Belgrade's urban transformation during the 19th century: A space syntax approach

This paper focuses on the change in terms of spatial structure of the city centre of Belgrade occurred during the 19th century with the urban renewal and sprawl. Space Syntax methodology was used in order to analyse and quantify the spatial configuration properties of the old town inherited from the Medieval and Ottoman period, but also to understand the changes produced by the remodeling of the borough during the Principality of Serbia according to the academic architectural style. A scan from the Radoje Dedinac plan of Belgrade from 1815-1830 conserved at the City Museum of Belgrade has been used in order to capture the old town morphology. Despite an abundant literature describing the incredible metamorphosis of the oriental part of the old town, the sources that have scientifically evaluated the urban transformation produced are very few. The Space Syntax methodology helps filling this gap. Axial maps of Belgrade between 1815-1830 and of nowadays have been generated and analysed in order to capture spatial intelligibility and synergy of the city before and after the urban transformation. Finally angular segment analysis has been used to understand the spatial morphology of both the organic urban form and the modern grid system

A Model-Based Security Testing Approach for Automotive Over-The-Air Updates

Modern connected cars are exposed to various cybersecurity threats due to the sophisticated computing and connectivity technologies they host for providing enhanced user experience for their occupants by offering numerous innovative applications. While prior studies exist that explore cybersecurity challenges, tools and techniques for automotive systems, over-the-air (OTA) software updates for automobiles can be exploited by the attackers to compromise vehicle security and safety has not been covered extensively. This paper presents our Model-Based Security Testing (MBST) approach, designed for cybersecurity evaluation of the OTA update system for automobiles, which has an integrated testbed and a software tool that is capable of automatically generating and executing test cases by using attack trees as an input. Integrating threat modelling in the testing provides several benefits, including clear and systematic identification of different threats. Automation of the test-case generation and execution has the obvious benefits of saving time and manual effort, as manual test-case generation is both a time-consuming and error-prone process (especially, when the testing involves several test-cases). A simple simulated attack is used to demonstrate the validity and effectiveness of our testing approach. To the best of our knowledge, there is no prior research that uses a testing approach similar to our approach for automotive OTA security evaluation

Boosting the agricultural production capabilities of Indian rural communities in the micro region of South Ahuachapán (El Salvador), in order to improve food safety and raise income for the local population

As is the case with many Latin American countries, El Salvador, which is regularly affected by hurricanes and is in transition towards democracy following a period of violent civil war, suffers from major inequality in the distribution of its national wealth, with almost half the population living below the poverty line. It was in light of this that, in 2002, the Secours populaire français intervened in the North-West of the country in the coffee growing area of the southern part of the Ahuachapán department, an area classified as a priority development area by governmental authorities.  This was in the form of a project undertaken in partnership with the NGO FUNDESYRAM (Fundación para el desarrollo socioeconómico y la restauración ambiental - the Foundation for Social-Economic Development and Environmental Rehabilitation), and was co-funded by the European Union and developed over a period of nine years. Its aim was to improve food security and family economics of those in conditions of extreme poverty and it was undertaken using the principles of inter-family solidarity and respect for the environment. The involvement of the partner and the beneficiaries led to a strengthening of communal associations (the ADESCO (Asociación de desarrollo comunal - Community Improvement Associations) as well as to the creation of a production association (‘AGROCESA’ Asociación de productores agropecuarios centro sur Ahuachapán – Association of Agriculture and Livestock Production) in order to improve the organization, management and support of social and economic development projects. It was this that guaranteed the success of the program and enabled both the capacity building for self-management and the autonomous and unified development of those communities that benefited from the project. This project, that, among other things, contributed to the eradication of infantile malnutrition by ensuring food safety within the family and empowered women in the community, far exceeded its original objectives.Régulièrement touché par les ouragans et évoluant dans un contexte démocratique récent suite à une violente période de guerre civile, le Salvador souffre comme beaucoup de pays latino-américains d’une forte inégalité dans la répartition des richesses nationales et près de la moitié de la population se trouve en dessous du seuil de pauvreté. C’est dans ce contexte que le Secours populaire français intervient en 2002 au nord-ouest du pays dans la région caféière d’Ahuachapán-Sud, région classée en zone de développement prioritaire par les autorités gouvernementales. Il s’agit d’un projet mené en partenariat avec l’ONG locale FUNDESYRAM cofinancé par l’Union européenne et développé sur neuf ans, visant à améliorer la sécurité alimentaire et l’économie familiale des populations en situation d’extrême pauvreté. Cela, à travers une logique de solidarité interfamiliale et la promotion de techniques respectueuses de l’environnement. L’implication du partenaire et des bénéficiaires aboutit au renforcement des associations communales (ADESCO) ainsi que la création d’une association de producteurs (AGROCESA) afin de mieux encadrer, gérer et appuyer les projets de développement social et économique. Ce qui a garanti le succès du programme et permet de renforcer les capacités d’autogestion et le développement autonome et solidaire des communautés bénéficiaires. Ce projet qui a permis, entre autre, d’éradiquer la dénutrition infantile en assurant la sécurité alimentaire des familles ainsi que de renforcer le rôle des femmes au sein de la communauté, a largement dépassé les objectifs fixés au départ.Regularmente afectado por los huracanes y tras un largo periodo de una violenta guerra civil, El Salvador conoce actualmente un contexto político democrático. Sin embargo, el país sufre, como muchos otros Estados latino-americanos, de un desequilibrio en la repartición de sus riquezas nacionales.  Cerca de la mitad de la población se encuentra bajo el nivel de pobreza. Es en este contexto que el Secours populaire français decide intervenir en el 2002 en la zona cafetalera de Ahuachapán-Sur; región clasificada por el Gobierno salvadoreño como una zona prioritaria de desarrollo. Se trata de un proyecto desarrollado durante nueve años por el SPF, en colaboración con la ONG local FUNDESYRAM (Fundación para el desarrollo socioeconómico y la restauración ambiental) y cofinanciado por la Unión europea.  El objetivo es de mejorar la seguridad alimentaria y la economía familiar de una población en extrema pobreza. Esto promoviendo una lógica de solidaridad interfamiliar y métodos respetuosos del medio ambiente. La estrecha colaboración entre el SPF, la FUNDESYRAM y las familias beneficiarias permitió fortalecer y crear asociaciones de desarrollo comunales (ADESCOs) así como la asociación de productores (AGROCESA). De esta manera se mejoró el seguimiento, la gestión y el apoyo a los proyectos de desarrollo socio-económicos. Se garantizó  el éxito del programa, el fortalecimiento de las capacidades de autogestión y de desarrollo autónomo de las comunidades beneficiarias. El programa logró erradicar la desnutrición infantil al garantizar la seguridad alimentaria familiar, así como fortalecer el papel de la mujer en la comunidad, entre otros aspectos. De este modo, podemos constar que el programa sobrepasó los objetivos definidos inicialmente

Boosting the agricultural production capabilities of Indian rural communities in the micro region of South Ahuachapán (El Salvador), in order to improve food safety and raise income for the local population

As is the case with many Latin American countries, El Salvador, which is regularly affected by hurricanes and is in transition towards democracy following a period of violent civil war, suffers from major inequality in the distribution of its national wealth, with almost half the population living below the poverty line. It was in light of this that, in 2002, the Secours populaire français intervened in the North-West of the country in the coffee growing area of the southern part of the Ahuachapán department, an area classified as a priority development area by governmental authorities.  This was in the form of a project undertaken in partnership with the NGO FUNDESYRAM (Fundación para el desarrollo socioeconómico y la restauración ambiental - the Foundation for Social-Economic Development and Environmental Rehabilitation), and was co-funded by the European Union and developed over a period of nine years. Its aim was to improve food security and family economics of those in conditions of extreme poverty and it was undertaken using the principles of inter-family solidarity and respect for the environment. The involvement of the partner and the beneficiaries led to a strengthening of communal associations (the ADESCO (Asociación de desarrollo comunal - Community Improvement Associations) as well as to the creation of a production association (‘AGROCESA’ Asociación de productores agropecuarios centro sur Ahuachapán – Association of Agriculture and Livestock Production) in order to improve the organization, management and support of social and economic development projects. It was this that guaranteed the success of the program and enabled both the capacity building for self-management and the autonomous and unified development of those communities that benefited from the project. This project, that, among other things, contributed to the eradication of infantile malnutrition by ensuring food safety within the family and empowered women in the community, far exceeded its original objectives.Régulièrement touché par les ouragans et évoluant dans un contexte démocratique récent suite à une violente période de guerre civile, le Salvador souffre comme beaucoup de pays latino-américains d’une forte inégalité dans la répartition des richesses nationales et près de la moitié de la population se trouve en dessous du seuil de pauvreté. C’est dans ce contexte que le Secours populaire français intervient en 2002 au nord-ouest du pays dans la région caféière d’Ahuachapán-Sud, région classée en zone de développement prioritaire par les autorités gouvernementales. Il s’agit d’un projet mené en partenariat avec l’ONG locale FUNDESYRAM cofinancé par l’Union européenne et développé sur neuf ans, visant à améliorer la sécurité alimentaire et l’économie familiale des populations en situation d’extrême pauvreté. Cela, à travers une logique de solidarité interfamiliale et la promotion de techniques respectueuses de l’environnement. L’implication du partenaire et des bénéficiaires aboutit au renforcement des associations communales (ADESCO) ainsi que la création d’une association de producteurs (AGROCESA) afin de mieux encadrer, gérer et appuyer les projets de développement social et économique. Ce qui a garanti le succès du programme et permet de renforcer les capacités d’autogestion et le développement autonome et solidaire des communautés bénéficiaires. Ce projet qui a permis, entre autre, d’éradiquer la dénutrition infantile en assurant la sécurité alimentaire des familles ainsi que de renforcer le rôle des femmes au sein de la communauté, a largement dépassé les objectifs fixés au départ.Regularmente afectado por los huracanes y tras un largo periodo de una violenta guerra civil, El Salvador conoce actualmente un contexto político democrático. Sin embargo, el país sufre, como muchos otros Estados latino-americanos, de un desequilibrio en la repartición de sus riquezas nacionales.  Cerca de la mitad de la población se encuentra bajo el nivel de pobreza. Es en este contexto que el Secours populaire français decide intervenir en el 2002 en la zona cafetalera de Ahuachapán-Sur; región clasificada por el Gobierno salvadoreño como una zona prioritaria de desarrollo. Se trata de un proyecto desarrollado durante nueve años por el SPF, en colaboración con la ONG local FUNDESYRAM (Fundación para el desarrollo socioeconómico y la restauración ambiental) y cofinanciado por la Unión europea.  El objetivo es de mejorar la seguridad alimentaria y la economía familiar de una población en extrema pobreza. Esto promoviendo una lógica de solidaridad interfamiliar y métodos respetuosos del medio ambiente. La estrecha colaboración entre el SPF, la FUNDESYRAM y las familias beneficiarias permitió fortalecer y crear asociaciones de desarrollo comunales (ADESCOs) así como la asociación de productores (AGROCESA). De esta manera se mejoró el seguimiento, la gestión y el apoyo a los proyectos de desarrollo socio-económicos. Se garantizó  el éxito del programa, el fortalecimiento de las capacidades de autogestión y de desarrollo autónomo de las comunidades beneficiarias. El programa logró erradicar la desnutrición infantil al garantizar la seguridad alimentaria familiar, así como fortalecer el papel de la mujer en la comunidad, entre otros aspectos. De este modo, podemos constar que el programa sobrepasó los objetivos definidos inicialmente

mTert induction in p21-positive cells counteracts capillary rarefaction and pulmonary emphysema

Lung diseases develop when telomeres shorten beyond a critical point. We constructed a mouse model in which the catalytic subunit of telomerase (mTert), or its catalytically inactive form (mTert), is expressed from the p21 locus. Expression of either TERT or TERT reduces global p21 levels in the lungs of aged mice, highlighting TERT non-canonical function. However, only TERT reduces accumulation of very short telomeres, oxidative damage, endothelial cell (ECs) senescence and senile emphysema in aged mice. Single-cell analysis of the lung reveals that p21 (and hence TERT) is expressed mainly in the capillary ECs. We report that a fraction of capillary ECs marked by CD34 and endowed with proliferative capacity declines drastically with age, and this is counteracted by TERT but not TERT. Consistently, only TERT counteracts decline of capillary density. Natural aging effects are confirmed using the experimental model of emphysema induced by VEGFR2 inhibition and chronic hypoxia. We conclude that catalytically active TERT prevents exhaustion of the putative CD34 + EC progenitors with age, thus protecting against capillary vessel loss and pulmonary emphysema.Work in VG’s Lab is supported by “La Ligue Contre le Cancer”, Equipe Labellisée, The Canceropole PACA (Projet Emergent), the “Institut National du Cancer” (INCA), PLBIO 2019, and the cross-cutting Inserm program on aging (AGEMED). SA’s Lab is supported by grants from the Inserm, Ministère de la Recherche, Agence Nationale pour la Recherche (ANR), Institut National du Cancer (INCA), and Fondation pour la Recherche Médicale (FRM), et la Fondation ARC. AL-V’s lab is supported by INCa (PLBIO2019) and La Ligue contre le cancer-Paris (RS21/75-24). SC-A is a recipient of a European CO-FUND PhD fellowship from Institut Curie (European Union’s Horizon 2020 research and innovation program under the Marie Skłodowska-Curie grant agreement No 666003). IF’s lab was funded by grants from the Spanish Ministry of Science and Innovation (PID2019-110339RB-I00) and the Comunidad de Madrid (S2017/BMD-3875). EG’s lab was supported by the Fondation ARC (Program ARC), and the cross-cutting Inserm program on aging (AGEMED). CIPHE is supported by PHENOMIN (French National Infrastructure for mouse Phenogenomics; ANR10-INBS-07)

Congruence between NOTCH3 mutations and GOM in 131 CADASIL patients

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is the most common hereditary subcortical vascular dementia. It is caused by mutations in NOTCH3 gene, which encodes a large transmembrane receptor Notch3. The key pathological finding is the accumulation of granular osmiophilic material (GOM), which contains extracellular domains of Notch3, on degenerating vascular smooth muscle cells (VSMCs). GOM has been considered specifically diagnostic for CADASIL, but the reports on the sensitivity of detecting GOM in patients’ skin biopsy have been contradictory. To solve this contradiction, we performed a retrospective investigation of 131 Finnish, Swedish and French CADASIL patients, who had been adequately examined for both NOTCH3 mutation and presence of GOM. The patients were examined according to the diagnostic practice in each country. NOTCH3 mutations were assessed by restriction enzyme analysis of specific mutations or by sequence analysis. Presence of GOM was examined by electron microscopy (EM) in skin biopsies. Biopsies of 26 mutation-negative relatives from CADASIL families served as the controls. GOM was detected in all 131 mutation positive patients. Altogether our patients had 34 different pathogenic mutations which included three novel point mutations (p.Cys67Ser, p.Cys251Tyr and p.Tyr1069Cys) and a novel duplication (p.Glu434_Leu436dup). The detection of GOM by EM in skin biopsies was a highly reliable diagnostic method: in this cohort the congruence between NOTCH3 mutations and presence of GOM was 100%. However, due to the retrospective nature of this study, exact figure for sensitivity cannot be determined, but it would require a prospective study to exclude possible selection bias. The identification of a pathogenic NOTCH3 mutation is an indisputable evidence for CADASIL, but demonstration of GOM provides a cost-effective guide for estimating how far one should proceed with the extensive search for a new or an uncommon mutations among the presently known over 170 different NOTCH3 gene defects. The diagnostic skin biopsy should include the border zone between deep dermis and upper subcutis, where small arterial vessels of correct size are located. Detection of GOM requires technically adequate biopsies and distinction of true GOM from fallacious deposits. If GOM is not found in the first vessel or biopsy, other vessels or additional biopsies should be examined

Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy: A Genetic Cause of Cerebral Small Vessel Disease

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a single-gene disorder of the cerebral small blood vessels caused by mutations in the Notch3 gene. The exact prevalence of this disorder was unknown currently, and the number of reported CADASIL families is steadily increasing as the clinical picture and diagnostic examinations are becoming more widely known. The main clinical manifestations are recurrent stroke, migraine, psychiatric symptoms, and progressive cognitive impairment. The clinical course of CADASIL is highly variable, even within families. The involvement of the anterior temporal lobe and the external capsule on brain magnetic resonance imaging was found to have high sensitivity and specificity in differentiating CADASIL from the much more common sporadic cerebral small-vessel disease (SVD). The pathologic hallmark of the disease is the presence of granular osmiophilic material in the walls of affected vessels. CADASIL is a prototype single-gene disorder that has evolved as a unique model for studying the mechanisms underlying cerebral SVD. At present, the incidence and prevalence of CADASIL seem to be underestimated due to limitations in clinical, neuroradiological, and genetic diagnoses of this disorder

Biological and Mechanical Synergies to Deal With Proton Therapy Pitfalls: Minibeams, FLASH, Arcs, and Gantryless Rooms

Proton therapy has advantages and pitfalls comparing with photon therapy in radiation therapy. Among the limitations of protons in clinical practice we can selectively mention: uncertainties in range, lateral penumbra, deposition of higher LET outside the target, entrance dose, dose in the beam path, dose constraints in critical organs close to the target volume, organ movements and cost. In this review, we combine proposals under study to mitigate those pitfalls by using individually or in combination: (a) biological approaches of beam management in time (very high dose rate “FLASH” irradiations in the order of 100 Gy/s) and (b) modulation in space (a combination of mini-beams of millimetric extent), together with mechanical approaches such as (c) rotational techniques (optimized in partial arcs) and, in an effort to reduce cost, (d) gantry-less delivery systems. In some cases, these proposals are synergic (e.g., FLASH and minibeams), in others theyare hardly compatible (mini-beam and rotation). Fixed lines have been used in pioneer centers, or for specific indications (ophthalmic, radiosurgery,…), they logically evolved to isocentric gantries. The present proposals to produce fixed lines are somewhat controversial. Rotational techniques, minibeams and FLASH in proton therapy are making their way, with an increasing degree of complexity in these three approaches, but with a high interest in the basic science and clinical communities. All of them must be proven in clinical applications