CDNF and MANF in an experimental model of Parkinson's disease in rats

Parkinson s disease (PD) is a neurodegenerative disorder associated with a progressive loss of dopaminergic neurons of the substantia nigra (SN). Current therapies of PD do not stop the progression of the disease and the efficacy of these treatments wanes over time. Neurotrophic factors are naturally occurring proteins promoting the survival and differentiation of neurons and the maintenance of neuronal contacts. Neurotrophic factors are attractive candidates for neuroprotective or even neurorestorative treatment of PD. Thus, searching for and characterizing trophic factors are highly important approaches to degenerative diseases. CDNF (cerebral dopamine neurotrophic factor) and MANF (mesencephalic astrocyte-derived neurotrophic factor) are secreted proteins that constitute a novel, evolutionarily conserved neurotrophic factor family expressed in vertebrates and invertebrates. The present study investigated the neuroprotective and restorative effects of human CDNF and MANF in rats with unilateral partial lesion of dopamine neurons by 6-hydroxydopamine (6-OHDA) using both behavioral (amphetamine-induced rotation) and immunohistochemical analyses. We also investigated the distribution and transportation profiles of intrastriatally injected CDNF and MANF in rats. Intrastriatal CDNF and MANF protected nigrostriatal dopaminergic neurons when administered six hours before or four weeks after the neurotoxin 6-OHDA. More importantly, the function of the lesioned nigrostriatal dopaminergic system was partially restored even when the neurotrophic factors were administered four weeks after 6-OHDA. A 14-day continuous infusion of CDNF but not of MANF restored the function of the midbrain neural circuits controlling movement when initiated two weeks after unilateral injection of 6-OHDA. Continuous infusion of CDNF also protected dopaminergic TH-positive cell bodies from toxin-induced degeneration in the substantia nigra pars compacta (SNpc) and fibers in the striatum. When injected into the striatum, CDNF and GDNF had similar transportation profiles from the striatum to the SNpc; thus CDNF may act via the same nerve tracts as GDNF. Intrastriatal MANF was transported to cortical areas which may reflect a mechanism of neurorestorative action that is different from that of CDNF and GDNF. CDNF and MANF were also shown to distribute more readily than GDNF. In conclusion, CDNF and MANF are potential therapeutic proteins for the treatment of PD.

Search for the associated production of the standard-model Higgs boson in the all-hadronic channel

"We report on a search for the standard-model Higgs boson in pp collisions at s=1.96 TeV using an integrated luminosity of 2.0 fb(-1). We look for production of the Higgs boson decaying to a pair of bottom quarks in association with a vector boson V (W or Z) decaying to quarks, resulting in a four-jet final state. Two of the jets are required to have secondary vertices consistent with B-hadron decays. We set the first 95% confidence level upper limit on the VH production cross section with V(-> qq/qq('))H(-> bb) decay for Higgs boson masses of 100-150 GeV/c(2) using data from run II at the Fermilab Tevatron. For m(H)=120 GeV/c(2), we exclude cross sections larger than 38 times the standard-model prediction."

Combination of Tevatron Searches for the Standard Model Higgs Boson in the W+W- Decay Mode

We combine searches by the CDF and D0 collaborations for a Higgs boson decaying to W+W-. The data correspond to an integrated total luminosity of 4.8 (CDF) and 5.4 (D0) fb-1 of p-pbar collisions at sqrt{s}=1.96 TeV at the Fermilab Tevatron collider. No excess is observed above background expectation, and resulting limits on Higgs boson production exclude a standard-model Higgs boson in the mass range 162-166 GeV at the 95% C.L.

Inclusive Search for Standard Model Higgs Boson Production in the WW Decay Channel using the CDF II Detector

We present a search for standard model (SM) Higgs boson production using ppbar collision data at sqrt(s) = 1.96 TeV, collected with the CDF II detector and corresponding to an integrated luminosity of 4.8 fb-1. We search for Higgs bosons produced in all processes with a significant production rate and decaying to two W bosons. We find no evidence for SM Higgs boson production and place upper limits at the 95% confidence level on the SM production cross section (sigma(H)) for values of the Higgs boson mass (m_H) in the range from 110 to 200 GeV. These limits are the most stringent for m_H > 130 GeV and are 1.29 above the predicted value of sigma(H) for mH = 165 GeV.

Search for the associated production of the standard-model Higgs boson in the all-hadronic channel

"We report on a search for the standard-model Higgs boson in pp collisions at s=1.96 TeV using an integrated luminosity of 2.0 fb(-1). We look for production of the Higgs boson decaying to a pair of bottom quarks in association with a vector boson V (W or Z) decaying to quarks, resulting in a four-jet final state. Two of the jets are required to have secondary vertices consistent with B-hadron decays. We set the first 95% confidence level upper limit on the VH production cross section with V(-> qq/qq('))H(-> bb) decay for Higgs boson masses of 100-150 GeV/c(2) using data from run II at the Fermilab Tevatron. For m(H)=120 GeV/c(2), we exclude cross sections larger than 38 times the standard-model prediction."

Designing a blended learning model for primary school language learning

In Finland, there is a desperate need for flexible, reliable and functional multi-e-learning settings for pupils aged 11-13. Southern Finland has several ongoing e-learning projects, but none that develop a multiple setting, with learning and teaching occurring between more than two schools. In 2006, internet connections were not broadband and data transfer was mainly audio data. Connections and technical problems occurred, which were an obstacle to multi-e-learning. Internet connections today enable web-based learning in major parts of
Lapland and by 2015, broadband will reach even the remotest villages up north. Therefore, it is important to research the possibilities of multi-e-learning and to build collaborative, learner-centred, versatile network models for primary school-aged pupils. The resulting model will facilitate distance learning to extend education to rural, sparsely populated areas, and it will give a model of using mobile devices in language portfolios. This will promote regional equality and prevent exclusion. Working with portfolios provides the opportunity to develop mobility from a pedagogical point of view. It is important to study the pros and cons of mobile devices in producing artefacts on portfolios in e-learning and language learning settings.
The current study represents a design-based research approach. The design research approach includes two important aspects concerning the current research: ‘a teacher as researcher’ aspect, which means there is the possibility to be strongly involved in developing processes and an obstacle-aspect, which means that problems while developing, are seen as a
promoter in evolving the designed model, as apposed to negative results.

Designing a blended learning model for primary school language learning

In Finland, there is a desperate need for flexible, reliable and functional multi-e-learning settings for pupils aged 11-13. Southern Finland has several ongoing e-learning projects, but none that develop a multiple setting, with learning and teaching occurring between more than two schools. In 2006, internet connections were not broadband and data transfer was mainly audio data. Connections and technical problems occurred, which were an obstacle to multi-e-learning. Internet connections today enable web-based learning in major parts of Lapland and by 2015, broadband will reach even the remotest villages up north. Therefore, it is important to research the possibilities of multi-e-learning and to build collaborative, learner-centred, versatile network models for primary school-aged pupils. The resulting model will facilitate distance learning to extend education to rural, sparsely populated areas, and it will give a model of using mobile devices in language portfolios. This will promote regional equality and prevent exclusion. Working with portfolios provides the opportunity to develop mobility from a pedagogical point of view. It is important to study the pros and cons of mobile devices in producing artefacts on portfolios in e-learning and language learning settings. The current study represents a design-based research approach. The design research approach includes two important aspects concerning the current research: ‘a teacher as researcher’ aspect, which means there is the possibility to be strongly involved in developing processes and an obstacle-aspect, which means that problems while developing, are seen as a promoter in evolving the designed model, as apposed to negative results.

Nonlinear mixture autoregressive model: economic applications

The aim of this dissertation is to model economic variables by a mixture autoregressive (MAR) model. The MAR model is a generalization of linear autoregressive (AR) model. The MAR -model consists of K linear autoregressive components. At any given point of time one of these autoregressive components is randomly selected to generate a new observation for the time series. The mixture probability can be constant over time or a direct function of a some observable variable. Many economic time series contain properties which cannot be described by linear and stationary time series models. A nonlinear autoregressive model such as MAR model can a plausible alternative in the case of these time series. In this dissertation the MAR model is used to model stock market bubbles and a relationship between inflation and the interest rate. In the case of the inflation rate we arrived at the MAR model where inflation process is less mean reverting in the case of high inflation than in the case of normal inflation. The interest rate move one-for-one with expected inflation. We use the data from the Livingston survey as a proxy for inflation expectations. We have found that survey inflation expectations are not perfectly rational. According to our results information stickiness play an important role in the expectation formation. We also found that survey participants have a tendency to underestimate inflation. A MAR model has also used to model stock market bubbles and crashes. This model has two regimes: the bubble regime and the error correction regime. In the error correction regime price depends on a fundamental factor, the price-dividend ratio, and in the bubble regime, price is independent of fundamentals. In this model a stock market crash is usually caused by a regime switch from a bubble regime to an error-correction regime. According to our empirical results bubbles are related to a low inflation. Our model also imply that bubbles have influences investment return distribution in both short and long run.

United We Stand - Divided We Fall : A Standard Model of Unit Cohesion

Research on unit cohesion has shown positive correlations between cohesion and valued outcomes such as strong performance, reduced stress, less indiscipline, and high re-enlistment intentions. However, the correlations have varied in strength and significance. The purpose of this study is to show that taking into consideration the multi-component nature of cohesion and relating the most applicable components to specific outcomes could resolve much of the inconsistency. Unit cohesion is understood as a process of social integration among members of a primary group with its leaders, and with the larger secondary groups of which they are a part. Correspondingly, included in the framework are four bonding components: horizontal (peer) and vertical (subordinate and leader) and organizational and institutional, respectively. The data were collected as part of a larger research project on cohesion, leadership, and personal adjustment to the military. In all, 1,534 conscripts responded to four questionnaires during their service in 2001-2002. In addition, sociometric questionnaires were given to 537 group members in 47 squads toward the end of their service. The results showed that platoons with strong primary-group cohesion differed from other platoons in terms of performance, training quality, secondary-group experiences, and attitudes toward refresher training. On the sociometric level it was found that soldiers who were chosen as friends by others were more likely to have higher expected performance, better performance ratings, more positive attitudes toward military service, higher levels of well-being during conscript service, and fewer exemptions from duty during it. On the group level, the selection of the respondents own group leader rather than naming a leader from outside (i.e., leader bonding) had a bearing not only on cohesion and performance, but also on the social, attitudinal, and behavioral criteria. Overall, the aim of the study was to contribute to the research on cohesion by introducing a model that takes into account the primary foci of bonding and their impact. The results imply that primary-group and secondary-group bonding processes are equally influential in explaining individual and group performance, whereas the secondary-group bonding components are far superior in explaining career intentions, personal growth, avoidance of duty, and attitudes toward refresher training and national defense. This should be considered in the planning and conducting of training. The main conclusion is that the different types of cohesion components have a unique, positive, significant, but varying impact on a wide range of criteria, confirming the need to match the components with the specific criteria.

Dual-trap optical tweezers with real-time force clamp control

Single molecule force clamp experiments are widely used to investigate how enzymes, molecular motors, and other molecular mechanisms work. We developed a dual-trap optical tweezers instrument with real-time (200 kHz update rate) force clamp control that can exert 0–100 pN forces on trapped beads. A model for force clamp experiments in the dumbbell-geometry is presented. We observe good agreement between predicted and observed power spectra of bead position and force fluctuations. The model can be used to predict and optimize the dynamics of real-time force clamp optical tweezers instruments. The results from a proof-of-principle experiment in which lambda exonuclease converts a double-stranded DNA tether, held at constant tension, into its single-stranded form, show that the developed instrument is suitable for experiments in single molecule biology.

Sensitivity of wetland methane emissions to model assumptions: application and model testing against site observations

Abstract. Methane emissions from natural wetlands and rice paddies constitute a large proportion of atmospheric methane, but the magnitude and year-to-year variation of these methane sources is still unpredictable. Here we describe and evaluate the integration of a methane biogeochemical model (CLM4Me; Riley et al., 2011) into the Community Land Model 4.0 (CLM4CN) in order to better explain spatial and temporal variations in methane emissions. We test new functions for soil pH and redox potential that impact microbial methane production in soils. We also constrain aerenchyma in plants in always-inundated areas in order to better represent wetland vegetation. Satellite inundated fraction is explicitly prescribed in the model because there are large differences between simulated fractional inundation and satellite observations. A rice paddy module is also incorporated into the model, where the fraction of land used for rice production is explicitly prescribed. The model is evaluated at the site level with vegetation cover and water table prescribed from measurements. Explicit site level evaluations of simulated methane emissions are quite different than evaluating the grid cell averaged emissions against available measurements. Using a baseline set of parameter values, our model-estimated average global wetland emissions for the period 1993–2004 were 256 Tg CH4 yr−1, and rice paddy emissions in the year 2000 were 42 Tg CH4 yr−1. Tropical wetlands contributed 201 Tg CH4 yr−1, or 78 % of the global wetland flux. Northern latitude (>50 N) systems contributed 12 Tg CH4 yr−1. We expect this latter number may be an underestimate due to the low high-latitude inundated area captured by satellites and unrealistically low high-latitude productivity and soil carbon predicted by CLM4. Sensitivity analysis showed a large range (150–346 Tg CH4 yr−1) in predicted global methane emissions. The large range was sensitive to: (1) the amount of methane transported through aerenchyma, (2) soil pH (± 100 Tg CH4 yr−1), and (3) redox inhibition (± 45 Tg CH4 yr−1).