Archivio Istituzionale della Ricerca - Università degli Studi di Pavia
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Mapping neutron biological effectiveness for DNA damage induction as a function of incident energy and depth in a human sized phantom
No full textWe present new developments for an ab-initio model of the neutron relative biological effectiveness (RBE) in inducing specific classes of DNA damage. RBE is evaluated as a function of the incident neutron energy and of the depth inside a human-sized reference spherical phantom. The adopted mechanistic approach traces neutron RBE back to its origin, i.e. neutron physical interactions with biological tissues. To this aim, we combined the simulation of radiation transport through biological matter, performed with the Monte Carlo code PHITS, and the prediction of DNA damage using analytical formulas, which ground on a large database of biophysical radiation track structure simulations performed with the code PARTRAC. In particular, two classes of DNA damage were considered: sites and clusters of double-strand breaks (DSBs), which are known to be correlated with cell fate following radiation exposure. Within a coherent modelling framework, this approach tackles the variation of neutron RBE in a wide energy range, from thermal neutrons to neutrons of hundreds of GeV, and reproduces effects related to depth in the human-sized receptor, as well as to the receptor size itself. Besides providing a better mechanistic understanding of neutron biological effectiveness, the new model can support better-informed decisions for radiation protection: indeed, current neutron weighting (ICRP)/quality (U.S. NRC) factors might be insufficient for use in some radiation protection applications, because they do not account for depth. RBE predictions obtained with the reported model were successfully compared to the currently adopted radiation protection standards when the depth information is not relevant (at the shallowest depth in the phantom or for very high energy neutrons). However, our results demonstrate that great care is needed when applying weighting factors as a function of incident neutron energy only, not explicitly considering RBE variation in the target. Finally, to facilitate the use of our results, we propose look-up RBE tables, explicitly considering the depth variable, and an analytical representation of the maximal RBE vs. neutron energy
Chiral heterogeneous photocatalysts for enantioselective synthesis: standing on the shoulders of organocatalysis
No full textCrafting organic molecules with control over their absolute stereochemistry is a challenging task for synthetic chemists. The present Perspective encompasses recent examples of enantioselective transformations based on chiral heterogeneous photocatalysts, including metal–organic frameworks (MOFs), covalent organic frameworks (COFs) and hybrid metal-halide perovskites (MHPs). Such materials combine a photocatalytic unit and a chiral element in a single component: the former is responsible for substrate activation, while the latter, typically a small organic molecule – i.e., an organocatalyst –, takes care of stereoinduction instead. Although synthetic applications are still limited to a handful of (benchmark) C–C and C–N bond formations and oxidation protocols, their number is expected to grow steadily in the near future. This trend is supported by cross-disciplinary knowledge transfer from the field of asymmetric organocatalysis, which is also driving the application of these materials in broader areas, such as solar-to-chemical energy conversion and chiral sensing technologies
Hyperbolic Relaxation of the Chemical Potential in the Viscous Cahn–Hilliard Equation
No full textIn this paper, we study a hyperbolic relaxation of the viscous Cahn–Hilliard system with zero Neumann boundary conditions. In fact, we consider a relaxation term involving the second time derivative of the chemical potential in the first equation of the system. We develop a well-posedness, continuous dependence and regularity theory for the initial-boundary value problem. Moreover, we investigate the asymptotic behavior of the system as the relaxation parameter tends to 0 and prove the convergence to the viscous Cahn–Hilliard system
HER2, HER3, and Mismatch Repair Protein Expression in Stage IV Small Bowel Adenocarcinoma: Results From a Multicenter Series
No full textSmall bowel adenocarcinoma (SBA) is a rare and aggressive malignancy. One-third of SBA cases are diagnosed at an advanced stage, often with limited treatment options. Recent clinical trials have underscored the importance of testing predictive biomarkers for therapy response in advanced solid tumors, particularly with respect to antibody-drug conjugates and immunotherapy. However, few studies have investigated the expression of mismatch repair (MMR) proteins, HER2, and HER3 in metastatic SBA. In this study, the immunohistochemical expression of MMR proteins, HER2 (using gastric cancer scoring criteria), and HER3 was assessed in a multicentric series of 26 stage IV SBAs. In 7 cases, tissues from both the primary tumor and paired distant metastasis were tested for all biomarkers, and any discordance in biomarker expression (ie, spatial heterogeneity) was recorded. For comparison, a cohort of 47 stage III SBA patients was also evaluated. MMR deficiency (MMRd), HER2 positivity (score 3+ or 2+ with gene amplification), and HER3 positivity were identified in 11.5%, 7.7%, and 40% of stage IV SBAs, respectively, with limited overlap among the biomarkers. One stage IV SBA showed heterogeneous MMR status, with a distinct subclone lacking MSH6 expression. When stage III SBAs were compared with stage IV SBAs, MMRd was more frequent (31.9%) among stage III SBAs. In 1 case (14%), the primary tumor was MMR-proficient, HER2-negative, and HER3-negative, whereas the metachronous distant metastasis was MMR-deficient, HER2-negative, and HER3-positive. The percentage of MMRd and HER2 positivity observed in stage IV SBAs highlights the need to assess HER2 and MMR status in these rare tumors. Our findings also suggest that evaluating the response of SBAs to anti-HER3 therapies should be considered in future clinical trials. Additionally, evidence of spatial heterogeneity in biomarker expression emphasizes the importance of assessing biomarkers in metastatic tissue to identify actionable alterations that may not be present in the primary tumor
The Mini-CAARMS: Development and Validation of a Short Version of the Comprehensive Assessment of AT Risk Mental States to Facilitate Preventive Psychiatry
No full textBackground and Hypothesis Accurate detection of individuals at risk for psychosis with established psychometric instruments such as the Comprehensive Assessment of At-Risk Mental States (CAARMS/2006) is crucial to implement effective preventive strategies. However, the CAARMS/2006's scalability is limited by its lengthy administration. This study developed and validated a shorter CAARMS/2006 version: the mini-CAARMS.Study Design A total of 490 participants (mean age 23.8 +/- 5 years) underwent the full CAARMS/2006 interview (60 items, all individually scored). The development and validation of the mini-CAARMS employed advanced statistical methods: regularized logistic regression with a LASSO penalty within a nested cross-validation framework to retain core items; Cohen's kappa, Harrell's C index, sensitivity, specificity, balanced accuracy, positive (PPV) and negative (NPV) predictive values to assess performance; Monte Carlo simulations to assess the 2-year prognostic accuracy for predicting psychosis onset. A sensitivity analysis developed and validated an ultra-mini-CAARMS.Study Results The mini-CAARMS retained only 23 items and demonstrated excellent accuracy compared to the full version: Cohen's kappa 0.90; Harrell's C index 0.93, sensitivity 95.6%, specificity 100%, balanced accuracy 97.8%, PPV 100%, and NPV 86.3%. The prognostic sensitivity and specificity of the mini-CAARMS were 82.2% and 55.1%, respectively. Sensitivity analyses further developed and validated an ultra-mini-CAARMS (based on 12 items only), which achieved comparable performance, with kappa 0.90, C index 0.91, sensitivity 94.4%, balanced accuracy 97.2%, PPV 100%, NPV 82.2%, and prognostic sensitivity and specificity 81.2% and 55.1%, respectively.Conclusions The mini-CAARMS maintains high accuracy while substantially reducing administration time, and it could facilitate scalability of preventive psychiatry in low-resource settings
A 17-mK Resolution ΣΔ-Based Temperature Sensor With an On-Chip Single-Point Calibrated Inaccuracy of ±1.5 °C (3σ)
No full textThis work presents the design of a bipolar junction transistor (BJT)-based temperature sensor with a sigma-delta analog-to-digital converter ( \Sigma \Delta ADC) fabricated in a 0.6 \mu m BiCMOS process. The sensor utilizes a proportional to absolute temperature (PTAT) current source embedding an auto-zeroing amplifier to bias the BJT core while effectively reducing offset errors. Additionally, this work achieves the combination of the temperature-sensing BJT core and the Σ∆ modulator, utilizing dynamic element matching (DEM) technique to accurately generate three different ratios (1:9, 9:1, 5:5) of BJT bias currents to cooperate with the modulator for modulation. The innovative modulation method in this work can reduce the errors caused by the operational amplifier offset voltage and BJT mismatch, completing the digitization of temperature without the need for a reference voltage source. Moreover, the sensor integrates a complete digital signal processor (DSP), allowing on-chip calibration by adjusting the operating cycle of the modulator and the initial value of the counter to obtain accurate and directly readable temperature data. It operates under a 3.3 V supply within a temperature range from −50 °C to 125 °C. Lastly, it achieves a 17 mK resolution and an inaccuracy of ±1.5 °C (3 σ ) after an on-chip single-point calibration
British Museum Burney 86, f. 113r: Hom., Il. 11.316-342 with scholia
No full textDigital diplomatic transcription produced with the web application DDEB for the RHT – Repertoire of Hypertext Transcriptions (https://paratext.unipv.it/rht-repertoire-of-hypertext-transcriptions/)
Verso la Valutazione Automatizzata dell’Italiano L2: ETET tra LLM e Tecnologie Vocali
No full textThis paper presents ETET, a web-based application for the automated assessment of L2 proficiency. The main contribution of this work lies in its focus on Italian – a language for which no comparable tools currently exist. Another novelty is the departure from traditional assessment models. In fact, the theoretical framework is grounded in CEFR and Processability Theory, allowing an assessment that reflects the natural developmental sequences of the learners’ interlanguage. ETET is not intended to replace human raters, but rather to serve as a complementary tool, since it ensures rapid scoring. Additionally, it has customizable and diversified test formats and items, making it a resource suitable for educational contexts, certification, and selection purposes
