The decreased PG content of pgp1 inhibits PSI photochemistry and limits reaction center and light-harvesting polypeptide accumulation in response to cold acclimation.

MAIN CONCLUSION: Decreased PG constrains PSI activity due to inhibition of transcript and polypeptide abundance of light-harvesting and reaction center polypeptides generating a reversible, yellow phenotype during cold acclimation of pgp1. Cold acclimation of the Arabidopsis pgp1 mutant at 5 °C resulted in a pale-yellow phenotype with abnormal chloroplast ultrastructure compared to its green phenotype upon growth at 20 °C despite a normal cold-acclimation response at the transcript level. In contrast, wild type maintained its normal green phenotype and chloroplast ultrastructure irrespective of growth temperature. In contrast to cold acclimation of WT, growth of pgp1 at 5 °C limited the accumulation of Lhcbs and Lhcas assessed by immunoblotting. However, a novel 43 kD polypeptide of Lhcb1 as well as a 29 kD polypeptide of Lhcb3 accumulated in the soluble fraction which was absent in the thylakoid membrane fraction of cold-acclimated pgp1 which was not observed in WT. Cold acclimation of pgp1 destabilized the Chl-protein complexes associated with PSI and predisposed energy distribution in favor of PSII rather than PSI compared to the WT. Functionally, in vivo PSI versus PSII photochemistry was inhibited in cold-acclimated pgp1 to a greater extent than in WT relative to controls. Greening of the pale-yellow pgp1 was induced when cold-acclimated pgp1 was shifted from 5 to 20 °C which resulted in a marked decrease in excitation pressure to a level comparable to WT. Concomitantly, Lhcbs and Lhcas accumulated with a simultaneous decrease in the novel 43 and 29kD polypeptides. We conclude that the reduced levels of phosphatidyldiacylglycerol in the pgp1 limit the capacity of the mutant to maintain the structure and function of its photosynthetic apparatus during cold acclimation. Thus, maintenance of normal thylakoid phosphatidyldiacylglycerol levels is essential to stabilize the photosynthetic apparatus during cold acclimation.

***ECD*** maternal C-reactive protein as a predictor of neonatal sepsis.

Systemic bacterial infection in the newborn has a significant impact on neonatal mortality and morbidity. Non-invasive prenatal markers of risk could be useful in the prediction and prevention of neonatal sepsis. We evaluated the association of maternal third-trimester serum level of C-Reactive Protein (CRP) with neonatal sepsis in a sample of infants in the JAKids pregnancy and birth cohort study. A population-based nested case-control design was used to identify cases and controls of neonatal sepsis from the subset of infants in the JAKids study whose mothers had serum archived in the early third trimester and who were admitted to newborn intensive care. Cases were 25 neonates with neonatal sepsis identified from hospital records. Controls were a random sample of 62 sepsis-free neonates matched to cases within three gestational age strata - ≤32 weeks, 33-36 weeks, and ≥37 weeks.Mothers of neonatal sepsis cases ≥37 weeks had significantly higher mean levels of maternal CRP protein than mothers of controls (11.0 mg/dL ± 3.0 vs. 8.7 mg/dL ± 5.9; p < .05). Differences in maternal CRP were not found in sepsis cases born ≤32 weeks (9.5 mg/dL ± 4.2 vs 5.8 mg/dL ± 4.0, p = .23) nor in sepsis cases born at 33-36 weeks (9.0 mg/dL ± 3.6 vs 11.9 mg/dL ± 7.8, p = .34). Maternal third-trimester C-reactive protein levels were elevated in mothers of term-born neonates with sepsis, but not in the mothers of preterm neonates with sepsis.

Swelling of Transported Smoke from Savanna fires over the Southeast Atlantic Ocean.

We use the recently released Cloud Aerosol Lidar and Infrared Pathfinder Satellite Observations (CALIPSO) Version 4.1 (V4) lidar data to study the smoke plumes transported from Southern African biomass burning areas. Significant improvements in the CALIPSO V4 Level 1 calibration and V4 Level 2 algorithms lead to a better representation of their optical properties, with the aerosol subtype improvements being particularly relevant to smoke over this area. For the first time, we show evidence of smoke particles increasing in size, evidenced in their particulate color ratios, as they are transported over the South Atlantic Ocean from the source regions over Southern Africa. We hypothesize that this is due to hygroscopic swelling of the smoke particles and is reflected in the higher relative humidity in the middle troposphere for profiles with smoke. This finding may have implications for radiative forcing estimates over this area and is also relevant to the ORACLES field mission.

Making EBSD on water ice routine.

Electron backscatter diffraction (EBSD) on ice is a decade old. We have built upon previous work to select and develop methods of sample preparation and analysis that give >90% success rate in obtaining high-quality EBSD maps, for the whole surface area (potentially) of low porosity (<15%) water ice samples, including very fine-grained (<10 µm) and very large (up to 70 mm by 30 mm) samples. We present and explain two new methods of removing frost and providing a damage-free surface for EBSD: pressure cycle sublimation and 'ironing'. In general, the pressure cycle sublimation method is preferred as it is easier, faster and does not generate significant artefacts. We measure the thermal effects of sample preparation, transfer and storage procedures and model the likelihood of these modifying sample microstructures. We show results from laboratory ice samples, with a wide range of microstructures, to illustrate effectiveness and limitations of EBSD on ice and its potential applications. The methods we present can be implemented, with a modest investment, on any scanning electron microscope system with EBSD, a cryostage and a variable pressure capability.

Directed delivery of terahertz frequency radiation from quantum cascade lasers within a dry 3He dilution refrigerator.

We present a scheme for the full integration of terahertz (THz) frequency quantum cascade lasers (QCLs) within a dilution refrigerator in order to provide a directed delivery of THz power into the sample space. We describe a successful operation of a 2.68 THz QCL located on the pulse tube cooler stage of the refrigerator, with its output coupled onto a two-dimensional electron gas (2DEG) located on a milli-kelvin sample stage via hollow metal waveguides and Hysol thermal isolators, achieving a total loss from QCL to the sample of ∼-9 dB. The thermal isolators limit heat leaks to the sample space, with a base temperature of ∼210 mK being achieved. We observe cyclotron resonance (CR) induced in the 2DEG by the QCL and explore the heating impact of the QCL on all stages of the refrigerator. The CR effect induced by the THz QCL is observable at electron temperatures as low as ∼430 mK. The results show a viable route for the exploitation of THz QCLs within the environment of a dilution refrigerator and for the THz power delivery in very low-temperature (<0.5 K) condensed matter experiments.

Cediranib in addition to chemotherapy for women with relapsed platinum-sensitive ovarian cancer (ICON6): overall survival results of a phase III randomised trial.

BACKGROUND: Cediranib, an oral anti-angiogenic VEGFR 1-3 inhibitor, was studied at a daily dose of 20 mg in combination with platinum-based chemotherapy and as maintenance in a randomised trial in patients with first relapse of 'platinum-sensitive' ovarian cancer and has been shown to improve progression-free survival (PFS). PATIENTS AND METHODS: ICON6 (NCT00532194) was an international three-arm, double-blind, placebo-controlled randomised trial. Between December 2007 and December 2011, 456 women were randomised, using stratification, to receive either chemotherapy with placebo throughout (arm A, reference); chemotherapy with concurrent cediranib, followed by maintenance placebo (arm B, concurrent); or chemotherapy with concurrent cediranib, followed by maintenance cediranib (arm C, maintenance). Due to an enforced redesign of the trial in September 2011, the primary endpoint became PFS between arms A and C which we have previously published, and the overall survival (OS) was defined as a secondary endpoint, which is reported here. RESULTS: After a median follow-up of 25.6 months, strong evidence of an effect of concurrent plus maintenance cediranib on PFS was observed [hazard ratio (HR) 0.56, 95% confidence interval (CI) 0.44-0.72, P < 0.0001]. In this final update of the survival analysis, 90% of patients have died. There was a 7.4-month difference in median survival and an HR of 0.86 (95% CI: 0.67-1.11, P = 0.24) in favour of arm C. There was strong evidence of a departure from the assumption of non-proportionality using the Grambsch-Therneau test (P = 0.0031), making the HR difficult to interpret. Consequently, the restricted mean survival time (RMST) was used and the estimated difference over 6 years by the RMST was 4.8 months (95% CI: -0.09 to 9.74 months). CONCLUSIONS: Although a statistically significant difference in time to progression was seen, the enforced curtailment in recruitment meant that the secondary analysis of OS was underpowered. The relative reduction in the risk of death of 14% risk of death was not conventionally statistically significant, but this improvement and the increase in the mean survival time in this analysis suggest that cediranib may have worthwhile activity in the treatment of recurrent ovarian cancer and that further research should be undertaken.

Impact of the Jamaican birth cohort study on maternal, child and adolescent health policy and practice.

The Jamaica Perinatal Morbidity and Mortality Survey (JPMMS) was a national study designed to identify modifiable risk factors associated with poor maternal and perinatal outcome. Needing to better understand factors that promote or retard child development, behaviour and academic achievement, we conducted follow-up studies of the birth cohort. The paper describes the policy developments from the JPMMS and two follow-up rounds. The initial study (1986-87) documented 94% of all births and their outcomes on the island over 2 months (n = 10 508), and perinatal (n = 2175) and maternal deaths (n = 62) for a further 10 months. A subset of the birth cohort, identified by their date of birth through school records, was seen at ages 11-12 (n = 1715) and 15-16 years (n = 1563). Findings from the initial survey led to, inter alia, clinic-based screening for syphilis, referral high-risk clinics run by visiting obstetricians, and the redesign and construction of new labour wards at referral hospitals. The follow-up studies documented inadequate academic achievement among boys and children attending public schools, and associations between under- and over-nutrition, excessive television viewing (>20 h/week), inadequate parental supervision and behavioural problems. These contributed to the development of a television programming code for children, a National Parenting Policy, policies aimed at improving inter-sectoral services to children from birth to 5 years (Early Childhood Commission) and behavioural interventions of the Violence Prevention Alliance (an inter-sectoral NGO) and the Healthy Lifestyles project (Ministry of Health). Indigenous maternal and child health research provided a local evidence base that informed public policy. Collaboration, good communication, being vigilant to opportunities to influence policy, and patience has contributed to our success.

Perinatal factors in students admitted to the University of the West Indies data from the Jamaican Perinatal Study.

OBJECTIVE: To compare perinatal and social factors in students admitted to The University of the West Indies (UWI), Kingston, Jamaica, at age 18 years with those in the rest of the Jamaican Perinatal Cohort. METHOD: The Jamaican Perinatal Survey recorded demographic and perinatal details in 10 527 or 97% of births in Jamaica in September and October 1986. Eighteen years later 140 of these were admitted to the UWI in Kingston, Jamaica. The perinatal features of these UWI students have been compared with the rest of the Perinatal Survey Cohort. RESULTS: Mothers of UWI students were older (p < 0.001), more likely to be married at the time of birth (p < 0.001), had earlier and more complete antenatal care (p < 0.05) and greater educational achievement at time of pregnancy (p < 0.001). These mothers of UWI students were also more likely to have diabetes (p < 0.01), operative deliveries (p < 0.01) and to attend private hospitals (p < 0.01). The UWI students had fewer siblings by their mothers (p < 0.05), were less likely to be low birthweight babies (p = 0.035) and more likely to be full-term (37-42 weeks) than lower gestational age (p = 0.005). Differences in Apgar scores did not reach statistical significance. CONCLUSIONS: The students of the University of the West Indies were more likely to come from smaller families with features indicative of a better quality of life. They were also of higher birthweight and tended to be full-term. The lack of association of Apgar scores with educational attainment is noteworthy.

The effects of severe plastic deformation on the mechanical and corrosion characteristics of a bioresorbable Mg-ZKQX6000 alloy.

In this work, a bioresorbable Mg-ZKQX6000 (Mg-6Zn-0.6Zr-0.4Ag-0.2Ca (wt%)) alloy was severely plastically deformed via equal channel angular pressing (ECAP) according to three unique hybrid routes at low temperatures (200 °C to 125 °C). The roles of ECAP processing on microstructure, and ensuing mechanical properties and corrosion rates, are assessed. Microstructurally, ECAP induces a complex plethora of features, especially variations in grain sizes and precipitates' sizes, distributions, and morphologies for individual cases. Mechanically, ECAP generally refined grain size, resulting in ultra-high strength levels of about 400 MPa in ultimate tensile strength for several cases; however, deformation via ECAP of precipitates induced embrittlement and low elongation to failure levels. Corrosion testing, conducted in simulated bodily fluid at bodily pH levels to mimic conditions in the human body, revealed consistent corrosion rates across several techniques (mass loss, hydrogen evolution, and electrochemical impedance spectroscopy (EIS)), showing that severe plastic deformation deteriorates corrosion resistance for this material. In-situ corrosion monitoring explained that corrosion accelerated after ECAP due to the creation of heterogeneous, anodic shear zones, which exhibited dense regions of refined grains and fine precipitates. Suggestions for future design and thermomechanical processing of Mg alloys for bioresorbable orthopedic implants are provided.

Sediment metal enrichment and ecological risk assessment of ten ports and estuaries in the World Harbours Project.

Ten global harbours were assessed for sediment quality by quantifying the magnitude of anthropogenic change and ecological risk. Anthropogenic change (enrichment) was high for Derwent River and Sydney estuary, moderate for Santander Harbour, Rio de Janeiro and Dublin Port, slight for Hong Kong, minimal for Darwin. All 10 enrichment indices used showed similar results. Derwent River sediment was rated at high ecological risk, followed by Sydney and Santander estuaries with moderate risk. Auckland and Darwin sediments exhibited minimal ecological risk and sediment in the remaining harbours (Dublin, Hong Kong, Ravenna, Ria de Vigo and Rio de Janeiro) were assessed at slight ecological risk. The extraordinary variety of environments and types/quantities/qualities of data investigated resulted in as much a critique and development of methodology, as an assessment of human impact, including unique techniques for elemental normalisation and contaminant classification. Recommendations for an improved technical framework for sediment quality assessment are provided.

Mutual optical injection in coupled DBR laser pairs.

We report an experimental study of nonlinear effects, characteristic of mutual optical coupling, in an ultra-short coupling regime observed in a distributed Bragg reflector laser pair fabricated on the same chip. Optical feedback is amplified via a double pass through a common on-chip optical amplifier, which introduces further nonlinear phenomena. Optical coupling has been introduced via back reflection from a cleave-ended fibre. The coupling may be varied in strength by varying the distance of the fibre from the output of the chip, without significantly affecting the coupling time.

The effect of puromycin on intranuclear steps in ribosome biosynthesis.

Inhibition of protein synthesis by puromycin (100 gamma/ml) is known to inhibit the synthesis of ribosomes. However, ribosomal precursor RNA (45S) continues to be synthesized, methylated, and processed. Cell fractionation studies revealed that, although the initial processing (45S --> 32S + 16S) occurs in the presence of puromycin, the 16S moiety is immediately degraded. No species of ribosomal RNA can be found to have emerged from the nucleolus. The RNA formed in the presence of puromycin is normal as judged by its ability to enter new ribosomal particles after puromycin is removed. This sequence of events is not a result of inhibition of protein synthesis, for cycloheximide, another inhibitor of protein synthesis, either alone or in combination with puromycin allows the completion of new ribosomes.

Comparison of the relative synthesis of the proteins of the 50S ribosomal subunit in growing and valine-deprived HeLa cells.

Quantitative studies of the synthesis of the ribosomal proteins of the 50S ribosomal subunit have been made with growing versus valine-deprived HeLa cells. The synthesis of total cell protein and 50S subunits was also compared between the growing and nongrowing cells. It was found that between 12 and 20 hr of valine deprivation the net synthesis of 50S subunits drops to approximately 8% of that in control cells while the over-all synthesis of 50S subunit ribosomal proteins declines to approximately 12% of that in the controls. However, the synthesis rates for each of two particular 50S subunit proteins decline to approximately 8% of the rates in the growing cells, indicating that the synthesis of one of these proteins may be rate limiting for 50S subunit biosynthesis in valine-deprived HeLa cells. Other evidence indicates that the regulation of synthesis of the ribosomal proteins in valine deprivation depends on control at the level of transcription or translation rather than being a function of the relative valine content of these proteins.

Effects of serotonin, carbamylcholine, and ascorbic acid on leukocyte cyclic GMP and chemotaxis.

Serotonin, ascorbic acid, and carbamylcholine enhanced the chemotactic responsiveness of human monocytes to endotoxin-treated serum. These agents caused significant accumulation of cyclic GMP in monocytes. PMN leukocyte chemotaxis was also enhanced by these agents although significant increases in cyclic GMP were not demonstrated.

Effect of cell density on binding and uptake of low density lipoprotein by human fibroblasts.

The effect of cell density on low density lipoprotein (LDL) binding by cultured human skin fibroblasts was investigated. Bound LDL was visualized by indirect immunofluorescence. Cellular lipid and cholesterol were monitored by fluorescence in cells stained with phosphine 3R and filipin, respectively. LDL binding and lipid accumulation were compared in cells in stationary and exponentially growing cultures, in sparsely and densely plated cultures, in wounded and non-wounded areas of stationary cultures, and in stationary cultures with and without the addition of lipoprotein-deficient serum. We conclude that LDL binding and cholesterol accumulation induced by LDL are influenced by cell density. It appears that, compared to rapidly growing cells, quiescent (noncycling) human fibroblasts exhibit fewer functional LDL receptors.

The turnover of nuclear DNA-like RNA in HeLa cells.

The subcellular distribution of various types of RNA in HeLa cells is described. In addition, the relative rate of synthesis of the major classes of nuclear RNA has been determined. From these experiments it can be deduced that the heterogeneous nuclear RNA fraction is rapidly synthesized and degraded within the cell nucleus.

Myosin 1c and myosin IIB serve opposing roles in lamellipodial dynamics of the neuronal growth cone.

The myosin family of motor proteins is implicated in mediating actin-based growth cone motility, but the roles of many myosins remain unclear. We previously implicated myosin 1c (M1c; formerly myosin I beta) in the retention of lamellipodia (Wang et al., 1996). Here we address the role of myosin II (MII) in chick dorsal root ganglion neuronal growth cone motility and the contribution of M1c and MII to retrograde F-actin flow using chromophore-assisted laser inactivation (CALI). CALI of MII reduced neurite outgrowth and growth cone area by 25%, suggesting a role for MII in lamellipodial expansion. Micro-CALI of MII caused a rapid reduction in local lamellipodial protrusion in growth cones with no effects on filopodial dynamics. This is opposite to micro-CALI of M1c, which caused an increase in lamellipodial protrusion. We used fiduciary beads (Forscher et al., 1992) to observe retrograde F-actin flow during the acute loss of M1c or MII. Micro-CALI of M1c reduced retrograde bead flow by 76%, whereas micro-CALI of MII or the MIIB isoform did not. Thus, M1c and MIIB serve opposite and nonredundant roles in regulating lamellipodial dynamics, and M1c activity is specifically required for retrograde F-actin flow.

Strength of diamond.

The yield strength of diamond is measured under a pressure of 10 gigapascals at temperatures up to 1550 degrees C by the analysis of x-ray peak shapes on diamond diffraction lines in a powdered sample as a function of pressure and temperature. At room temperature, the diamond crystals exhibit elastic behavior with increasing pressure. Significant ductile deformation is observed only at temperatures above 1000 degrees C at this pressure. The differential yield strength of diamond decreases with temperature from 16 gigapascals at 1100 degrees C to 4 gigapascals at 1550 degrees C. Transmission electron microscopy observations on the recovered sample indicate that the dominant deformation mechanism under high pressure and temperature is crystal plasticity.

Arginine vasotocin: effects on development of reproductive organs.

Immature 25-day-old mice were injected daily with 1 microgram of arginine vasotocin for 3 or 4 days and killed 24 hours after the last injection. The ovaries were 30 percent smaller in treated females than in controls. The ventral prostates and accessory organs (seminal vesicles and coagulating glands) were less than half the size of these structures in control males. Similar results were observed when 15-day-old mice were given similar injections and killed 2 weeks after the last injection; furthermore, testis weights were 28 percent smaller than those of controls. It is speculated that arginine vasotocin, which has been found in mammalian pineal glands, might mediate effects of the pineal gland on normal sexual development.