Visualizing the role of Cbl-b in control of islet-reactive CD4 T cells and susceptibility to Type 1 Diabetes

The E3 ubiquitin ligase Cbl-b regulates T cell activation thresholds and has been associated with protecting against Type 1 diabetes, but its in vivo role in the process of self-tolerance has not been examined at the level of potentially auto-aggressive CD4+ T cells. Here we visualize the consequences of Cbl-b deficiency on self-tolerance to lysozyme antigen expressed in transgenic mice under control of the insulin promoter (insHEL). By tracing the fate of pancreatic islet-reactive CD4+ T cells in pre-diabetic 3A9-TCR x insHEL double-transgenic mice, we find that Cbl-b deficiency contrasts with AIRE or IL-2 deficiency because it does not affect thymic negative selection of islet-reactive CD4+ cells nor the numbers of islet-specific CD4+ or CD4+ FOXP3+ T cells in the periphery, although it decreased differentiation of inducible Treg (iTreg) cells from TGF-b treated 3A9-TCR cells in vitro. When removed from Tregs and placed in culture, Cblb-deficient islet-reactive CD4+ cells reveal a capacity to proliferate to HEL antigen that is repressed in wild-type cells. This latent failure of T cell anergy is nevertheless controlled in vivo in pre-diabetic mice, so that islet-reactive CD4+ cells in spleen and pancreatic lymph node of Cblb-deficient mice show no evidence of increased activation or proliferation in situ. Cblb-deficiency subsequently precipitated diabetes in most TCR:insHEL animals by 15 wks of age. These results reveal a role for peripheral T cell anergy in organ-specific self-tolerance, and illuminate the interplay between Cblb-dependent anergy and other mechanisms for preventing organ-specific autoimmunity

Fuoriclasse. Migranti e figli di migranti (dis)persi nel sistema scolastico di un'area di frontiera.

Fuoriclasse è una pubblicazione che raccoglie l’interpretazione scientifica dei ricercatori, ricercatrici, insegnanti e formatori che sono stati parte attiva nel progetto FAMI-IMPACT FVG 2014-20, per restituire una sintesi ed una riflessione critica al termine di quattro anni di progetto strutturato in azioni di ricerca e di formazione volte a contrastare la dispersione scolastica di alunne/i con background migratorio in Friuli Venezia Giulia. Il volume riporta gli apporti della prospettiva antropologica, pedagogica e didattica con approcci qualitativi e metodologie trasversali per offrire un ripensamento sulle potenziali azioni di inclusione scolastica e sulle criticità emerse. Il titolo è dedicato a questa nuova generazione di giovani spesso italiani di fatto, ma non di diritto, che in ogni caso fanno parte della comunità di pratiche scolastiche quotidiane con cui cercano di costruire, giorno per giorno, un orizzonte di senso e di futuro sostenibile, nonostante la scuola italiana mostri una propensione quasi perversa ad escluderli, lasciandoli “fuori dalla classe”. I fuoriclasse possono essere gli alunni estranei in quanto non pienamente cittadini italiani, a causa del background migratorio, oppure gli outsider, quelli che riescono a farcela e a imporsi nonostante lo svantaggio iniziale e la situazione marginale. Le future direzioni dipenderanno soprattutto da quanto effettivamente le politiche sociali di inclusione scolastica metteranno in gioco come esercizi quotidiani di cittadinanza attiva per tutti/e, a prescindere dal background di partenza

Precision atomic gravimeter based on Bragg diffraction

We present a precision gravimeter based on coherent Bragg diffraction of freely falling cold atoms. Traditionally, atomic gravimeters have used stimulated Raman transitions to separate clouds in momentum space by driving transitions between two internal atomic states. Bragg interferometers utilize only a single internal state, and can therefore be less susceptible to environmental perturbations. Here we show that atoms extracted from a magneto-optical trap using an accelerating optical lattice are a suitable source for a Bragg atom interferometer, allowing efficient beamsplitting and subsequent separation of momentum states for detection. Despite the inherently multi-state nature of atom diffraction, we are able to build a Mach-Zehnder interferometer using Bragg scattering which achieves a sensitivity to the gravitational acceleration of $\Delta g/g = 2.7\times10^{-9}$ with an integration time of 1000s. The device can also be converted to a gravity gradiometer by a simple modification of the light pulse sequence.Comment: 13 pages, 11 figure

Shear strengthening of continuous reinforced concrete T-beams using wire rope units

A simple unbonded-type shear strengthening technique for reinforced concrete beams using wire rope units is presented. Ten two-span reinforced concrete T-beams externally strengthened with wire rope units and an unstrengthened control beam were tested to failure, to explore the significance and shortcomings of the developed unbonded-type shear strengthening technique. The main parameters investigated were the type, amount and prestressing force of wire rope units. All beams tested failed, owing to significant diagonal cracks within the interior shear span. However, beams strengthened with closed type wire rope units exhibited more ductile failure than the unstrengthened, control beam or those strengthened with U-type wire rope units. The diagonal cracking load and ultimate shear capacity of beams with closed-type were linearly increased with the increase of vertical confinement stresses in concrete owing to the prestressing force in wire rope units, while those of beams with U-type were minimally influenced. It was also observed that average stresses in closed-type wire ropes crossing diagonal cracks at ultimate strength of beams tested were much higher than those in U-type wire ropes, showing better utilization in the former case. The shear capacity of beams with closed-type wire rope units is conservatively predicted using the equations of ACI 318-05, modified to account for the external wire rope units. A mechanism analysis based on the upper bound approach of the plasticity theory is also developed to assess the load capacity of beams tested. The predictions by the mechanism analysis for beams with closed-type wire rope units are in good agreement with test results and showed a coefficient of variation slightly less than the modified ACI 318-05 equations. However, the modified ACI 318-05 equations are more conservative and simpler to use for design purposes

All-sky search for short gravitational-wave bursts in the second Advanced LIGO and Advanced Virgo run

We present the results of a search for short-duration gravitational-wave transients in the data from the second observing run of Advanced LIGO and Advanced Virgo. We search for gravitational-wave transients with a duration of milliseconds to approximately one second in the 32-4096 Hz frequency band with minimal assumptions about the signal properties, thus targeting a wide variety of sources. We also perform a matched-filter search for gravitational-wave transients from cosmic string cusps for which the waveform is well modeled. The unmodeled search detected gravitational waves from several binary black hole mergers which have been identified by previous analyses. No other significant events have been found by either the unmodeled search or the cosmic string search. We thus present the search sensitivities for a variety of signal waveforms and report upper limits on the source rate density as a function of the characteristic frequency of the signal. These upper limits are a factor of 3 lower than the first observing run, with a 50% detection probability for gravitational-wave emissions with energies of ∼10-9 Mc2 at 153 Hz. For the search dedicated to cosmic string cusps we consider several loop distribution models, and present updated constraints from the same search done in the first observing run