RI-abitare l’oggi : intorno al progetto di riuso

Interi paesi fantasma, un patrimonio demaniale in disuso e in cerca di valorizzazione, caserme e carceri obsolete o abbandonate collocate all’interno dei centri urbani, capannoni industriali vuoti e un numero crescente di centri commerciali poco o per niente frequentati nelle aree di connessione tra città e campagna, interi complessi industriali abbandonati, palazzi pubblici e privati di dimensione, organizzazione e dotazione di servizi non adeguati alle esigenze odierne. E ancora, chiese, barchesse, scuole, ex colonie ma anche edifici residenziali del tessuto storico urbano e non, architetture storiche e monumentali dal grande valore culturale da rendere funzionali per i diversi usi attuali: sono diversi e sempre più evidenti gli esempi di un patrimonio da riconsiderare, in un’ottica di riutilizzo sostenibile del costruito inteso come risorsa da non sprecare, su cui convergono molteplici obiettivi europei, quali l’incremento dell’efficienza energetica legata al Green New Deal e il raggiungimento del traguardo di zero consumo di suolo, mediante un riuso selettivo e appropriato dell’esistente. In Italia, per la storia plurimillenaria e la forte tradizione identitaria caratterizzata dal ruolo significativo del costruito storico, in cui affondano le radici culturali del Paese, queste sfide richiedono lo sviluppo di un pensiero evoluto sul progetto, in cui l’innovazione e la continuità possano integrarsi, confrontandosi con i principi della Dichiarazione di Davos 2018 Verso una Baukultur di alta qualità per l’Europa e del New European Bauhaus. Sono questi i nuovi temi – o temi noti da riconsiderare – che l’architettura contemporanea deve affrontare, sollecitando una riflessione sui modi di intervenire sul patrimonio costruito e sul ruolo esercitato dalle diverse discipline

AGILE Observations of the LIGO-Virgo Gravitational-wave Events of the GWTC-1 Catalog

We present a comprehensive review of AGILE follow-up observations of the Gravitational Wave (GW) events and the unconfirmed marginal triggers reported in the first LIGO-Virgo (LV) Gravitational Wave Transient Catalog (GWTC-1). For seven GW events and 13 LV triggers, the associated 90% credible region was partially or fully accessible to the AGILE satellite at the T 0; for the remaining events, the localization region was not accessible to AGILE due to passages into the South Atlantic Anomaly, or complete Earth occultations (as in the case of GW170817). A systematic search for associated transients, performed on different timescales and on different time intervals about each event, led to the detection of no gamma-ray counterparts. We report AGILE MCAL upper limit fluences in the 400 keV-100 MeV energy range, evaluated in a time window of T 0 ± 50 s around each event, as well as AGILE GRID upper limit (UL) fluxes in the 30 MeV-50 GeV energy range, evaluated in a time frame of T 0 ± 950 s around each event. All ULs are estimated at different integration times and are evaluated within the portions of GW credible region accessible to AGILE at the different times under consideration. We also discuss the possibility of AGILE MCAL to trigger and detect a weak soft-spectrum burst such as GRB 170817A

Relevance of Stereotyped B-Cell Receptors in the Context of the Molecular, Cytogenetic and Clinical Features of Chronic Lymphocytic Leukemia

Highly homologous B-cell receptors, characterized by non-random combinations of immunoglobulin heavy-chain variable (IGHV) genes and heavy-chain complementarity determining region-3 (HCDR3), are expressed in a recurrent fraction of patients affected by chronic lymphocytic leukemia (CLL). We investigated the IGHV status of 1131 productive IG rearrangements from a panel of 1126 CLL patients from a multicenter Italian study group, and correlated the presence and class of HCDR3 stereotyped subsets with the major cytogenetic alterations evaluated by FISH, molecular prognostic factors, and the time to first treatment (TTFT) of patients with early stage disease (Binet A). Stereotyped HCDR3 sequences were found in 357 cases (31.7%), 231 of which (64.7%) were unmutated. In addition to the previously described subsets, 31 new putative stereotypes subsets were identified. Significant associations between different stereotyped HCDR3 sequences and molecular prognostic factors, such as CD38 and ZAP-70 expression, IGHV mutational status and genomic abnormalities were found. In particular, deletion of 17p13 was significantly represented in stereotype subset #1. Notably, subset #1 was significantly correlated with a substantially reduced TTFT compared to other CLL groups showing unmutated IGHV, ZAP-70 or CD38 positivity and unfavorable cytogenetic lesions including del(17)(p13). Moreover, subset #2 was strongly associated with deletion of 13q14, subsets #8 and #10 with trisomy 12, whereas subset #4 was characterized by the prevalent absence of the common cytogenetic abnormalities. Our data from a large and representative panel of CLL patients indicate that particular stereotyped HCDR3 sequences are associated with specific cytogenetic lesions and a distinct clinical outcome

AGILE TGFS AND GLOBAL LIGHTNING ACTIVITY

[1] The AGILE satellite detects Terrestrial Gamma-ray Flashes (TGFs) in the 0.35–100 MeV energy range using its Mini-Calorimeter (MCAL) instrument with an average detection rate of 10 TGFs/month. Thanks to its Low Earth Orbit with only 2.5 degree of inclination, AGILE guarantees an unprecedented exposure above the equator, where both lightning activity and TGF detection peak. Here we report the comparison between the AGILE TGFs detected between March 2009 and February 2010 and full climatology lightning worldwide distribution based on satellite optical observations from LIS (Lightning Imaging Sensor) and OTD (Optical Transient Detector) instruments. This approach is complementary to the one-to-one TGF/lightning correlations by ground-based sferics measurements. Based on mono and bi-dimensional Kolmogorov-Smirnov tests, we show that the AGILE TGFs and time-averaged global lightning in the equatorial area are not drawn from the same distribution. However, we find significant regional differences in the degree of correlation as well as in the TGF/lightning ratio. In the case of south east Asia we find a 87% probability for the TGF and lightning being samples of the same distribution. This result supports the idea that the physical conditions at play in TGF generation can have strong geographical and climatological modulation. Based on the assumption that the observed range of TGF/flash ratio holds at all latitudes we can estimate a global rate of ≃ 220 ÷ 570 TGFs per day. The observed TGF/flash geographical modulation as well as the TGF global rate estimate are in agreement with previous observations

Health Assessment Questionnaire-Disability Index (HAQ-DI) use in modelling disease progression in diffuse cutaneous systemic sclerosis: an analysis from the EUSTAR database

BACKGROUND: Patients with diffuse cutaneous systemic sclerosis (dcSSc) have a poor prognosis. The importance of monitoring subjective measures of functioning and disability, such as the Health Assessment Questionnaire-Disability Index (HAQ-DI), is important as dcSSc is rated by patients as worse than diabetes or hemodialysis for quality of life impairment. This European Scleroderma Trials and Research (EUSTAR) database analysis was undertaken to examine the importance of impaired functionality in dcSSc prognosis. The primary objectives were to identify predictors of death and HAQ-DI score progression over 1 year. HAQ-DI score, major advanced organ involvement, and death rate were also used to develop a comprehensive model to predict lifetime dcSSc progression. METHODS: This was an observational, longitudinal study in patients with dcSSc registered in EUSTAR. Death and HAQ-DI scores were, respectively, analyzed by Cox regression and linear regression analyses in relation to baseline covariates. A microsimulation Markov model was developed to estimate/predict natural progression of dcSSc over a patient's lifetime. RESULTS: The analysis included dcSSc patients with (N = 690) and without (N = 4132) HAQ-DI score assessments from the EUSTAR database. Baseline HAQ-DI score, corticosteroid treatment, and major advanced organ involvement were predictive of death on multivariable analysis; a 1-point increase in baseline HAQ-DI score multiplied the risk of death by 2.7 (p <  0.001) and multiple advanced major organ involvement multiplied the risk of death by 2.8 (p <  0.05). Multivariable analysis showed that baseline modified Rodnan Skin Score (mRSS) and baseline HAQ-DI score were associated with HAQ-DI score progression at 1 year (p <  0.05), but there was no association between baseline organ involvement and HAQ-DI score progression at 1 year. HAQ-DI score, major advanced organ involvement, and death were successfully used to model long-term disease progression in dcSSc. CONCLUSIONS: HAQ-DI score and major advanced organ involvement were comparable predictors of mortality risk in dcSSc. Baseline mRSS and baseline HAQ-DI score were predictive of HAQ-DI score progression at 1 year, indicating a correlation between these endpoints in monitoring disease progression. It is hoped that this EUSTAR analysis may change physician perception about the importance of the HAQ-DI score in dcSSc

Heterozygous frameshift variants in HNRNPA2B1 cause early-onset oculopharyngeal muscular dystrophy

Missense variants in RNA-binding proteins (RBPs) underlie a spectrum of disease phenotypes, including amyotrophic lateral sclerosis, frontotemporal dementia, and inclusion body myopathy. Here, we present ten independent families with a severe, progressive muscular dystrophy, reminiscent of oculopharyngeal muscular dystrophy (OPMD) but of much earlier onset, caused by heterozygous frameshift variants in the RBP hnRNPA2/B1. All disease-causing frameshift mutations abolish the native stop codon and extend the reading frame, creating novel transcripts that escape nonsense-mediated decay and are translated to produce hnRNPA2/B1 protein with the same neomorphic C-terminal sequence. In contrast to previously reported disease-causing missense variants in HNRNPA2B1, these frameshift variants do not increase the propensity of hnRNPA2 protein to fibrillize. Rather, the frameshift variants have reduced affinity for the nuclear import receptor karyopherin β2, resulting in cytoplasmic accumulation of hnRNPA2 protein in cells and in animal models that recapitulate the human pathology. Thus, we expand the phenotypes associated with HNRNPA2B1 to include an early-onset form of OPMD caused by frameshift variants that alter its nucleocytoplasmic transport dynamics

X-ray pulsar GRO J1008−-57 as an orthogonal rotator

X-ray polarimetry is a unique way to probe geometrical configuration of highly-magnetized accreting neutron stars (X-ray pulsars). GRO J1008$-$57 is the first transient X-ray pulsar observed at two different flux levels by the Imaging X-ray Polarimetry Explorer (IXPE) during its outburst in November 2022. The polarization properties were found to be independent of the source luminosity, with the polarization degree varying between non-detection to about 15% over the pulse phase. Fitting the phase-resolved spectro-polarimetric data with the rotating vector model allowed us to estimate the pulsar inclination (130 deg, which is in good agreement with the orbital inclination), the position angle (75 deg) of the pulsar spin axis, and the magnetic obliquity (74 deg). This makes GRO J1008$-$57 the first confidently identified X-ray pulsar as a nearly orthogonal rotator. The results are discussed in the context of the neutron star atmosphere models and theories of pulsars' axis alignment.Comment: 11 pages, 7 figures, submitted to A&A. arXiv admin note: text overlap with arXiv:2209.0244

Tracking the X-ray Polarization of the Black Hole Transient Swift J1727.8-1613 during a State Transition

We report on a campaign on the bright black hole X-ray binary Swift J1727.8$-$1613 centered around five observations by the Imaging X-ray Polarimetry Explorer (IXPE). This is the first time it has been possible to trace the evolution of the X-ray polarization of a black hole X-ray binary across a hard to soft state transition. The 2--8 keV polarization degree slowly decreased from $\sim$4\% to $\sim$3\% across the five observations, but remained in the North-South direction throughout. Using the Australia Telescope Compact Array (ATCA), we measure the intrinsic 7.25 GHz radio polarization to align in the same direction. Assuming the radio polarization aligns with the jet direction (which can be tested in the future with resolved jet images), this implies that the X-ray corona is extended in the disk plane, rather than along the jet axis, for the entire hard intermediate state. This in turn implies that the long ($\gtrsim$10 ms) soft lags that we measure with the Neutron star Interior Composition ExploreR (NICER) are dominated by processes other than pure light-crossing delays. Moreover, we find that the evolution of the soft lag amplitude with spectral state differs from the common trend seen for other sources, implying that Swift J1727.8$-$1613 is a member of a hitherto under-sampled sub-population.Comment: Submitted to ApJ. 20 pages, 8 figure