High-density information storage in an absolutely defined aperiodic sequence of monodisperse copolyester

Synthesis of a polymer composed of a large discrete number of chemically distinct monomers in an absolutely defined aperiodic sequence remains a challenge in polymer chemistry. The synthesis has largely been limited to oligomers having a limited number of repeating units due to the difficulties associated with the step-by-step addition of individual monomers to achieve high molecular weights. Here we report the copolymers of ??-hydroxy acids, poly(phenyllactic-co-lactic acid) (PcL) built via the cross-convergent method from four dyads of monomers as constituent units. Our proposed method allows scalable synthesis of sequence-defined PcL in a minimal number of coupling steps from reagents in stoichiometric amounts. Digital information can be stored in an aperiodic sequence of PcL, which can be fully retrieved as binary code by mass spectrometry sequencing. The information storage density (bit/Da) of PcL is 50% higher than DNA, and the storage capacity of PcL can also be increased by adjusting the molecular weight (~38???kDa)

A new perspective of the climatological features of upper-level cut-off lows in the Southern Hemisphere

This study presents a detailed view of the seasonal variability of upper-level cut-off lows (COLs) in the Southern Hemisphere. The COLs are identified and tracked using data from a 36-year period of the European Centre for Medium Range Weather Forecast reanalysis (ERA-Interim). The objective identification of the COLs uses a new approach, which is based on 300 hPa relative vorticity minima, and three restrictive criteria of the presence of a cold-core, stratospheric potential vorticity intrusion, and cut-off cyclonic circulation. The highest COL activity is in agreement with previous studies, located near three main continental areas (Australia, South America, and Africa), with maximum frequencies usually observed in the austral autumn. The COL mean intensity values show a marked seasonal and spatial variation, with maximum (minimum) values during the austral winter (summer), a unique feature that has not been observed previously in studies based on the geopotential. The link between intensity and lysis is examined, and finds that weaker systems are more susceptible to lysis in the vicinity of the Andes Cordillera, associated with the topographic Rossby wave. Lysis and genesis regions are close to each other, confirming that COLs are quasi-stationary systems. Also, COLs tend to move eastward and are faster over the higher latitudes. The mean growth/decay rates coincide with the major genesis and lysis density regions, such as the significant decay values across the Andes all year. As a consequence of using vorticity for the tracking method a longer lifetime of COLs is detected than in other studies, but this does not affect the total frequency of occurrence. Comparisons with other studies suggest that the differences in seasonality are due to uncertainties in the reanalyses and the methods used to identify COLs

Simulating the midlatitude atmospheric circulation: what might we gain from high-resolution modeling of air-sea interactions?

Purpose of Review. To provide a snapshot of the current research on the oceanic forcing of the atmospheric circulation in midlatitudes and a concise update on previous review papers. Recent findings. Atmospheric models used for seasonal and longer timescales predictions are starting to resolve motions so far only studied in conjunction with weather forecasts. These phenomena have horizontal scales of ~ 10–100 km which coincide with energetic scales in the ocean circulation. Evidence has been presented that, as a result of this matching of scale, oceanic forcing of the atmosphere was enhanced in models with 10–100 km grid size, especially at upper tropospheric levels. The robustness of these results and their underlying mechanisms are however unclear. Summary. Despite indications that higher resolution atmospheric models respond more strongly to sea surface temperature anomalies, their responses are still generally weaker than those estimated empirically from observations. Coarse atmospheric models (grid size greater than 100 km) will miss important signals arising from future changes in ocean circulation unless new parameterizations are developed

A randomised phase II trial of docetaxel vs docetaxel and irinotecan in patients with stage IIIb–IV non-small-cell lung cancer who failed first-line treatment

Response rate and toxicity of second-line therapy with docetaxel (75 mg m−2) or docetaxel, irinotecan, and lenogastrim (60 mg m−2, 200 mg m−2, and 150 μg m−2 day−1, respectively) were compared in 108 patients with stage IIIb–IV non-small-cell lung cancer. Addition of irinotecan to docetaxel does not improve response rate, and increases gastrointestinal toxicity

Mechanism and timing of Mcm2–7 ring closure during DNA replication origin licensing

The opening and closing of two ring-shaped Mcm2-7 DNA helicases is necessary to license eukaryotic origins of replication, although the mechanisms controlling these events are unclear. The origin-recognition complex (ORC), Cdc6 and Cdt1 facilitate this process by establishing a topological link between each Mcm2-7 hexamer and origin DNA. Using colocalization single-molecule spectroscopy and single-molecule Förster resonance energy transfer (FRET), we monitored ring opening and closing of Saccharomyces cerevisiae Mcm2-7 during origin licensing. The two Mcm2-7 rings were open during initial DNA association and closed sequentially, concomitant with the release of their associated Cdt1. We observed that ATP hydrolysis by Mcm2-7 was coupled to ring closure and Cdt1 release, and failure to load the first Mcm2-7 prevented recruitment of the second Mcm2-7. Our findings identify key mechanisms controlling the Mcm2-7 DNA-entry gate during origin licensing, and reveal that the two Mcm2-7 complexes are loaded via a coordinated series of events with implications for bidirectional replication initiation and quality control.National Institutes of Health (U.S.) (Grant R01 GM52339)National Institutes of Health (U.S.) (Pre-Doctoral Training Grant GM007287)National Cancer Institute (U.S.) (Koch Institute Support Grant P30-CA14051

The variable link between PNA and NAO in observations and in multi-century CGCM simulations

The link between the Pacific/North American pattern (PNA) and the North Atlantic Oscillation (NAO) is investigated in reanalysis data (NCEP, ERA40) and multi-century CGCM runs for present day climate using three versions of the ECHAM model. PNA and NAO patterns and indices are determined via rotated principal component analysis on monthly mean 500 hPa geopotential height fields using the varimax criteria. On average, the multi-century CGCM simulations show a significant anti-correlation between PNA and NAO. Further, multi-decadal periods with significantly enhanced (high anti-correlation, active phase) or weakened (low correlations, inactive phase) coupling are found in all CGCMs. In the simulated active phases, the storm track activity near Newfoundland has a stronger link with the PNA variability than during the inactive phases. On average, the reanalysis datasets show no significant anti-correlation between PNA and NAO indices, but during the sub-period 1973–1994 a significant anti-correlation is detected, suggesting that the present climate could correspond to an inactive period as detected in the CGCMs. An analysis of possible physical mechanisms suggests that the link between the patterns is established by the baroclinic waves forming the North Atlantic storm track. The geopotential height anomalies associated with negative PNA phases induce an increased advection of warm and moist air from the Gulf of Mexico and cold air from Canada. Both types of advection contribute to increase baroclinicity over eastern North America and also to increase the low level latent heat content of the warm air masses. Thus, growth conditions for eddies at the entrance of the North Atlantic storm track are enhanced. Considering the average temporal development during winter for the CGCM, results show an enhanced Newfoundland storm track maximum in the early winter for negative PNA, followed by a downstream enhancement of the Atlantic storm track in the subsequent months. In active (passive) phases, this seasonal development is enhanced (suppressed). As the storm track over the central and eastern Atlantic is closely related to the NAO variability, this development can be explained by the shift of the NAO index to more positive values

National policy development for cotrimoxazole prophylaxis in Malawi, Uganda and Zambia: the relationship between Context, Evidence and Links

BACKGROUND: Several frameworks have been constructed to analyse the factors which influence and shape the uptake of evidence into policy processes in resource poor settings, yet empirical analyses of health policy making in these settings are relatively rare. National policy making for cotrimoxazole (trimethoprim-sulfamethoxazole) preventive therapy in developing countries offers a pertinent case for the application of a policy analysis lens. The provision of cotrimoxazole as a prophylaxis is an inexpensive and highly efficacious preventative intervention in HIV infected individuals, reducing both morbidity and mortality among adults and children with HIV/AIDS, yet evidence suggests that it has not been quickly or evenly scaled-up in resource poor settings. METHODS: Comparative analysis was conducted in Malawi, Uganda and Zambia, using the case study approach. We applied the 'RAPID' framework developed by the Overseas Development Institute (ODI), and conducted a total of 47 in-depth interviews across the three countries to examine the influence of context (including the influence of donor agencies), evidence (both local and international), and the links between researcher, policy makers and those seeking to influence the policy process. RESULTS: Each area of analysis was found to have an influence on the creation of national policy on cotrimoxazole preventive therapy (CPT) in all three countries. In relation to context, the following were found to be influential: government structures and their focus, donor interest and involvement, healthcare infrastructure and other uses of cotrimoxazole and related drugs in the country. In terms of the nature of the evidence, we found that how policy makers perceived the strength of evidence behind international recommendations was crucial (if evidence was considered weak then the recommendations were rejected). Further, local operational research results seem to have been taken up more quickly, while randomised controlled trials (the gold standard of clinical research) was not necessarily translated into policy so swiftly. Finally the links between different research and policy actors were of critical importance, with overlaps between researcher and policy maker networks crucial to facilitate knowledge transfer. Within these networks, in each country the policy development process relied on a powerful policy entrepreneur who helped get cotrimoxazole preventive therapy onto the policy agenda. CONCLUSIONS: This analysis underscores the importance of considering national level variables in the explanation of the uptake of evidence into national policy settings, and recognising how local policy makers interpret international evidence. Local priorities, the ways in which evidence was interpreted, and the nature of the links between policy makers and researchers could either drive or stall the policy process. Developing the understanding of these processes enables the explanation of the use (or non-use) of evidence in policy making, and potentially may help to shape future strategies to bridge the research-policy gaps and ultimately improve the uptake of evidence in decision making

Blocking and its response to climate change

Purpose of review: Atmospheric blocking events represent some of the most high-impact weather patterns in the mid-latitudes, yet they have often been a cause for concern in future climate projections. There has been low confidence in predicted future changes in blocking, despite relatively good agreement between climate models on a decline in blocking. This is due to the lack of a comprehensive theory of blocking and a pervasive underestimation of blocking occurrence by models. This paper reviews the state of knowledge regarding blocking under climate change, with the aim of providing an overview for those working in related fields. Recent Findings: Several avenues have been identified by which blocking can be improved in numerical models, though a fully reliable simulation remains elusive (at least, beyond a few days lead time). Models are therefore starting to provide some useful information on how blocking and its impacts may change in the future, although deeper understanding of the processes at play will be needed to increase confidence in model projections. There are still major uncertainties regarding the processes most important to the onset, maintenance and decay of blocking and advances in our understanding of atmospheric dynamics, for example in the role of diabatic processes, continue to inform the modelling and prediction efforts. Summary: The term ‘blocking’ covers a diverse array of synoptic patterns, and hence a bewildering range of indices has been developed to identify events. Results are hence not considered fully trustworthy until they have been found using several different methods. Examples of such robust results are the underestimation of blocking by models, and an overall decline in future occurrence, albeit with a complex regional and seasonal variation. In contrast, hemispheric trends in blocking over the recent historical period are not supported by different methods, and natural variability will likely dominate regional variations over the next few decades

A population-based study of race-specific risk for placental abruption

<p>Abstract</p> <p>Background</p> <p>Efforts to elucidate risk factors for placental abruption are imperative due to the severity of complications it produces for both mother and fetus, and its contribution to preterm birth. Ethnicity-based differences in risk of placental abruption and preterm birth have been reported. We tested the hypotheses that race, after adjusting for other factors, is associated with the risk of placental abruption at specific gestational ages, and that there is a greater contribution of placental abruption to the increased risk of preterm birth in Black mothers, compared to White mothers.</p> <p>Methods</p> <p>We conducted a population-based cohort study using the Missouri Department of Health's maternally-linked database of all births in Missouri (1989–1997) to assess racial effects on placental abruption and the contribution of placental abruption to preterm birth, at different gestational age categories (n = 664,303).</p> <p>Results</p> <p>Among 108,806 births to Black mothers and 555,497 births to White mothers, 1.02% (95% CI 0.96–1.08) of Black births were complicated by placental abruption, compared to 0.71% (95% CI 0.69–0.73) of White births (aOR 1.32, 95% CI 1.22–1.43). The magnitude of risk of placental abruption for Black mothers, compared to White mothers, increased with younger gestational age categories. The risk of placental abruption resulting in term and extreme preterm births (< 28 weeks) was higher for Black mothers (aOR 1.15, 95% CI 1.02–1.29 and aOR 1.98, 95% CI 1.58–2.48, respectively). Compared to White women delivering in the same gestational age category, there were a significantly higher proportion of placental abruption in Black mothers who delivered at term, and a significantly lower proportion of placental abruption in Black mothers who delivered in all preterm categories (p < 0.05).</p> <p>Conclusion</p> <p>Black women have an increased risk of placental abruption compared to White women, even when controlling for known coexisting risk factors. This risk increase is greatest at the earliest preterm gestational ages when outcomes are the poorest. The relative contribution of placental abruption to term births was greater in Black women, whereas the relative contribution of placental abruption to preterm birth was greater in White women.</p