134 research outputs found
At the crossroads. Management and business history in entrepreneurship research
Recent calls for a historic turn in organization studies offer the opportunity to relaunch dialogue between management and business history research. Focusing on the specific domain of entrepreneurship research, this article illustrates the potential of mutual contributions from management and business history. In doing so, it highlights how historical approaches strongly influenced the early theoretical developments within entrepreneurship and demonstrates the potential to contribute to future scholarly debates. In sum, this article brings closer together business history and management studies stressing that their different perspectives and approaches are very valuable to enriching entrepreneurship research
Association of clusterin with the BRI2-derived amyloid molecules ABri and ADan
Familial British and Danish dementias (FBD and FDD) share striking neuropathological similarities with Alzheimer's disease (AD), including intraneuronal neurofibrillary tangles as well as parenchymal and vascular amyloid deposits. Multiple amyloid associated proteins with still controversial role in amyloidogenesis colocalize with the structurally different amyloid peptides ABri in FBD, ADan in FDD, and Aβ in AD. Genetic variants and plasma levels of one of these associated proteins, clusterin, have been identified as risk factors for AD. Clusterin is known to bind soluble Aβ in biological fluids, facilitate its brain clearance, and prevent its aggregation. The current work identifies clusterin as the major ABri- and ADan-binding protein and provides insight into the biochemical mechanisms leading to the association of clusterin with ABri and ADan deposits. Mirroring findings in AD, the studies corroborate clusterin co-localization with cerebral parenchymal and vascular amyloid deposits in both disorders. Ligand affinity chromatography with downstream Western blot and amino acid sequence analyses unequivocally identified clusterin as the major ABri- and ADan-binding plasma protein. ELISA highlighted a specific saturable binding of clusterin to ABri and ADan with low nanomolar Kd values within the same range as those previously demonstrated for the clusterin-Aβ interaction. Consistent with its chaperone activity, thioflavin T binding assays clearly showed a modulatory effect of clusterin on ABri and ADan aggregation/fibrillization properties. Our findings, together with the known multifunctional activity of clusterin and its modulatory activity on the complex cellular pathways leading to oxidative stress, mitochondrial dysfunction, and the induction of cell death mechanisms - all known pathogenic features of these protein folding disorders - suggests the likelihood of a more complex role and a translational potential for the apolipoprotein in the amelioration/prevention of these pathogenic mechanisms.This work was supported by grants from the National Institutes of Health NS051715 (to AR) and AG030539, AG051266, AG059695, and AG065651 (to JG) and from CIBERNED and the Spanish Ministry of Science (SAF2016-78603-R and PID2019-110401RB-I00) and Institutional grants from the Queen Sofia Foundation, CIEN Foundation and the Carlos III Institutes of Health (to MC). TL is supported by an Alzheimer's Research UK senior fellowship. TR is supported by a grant from the Karin & Sten Mortstedt CBD Solutions AB, Stockholm, Sweden and by the National Institute for Health Research (NIHR) Queen Square Biomedical Research Unit in Dementia based at University College London Hospitals (UCLH), University College London (UCL). The views expressed are those of the authors and not necessarily those of the NIH, NHS, the NIHR or the Department of Health.S
Drift-induced deceleration of Solar Energetic Particles
We investigate the deceleration of Solar Energetic Particles (SEPs) during their propagation from the Sun through interplanetary space, in the presence of weak to strong scattering in a Parker spiral configuration, using relativistic full orbit test particle simulations. The calculations retain all three spatial variables describing particles’ trajectories, allowing to model any transport across the magnetic field. Large energy change is shown to occur for protons, due to the combined effect of standard adiabatic deceleration and a significant contribution from particle drift in the direction opposite to that of the solar wind electric field. The latter drift-induced deceleration is found to have a stronger effect for SEP energies than for galactic cosmic rays. The kinetic energy of protons injected at 1 MeV is found to be reduced by between 35 and 90% after four days, and for protons injected at 100 MeV by between 20 and 55%. The overall degree of deceleration is a weak function of the scattering mean free path, showing that, although adiabatic deceleration plays a role, a large contribution is due to particle drift. Current SEP transport models are found to account for drift-induced deceleration in an approximate way and their accuracy will need to be assessed in future work
Facies generadoras de carbón en el Westfaliense superior de la Cuenca Carbonífera Central Asturiana
La Cuenca Carbonífera Central Asturiana constituye una cuenca de antepais individualizada en la Zona Cantábrica durante el Carbonifero Superior coincidiendo con la máxima actividad de la orogenia Hercinica. Durante el Westfaliense, se acumularon en ella importantes volúmenes de material clástico procedentes de los relieves en elevación situados al W. Los abanicos aluviales costeros constituyeron unos sistemas deposicionales muy eficientes en la dispersión de estos materiales, generaron extensas cuñas clásticas en relación con las cuales se originaron capas de carbón explotables. En este trabajo se estudian varios litosomas de edad Westfaliense Superior que representan episodios progradantes de estos sistemas sobre ambientes marinos someros v de transición. El análisis e interpretación de sus facies y geometrías permite la reconstrucción de las condiciones ambientales en que se generaron las capas de carbón asociadas a cada una de las unidades estudiadas. Estas se desarrollaron: 1) en zonas marginales a los lóbulos progradantes y zonas interlóbulos y 2) sobre los mismos una vez que éstos fueron abandonados y previamente a su enterramiento
Heliospheric Transport of Neutron-Decay Protons
We report on new simulations of the transport of energetic protons
originating from the decay of energetic neutrons produced in solar flares.
Because the neutrons are fast-moving but insensitive to the solar wind magnetic
field, the decay protons are produced over a wide region of space, and they
should be detectable by current instruments over a broad range of longitudes
for many hours after a sufficiently large gamma-ray flare. Spacecraft closer to
the Sun are expected to see orders-of magnitude higher intensities than those
at the Earth-Sun distance. The current solar cycle should present an excellent
opportunity to observe neutron-decay protons with multiple spacecraft over
different heliographic longitudes and distances from the Sun.Comment: 12 pages, 4 figures, to be published in special issue of Solar
Physic
Predictors of response to TNF blockers in patients with polyarticular psoriatic arthritis
Psoriatic arthritis (PsA) is a chronic inflammatory
rheumatic disease with a broad clinical spectrum. PsA
can affect the axialskeleton, peripheral joints, entheses,
synovial sheaths of tendons, skin, nails and extra-articular
organs. Tumour necrosis factor alpha blockers
(TNF blockers) were a breakthrough development in
the treatment of PsA. Identifying predictors of response
to biological therapiesin patients with PsA is of utmost
importance, especially in view of the costs and potential
side effects of these agents. The aims of the present
study were to determine baseline predictive factors of
response to biological therapies, at 3 and 6 months, in
PsA patients with polyarticular involvement (with or
without axial involvement). Data were collected from
the RheumaticDiseases Portuguese Register(Reuma.pt).
Eligible patients had to be anti-TNF-naive at baseline
and to have at least 3 months of follow-up after the beginning
of TNF blocker therapy. Only patients with information
on at least one of the response measures (at
3 or 6 months of follow-up) were included in the analysis.
Univariable logistic regression analysis of potential
baseline predictors of European League Against Rheu-matism (EULAR) good clinical response, EULAR good/
/moderate response, 28-joint Disease Activity Score
with three variables including the erythrocyte sedimentation
rate (DAS28-3V-ESR) remission and Health
Assessment Questionnaire (HAQ) response were performed.
Multivariable logistic regression using a forward
selection procedure was used until the best-fit
model was obtained, taking confounding effects into
account. A total of 180 patients were eligible for the
study (mean age 52 years, 54% women). In multivariable
analysis at 3 months, females were less likely to attain
a good EULAR response [OR=0.082 (95%
CI=0.024, 0.278)], a DAS28-3V-ESR remission
[OR=0.083 (95% CI=0.017, 0.416)], a moderate or
good EULAR response [OR=0.091 (95% CI=0.011,
0.091)] and a HAQ response [OR=0.074 (95%
CI=0.009, 0.608)]. At 6 months, female gender was
also less likely to achieve a good EULAR response
[OR=0.060 (95% CI=0.011, 0.325)], DAS28-3V-ESR
remission [OR=0.060 (95% CI=0.012, 0.297)], and a
HAQ response [OR=0.138 (95% CI= 0.029, 0.654)]. In
this study we found that gender was the most consistent
predictor of response to TNF blocker therapy in
patients with polyarticular PsA, with females having a
lower probability ofresponse compared to males. These
findings suggest that gender-related biochemical, hormonal
and psychological factors could play an importantrole
in the response to TNF blockertherapy in PsA
Burnout Syndrome in Healthcare Personnel from Arequipa City (Peru)
Originales[ES] Introducción: El síndrome de burnout fue descrito por primera vez en 1974 por Freudenberger, y desde entonces ha generado una gran cantidad de investigación sobre sus síntomas más característicos como son el agotamiento emocional, la despersonalización y la baja realización personal. Entre las tres profesiones de mayor riesgo se tiene al personal de salud, los profesores y los policías. Objetivo: El objetivo de la presente investigación fue valorar la prevalencia del síndrome de burnout en personal de salud de la ciudad de Arequipa (Perú), y analizar comparativamente los datos en función del sexo, los ingresos económicos, el estado civil, el tiempo de servicio, el cargo, la profesión y la institución de procedencia. Método: Se trabajó con un diseño de investigación de tipo descriptivo y se aplicó el Inventario de Burnout de Maslach, que consta de 22 ítems y cuenta con adecuados índices de validez y confiabilidad (α= .76). Resultados: Se evaluaron a 213 trabajadores del sector salud que laboran en hospitales y postas de salud de la ciudad. El 35.7% son varones y el 63.8% son mujeres, con 37 años de edad como promedio. Los resultados indican que altos porcentajes de profesionales del sector salud tienen algunos síntomas del síndrome de burnout, y solo un 5.6% tiene el síndrome de burnout en nivel severo. Además, se registraron diferencias entre los trabajadores en función del sexo, el tiempo de servicio, el cargo, la profesión y la institución en la que laboran. [EN] Introduction: Burnout syndrome was described for the first time by Freudenberger in 1974. It has been generating since then a large amount of research about its main symptoms, such as emotional exhaustion, depersonalization and inefficacy. Healthcare personnel, teachers and policemen are described as being amongst the three highest-risk professional jobs.Objective: The aim of the current research was not only to value the prevalence of the burnout syndrome in the health personnel from Arequipa city (Peru), but to compare the data according to genre, economic income, marital status, working period, job tittle, profession and home institution. Method: A descriptive design was used applying the Maslach Burnout Inventory, which consists of 22 items and counts with validity and reliability (α= .76) adequate indexes. Results: 213 people from the healthcare sector who work in hospitals and healthcare centers at Arequipa city were tested. 35,7% are males and 63,8% are females, with an average age of 37 years old. The results indicate that high percentages of professionals in healthcare services suffer some symptoms of burnout syndrome, and only 5,6% have the burnout syndrome at severe levels. Moreover, differences among workers relating genre, working period, job tittle, profession and work institution were registered. Discussion: It was concluded not only that the burnout syndrome have a concerned presence in healthcare personnel, especially in the depersonalization dimension, but also that the differences according to demographic variables could be explained by work environment and job conditions.N
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The first SEPServer event catalogue ~68-MeV solar proton events observed at 1 AU in 1996-2010
SEPServer is a three-year collaborative project funded by the seventh framework programme (FP7-SPACE) of the European Union. The objective of the project is to provide access to state-of-the-art observations and analysis tools for the scientific community on solar energetic particle (SEP) events and related electromagnetic (EM) emissions. The project will eventually lead to better understanding of the particle acceleration and transport processes at the Sun and in the inner heliosphere. These processes lead to SEP events that form one of the key elements of space weather. In this paper we present the first results from the systematic analysis work performed on the following datasets: SOHO/ERNE, SOHO/EPHIN, ACE/EPAM, Wind/WAVES and GOES X-rays. A catalogue of SEP events at 1 AU, with complete coverage over solar cycle 23, based on high-energy (~68-MeV) protons from SOHO/ERNE and electron recordings of the events by SOHO/EPHIN and ACE/EPAM are presented. A total of 115 energetic particle events have been identified and analysed using velocity dispersion analysis (VDA) for protons and time-shifting analysis (TSA) for electrons and protons in order to infer the SEP release times at the Sun. EM observations during the times of the SEP event onset have been gathered and compared to the release time estimates of particles. Data from those events that occurred during the European day-time, i.e., those that also have observations from ground-based observatories included in SEPServer, are listed and a preliminary analysis of their associations is presented. We find that VDA results for protons can be a useful tool for the analysis of proton release times, but if the derived proton path length is out of a range of 1 AU < s a 2 3 AU, the result of the analysis may be compromised, as indicated by the anti-correlation of the derived path length and release time delay from the associated X-ray flare. The average path length derived from VDA is about 1.9 times the nominal length of the spiral magnetic field line. This implies that the path length of first-arriving MeV to deka-MeV protons is affected by interplanetary scattering. TSA of near-relativistic electrons results in a release time that shows significant scatter with respect to the EM emissions but with a trend of being delayed more with increasing distance between the flare and the nominal footpoint of the Earth-connected field line
CIGB-300, a synthetic peptide-based drug that targets the CK2 phosphoaceptor domain. Translational and clinical research
CK2 represents an oncology target scientifically validated. However, clinical research with inhibitors of the CK2-mediated phosphorylation event is still insufficient to recognize it as a clinically validated target. CIGB-300, an investigational peptide-based drug that targets the phosphoaceptor site, binds to a CK2 substrate array in vitro but mainly to B23/nucleophosmin in vivo. The CIGB-300 proapoptotic effect is preceded by its nucleolar localization, inhibition of the CK2-mediated phosphorylation on B23/nucleophosmin and nucleolar disassembly. Importantly, CIGB-300 shifted a protein array linked to apoptosis, ribosome biogenesis, cell proliferation, glycolisis, and cell motility in proteomic studies which helped to understand its mechanism of action. In the clinical ground, CIGB-300 has proved to be safe and well tolerated in a First-in-Human trial in women with cervical malignancies who also experienced signs of clinical benefit. In a second Phase 1 clinical trial in women with cervical cancer stage IB2/II, the MTD and DLT have been also identified in the clinical setting. Interestingly, in cervical tumors the B23/nucleophosmin protein levels were significantly reduced after CIGB-300 treatment at the nucleus compartment. In addition, expanded use of CIGB-300 in case studies has evidenced antitumor activity when administered as compassional option. Collectively, our data outline important clues on translational and clinical research from this novel peptide-based drug reinforcing its perspectives to treat cancer and paving the way to validate CK2 as a promising target in oncology.Fil: Perea, Silvio E.. Center for Genetic Engineering and Biotechnology; CubaFil: Baladron, Idania. Center for Genetic Engineering and Biotechnology; CubaFil: Garcia, Yanelda. Center for Genetic Engineering and Biotechnology; CubaFil: Perera, Yasser. Center for Genetic Engineering and Biotechnology; CubaFil: Lopez, Adlin. Center for Genetic Engineering and Biotechnology; CubaFil: Soriano, Jorge L.. Center for Genetic Engineering and Biotechnology; Cuba. General Hospital ‘‘Hermanos Ameijeiras’; CubaFil: Batista, Noyde. Center for Genetic Engineering and Biotechnology; Cuba. General Hospital ‘‘Hermanos Ameijeiras’; CubaFil: Palau, Aley. Center for Genetic Engineering and Biotechnology; Cuba. General Hospital ‘‘Hermanos Ameijeiras’; CubaFil: Hernández, Ignacio. Center for Genetic Engineering and Biotechnology; CubaFil: Farina, Hernán Gabriel. Universidad Nacional de Quilmes; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Garcia, Idrian. Center for Genetic Engineering and Biotechnology; CubaFil: Gonzalez, Lidia. Center for Genetic Engineering and Biotechnology; CubaFil: Gil, Jeovanis. Center for Genetic Engineering and Biotechnology; CubaFil: Rodriguez, Arielis. Center for Genetic Engineering and Biotechnology; CubaFil: Solares, Margarita. Center for Genetic Engineering and Biotechnology; CubaFil: Santana, Agueda. Center for Genetic Engineering and Biotechnology; CubaFil: Cruz, Marisol. Center for Genetic Engineering and Biotechnology; CubaFil: Lopez, Matilde. Center for Genetic Engineering and Biotechnology; CubaFil: Valenzuela, Carmen. Center for Genetic Engineering and Biotechnology; CubaFil: Reyes, Osvaldo. Center for Genetic Engineering and Biotechnology; CubaFil: López Saura, Pedro A.. Center for Genetic Engineering and Biotechnology; CubaFil: González, Carlos A.. Center for Genetic Engineering and Biotechnology; CubaFil: Diaz, Alina. Center for Genetic Engineering and Biotechnology; CubaFil: Castellanos, Lila. Center for Genetic Engineering and Biotechnology; CubaFil: Sanchez, Aniel. Center for Genetic Engineering and Biotechnology; CubaFil: Betancourt, Lazaro. Center for Genetic Engineering and Biotechnology; CubaFil: Besada, Vladimir. Center for Genetic Engineering and Biotechnology; CubaFil: González, Luis J.. Center for Genetic Engineering and Biotechnology; CubaFil: Garay, Hilda. Center for Genetic Engineering and Biotechnology; CubaFil: Gómez, Roberto. Center for Genetic Engineering and Biotechnology; CubaFil: Gomez, Daniel Eduardo. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de Quilmes; ArgentinaFil: Alonso, Daniel Fernando. Universidad Nacional de Quilmes; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Perrin, Phillipe. No especifíca;Fil: Renualt, Jean Yves. No especifíca;Fil: Sigman, Hugo. No especifíca;Fil: Herrera, Luis. Center for Genetic Engineering and Biotechnology; CubaFil: Acevedo, Boris. Center for Genetic Engineering and Biotechnology; Cub
Seasonal and spatial variability in condition of age-0+ Argentine hake Merluccius hubbsi Marini, 1933, in the San Jorge Gulf (Argentina): A bottom-up perspective
In the north Patagonian region of the Argentinean Continental Shelf, the San Jorge Gulf (SJG; 45°‐47°S, 65°30ʹ‐67°30ʹW) is the main nursery ground of age‐0+ Argentine hake Merluccius hubbsi Marini, 1933, one of the most important fishery resources in Argentina. The gulf exhibits strong seasonal and spatial fluctuations in environmental features, which might affect survival of age‐0+ individuals and recruitment to the adult population. Our main goal was to evaluate the seasonal and spatial dynamics of their nutritional status within the SJG in winter 2016, spring 2016 and summer 2017. Condition indices (relative condition factor Kn, hepatosomatic index HSI and liver lipid content %L) and diet information (feeding incidence and relative importance of prey) were combined with physical (temperature and salinity) and biological (satellite chlorophyll‐a concentration; chl‐a) data. Age‐0+ condition indices and prey intake showed significant seasonal variations, with minimum values in winter, intermediate in summer and maximum in spring, strongly coupled to the mean chl‐a concentration in each season. Herbivorous euphausiids Euphausia spp. were the preferred prey along the study period. A bottom‐up effect on condition of age‐0+ hake is suggested, manifested as lower condition values in winter, the less productive season. Spatially, better conditioned individuals matched sectors of the gulf where chl‐a concentrations were higher, coupled to the presence of frontal systems. Monitoring age‐0+ hake nutritional status is relevant in the current global change scenario, which might modify phytoplankton biomass and composition and, consequently, the herbivorous zooplankton abundances.Fil: Temperoni, Brenda. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Mar del Plata. Instituto de Investigaciones Marinas y Costeras. Subsede Instituto Nacional de Investigación y Desarrollo Pesquero; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mar del Plata. Instituto de Investigaciones Marinas y Costeras. Universidad Nacional de Mar del Plata. Facultad de Ciencias Exactas y Naturales. Instituto de Investigaciones Marinas y Costeras; ArgentinaFil: Massa, Agueda Elena. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Mar del Plata. Instituto de Investigaciones Marinas y Costeras. Subsede Instituto Nacional de Investigación y Desarrollo Pesquero; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mar del Plata. Instituto de Investigaciones Marinas y Costeras. Universidad Nacional de Mar del Plata. Facultad de Ciencias Exactas y Naturales. Instituto de Investigaciones Marinas y Costeras; ArgentinaFil: Martos, Patricia. Universidad Nacional de Mar del Plata. Facultad de Ciencias Exactas y Naturales. Departamento de Ciencias Marinas; ArgentinaFil: Marrari, Marina. Ministerio de Defensa. Armada Argentina. Servicio de Hidrografía Naval. Departamento Oceanografía; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentin
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