A Comparison Between Stochastic and Deterministic Models of a Biological Oscillator

We look at the behavior of biological oscillators, specifically analyzing a genetic circuit that has oscillatory behavior. Implementing the system in deterministic and stochastic models, we compare the two models using various tests and analyze the effect of stochastic noise on these oscillations. We first investigate the effect of volume and find that at small system volumes, stochastic events cause the system to exhibit more sporadic oscillations and a longer period of oscillation. Next, we develop classification systems for discerning the boundary in the parameter space where the model begins to show oscillations. This is more challenging in the stochastic model, due to persistent fluctuations. We compare different methods of analysis of our deterministic and stochastic models and visualize the conditions which lead to oscillation in each model. We find that the parameter range of oscillation is larger in the stochastic model than in the deterministic model. Finally, we find an increased rate of mRNA production can create greater noise in a system and amplify the difference between a stochastic and deterministic system

KELT-4Ab: An inflated Hot Jupiter transiting the bright (V~10) component of a hierarchical triple

We report the discovery of KELT-4Ab, an inflated, transiting Hot Jupiter orbiting the brightest component of a hierarchical triple stellar system. The host star is an F star with T_(eff) = 6206 ± 75 K, log g = 4.108 ± 0.014, [Fe/H] = -0.116_(-0.069)^(+0.065, M_* = 1.201_(-0.061)^(+0.067) M_☉, and R_* = 1.603_(-0.038)^(+0.039) R_☉. The best-fit linear ephemeris is BJD_(TDB); = 2456193.29157 ± 0.00021 + E(2.9895936 ± 0.0000048). With a magnitude of V ~ 10, a planetary radius of 1.699_(-0.045)^(+0.046); R_J, and a mass of 0.902_(-0.059)^(+0.060) M_J, it is the brightest host among the population of inflated Hot Jupiters (R_P > 1.5 R_J), making it a valuable discovery for probing the nature of inflated planets. In addition, its existence within a hierarchical triple and its proximity to Earth (210 pc) provide a unique opportunity for dynamical studies with continued monitoring with high resolution imaging and precision radial velocities. The projected separation between KELT-4A and KELT-4BC is 328 ± 16 AU and the projected separation between KELT-4B and KELT-4C is 10.30 ± 0.74 AU. Assuming face-on, circular orbits, their respective periods would be 3780 ± 290 and 29.4 ± 3.6 years and the astrometric motions relative to the epoch in this work of both the binary stars around each other and of the binary around the primary star would be detectable now and may provide meaningful constraints on the dynamics of the system

Understanding the Digital Gap Among US Adults With Disability: Cross-Sectional Analysis of the Health Information National Trends Survey 2013

BACKGROUND: Disabilities affect more than 1 in 5 US adults, and those with disabilities face multiple barriers in accessing health care. A digital gap, defined as the disparity caused by differences in the ability to use advanced technologies, is assumed to be prevalent among individuals with disabilities. OBJECTIVE: This study examined the associations between disability and use of information technology (IT) in obtaining health information and between trust factors and IT use. We hypothesized that compared to US adults without disabilities, those with disabilities are less likely to refer to the internet for health information, more likely to refer to a health care provider to obtain health information, and less likely to use IT to exchange medical information with a provider. Additionally, we hypothesized that trust factors, such as trust toward health information source and willingness to exchange health information, are associated with IT use. METHODS: The primary database was the 2013 Health Information National Trends Survey 4 Cycle 3 (N=3185). Disability status, the primary study covariate, was based on 6 questions that encompassed a wide spectrum of conditions, including impairments in mobility, cognition, independent living, vision, hearing, and self-care. Study covariates included sociodemographic factors, respondents\u27 trust toward the internet and provider as information sources, and willingness to exchange medical information via IT with providers. Study outcomes were the use of the internet as the primary health information source, use of health care providers as the primary health information source, and use of IT to exchange medical information with providers. We conducted multivariate logistic regressions to examine the association between disability and study outcomes controlling for study covariates. Multiple imputations with fully conditional specification were used to impute missing values. RESULTS: We found presence of any disability was associated with decreased odds (adjusted odds ratio [AOR] 0.65, 95% CI 0.43-0.98) of obtaining health information from the internet, in particular for those with vision disability (AOR 0.27, 95% CI 0.11-0.65) and those with mobility disability (AOR 0.51, 95% CI 0.30-0.88). Compared to those without disabilities, those with disabilities were significantly more likely to consult a health care provider for health information in both actual (OR 2.21, 95% CI 1.54-3.18) and hypothetical situations (OR 1.80, 95% CI 1.24-2.60). Trust toward health information from the internet (AOR 3.62, 95% CI 2.07-6.33), and willingness to exchange via IT medical information with a provider (AOR 1.88, 95% CI 1.57-2.24) were significant predictors for seeking and exchanging such information, respectively. CONCLUSIONS: A potential digital gap may exist among US adults with disabilities in terms of their recent use of the internet for health information. Trust toward health information sources and willingness play an important role in people\u27s engagement in use of the internet for health information. Future studies should focus on addressing trust factors associated with IT use and developing tools to improve access to care for those with disabilities

Fundamental Performance of a Dispersed Fixed Delay Interferometer In Searching For Planets Around M Dwarfs

We present a new method to calculate fundamental Doppler measurement limits with a dispersed fixed-delay interferometer (DFDI) in the near infrared wavelength region for searching for exoplanets around M dwarfs in the coming decade. It is based on calculating the Q factor, a measure of flux-normalized Doppler sensitivity in the fringing spectra created with DFDI. We calculate the Q factor as a function of spectral resolution R, stellar projected rotational velocity V sini, stellar effective temperature T_eff and optical path difference (OPD) of the interferometer. We also compare the DFDI Q factor to that for the popular cross-dispersed echelle spectrograph method (the direct echelle (DE) method). Given the IR Doppler measurement is likely to be detector-limited for a while, we introduce new merit functions, which is directly related to photon-limited RV uncertainty, to evaluate Doppler performance with the DFDI and DE methods. We find that DFDI has strength in wavelength coverage and multi-object capability over the DE for a limited detector resource. We simulate the performance of the InfraRed Exoplanet Tracker (IRET) based on the DFDI design, being considered for the next generation IR Doppler measurements. The predicted photon-limited RV uncertainty suggests that IRET is capable of detecting Earth-like exoplanets in habitable zone around nearby bright M dwarfs if they exist. A new method is developed to quantitatively estimate the influence of telluric lines on RV uncertainty. Our study shows that photon-limited RV uncertainty can be reached if 99% of the strength of telluric lines can be removed from the measured stellar spectra. At low to moderate levels of telluric line strength removal (50% to 90%), the optimal RV uncertainty is typically a factor of 2-3 times larger than photon-limited RV uncertainty.Comment: 43 pages, 20 figures, 6 tables. Accepted by Ap

Preferential tau aggregation in von Economo neurons and fork cells in frontotemporal lobar degeneration with specific MAPT variants.

Tau aggregation is a hallmark feature in a subset of patients with frontotemporal dementia (FTD). Early and selective loss of von Economo neurons (VENs) and fork cells within the frontoinsular (FI) and anterior cingulate cortices (ACC) is observed in patients with sporadic behavioral variant FTD (bvFTD) due to frontotemporal lobar degeneration (FTLD), including FTLD with tau inclusions (FTLD-tau). Recently, we further showed that these specialized neurons show preferential aggregation of TDP-43 in FTLD-TDP. Whether VENs and fork cells are prone to tau accumulation in FTLD-tau remains unclear, and no previous studies of these neurons have focused on patients with pathogenic variants in the gene encoding microtubule-associated protein tau (FTLD-tau/MAPT). Here, we examined regional profiles of tau aggregation and neurodegeneration in 40 brain regions in 8 patients with FTLD-tau/MAPT and 7 with Pick's disease (PiD), a sporadic form of FTLD-tau that often presents with bvFTD. We further qualitatively assessed the cellular patterns of frontoinsular tau aggregation in FTLD-tau/MAPT using antibodies specific for tau hyperphosphorylation, acetylation, or conformational change. ACC and mid-insula were among the regions most affected by neurodegeneration and tau aggregation in FTLD-tau/MAPT and PiD. In these two forms of FTLD-tau, severity of regional neurodegeneration and tau protein aggregation were highly correlated across regions. In FTLD-tau/MAPT, VENs and fork cells showed disproportionate tau protein aggregation in patients with V337 M, A152T, and IVS10 + 16 variants, but not in patients with the P301L variant. As seen in FTLD-TDP, our data suggest that VENs and fork cells represent preferentially vulnerable neuron types in most, but not all of the MAPT variants we studied

Oscillatory correlates of auditory working memory examined with human electrocorticography

This work examines how sounds are held in auditory working memory (AWM) in humans by examining oscillatory local field potentials (LFPs) in candidate brain regions. Previous fMRI studies by our group demonstrated blood oxygenation level-dependent (BOLD) response increases during maintenance in auditory cortex, inferior frontal cortex and the hippocampus using a paradigm with a delay period greater than 10s. The relationship between such BOLD changes and ensemble activity in different frequency bands is complex, and the long delay period raised the possibility that long-term memory mechanisms were engaged. Here we assessed LFPs in different frequency bands in six subjects with recordings from all candidate brain regions using a paradigm with a short delay period of 3 s. Sustained delay activity was demonstrated in all areas, with different patterns in the different areas. Enhancement in low frequency (delta) power and suppression across higher frequencies (beta/ gamma) were demonstrated in primary auditory cortex in medial Heschl’s gyrus (HG) whilst non-primary cortex showed patterns of enhancement and suppression that altered at different levels of the auditory hierarchy from lateral HG to superior- and middle-temporal gyrus. Inferior frontal cortex showed increasing suppression with increasing frequency. The hippocampus and parahippocampal gyrus showed low frequency increases and high frequency decreases in oscillatory activity. This work demonstrates sustained activity patterns during AWM maintenance, with prominent low-frequency increases in medial temporal lobe regions

Direct Imaging in Reflected Light: Characterization of Older, Temperate Exoplanets With 30-m Telescopes

Direct detection, also known as direct imaging, is a method for discovering and characterizing the atmospheres of planets at intermediate and wide separations. It is the only means of obtaining spectra of non-transiting exoplanets. Characterizing the atmospheres of planets in the <5 AU regime, where RV surveys have revealed an abundance of other worlds, requires a 30-m-class aperture in combination with an advanced adaptive optics system, coronagraph, and suite of spectrometers and imagers - this concept underlies planned instruments for both TMT (the Planetary Systems Imager, or PSI) and the GMT (GMagAO-X). These instruments could provide astrometry, photometry, and spectroscopy of an unprecedented sample of rocky planets, ice giants, and gas giants. For the first time habitable zone exoplanets will become accessible to direct imaging, and these instruments have the potential to detect and characterize the innermost regions of nearby M-dwarf planetary systems in reflected light. High-resolution spectroscopy will not only illuminate the physics and chemistry of exo-atmospheres, but may also probe rocky, temperate worlds for signs of life in the form of atmospheric biomarkers (combinations of water, oxygen and other molecular species). By completing the census of non-transiting worlds at a range of separations from their host stars, these instruments will provide the final pieces to the puzzle of planetary demographics. This whitepaper explores the science goals of direct imaging on 30-m telescopes and the technology development needed to achieve them.Comment: (March 2018) Submitted to the Exoplanet Science Strategy committee of the NA

Polymorphisms in the WNK1 gene are asociated with blood pressure variation and urinary potassium excretion

WNK1 - a serine/threonine kinase involved in electrolyte homeostasis and blood pressure (BP) control - is an excellent candidate gene for essential hypertension (EH). We and others have previously reported association between WNK1 and BP variation. Using tag SNPs (tSNPs) that capture 100% of common WNK1 variation in HapMap, we aimed to replicate our findings with BP and to test for association with phenotypes relating to WNK1 function in the British Genetics of Hypertension (BRIGHT) study case-control resource (1700 hypertensive cases and 1700 normotensive controls). We found multiple variants to be associated with systolic blood pressure, SBP (7/28 tSNPs min-p = 0.0005), diastolic blood pressure, DBP (7/28 tSNPs min-p = 0.002) and 24 hour urinary potassium excretion (10/28 tSNPs min-p = 0.0004). Associations with SBP and urine potassium remained significant after correction for multiple testing (p = 0.02 and p = 0.01 respectively). The major allele (A) of rs765250, located in intron 1, demonstrated the strongest evidence for association with SBP, effect size 3.14 mmHg (95%CI:1.23–4.9), DBP 1.9 mmHg (95%CI:0.7–3.2) and hypertension, odds ratio (OR: 1.3 [95%CI: 1.0–1.7]).We genotyped this variant in six independent populations (n = 14,451) and replicated the association between rs765250 and SBP in a meta-analysis (p = 7×10−3, combined with BRIGHT data-set p = 2×10−4, n = 17,851). The associations of WNK1 with DBP and EH were not confirmed. Haplotype analysis revealed striking associations with hypertension and BP variation (global permutation p10 mmHg reduction) and risk for hypertension (OR<0.60). Our data indicates that multiple rare and common WNK1 variants contribute to BP variation and hypertension, and provide compelling evidence to initiate further genetic and functional studies to explore the role of WNK1 in BP regulation and EH

Antibacterial Activities of a New Brominated Diterpene from Borneon Laurencia spp

In our continuous interest to study the diversity of halogenated metabolites of Malaysian species of the red algal genus Laurencia, we examined the chemical composition of five populations of unrecorded Laurencia sp. A new brominated diterpene, 10-acetoxyangasiol (1), and four other known metabolites, aplysidiol (2), cupalaurenol (3), 1-methyl-2,3,5-tribromoindole (4), and chamigrane epoxide (5), were isolated and identified. Isolated metabolites exhibited potent antibacterial activities against clinical bacteria, Staphylococcus aureus, Staphylococcus sp., Streptococcus pyogenes, Salmonella sp. and Vibrio cholerae