Conformational Spread in the Flagellar Motor Switch: A Model Study

The reliable response to weak biological signals requires that they be amplified with fidelity. In E. coli, the flagellar motors that control swimming can switch direction in response to very small changes in the concentration of the signaling protein CheY-P, but how this works is not well understood. A recently proposed allosteric model based on cooperative conformational spread in a ring of identical protomers seems promising as it is able to qualitatively reproduce switching, locked state behavior and Hill coefficient values measured for the rotary motor. In this paper we undertook a comprehensive simulation study to analyze the behavior of this model in detail and made predictions on three experimentally observable quantities: switch time distribution, locked state interval distribution, Hill coefficient of the switch response. We parameterized the model using experimental measurements, finding excellent agreement with published data on motor behavior. Analysis of the simulated switching dynamics revealed a mechanism for chemotactic ultrasensitivity, in which cooperativity is indispensable for realizing both coherent switching and effective amplification. These results showed how cells can combine elements of analog and digital control to produce switches that are simultaneously sensitive and reliable

Oral bisphosphonate-related osteonecrosis of the jaws in rheumatoid arthritis patients: a critical discussion and two case reports

<p>Abstract</p> <p>Background</p> <p>Bisphosphonate-related osteonecrosis of the jaw (BRONJ) is a clinical condition characterized by the presence of exposed bone in the maxillofacial region. Its pathogenesis is still undetermined, but may be associated with risk factors such as rheumatoid arthritis (RA). The aim of this paper is to report two unpublished cases of BRONJ in patients with RA and to conduct a literature review of similar clinical cases with a view to describe the main issues concerning these patients, including demographic characteristics and therapeutic approaches applied.</p> <p>Methods</p> <p>Two case reports of BRONJ involving RA patients were discussed</p> <p>Results</p> <p>Both patients were aging female taking alendronate for more than 3 years. Lesions were detected in stage II in posterior mandible with no clear trigger agent. The treatment applied consisted of antibiotics, oral rinses with chlorhexidine, drug discontinuation and surgical procedures. Complete healing of the lesions was achieved.</p> <p>Conclusions</p> <p>This paper brings to light the necessity for rheumatologists to be aware of the potential risk to their patients of developing BRONJ and to work together with dentists for the prevention and early detection of the lesions. Although some features seem to link RA with oral BRONJ and act as synergistic effects, more studies should be developed to support the scientific bases for this hypothesis.</p

Voto econômico retrospectivo e sofisticação política na eleição presidencial de 2002

Este artigo aborda o tema do voto econômico a partir da perspectiva da desigualdade de sofisticação política entre os eleitores. Diversos estudos mostram que os eleitores brasileiros tendem a se basear na economia para votar e avaliar os presidentes. Essas evidências algumas vezes servem de suporte para a afirmação de que, mesmo não utilizando os partidos, os rótulos ideológicos e outras questões politicamente relevantes como referências para suas escolhas, o eleitorado de massa no Brasil seria capaz de tomar decisões criteriosas na política. Utilizando dados de pesquisa de painel coletados ao longo de 2002 em Caxias do Sul e Juiz de Fora, o artigo testa até que ponto o efeito da avaliação retrospectiva da economia (tanto do país quanto pessoal) sobre o voto para presidente depende do nível de sofisticação política do respondente. Os resultados mostram que a avaliação da economia tende a ser uma opinião instável ao longo do período analisado, e tem impacto sobre a escolha do candidato a presidente apenas entre os eleitores mais politicamente sofisticados. As implicações dos achados são discutidas e aponta-se para a relevância de se levar em conta o impacto da desigualdade de sofisticação política entre os eleitores no entendimento da dinâmica das eleições e da opinião pública no Brasil

Relationship of Weather Types on the Seasonal and Spatial Variability of Rainfall, Runoff, and Sediment Yield in the Western Mediterranean Basin

Rainfall is the key factor to understand soil erosion processes, mechanisms, and rates. Most research was conducted to determine rainfall characteristics and their relationship with soil erosion (erosivity) but there is little information about how atmospheric patterns control soil losses, and this is important to enable sustainable environmental planning and risk prevention. We investigated the temporal and spatial variability of the relationships of rainfall, runoff, and sediment yield with atmospheric patterns (weather types, WTs) in the western Mediterranean basin. For this purpose, we analyzed a large database of rainfall events collected between 1985 and 2015 in 46 experimental plots and catchments with the aim to: (i) evaluate seasonal differences in the contribution of rainfall, runoff, and sediment yield produced by the WTs; and (ii) to analyze the seasonal efficiency of the different WTs (relation frequency and magnitude) related to rainfall, runoff, and sediment yield. The results indicate two different temporal patterns: the first weather type exhibits (during the cold period: autumn and winter) westerly flows that produce the highest rainfall, runoff, and sediment yield values throughout the territory; the second weather type exhibits easterly flows that predominate during the warm period (spring and summer) and it is located on the Mediterranean coast of the Iberian Peninsula. However, the cyclonic situations present high frequency throughout the whole year with a large influence extended around the western Mediterranean basin. Contrary, the anticyclonic situations, despite of its high frequency, do not contribute significantly to the total rainfall, runoff, and sediment (showing the lowest efficiency) because of atmospheric stability that currently characterize this atmospheric pattern. Our approach helps to better understand the relationship of WTs on the seasonal and spatial variability of rainfall, runoff and sediment yield with a regional scale based on the large dataset and number of soil erosion experimental stations.Spanish Government (Ministry of Economy and Competitiveness, MINECO) and FEDER Projects: CGL2014 52135-C3-3-R, ESP2017-89463-C3-3-R, CGL2014-59946-R, CGL2015-65569-R, CGL2015-64284-C2-2-R, CGL2015-64284-C2-1-R, CGL2016-78075-P, GL2008-02879/BTE, LEDDRA 243857, RECARE-FP7, CGL2017-83866-C3-1-R, and PCIN-2017-061/AEI. Dhais Peña-Angulo received a “Juan de la Cierva” postdoctoral contract (FJCI-2017-33652 Spanish Ministry of Economy and Competitiveness, MEC). Ana Lucia acknowledge the "Brigitte-Schlieben-Lange-Programm". The “Geoenvironmental Processes and Global Change” (E02_17R) was financed by the Aragón Government and the European Social Fund. José Andrés López-Tarazón acknowledges the Secretariat for Universities and Research of the Department of the Economy and Knowledge of the Autonomous Government of Catalonia for supporting the Consolidated Research Group 2014 SGR 645 (RIUS- Fluvial Dynamics Research Group). Artemi Cerdà thank the funding of the OCDE TAD/CRP JA00088807. José Martínez-Fernandez acknowledges the project Unidad de Excelencia CLU-2018-04 co-funded by FEDER and Castilla y León Government. Ane Zabaleta is supported by the Hydro-Environmental Processes consolidated research group (IT1029-16, Basque Government). This paper has the benefit of the Lab and Field Data Pool created within the framework of the COST action CONNECTEUR (ES1306)

The KM3NeT potential for the next core-collapse supernova observation with neutrinos

The authors acknowledge the financial support of the funding agencies: Agence Nationale de la Recherche (contract ANR-15-CE31-0020), Centre National de la Recherche Scientifique (CNRS), Commission Europeenne (FEDER fund and Marie Curie Program), Institut Universitaire de France (IUF), LabEx UnivEarthS (ANR-10-LABX-0023 and ANR-18-IDEX-0001), Paris Ile-de-France Region, France; Shota Rustaveli National Science Foundation of Georgia (SRNSFG, FR-18-1268), Georgia; Deutsche Forschungsgemeinschaft (DFG), Germany; The General Secretariat of Research and Technology (GSRT), Greece; Istituto Nazionale di Fisica Nucleare (INFN), Ministero dell'Universita e della Ricerca (MIUR), PRIN 2017 program (Grant NAT-NET 2017W4HA7S) Italy; Ministry of Higher Education Scientific Research and Professional Training, ICTP through Grant AF-13, Morocco; Nederlandse organisatie voor Wetenschappelijk Onderzoek (NWO), the Netherlands; The National Science Centre, Poland (2015/18/E/ST2/00758); National Authority for Scientific Research (ANCS), Romania; Ministerio de Ciencia, Innovacion, Investigacion y Universidades (MCIU): Programa Estatal de Generacion de Conocimiento (refs. PGC2018-096663-B-C41, -A-C42, -B-C43, -B-C44) (MCIU/FEDER), Severo Ochoa Centre of Excellence and MultiDark Consolider (MCIU), Junta de Andalucia (ref. SOMM17/6104/UGR), Generalitat Valenciana: Grisolia (ref. GRISO-LIA/2018/119) and GenT (ref. CIDEGENT/2018/034 and CIDE-GENT/2019/043) programs, La Caixa Foundation (ref. LCF/BQ/IN17/11620019), EU: MSC program (ref. 713673), Spain. This work has also received funding from the European Union'sHorizon 2020 research and innovation program under Grant agreement no 739560.The KM3NeT research infrastructure is under construction in the Mediterranean Sea. It consists of two water Cherenkov neutrino detectors, ARCA and ORCA, aimed at neutrino astrophysics and oscillation research, respectively. Instrumenting a large volume of sea water with similar to 6200 optical modules comprising a total of similar to 200,000 photomultiplier tubes, KM3NeT will achieve sensitivity to similar to 10 MeV neutrinos from Galactic and near-Galactic core-collapse supernovae through the observation of coincident hits in photomultipliers above the background. In this paper, the sensitivity of KM3NeT to a supernova explosion is estimated from detailed analyses of background data from the first KM3NeT detection units and simulations of the neutrino signal. The KM3NeT observational horizon (for a 5 sigma discovery) covers essentially the Milky-Way and for the most optimistic model, extends to the Small Magellanic Cloud (similar to 60 kpc). Detailed studies of the time profile of the neutrino signal allow assessment of the KM3NeT capability to determine the arrival time of the neutrino burst with a few milliseconds precision for sources up to 5-8 kpc away, and detecting the peculiar signature of the standing accretion shock instability if the core-collapse supernova explosion happens closer than 3-5 kpc, depending on the progenitor mass. KM3NeT's capability to measure the neutrino flux spectral parameters is also presented.French National Research Agency (ANR) ANR-15-CE31-0020Centre National de la Recherche Scientifique (CNRS)Commission Europeenne, FranceInstitut Universitaire de France (IUF), FranceLabEx UnivEarthS, France ANR-10-LABX-0023 ANR-18-IDEX-0001Paris Ile-de-France Region, FranceShota Rustaveli National Science Foundation of Georgia (SRNSFG), Georgia FR-18-1268German Research Foundation (DFG)Greek Ministry of Development-GSRTGreek Ministry of Development-GSRTIstituto Nazionale di Fisica Nucleare (INFN)Ministry of Education, Universities and Research (MIUR)PRIN 2017 program, Italy NAT-NET 2017W4HA7SMinistry of Higher Education Scientific Research and Professional Training, ICTP, Morocco AF-13Netherlands Organization for Scientific Research (NWO)Netherlands GovernmentNational Science Centre, Poland 2015/18/E/ST2/00758National Authority for Scientific Research (ANCS), RomaniaMinisterio de Ciencia, Innovacion, Investigacion y Universidades (MCIU): Programa Estatal de Generacion de Conocimiento, Spain PGC2018-096663-B-C41 PGC2018-096663-A-C42 PGC2018-096663-B-C43 PGC2018-096663-B-C44Severo Ochoa Centre of Excellence and MultiDark Consolider (MCIU), SpainJunta de Andalucia European Commission SOMM17/6104/UGRGeneralitat Valenciana: Grisolia, Spain GRISO-LIA/2018/119 GenT program, Spain CIDEGENT/2018/034 CIDE-GENT/2019/043La Caixa Foundation LCF/BQ/IN17/11620019 EU: MSC program, Spain 713673European Commission 73956

Prospects for combined analyses of hadronic emission from γ\gamma-ray sources in the Milky Way with CTA and KM3NeT

The Cherenkov Telescope Array and the KM3NeT neutrino telescopes are major upcoming facilities in the fields of $\gamma$-ray and neutrino astronomy, respectively. Possible simultaneous production of $\gamma$ rays and neutrinos in astrophysical accelerators of cosmic-ray nuclei motivates a combination of their data. We assess the potential of a combined analysis of CTA and KM3NeT data to determine the contribution of hadronic emission processes in known Galactic $\gamma$-ray emitters, comparing this result to the cases of two separate analyses. In doing so, we demonstrate the capability of Gammapy, an open-source software package for the analysis of $\gamma$-ray data, to also process data from neutrino telescopes. For a selection of prototypical $\gamma$-ray sources within our Galaxy, we obtain models for primary proton and electron spectra in the hadronic and leptonic emission scenario, respectively, by fitting published $\gamma$-ray spectra. Using these models and instrument response functions for both detectors, we employ the Gammapy package to generate pseudo data sets, where we assume 200 hours of CTA observations and 10 years of KM3NeT detector operation. We then apply a three-dimensional binned likelihood analysis to these data sets, separately for each instrument and jointly for both. We find that the largest benefit of the combined analysis lies in the possibility of a consistent modelling of the $\gamma$-ray and neutrino emission. Assuming a purely leptonic scenario as input, we obtain, for the most favourable source, an average expected 68% credible interval that constrains the contribution of hadronic processes to the observed $\gamma$-ray emission to below 15%.Comment: 18 pages, 15 figures. Submitted to journa

Probing invisible neutrino decay with KM3NeT-ORCA

In the era of precision measurements of the neutrino oscillation parameters, upcoming neutrino experiments will also be sensitive to physics beyond the Standard Model. KM3NeT/ORCA is a neutrino detector optimised for measuring atmospheric neutrinos from a few GeV to around 100 GeV. In this paper, the sensitivity of the KM3NeT/ORCA detector to neutrino decay has been explored. A three-flavour neutrino oscillation scenario, where the third neutrino mass state $\nu_3$ decays into an invisible state, e.g. a sterile neutrino, is considered. We find that KM3NeT/ORCA would be sensitive to invisible neutrino decays with $1/\alpha_3=\tau_3/m_3 < 180$~$\mathrm{ps/eV}$ at $90\%$ confidence level, assuming true normal ordering. Finally, the impact of neutrino decay on the precision of KM3NeT/ORCA measurements for $\theta_{23}$, $\Delta m^2_{31}$ and mass ordering have been studied. No significant effect of neutrino decay on the sensitivity to these measurements has been found.Comment: 27 pages, 14 figures, bibliography updated, typos correcte