Multiple roles of mouse Numb in tuning developmental cell fates.

BACKGROUND: Notch signaling regulates multiple differentiation processes and cell fate decisions during both invertebrate and vertebrate development. Numb encodes an intracellular protein that was shown in Drosophila to antagonize Notch signaling at binary cell fate decisions of certain cell lineages. Although overexpression experiments suggested that Numb might also antagonize some Notch activity in vertebrates, the developmental processes in which Numb is involved remained elusive. RESULTS: We generated mice with a homozygous inactivation of Numb. These mice died before embryonic day E11.5, probably because of defects in angiogenic remodeling and placental dysfunction. Mutant embryos had an open anterior neural tube and impaired neuronal differentiation within the developing cranial central nervous system (CNS). In the developing spinal cord, the number of differentiated motoneurons was reduced. Within the peripheral nervous system (PNS), ganglia of cranial sensory neurons were formed. Trunk neural crest cells migrated and differentiated into sympathetic neurons. In contrast, a selective differentiation anomaly was observed in dorsal root ganglia, where neural crest--derived progenitor cells had migrated normally to form ganglionic structures, but failed to differentiate into sensory neurons. CONCLUSIONS: Mouse Numb is involved in multiple developmental processes and required for cell fate tuning in a variety of lineages. In the nervous system, Numb is required for the generation of a large subset of neuronal lineages. The restricted requirement of Numb during neural development in the mouse suggests that in some neuronal lineages, Notch signaling may be regulated independently of Numb.

Multiple edges of a quantum Hall system in a strong electric

In this paper we show that if the electrons in a quantum Hall sample are subjected to a constant electric field in the plane of the material, comparable in magnitude to the background magnetic field on the system of electrons, a multiplicity of edge states localized at different regions of space is produced in the sample. The actions governing the dynamics of these edge states are obtained starting from the well-known Schrödinger field theory for a system of nonrelativistic electrons, where on top of the constant background electric and magnetic fields, the electrons are further subject to slowly varying weak electromagnetic fields. In the regions between the edges, dubbed as the "bulk," the fermions can be integrated out entirely and the dynamics expressed in terms of a local effective action involving the slowly varying electromagnetic potentials. It is further shown how the bulk action is gauge noninvariant in a particular way, and how the edge states conspire to restore the U(1) electromagnetic gauge invariance of the system. In the edge action we obtain a heretofore unnoticed gauge-invariant term that depends on the particular edge. We argue that this term may be detected experimentally as different edges respond differently to a monochromatic probe due to this term

2011 Road Use Tax Fund (RUTF) Study A report to the Iowa Legislature, per 2011 Iowa Code Section 307.31

The transportation system is in demand 24/7 and 365 days a year irrespective of neither the weather nor the conditions. Iowa’s transportation system is an integral and essential part of society serving commerce and daily functions of all Iowans across the state. A high quality transportation system serves as the artery for economic activity and, the condition of the infrastructure is a key element for our future growth opportunities. A key component of Iowa’s transportation system is the public roadway system owned and maintained by the state, cities and counties. In order to regularly re-evaluate the conditions of Iowa’s public roadway infrastructure and assess the ability of existing revenues to meet the needs of the system, the Iowa Department of Transportation’s 2006 Road Use Tax Fund (RUTF) report to the legislature included a recommendation that a study be conducted every five years. That recommendation was included in legislation adopted in 2007 and signed into law. The law specifically requires the following (2011 Iowa Code Section 307.31): •“The department shall periodically review the current revenue levels of the road use tax fund and the sufficiency of those revenues for the projected construction and maintenance needs of city, county, and state governments in the future. The department shall submit a written report to the general assembly regarding its findings by December 31 every five years, beginning in 2011. The report may include recommendations concerning funding levels needed to support the future mobility and accessibility for users of Iowa's public road system.” •“The department shall evaluate alternative funding sources for road maintenance and construction and report to the general assembly at least every five years on the advantages and disadvantages and the viability of alternative funding mechanisms.” Consistent with this requirement, the Iowa Department of Transportation (DOT) has prepared this study. Recognizing the importance of actively engaging with the public and transportation stakeholders in any discussion of public roadway conditions and needs, Governor Terry E. Branstad announced on March 8, 2011, the creation of, and appointments to, the Governor’s Transportation 2020 Citizen Advisory Commission (CAC). The CAC was tasked with assisting the Iowa DOT as they assess the condition of Iowa’s roadway system and evaluate current and future funding available to best address system needs. In particular the CAC was directed to gather input from the public and stakeholders regarding the condition of Iowa’s public roadway system, the impact of that system, whether additional funding is needed to maintain/improve the system, and, if so, what funding mechanisms ought to be considered. With this input, the CAC prepared a report and recommendations that were presented to Governor Branstad and the Iowa DOT in November 2011 for use in the development of this study. The CAC’s report is available at www.iowadot.gov/transportation2020/pdfs/CAC%20REPORT%20FINAL%20110211.pdf. The CAC’s report was developed utilizing analysis and information from the Iowa DOT. Therefore, the report forms the basis for this study and the two documents are very similar. Iowa is fortunate to have an extensive public roadway system that provides access to all areas of the state and facilitates the efficient movement of goods and people. However, it is also a tremendous challenge for the state, cities and counties to maintain and improve this system given flattening revenue, lost buying power, changing demands on the system, severe weather, and an aging system. This challenge didn’t appear overnight and for the last decade many studies have been completed to look into the situation and the legislature has taken significant action to begin addressing the situation. In addition, the Iowa DOT and Iowa’s cities and counties have worked jointly and independently to increase efficiency and streamline operations. All of these actions have been successful and resulted in significant changes; however, it is apparent much more needs to be done. A well-maintained, high-quality transportation system reduces transportation costs and provides consistent and reliable service. These are all factors that are critical in the evaluation companies undertake when deciding where to expand or locate new developments. The CAC and Iowa DOT heard from many Iowans that additional investment in Iowa’s roadway system is vital to support existing jobs and continued job creation in the state of Iowa. Beginning June 2011, the CAC met regularly to review material and discuss potential recommendations to address Iowa’s roadway funding challenges. This effort included extensive public outreach with meetings held in seven locations across Iowa and through a Transportation 2020 website hosted by the Iowa DOT (www.iowadot.gov/transportation2020). Over 500 people attended the public meetings held through the months of August and September, with 198 providing verbal or written comment at the meetings or through the website. Comments were received from a wide array of individuals. The public comments demonstrated overwhelming support for increased funding for Iowa’s roads. Through the public input process, several guiding principles were established to guide the development of recommendations. Those guiding principles are: • Additional revenues are restricted for road and bridge improvements only, like 95 percent of the current state road revenue is currently. This includes the fuel tax and registration fees. • State and local governments continue to streamline and become more efficient, both individually and by looking for ways to do things collectively. • User fee concept is preserved, where those who use the roads pay for them, including non¬residents. • Revenue-generating methods equitable across users. • Increase revenue generating mechanisms that are viable now but begin to implement and set the stage for longer-term solutions that bring equity and stability to road funding. • Continue Iowa’s long standing tradition of state roadway financing coming from pay-as-you-go financing. Iowa must not fall into the situation that other states are currently facing where the majority of their new program dollars are utilized to pay the debt service of past bonding. Based on the analysis of Iowa’s public roadway needs and revenue and the extensive work of the Governor’s Transportation 2020 Citizen Advisory Commission, the Iowa DOT has identified specific recommendations. The recommendations follow very closely the recommendations of the CAC (CAC recommendations from their report are repeated in Appendix B). Following is a summary of the recommendations which are fully documented beginning on page 21. 1. Through a combination of efficiency savings and increased revenue, a minimum of $215 million of revenue per year should be generated to meet Iowa’s critical roadway needs. 2. The Code of Iowa should be changed to require the study of the sufficiency of the state’s road funds to meet the road system’s needs every two years instead of every five years to coincide with the biennial legislative budget appropriation schedule. 3.Modify the current registration fee for electric vehicles to be based on weight and value using the same formula that applies to most passenger vehicles. 4.Consistent with existing Code of Iowa requirements, new funding should go to the TIME-21 Fund up to the cap ($225 million) and remaining new funding should be distributed consistent with the Road Use Tax Fund distribution formula. 5.The CAC recommended the Iowa DOT at least annually convene meetings with cities and counties to review the operation, maintenance and improvement of Iowa’s public roadway system to identify ways to jointly increase efficiency. In direct response to this recommendation, Governor Branstad directed the Iowa DOT to begin this effort immediately with a target of identifying $50 million of efficiency savings that can be captured from the over $1 billion of state revenue already provided to the Iowa DOT and Iowa’s cities and counties to administer, maintain and improve Iowa’s public roadway system. This would build upon past joint and individual actions that have reduced administrative costs and resulted in increased funding for improvement of Iowa’s public roadway system. Efficiency actions should be quantified, measured and reported to the public on a regular basis. 6.By June 30, 2012, Iowa DOT should complete a study of vehicles and equipment that use Iowa’s public roadway system but pay no user fees or substantially lower user fees than other vehicles and equipment.

Policy of the Iowa Department of Transportation Highway Division For Accommodating Utilities on the Primary Road System, 1992

This chapter covers initial placement, adjustment, improvement, relocation, replacement and maintenance of utility facilities in, on, above or below the right-of-way over of primary highways, including attachments to primary highway structures. It embodies the basic specifications and standards needed, to ensure the safety of the highway user and the integrity of the highway. (1992 revision to 1990 policy.)

FY 2016 State Justice System Legislation Monitoring Report, December 1, 2015

The Criminal and Juvenile Justice Planning Advisory Council (CJJPAC) has requested that the Division of Criminal and Juvenile Justice Planning (CJJP) monitor the correctional impact of enacted legislation of particular interest. Completion of this report fulfills the CJJPAC’s legislative obligations outlined in Iowa Code section §216A.133. The following information provides a summary of select data identified as having a correctional impact. The total report provides data used to monitor other legislation for which the CJJPAC has interest in monitoring.

From pathogen defence to food allergy; The multiple facets of the mucosal immune system

Résumé destiné à un large public Le système immunitaire associé aux muqueuses gastro-intestinales doit être capable de protéger notre organisme contre l'invasion de pathogènes. Parallèlement, il doit identifier en Cant que tels, des composés inoffensifs comme la nourriture ou les milliards de bactéries qui résident dans notre intestin. Le travail présenté ici aborde ces deux aspects essentiels au bon fonctionnement de notre muqueuse intestinale. Dans une première partie, la protéine nommée pièce sécrétoire a été étudiée pour ses propriétés protectrices contre le pathogène viral rotavirus. Le rôle de la pièce sécrétoire est de transporter les anticorps que nous produisons vers la surface des muqueuses. En dehors de cette fonction bien connue, il se peut que cette protéine soit également capable de protéger notre organisme contre certains virus. L'hypothèse de travail était donc que la pièce sécrétoire se lie directement au virus, l'empêchant ainsi d'infecter des cellules épithéliales de l'intestin. En utilisant différentes techniques biochimiques, cette hypothèse s'est révélée fausse car aucune interaction entre la pièce sécrétoire et le virus n'a pu être observée, et logiquement, aucune protection n'a pu prendre place. En revanche, la pièce sécrétoire se lie à d'autres structures pathogéniques et permet ainsi de neutraliser leurs effets néfastes. La pièce sécrétoire participe donc activement à la protection de nos muqueuses, en plus de son rôle de transporteur. La deuxième partie de ce travail avait pour sujet les réactions inappropriées que le système immunitaire induit parfois contre un aliment, ou, autrement dit, les allergies alimentaires. Un modèle d'allergie alimentaire à donc été développé chez la souris et a permis de mesurer plusieurs symptômes et facteurs liés à l'allergie. Puis, ce modèle a été utilisé afin de tester les effets bénéfiques d'une bactérie lactique, dite probiotique, sur le développement de l'allergie. Il a été observé que, sous certaines circonstances, l'administration de la bactérie lactique protégeait entièrement les souris contre les réactions allergiques. L'effet bénéfique dépend donc du probiotique mais également d'autres facteurs encore inconnus â ce jour. Cette étude ouvre la voie sur la compréhension des mécanismes liés aux allergies alimentaires et sur l'impact que peuvent avoir les bactéries probiotiques sur cette maladie. Résumé Le système immunitaire associé aux muqueuses intestinales doit être capable de différencier les antigènes inoffensifs tels que 1a nourriture ou les bactéries commensales des microorganismes potentiellement dangereux. Cet aspect est essentiel pour le maintien de l'homéostase intestinale et fait l'objet du travail présenté ici. Dans un premier projet, les propriétés protectrices de la protéine appelée pièce sécrétoire (SC) ont été étudiées. SC est une protéine connue pour le transport des immunoglobulines à la surface des muqueuses. Cette protéine est fortement glycosylée paz des sucres complexes, ce qui nous a mené à postuler que SC puisse interagir avec le pathogène rotavirus. Cette hypothèse était soutenue par le fait que ce virus adhère aux cellules épithéliales par des résidus glycosylés. Des analyses biochimiques et biologiques ont démontré qu'aucune interaction entre SC et le virus ne prenait place, et que par conséquent SC n'offrait aucune protection contre ce pathogène. En revanche, SC interagit avec d'autres structures pathogéniques, comme la toxine A de Clostridium difficile, et la molécule d'adhésion intimine de la bactérie entéropathogène Escherichia coli. La liaison se fait par l'intermédiaire des sucres et confère ainsi une protection contre ces pathogènes. Ainsi, SC a été identifié comme agent neutralisant au niveau de l'intestin. La deuxième partie de ce travail abordait le sujet des allergies alimentaires, et avait pour but de tester les effets bénéfiques potentiels d'une bactérie probiotique, Lactobacillus paracasei NCC2461, contre les réactions allergiques. Un modèle marin d'allergie alimentaire a été mis au point, permettant de mesurer des immunoglobulines E, des symptômes allergiques, et la dégranulation de mastocytes. Lorsque le probiotique a été administré aux souris, celles-ci ont été complètement protégées des réactions allergiques dans une première expérience. Cependant, cette protection n'a pas été reproduite et suggère que des facteurs environnementaux encore inconnus sont critiques pour que le probiotique agisse positivement. Ce travail a permis de mettre en évidence la complexité de l'approche des traitements liés aux probiotiques et ouvre la voie sur la compréhension des mécanismes liés à l'allergie. Abstract The mucosal immune system associated to the gastrointestinal mucosa must efficiently distinguish between innocuous antigens, such as food proteins and commensal bacteria and potentially infectious agents. The work presented here deals with these two essential aspects guaranteeing intestinal homeostasis. In the first part of this work, the protective properties of secretory component (SC) toward the pathogen rotavirus were investigated. SC, which allows the transport of polymeric immunoglobulins (Ig) to mucosal surfaces, is highly glycosylated with complex glycan structures. The abundance and the nature of these carbohydrates led us to speculate that SC might interact with rotavirus, which is known to bind target cells with glycan receptors. Using various biological and biochemical techniques, we demonstrated that SC did not interact with rotaviruses, nor protected epithelial cells from infection. However, SC was shown to bind to Clostridium difficile toxin A and to the enteropathogenic Echerischia coli adhesion molecule intimin in a glycan-dependent fashion. These interactions allow in vitro protection of epithelial cells using physiological concentrations of SC. These data identify SC as a microbial scavenger at mucosal surfaces, and in the context of secretory IgA, further enhance the neutralising properties of the complex. The second project was inscribed in the domain of food allergy and aimed to test the modulatory functions of a probiotic strain of Lactobacillus paracasei toward allergic reactions. A model of food-mediated allergy was developed in the mouse using mucosal sensitisation. Several parameters associated to allergy were quantified after allergen challenge, and included allergen-specific IgE, allergic signs like diarrhea and temperature drop, and degranulation of mast cells. Administration of the probiotic strain was shown to completely protect mice from allergic reactions. However, these data were not reproduced, suggesting that unknown environmental factors are required so that protection mediated by the probiotic strain occurs. This study paves the way to the understanding of the mechanisms associated to allergy, and highlights the tremendous complexity that probiotic treatments will have to face.

Wireless Authentication and Authorization, case Wireless Access Control System

Lyhyen kantaman radiotekniikoiden hyödyntäminen mahdollistaa uudenlaisten paikallisten palveluiden käytön ja vanhojen palveluiden kehittämisen. Kulunvalvonta on päivittäisenä palveluna valittu työn esimerkkisovellukseksi. Useita tunnistus- ja valtuutustapoja tutkitaan, ja julkisen avaimen infrastruktuuri on esitellään tarkemmin. Langattomat tekniikat Bluetooth, Zigbee, RFID ja IrDA esitellän yleisellä tasolla langattomat tekniikat –luvussa. Bluetooth-tekniikan rakennetta, mukaan lukien sen tietoturva-arkkitehtuuria, tutkitaan tarkemmin. Bluetooth-tekniikkaa käytetään työssä suunnitellun langattoman kulunvalvontajärjestelmän tietojen siirtoon. Kannettava päätelaite toimii käyttäjän henkilökohtaisena luotettuna laitteena, jota voi käyttää avaimena. Käyttäjän tunnistaminen ja valtuuttaminen perustuu julkisen avaimen infrastruktuuriin. Ylläpidon allekirjoittamat varmenteet sisältävät käyttäjän julkisen avaimen lisäksi tietoa hänestä ja hänen oikeuksistaan. Käyttäjän tunnistaminen kulunvalvontapisteissä tehdään julkisen ja salaisen avaimen käyttöön perustuvalla haaste-vastaus-menetelmällä. Lyhyesti, järjestelmässä käytetään Bluetooth-päätelaitteita langattomina avaimina.

Social insurances system's shortcomings : the example of the low-income young retirees' access to healthcare [Imperfections du système d'assurances sociales : l'exemple de l'accès aux soins des jeunes retraité(e)s à revenu modeste]

This article presents the results of a study involving 2445 recently retired persons from the Canton of Vaud in Switzerland who choose to forego health care. These persons of modest means barely qualify for government assistance programs and do not benefit from the social safety net that is provided to the truly destitute. 17.9% of the respondents to the questionnaire said that they forego health care for financial reasons. Interviews reveal the complex reasons that lie behind such a choice, as well as the compensation strategies that are sometimes used to get medical treatment. These strategies show that the people are able to act when the circumstances require them to do so. Despite that, their situation remains insecure. Cet article analyse les résultats d'une étude sur le renoncement aux soins menée auprès de 2445 Vaudois∙e∙s récemment retraité∙e∙s. Ces personnes de situation modeste sont proches des limites d'accès aux aides étatiques et ne bénéficient pas du même filet de protection sociale que d'autres plus démunies. 17.9% des répondant∙e∙s au questionnaire déclarent renoncer à des soins pour raisons financières. Des entretiens mettent en évidence la complexité du renoncement, ainsi que les stratégies compensatoires que les personnes adoptent pour accéder à certains soins. Ces dernières démontrent une capacité d'agir en situation qui reste toutefois précaire.

Building object-oriented software with the D-Bus messaging system

Object-oriented programming is a widely adopted paradigm for desktop software development. This paradigm partitions software into separate entities, objects, which consist of data and related procedures used to modify and inspect it. The paradigm has evolved during the last few decades to emphasize decoupling between object implementations, via means such as explicit interface inheritance and event-based implicit invocation. Inter-process communication (IPC) technologies allow applications to interact with each other. This enables making software distributed across multiple processes, resulting in a modular architecture with benefits in resource sharing, robustness, code reuse and security. The support for object-oriented programming concepts varies between IPC systems. This thesis is focused on the D-Bus system, which has recently gained a lot of users, but is still scantily researched. D-Bus has support for asynchronous remote procedure calls with return values and a content-based publish/subscribe event delivery mechanism. In this thesis, several patterns for method invocation in D-Bus and similar systems are compared. The patterns that simulate synchronous local calls are shown to be dangerous. Later, we present a state-caching proxy construct, which avoids the complexity of properly asynchronous calls for object inspection. The proxy and certain supplementary constructs are presented conceptually as generic object-oriented design patterns. The e ect of these patterns on non-functional qualities of software, such as complexity, performance and power consumption, is reasoned about based on the properties of the D-Bus system. The use of the patterns reduces complexity, but maintains the other qualities at a good level. Finally, we present currently existing means of specifying D-Bus object interfaces for the purposes of code and documentation generation. The interface description language used by the Telepathy modular IM/VoIP framework is found to be an useful extension of the basic D-Bus introspection format.

Avalon Media System project update: a Hydra solution for digital audio and video access

Presentation at Open Repositories 2014, Helsinki, Finland, June 9-13, 2014

Designing a Bit Preservation System

Poster at Open Repositories 2014, Helsinki, Finland, June 9-13, 2014

The cumate gene-switch: a system for regulated expression in mammalian cells

Affiliation: Sophie Broussau, Amelie Pilotte & Bernard Massie : Départment de microbiologie et immunologie, Faculté de médecine, Université de Montréal

Qualitative Air Flow Modelling and Analysis of Data Centre Air Conditioning as Multiple Jet Array

Data centre is a centralized repository,either physical or virtual,for the storage,management and dissemination of data and information organized around a particular body and nerve centre of the present IT revolution.Data centre are expected to serve uniinterruptedly round the year enabling them to perform their functions,it consumes enormous energy in the present scenario.Tremendous growth in the demand from IT Industry made it customary to develop newer technologies for the better operation of data centre.Energy conservation activities in data centre mainly concentrate on the air conditioning system since it is the major mechanical sub-system which consumes considerable share of the total power consumption of the data centre.The data centre energy matrix is best represented by power utilization efficiency(PUE),which is defined as the ratio of the total facility power to the IT equipment power.Its value will be greater than one and a large value of PUE indicates that the sub-systems draw more power from the facility and the performance of the data will be poor from the stand point of energy conservation. PUE values of 1.4 to 1.6 are acievable by proper design and management techniques.Optimizing the air conditioning systems brings enormous opportunity in bringing down the PUE value.The air conditioning system can be optimized by two approaches namely,thermal management and air flow management.thermal management systems are now introduced by some companies but they are highly sophisticated and costly and do not catch much attention in the thumb rules.

Multiple edges of a quantum Hall system in a strong electric

In this paper we show that if the electrons in a quantum Hall sample are subjected to a constant electric field in the plane of the material, comparable in magnitude to the background magnetic field on the system of electrons, a multiplicity of edge states localized at different regions of space is produced in the sample. The actions governing the dynamics of these edge states are obtained starting from the well-known Schrödinger field theory for a system of nonrelativistic electrons, where on top of the constant background electric and magnetic fields, the electrons are further subject to slowly varying weak electromagnetic fields. In the regions between the edges, dubbed as the "bulk," the fermions can be integrated out entirely and the dynamics expressed in terms of a local effective action involving the slowly varying electromagnetic potentials. It is further shown how the bulk action is gauge noninvariant in a particular way, and how the edge states conspire to restore the U(1) electromagnetic gauge invariance of the system. In the edge action we obtain a heretofore unnoticed gauge-invariant term that depends on the particular edge. We argue that this term may be detected experimentally as different edges respond differently to a monochromatic probe due to this term