The Active and Periactive Zone Organization and the Functional Properties of Small and Large Synapses

The arrival of an action potential (AP) at a synaptic terminal elicits highly synchronized quanta release. Repetitive APs produce successive synaptic vesicle (SV) fusions that require management of spent synaptic vesicle components in the presynaptic membrane with minimum disturbance of the secretory apparatus. To this end, the synaptic machinery is structured accordingly to the strength and the range of frequencies at which each particular synapse operates. This results in variations in the number and dimension of Active Zones (AZs), amount and distribution of SVs, and, probably, in the primary endocytic mechanisms they use. Understanding better how these structural differences determine the functional response in each case has been a matter of long-term interest. Here we review the structural and functional properties of three distinct types of synapses: the neuromuscular junction (NMJ; a giant, highly reliable synapse that must exocytose a large number of quanta with each stimulus to guarantee excitation of the postsynaptic cell), the hippocampal excitatory small synapse (which most often has a single release site and a relatively small pool of vesicles), and the cerebellar mossy fiber-granule cell synapse (which possesses hundreds of release sites and is able to translocate, dock and prime vesicles at high speed). We will focus on how the release apparatus is organized in each case, the relative amount of vesicular membrane that needs to be accommodated within the periAZ upon stimulation, the different mechanisms for retrieving the excess of membrane and, finally, how these factors may influence the functioning of the release sites

SMN Requirement for Synaptic Vesicle, Active Zone and Microtubule Postnatal Organization in Motor Nerve Terminals

Low levels of the Survival Motor Neuron (SMN) protein produce Spinal Muscular Atrophy (SMA), a severe monogenetic disease in infants characterized by muscle weakness and impaired synaptic transmission. We report here severe structural and functional alterations in the organization of the organelles and the cytoskeleton of motor nerve terminals in a mouse model of SMA. The decrease in SMN levels resulted in the clustering of synaptic vesicles (SVs) and Active Zones (AZs), reduction in the size of the readily releasable pool (RRP), and the recycling pool (RP) of synaptic vesicles, a decrease in active mitochondria and limiting of neurofilament and microtubule maturation. We propose that SMN is essential for the normal postnatal maturation of motor nerve terminals and that SMN deficiency disrupts the presynaptic organization leading to neurodegeneration

Prophylaxis in hemophilia

Hemophilia is an inherited X-linked coagulopathy defined by a deficiency or abnormality in the clotting function of factor VIII (Hemophilia A) or factor IX (Hemophilia B). Prophylaxis – the regular administration of therapeutic products to maintain hemostasis and prevent bleeding – is the mainstream of treatment. Addressing the development and scientific evidence for administrating prophylaxis is the goal of this review. Prophylaxis is the therapeutic modality of choice for people with severe hemophilia, being considered, in principle, a lifelong treatment. It should have an early onset, ideally as a primary, or at least secondary. Even lifelong tertiary prophylaxis seems to offer benefit, although further studies are still lacking. Individualized strategies should lead to an optimization of the dilemma between better joint outcomes versus involved costs

Efficient Combination of Surface Texturing and Functional Coating for Very Low Secondary Electron Yield Surfaces and Rough Nonevaporable Getter Films

Abstract The formation of a fissured copper surface by picosecond pulsed laser irradiation is combined with functional coatings consisting of Ti and amorphous carbon layers or a Ti–Zr–V compound film to fabricate surfaces with the maximum of the secondary electron yield being as low as 0.4. By structural and spectroscopic analysis of the formed surfaces it is demonstrated that both coatings enclose the nanostructures generated by redeposition of metal structures from the laser‐induced plasma plume, keeping the initial topography intact. This allows an efficient elimination of secondary electron emission by combining the benefits from structural surface modification and adaption of electronic surface properties to efficiently dissipate the energy of impinging electrons. Thermal activation tests of the Ti–Zr–V nonevaporable getter films revealed that for films on nanostructured substrates, which have a much higher effective surface, a slight diminution of surface activation occurs at 160 and 200 °C, while this effect is completely compensated when heating up to 250 °C indicating promising pumping capabilities. Both examples highlight the benefits from combining 3D substrate patterning with classical 2D deposition technologies

Hemophilia: a biography on therapeutical approaches

The history of hemophilia is ancient, with descriptions dated to the 2nd century AD. The first modern narratives appeared in 1800s, when total blood transfusion was the only available treatment and life expectancy was remarkably low. Advances occurred with the use of plasma and cryoprecipitate, but only the discovered of factor concentrates revolutionized the treatment. The implantation of prophylaxis allowed hemophilic patients to prevent bleeding and the development of chronic arthropathy, although with a significant burdensome with the regular infusions. In the past 20 years, this field has witnessed major improvements, including the development of gene therapy and other pharmacological approaches

Prophylaxis in Hemophilia

Hemophilia is an inherited X-linked coagulopathy defined by a deficiency or abnormality in the clotting function of factor VIII (Hemophilia A) or factor IX (Hemophilia B). Prophylaxis – the regular administration of therapeutic products to maintain hemostasis and prevent bleeding – is the mainstream of treatment. Addressing the development and scientific evidence for administrating prophylaxis is the goal of this review. Prophylaxis is the therapeutic modality of choice for people with severe hemophilia, being considered, in principle, a lifelong treatment. It should have an early onset, ideally as a primary, or at least secondary. Even lifelong tertiary prophylaxis seems to offer benefit, although further studies are still lacking. Individualized strategies should lead to an optimization of the dilemma between better joint outcomes versus involved costs

Matemáticas en contexto

El libro compila estrategias didácticas derivadas del programa de formación complementario escritas por instructores técnicos de diferentes regionales del país, describe la forma en que se incorpora el conocimiento matemático en campos específicos de diferentes áreas de formación laboral basado en las teorías didácticas y reflexiones pedagógicas de instructores.The book compiles the didactic strategies derived from the complementary training program by the technical instructors of the regional media of the country, describes the way in which mathematical knowledge is incorporated in the fields of different areas of work training based on theories didactic and pedagogical reflections of instructors.Consideraciones frente al aprendizaje de las matemáticas -- Perspectiva constructivista -- Teoría de las situaciones didácticas -- Modelación matemática -- Mediación tecnológica -- Pensamiento numérico variacional -- Pensamiento numérico -- Pensamiento variacional -- Diseño de modelo matemático con aplicación de costos de producción -- Modelo matemático del consumo de gas en un artefacto afectado por su presión de trabajo -- Planeación de la producción agrícola: Caso plan óptimo de siembra que permita alcanzar la máxima rentabilidad del cultivo -- Estudio del Álgebra de Boole -- Diseño de un modelo de inventarios para una pequeña empresa de calzado de dotación -- Estudio de la Ley de Ohm mediante herramienta interactiva -- Pensamiento métrico-geométrico -- Pensamiento geométrico -- Pensamiento métrico -- Caso de optimización de recursos en el sector industrial de la confección -- Optimización de espacios para huertas urbanas -- Optimización de los costos del espacio de almacenamiento en microempresas y pequeñas empresas de acuerdo con las normas de seguridad vigentes -- Unidad de medida métrica para confección de ropa exterior femenina -- Optimización de recursos aplicando el proceso administrativo -- Pensamiento aleatorio -- Estadística Básica para Articulación con la Media -- Evaluación del impacto de la accidentalidad en la implementación del Sistema de Gestión de Seguridad y Salud en el Trabajo (sg-sst) por medio de indicadores -- Identificar los aspectos de la declaración de renta para una persona natural no obligada a llevar contabilidad -- Fortalecimiento de la estadística: caso de las unidades productivas del Centro de Biotecnología Agropecuaria -- Estadística dinámica -- Resultados preliminaresna[270 páginas

HE-LHC: The High-Energy Large Hadron Collider: Future Circular Collider Conceptual Design Report Volume 4

In response to the 2013 Update of the European Strategy for Particle Physics (EPPSU), the Future Circular Collider (FCC) study was launched as a world-wide international collaboration hosted by CERN. The FCC study covered an energy-frontier hadron collider (FCC-hh), a highest-luminosity high-energy lepton collider (FCC-ee), the corresponding 100 km tunnel infrastructure, as well as the physics opportunities of these two colliders, and a high-energy LHC, based on FCC-hh technology. This document constitutes the third volume of the FCC Conceptual Design Report, devoted to the hadron collider FCC-hh. It summarizes the FCC-hh physics discovery opportunities, presents the FCC-hh accelerator design, performance reach, and staged operation plan, discusses the underlying technologies, the civil engineering and technical infrastructure, and also sketches a possible implementation. Combining ingredients from the Large Hadron Collider (LHC), the high-luminosity LHC upgrade and adding novel technologies and approaches, the FCC-hh design aims at significantly extending the energy frontier to 100 TeV. Its unprecedented centre-of-mass collision energy will make the FCC-hh a unique instrument to explore physics beyond the Standard Model, offering great direct sensitivity to new physics and discoveries

FCC-ee: The Lepton Collider: Future Circular Collider Conceptual Design Report Volume 2

In response to the 2013 Update of the European Strategy for Particle Physics, the Future Circular Collider (FCC) study was launched, as an international collaboration hosted by CERN. This study covers a highest-luminosity high-energy lepton collider (FCC-ee) and an energy-frontier hadron collider (FCC-hh), which could, successively, be installed in the same 100 km tunnel. The scientific capabilities of the integrated FCC programme would serve the worldwide community throughout the 21st century. The FCC study also investigates an LHC energy upgrade, using FCC-hh technology. This document constitutes the second volume of the FCC Conceptual Design Report, devoted to the electron-positron collider FCC-ee. After summarizing the physics discovery opportunities, it presents the accelerator design, performance reach, a staged operation scenario, the underlying technologies, civil engineering, technical infrastructure, and an implementation plan. FCC-ee can be built with today’s technology. Most of the FCC-ee infrastructure could be reused for FCC-hh. Combining concepts from past and present lepton colliders and adding a few novel elements, the FCC-ee design promises outstandingly high luminosity. This will make the FCC-ee a unique precision instrument to study the heaviest known particles (Z, W and H bosons and the top quark), offering great direct and indirect sensitivity to new physics

FCC Physics Opportunities: Future Circular Collider Conceptual Design Report Volume 1

We review the physics opportunities of the Future Circular Collider, covering its e+e-, pp, ep and heavy ion programmes. We describe the measurement capabilities of each FCC component, addressing the study of electroweak, Higgs and strong interactions, the top quark and flavour, as well as phenomena beyond the Standard Model. We highlight the synergy and complementarity of the different colliders, which will contribute to a uniquely coherent and ambitious research programme, providing an unmatchable combination of precision and sensitivity to new physics