The Distribution and Excitation of CH₃CN in a Solar Nebula Analog

Cometary studies suggest that the organic composition of the early Solar Nebula was rich in complex nitrile species such CH3CN. Recent ALMA detections in protoplanetary disks suggest that these species may be common during planet and comet formation, but connecting gas-phase measurements to cometary abundances first requires constraints on formation chemistry and distributions of these species. We present here the detection of seven spatially resolved transitions of CH3CN in the protoplanetary disk around the T-Tauri star TW Hya. Using a rotational diagram analysis, we find a disk-averaged column density of ${N}_{T}={1.45}_{-0.15}^{+0.19}\times {10}^{12}$ cm−2 and a rotational temperature of ${T}_{\mathrm{rot}}={32.7}_{-3.4}^{+3.9}$ K. A radially resolved rotational diagram shows the rotational temperature to be constant across the disk, suggesting that the CH3CN emission originates from a layer at z/r ~ 0.3. Through comparison of the observations with predictions from a disk chemistry model, we find that grain-surface reactions likely dominate CH3CN formation and that in situ disk chemistry is sufficient to explain the observed CH3CN column density profile without invoking inheritance from the protostellar phase. However, the same model fails to reproduce a solar system cometary abundance of CH3CN relative to H2O in the midplane, suggesting that either vigorous vertical mixing or some degree of inheritance from interstellar ices occurred in the Solar Nebula

Mexico City and the biogeochemistry of global urbanization

Mexico City is far advanced in its urban evolution, and cities in currently developing nations may soon follow a similar course. This paper investigates the strengths and weaknesses of infrastructures for the emerging megacities. The major driving force for infrastructure change in Mexico City is concern over air quality. Air chemistry data from recent field campaigns have been used to calculate fluxes in the atmosphere of the Valley of Mexico, for compounds that are important to biogeochemistry including methane (CH4), carbon monoxide (CO), nonmethane hydrocarbons (NMHCs), ammonia (NH3), sulfur dioxide (SO2), nitrogen oxides (NOx and NOy), soot, and dust. Leakage of liquified petroleum gas approached 10% during sampling periods, and automotive pollutant sources in Mexico City were found to match those in developed cities, despite a lower vehicle-to-person ratio of 0.1. Ammonia is released primarily from residential areas, at levels sufficient to titrate pollutant acids into particles across the entire basin. Enhancements of reduced nitrogen and hydrocarbons in the vapor phase skew the distribution of NOy species towards lower average deposition velocities. Partly as a result, downwind nutrient deposition occurs on a similar scale as nitrogen fixation across Central America, and augments marine nitrate upwelling. Dust suspension from unpaved roads and from the bed of Lake Texcoco was found to be comparable to that occurring on the periphery of the Sahara, Arabian, and Gobi deserts. In addition, sodium chloride (NaCl) in the dust may support heterogeneous chlorine oxide (ClOx) chemistry. The insights from our Mexico City analysis have been tentatively applied to the upcoming urbanization of Asia

Constitutive cytoplasmic localization of p21Waf1/Cip1 affects the apoptotic process in monocytic leukaemia

In the present study, we analysed the expression and localization of p21Waf1/Cip1 in normal and malignant haematopoietic cells. We demonstrate that in normal monocytic cells, protein kinase C (PKC)-induced p21 gene activation, which is nuclear factor-κB (NF-κB) independent, results in predominantly cytoplasmic localized p21 protein. In acute monocytic leukaemia (M4, M5), monocytic blasts (N=12) show constitutive cytoplasmic p21 expression in 75% of the cases, while in myeloid leukaemic blasts (N=10), low nuclear and cytoplasmic localization of p21 could be detected, which is also PKC dependent. Constitutive p21 expression in monocytic leukaemia might have important antiapoptotic functions. This is supported by the finding that in U937 cells overexpressing p21, VP16-induced apoptosis is significantly reduced (20.0±0.9 vs 55.8±3.8%, P<0.01, N=5), reflected by a reduced phosphorylation of p38 and JNK. Similarly, AML blasts with high cytoplasmic p21 were less sensitive to VP16-induced apoptosis as compared to AML cases with low or undetectable p21 expression (42.25 vs 12.3%, P<0.01). Moreover, complex formation between p21 and ASK1 could be demonstrated in AML cells, by means of coimmunoprecipitation. In summary, these results indicate that p21 has an antiapoptotic role in monocytic leukaemia, and that p21 expression is regulated in a PKC-dependent and NF-κB independent manner.

The TW Hya Rosetta Stone Project IV: A Hydrocarbon-rich Disk Atmosphere

Connecting the composition of planet-forming disks with that of gas giant exoplanet atmospheres, in particular through C/O ratios, is one of the key goals of disk chemistry. Small hydrocarbons like C2H and C3H2 have been identified as tracers of C/O, as they form abundantly under high C/O conditions. We present resolved c–C3H2 observations from the TW Hya Rosetta Stone Project, a program designed to map the chemistry of common molecules at 15–20 au resolution in the TW Hya disk. Augmented by archival data, these observations comprise the most extensive multi-line set for disks of both ortho and para spin isomers spanning a wide range of energies, Eu = 29–97 K. We find the ortho-to-para ratio of c–C3H2 is consistent with 3 throughout extent of the emission, and the total abundance of both c–C3H2 isomers is (7.5–10) × 10−11 per H atom, or 1%–10% of the previously published C2H abundance in the same source. We find c–C3H2 comes from a layer near the surface that extends no deeper than z/r = 0.25. Our observations are consistent with substantial radial variation in gas-phase C/O in TW Hya, with a sharp increase outside ~30 au. Even if we are not directly tracing the midplane, if planets accrete from the surface via, e.g., meridional flows, then such a change should be imprinted on forming planets. Perhaps interestingly, the HR 8799 planetary system also shows an increasing gradient in its giant planets' atmospheric C/O ratios. While these stars are quite different, hydrocarbon rings in disks are common, and therefore our results are consistent with the young planets of HR 8799 still bearing the imprint of their parent disk's volatile chemistry

The TW Hya Rosetta Stone Project. II. Spatially Resolved Emission of Formaldehyde Hints at Low-temperature Gas-phase Formation

Formaldehyde (H2CO) is an important precursor to organics like methanol (CH3OH). It is important to understand the conditions that produce H2CO and prebiotic molecules during star and planet formation. H2CO possesses both gas-phase and solid-state formation pathways, involving either UV-produced radical precursors or CO ice and cold (lesssim20 K) dust grains. To understand which pathway dominates, gaseous H2CO's ortho-to-para ratio (OPR) has been used as a probe, with a value of 3 indicating "warm" conditions and <3 linked to cold formation in the solid state. We present spatially resolved Atacama Large Millimeter/submillimeter Array observations of multiple ortho- and para-H2CO transitions in the TW Hya protoplanetary disk to test H2CO formation theories during planet formation. We find disk-averaged rotational temperatures and column densities of 33 ± 2 K, (1.1 ± 0.1) × 1012 cm−2 and 25 ± 2 K, (4.4 ± 0.3) × 1011 cm−2 for ortho- and para-H2CO, respectively, and an OPR of 2.49 ± 0.23. A radially resolved analysis shows that the observed H2CO emits mostly at rotational temperatures of 30–40 K, corresponding to a layer with z/R ≥ 0.25. The OPR is consistent with 3 within 60 au, the extent of the pebble disk, and decreases beyond 60 au to 2.0 ± 0.5. The latter corresponds to a spin temperature of 12 K, well below the rotational temperature. The combination of relatively uniform emitting conditions, a radial gradient in the OPR, and recent laboratory experiments and theory on OPR ratios after sublimation, led us to speculate that gas-phase formation is responsible for the observed H2CO across the TW Hya disk

Design considerations in a clinical trial of a cognitive behavioural intervention for the management of low back pain in primary care : Back Skills Training Trial

Background Low back pain (LBP) is a major public health problem. Risk factors for the development and persistence of LBP include physical and psychological factors. However, most research activity has focused on physical solutions including manipulation, exercise training and activity promotion. Methods/Design This randomised controlled trial will establish the clinical and cost-effectiveness of a group programme, based on cognitive behavioural principles, for the management of sub-acute and chronic LBP in primary care. Our primary outcomes are disease specific measures of pain and function. Secondary outcomes include back beliefs, generic health related quality of life and resource use. All outcomes are measured over 12 months. Participants randomised to the intervention arm are invited to attend up to six weekly sessions each of 90 minutes; each group has 6–8 participants. A parallel qualitative study will aid the evaluation of the intervention. Discussion In this paper we describe the rationale and design of a randomised evaluation of a group based cognitive behavioural intervention for low back pain

Enhanced insulin sensitivity associated with provision of mono and polyunsaturated fatty acids in skeletal muscle cells involves counter modulation of PP2A

International audienceAims/Hypothesis: Reduced skeletal muscle insulin sensitivity is a feature associated with sustained exposure to excess saturated fatty acids (SFA), whereas mono and polyunsaturated fatty acids (MUFA and PUFA) not only improve insulin sensitivity but blunt SFA-induced insulin resistance. The mechanisms by which MUFAs and PUFAs institute these favourable changes remain unclear, but may involve stimulating insulin signalling by counter-modulation/repression of protein phosphatase 2A (PP2A). This study investigated the effects of oleic acid (OA; a MUFA), linoleic acid (LOA; a PUFA) and palmitate (PA; a SFA) in cultured myotubes and determined whether changes in insulin signalling can be attributed to PP2A regulation. Principal Findings: We treated cultured skeletal myotubes with unsaturated and saturated fatty acids and evaluated insulin signalling, phosphorylation and methylation status of the catalytic subunit of PP2A. Unlike PA, sustained incubation of rat or human myotubes with OA or LOA significantly enhanced Akt-and ERK1/2-directed insulin signalling. This was not due to heightened upstream IRS1 or PI3K signalling nor to changes in expression of proteins involved in proximal insulin signalling, but was associated with reduced dephosphorylation/inactivation of Akt and ERK1/2. Consistent with this, PA reduced PP2Ac demethylation and tyrosine 307 phosphorylation-events associated with PP2A activation. In contrast, OA and LOA strongly opposed these PA-induced changes in PP2Ac thus exerting a repressive effect on PP2A.Conclusions/Interpretation: Beneficial gains in insulin sensitivity and the ability of unsaturated fatty acids to oppose palmitate-induced insulin resistance in muscle cells may partly be accounted for by counter-modulation of PP2A

Relationship between Transmission Intensity and Incidence of Dengue Hemorrhagic Fever in Thailand

An infection with dengue virus may lead to dengue hemorrhagic fever (DHF), a dangerous illness. There is no approved vaccine for this most prevalent mosquito-borne virus, which infects tens of millions (or more) people annually. Therefore, health authorities have been putting an emphasis on reduction of vector mosquitoes, genus Aedes. However, a new mathematical hypothesis predicted, quite paradoxically, that reducing Aedes mosquitoes in highly endemic countries may “increase” the incidence of DHF. To test this hypothesis based upon actual data, we compared DHF incidence collected from each of 1,000 districts in Thailand to data of Aedes abundance, which was obtained by surveying one million households. This analysis showed that reducing Aedes abundance from the highest level in Thailand to a moderate level would increase the incidence by more than 40%. In addition, we developed computer simulation software based upon the above hypothesis. The simulation predicted that epidemiological studies should be continued for a very long duration, preferably over a decade, to clearly detect such a paradoxical relationship between Aedes abundance and incidence of DHF. Such long-term studies are necessary, especially because tremendous efforts and resources have been (and perhaps will be) spent on combating Aedes

The Diagnostic Sensitivity of Dengue Rapid Test Assays Is Significantly Enhanced by Using a Combined Antigen and Antibody Testing Approach

Dengue is a serious public health concern with around 3 billion people at risk of infection. Severe forms of the infection can be fatal and with no licensed vaccine or effective therapeutic currently available, early detection is important to assist with the clinical management of symptoms. Isolation of the virus and the detection of viral RNA using RT-PCR are commonly used methods for early diagnosis but are time-consuming, expensive and require skilled operation. Rapid immunochromatographic tests (ICT) are relatively simple, inexpensive and easy to perform at or near the point of care. Here, we report on the clinical performance of a new rapid ICT for the non-structural protein 1 (NS1) of dengue virus, a marker of acute infection. At two clinical study sites, NS1 was detected in 60–70% of laboratory-confirmed dengue cases and specificity of the test was >95%. We have also shown that a combined testing approach for both circulating NS1 antigen and antibody responses to the glycoprotein E of the virus can significantly improve diagnostic sensitivity compared to the detection of NS1 alone. Importantly, the combined antigen and antibody testing approach also provides an expanded window of detection from as early as day 1 post-onset of illness