Identification of signaling pathways in early mammary gland development by mouse genetics

The mammary gland develops as an appendage of the ectoderm. The prenatal stage of mammary development is hormone independent and is regulated by sequential and reciprocal signaling between the epithelium and the mesenchyme. A number of recent studies using human and mouse genetics, in particular targeted gene deletion and transgenic expression, have identified some of the signals that control specific steps in development. This process involves cell specification and proliferation, reciprocal tissue interactions and cell migration. Since some of these events are recapitulated during tumorigenesis, an understanding of these signaling pathways may contribute to the development of targeted therapies and novel drugs

p63 regulates multiple signalling pathways required for ectodermal organogenesis and differentiation

Heterozygous germline mutations in p63, a transcription factor of the p53 family, result in abnormal morphogenesis of the skin and its associated structures, including hair follicles and teeth. In mice lacking p63, all ectodermal organs fail to develop, and stratification of the epidermis is absent. We show that the ectodermal placodes that mark early tooth and hair follicle morphogenesis do not form in p63-deficient embryos, although the multilayered dental lamina that precedes tooth placode formation develops normally. The N-terminally truncated isoform of p63 (?Np63) was expressed at high levels in embryonic ectoderm at all stages of tooth and hair development, and it was already dominant over the transactivating TAp63 isoform prior to epidermal stratification. Bmp7, Fgfr2b, Jag1 and Notch1 transcripts were co-expressed with ANp63 in wild-type embryos, but were not detectable in the ectoderm of p63 mutants. In addition, ?-catenin and Edar transcripts were significantly reduced in skin ectoderm. We also demonstrate that BMP2, BMP7 and FGF10 are potent inducers of p63 in cultured tissue explants. Hence, we suggest that p63 regulates the morphogenesis of surface ectoderm and its derivatives via multiple signalling pathways

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

Different Time, Same Place, Same Story? A Social Disorganization Perspective To Examining Juvenile Homicides

In 2007, juveniles were involved in a minimum of 1,063 murders in the United States (Federal Bureau of Investigation, 2008), and a concern over juvenile homicide offenders remains. While increasingly more macrolevel research on juvenile homicide offending has been accumulated, particularly since the 1980s, research focusing on macrolevel correlates of juvenile homicides is still relatively scarce (MacDonald & Gover, 2005; Ousey & Campbell Augustine, 2001). In the first part of this study, several variables relating to the offender, victim, setting, and precursors to the homicide by race and gender were examined in order to provide details on the context of youth homicides between 1965 and 1995 in Chicago. The Homicides in Chicago, 1965-1995 data set and Census data for 1970, 1980, and 1990 were used in this study. The results indicate that changes in youth homicides over the 31-year time period involved increases in lethal gang altercations, particularly among Latinos, and increases in the use of automatic weapons. Young females had very little impact on homicide rates in Chicago. The second part of the study examined whether measures of social disorganization can aid in the prediction of homicides committed by youths, and a total of ten negative binomial models were run. The results of the analyses in the three time periods indicate that racial/ethnic heterogeneity, educational deprivation, unemployment, and family disruption are significantly and positively related to homicides. Foreign-born population and median household income were found to be significantly and negatively related to homicides. The significant indicators of social disorganization varied in the seven models for the disaggregated groups. Overall, the results reflect support for social disorganization theory. Limitations, suggestion for future research, and policy implications are also addressed

Virkasalaisuusrikoksista

Tutkimuksen tarkoituksena on tutkia virkasalaisuusrikosten toteutumista ja virkasalaisuusrikosten eri osatekijöitä. Tutkimuksessa tarkastellaan virkarikosten lyhyen taustoituksen lisäksi virkasalaisuusrikosten rakenteen eri osa-alueita: salassa pidettävän tiedon tai asiakirjan tai muun ilmaisukiellon alaisen tiedon käsitettä, sivullisen käsitettä, oikeudettomuuden käsitettä, paljastamisen käsitettä, asiakirjan tai tiedon käyttämistä omaksi tai toisen hyödyksi tai toisen vahingoksi, virkasalaisuusrikoksia koskevaa tahallisuutta ja tuottamuksellisuutta sekä virkasalaisuusrikoksen vähäisyyden käsitettä. Tutkimuksen tutkimusmenetelmä on käytännöllinen lainoppi. Virkasalaisuusrikokset kuuluvat virkarikoksiin, joista on säännelty rikoslain (19.12.1889/39) 40 luvussa (12.7.2002/604). Virkarikossäännöksiä voidaan soveltaa ainoastaan rikoslain 40 luvun 11 §:n mukaisiin virkamiehiin, jota käsitettä on määritelty tutkimuksen 2 luvussa. Kyseisessä luvussa on taustoitettu myös lyhyesti virkasalaisuuden kriminalisointiin johtaneita syitä ja eritelty virkasalaisuusrikosten rikostyyppiä. Tutkimuksen 3 luvussa on käsitelty virkasalaisuusrikosten tunnusmerkistön varsinaisia osa-alueita, jotka on lueteltu edellä. Virkasalaisuusrikosten eri osa-alueiden sisältöä on mahdotonta määritellä täysin täsmällisesti erilaisten virkasalaisuusrikosten toteuttamistapojen sekä virkasalaisuusrikossäännösten huomattavan avoimuuden vuoksi, joten tutkimuksen 3 luku tarjoaa lähinnä esimerkkejä virkasalaisuusrikosten eri osa-alueiden mahdollisesta sisällöstä. Tutkimuksen tutkimustulosten mukaan virkasalaisuusrikossäännöksen väljä muotoilu aiheuttaa tällä hetkellä korostettuja vaatimuksia virkasalaisuusrikosten täyttymistä koskevalle perusteluvelvollisuudelle, jotta perustuslain (11.6.1999/731) 21 §:n mukaisen oikeusturvaperussäännöksen toteutuminen voitaisiin taata mahdollisimman kattavasti. Tutkimus osoittaa legaliteettiperiaatteen ja blankorangaistuksen ongelmallisuuden virkarikossäännöksen kannalta. Tutkimustulosten mukaan salassapitonormistoja tulisi de lege ferenda pyrkiä edelleen keskittämään viranomaisten toiminnan julkisuudesta annettuun lakiin (21.5.1999/621) ja salassa pidettäviä seikkoja koskevaa erityissääntelyä tulisi vastaavasti pyrkiä vähentämään. Myös virkasalaisuusnormistoihin liittyvää virkamiesten koulutusta tulisi pyrkiä lisäämään, ja pidemmällä aikavälillä saattaisi olla perusteltua pohtia myös virkamiesten kelpoisuusvaatimusten tiukentamista eräiltä osin. Myös virkasalaisuusrikoksiin liittyviä eettisiä kysymyksiä tulisi tutkimuksen tutkimustulosten mukaan painottaa nykyistä enemmän

Improving Risk Predictions by Preprocessing Imbalanced Credit Data

Imbalanced credit data sets refer to databases in which the class of defaulters is heavily under-represented in comparison to the class of non-defaulters. This is a very common situation in real-life credit scoring applications, but it has still received little attention. This paper investigates whether data resampling can be used to improve the performance of learners built from imbalanced credit data sets, and whether the effectiveness of resampling is related to the type of classifier. Experimental results demonstrate that learning with the resampled sets consistently outperforms the use of the original imbalanced credit data, independently of the classifier used

Overview of MPC applications in supply chains: Potential use and benefits in the management of forest-based supply chains

Aim of study: This work aims to provide an overview of Model Predictive Controllers (MPC) applications in supply chains, to describe the forest-based supply chain and to analyse the potential use and benefits of MPC in a case study concerning a biomass supply chain.Area of study: The proposed methods are being applied to a company located in Finland.Material and methods: Supply chains are complex systems where actions and partners’ coordination influence the whole system performance. The increase of competitiveness and need of quick responses to the costumers implies the use of efficient management techniques. The control theory, particularly MPC, has been successfully used as a supply chain management tool. MPC is able to deal with dynamic interactions between the partners and to globally optimize the supply chain performance in the presence of disturbances. However, as far as is authors’ knowledge, there are no applications of this methodology in the forest-based supply chains. This work proposes a control architecture to improve the performance of the forest supply chain. The controller is based on prediction models which are able to simulate the system and deal with disturbances.Main results: The preliminary results enable to evaluate the impacts of disturbances in the supply chain. Thus, it is possible to react beforehand, controlling the schedules and tasks’ allocation, or alert the planning level in order to generate a new plan.Research highlights:   Overview of MPC applications in supply chains; forest-based supply chain description; case study presentation: wood biomass supply chain for energy production; MPC architecture proposal to decrease the operation times.Keywords: biomass; forest; Model Predictive Control; planning; supply chain.</p

Hierarchical clustering of a Finnish newspaper article collection with graded relevance assessments

Abstract Search facilitated with agglomerative hierarchical clustering methods was studied in a collection of Finnish newspaper articles (N = 53,893). To allow quick experiments, clustering was applied to a sample (N = 5,000) that was reduced with principal components analysis. The dendrograms were heuristically cut to find an optimal partition, whose clusters were compared with each of the 30 queries to retrieve the best-matching cluster. The fourlevel relevance assessment was collapsed into a binary one by (A) considering all the relevant and (B) only the highly relevant documents relevant, respectively. Single linkage (SL) was the worst method. It created many tiny clusters, and, consequently, searches enabled with it had high precision and low recall. The complete linkage (CL), average linkage (AL), and Ward&apos;s methods (WM) returned reasonably-sized clusters typically of 18-32 documents. Their recall (A: 27-52%, B: 50-82%) and precision (A: 83-90%, B: 18-21%) was higher than and comparable to those of the SL clusters, respectively. The AL and WM clustering had 1-8% better effectiveness than nearest neighbor searching (NN), and SL and CL were 1-9% less efficient that NN. However, the differences were statistically insignificant. When evaluated with the liberal assessment A, the results suggest that the AL and WM clustering offer better retrieval ability than NN. Assessment B renders the AL and WM clustering better than NN, when recall is considered more important than precision. The results imply that collections in the highly inflectional and agglutinative languages, such as Finnish, may be clustered as the collections in English, provided that documents are appropriately preprocessed