Relationship between estrogen receptor alpha location and gene induction reveals the importance of downstream sites and cofactors.

BACKGROUND: To understand cancer-related modifications to transcriptional programs requires detailed knowledge about the activation of signal-transduction pathways and gene expression programs. To investigate the mechanisms of target gene regulation by human estrogen receptor alpha (hERalpha), we combine extensive location and expression datasets with genomic sequence analysis. In particular, we study the influence of patterns of DNA occupancy by hERalpha on expression phenotypes. RESULTS: We find that strong ChIP-chip sites co-localize with strong hERalpha consensus sites and detect nucleotide bias near hERalpha sites. The localization of ChIP-chip sites relative to annotated genes shows that weak sites are enriched near transcription start sites, while stronger sites show no positional bias. Assessing the relationship between binding configurations and expression phenotypes, we find binding sites downstream of the transcription start site (TSS) to be equally good or better predictors of hERalpha-mediated expression as upstream sites. The study of FOX and SP1 cofactor sites near hERalpha ChIP sites shows that induced genes frequently have FOX or SP1 sites. Finally we integrate these multiple datasets to define a high confidence set of primary hERalpha target genes. CONCLUSION: Our results support the model of long-range interactions of hERalpha with the promoter-bound cofactor SP1 residing at the promoter of hERalpha target genes. FOX motifs co-occur with hERalpha motifs along responsive genes. Importantly we show that the spatial arrangement of sites near the start sites and within the full transcript is important in determining response to estrogen signaling.

Location-independent and location-linked representations of sound objects.

For the recognition of sounds to benefit perception and action, their neural representations should also encode their current spatial position and their changes in position over time. The dual-stream model of auditory processing postulates separate (albeit interacting) processing streams for sound meaning and for sound location. Using a repetition priming paradigm in conjunction with distributed source modeling of auditory evoked potentials, we determined how individual sound objects are represented within these streams. Changes in perceived location were induced by interaural intensity differences, and sound location was either held constant or shifted across initial and repeated presentations (from one hemispace to the other in the main experiment or between locations within the right hemispace in a follow-up experiment). Location-linked representations were characterized by differences in priming effects between pairs presented to the same vs. different simulated lateralizations. These effects were significant at 20-39 ms post-stimulus onset within a cluster on the posterior part of the left superior and middle temporal gyri; and at 143-162 ms within a cluster on the left inferior and middle frontal gyri. Location-independent representations were characterized by a difference between initial and repeated presentations, independently of whether or not their simulated lateralization was held constant across repetitions. This effect was significant at 42-63 ms within three clusters on the right temporo-frontal region; and at 165-215 ms in a large cluster on the left temporo-parietal convexity. Our results reveal two varieties of representations of sound objects within the ventral/What stream: one location-independent, as initially postulated in the dual-stream model, and the other location-linked.

Hierarchical modeling gave plausible estimates of associations between metabolic syndrome and components of antiretroviral therapy.

OBJECTIVE: Hierarchical modeling has been proposed as a solution to the multiple exposure problem. We estimate associations between metabolic syndrome and different components of antiretroviral therapy using both conventional and hierarchical models. STUDY DESIGN AND SETTING: We use discrete time survival analysis to estimate the association between metabolic syndrome and cumulative exposure to 16 antiretrovirals from four drug classes. We fit a hierarchical model where the drug class provides a prior model of the association between metabolic syndrome and exposure to each antiretroviral. RESULTS: One thousand two hundred and eighteen patients were followed for a median of 27 months, with 242 cases of metabolic syndrome (20%) at a rate of 7.5 cases per 100 patient years. Metabolic syndrome was more likely to develop in patients exposed to stavudine, but was less likely to develop in those exposed to atazanavir. The estimate for exposure to atazanavir increased from hazard ratio of 0.06 per 6 months' use in the conventional model to 0.37 in the hierarchical model (or from 0.57 to 0.81 when using spline-based covariate adjustment). CONCLUSION: These results are consistent with trials that show the disadvantage of stavudine and advantage of atazanavir relative to other drugs in their respective classes. The hierarchical model gave more plausible results than the equivalent conventional model.

GIS-Based Accident Location and Analysis System (GIS-ALAS) Project Report: Phase 1, 1998

This report summarizes progress made in Phase 1 of the GIS-based Accident Location and Analysis System (GIS-ALAS) project. The GIS-ALAS project builds on several longstanding efforts by the Iowa Department of Transportation (DOT), law enforcement agencies, Iowa State University, and several other entities to create a locationally-referenced highway accident database for Iowa. Most notable of these efforts is the Iowa DOT’s development of a PC-based accident location and analysis system (PC-ALAS), a system that has been well received by users since it was introduced in 1989. With its pull-down menu structure, PC-ALAS is more portable and user-friendly than its mainframe predecessor. Users can obtain accident statistics for locations during specified time periods. Searches may be refined to identify accidents of specific types or involving drivers with certain characteristics. Output can be viewed on a computer screen, sent to a file, or printed using pre-defined formats.

A Playful Glance at Hierarchical Questions for Two-Way Alternating Automata

Two-way alternating automata were introduced by Vardi in order to study the satisfiability problem for the modal μ-calculus extended with backwards modalities. In this paper, we present a very simple proof by way of Wadge games of the strictness of the hierarchy of Motowski indices of two-way alternating automata over trees.

Priorities and hierarchical accounts of translation

This paper is a study of the concept of priority and its use together with the notion of hierarchy in academic writing and theoretical models of translation. Hierarchies and priorities can be implicit or explicit, prescribed, suggested or described. The paper starts, chronologically, wtih Nida and Levý’s hierarchical accounts of translation and follows their legacy in scholars as different as Newmark and Gutt. The concept of priorities is hinted at also in didactic models (Nord) as well as in norm-theoretical and accounts of translation (Toury and Chesterman) within Descriptive Translation Studies. All of these authors are analyzed and commented. The paper calls for a more systematic and straightforward account of translational priorities, and proposes a few conceptual tools that stem from this research model, including the concepts of ambition and richness of a translation. Finally, the paper concludes with an adaptation of Lakoff and Johnson’s view of prototypicality and its potential usefulness in research into and the understanding of translation.

The neural basis for writing from dictation in the temporoparietal cortex.

Cortical electrical stimulation mapping was used to study neural substrates of the function of writing in the temporoparietal cortex. We identified the sites involved in oral language (sentence reading and naming) and writing from dictation, in order to spare these areas during removal of brain tumours in 30 patients (23 in the left, and 7 in the right hemisphere). Electrostimulation of the cortex impaired writing ability in 62 restricted cortical areas (.25 cm2). These were found in left temporoparietal lobes and were mostly located along the superior temporal gyrus (Brodmann's areas 22 and 42). Stimulation of right temporoparietal lobes in right-handed patients produced no writing impairments. However there was a high variability of location between individuals. Stimulation resulted in combined symptoms (affecting oral language and writing) in fourteen patients, whereas in eight other patients, stimulation-induced pure agraphia symptoms with no oral language disturbance in twelve of the identified areas. Each detected area affected writing in a different way. We detected the various different stages of the auditory-to-motor pathway of writing from dictation: either through comprehension of the dictated sentences (word deafness areas), lexico-semantic retrieval, or phonologic processing. In group analysis, barycentres of all different types of writing interferences reveal a hierarchical functional organization along the superior temporal gyrus from initial word recognition to lexico-semantic and phonologic processes along the ventral and the dorsal comprehension pathways, supporting the previously described auditory-to-motor process. The left posterior Sylvian region supports different aspects of writing function that are extremely specialized and localized, sometimes being segregated in a way that could account for the occurrence of pure agraphia that has long-been described in cases of damage to this region.

Mobile Communications within the European Union: The Role of Location in the Evolution and Forecasting of the Diffusion Process

In the European Union, the importance of mobile communications was realized early on. The process of mobile communications becoming ubiquitous has taken time, as the innovation of mobile communications diffused into the society. The aim of this study is to find out how the evolution and spatial patterns of the diffusion of mobile communications within the European Union could be taken into account in forecasting the diffusion process. There is relatively lot of research of innovation diffusion on the individual (micro) andthe country (macro) level, if compared to the territorial level. Territorial orspatial diffusion refers either to the intra-country or inter-country diffusionof an innovation. In both settings, the dif- fusion of a technological innovation has gained scarce attention. This study adds knowledge of the diffusion between countries, focusing especially on the role of location in this process. The main findings of the study are the following: The penetration rates of the European Union member countries have become more even in the period of observation, from the year 1981 to 2000. The common digital GSM system seems to have hastened this process. As to the role of location in the diffusion process, neighboring countries have had similar diffusion processes. They can be grouped into three, the Nordic countries, the central and southern European countries, and the remote southern European countries. The neighborhood effect is also domi- nating in thegravity model which is used for modeling the adoption timing of the countries. The subsequent diffusion within a country, measured by the logistic model in Finland, is af- fected positively by its economic situation, and it seems to level off at some 92 %. Considering the launch of future mobile communications systemsusing a common standard should implicate an equal development between the countries. The launching time should be carefully selected as the diffusion is probably delayed in economic downturns. The location of a country, measured by distance, can be used in forecasting the adoption and diffusion. Fi- nally, the result of penetration rates becoming more even implies that in a relatively homoge- nous set of countries, such as the European Union member countries, the estimated final pene- tration of a single country can be used for approximating the penetration of the others. The estimated eventual penetration of Finland, some 92 %, should thus also be the eventual level for all the European Union countries and for the European Union as a whole.

External Location Factors of Foreign Direct Investment in Russia – Finnish Perspective

Tämän diplomityön tavoitteena on selvittää, mitä alueellisia tekijöitä suomalaiset yritykset ottavat huomioon valitessaan sopivaa sijaintia suoralle investoinnille Venäjän sisällä. Muutamia yrityksen sisäisiä tekijöitä käytetään taustamuuttujina selittämään sijaintitekijöiden painotuksissa havaittavia eroja erilaisten yritysten välillä. Venäjän alueita vertaillaan lopuksi painotusten valossa. Työn ensimmäisessä osassa keskitytään suorien ulkomaisten investointien teoreettiseen taustaan. Aiempia tutkimuksia käydään läpi, jotta tekijät, joilla on havaittu olevan vaikutusta investointien sijoittumiseen maan sisällä, saadaan kartoitettua. Työn jälkimmäinen osa perustuu yrityskyselyn avulla kerättyyn empiiriseen aineistoon. Aineiston avulla selvitetään mitä tekijöitä suomalaisyritykset huomioivat sijaintipäätöstä tehdessään. Tulosten valossa on ilmeistä, että alueen markkinapotentiaali on suomalaisyrityksissä tärkein huomioitava tekijä investoinnin sijainnista päätettäessä. Myös infrastruktuuri ja kustannushyödyt vaikuttavat päätökseen. Erityyppisten yritysten painotukset ovat hyvin samanlaisia. Moskova ja Pietari vastaavat Venäjän alueista parhaiten suomalaisyritysten investoinnin sijainnille asettamia kriteerejä.

Privacy-friendly Business Models for Location-Based Mobile Services

This paper presents a theoretical model to analyze the privacy issues around location based mobile business models. We report the results of an exploratory field experiment in Switzerland that assessed the factors driving user payoff in mobile business. We found that (1) the personal data disclosed has a negative effect on user payoff; (2) the amount of personalization available has a direct and positive effect, as well as a moderating effect on user payoff; (3) the amount of control over user's personal data has a direct and positive effect, as well as a moderating effect on user payoff. The results suggest that privacy protection could be the main value proposition in the B2C mobile market. From our theoretical model we derive a set of guidelines to design a privacy-friendly business model pattern for third-party services. We discuss four examples to show the mobile platform can play a key role in the implementation of these new business models.

Business Model Considerations for Privacy Protection in a Mobile Location Based Context

In this paper we discuss the main privacy issues around mobile business models and we envision new solutions having privacy protection as a main value proposition. We construct a framework to help analyze the situation and assume that a third party is necessary to warrant transactions between mobile users and m-commerce providers. We then use the business model canvas to describe a generic business model pattern for privacy third party services. This pattern is then illustrated in two different variations of a privacy business model, which we call privacy broker and privacy management software. We conclude by giving examples for each business model and by suggesting further directions of investigation

External Location Factors of Finnish Direct Investment in Central and Eastern European Transitional Economies

Tutkimuksen päätavoitteena oli selvittää suomalaisten suorien investointien maan valintaan vaikuttavia tekijöitä Itä- ja Keski-Euroopan kymmenessä siirtymätaloudessa. Empiirisessä osuudessa tarkasteltiin suomalaisten yritysten tärkeimpiä sijaintitekijöitä alueella ja yrityskohtaisten tekijöiden vaikutusta sijaintitekijöihin. Tutkimuksessa selvitettiin myös yritysten päämotiiveja investoida maihin. Laaditun investointikriteeristön mukaan maat pystyttiin laittamaan paremmuusjärjestykseen suomalaisen investoijan kannalta. Empiirisen osuuden aineisto kerättiin postikyselylomakkeella yrityksiltä, joilla on tai jotka ovat suunnittelemassa investointeja näihin maihin. Tutkimusote oli kvantitatiivinen. Tutkimustulokset osoittavat, että suomalaiset investoijat valitsevat Itä- ja Keski-Euroopan maan investointikohteeksi pääasiassa markkinapotentiaalin ja edullisten kustannusten perusteella. Myös infrastruktuuri vaikuttaa maan valintaan. Eri aloilla toimivien yritysten sijaintitekijöiden painotuksissa havaittiin eroja. Yrityksen koko ja päämotiivi vaikuttivat sijaintitekijöiden painotuksiin. Investointikriteereiden mukaan kaksi parasta investointimaata suomalaisille investoijille ovat Puola ja Viro. Vertailtaessa investointikriteereitä toteutuneisiin investointeihin voidaan todeta, että suomalaiset investoijat eivät ole hyödyntäneet investoinneilla saatavia etuja kaikissa kohdemaissa.

Hierarchical linear models in Psychiatry: A bibliometric study

Development of research methods requires a systematic review of their status. This study focuses on the use of Hierarchical Linear Modeling methods in psychiatric research. Evaluation includes 207 documents published until 2007, included and indexed in the ISI Web of Knowledge databases; analyses focuses on the 194 articles in the sample. Bibliometric methods are used to describe the publications patterns. Results indicate a growing interest in applying the models and an establishment of methods after 2000. Both Lotka"s and Bradford"s distributions are adjusted to the data.

Delivery system for location based information in wireless IP networks

Tämä työ esittelee uuden tarjota paikasta riippuvaa tietoa langattomien tietoverkkojen käyttäjille. Tieto välitetään jokaiselle käyttäjälle tietämättä mitään käyttäjän henkilöllisyydestä. Sovellustason protokollaksi valittiin HTTP, joka mahdollistaa tämän järjestelmän saattaa tietoa perille useimmille käyttäjille, jotka käyttävät hyvinkin erilaisia päätelaitteita. Tämä järjestelmä toimii sieppaavan www-liikenteen välityspalvelimen jatkeena. Erilaisten tietokantojen sisällä on perusteella järjestelmä päättää välitetäänkö tietoa vai ei. Järjestelmä sisältää myös yksinkertaisen ohjelmiston käyttäjien paikantamiseksi yksittäisen tukiaseman tarkkuudella. Vaikka esitetty ratkaisu tähtääkin paikkaan perustuvien mainosten tarjoamiseen, se on helposti muunnettavissa minkä tahansa tyyppisen tiedon välittämiseen käyttäjille.