Disk-Corona Model of Active Galactic Nuclei with Nonthermal Pairs

As a promising model for the X-ray emission from radio-quiet quasars and Seyfert 1 nuclei, we present a nonthermal disk-corona model, where soft photons from a disk are Comptonized by the nonthermal electron-positron pairs in a coronal region above the disk. Various characteristics of our model are qualitatively similar to the homogeneous, spherical, nonthermal pair models previously studied, but the important difference is that in our disk-corona model gamma-ray depletion is far more efficient, and, moreover, the gamma-ray annihilation line is much less prominent. Consequently, this model naturally satisfies the observed constraints on active galactic nuclei

Developing Predictive Molecular Maps of Human Disease through Community-based Modeling

The failure of biology to identify the molecular causes of disease has led to disappointment in the rate of development of new medicines. By combining the power of community-based modeling with broad access to large datasets on a platform that promotes reproducible analyses we can work towards more predictive molecular maps that can deliver better therapeutics

The mPower Study, Parkinson Disease Mobile Data Collected Using Researchkit

Current measures of health and disease are often insensitive, episodic, and subjective. Further, these measures generally are not designed to provide meaningful feedback to individuals. The impact of high-resolution activity data collected from mobile phones is only beginning to be explored. Here we present data from mPower, a clinical observational study about Parkinson disease conducted purely through an iPhone app interface. The study interrogated aspects of this movement disorder through surveys and frequent sensor-based recordings from participants with and without Parkinson disease. Benefitting from large enrollment and repeated measurements on many individuals, these data may help establish baseline variability of real-world activity measurement collected via mobile phones, and ultimately may lead to quantification of the ebbs-and-flows of Parkinson symptoms. App source code for these data collection modules are available through an open source license for use in studies of other conditions. We hope that releasing data contributed by engaged research participants will seed a new community of analysts working collaboratively on understanding mobile health data to advance human health

Mass Spectrometry Quantification, Localization, and Discovery of Feeding-Related Neuropeptides in Cancer borealis

The crab Cancer borealis nervous system is an important model for understanding neural circuit dynamics and modulation, but the identity of neuromodulatory substances and their influence on circuit dynamics in this system remains incomplete, particularly with respect to behavioral state-dependent modulation. Therefore, we used a multifaceted mass spectrometry (MS) method to identify neuropeptides that differentiate the unfed and fed states. Duplex stable isotope labeling revealed that the abundance of 80 of 278 identified neuropeptides was distinct in ganglia and/or neurohemal tissue from fed vs unfed animals. MS imaging revealed that an additional 7 and 11 neuropeptides exhibited altered spatial distributions in the brain and the neuroendocrine pericardial organs (POs), respectively, during these two feeding states. Furthermore, de novo sequencing yielded 69 newly identified putative neuropeptides that may influence feeding state-related neuromodulation. Two of these latter neuropeptides were determined to be upregulated in PO tissue from fed crabs, and one of these two peptides influenced heartbeat in ex vivo preparations. Overall, the results presented here identify a cohort of neuropeptides that are poised to influence feeding-related behaviors, providing valuable opportunities for future functional studies

Secondary nucleating sequences affect kinetics and thermodynamics of tau aggregation

Tau protein was scanned for highly amyloidogenic sequences in amphiphilic motifs (X)nZ, Z(X)nZ (n≥2) or (XZ)n (n≥2), where X is a hydrophobic residue and Z is a charged or polar residue. N-acetyl peptides homologous to these sequences were used to study aggregation. Transmission electron microscopy (TEM) showed 7 peptides, in addition to well known primary nucleating sequences c275VQIINK (AcPHF6*) and Ac306VQIVYK (AcPHF6), formed fibers, tubes, ribbons or rolled sheets. Of the peptides shown by TEM to form amyloid, Ac10VME, AcPHF6*, Ac375KLTFR, and Ac393VYK were found to enhance the fraction of β-structure of AcPHF6 formed at equilibrium, and Ac375KLTFR was found to inhibit AcPHF6 and AcPHF6* aggregation kinetics in a dose-dependent manner, consistent with its participation in a hybrid steric zipper model. Single site mutants were generated which transformed predicted amyloidogenic sequences in tau into non-amyloidogenic ones. A M11K mutant had fewer filaments and showed a decrease in aggregation kinetics and an increased lag time compared to wild type tau, while a F378K mutant showed significantly more filaments. Our results infer that sequences throughout tau, in addition to PHF6 and PHF6*, can seed amyloid formation or affect aggregation kinetics or thermodynamics

Laboratory Selection Quickly Erases Historical Differentiation

The roles of history, chance and selection have long been debated in evolutionary biology. Though uniform selection is expected to lead to convergent evolution between populations, contrasting histories and chance events might prevent them from attaining the same adaptive state, rendering evolution somewhat unpredictable. The predictability of evolution has been supported by several studies documenting repeatable adaptive radiations and convergence in both nature and laboratory. However, other studies suggest divergence among populations adapting to the same environment. Despite the relevance of this issue, empirical data is lacking for real-time adaptation of sexual populations with deeply divergent histories and ample standing genetic variation across fitness-related traits. Here we analyse the real-time evolutionary dynamics of Drosophila subobscura populations, previously differentiated along the European cline, when colonizing a new common environment. By analysing several life-history, physiological and morphological traits, we show that populations quickly converge to the same adaptive state through different evolutionary paths. In contrast with other studies, all analysed traits fully converged regardless of their association with fitness. Selection was able to erase the signature of history in highly differentiated populations after just a short number of generations, leading to consistent patterns of convergent evolution

Clinton Street MAX Visioning

This report documents the initial analysis and visioning process performed in the area surrounding the Clinton Street Station, which is nestled between Hosford-Abernethy and Brooklyn neighborhoods and the Central Eastside Industrial District. This project focuses on the future of the Clinton Street Station and how its development will impact the surrounding area over the next 50 years. This task involved acknowledging and balancing the current needs of the various stakeholders. The purpose of this report is to act as a tool for the Hosford-Abernethy Neighborhood Association (HAND) to more adequately understand the opportunities and constraints that the future station area holds. In order to begin imagining the future of the area, a thorough understanding and analysis is presented. Following this, design principles that shape the vision for the future are described. The document concludes with next steps and implementation recommendations. This project was conducted under the supervision of Donald J. Stastny and Edward Starkie

The organization of the transcriptional network in specific neuronal classes

Genome-wide expression profiling has aided the understanding of the molecular basis of neuronal diversity, but achieving broad functional insight remains a considerable challenge. Here, we perform the first systems-level analysis of microarray data from single neuronal populations using weighted gene co-expression network analysis to examine how neuronal transcriptome organization relates to neuronal function and diversity. We systematically validate network predictions using published proteomic and genomic data. Several network modules of co-expressed genes correspond to interneuron development programs, in which the hub genes are known to be critical for interneuron specification. Other co-expression modules relate to fundamental cellular functions, such as energy production, firing rate, trafficking, and synapses, suggesting that fundamental aspects of neuronal diversity are produced by quantitative variation in basic metabolic processes. We identify two transcriptionally distinct mitochondrial modules and demonstrate that one corresponds to mitochondria enriched in neuronal processes and synapses, whereas the other represents a population restricted to the soma. Finally, we show that galectin-1 is a new interneuron marker, and we validate network predictions in vivo using Rgs4 and Dlx1/2 knockout mice. These analyses provide a basis for understanding how specific aspects of neuronal phenotypic diversity are organized at the transcriptional level

The cytotoxic effect of TiF4 and NaF on fibroblasts is influenced by the experimental model, fluoride concentration and exposure time.

OBJECTIVE: Titanium tetrafluoride (TiF4) has shown promising effect in preventing tooth lesions. Therefore, we compared the cytotoxicity of TiF4 with sodium fluoride (NaF) (already applied in Dentistry) considering different fluoride concentrations, pH values and experimental models. MATERIALS AND METHODS: Step 1) NIH/3T3 fibroblasts were exposed to mediums containing NaF or TiF4 (from 0.15 to 2.45% F), both at native and adjusted pH, for 6 h. Step 2) NIH/3T3 were exposed to NaF or TiF4 varnishes with 0.95, 1.95 or 2.45% F (native pH), for 6, 12 or 24 h. We applied MTT (1st and 2nd steps) and Hoescht/PI stain (2nd step) assays. Step 3) NIH/3T3 were exposed to NaF or TiF4 varnish (2.45% F), at native pH, for 6 or 12 h. The cell stiffness was measured by atomic force microscopy (AFM). RESULTS: Step 1) All cells exposed to NaF or TiF4 mediums died, regardless of the F concentration and pH. Step 2) Both varnishes, at 1.90 and 2.45% F, reduced cell viability by similar extents (33-86% at 6 h, 35-93% at 12 h, and 87-98% at 24 h) compared with control, regardless of the type of fluoride. Varnishes with 0.95% F did not differ from control. Step 3) TiF4 and NaF reduced cell stiffness to a similar extent, but only TiF4 differed from control at 6 h. CONCLUSIONS: Based on the results of the 3 experimental steps, we conclude that TiF4 and NaF have similar cytotoxicity. The cytotoxicity was dependent on F concentration and exposure time. This result gives support for testing the effect of TiF4 varnish in vivo

Direct images and spectroscopy of a giant protoplanet driving spiral arms in MWC 758

Understanding the driving forces behind spiral arms in protoplanetary disks remains a challenge due to the faintness of young giant planets. MWC 758 hosts such a protoplanetary disk with a two-armed spiral pattern that is suggested to be driven by an external giant planet. We present new thermal infrared observations that are uniquely sensitive to redder (i.e., colder or more attenuated) planets than past observations at shorter wavelengths. We detect a giant protoplanet, MWC 758c, at a projected separation of ~100 au from the star. The spectrum of MWC 758c is distinct from the rest of the disk and consistent with emission from a planetary atmosphere with Teff = 500 +/- 100 K for a low level of extinction (AV<30), or a hotter object with a higher level of extinction. Both scenarios are commensurate with the predicted properties of the companion responsible for driving the spiral arms. MWC 758c provides evidence that spiral arms in protoplanetary disks can be caused by cold giant planets or by those whose optical emission is highly attenuated. MWC 758c stands out both as one of the youngest giant planets known, and also as one of the coldest and/or most attenuated. Furthermore, MWC 758c is among the first planets to be observed within a system hosting a protoplanetary disk.Comment: Published in Nature Astronom