First appraisal to define prospective seismogenic sources from historical earthquake damages in southern Upper Rhine Graben

The southern portion ofthe Upper Rhine Graben, a major oblique rift among France, Germany and Switzerland, shows a weak instrumental seismic record despite its remarkable physiographic imprint within the Northern Alpine foreland. Since traces of active deformation can be found in this region and based on experience in other European areas with high seismic hazard and dense population, we searched for past earthquakes recorded in historical catalogues. Based on the fact that tectonic deformation cumulates through geological time and considering that long-term effects tend to leave characteristic signatures on present-day landscape arrangement, our goal was to identify faults that could have caused the damage of recorded historical events. We isolated five main earthquakes, ofmoderate Richter magnitude, essentially located on the E flank of the graben (as is the case with recent seismic activity). To such events, we were able to associate a specific prospective structure through the use ofa procedure thus far successfully employed in Southern European contexts. We concentrated on three events which showed (a) notable sensitivity to the density of the historical felt reports and (b) accordance with on-going subtle deformation pattern. Another, most relevant earthquake (M 5.5) yielded a promising match with the known deformation network in the region. As a template to better constrain earthquake cycle and damage potential, historical seismicity offers an invaluable tool, since it contains a specific record, although not always unambiguous. Cross-checking such data with pertinent geological information allows to devise a realistic fault geometry capable of being responsible for a specific seismic event

Calcified Plaques in Patients With Acute Coronary Syndromes

OBJECTIVES: This study conducted detailed analysis of calcified culprit plaques in patients with acute coronary syndromes (ACS). BACKGROUND: Calcified plaques as an underlying pathology in patients with ACS have not been systematically studied. METHODS: From 1,241 patients presenting with ACS who had undergone pre-intervention optical coherence tomography imaging, 157 (12.7%) patients were found to have a calcified plaque at the culprit lesion. Calcified plaque was defined as a plaque with superficial calcification at the culprit site without evidence of ruptured lipid plaque. RESULTS: Three distinct types were identified: eruptive calcified nodules, superficial calcific sheet, and calcified protrusion (prevalence of 25.5%, 67.4%, and 7.1%, respectively). Eruptive calcified nodules were frequently located in the right coronary arteries (44.4%), whereas superficial calcific sheet was most frequently found in the left anterior descending coronary arteries (68.4%) (p = 0.012). Calcification index (mean calcification arc × calcification length) was greatest in eruptive calcified nodules, followed by superficial calcific sheet, and smallest in calcified protrusion (median 3,284.9 [interquartile range (IQR): 2,113.3 to 5,385.3] vs. 1,644.3 [IQR: 1,012.4 to 3,058.7] vs. 472.5 [IQR: 176.7 to 865.2]; p < 0.001). The superficial calcific sheet group had the highest peak post-intervention creatine kinase values among the groups (eruptive calcified nodules vs. superficial calcific sheet vs. calcified protrusion: 241 [IQR: 116 to 612] IU/l vs. 834 [IQR: 141 to 3,394] IU/l vs. 745 [IQR: 69 to 1,984] IU/l; p = 0.032). CONCLUSIONS: Three distinct types of calcified culprit plaques are identified in patients with ACS. Superficial calcific sheet, which is frequently located in the left anterior descending coronary artery, is the most prevalent type and is also associated with greatest post-intervention myocardial damage. (Identification of Predictors for Coronary Plaque Erosion in Patients With Acute Coronary Syndrome; NCT03479723).status: publishe

Visible LED-Based Instrumentation for Photometric Determination of Electroosmotic Flow in Microchannels

An instrumental setup for electroosmotic flow (EOF) determination in microfluidic devices is described. The system is based on a trinocular microscope and an integrated photodiode OPT101. The radiation was provided by a high-intensity white LED. For the determinations, patent blue V and methylene blue aqueous solutions were used. The setup was applied for EOF monitoring in hybrid toner/glass and PDMS microchips. For the toner/glass device, the EOF mobility was determined to be (5.75 ± 0.01) 10-4 cm² V-1 s-1 at pH 7.0. For PDMS devices the measured EOF mobility was (3.2 ± 0.1) 10-4 cm² V-1 s-1. Reproducible measurements were obtained in all experiments, which produced results with small errors. The proposed method was compared to the conventional current monitoring method

Visible LED-Based Instrumentation for Photometric Determination of Electroosmotic Flow in Microchannels

An instrumental setup for electroosmotic flow (EOF) determination in microfluidic devices is described. The system is based on a trinocular microscope and an integrated photodiode OPT101. The radiation was provided by a high-intensity white LED. For the determinations, patent blue V and methylene blue aqueous solutions were used. The setup was applied for EOF monitoring in hybrid toner/glass and PDMS microchips. For the toner/glass device, the EOF mobility was determined to be (5.75 ± 0.01) 10-4 cm² V-1 s-1 at pH 7.0. For PDMS devices the measured EOF mobility was (3.2 ± 0.1) 10-4 cm² V-1 s-1. Reproducible measurements were obtained in all experiments, which produced results with small errors. The proposed method was compared to the conventional current monitoring method.A instrumentação para a determinação fotométrica do fluxo eletrosmótico (EOF) em dispositivos microfluídicos é descrita neste trabalho. A instrumentação é baseada em componentes acessíveis e consiste em um microscópio trinocular e no fotodiodo integrado OPT101. Um diodo emissor de luz (LED) de alta intensidade foi utilizado como fonte de radiação. Para as determinações foram utilizadas soluções aquosas dos corantes azul patente V e azul de metileno. O sistema foi utilizado no monitoramento do EOF em microdispositivos de poli(dimetilsiloxano) (PDMS) e híbridos de toner/vidro. As mobilidades do EOF determinadas em pH 7,0 foram (5,75 ± 0,01)10-4 cm² V-1 s-1 e (3,2 ± 0,1)10-4 cm² V-1 s-1 para os dispositivos de toner/vidro e PDMS, respectivamente. Medidas reprodutíveis foram obtidas em todos os experimentos, levando a uma alta precisão na determinação. O método proposto foi comparado com o método tradicional de determinação do EOF que envolve a medida da corrente nos microcanais.736740Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq

Time spent with cats is never wasted: Lessons learned from feline acromegalic cardiomyopathy, a naturally occurring animal model of the human disease

<div><p>Background</p><p>In humans, acromegaly due to a pituitary somatotrophic adenoma is a recognized cause of increased left ventricular (LV) mass. Acromegalic cardiomyopathy is incompletely understood, and represents a major cause of morbidity and mortality. We describe the clinical, echocardiographic and histopathologic features of naturally occurring feline acromegalic cardiomyopathy, an emerging disease among domestic cats.</p><p>Methods</p><p>Cats with confirmed hypersomatotropism (IGF-1>1000ng/ml and pituitary mass; n = 67) were prospectively recruited, as were two control groups: diabetics (IGF-1<800ng/ml; n = 24) and healthy cats without known endocrinopathy or cardiovascular disease (n = 16). Echocardiography was performed in all cases, including after hypersomatotropism treatment where applicable. Additionally, tissue samples from deceased cats with hypersomatotropism, hypertrophic cardiomyopathy and age-matched controls (n = 21 each) were collected and systematically histopathologically reviewed and compared.</p><p>Results</p><p>By echocardiography, cats with hypersomatotropism had a greater maximum LV wall thickness (6.5mm, 4.1–10.1mm) than diabetic (5.9mm, 4.2–9.1mm; Mann Whitney, p<0.001) or control cats (5.2mm, 4.1–6.5mm; Mann Whitney, p<0.001). Left atrial diameter was also greater in cats with hypersomatotropism (16.6mm, 13.0–29.5mm) than in diabetic (15.4mm, 11.2–20.3mm; Mann Whitney, p<0.001) and control cats (14.0mm, 12.6–17.4mm; Mann Whitney, p<0.001). After hypophysectomy and normalization of IGF-1 concentration (n = 20), echocardiographic changes proved mostly reversible. As in humans, histopathology of the feline acromegalic heart was dominated by myocyte hypertrophy with interstitial fibrosis and minimal myofiber disarray.</p><p>Conclusions</p><p>These results demonstrate cats could be considered a naturally occurring model of acromegalic cardiomyopathy, and as such help elucidate mechanisms driving cardiovascular remodeling in this disease.</p></div

Construction and Modelling of an Inducible Positive Feedback Loop Stably Integrated in a Mammalian Cell-Line

Understanding the relationship between topology and dynamics of transcriptional regulatory networks in mammalian cells is essential to elucidate the biology of complex regulatory and signaling pathways. Here, we characterised, via a synthetic biology approach, a transcriptional positive feedback loop (PFL) by generating a clonal population of mammalian cells (CHO) carrying a stable integration of the construct. The PFL network consists of the Tetracycline-controlled transactivator (tTA), whose expression is regulated by a tTA responsive promoter (CMV-TET), thus giving rise to a positive feedback. The same CMV-TET promoter drives also the expression of a destabilised yellow fluorescent protein (d2EYFP), thus the dynamic behaviour can be followed by time-lapse microscopy. The PFL network was compared to an engineered version of the network lacking the positive feedback loop (NOPFL), by expressing the tTA mRNA from a constitutive promoter. Doxycycline was used to repress tTA activation (switch off), and the resulting changes in fluorescence intensity for both the PFL and NOPFL networks were followed for up to 43 h. We observed a striking difference in the dynamics of the PFL and NOPFL networks. Using non-linear dynamical models, able to recapitulate experimental observations, we demonstrated a link between network topology and network dynamics. Namely, transcriptional positive autoregulation can significantly slow down the “switch off” times, as comparared to the nonautoregulatated system. Doxycycline concentration can modulate the response times of the PFL, whereas the NOPFL always switches off with the same dynamics. Moreover, the PFL can exhibit bistability for a range of Doxycycline concentrations. Since the PFL motif is often found in naturally occurring transcriptional and signaling pathways, we believe our work can be instrumental to characterise their behaviour

Evidence for surface rupture associated with the Mw 6.3 L’Aquila earthquake sequence of April 2009 (central Italy)

An earthquake of Mw = 6.3 struck L Aquila town (central Italy) on 6 April 2009 rupturing an ~18-km-long SW-dipping normal fault. The aftershock area extended for a length of more than 35 km and included major aftershocks on 7 and 9 April and thousands of minor events. Surface faulting occurred along the SW-dipping Paganica fault with a continuous extent of ~2.5 km. Ruptures consist of open cracks and vertical dislocations or warps (0.1m maximum throw) with an orientation of N130°–140°. Small triggered slip and shaking effects also took place along nearby synthetic and antithetic normal faults. The observed limited extent and small surface displacement of the Paganica ruptures with respect to the height of the fault scarps and vertical throws of palaeo-earthquakes along faults in the area put the faulting associated with the L' Aquila earthquake in perspective with respect to the maximum expected magnitude and the regional seismic hazard.Published43-513.2. Tettonica attivaJCR Journalreserve

Evidence for surface rupture associated with the Mw 6.3 L’Aquila earthquake sequence of April 2009 (central Italy)

An earthquake of Mw = 6.3 struck L Aquila town (central Italy) on 6 April 2009 rupturing an ~18-km-long SW-dipping normal fault. The aftershock area extended for a length of more than 35 km and included major aftershocks on 7 and 9 April and thousands of minor events. Surface faulting occurred along the SW-dipping Paganica fault with a continuous extent of ~2.5 km. Ruptures consist of open cracks and vertical dislocations or warps (0.1m maximum throw) with an orientation of N130°–140°. Small triggered slip and shaking effects also took place along nearby synthetic and antithetic normal faults. The observed limited extent and small surface displacement of the Paganica ruptures with respect to the height of the fault scarps and vertical throws of palaeo-earthquakes along faults in the area put the faulting associated with the L' Aquila earthquake in perspective with respect to the maximum expected magnitude and the regional seismic hazard

Evidence for surface rupture associated with the Mw 6.3 L’Aquila earthquake sequence of April 2009 (central Italy)

An earthquake of Mw=6.3 struck L’Aquila town (central Italy) on April 6, 2009 rupturing an approximately 18 km long SW-dipping normal fault. The aftershock area extended for a length of more than 35 km and included major aftershocks on April 7 and 9, and thousands of minor events. Surface faulting occurred along the SW-dipping Paganica fault with a continuous extent of ~2.5 km. Ruptures consist of open cracks and vertical dislocations or warps (0.1 maximum throw) with an orientation of N130°-N140°. Small triggered slip and shaking effects also took place along nearby synthetic and antithetic normal faults. The observed limited extent, and small surface displacement, of the Paganica ruptures with respect to the height of the fault scarps and vertical throws of paleoearthquakes along faults in the area, puts the faulting associated with the L’Aquila earthquake in perspective with respect to the maximum expected magnitude, and the regional seismic hazard