Cuprate addition to a 6-substituted pentafulvene: preparation of sec-alkyl substituted titanocene dichlorides and their biological activity

The copper-catalysed (10 mol-% CuBr·SMe2, CuCN·LiCl or CuI/PPh3) addition of RMgBr to the pentafulvene 1-(cyclopenta-2,4-dien-1-ylidenemethyl)-2-methoxybenzene allows the formation of cyclopentadienyl derivatives with α-CHR(2-MeOPh) sidechains (R = Me, Et, nBu, iBu, allyl, Ph) without H– transfer. The deprotonation of these sec-alkyl-substituted cyclopentadienyls followed by the addition of TiCl4 allows the isolation of TiCl2{η5-C5H4CHR(2-OMePh)} as rac/meso mixtures that show activity against human colon, breast and pancreatic cell lines (GI50 2.3–42.4 μM)

TURBULENT HEATING OF THE DISTANT SOLAR WIND BY INTERSTELLAR PICKUP PROTONS IN A DECELERATING FLOW

Previous models of solar wind heating by interstellar pickup proton-driven turbulence have assumed that the wind speed is a constant in heliocentric radial position. However, the same pickup process, which is taken to provide the turbulent energy, must also decelerate the wind. In this paper, we extend our phenomenological turbulence model to include variable wind speed, and then incorporate the deceleration due to interstellar pickup protons into the model. We compare the model results with plasma and field data from Voyager 2, taking this opportunity to present an extended and improved data set of proton core temperature, magnetic field fluctuation intensity, and correlation length along the Voyager trajectory. A particular motivation for including the solar wind deceleration in this model is the expectation that a slower wind would reduce the resulting proton core temperature in the region beyond ~60 AU, where the previous model predictions were higher than the observed values. However, we find instead that the deceleration of the steady-state wind increases the energy input to the turbulence, causing even higher temperatures in that region. The increased heating is shown to result from the larger values of the ratio of Alfven speed to solar wind speed that develop in the decelerating wind.Jet Propulsion Laboratory (U.S.) (NASA contract 959203)United States. National Aeronautics and Space Administration (NASA grant NNX08A147G)United States. National Aeronautics and Space Administration (NASA Guest Investigator grant NNX07AH75G)United States. National Aeronautics and Space Administration (NASA Guest Investigator grant NNX08AJ19G

Evidence for a correlation between the sizes of quiescent galaxies and local environment to z ~ 2

We present evidence for a strong relationship between galaxy size and environment for the quiescent population in the redshift range 1 < z < 2. Environments were measured using projected galaxy overdensities on a scale of 400 kpc, as determined from ~ 96,000 K-band selected galaxies from the UKIDSS Ultra Deep Survey (UDS). Sizes were determined from ground-based K-band imaging, calibrated using space-based CANDELS HST observations in the centre of the UDS field, with photometric redshifts and stellar masses derived from 11-band photometric fitting. From the resulting size-mass relation, we confirm that quiescent galaxies at a given stellar mass were typically ~ 50 % smaller at z ~ 1.4 compared to the present day. At a given epoch, however, we find that passive galaxies in denser environments are on average significantly larger at a given stellar mass. The most massive quiescent galaxies (M_stellar > 2 x 10^11 M_sun) at z > 1 are typically 50 % larger in the highest density environments compared to those in the lowest density environments. Using Monte Carlo simulations, we reject the null hypothesis that the size-mass relation is independent of environment at a significance > 4.8 sigma for the redshift range 1 < z < 2. In contrast, the evidence for a relationship between size and environment is much weaker for star-forming galaxies.Comment: Accepted for publication in MNRAS. 16 pages, 11 figures, 6 table

Modulation of the acidity of the 8-carboxamide group in the temozolomide family of antitumor imidazo[5,1-d][1,2,3,5]tetrazines

Imidazo[5,1-d][1,2,3,5]tetrazines related in structure to the anticancer drugs temozolomide and mitozolomide with modification of the 8-carboxamide group, have been synthesized, N-nitrocarboxamides by direct nitration of the corresponding carboxamides, and N-cyanomitazolomide by sodium cyanamide acylation. The NH groups in the N-nitro- and N-cyano-carboxamides were considerably more acidic than the parent carboxamide, and readily formed salts with morpholine and imidazole. X-Ray crystallography revealed that the N-nitro compound existed as such rather than the nitronic acid tautomer. Preliminary evaluation showed that enhancing the acidity of the carboxamide NH in mitozolomide analogues was detrimental to the growth inhibitory activity

The NDE1 genomic locus can affect treatment of psychiatric illness through gene expression changes related to microRNA-484

Genetic studies of familial schizophrenia in Finland have observed significant associations with a group of biologically related genes, DISCI1, NDE1,NDEL1, PDE4B and PDE4D, the 'DISCI network'. Here, we use gene expression and psychoactive medication use data to study their biological consequences and potential treatment implications. Gene expression levels were determined in 64 individuals from 18 families, while prescription medication information has been collected over a 10 -year period for 931 affected individuals. We demonstrate that the NDE1 SNP rs2242549 associates with significant changes in gene expression for 2908 probes (2542 genes), of which 794 probes (719 genes) were replicable. A significant number of the genes altered were predicted targets of microRNA-484 (p = 3.0 x 10(-8)), located on a non -coding exon of NDE1. Variants within the NM. locus also displayed significant genotype by gender interaction to early cessation of psychoactive medications metabolized by CYP2C19. Furthermore, we demonstrate that miR-484 can affect the expression of CYP2C19 in a cell culture system. Thus, variation at the IVDET locus may alter risk of mental illness, in part through modification of miR-484, and such modification alters treatment response to specific psychoactive medications, leading to the potential for use of this locus in targeting treatment.Peer reviewe

Mortality trends and diff erentials in South Africa from 1997 to 2012: second National Burden of Disease Study

Background The poor health of South Africans is known to be associated with a quadruple disease burden. In the second National Burden of Disease (NBD) study, we aimed to analyse cause of death data for 1997–2012 and develop national, population group, and provincial estimates of the levels and causes of mortality. Method We used underlying cause of death data from death notifi cations for 1997–2012 obtained from Statistics South Africa. These data were adjusted for completeness using indirect demographic techniques for adults and comparison with survey and census estimates for child mortality. A regression approach was used to estimate misclassifi ed HIV/AIDS deaths and so-called garbage codes were proportionally redistributed by age, sex, and population group population group (black African, Indian or Asian descent, white [European descent], and coloured [of mixed ancestry according to the preceding categories]). Injury deaths were estimated from additional data sources. Age-standardised death rates were calculated with mid-year population estimates and the WHO age standard. Institute of Health Metrics and Evaluation Global Burden of Disease (IHME GBD) estimates for South Africa were obtained from the IHME GHDx website for comparison. Findings All-cause age-standardised death rates increased rapidly since 1997, peaked in 2006 and then declined, driven by changes in HIV/AIDS. Mortality from tuberculosis, non-communicable diseases, and injuries decreased slightly. In 2012, HIV/AIDS caused the most deaths (29·1%) followed by cerebrovascular disease (7·5%) and lower respiratory infections (4·9%). All-cause age-standardised death rates were 1·7 times higher in the province with the highest death rate compared to the province with the lowest death rate, 2·2 times higher in black Africans compared to whites, and 1·4 times higher in males compared with females. Comparison with the IHME GBD estimates for South Africa revealed substantial diff erences for estimated deaths from all causes, particularly HIV/AIDS and interpersonal violence. Interpretation This study shows the reversal of HIV/AIDS, non-communicable disease, and injury mortality trends in South Africa during the study period. Mortality diff erentials show the importance of social determinants, raise concerns about the quality of health services, and provide relevant information to policy makers for addressing inequalities. Diff erences between GBD estimates for South Africa and this study emphasise the need for more careful calibration of global models with local data

Monitoring Vibration and Other Critical Machine Conditions

Discussion Grou

Persistent burden from non-communicable diseases in South Africa needs strong action

Continued effort and politcal will must be directed towards preventing, delaying the onset of and managing non-communicable diseases in South Africa

Emerging trends in non-communicable disease mortality in South Africa, 1997 - 2010

Objectives. National trends in age-standardised death rates (ASDRs) for non-communicable diseases (NCDs) in South Africa (SA) were identified between 1997 and 2010.Methods. As part of the second National Burden of Disease Study, vital registration data were used after validity checks, proportional redistribution of missing age, sex and population group, demographic adjustments for registration incompleteness, and identification of misclassified AIDS deaths. Garbage codes were redistributed proportionally to specified codes by age, sex and population group. ASDRs were calculated using mid-year population estimates and the World Health Organization world standard.Results. Of 594 071 deaths in 2010, 38.9% were due to NCDs (42.6% females). ASDRs were 287/100 000 for cardiovascular diseases (CVDs), 114/100 000 for cancers (malignant neoplasms), 58/100 000 for chronic respiratory conditions and 52/100 000 for diabetes mellitus. An overall annual decrease of 0.4% was observed resulting from declines in stroke, ischaemic heart disease, oesophageal and lung cancer, asthma and chronic respiratory disease, while increases were observed for diabetes, renal disease, endocrine and nutritional disorders, and breast and prostate cancers. Stroke was the leading NCD cause of death, accounting for 17.5% of total NCD deaths. Compared with those for whites, NCD mortality rates for other population groups were higher at 1.3 for black Africans, 1.4 for Indians and 1.4 for coloureds, but varied by condition.Conclusions. NCDs contribute to premature mortality in SA, threatening socioeconomic development. While NCD mortality rates have decreased slightly, it is necessary to strengthen prevention and healthcare provision and monitor emerging trends in cause-specific mortality to inform these strategies if the target of 2% annual decline is to be achieved