Coordination cages as permanently porous ionic liquids

Porous materials are widely used in industry for applications that include chemical separations and gas scrubbing. These materials are typically porous solids, although the liquid state can be easier to manipulate in industrial settings. The idea of combining the size and shape selectivity of porous domains with the fluidity of liquids is a promising one and porous liquids composed of functionalized organic cages have recently attracted attention. Here we describe an ionic-liquid, porous, tetrahedral coordination cage. Complementing the gas binding observed in other porous liquids, this material also encapsulates non-gaseous guests—shape and size selectivity was observed for a series of isomeric alcohols. Three gaseous chlorofluorocarbon guests, trichlorofluoromethane, dichlorodifluoromethane and chlorotrifluoromethane, were also shown to be taken up by the liquid coordination cage with an affinity that increased with their size. We hope that these findings will lead to the synthesis of other porous liquids whose guest-uptake properties may be tailored to fulfil specific functions

A functional polymorphism in the 5HTR2C gene associated with stress responses also predicts incident cardiovascular events.

Previously we have shown that a functional nonsynonymous single nucleotide polymorphism (rs6318) of the 5HTR2C gene located on the X-chromosome is associated with hypothalamic-pituitary-adrenal axis response to a stress recall task, and with endophenotypes associated with cardiovascular disease (CVD). These findings suggest that individuals carrying the rs6318 Ser23 C allele will be at higher risk for CVD compared to Cys23 G allele carriers. The present study examined allelic variation in rs6318 as a predictor of coronary artery disease (CAD) severity and a composite endpoint of all-cause mortality or myocardial infarction (MI) among Caucasian participants consecutively recruited through the cardiac catheterization laboratory at Duke University Hospital (Durham, NC) as part of the CATHGEN biorepository. Study population consisted of 6,126 Caucasian participants (4,036 [65.9%] males and 2,090 [34.1%] females). A total of 1,769 events occurred (1,544 deaths and 225 MIs; median follow-up time = 5.3 years, interquartile range = 3.3-8.2). Unadjusted Cox time-to-event regression models showed, compared to Cys23 G carriers, males hemizygous for Ser23 C and females homozygous for Ser23C were at increased risk for the composite endpoint of all-cause death or MI: Hazard Ratio (HR) = 1.47, 95% confidence interval (CI) = 1.17, 1.84, p = .0008. Adjusting for age, rs6318 genotype was not related to body mass index, diabetes, hypertension, dyslipidemia, smoking history, number of diseased coronary arteries, or left ventricular ejection fraction in either males or females. After adjustment for these covariates the estimate for the two Ser23 C groups was modestly attenuated, but remained statistically significant: HR = 1.38, 95% CI = 1.10, 1.73, p = .005. These findings suggest that this functional polymorphism of the 5HTR2C gene is associated with increased risk for CVD mortality and morbidity, but this association is apparently not explained by the association of rs6318 with traditional risk factors or conventional markers of atherosclerotic disease

Changes in rod and frame test scores recorded in schoolchildren during development--a longitudinal study.

The Rod and Frame Test has been used to assess the degree to which subjects rely on the visual frame of reference to perceive vertical (visual field dependence-independence perceptual style). Early investigations found children exhibited a wide range of alignment errors, which reduced as they matured. These studies used a mechanical Rod and Frame system, and presented only mean values of grouped data. The current study also considered changes in individual performance. Changes in rod alignment accuracy in 419 school children were measured using a computer-based Rod and Frame test. Each child was tested at school Grade 2 and retested in Grades 4 and 6. The results confirmed that children displayed a wide range of alignment errors, which decreased with age but did not reach the expected adult values. Although most children showed a decrease in frame dependency over the 4 years of the study, almost 20% had increased alignment errors suggesting that they were becoming more frame-dependent. Plots of individual variation (SD) against mean error allowed the sample to be divided into 4 groups; the majority with small errors and SDs; a group with small SDs, but alignments clustering around the frame angle of 18°; a group showing large errors in the opposite direction to the frame tilt; and a small number with large SDs whose alignment appeared to be random. The errors in the last 3 groups could largely be explained by alignment of the rod to different aspects of the frame. At corresponding ages females exhibited larger alignment errors than males although this did not reach statistical significance. This study confirms that children rely more heavily on the visual frame of reference for processing spatial orientation cues. Most become less frame-dependent as they mature, but there are considerable individual differences

SHIELD: Neutral Gas Kinematics and Dynamics

We present kinematic analyses of the 12 galaxies in the "Survey of HI in Extremely Low-mass Dwarfs" (SHIELD). We use multi-configuration interferometric observations of the HI 21cm emission line from the Karl G. Jansky Very Large Array (VLA) to produce image cubes at a variety of spatial and spectral resolutions. Both two- and three-dimensional fitting techniques are employed in an attempt to derive inclination-corrected rotation curves for each galaxy. In most cases, the comparable magnitudes of velocity dispersion and projected rotation result in degeneracies that prohibit unambiguous circular velocity solutions. We thus make spatially resolved position-velocity cuts, corrected for inclination using the stellar components, to estimate the circular rotation velocities. We find circular velocities <30 km/s for the entire survey population. Baryonic masses are calculated using single-dish HI fluxes from Arecibo and stellar masses derived from HST and Spitzer imaging. Comparison is made with total dynamical masses estimated from the position-velocity analysis. The SHIELD galaxies are then placed on the baryonic Tully-Fisher relation. There exists an empirical threshold rotational velocity <15 km/s, below which current observations cannot differentiate coherent rotation from pressure support. The SHIELD galaxies are representative of an important population of galaxies whose properties cannot be described by current models of rotationally-dominated galaxy dynamics

SHIELD: Comparing Gas and Star Formation in Low Mass Galaxies

We analyze the relationships between atomic, neutral hydrogen (HI) and star formation (SF) in the 12 low-mass SHIELD galaxies. We compare high spectral (~0.82 km/s/channel) and spatial resolution (physical resolutions of 170 pc - 700 pc) HI imaging from the VLA with H\alpha and far-ultraviolet imaging. We quantify the degree of co-spatiality between star forming regions and regions of high HI column densities. We calculate the global star formation efficiencies (SFE, $\Sigma_{\rm SFR}$ / $\Sigma_{\rm HI}$), and examine the relationships among the SFE and HI mass, HI column density, and star formation rate (SFR). The systems are consuming their cold neutral gas on timescales of order a few Gyr. While we derive an index for the Kennicutt-Schmidt relation of N ~ 0.68 $\pm$ 0.04 for the SHIELD sample as a whole, the values of N vary considerably from system to system. By supplementing SHIELD results with those from other surveys, we find that HI mass and UV-based SFR are strongly correlated over five orders of magnitude. Identification of patterns within the SHIELD sample allows us to bin the galaxies into three general categories: 1) mainly co-spatial HI and SF regions, found in systems with highest peak HI column densities and highest total HI masses, 2) moderately correlated HI and SF regions, found in systems with moderate HI column densities, and 3) obvious offsets between HI and SF peaks, found in systems with the lowest total HI masses. SF in these galaxies is dominated by stochasticity and random fluctuations in their ISM

Exoplanet Atmosphere Measurements from Transmission Spectroscopy and other Planet-Star Combined Light Observations

It is possible to learn a great deal about exoplanet atmospheres even when we cannot spatially resolve the planets from their host stars. In this chapter, we overview the basic techniques used to characterize transiting exoplanets - transmission spectroscopy, emission and reflection spectroscopy, and full-orbit phase curve observations. We discuss practical considerations, including current and future observing facilities and best practices for measuring precise spectra. We also highlight major observational results on the chemistry, climate, and cloud properties of exoplanets.Comment: Accepted review chapter; Handbook of Exoplanets, eds. Hans J. Deeg and Juan Antonio Belmonte (Springer-Verlag). 22 pages, 6 figure

Functional Diversity and Structural Disorder in the Human Ubiquitination Pathway

The ubiquitin-proteasome system plays a central role in cellular regulation and protein quality control (PQC). The system is built as a pyramid of increasing complexity, with two E1 (ubiquitin activating), few dozen E2 (ubiquitin conjugating) and several hundred E3 (ubiquitin ligase) enzymes. By collecting and analyzing E3 sequences from the KEGG BRITE database and literature, we assembled a coherent dataset of 563 human E3s and analyzed their various physical features. We found an increase in structural disorder of the system with multiple disorder predictors (IUPred - E1: 5.97%, E2: 17.74%, E3: 20.03%). E3s that can bind E2 and substrate simultaneously (single subunit E3, ssE3) have significantly higher disorder (22.98%) than E3s in which E2 binding (multi RING-finger, mRF, 0.62%), scaffolding (6.01%) and substrate binding (adaptor/substrate recognition subunits, 17.33%) functions are separated. In ssE3s, the disorder was localized in the substrate/adaptor binding domains, whereas the E2-binding RING/HECT-domains were structured. To demonstrate the involvement of disorder in E3 function, we applied normal modes and molecular dynamics analyses to show how a disordered and highly flexible linker in human CBL (an E3 that acts as a regulator of several tyrosine kinase-mediated signalling pathways) facilitates long-range conformational changes bringing substrate and E2-binding domains towards each other and thus assisting in ubiquitin transfer. E3s with multiple interaction partners (as evidenced by data in STRING) also possess elevated levels of disorder (hubs, 22.90% vs. non-hubs, 18.36%). Furthermore, a search in PDB uncovered 21 distinct human E3 interactions, in 7 of which the disordered region of E3s undergoes induced folding (or mutual induced folding) in the presence of the partner. In conclusion, our data highlights the primary role of structural disorder in the functions of E3 ligases that manifests itself in the substrate/adaptor binding functions as well as the mechanism of ubiquitin transfer by long-range conformational transitions. © 2013 Bhowmick et al

Protective Coupling of Mitochondrial Function and Protein Synthesis via the eIF2α Kinase GCN-2

Cells respond to defects in mitochondrial function by activating signaling pathways that restore homeostasis. The mitochondrial peptide exporter HAF-1 and the bZip transcription factor ATFS-1 represent one stress response pathway that regulates the transcription of mitochondrial chaperone genes during mitochondrial dysfunction. Here, we report that GCN-2, an eIF2α kinase that modulates cytosolic protein synthesis, functions in a complementary pathway to that of HAF-1 and ATFS-1. During mitochondrial dysfunction, GCN-2–dependent eIF2α phosphorylation is required for development as well as the lifespan extension observed in Caenorhabditis elegans. Reactive oxygen species (ROS) generated from dysfunctional mitochondria are required for GCN-2–dependent eIF2α phosphorylation but not ATFS-1 activation. Simultaneous deletion of ATFS-1 and GCN-2 compounds the developmental defects associated with mitochondrial stress, while stressed animals lacking GCN-2 display a greater dependence on ATFS-1 and stronger induction of mitochondrial chaperone genes. These findings are consistent with translational control and stress-dependent chaperone induction acting in complementary arms of the UPRmt

Improving adherence to glaucoma medication: a randomised controlled trial of a patient-centred intervention (The Norwich Adherence Glaucoma Study)

Background Improving adherence to ocular hypertension (OH)/glaucoma therapy is highly likely to prevent or reduce progression of optic nerve damage. The present study used a behaviour change counselling intervention to determine whether education and support was beneficial and cost-effective in improving adherence with glaucoma therapy. Methods A randomised controlled trial with a 13-month recruitment and 8-month follow-up period was conducted. Patients with OH/glaucoma attending a glaucoma clinic and starting treatment with travoprost were approached. Participants were randomised into two groups and adherence was measured over 8 months, using an electronic monitoring device (Travalert® dosing aid, TDA). The control group received standard clinical care, and the intervention group received a novel glaucoma education and motivational support package using behaviour change counselling. Cost-effectiveness framework analysis was used to estimate any potential cost benefit of improving adherence. Results Two hundred and eight patients were recruited (102 intervention, 106 control). No significant difference in mean adherence over the monitoring period was identified with 77.2% (CI, 73.0, 81.4) for the control group and 74.8% (CI, 69.7, 79.9) for the intervention group (p = 0.47). Similarly, there was no significant difference in percentage intraocular pressure reduction; 27.6% (CI, 23.5, 31.7) for the control group and 25.3% (CI, 21.06, 29.54) for the intervention group (p = 0.45). Participants in the intervention group were more satisfied with information about glaucoma medication with a mean score of 14.47/17 (CI, 13.85, 15.0) compared with control group which was 8.51 (CI, 7.72, 9.30). The mean intervention cost per patient was GB£10.35 (<US$16) and not cost-effective. Conclusions Adherence with travoprost was high and not further increased by the intervention. Nevertheless, the study demonstrated that provision of information, tailored to the individual, was inexpensive and able to achieve high patient satisfaction with respect to information about glaucoma medication. Measurement of adherence remains problematic since awareness of study participation may cause a change in participant behaviour