Small GTPase RhoE/Rnd3 is a critical regulator of Notch1 signaling.

Aberrations of Notch signaling have been implicated in a variety of human cancers. Oncogenic mutations in NOTCH1 are common in human T-cell leukemia and lymphomas. However, loss-of-function somatic mutations in NOTCH1 arising in solid tumors imply a tumor suppressor function, which highlights the need to understand Notch signaling more completely. Here, we describe the small GTPase RhoE/Rnd3 as a downstream mediator of Notch signaling in squamous cell carcinomas (SCC) that arise in skin epithelia. RhoE is a transcriptional target of activated Notch1, which is attenuated broadly in SCC cells. RhoE depletion suppresses Notch1-mediated signaling in vitro, rendering primary keratinocytes resistant to Notch1-mediated differentiation and thereby favoring a proliferative cell fate. Mechanistic investigations indicated that RhoE controls a key step in Notch1 signaling by mediating nuclear translocation of the activated portion of Notch1 (N1IC) through interaction with importins. Our results define RhoE as a Notch1 target that is essential for recruitment of N1IC to the promoters of Notch1 target genes, establishing a regulatory feedback loop in Notch1 signaling. This molecular circuitry may inform distinct cell fate decisions to Notch1 in epithelial tissues, where carcinomas such as SCC arise. Cancer Res; 74(7); 2082-93. ©2014 AACR.

La actividad productiva de la fábrica de harinas “La Montserrat” (Girona) en el año agrícola de 1903-1904 = The Production Activities at the Company Harinera “La Montserrat” (Girona) over the Agricultural Year 1903-1904

Harinera La Montserrat, S.A, a company involved in the manufacturing and trading of cereals and flour, was founded in Girona in 1898 by José Ensesa y Cía., Sociedad en Comandita. With the objective to determine how the product activity of this business was structured, we have studied in detail the operations that were carried out over the agricultural year 1903-1904. We have focused on three main aspects. Firstly, the purchasing of wheat (origin, transportation, prices); secondly, the production of flour (using internal and external wheat, profits); and thirdly, its distribution (customers, destination). Finally, we have analyzed the profit and loos account for this period in order to find out if this business was profitable

Objectives and motivations of small-scale forest owners : theoretical modelling and qualitative assessment

Abstract

A pathogenic mechanism in Huntington"s disease involves small CAG-repeated RNAs with neurotoxic activity

Huntington's disease (HD) is an autosomal dominantly inherited disorder caused by the expansion of CAG repeats in the Huntingtin (HTT) gene. The abnormally extended polyglutamine in the HTT protein encoded by the CAG repeats has toxic effects. Here, we provide evidence to support that the mutant HTT CAG repeats interfere with cell viability at the RNA level. In human neuronal cells, expanded HTT exon-1 mRNA with CAG repeat lengths above the threshold for complete penetrance (40 or greater) induced cell death and increased levels of small CAG-repeated RNAs (sCAGs), of ≈21 nucleotides in a Dicer-dependent manner. The severity of the toxic effect of HTT mRNA and sCAG generation correlated with CAG expansion length. Small RNAs obtained from cells expressing mutant HTT and from HD human brains significantly decreased neuronal viability, in an Ago2-dependent mechanism. In both cases, the use of anti-miRs specific for sCAGs efficiently blocked the toxic effect, supporting a key role of sCAGs in HTT-mediated toxicity. Luciferase-reporter assays showed that expanded HTT silences the expression of CTG-containing genes that are down-regulated in HD. These results suggest a possible link between HD and sCAG expression with an aberrant activation of the siRNA/miRNA gene silencing machinery, which may trigger a detrimental response. The identification of the specific cellular processes affected by sCAGs may provide insights into the pathogenic mechanisms underlying HD, offering opportunities to develop new therapeutic approaches

A realistic Computed Tomography simulator for small motion analysis of cerebral aneurysms.

This paper describes a realistic simulator for the Computed Tomography (CT) scan process for motion analysis. In fact, we are currently developing a new framework to find small motion from the CT scan. In order to prove the fidelity of this framework, or potentially any other algorithm, we present in this paper a simulator to simulate the whole CT acquisition process with a priori known parameters. In other words, it is a digital phantom for the motion analysis that can be used to compare the results of any related algorithm with the ground-truth realistic analytical model. Such a simulator can be used by the community to test different algorithms in the biomedical imaging domain. The most important features of this simulator are its different considerations to simulate the best the real acquisition process and its generality.

The adjective petit 'small, little' in French acquisition data: an example of the relationship between pragmatics and morphosyntactic development

In French the adjective petit 'small, little' has a special status: it fulfills various pragmatic functions in addition to semantic meanings and it is thus highly frequent in discourse. Résumé: This study, based on the data of two children, aged 1;6 to 2;11, argues that petit and its pragmatic meanings play a specific role in the acquisition of French adjectives. In contrast to what is expected in child language, petit favours the early development of a pattern of noun phrase with prenominal attributive adjective. The emergence and distribution of petit in the children's production is examined and related to its distribution in the input, and the detailed pragmatic meanings and functions of petit are analysed. Prenominal petit emerges early as the preferred and most productive adjective. Pragmatic meanings of petit appear to be predominant in this early age and are of two main types: expressions of endearment (in noun phrases) and mitigating devices whose scope is the entire utterance. These results, as well as instances of children's pragmatic overgeneralizations, provide new evidence that at least some pragmatic meanings are prior to semantic meanings in early acquisition.

Iowa Historic Property Study: Iowana Farms Milk Company, 1416 State Street, City of Bettendorf, Scott County, Iowa, 2012

The Iowana Farms Milk Company factory building was considered to retain sufficient integrity and possess sufficient significance to be considered eligible for the National Register of Historic Places under Criteria A and C for its historical and architectural significance in the Bettendorf community. The Iowana Farms Milk Company was an important early to mid-twentieth-century business in Bettendorf, and was among the few that was not owned or operated by the Bettendorf Company. It was a strong and thriving business for many years, and its products were well known in the Quad Cities region. The importance of this property becomes even more significant when one considers that most of the buildings once associated with the actual Bettendorf Company, which was undeniably the most important business and industry in town, are now gone. As a result, the Iowana Farms Milk Company factory building was a physical vestige of the once-thriving commercial industries that made Bettendorf into a city in the twentieth century. This property was further significant for its representation of the evolution of the dairy industry in the twentieth century from farm to factory production. It also reflected the changes to the industry based on scientific discoveries, mechanical innovations, and governmental regulations related to improved sanitation and the pure milk movement. The Iowana Farms Milk Company represented a model plant for the time, and the marketing strategies it employed followed the trends of the industry. The Iowana Farms Milk Company plant had to be removed to make room for a new I-74 bridge over the Mississippi River at Bettendorf. The construction of the new bridge also required removal of the historic Iowa-Illinois Memorial Bridge. The documentation reported herein and for that of the Iowa-Illinois Memorial Bridge fulfills the requirements of the Memorandum of Agreement regarding the removal of these historic properties.

A quorum sensing regulated small volatile molecule reduces acute virulence and promotes chronic infection phenotypes.

A significant number of environmental microorganisms can cause serious, even fatal, acute and chronic infections in humans. The severity and outcome of each type of infection depends on the expression of specific bacterial phenotypes controlled by complex regulatory networks that sense and respond to the host environment. Although bacterial signals that contribute to a successful acute infection have been identified in a number of pathogens, the signals that mediate the onset and establishment of chronic infections have yet to be discovered. We identified a volatile, low molecular weight molecule, 2-amino acetophenone (2-AA), produced by the opportunistic human pathogen Pseudomonas aeruginosa that reduces bacterial virulence in vivo in flies and in an acute mouse infection model. 2-AA modulates the activity of the virulence regulator MvfR (multiple virulence factor regulator) via a negative feedback loop and it promotes the emergence of P. aeruginosa phenotypes that likely promote chronic lung infections, including accumulation of lasR mutants, long-term survival at stationary phase, and persistence in a Drosophila infection model. We report for the first time the existence of a quorum sensing (QS) regulated volatile molecule that induces bistability phenotype by stochastically silencing acute virulence functions in P. aeruginosa. We propose that 2-AA mediates changes in a subpopulation of cells that facilitate the exploitation of dynamic host environments and promote gene expression changes that favor chronic infections.

Determination of Flood Dischard Characteristics of Small Drainage Areas, HR-3, Progress Report, 1960

Project HR-3 of the Iowa Highway Research Board has been active since October 1, 1950. The project objective is the determination of flood discharge characteristics of small drainage areas. Funds for the project amount to $10,000 per year of which, by cooperative agreement, the Highway Commission and the U. S. Geological Survey each furnish $5,000. Previous reports have explained the set-up of the project and these explanations will not be repeated in this report.

Nullification of small knots

in the paper we consider the nullification number of small knots with at most 9 crossings. We establish two inequalities (Corollary 2.1) relating the nullification number to other knot invariants and properties of the knot diagram. We show that these inequalities allow us to settle the nullification number for all of the 84 prime knots with at most 9 crossings.

Therapeutic advances in non-small cell lung cancer.

Despite decades of research, therapeutic advances in non-small cell lung cancer (NSCLC) have progressed at a painstaking slow rate with few improvements in standard surgical resection for early stage disease and chemotherapy or radiotherapy for patients with advanced disease. In the past 18 months, however, we seemed to have reached an inflexion point: therapeutic advances that are centred on improvements in the understanding of patient selection, surgery that is undertaken through smaller incisions, identification of candidate mutations accompanied by the development of targeted anticancer treatments with a focus on personalised medicine, improvements to radiotherapy technology, emergence of radiofrequency ablation (RFA), and last but by no means least, the recognition of palliative care as a therapeutic modality in its own right. The contributors to this review are a distinguished international panel of experts who highlight recent advances in each of the major disciplines.