Tools for single cell proteomics

Despite recent advances that offer control of single cells, in terms of manipulation and sorting and the ability to measure gene expression, the need to measure protein copy number remains unmet. Measuring protein copy number in single cells and related quantities such as levels of phosphorylation and protein-protein interaction is the basis of single cell proteomics. A technology platform to undertake the analysis of protein copy number from single cells has been developed. The approach described is ‘all-optical’ whereby single cells are manipulated into separate analysis chambers using an optical trap; single cells are lysed by mechanical shearing caused by laser-induced microcavitation; and the protein released from a single cell is measured by total internal reflection microscopy as it is bound to micro-printed antibody spots within the device. The platform was tested using GFP transfected cells and the relative precision of the measurement method was determined to be 88%. Single cell measurements were also made on a breast cancer cell line to measure the relative levels of unlabelled human tumour suppressor protein p53 using a chip incorporating an antibody sandwich assay format. This demonstrates the ability count protein copy number from single cells in a manner which could be applied in principle to any set of proteins and for any cell type without the need for genetic engineering. Metabolism can undergo alteration in diseases such as cancer and heart failure and also as cells differentiate during development. In order to assess how it may inform a proteomic measurement, multidimensional two-photon fluorescence metabolic imaging is conducted on a cultured cancer cell line, primary adult rat cardiomyocytes and human embryonic stem cells. By measuring the parameters of fluorescence such as intensity and lifetime of the autofluorescent metabolic co-factors NADH and FAD, it was found to be possible to contrast cells under various conditions and metabolic stimuli. In particular, human embryonic stem cells were able to be contrasted at 3 stages of development as they underwent differentiation into embryonic stem cell derived cardiomyocytes. Metabolic imaging provides a non-destructive method to monitor cellular metabolic activity with high resolution. This is complimentary to the single cell proteomic platform and the convergence of both techniques holds promise in future investigations into how metabolism influences cell function and the proteome in development and disease

Variance Analysis of Randomized Consensus in Switching Directed Networks

In this paper, we study the asymptotic properties of distributed consensus algorithms over switching directed random networks. More specifically, we focus on consensus algorithms over independent and identically distributed, directed Erdos-Renyi random graphs, where each agent can communicate with any other agent with some exogenously specified probability $p$. While it is well-known that consensus algorithms over Erdos-Renyi random networks result in an asymptotic agreement over the network, an analytical characterization of the distribution of the asymptotic consensus value is still an open question. In this paper, we provide closed-form expressions for the mean and variance of the asymptotic random consensus value, in terms of the size of the network and the probability of communication $p$. We also provide numerical simulations that illustrate our results.Comment: 6 pages, 3 figures, submitted to American Control Conference 201

Non-Bayesian Social Learning, Second Version

We develop a dynamic model of opinion formation in social networks. Relevant information is spread throughout the network in such a way that no agent has enough data to learn a payoff-relevant parameter. Individuals engage in communication with their neighbors in order to learn from their experiences. However, instead of incorporating the views of their neighbors in a fully Bayesian manner, agents use a simple updating rule which linearly combines their personal experience and the views of their neighbors (even though the neighbors’ views may be quite inaccurate). This non-Bayesian learning rule is motivated by the formidable complexity required to fully implement Bayesian updating in networks. We show that, under mild assumptions, repeated interactions lead agents to successfully aggregate information and to learn the true underlying state of the world. This result holds in spite of the apparent naıvite of agents’ updating rule, the agents’ need for information from sources (i.e., other agents) the existence of which they may not be aware of, the possibility that the most persuasive agents in the network are precisely those least informed and with worst prior views, and the assumption that no agent can tell whether their own views or their neighbors’ views are more accurate.Social networks, learning, information aggregation

Firm size, audit regulation and fraud detection

Revizor je odgovoren za preprečevanje, odkrivanje in poročanje o goljufijah. Pri revidiranju so najspornejši nezakoniti akti in napake. Ti področji sta tudi najpogostejši predmet razprave med revizorji, politiki, mediji, zakonodajalci in javnostjo (Gaz in dr. 1997). S predhodno raziskavo je bila ugotovljena pozitivna povezanost med kakovostjo revizije ter velikostjo revizorskega podjetja. Medtem ko so nekatere študije kot nadomestilo za kakovost revidiranja uporabile revizijske stroške, so druge študije uporabile bolj neposredna merila, kot so rezultati poročil o nadzoru kakovosti. Vendar so slednje študije uporabljale vzorce, ki so močno geografsko omejeni ali pa so omejeni v smislu vrste naročnika. To še ni vse. Večina raziskav o povezanosti med velikostjo in kakovostjo se je tudi osredotočila na dokaj velika pooblaščena revizijska (CPA) podjetja. Zadnja leta se je veliko razpravljalo o naravi revizijske prakse (Salehi 2007). Revizorji so odgovorni tudi za zagotavljanje točnosti in natančnosti izjav, ki jih pripravijo managerji

In vitro interaction and colocalization of HSV-1 ORF P with a cellular splicing factor (SC35) using pulldown assay

Herpes simplex virus type-1 (HSV-1) causes a variety of diseases in human. This virus is a neurotropic pathogen of human that establishes latent infection in the sensory ganglia innervating the site of primary infection. A number of genes including ICP34.5 control HSV-1 pathogenicity and ICP34.5 has been identified as HSV-1 virulence gene. Open reading frame P (ORF P) is also a HSV-1 gene that might have a role in latency. A complication in the analysis of the role of ICP34.5 and ORF P in the HSV-1 life cycle is that these two are overlapping antisense genes. ORF P is also deleted in ICP34.5 negative mutants and to date, no definite function is attributed to it. To attribute characteristics which were originally attributed solely to ICP34.5 to each of these two genes (ORF P or ICP34.5), an approach is to construct a number of HSV-1 recombinant viruses that express ICP34.5 and ORF P independently. An alternative way is to determine if ORF P interacts with any of the cellular and viral proteins both in vitro and in vivo. Using Glutathione-S-transferase (GST) pulldown assay and Western-blotting, we showed that ORF P interacts with a cellular splicing factor (SC35) in vitro. To investigate the colocalization of ORF P and SC35, nuclear and cytoplasmic fractionation of ORF P/SC35 was also carried out. Our results showed that both SC35 and ORF P are located in the nucleus of HSV-1 infected cells. Conclusively, because ORF P interacts and colocalizes with SC35, it might have a role in splicing

Distributed Coverage Verification in Sensor Networks Without Location Information

In this paper, we present three distributed algorithms for coverage verification in sensor networks with no location information. We demonstrate how, in the absence of localization devices, simplicial complexes and tools from algebraic topology can be used in providing valuable information about the properties of the cover. Our approach is based on computation of homologies of the Rips complex corresponding to the sensor network. First, we present a decentralized scheme based on Laplacian flows to compute a generator of the first homology, which represents coverage holes. Then, we formulate the problem of localizing coverage holes as an optimization problem for computing a sparse generator of the first homology. Furthermore, we show that one can detect redundancies in the sensor network by finding a sparse generator of the second homology of the cover relative to its boundary. We demonstrate how subgradient methods can be used in solving these optimization problems in a distributed manner. Finally, we provide simulations that illustrate the performance of our algorithms

Ocular complications of solar eclipse

باتوجه به اثرات و عوارض چشمی ناشی از نگاه به خورشید گرفتگی در یک مطالعه آینده نگر برآن شدیم تا افرادی را که متعاقب نگاه مستقیم یا غیر مستقیم به پدیده خورشید گرفتگی دچار عوارض چشمی شده اند را در سطح شهرکرد مورد معاینه و پیگیری قرار دهیم. 155 نفر با ناراحتی چشمی که در اثر نگاه به کسوف ایجاد شده بود به مطب ها و کلینیک ویژه چشم پزشکی مراجعه کرده و پس از معاینات لازم علائم بیمار در پرسشنامه مخصوصی ثبت و در فواصل زمانی یک هفته، یک ماه، سه ماه و شش ماه بعد مجددا بیماران معاینه گردیدند. 80 افراد مراجعه کننده در سن بین 20 تا 45 سالگی بوده و 55 نفر آنها بدون استفاده از فیلترهای حفاظتی به کسوف نگاه کرده بودند. بیشترین شکایات بیماران سوزش، خارش، آبریزش، فتوفوبی، تاری دید و سردرد بود. کاهش بینایی در 30 نفر، اسکوتوم بینایی در 10 نفر و متامورفوپسی در 5 نفر مشاهده شد. در هفته دوم در اکثر مراجعین علایم ابتدایی بطور کامل برطرف شده و تنها در 5 چشم کاهش حدت بینایی به میزان 2 تا 4 خط اسنلن موجود بود. 5 بیمار فوق تماما بدون استفاده از فیلتر و به مدت طولانی تقریبا کل مدت کسوف را مشاهده کرده بودند. در ماه سوم کاهش بینایی فوق همراه با سوختگی ملایم ماکولا در رتین در 5 چشم ذکر شده باقی بود ولی در فلوئورسئین آنژیوگرافی نکته غیر طبیعی مشاهده نشد. پس از شش ماه در 4 چشم حدت بینایی به 20/30 برگشته و در یک چشم دید 20/40 بود