Selection response of growth rate in rabbits for meat production

Genetic and environmental trends in 2 lines of rabbit (B and R) selected on individual weight gain (WG) from weaning (4 wk) to slaughter (11 wk) were estimated using mixed model methodology. Line B was derived from the California breed and line R was a synthetic of stock of different origin. The data were collected from a single herd and comprised 7 718 individuals in line B and 9 391 in line R, the lines having 12 and 9 generations of selection respectively. Realized responses in the 2 lines were 2.7% and 2.2% of the initial mean per year respectively and showed that selection on WG was effective but was less than expected. Selection on slaughter weight (SW) and effects of selection on other economic traits are discussed. It is concluded that selection on either WG or SW is a simple method for improving growth rate in rabbit sire line stocks.

Spontaneous Cdc42 polarization independent of GDI-mediated extraction and actin-based trafficking.

The small Rho-family GTPase Cdc42 is critical for cell polarization and polarizes spontaneously in absence of upstream spatial cues. Spontaneous polarization is thought to require dynamic Cdc42 recycling through Guanine nucleotide Dissociation Inhibitor (GDI)-mediated membrane extraction and vesicle trafficking. Here, we describe a functional fluorescent Cdc42 allele in fission yeast, which demonstrates Cdc42 dynamics and polarization independent of these pathways. Furthermore, an engineered Cdc42 allele targeted to the membrane independently of these recycling pathways by an amphipathic helix is viable and polarizes spontaneously to multiple sites in fission and budding yeasts. We show that Cdc42 is highly mobile at the membrane and accumulates at sites of activity, where it displays slower mobility. By contrast, a near-immobile transmembrane domain-containing Cdc42 allele supports viability and polarized activity, but does not accumulate at sites of activity. We propose that Cdc42 activation, enhanced by positive feedback, leads to its local accumulation by capture of fast-diffusing inactive molecules.

Data collection and criticality analysis for cost effective maintenance during the life cycle of a flue gas line

Työn tarkoituksena oli kerätä käyttövarmuustietoa savukaasulinjasta kahdelta suomalaiselta sellutehtaalta niiden käyttöönotosta aina tähän päivään asti. Käyttövarmuustieto koostuu luotettavuustiedoista sekä kunnossapitotiedoista. Kerätyn tiedon avulla on mahdollista kuvata tarkasti laitoksen käyttövarmuutta seuraavilla tunnusluvuilla: suunnittelemattomien häiriöiden lukumäärä ja korjausajat, laitteiden seisokkiaika, vikojen todennäköisyys ja korjaavan kunnossapidon kustannukset suhteessa savukaasulinjan korjaavan kunnossapidon kokonaiskustannuksiin. Käyttövarmuustiedon keräysmetodi on esitelty. Savukaasulinjan kriittisten laitteiden määrittelyyn käytetty metodi on yhdistelmä kyselytutkimuksesta ja muunnellusta vian vaikutus- ja kriittisyysanalyysistä. Laitteiden valitsemiskriteerit lopulliseen kriittisyysanalyysiin päätettiin käyttövarmuustietojen sekä kyselytutkimuksen perusteella. Kriittisten laitteiden määrittämisen tarkoitus on löytää savukaasulinjasta ne laitteet, joiden odottamaton vikaantuminen aiheuttaa vakavimmat seuraukset savukaasulinjan luotettavuuteen, tuotantoon, turvallisuuteen, päästöihin ja kustannuksiin. Tiedon avulla rajoitetut kunnossapidon resurssit voidaan suunnata oikein. Kriittisten laitteiden määrittämisen tuloksena todetaan, että kolme kriittisintä laitetta savukaasulinjassa ovat molemmille sellutehtaille yhteisesti: savukaasupuhaltimet, laahakuljettimet sekä ketjukuljettimet. Käyttövarmuustieto osoittaa, että laitteiden luotettavuus on tehdaskohtaista, mutta periaatteessa samat päälinjat voidaan nähdä suunnittelemattomien vikojen todennäköisyyttä esittävissä kuvissa. Kustannukset, jotka esitetään laitteen suunnittelemattomien kunnossapitokustannusten suhteena savukaasulinjan kokonaiskustannuksiin, noudattelevat hyvin pitkälle luotettavuuskäyrää, joka on laskettu laitteen seisokkiajan suhteena käyttötunteihin. Käyttövarmuustiedon keräys yhdistettynä kriittisten laitteiden määrittämiseen mahdollistavat ennakoivan kunnossapidon oikean kohdistamisen ja ajoittamisen laitteiston elinaikana siten, että luotettavuus- ja kustannustehokkuusvaatimukset saavutetaan.

Potential impact of environmental bacteriophages in spreading antibiotic resistance genes

The idea that bacteriophage transduction plays a role in the horizontal transfer of antibiotic resistance genes is gaining momentum. Such transduction might be vital in horizontal transfer from environmental to human body-associated biomes and here we review many lines of evidence supporting this notion. It is well accepted that bacteriophages are the most abundant entities in most environments, where they have been shown to be quite persistent. This fact, together with the ability of many phages to infect bacteria belonging to different taxa, makes them suitable vehicles for gene transfer. Metagenomic studies confirm that substantial percentages of the bacteriophage particles present in most environments contain bacterial genes, including mobile genetic elements and antibiotic resistance genes. When specific genes of resistance to antibiotics are detected by real-time PCR in the bacteriophage populations of different environments, only tenfold lower numbers of these genes are observed, compared with those found in the corresponding bacterial populations. In addition, the antibiotic resistance genes from these bacteriophages are functional and generate resistance to the bacteria when these genes are transfected. Finally, reports about the transduction of antibiotic resistance genes are on the increase.

CITRICULTURE ECONOMIC AND FINANCIAL EVALUATION UNDER CONDITIONS OF UNCERTAINTY

ABSTRACT The citriculture consists in several environmental risks, as weather changes and pests, and also consists in considerable financial risk, mainly due to the period ofreturn on the initial investment. This study was motivated by the need to assess the risks of a business activity such as citriculture. Our objective was to build a stochastic simulation model to achieve the economic and financial analysis of an orange producer in the Midwest region of the state of Sao Paulo, under conditions of uncertainty. The parameters used were the Net Present Value (NPV), the Modified Internal Rate of Return(MIRR), and the Discounted Payback. To evaluate the risk conditions we built a probabilistic model of pseudorandom numbers generated with Monte Carlo method. The results showed that the activity analyzed provides a risk of 42.8% to reach a NPV negative; however, the yield assessed by MIRR was 7.7%, higher than the yield from the reapplication of the positive cash flows. The financial investment pays itself after the fourteenth year of activity.

Structural Insight into the Mode of Action of a Direct Inhibitor of Coregulator Binding to the Thyroid Hormone Receptor.

The development of nuclear hormone receptor antagonists that directly inhibit the association of the receptor with its essential coactivators would allow useful manipulation of nuclear hormone receptor signaling. We previously identified 3-(dibutylamino)-1-(4-hexylphenyl)-propan-1-one (DHPPA), an aromatic β-amino ketone that inhibits coactivator recruitment to thyroid hormone receptor β (TRβ), in a high-throughput screen. Initial evidence suggested that the aromatic β-enone 1-(4-hexylphenyl)-prop-2-en-1-one (HPPE), which alkylates a specific cysteine residue on the TRβ surface, is liberated from DHPPA. Nevertheless, aspects of the mechanism and specificity of action of DHPPA remained unclear. Here, we report an x-ray structure of TRβ with the inhibitor HPPE at 2.3-Å resolution. Unreacted HPPE is located at the interface that normally mediates binding between TRβ and its coactivator. Several lines of evidence, including experiments with TRβ mutants and mass spectroscopic analysis, showed that HPPE specifically alkylates cysteine residue 298 of TRβ, which is located near the activation function-2 pocket. We propose that this covalent adduct formation proceeds through a two-step mechanism: 1) β-elimination to form HPPE; and 2) a covalent bond slowly forms between HPPE and TRβ. DHPPA represents a novel class of potent TRβ antagonist, and its crystal structure suggests new ways to design antagonists that target the assembly of nuclear hormone receptor gene-regulatory complexes and block transcription.

STRATEGIC-1: A multiple-lines, randomized, open-label GERCOR phase III study in patients with unresectable wild-type RAS metastatic colorectal cancer.

BACKGROUND: The management of unresectable metastatic colorectal cancer (mCRC) is a comprehensive treatment strategy involving several lines of therapy, maintenance, salvage surgery, and treatment-free intervals. Besides chemotherapy (fluoropyrimidine, oxaliplatin, irinotecan), molecular-targeted agents such as anti-angiogenic agents (bevacizumab, aflibercept, regorafenib) and anti-epidermal growth factor receptor agents (cetuximab, panitumumab) have become available. Ultimately, given the increasing cost of new active compounds, new strategy trials are needed to define the optimal use and the best sequencing of these agents. Such new clinical trials require alternative endpoints that can capture the effect of several treatment lines and be measured earlier than overall survival to help shorten the duration and reduce the size and cost of trials. METHODS/DESIGN: STRATEGIC-1 is an international, open-label, randomized, multicenter phase III trial designed to determine an optimally personalized treatment sequence of the available treatment modalities in patients with unresectable RAS wild-type mCRC. Two standard treatment strategies are compared: first-line FOLFIRI-cetuximab, followed by oxaliplatin-based second-line chemotherapy with bevacizumab (Arm A) vs. first-line OPTIMOX-bevacizumab, followed by irinotecan-based second-line chemotherapy with bevacizumab, and by an anti-epidermal growth factor receptor monoclonal antibody with or without irinotecan as third-line treatment (Arm B). The primary endpoint is duration of disease control. A total of 500 patients will be randomized in a 1:1 ratio to one of the two treatment strategies. DISCUSSION: The STRATEGIC-1 trial is designed to give global information on the therapeutic sequences in patients with unresectable RAS wild-type mCRC that in turn is likely to have a significant impact on the management of this patient population. The trial is open for inclusion since August 2013. TRIAL REGISTRATION: STRATEGIC-1 is registered at Clinicaltrials.gov: NCT01910610, 23 July, 2013. STRATEGIC-1 is registered at EudraCT-No.: 2013-001928-19, 25 April, 2013.

Fifty years after Ehrlich and Raven, is there support for plant-insect coevolution as a major driver of species diversification?

Since Ehrlich & Raven's seminal paper 50 years ago, coevolution has been seen as a major driver of species diversification. Here, we review classical and more recent case studies on the coevolution of plants and associated insects, to examine whether the coevolutionary component holds as an explanation of their current diversity. We discuss the main dogmas in coevolution and argue that coevolutionary processes should not be considered as major drivers of diversification in plants and insects. Instead, we suggest that coevolution essentially occurs through relatively short 'interludes', making the pattern difficult to detect. We also criticize the use of comparative phylogenetics to investigate coevolutionary processes, as coevolution may not necessarily produce congruent phylogenies among interacting lineages and, in turn, other processes may produce patterns of codivergence. Finally, we propose new lines of investigation for future research.

An active zone characterized by slow normal faults, the northwestern margin of the València trough (NE Iberia): a review

The northwestern margin of the Valencia trough is an area of low strain characterized by slow normal faults and low to moderate seismicity. Since the mid 1990s this area has been the subject of a number of studies on active tectonic which have proposed different approaches to the location of active faults and to the calculation of the parameters that describe their seismic cycle. Fifty-six active faults have been found and a classification has been made in accordance with their characteristics: a) faults with clear evidence of large paleo-, historic or instrumental earthquakes (2/56); b) faults with evidence of accumulated activity during the Plio-Quaternary and with associated instrumental seismicity (7/56); c) faults with evidence of accumulated activity during the Plio-Quaternary and without associated instrumental seismicity (17/56); d) faults with associated instrumental seismicity and without evidence of accumulated activity during the Plio-Quaternary (30/56), and e) faults without evidence of activity or inactive faults. The parameters that describe the seismic cycle of these faults have been evaluated by different methods that use the geological data obtained for each fault except when paleoseismological studies were available. This classification can be applied to other areas with low slip faults because of the simplicity of the approaches adopted. This study reviews the different approaches proposed and describes the active faults located, highlighting the need a) to better understand active faults in slow strain zones through paleoseismological studies, and b) to include them in seismic hazard studies.

Uncertainty evaluation in activity measurements using ionization chambers

Pressurized re-entrant (or 4 pi) ionization chambers (ICs) connected to current-measuring electronics are used for activity measurements of photon emitting radionuclides and some beta emitters in the fields of metrology and nuclear medicine. As a secondary method, these instruments need to be calibrated with appropriate activity standards from primary or direct standardization. The use of these instruments over 50 years has been well described in numerous publications, such as the Monographie BIPM-4 and the special issue of Metrologia on radionuclide metrology (Ratel 2007 Metrologia 44 S7-16, Schrader1997 Activity Measurements With Ionization Chambers (Monographie BIPM-4) Schrader 2007 Metrologia 44 S53-66, Cox et al 2007 Measurement Modelling of the International Reference System (SIR) for Gamma-Emitting Radionuclides (Monographie BIPM-7)). The present work describes the principles of activity measurements, calibrations, and impurity corrections using pressurized ionization chambers in the first part and the uncertainty analysis illustrated with example uncertainty budgets from routine source-calibration as well as from an international reference system (SIR) measurement in the second part.

Suggestion of a national diagnostic reference level for 18F-FDG/PET scans in adult cancer patients in Brazil

Objective To suggest a national value for the diagnostic reference level (DRL) in terms of activity in MBq.kg–1, for nuclear medicine procedures with fluorodeoxyglucose (18F-FDG) in whole body positron emission tomography (PET) scans of adult patients. Materials and Methods A survey on values of 18F-FDG activity administered in Brazilian clinics was undertaken by means of a questionnaire including questions about number and manufacturer of the installed equipment, model and detector type. The suggested DRL value was based on the calculation of the third quartile of the activity values distribution reported by the clinics. Results Among the surveyed Brazilian clinics, 58% responded completely or partially the questionnaire; and the results demonstrated variation of up to 100% in the reported radiopharmaceutical activity. The suggested DRL for 18F-FDG/PET activity was 5.54 MBq.kg–1 (0.149 mCi.kg–1). Conclusion The present study has demonstrated the lack of standardization in administered radiopharmaceutical activities for PET procedures in Brazil, corroborating the necessity of an official DRL value to be adopted in the country. The suggested DLR value demonstrates that there is room for optimization of the procedures and 18F-FDG/PET activities administered in Brazilian clinics to reduce the doses delivered to patients. It is important to highlight that this value should be continually revised and optimized at least every five years.

A correlation sensitivity analysis of non-life underwriting risk in solvency capital requirement estimation

This paper analyses the impact of using different correlation assumptions between lines of business when estimating the risk-based capital reserve, the Solvency Capital Requirement -SCR-, under Solvency II regulations. A case study is presented and the SCR is calculated according to the Standard Model approach. Alternatively, the requirement is then calculated using an Internal Model based on a Monte Carlo simulation of the net underwriting result at a one-year horizon, with copulas being used to model the dependence between lines of business. To address the impact of these model assumptions on the SCR we conduct a sensitivity analysis. We examine changes in the correlation matrix between lines of business and address the choice of copulas. Drawing on aggregate historical data from the Spanish non-life insurance market between 2000 and 2009, we conclude that modifications of the correlation and dependence assumptions have a significant impact on SCR estimation.

Numerical Dominance of the Argentine Ant vs Native Ants and Consequences on Soil Resource Searching in Mediterranean Cork-Oak Forests (Hymenoptera: Formicidae)

This study is focused on the dominance exerted by the invasive Argentine ant over native ants in a coastal Mediterranean area. Theimpact of this invasive ant on native ant assemblages and its consequences on total ant biomass and on the intensity of habitat explorationwere evaluated. Foraging ants were observed and their trajectories recorded during 5-minute periods in two study zones, one invaded andthe other non-invaded. Ant species detected, ant worker abundance, ant biomass and the intensity of soil surface searching done by antswere compared between the two zones. The Argentine ant invasion provoked a drastic reduction of the ant species richness. Apparentlyonly one native ant species is able to coexist with the Argentine ant, the cryptic Plagiolepis pygmaea. Ant worker abundance was also modified after the invasion: the number of Argentine ant workers detected, which represented 92% of the invaded zone, was two times higher than the number of native ant workers detected in the non-invaded zone. The total ant biomass was inversely affected, becoming four times lower in the invaded zone highly dominated by Linepithema humile. The higher number of Argentine ant workers and their fast tempo of activity implied an alteration of the intensity of soil surface searching: scanning by the Argentine ants in the invaded zone was higher than that done by the native ants in the non-invaded zone, and the estimated time for a complete soil surface scan was 64 minutes in the invaded zone and 108 minutes in the non-invaded zone. Consequently, resources will be discovered faster by ants in the invaded zone than in the non-invaded zone. The increase of the mean temperature and the decrease of the relative humidity from May to August reduced the ant activity in the two study zones but this reduction was greater in the invaded zone

Fate of peat utilization

Peat is an organic substance with the maintenance of a mineral part, what shows it as interesting object for studying. Both organic and mineral parts of peat find application in various fields of activity of the people. Antibacterial properties of peat are known since an antiquity. Today people have expanded a spectrum of application of peat to use of by-products of its processing for reception of rather ecologically harmless fuel. The master theses are focused on peat, as on ambiguous raw materials for processing and fuel manufacture. The purpose of theses to show how much widely applied peat, technologies on its processing and its influence on environment at all stages of its working out.

Contribution of subcortical structures to cognition assessed with invasive electrophysiology in humans

Implantation of deep brain stimulation (DBS) electrodes via stereotactic neurosurgery has become a standard procedure for the treatment of Parkinson's disease. More recently, the range of neuropsychiatric conditions and the possible target structures suitable for DBS have greatly increased. The former include obsessive compulsive disease, depression, obesity, tremor, dystonia, Tourette's syndrome and cluster-headache. In this article we argue that several of the target structures for DBS (nucleus accumbens, posterior inferior hypothalamus, nucleus subthalamicus, nuclei in the thalamus, globus pallidus internus, nucleus pedunculopontinus) are located at strategic positions within brain circuits related to motivational behaviors, learning, and motor regulation. Recording from DBS electrodes either during the operation or post-operatively from externalized leads while the patient is performing cognitive tasks tapping the functions of the respective circuits provides a new window on the brain mechanisms underlying these functions. This is exemplified by a study of a patient suffering from obsessive-compulsive disease from whom we recorded in a flanker task designed to assess action monitoring processes while he received a DBS electrode in the right nucleus accumbens. Clear error-related modulations were obtained from the target structure, demonstrating a role of the nucleus accumbens in action monitoring. Based on recent conceptualizations of several different functional loops and on neuroimaging results we suggest further lines of research using this new window on brain functions.