being more reactive than chlorophyll a. It is concluded that aggregation decreases the reactivity of chlorophylls towards NaBH4 in vitro, and may similarly decrease reactivity in naturally-occurring chlorophyll-protein complexes

Assessing MWCNT-graphene surface energy through in situ SEM peeling

Carbon nanotubes (CNTs) are envisioned as ideal filaments for next-generation nanocomposites due to their high strength-to-weight ratios. However, while individual nanotubes are strong, interfaces between tubes cannot bear significant load due to the weak van der Waals forces that govern their behavior. Premature interfacial failure could thus counteract the inherent strength of carbon nanotubes and, in turn, prevent CNT-based composites from achieving optimal mechanical performance. To increase the load bearing capacity of these interfaces, interlayer crosslinking schemes have been proposed using chemical functionalization. For instance, introduction of hydrogen bonds or additional van der Waals bonds between tubes could improve load transfer between CNTs. While introducing chemical groups on CNT surfaces may enhance intermolecular interactions at these interfaces, a means of quantitatively evaluating changes in interlayer adhesion as a result of to these treatments needs to be defined. In addition, as sizes of CNTs will inherently vary within a composite, it is important that such energy measurements be normalized irrespective of tube dimensions. Here we report an experimental peeling technique that can be used to measure the adhesion energy between multiwalled carbon nanotubes (MWCNTs) and graphene. Peeling tests conducted in situ a scanning electron microscope allow direct visualization of the nanoscale peeling process which, in turn, enables adhesion energy to be estimated through classical fracture analysis. The applicability of this analysis is validated by finite element simulations with boundary conditions derived from experiments. The effective contact width between tubes and graphene is estimated via atomistic simulations, providing a means to normalize interaction energy per unit area. The surface energies of bare MWCNT-graphene interfaces found in this study compare favorably with theoretical and experimental values reported for graphite. This method can serve as a foundation for evaluating the enhancements afforded by chemical functionalization, which is a critical step toward the development of strong, lightweight composites that effectively utilize the full mechanical potential of CNTs

Instrument-based Tests for Measuring Anterior Chamber Cells in Uveitis: A Systematic Review

Purpose: New instrument-based techniques for anterior chamber (AC) cell counting can offer automation and objectivity above clinician assessment. This review aims to identify such instruments and its correlation with clinician estimates. Methods: Using standard systematic review methodology, we identified and tabulated the outcomes of studies reporting reliability and correlation between instrument-based measurements and clinician AC cell grading. Results: From 3470 studies, 6 reported correlation between an instrument-based AC cell count to clinician grading. The two instruments were optical coherence tomography (OCT) and laser flare-cell photometry (LFCP). Correlation between clinician grading and LFCP was 0.66–0.87 and 0.06–0.97 between clinician grading and OCT. OCT volume scans demonstrated correlation between 0.75 and 0.78. Line scans in the middle AC demonstrated higher correlation (0.73–0.97) than in the inferior AC (0.06–0.56). Conclusion: AC cell count by OCT and LFP can achieve high levels of correlation with clinician grading, whilst offering additional advantages of speed, automation, and objectivity

A Histone Methylation Network Regulates Transgenerational Epigenetic Memory in C. elegans

How epigenetic information is transmitted from generation to generation remains largely unknown. Deletion of the C. elegans Histone H3 lysine 4 dimethyl (H3K4me2) demethylase spr-5 leads to inherited accumulation of the euchromatic H3K4me2 mark and progressive decline in fertility. Here we identified multiple chromatin-modifying factors, including novel H3K4me1/me2 and H3K9me3 methyltransferases, an H3K9me3 demethylase and an H3K9me reader, which either suppress or accelerate the progressive transgenerational phenotypes of spr-5 mutant worms. Our findings uncover a network of chromatin regulators that control the trans-generational flow of epigenetic information, and suggest that the balance between euchromatic H3K4 and heterochromatic H3K9 methylation regulates trans-generational effects on fertility

Rapid, point‐of‐care antigen and molecular‐based tests for diagnosis of SARS‐CoV‐2 infection

Background Accurate rapid diagnostic tests for SARS‐CoV‐2 infection could contribute to clinical and public health strategies to manage the COVID‐19 pandemic. Point‐of‐care antigen and molecular tests to detect current infection could increase access to testing and early confirmation of cases, and expediate clinical and public health management decisions that may reduce transmission. Objectives To assess the diagnostic accuracy of point‐of‐care antigen and molecular‐based tests for diagnosis of SARS‐CoV‐2 infection. We consider accuracy separately in symptomatic and asymptomatic population groups. Search methods Electronic searches of the Cochrane COVID‐19 Study Register and the COVID‐19 Living Evidence Database from the University of Bern (which includes daily updates from PubMed and Embase and preprints from medRxiv and bioRxiv) were undertaken on 30 Sept 2020. We checked repositories of COVID‐19 publications and included independent evaluations from national reference laboratories, the Foundation for Innovative New Diagnostics and the Diagnostics Global Health website to 16 Nov 2020. We did not apply language restrictions. Selection criteria We included studies of people with either suspected SARS‐CoV‐2 infection, known SARS‐CoV‐2 infection or known absence of infection, or those who were being screened for infection. We included test accuracy studies of any design that evaluated commercially produced, rapid antigen or molecular tests suitable for a point‐of‐care setting (minimal equipment, sample preparation, and biosafety requirements, with results within two hours of sample collection). We included all reference standards that define the presence or absence of SARS‐CoV‐2 (including reverse transcription polymerase chain reaction (RT‐PCR) tests and established diagnostic criteria). Data collection and analysis Studies were screened independently in duplicate with disagreements resolved by discussion with a third author. Study characteristics were extracted by one author and checked by a second; extraction of study results and assessments of risk of bias and applicability (made using the QUADAS‐2 tool) were undertaken independently in duplicate. We present sensitivity and specificity with 95% confidence intervals (CIs) for each test and pooled data using the bivariate model separately for antigen and molecular‐based tests. We tabulated results by test manufacturer and compliance with manufacturer instructions for use and according to symptom status. Main results Seventy‐eight study cohorts were included (described in 64 study reports, including 20 pre‐prints), reporting results for 24,087 samples (7,415 with confirmed SARS‐CoV‐2). Studies were mainly from Europe (n = 39) or North America (n = 20), and evaluated 16 antigen and five molecular assays. We considered risk of bias to be high in 29 (37%) studies because of participant selection; in 66 (85%) because of weaknesses in the reference standard for absence of infection; and in 29 (37%) for participant flow and timing. Studies of antigen tests were of a higher methodological quality compared to studies of molecular tests, particularly regarding the risk of bias for participant selection and the index test. Characteristics of participants in 35 (45%) studies differed from those in whom the test was intended to be used and the delivery of the index test in 39 (50%) studies differed from the way in which the test was intended to be used. Nearly all studies (97%) defined the presence or absence of SARS‐CoV‐2 based on a single RT‐PCR result, and none included participants meeting case definitions for probable COVID‐19. Antigen tests Forty‐eight studies reported 58 evaluations of antigen tests. Estimates of sensitivity varied considerably between studies. There were differences between symptomatic (72.0%, 95% CI 63.7% to 79.0%; 37 evaluations; 15530 samples, 4410 cases) and asymptomatic participants (58.1%, 95% CI 40.2% to 74.1%; 12 evaluations; 1581 samples, 295 cases). Average sensitivity was higher in the first week after symptom onset (78.3%, 95% CI 71.1% to 84.1%; 26 evaluations; 5769 samples, 2320 cases) than in the second week of symptoms (51.0%, 95% CI 40.8% to 61.0%; 22 evaluations; 935 samples, 692 cases). Sensitivity was high in those with cycle threshold (Ct) values on PCR ≤25 (94.5%, 95% CI 91.0% to 96.7%; 36 evaluations; 2613 cases) compared to those with Ct values >25 (40.7%, 95% CI 31.8% to 50.3%; 36 evaluations; 2632 cases). Sensitivity varied between brands. Using data from instructions for use (IFU) compliant evaluations in symptomatic participants, summary sensitivities ranged from 34.1% (95% CI 29.7% to 38.8%; Coris Bioconcept) to 88.1% (95% CI 84.2% to 91.1%; SD Biosensor STANDARD Q). Average specificities were high in symptomatic and asymptomatic participants, and for most brands (overall summary specificity 99.6%, 95% CI 99.0% to 99.8%). At 5% prevalence using data for the most sensitive assays in symptomatic people (SD Biosensor STANDARD Q and Abbott Panbio), positive predictive values (PPVs) of 84% to 90% mean that between 1 in 10 and 1 in 6 positive results will be a false positive, and between 1 in 4 and 1 in 8 cases will be missed. At 0.5% prevalence applying the same tests in asymptomatic people would result in PPVs of 11% to 28% meaning that between 7 in 10 and 9 in 10 positive results will be false positives, and between 1 in 2 and 1 in 3 cases will be missed. No studies assessed the accuracy of repeated lateral flow testing or self‐testing. Rapid molecular assays Thirty studies reported 33 evaluations of five different rapid molecular tests. Sensitivities varied according to test brand. Most of the data relate to the ID NOW and Xpert Xpress assays. Using data from evaluations following the manufacturer’s instructions for use, the average sensitivity of ID NOW was 73.0% (95% CI 66.8% to 78.4%) and average specificity 99.7% (95% CI 98.7% to 99.9%; 4 evaluations; 812 samples, 222 cases). For Xpert Xpress, the average sensitivity was 100% (95% CI 88.1% to 100%) and average specificity 97.2% (95% CI 89.4% to 99.3%; 2 evaluations; 100 samples, 29 cases). Insufficient data were available to investigate the effect of symptom status or time after symptom onset. Authors' conclusions Antigen tests vary in sensitivity. In people with signs and symptoms of COVID‐19, sensitivities are highest in the first week of illness when viral loads are higher. The assays shown to meet appropriate criteria, such as WHO's priority target product profiles for COVID‐19 diagnostics (‘acceptable’ sensitivity ≥ 80% and specificity ≥ 97%), can be considered as a replacement for laboratory‐based RT‐PCR when immediate decisions about patient care must be made, or where RT‐PCR cannot be delivered in a timely manner. Positive predictive values suggest that confirmatory testing of those with positive results may be considered in low prevalence settings. Due to the variable sensitivity of antigen tests, people who test negative may still be infected. Evidence for testing in asymptomatic cohorts was limited. Test accuracy studies cannot adequately assess the ability of antigen tests to differentiate those who are infectious and require isolation from those who pose no risk, as there is no reference standard for infectiousness. A small number of molecular tests showed high accuracy and may be suitable alternatives to RT‐PCR. However, further evaluations of the tests in settings as they are intended to be used are required to fully establish performance in practice. Several important studies in asymptomatic individuals have been reported since the close of our search and will be incorporated at the next update of this review. Comparative studies of antigen tests in their intended use settings and according to test operator (including self‐testing) are required

Multiple novel prostate cancer susceptibility signals identified by fine-mapping of known risk loci among Europeans

Genome-wide association studies (GWAS) have identified numerous common prostate cancer (PrCa) susceptibility loci. We have fine-mapped 64 GWAS regions known at the conclusion of the iCOGS study using large-scale genotyping and imputation in 25 723 PrCa cases and 26 274 controls of European ancestry. We detected evidence for multiple independent signals at 16 regions, 12 of which contained additional newly identified significant associations. A single signal comprising a spectrum of correlated variation was observed at 39 regions; 35 of which are now described by a novel more significantly associated lead SNP, while the originally reported variant remained as the lead SNP only in 4 regions. We also confirmed two association signals in Europeans that had been previously reported only in East-Asian GWAS. Based on statistical evidence and linkage disequilibrium (LD) structure, we have curated and narrowed down the list of the most likely candidate causal variants for each region. Functional annotation using data from ENCODE filtered for PrCa cell lines and eQTL analysis demonstrated significant enrichment for overlap with bio-features within this set. By incorporating the novel risk variants identified here alongside the refined data for existing association signals, we estimate that these loci now explain ∼38.9% of the familial relative risk of PrCa, an 8.9% improvement over the previously reported GWAS tag SNPs. This suggests that a significant fraction of the heritability of PrCa may have been hidden during the discovery phase of GWAS, in particular due to the presence of multiple independent signals within the same regio