On the Properties of the Reaction Counts Chemical Master Equation

The reaction counts chemical master equation (CME) is a high-dimensional variant of the classical population counts CME. In the reaction counts CME setting, we count the reactions which have fired over time rather than monitoring the population state over time. Since a reaction either fires or not, the reaction counts CME transitions are only forward stepping. Typically there are more reactions in a system than species, this results in the reaction counts CME being higher in dimension, but simpler in dynamics. In this work, we revisit the reaction counts CME framework and its key theoretical results. Then we will extend the theory by exploiting the reactions counts’ forward stepping feature, by decomposing the state space into independent continuous-time Markov chains (CTMC). We extend the reaction counts CME theory to derive analytical forms and estimates for the CTMC decomposition of the CME. This new theory gives new insights into solving hitting times-, rare events-, and a priori domain construction problems

New visible light absorber for solar fuels : Ga(Sbx)N1-x alloys.

Solar energy conversion to fuels via photoelectrochemical water splitting is one of the most important technological directions toward meeting the global energy and environmental challenge. However, till date, there are no suitable semiconductor materials available that can absorb visible light, possess right kind of band edge energetics and are stable in aqueous environments. In this work, a new III-V alloy material Ga(Sbx)N1-x with dilute antimony concentration is proposed and developed for photoelectrochemical water splitting. Experimental studies were conducted first to synthesize the proposed alloy materials to understand structure-property relationships and compare them to those obtained using first principles computations. Finally, efforts were made to improve the quality of materials synthesized within the context of improving their photoactivity with water splitting reaction. In general, III-V nitrides have garnered immense interest as suitable materials for solar hydrogen generation due to their tunable band gaps with composition, high carrier mobilities and high absorption coefficients. Computations using first principles density functional theory (DFT+U) revealed that a small amount of Sb incorporation is sufficient to achieve a significant band gap reduction in GaN from 3.4eV to 2eV. Theoretical computations predicted that Ga(Sb)xN1-x alloys with 2 eV band gap straddle the electrochemical redox potentials. The synthesis of dilute GaSbxN1-x alloys is conducted using a custom-built metalorganic chemical vapor deposition reactor. Extensive characterization of the resulting films suggests that there is a large band gap bowing even with small amounts (few percent ~ 2-3%) of antimony incorporation into GaN. In addition, photoelectrochemical characterization confirmed the band edges straddling redox potentials. All the experimental data regarding band gap bowing, lattice expansion and band edge straddling matched very well with the theoretical predictions. Moreover, the alloys with Sb incorporation \u3e7% exhibited indirect band gap transition as predicted by DFT + U calculations. The polycrystalline Ga(Sbx)N1-x thin films were shown to be capable of unassisted water splitting but with low efficiencies. So, two different approaches are investigated to improve the quality of resulting films: thick films with high texture and single crystal quality, Ga(Sbx)N1-x nanowires. The use of a pre-treatment step at 900° C, 40:1 ratio of antimony to gallium precursors and temperatures above 750 °C allowed for good quality crystal growth while allowing for incorporation of antimony. Photoactivity as high as 1 mA/cm2 was obtained. In addition, VLS approach has been demonstrated to obtain high crystalline quality films using copper as catalyst. Vapor-liquid-solid growth experiments using copper particles allowed for tip led growth of GaSbxN1-x nanowires at temperatures beyond 600° C. The antimony composition in the resulting nanowires increased with growth temperature up to 5 at% while improving the quality. Also the photoactivity obtained from nanowires has been increased by two orders of magnitude when compared with polycrystalline films. In summary, a new class of III-V nitride alloys using dilute antimonides is demonstrated to have suitable properties for solar fuels applications but can find other applications

Exploration in Academic Medicine

Medical Schoolhttps://deepblue.lib.umich.edu/bitstream/2027.42/148201/1/sunkarab.pd

Association of genetic variation, gene expression, and protein abundance within the natriuretic peptide pathway

Background: The natriuretic peptide (NP) system is a critical physiologic pathway in heart failure, but there is marked individual variability in its functioning which may be genetic in origin. We investigated how genetic variations in NP pathway genes correlate with gene expression and protein abundance. Methods: DNA, RNA, and tissue from human kidney (n=77) were obtained. Kidney was chosen as target tissue because each of the four candidate genes and proteins (natriuretic peptide receptor 1 (NPR1), NPR2, NPR3 and membrane metallo-endopeptidase (MME)) are expressed there. DNA samples were genotyped for 120 single nucleotide polymorphisms (SNP) in these four genes using a custom Illumina array. mRNA levels were quantified using real-time reverse transcriptase polymerase chain reaction. Protein concentration was determined in tissue lysates using commercially available assays for each target. The association of SNPs with RNA and protein quantity was tested with ANOVA adjusted for gender and race. A principal components (PC) based method was also used to test the association of overall gene variation with RNA and protein quantity. Findings with false discovery rate (FDR) \u3c0.05 were considered significant. Results: Eleven SNPs in NPR2 were significantly associated with protein expression after controlling for FDR at 0.05, but none of these were associated with RNA quantity. Several genotypes in MME and NPR3 showed crude associations (unadjusted p\u3c0.05) for protein and RNA quantity, but not after controlling for FDR. There were no SNPs associated with RNA or protein expression in NPR1. RNA and Protein quantity poorly correlated with each other; NPR1 and MME showed weak but significant positive correlations (p = 0.04 and 0.03, respectively). The PC analysis yielded similar overall results, with PC1 of NPR2 (accounting for 71% of variability) being the only significant association with protein (p=0.04), and no associations for RNA. Conclusions: Genetic variation NPR2 is associated with altered protein expression, but this is not explained via gene expression. There were crude associations for MME and NPR3 variants but these did not reach adjusted significance in this small study. Additional studies are needed to assess the clinical impact, if any, of NPR2 genetic variation

Joint Representation of Translational and Rotational Components of Self-Motion in the Parietal Cortex

Navigating through the world involves processing complex visual inputs to extract information about self-motion relative to one\u27s surroundings. When translations (T) and rotations (R) are present together, the velocity patterns projected onto the retina (optic flow) are a combination of the two. Since navigational tasks can be extremely varied, such as deciphering heading or tracking moving prey or estimating one\u27s motion trajectory, it is imperative that the visual system represent both the T and R components. Despite the importance of such joint representations, most previous studies have only focused on the representation of translations. Moreover, these studies emphasized the role of extra-retinal cues (efference copies of self-generated rotations) rather than visual cues for decomposing the optic flow. We recorded single units in the macaque ventral intraparietal area (VIP) to understand the role of visual cues in decomposing optic flow and jointly representing both the T and R components. Through the following studies, we establish that the visual system can rely on purely visual cues to derive the translational and rotational components of self-motion. We also show for the first time, joint representation of T and R at the level of single neurons

Sexual Health Misinformation and Potential Interventions Among Youth on Social Media

With the rise of the internet and social media, many adolescents and young adults have turned to the internet and social media for sexual health information. However, this can be problematic because sexual health misinformation on social media utilizes a variety of techniques to quickly disseminate and retain that misinformation in users. Historically, the spread of sexual health misinformation has specifically negatively impacted adolescents and young adults regarding two sexual health topics: contraceptives and HPV vaccination. Current evidence demonstrates that a combination of corrections and inoculation would be effective against general health misinformation. However, there is a lack of research on interventions aimed specifically at sexual health misinformation among adolescents and young adults. It is imperative that researchers further investigate interventions against sexual health misinformation among adolescents and young adults since confounding factors may influence the efficacy of currently studied methods

A Tablet PC application for construction site safety inspection and fatality prevention

Construction industry accounts for the largest number of occupational injuries and fatalities every year. Occupational Safety and Health Administration (OSHA) is an organization responsible for regulating and enforcing standards for various occupations to ensure safe working conditions including construction industry. As an OSHA requirement, every construction employer should employ a safety program that involves both training of the employees and frequent site inspections. OSHA has provided an online ‘construction eTool’ as a training tool which also aids in the development of safety inspection procedures. Traditionally, safety inspections are paper based and usually designed to address a specific work area or procedure. The inspection reports did not include any detailed visual data which may increase the cost of maintenance and data mining for problem areas. This project explains the possibility of using Tablet PC’s as tool for performing safety inspections at a construction site to identify occupational hazards. As a part of the project, a Tablet PC application, Hazard Prevention Tool (HPT), is developed that concentrates on the four prime hazard areas, Electrical, Falls, Struck By, and Trenching and Excavation, hazards. The application makes it possible to capture the image of the worksite and marking the problem areas on the image. After each site inspection, a report is generated which includes the worksite image with problem areas marked and possible solutions for each problem area based on the OSHA recommendations. A usability test is also conducted as a part of the project using three sample work sites

Clementine Observations of the Zodiacal Light and the Dust Content of the Inner Solar System

Using the Moon to occult the Sun, the Clementine spacecraft used its navigation cameras to map the inner zodiacal light at optical wavelengths over elongations of 3-30 degrees from the Sun. This surface brightness map is then used to infer the spatial distribution of interplanetary dust over heliocentric distances of about 10 solar radii to the orbit of Venus. We also apply a simple model that attributes the zodiacal light as being due to three dust populations having distinct inclination distributions, namely, dust from asteroids and Jupiter-family comets (JFCs), dust from Halley-type comets, and an isotropic cloud of dust from Oort Cloud comets. The best-fitting scenario indicates that asteroids + JFCs are the source of about 45% of the optical dust cross-section seen in the ecliptic at 1 AU, but that at least 89% of the dust cross-section enclosed by a 1 AU radius sphere is of a cometary origin. When these results are extrapolated out to the asteroid belt, we find an upper limit on the mass of the light-reflecting asteroidal dust that is equivalent to a 12 km asteroid, and a similar extrapolation of the isotropic dust cloud out to Oort Cloud distances yields a mass equivalent to a 30 km comet, although the latter mass is uncertain by orders of magnitude.Comment: To be published in Icaru

Die Rolle der einzelnen Untereinheiten beim Schalten des durch Hyperpolarisation aktivierten und durch zyklische Nucleotide modulierten (HCN) Kanals

Hyperpolarization-activated cyclic nucleotide-modulated (HCN) channels are tetramers that elicit electrical rhythmicity in special brain neurons and cardiomyocytes. These channels are non-selective cationic channels which are activated by hyperpolarizing voltages and modulated by the binding of adenosine 3, 5 -cyclic monophosphate (cAMP) to the four cyclic nucleotidebinding domains (CNBD). The binding of cAMP shifts steady-state activation to more positive voltages, thereby accelerating the activation and increasing the current along with a slowing effect on deactivation. Inspite of knowing the structure of the isolated CNBDs by crystals and X-ray analysis and very recent insights into the HCN1 structure by cryo-electron microscopy, many questions on the function of these channels remain open. In particular, how the successive binding of four cyclic nucleotides is transmitted to change the operation of the channels and how the two stimuli,hyperpolarization and cAMP binding, are interlinked. So, the aim of this work was to study the role of individual subunits in the ligand (cAMP)-dependent activation and deactivation process of HCN2 channels with the help of patch-clamp technique and Xenopus laevis oocytes as an expression system. This project was focused to analyze the effects of cAMP binding to the subunits of HCN2 concatameric channels with a defined number of functional CNBDs. It was found that each liganded CNBD promotes channel activation in an additive manner irrespective of their position within the tetramer. In contrast, the open probability reached its maximum already when only two subunits were liganded. However, the process of deactivation was differently influenced by cAMP binding. Liganding of four, three, or at least two CNBDs in trans position slowed the deactivation process, whereas channels with either two functional CNBDs in cis position or with a single functional subunit were ineffective to decelerate the deactivation process. Together the results showed herein support an activation mechanism in which each single liganded CNBD (out of four) supports channel opening by causing a turning momentum on the tetrameric intracellular gating ring, thereby stabilizing the open pore. For maintaining activation, however, at least two subunits in trans position are needed to be liganded.Durch Hyperpolarisation aktivierte und zyklische Nukleotide modulierte (HCN-) Kanäle sind Tetramere, die die elektrische Rhythmizität in spezialisierten Neuronen und Herzzellen vermitteln. Sie sind nicht-selektive Kationenkanäle, die durch Hyperpolarisation geöffnet und durch die Bindung von zyklischem Adenosinmonophosphat (cAMP) an vier intrazelluläre Bindungsstellen (CNBDs) moduliert werden. Die Bindung von cAMP führt zu einer Verschiebung der Gleichgewichts-Aktivierung zu positiveren Spannungen, zu einer Beschleunigung der Aktivierung, zu einer Zunahme der Stromamplitude bei sättigender Hyperpolarisation sowie zu einer Verlangsamung der Deaktivierung. Trotz der Aufklärung der Struktur isolierter Bindungsstellen, sowie eines gesamten HCN-Kanals durch Röntgenstrukturanalyse bzw. Cryo-Elektronenmikroskopie, bleiben viele Fragen bezüglich des Kanalverhaltens offen. Dazu gehört die Frage, wie die Bindung der zyklischen Nukleotide in eine Konformationsänderung der Pore übersetzt wird und wie die beiden Stimuli Spannung und cAMP zusammenwirken. Ziel dieser Studie war es daher, die Rolle der individuellen Untereinheiten in der ligandenabhängigen Kanalaktivierung und –deaktivierung mit Hilfe der Patch-Clamp-Technik unter Verwendung von Xenopus laevis-Oozyten als heterologem Expressionssystem zu untersuchen. Dabei lag der Fokus auf der Analyse des cAMP-abhängigen Schaltens in konkatenierten HCN2-Kanälen mit einer definierten Anzahl funktioneller Bindungsstellen. Es konnte gezeigt werden, dass jede ligandierte Bindungsstelle die Kanalaktivierung fördert und in einer additiven Weise zur cAMP-abhängigen Verschiebung der halbmaximalen Spannung beiträgt. Dabei spielt die Position innerhalb des Tetramers keine Rolle. Die maximale Offenwahrscheinlichkeit dagegen wurde bereits durch die Ligandierung von nur zwei Bindungsstellen erreicht. Auch in diesem Fall war die Position der zwei besetzten Bindungsstellen im Tetramer nicht relevant. Im Fall der Deaktivierung ist dagegen die Position der Besetzung wichtig: Nur die Ligandierung von vier, drei oder zwei Bindungsstellen in trans-Position konnte die Deaktivierung verlangsamen. Die Besetzung von zwei Bindungsstellen in cis-Position bzw. von nur einer Bindungsstelle blieb wirkungslos. Zusammenfassend unterstützen die vorliegenden Ergebnisse einen Aktivierungsmechanismus, in dem jede einzelne ligandierte Bindungsstelle die Öffnung des Kanals begünstigt, indem eine Drehbewegung im intrazellulären Gatingringbewirkt wird, die den offenen Zustand des Kanals stabilisiert. Die Beibehaltung dieses offenen Zustandes erfordert mindestens zwei ligandierte Bindungsstellen in trans-Position

A DATA DRIVEN APPROACH TO IDENTIFY JOURNALISTIC 5WS FROM TEXT DOCUMENTS

Textual understanding is the process of automatically extracting accurate high-quality information from text. The amount of textual data available from different sources such as news, blogs and social media is growing exponentially. These data encode significant latent information which if extracted accurately can be valuable in a variety of applications such as medical report analyses, news understanding and societal studies. Natural language processing techniques are often employed to develop customized algorithms to extract such latent information from text. Journalistic 5Ws refer to the basic information in news articles that describes an event and include where, when, who, what and why. Extracting them accurately may facilitate better understanding of many social processes including social unrest, human rights violations, propaganda spread, and population migration. Furthermore, the 5Ws information can be combined with socio-economic and demographic data to analyze state and trajectory of these processes. In this thesis, a data driven pipeline has been developed to extract the 5Ws from text using syntactic and semantic cues in the text. First, a classifier is developed to identify articles specifically related to social unrest. The classifier has been trained with a dataset of over 80K news articles. We then use NLP algorithms to generate a set of candidates for the 5Ws. Then, a series of algorithms to extract the 5Ws are developed. These algorithms based on heuristics leverage specific words and parts-of-speech customized for individual Ws to compute their scores. The heuristics are based on the syntactic structure of the document as well as syntactic and semantic representations of individual words and sentences. These scores are then combined and ranked to obtain the best answers to Journalistic 5Ws. The classification accuracy of the algorithms is validated using a manually annotated dataset of news articles