Recording advances for neural prosthetics

An important challenge for neural prosthetics research is to record from populations of neurons over long periods of time, ideally for the lifetime of the patient. Two new advances toward this goal are described, the use of local field potentials (LFPs) and autonomously positioned recording electrodes. LFPs are the composite extracellular potential field from several hundreds of neurons around the electrode tip. LFP recordings can be maintained for longer periods of time than single cell recordings. We find that similar information can be decoded from LFP and spike recordings, with better performance for state decodes with LFPs and, depending on the area, equivalent or slightly less than equivalent performance for signaling the direction of planned movements. Movable electrodes in microdrives can be adjusted in the tissue to optimize recordings, but their movements must be automated to be a practical benefit to patients. We have developed automation algorithms and a meso-scale autonomous electrode testbed, and demonstrated that this system can autonomously isolate and maintain the recorded signal quality of single cells in the cortex of awake, behaving monkeys. These two advances show promise for developing very long term recording for neural prosthetic applications

Worldline approach to helicity flip in plane waves

We apply worldline methods to the study of vacuum polarisation effects in plane wave backgrounds, in both scalar and spinor QED. We calculate helicity-flip probabilities to one loop order and treated exactly in the background field, and provide a toolkit of methods for use in investigations of higher-order processes. We also discuss the connections between the worldline, S-matrix, and lightfront approaches to vacuum polarisation effects.Comment: 11 pages, 1 figur

Forced Evictions, Mass Displacement, and the Uncertain Promise of Land and Property Restitution in Haiti

Haiti\u27s devastating 2010 earthquake produced human suffering on an unimaginable scale. The disaster\u27s aftermath-marked by widespread displacement, secondary occupation of land, and consequent forced evictions-raises critical questions of land ownership and housing rights. It also provided a testing ground for the body of restitutionary legal norms developed in the decades following the Cold War. Using the earthquake in Haiti as a lens, this article critically examines the development of the restitution model, from its inception in the Balkans conflicts of the 1990s to its current expression in the United Nation\u27s Pinheiro Principles. While the Pinheiro Principles are positive in many regards, the Haitian displacement crisis lays bare their shortcomings. In four major ways, the assumptions underlying the restitutionary model have failed to match up with the actual human needs of displaced persons in urban Port-au-Prince and surrounding cities. This article identifies those conceptual mismatches-centered around causes of displacement, informality of land title and tenure, the role of secondary occupation, and an unsupported distinction between the deserving and undeserving displaced-and concludes with a tentative, rights-based template for improvement tailored to the specific needs of Haiti\u27s poor

Verdsettelse av Selvaag Bolig ASA

Formålet med masteroppgaven er å besvare problemstillingen «Er aksjen til Selvaag Bolig ASA underpriset, overpriset eller rimelig priset i markedet?». Oppgaven innledes med en presentasjon av Selvaag Bolig hvor vi introduserer selskapet og gir en innføring i selskapets historie, visjon, forretningsmodell og organisering. Videre gir vi en kort presentasjon av eiendomsbransjen og bransjeutvalget som vil benyttes som sammenlignbare selskaper i den økonomiske analysen og den relative verdsettelsen. Deretter drøfter vi potensielle verdsettelsesmetoder vi er interessert i å ta i bruk for å besvare problemstillingen. Vi bestemmer oss for å gjennomføre en fundamental verdsettelse i form av en diskontert kontantstrømanalyse i kombinasjon med en relativ verdsettelse som supplement. Den fundamentale verdsettelsen starter med en rekke strategiske analyser (PESTEL, Porters og VRIO analyser) hvor vi analyserer de eksterne og interne forholdene som har betydning for Selvaag Boligs fremtidige verdiskapning og utvikling. Videre benytter vi økonomiske analyser i form av nøkkeltallsanalyser for å måle sentrale økonomiske parametere (rentabilitet, finansiering/soliditet og likviditet) knyttet til selskapets finansielle prestasjon og helse, og måler disse opp mot samme nøkkeltall fra bransjeutvalget. Neste trinn i den fundamentale verdsettelsen blir å gjennomføre den diskonterte kontantstrømanalysen hvor de strategiske- og økonomiske analysene i kombinasjon med historisk regnskapsdata legger grunnlaget for prognostisering og måling av selskapets fremtidige verdiskapning, som til slutt uttrykkes i form av en estimert aksjepris på kr 37,77 for Selvaag Bolig, som ligger 1,81% over dagens kurs (per 11.06.2024). Som et supplement til den estimerte aksjeprisen vi kom frem til i den fundamentale verdsettelsen av Selvaag Bolig, gjennomfører vi en relativ verdsettelse av selskapet hvor vi kommer frem til en estimert aksjepris på kr 74,28. For å teste robustheten av aksjeprisestimatet fra den fundamentale verdsettelsen gjennomfører vi en sensitivitetsanalyse i form av en Monte Carlo-simulering for å skape gjennomsiktighet og måle usikkerheten i estimeringen. Simuleringen beregner en gjennomsnittlig aksjepris på kr 35,59 for selskapet. Til slutt besvarer vi problemstillingen og konkluderer med at Selvaag Bolig ASA er rimelig priset i markedet basert på våre estimater.The purpose of this master's thesis is to address the research question: 'Is the stock of Selvaag Bolig ASA underpriced, overpriced, or fairly priced in the market?'. The thesis begins with a presentation of Selvaag Bolig, where we introduce the company and provide an overview of its history, vision, business model, and organizational structure. Furthermore, we provide a brief presentation of the real estate industry and the industry selection that will be used as comparable companies in the economic analysis and relative valuation. We then discuss potential valuation methods we are interested in employing to address the research question. We decide to conduct a fundamental valuation in the form of a discounted cash flow analysis, supplemented by a relative valuation. The fundamental valuation starts with a series of strategic analyses (PESTEL, Porter's, and VRIO analyses) where we examine the external and internal factors that influence Selvaag Bolig's future value creation and development. Subsequently, we use financial analyses in the form of key ratio analyses to measure key financial parameters (profitability, financing/solvency, and liquidity) related to the company's financial performance and health, and compare these with the same key ratios from the selected industry peers. The next step in the fundamental valuation is to conduct the discounted cash flow analysis, where the strategic and financial analyses, combined with historical financial data, form the basis for forecasting and measuring the company's future value creation, ultimately expressed as an estimated stock price of NOK 37.77 for Selvaag Bolig, which is 1.81% above the current price (as of June 11, 2024). As a supplement to the estimated stock price derived from the fundamental valuation of Selvaag Bolig, we conduct a relative valuation of the company, arriving at an estimated stock price of NOK 74.28. To test the robustness of the stock price estimate from the fundamental valuation, we conduct a sensitivity analysis in the form of a Monte Carlo simulation to create transparency and measure the uncertainty in the estimation. The simulation calculates an average stock price of NOK 35.59 for the company. Finally, we address the research question and conclude that Selvaag Bolig ASA is fairly priced in the market based on our estimates

Getting The Biggest Bang For Your Buck: Wildlife Monitoring On Shrublands Of The Nevada Test Site

The Nevada Test Site (NTS) covers 3,561 km2 and extends over portions of both the Mojave and Great Basin Deserts. The resulting diverse and complex flora and fauna exhibit elements of both deserts. There are 20 vegetation associations, composed primarily of shrubs, nested within 10 vegetation alliances. Of the more than 1,200 invertebrate and 339 vertebrate species found in these shrubland habitats, 267 are considered sensitive or protected/regulated by federal or state laws. Wildlife and wildlife habitat monitoring ensures NTS activities comply with all federal and state laws enacted for the protection of these valuable biological resources and provides ecological information that can be used to predict and evaluate the potential impacts of proposed projects and current activities on these resources. This paper describes the monitoring approach used at this large site. Monitoring strategies include conducting preactivity surveys, proactively monitoring sensitive species, monitoring long-term population trends, and collaborating with other agencies and biologists. Ways to make monitoring more efficient and examples of successful monitoring and collaborations are discussed

Factors influencing success of clinical genome sequencing across a broad spectrum of disorders

To assess factors influencing the success of whole-genome sequencing for mainstream clinical diagnosis, we sequenced 217 individuals from 156 independent cases or families across a broad spectrum of disorders in whom previous screening had identified no pathogenic variants. We quantified the number of candidate variants identified using different strategies for variant calling, filtering, annotation and prioritization. We found that jointly calling variants across samples, filtering against both local and external databases, deploying multiple annotation tools and using familial transmission above biological plausibility contributed to accuracy. Overall, we identified disease-causing variants in 21% of cases, with the proportion increasing to 34% (23/68) for mendelian disorders and 57% (8/14) in family trios. We also discovered 32 potentially clinically actionable variants in 18 genes unrelated to the referral disorder, although only 4 were ultimately considered reportable. Our results demonstrate the value of genome sequencing for routine clinical diagnosis but also highlight many outstanding challenges

DNAzyme Hybridization, Cleavage, Degradation and Sensing in Undiluted Human Blood Serum

This document is the Accepted Manuscript version of a Published Work that appeared in final form in Analytical Chemistry, copyright © American Chemical Society after peer review and technical editing by publisher. To access the final edited and published work see http://dx.doi.org/10.1021/acs.analchem.5b00220.RNA-cleaving DNAzymes provide a unique platform for developing biosensors. However, a majority of the work has been performed in clean buffer solutions, while the activity of some important DNAzymes in biological sample matrices is still under debate. Two RNA-cleaving DNAzymes (17E and 10-23) are the most widely used. In this work, we carefully studied a few key aspects of the 17E DNAzyme in human blood serum, including hybridization, cleavage activity, and degradation kinetics. Since direct fluorescence monitoring is difficult due to the opacity of serum, denaturing and nondenaturing gel electrophoresis were combined for studying the interaction between serum proteins and DNAzymes. The 17E DNAzyme retains its activity in 90% human blood serum with a cleavage rate of 0.04 min–1, which is similar to that in the PBS buffer (0.06 min–1) with a similar ionic strength. The activity in serum can be accelerated to 0.3 min–1 with an additional 10 mM Ca2+. As compared to 17E, the 10-23 DNAzyme produces negligible cleavage in serum. Degradation of both the substrate and the DNAzyme strand is very slow in serum, especially at room temperature. Degradation occurs mainly at the fluorophore label (linked to DNA via an amide bond) instead of the DNA phosphodiester bonds. Serum proteins can bind more tightly to the 17E DNAzyme complex than to the single-stranded substrate or enzyme. The 17E DNAzyme hybridizes extremely fast in serum. With this understanding, the detection of DNA using the 17E DNAzyme is demonstrated in serum.University of Waterloo || Natural Sciences and Engineering Research Council || Foundation for Shenghua Scholar of Central South University|| National Natural Science Foundation of China || Grant No. 21301195 Fellowship from the China Scholarship Council || CSC, Grant No. 20140637011

Transcriptome and genome sequencing uncovers functional variation in humans

Summary Genome sequencing projects are discovering millions of genetic variants in humans, and interpretation of their functional effects is essential for understanding the genetic basis of variation in human traits. Here we report sequencing and deep analysis of mRNA and miRNA from lymphoblastoid cell lines of 462 individuals from the 1000 Genomes Project – the first uniformly processed RNA-seq data from multiple human populations with high-quality genome sequences. We discovered extremely widespread genetic variation affecting regulation of the majority of genes, with transcript structure and expression level variation being equally common but genetically largely independent. Our characterization of causal regulatory variation sheds light on cellular mechanisms of regulatory and loss-of-function variation, and allowed us to infer putative causal variants for dozens of disease-associated loci. Altogether, this study provides a deep understanding of the cellular mechanisms of transcriptome variation and of the landscape of functional variants in the human genome