Ectodysplasin A1 promotes placodal cell fate during early morphogenesis of ectodermal appendages.

Organs developing as appendages of the ectoderm are initiated from epithelial thickenings called placodes. Their formation is regulated by interactions between the ectoderm and underlying mesenchyme, and several signalling molecules have been implicated as activators or inhibitors of placode formation. Ectodysplasin (Eda) is a unique signalling molecule in the tumour necrosis factor family that, together with its receptor Edar, is necessary for normal development of ectodermal organs both in humans and mice. We have shown previously that overexpression of the Eda-A1 isoform in transgenic mice stimulates the formation of several ectodermal organs. In the present study, we have analysed the formation and morphology of placodes using in vivo and in vitro models in which both the timing and amount of Eda-A1 applied could be varied. The hair and tooth placodes of K14-Eda-A1 transgenic embryos were enlarged, and extra placodes developed from the dental lamina and mammary line. Exposure of embryonic skin to Eda-A1 recombinant protein in vitro stimulated the growth and fusion of placodes. However, it did not accelerate the initiation of the first wave of hair follicles giving rise to the guard hairs. Hence, the function of Eda-A1 appears to be downstream of the primary inductive signal required for placode initiation during skin patterning. Analysis of BrdU incorporation indicated that the formation of the epithelial thickening in early placodes does not involve increased cell proliferation and also that the positive effect of Eda-A1 on placode expansion is not a result of increased cell proliferation. Taken together, our results suggest that Eda-A1 signalling promotes placodal cell fate during early development of ectodermal organs.

Expectations, Learning and Monetary Policy: An Overview of Recent Research

Expectations about the future are central for determination of current macroeconomic outcomes and the formulation of monetary policy. Recent literature has explored ways for supplementing the benchmark of rational expectations with explicit models of expectations formation that rely on econometric learning. Some apparently natural policy rules turn out to imply expectational instability of private agents’ learning. We use the standard New Keynesian model to illustrate this problem and survey the key results about interest-rate rules that deliver both uniqueness and stability of equilibrium under econometric learning. We then consider some practical concerns such as measurement errors in private expectations, observability of variables and learning of structural parameters required for policy. We also discuss some recent applications including policy design under perpetual learning, estimated models with learning, recurrent hyperinflations, and macroeconomic policy to combat liquidity traps and deflation.

A Model of Near-Rational Exuberance

We study how the use of judgement or “add-factors” in forecasting may disturb the set of equilibrium outcomes when agents learn using recursive methods. We isolate conditions under which new phenomena, which we call exuberance equilibria, can exist in a standard self-referential environment. Local indeterminacy is not a requirement for existence. We construct a simple asset pricing example and find that exuberance equilibria, when they exist, can be extremely volatile relative to fundamental equilibria.

Does Ricardian Equivalence Hold When Expectations are not Rational?

This paper considers the Ricardian Equivalence proposition when expectations are not rational and are instead formed using adaptive learning rules. We show that Ricardian Equivalence continues to hold provided suitable additional conditions on learning dynamics are satisfied. However, new cases of failure can also emerge under learning. In particular, for Ricardian Equivalence to obtain, agents’ expectations must not depend on government’s financial variables under deficit financing.

Notes on Agents’ Behavioral Rules Under Adaptive Learning and Studies of Monetary Policy

These notes try to clarify some discussions on the formulation of individual intertemporal behavior under adaptive learning in representative agent models. First, we discuss two suggested approaches and related issues in the context of a simple consumption-saving model. Second, we show that the analysis of learning in the NewKeynesian monetary policy model based on “Euler equations” provides a consistent and valid approach.

Fiscal Policy and Learning

Using the standard real business cycle model with lump-sum taxes, we analyze the impact of fiscal policy when agents form expectations using adaptive learning rather than rational expectations (RE). The output multipliers for government purchases are significantly higher under learning, and fall within empirical bounds reported in the literature (in sharp contrast to the implausibly low values under RE). Effectiveness of fiscal policy is demonstrated during times of economic stress like the recent Great Recession. Finally it is shown how learning can lead to dynamics empirically documented during episodes of 'fiscal consolidations.'

Baysian Model Averaging, Learning and Model Selection

Agents have two forecasting models, one consistent with the unique rational expectations equilibrium, another that assumes a time-varying parameter structure. When agents use Bayesian updating to choose between models in a self-referential system, we find that learning dynamics lead to selection of one of the two models. However, there are parameter regions for which the non-rational forecasting model is selected in the long-run. A key structural parameter governing outcomes measures the degree of expectations feedback in Muth's model of price determination.

Ectodysplasin regulates hormone-independent mammary ductal morphogenesis via NF-κB.

Ductal growth of the mammary gland occurs in two distinct stages. The first round of branching morphogenesis occurs during embryogenesis, and the second round commences at the onset of puberty. Currently, relatively little is known about the genetic networks that control the initial phases of ductal expansion, which, unlike pubertal development, proceeds independent of hormonal input in female mice. Here we identify NF-κB downstream of the TNF-like ligand ectodysplasin (Eda) as a unique regulator of embryonic and prepubertal ductal morphogenesis. Loss of Eda, or inhibition of NF-κB, led to smaller ductal trees with fewer branches. On the other hand, overexpression of Eda caused a dramatic NF-κB-dependent phenotype in both female and male mice characterized by precocious and highly increased ductal growth and branching that correlated with enhanced cell proliferation. We have identified several putative transcriptional target genes of Eda/NF-κB, including PTHrP, Wnt10a, and Wnt10b, as well as Egf family ligands amphiregulin and epigen. We developed a mammary bud culture system that allowed us to manipulate mammary development ex vivo and found that recombinant PTHrP, Wnt3A, and Egf family ligands stimulate embryonic branching morphogenesis, suggesting that these pathways may cooperatively mediate the effects of Eda.

Ectodysplasin has a dual role in ectodermal organogenesis: inhibition of Bmp activity and induction of Shh expression.

Ectodermal organogenesis is regulated by inductive and reciprocal signalling cascades that involve multiple signal molecules in several conserved families. Ectodysplasin-A (Eda), a tumour necrosis factor-like signalling molecule, and its receptor Edar are required for the development of a number of ectodermal organs in vertebrates. In mice, lack of Eda leads to failure in primary hair placode formation and missing or abnormally shaped teeth, whereas mice overexpressing Eda are characterized by enlarged hair placodes and supernumerary teeth and mammary glands. Here, we report two signalling outcomes of the Eda pathway: suppression of bone morphogenetic protein (Bmp) activity and upregulation of sonic hedgehog (Shh) signalling. Recombinant Eda counteracted Bmp4 activity in developing teeth and, importantly, inhibition of BMP activity by exogenous noggin partially restored primary hair placode formation in Eda-deficient skin in vitro, indicating that suppression of Bmp activity was compromised in the absence of Eda. The downstream effects of the Eda pathway are likely to be mediated by transcription factor nuclear factor-kappaB (NF-kappaB), but the transcriptional targets of Edar have remained unknown. Using a quantitative approach, we show in cultured embryonic skin that Eda induced the expression of two Bmp inhibitors, Ccn2/Ctgf (CCN family protein 2/connective tissue growth factor) and follistatin. Moreover, our data indicate that Shh is a likely transcriptional target of Edar, but, unlike noggin, recombinant Shh was unable to rescue primary hair placode formation in Eda-deficient skin explants.

Secondary Aural Symptoms in Relation to Cranio-Cervical and General Disorders

The present thesis comprises two study populations. The first study sample (SS1) consisted of 411 adults examined and interviewed at three annual visits. The second study sample (SS2) consisted of 1720 adults who filled in a mailed questionnaire about secondary otalgia, tinnitus and fullness of ears. In the second phase of the SS2, 100 subjects with otalgia were examined and interviewed by specialist in stomatognathic physiology and otorhinolaryngology. In the third phase, 36 subjects participated in a randomized, controlled and blinded trial of effectiveness of occlusal appliance on secondary otalgia, facial pain, headache and treatment need of temporomandibular disorders (TMD). The standardized prevalence of recurrent secondary otalgia was 6%, tinnitus 15% and fullness of ears 8%. Aural symptoms were more frequent among young than old subjects. They were associated with other, simultaneous aural symptoms, TMD pain, head and neck region pain, and visits to a physician. The subjects with aural symptoms more often had tenderness on palpation of masticatory muscles and clinical signs of temporomandibular joint than the subjects without. 85% of the subjects reporting secondary otalgia had cervical spine or temporomandibular disorder or both. In SS1, the final model of secondary otalgia included active need treatment for TMD, elevated level of stress symptoms, and bruxism. In SS2, the final models of aural symptoms included associated aural symptoms, young age, TMD pain, headache and shoulder ache. Stabilization splint more effectively alleviated secondary otalgia and active treatment need for TMD than a palatal control splint. In patients with aural pain, tinnitus or fullness of ears, it is important to first rule out otologic and nasopharyngeal diseases that may cause the symptoms. If no explanation for aural symptoms is found, temporomandibular and cervical spine disorders should be rouled out to minimize unnecessary visits to a physician.

Uusien tuotantotapojen haasteet : esimerkkitapauksina mobiili-TV ja monimediaisuus YLE Uutisissa

Opinnäytetyön tavoitteena oli selvittää, millaisia ovat uusien tuotantotapojen haasteet uudenlaiselle sisällöntuotannolle ja uutisympäristölle. Monimediaisen tuotannon esimerkkitapauksiksi rajattiin mobiili-TV ja YLE Uutiset. Mobiili-TV:n tutkimusta varten kootulle testiryhmälle tehtiin subjektiivisen laadun kokemista mittaava MOS-testi (Mean Opinion Score), jossa selvitettiin testattavien mielipiteitä matkapuhelimen kautta esitettyjen videotiedostojen kuvan- ja äänenlaadusta sekä eri pakkaustapojen käyttökelpoisuudesta mobiili-TV:ssä. Testillä haettiin esille myös sisällöllisesti sopiva ja käyttökelpoinen suhde, jolla mobiili-TV:n lähetteen kokonaiskaistanleveys olisi kuvan ja äänen välillä hyvä jakaa. Lisäksi samalla testiryhmällä tutkittiin, mitä mobiili-TV:stä yleensä tiedetään, millaisena palvelu koetaan ja millaista sisältöä siihen kaivattaisiin. Tämän kuluttajatutkimuksen mukaan mobiili-TV:hen soveltuvimmiksi sisältötyypeiksi koettiin uutiset, ajankohtaisohjelmat ja osin urheilu. Mobiili-TV:ssä ei ole vielä paljoakaan tarjontaa, joten väline on suurelle yleisölle oikeastaan täysin tuntematon. Testiryhmän mielestä se voisi kuitenkin joissakin tilanteissa korvata tai täydentää perinteisen TV-vastaanottimen käyttöä. Mobiili-TV:n sisältötyyppitutkimuksen lisäksi tutkittiin YLE Uutisten sisällöntuotantomenettelyjä. Teemahaastattelujen avulla selvitettiin, millainen on toimituksen tuotantotapa, miten ylivälineellinen sisällöntuotanto siellä mahdollisesti toteutuu, millainen on sen mahdollinen mobiili-TV-palvelu ja miten siellä suhtaudutaan niin sanottuun kansalaisjournalismiin. Haastattelujen johtopäätöksinä YLE Uutisissa ei vielä toteudu aito ylivälineellinen tuotanto, mutta merkkejä muutoksesta on näkyvissä. Kansalaisjournalismin nousu on havaittu, mutta käytännön vastauksia siihen ei vielä ole. YLE Uutisten nykyinen 3G-matkapuhelimillakin käytettävä internet-TV-palvelu on toteutettu suoratoistopalveluna (engl. streaming), eikä vielä DVB-H-verkkotekniikkaa hyödyntäen, joten se on teknisesti melko matalalaatuista. Esimerkkinä toteutuneesta ylivälineellisestä tuotannosta on opinnäytetyössä esitelty Kansainvälisen Jean Sibelius -viulukilpailun monimediainen uutispalvelu. Lopuksi esitetään tutkimuksen pohjalta löytyneitä mahdollisuuksia, jotka tukevat YLE Uutisten tuotannon järjestämistä ylivälineelliseksi ja kansalaisten sisällöntuotantoa. aktivoivaksi.

Stable sunspot equilibria in a cash-in-advance economy

We analyze a monetary model with flexible labor supply, cash-inadvance constraints and seigniorage-financed government deficits. If the intertemporal elasticity of substitution of labor is greater than one, there are two steady states, one determinate and the other indeterminate. If the elasticity is less than one, there is a unique steady state, which can be indeterminate. Only in the latter case do there exist sunspot equilibria that are stable under adaptive learning. A sufficient reduction in government purchases can in many cases eliminate the sunspot equilibria while raising consumption/labor taxes even enough to balance the budget may fail to achieve determinacy.