Rac1 Deletion Causes Thymic Atrophy

The thymic stroma supports T lymphocyte development and consists of an epithelium maintained by thymic epithelial progenitors. The molecular pathways that govern epithelial homeostasis are poorly understood. Here we demonstrate that deletion of Rac1 in Keratin 5/Keratin 14 expressing embryonic and adult thymic epithelial cells leads to loss of the thymic epithelial compartment. Rac1 deletion led to an increase in c-Myc expression and a generalized increase in apoptosis associated with a decrease in thymic epithelial proliferation. Our results suggest Rac1 maintains the epithelial population, and equilibrium between Rac1 and c-Myc may control proliferation, apoptosis and maturation of the thymic epithelial compartment. Understanding thymic epithelial maintenance is a step toward the dual goals of in vitro thymic epithelial cell culture and T cell differentiation, and the clinical repair of thymic damage from graft-versus-host-disease, chemotherapy or irradiation

Calorimeters for the FCC-hh

The future proton-proton collider (FCC-hh) will deliver collisions at a center of mass energy up to $\sqrt{s}=100$ TeV at an unprecedented instantaneous luminosity of $L=3~10^{35}$ cm$^{-2}$s$^{-1}$, resulting in extremely challenging radiation and luminosity conditions. By delivering an integrated luminosity of few tens of ab$^{-1}$, the FCC-hh will provide an unrivalled discovery potential for new physics. Requiring high sensitivity for resonant searches at masses up to tens of TeV imposes strong constraints on the design of the calorimeters. Resonant searches in final states containing jets, taus and electrons require both excellent energy resolution at multi-TeV energies as well as outstanding ability to resolve highly collimated decay products resulting from extreme boosts. In addition, the FCC-hh provides the unique opportunity to precisely measure the Higgs self-coupling in the di-photon and b-jets channel. Excellent photon and jet energy resolution at low energies as well as excellent angular resolution for pion background rejection are required in this challenging environment. This report describes the calorimeter studies for a multi-purpose detector at the FCC-hh. The calorimeter active components consist of Liquid Argon, scintillating plastic tiles and Monolithic Active Pixel Sensors technologies. The technological choices, design considerations and achieved performances in full Geant4 simulations are discussed and presented. The simulation studies are focused on the evaluation of the concepts. Standalone studies under laboratory conditions as well as first tests in realistic FCC-hh environment, including pileup rejection capabilities by making use of fast signals and high granularity, have been performed. These studies have been performed within the context of the preparation of the FCC conceptual design reports (CDRs)

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 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

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

HE-LHC: The High-Energy Large Hadron Collider

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

Pax genes and organogenesis: Pax9 meets tooth development.

Pax genes encode a family of transcription factors that play key roles during embryogenesis. They are required for the development of a variety of organs including the nervous and muscular system, skeleton, eye, ear, kidney, thymus, and pancreas. Whereas the developmental roles of many of the nine known Pax genes have been analyzed in great detail, a functional analysis of Pax9 has just begun. During mouse embryogenesis, Pax9 exhibits a highly specific expression pattern in derivatives of the foregut endoderm, somites, limb mesenchyme, midbrain, and the cephalic neural crest. In the mandibular arch mesenchyme, the expression of Pax9 marks the prospective sites of tooth development prior to any morphological signs of odontogenesis and is maintained in the developing tooth mesenchyme thereafter. To understand the function of Pax9 during mouse embryogenesis, we recently have created a null allele by gene targeting. Preliminary analyses show that Pax9 is essential for the formation of teeth, and we conclude that Pax9 is required for tooth development to proceed beyond the bud stage. Here, we briefly summarize our current knowledge about Pax genes and introduce Pax9 to the growing family of factors which are involved in tooth development