Cooperative Oxygen Binding to Scapharca inaequivalvis Hemoglobin in the Crystal

Oxygen binding to homodimeric Scapharca inaequivalvis hemoglobin (HbI) crystals has been investigated by single-crystal polarized absorption microspectrophotometry. The saturation curve, characterized by a Hill coefficient n(H) = 1.45 and an oxygen pressure at half saturation p(50) = 4.8 torr, at 15 degrees C, shows that HbI in the crystalline state retains positive cooperativity in ligand binding. This finding will permit the correlation of the oxygen-linked conformational changes in the crystal with the expression of cooperativity. Polarized absorption spectra of deoxy-HbI, oxy-HbI, and oxidized HbI crystals indicate that oxygenation does not induce heme reorientation, whereas oxidation does. Lattice interactions prevent the dissociation of oxidized dimers that occurs in solution and stabilize an equilibrium distribution of pentacoordinate and hexacoordinate high spin species

The first ASIC prototype of a 28 nm time-space front-end electronics for real-time tracking

A front-end ASIC for 4D tracking is presented. The prototype includes the block necessary to build a pixel front-end chain for timing measurement, as independent circuits. The architecture includes a charge-sensitive amplifier, a discriminator with programmable threshold, and a time- to-digital converter. The blocks were designed with target specifications in mind including: an area occupation of 55 μm × 55 μm, a power consumption tens of micro ampere per channel and timing a resolution of at least 100 ps. The prototype has been designed and integrated in 28 nm CMOS technology. The presented design is part of the TimeSpOT project which aims to reach a high-resolution particle tracking both in space and in time, in order to provide front-end circuitry suitable for next generation colliders

Results from CHIPIX-FE0, a Small Scale Prototype of a New Generation Pixel Readout ASIC in 65nm CMOS for HL-LHC

CHIPIX65-FE0 is a readout ASIC in CMOS 65nm designed by the CHIPIX65 project for a pixel detector at the HL-LHC, consisting of a matrix of 64x64 pixels of dimension 50x50 μm2. It is fully functional, can work at low thresholds down to 250e− and satisfies all the specifications. Results confirm low-noise, fast performance of both the synchronous and asynchronous front-end in a complex digital chip. CHIPIX65-FE0 has been irradiated up to 600 Mrad and is only marginally affected on analog performance. Further irradiation to 1 Grad will be performed. Bump bonding to silicon sensors is now on going and detailed measurements will be presented. The HL-LHC accelerator will constitute a new frontier for particle physics after year 2024. One major experimental challenge resides in the inner tracking detectors, measuring particle position: here the dimension of the sensitive area (pixel) has to be scaled down with respect to LHC detectors. This paper describes the results obtained by CHIPIX65-FE0, a readout ASIC in CMOS 65nm designed by the CHIPIX65 project as small-scale demonstrator for a pixel detector at the HL-LHC. It consists of a matrix of 64x64 pixels of dimension 50x50 um2 pixels and contains several pieces that are included in RD53A, a large scale ASIC designed by the RD53 Collaboration: two out of three front-ends (a synchronous and an asynchronous architecture); several building blocks; a (4x4) pixel region digital architecture with central local buffer storage, complying with a 3 GHz/cm2 hit rate and a 1 MHz trigger rate maintaining a very high efficiency (above 99%). The chip is 100% functional, either running in triggered or trigger-less mode. All building-blocks (DAC, ADC, Band Gap, SER, sLVS-TX/RX) and very front ends are working as expected. Analog performance shows a remarkably low ENC of 90e-, a fast-rise time below 25ns and low-power consumption (about 4μA/pixel) in both synchronous and asynchronous front-ends; a very linear behavior of CSA and discriminator. No significant cross talk from digital electronics has been measured, achieving a low threshold of 250e-. Signal digitization is obtained with a 5b-Time over Threshold technique and is shown to be fairly linear, working well either at 80 MHz or with higher frequencies of 300 MHz obtained with a tunable local oscillator. Irradiation results up to 600 Mrad at low temperature (-20°C) show that the chip is still fully functional and analog performance is only marginally degraded. Further irradiation will be performed up to 1 Grad either at low or room temperature, to further understand the level of radiation hardness of CHIPIX65-FE0. We are now in the process of bump bonding CHIPIX65-FE0 to 3D and possibly planar silicon sensors during spring. Detailed results will be presented in the conference paper

Acute Delta Hepatitis in Italy spanning three decades (1991–2019): Evidence for the effectiveness of the hepatitis B vaccination campaign

Updated incidence data of acute Delta virus hepatitis (HDV) are lacking worldwide. Our aim was to evaluate incidence of and risk factors for acute HDV in Italy after the introduction of the compulsory vaccination against hepatitis B virus (HBV) in 1991. Data were obtained from the National Surveillance System of acute viral hepatitis (SEIEVA). Independent predictors of HDV were assessed by logistic-regression analysis. The incidence of acute HDV per 1-million population declined from 3.2 cases in 1987 to 0.04 in 2019, parallel to that of acute HBV per 100,000 from 10.0 to 0.39 cases during the same period. The median age of cases increased from 27 years in the decade 1991-1999 to 44 years in the decade 2010-2019 (p < .001). Over the same period, the male/female ratio decreased from 3.8 to 2.1, the proportion of coinfections increased from 55% to 75% (p = .003) and that of HBsAg positive acute hepatitis tested for by IgM anti-HDV linearly decreased from 50.1% to 34.1% (p < .001). People born abroad accounted for 24.6% of cases in 2004-2010 and 32.1% in 2011-2019. In the period 2010-2019, risky sexual behaviour (O.R. 4.2; 95%CI: 1.4-12.8) was the sole independent predictor of acute HDV; conversely intravenous drug use was no longer associated (O.R. 1.25; 95%CI: 0.15-10.22) with this. In conclusion, HBV vaccination was an effective measure to control acute HDV. Intravenous drug use is no longer an efficient mode of HDV spread. Testing for IgM-anti HDV is a grey area requiring alert. Acute HDV in foreigners should be monitored in the years to come

Il diritto allo studio e le problematiche connesse all'accesso programmato ai corsi di stuio universitari. Il numero chiuso all'Università di Pisa.

Nel nostro ordinamento il diritto allo studio è un diritto soggettivo che trova il suo fondamento nei comma 3 e 4 dell'art. 34 della Costituzione, nei quali si afferma il diritto dei capaci e meritevoli, anche se privi di mezzi economici, di raggiungere i gradi più alti degli studi, e il dovere della Repubblica a rendere effettivo questo diritto. Il diritto allo studio trova un fondamento anche nell'art. 3 della Costituzione dove si afferma che è “compito della Repubblica rimuovere gli ostacoli di ordine economico e sociale che, limitando di fatto la libertà e l'uguaglianza dei cittadini, impediscono il pieno sviluppo della persona umana”. Dunque tutti i cittadini capaci hanno il diritto di proseguire gli studi al termine degli otto anni di scuola obbligatoria prescritti dalla Carta Costituzionale (comma 1 e 2 dell'art. 34) e la Repubblica ha il dovere di rimuovere quegli ostacoli economici che impediscono agli studenti capaci di continuare e completare gli studi scolastici non obbligatori nonché quelli universitari. Questo lavoro è indirizzato allo studio delle politiche attuate dal legislatore dall'unità d'Italia fino ai giorni nostri finalizzate alla tutela del diritto allo studio universitario dando grande attenzione alle problematiche effettive che in ogni epoca gli studenti universitari si sono trovati ad affrontare e le azioni attuate dal Parlamento, dai Governi e dai Consigli regionali per rendere concreti i principi espressi nell'art. 34 della Costituzione. Rispetto ad ogni scelta del legislatore sono stati riportati anche i diversi punti di vista della dottrina, con l'obiettivo di offrire al lettore un quadro il più possibile completo degli aspetti critici di ciascun atto normativo, nonché dei risultati conseguenti. Nell'analisi delle leggi e dei decreti riguardanti il diritto allo studio universitario possiamo notare che nel corso degli anni, quattro sono stati i temi che più di altri sono stati oggetto di analisi e di dibattito politico e dottrinario: il tipo di ripartizione di competenze tra Stato, Regioni e Università, il passaggio dell'assistenza universitaria da azione quasi caritatevole a diritto soggettivo degli studenti, la controversia riguardante i criteri di reddito e quelli di merito nell'individuazione dei beneficiari delle prestazioni e, infine, le specifiche tipologie di servizi da garantire agli studenti. Particolare attenzione è stata dedicata all'analisi della programmazione degli accessi (cd numero chiuso) e alle conseguenze sulla disciplina del diritto allo studio

DNA condensation and self-aggregation of Escherichia coli DPS are coupled phenomena related to the properties of the N-terminus

Escherichia coli Dps (DNA-binding proteins from starved cells) is the prototype of a DNA-protecting protein family expressed by bacteria under nutritional and oxidative stress. The role of the lysine-rich and highly mobile Dps N-terminus in DNA protection has been investigated by comparing the self-aggregation and DNA-condensation capacity of wild-type Dps and two N-terminal deletion mutants, DpsDelta8 and DpsDelta18, lacking two or all three lysine residues, respectively. Gel mobility and atomic force microscopy imaging showed that at pH 6.3, both wild type and DpsDelta8 self-aggregate, leading to formation of oligomers of variable size, and condense DNA with formation of large Dps-DNA complexes. Conversely, DpsDelta18 does not self-aggregate and binds DNA without causing condensation. At pH 8.2, DpsDelta8 and DpsDelta18 neither self-aggregate nor cause DNA condensation, a behavior also displayed by wild-type Dps at pH 8.7. Thus, Dps self-aggregation and Dps-driven DNA condensation are parallel phenomena that reflect the properties of the N-terminus. DNA protection against the toxic action of Fe(II) and H2O2 is not affected by the N-terminal deletions either in vitro or in vivo, in accordance with the different structural basis of this property

DNA condensation and self-aggregation of Escherichia coli Dps are coupled phenomena related to the properties of the N-terminus

Escherichia coli Dps (DNA-binding proteins from starved cells) is the prototype of a DNA-protecting protein family expressed by bacteria under nutritional and oxidative stress. The role of the lysine-rich and highly mobile Dps N-terminus in DNA protection has been investigated by comparing the self-aggregation and DNA-condensation capacity of wild-type Dps and two N-terminal deletion mutants, DpsΔ8 and DpsΔ18, lacking two or all three lysine residues, respectively. Gel mobility and atomic force microscopy imaging showed that at pH 6.3, both wild type and DpsΔ8 self-aggregate, leading to formation of oligomers of variable size, and condense DNA with formation of large Dps–DNA complexes. Conversely, DpsΔ18 does not self-aggregate and binds DNA without causing condensation. At pH 8.2, DpsΔ8 and DpsΔ18 neither self-aggregate nor cause DNA condensation, a behavior also displayed by wild-type Dps at pH 8.7. Thus, Dps self-aggregation and Dps-driven DNA condensation are parallel phenomena that reflect the properties of the N-terminus. DNA protection against the toxic action of Fe(II) and H(2)O(2) is not affected by the N-terminal deletions either in vitro or in vivo, in accordance with the different structural basis of this property