Comparison theorems of GAGA type and Serre duality

Nella tesi si studiano le varietà algebriche e in particolare quelle proiettive. Data una varietà algebrica definita sul campo complesso con la topologia di Zariski, si analizza la corrispondenza tra le proprietà topologiche di separatezza, completezza e irriducibilità e, rispettivamente, l'essere Hausdoff, la compattezza e la connessione dello spazio analitico associato. In particolare si dimostra che lo spazio proiettivo, e di conseguenza tutte le varietà proiettive, sono separate e complete. Si generalizza inoltre la nozione di varietà a quella di schema e si calcola la coomologia di fasci coerenti sullo spazio proiettivo. Si dimostra infine il teorema di dualità di Serre per fasci coerenti su uno schema proiettivo arbitrario

Classificazione delle curve ellittiche viste come curve algebriche piane

Nel presente lavoro è affrontato lo studio delle curve ellittiche viste come curve algebriche piane, più precisamente come cubiche lisce nel piano proiettivo complesso. Dopo aver introdotto nella prima parte le nozioni di Superfici compatte e orientabili e curve algebriche, tramite il teorema di classificazione delle Superfici compatte, se ne fornisce una preliminare classificazione basata sul genere della superficie e della curva, rispettivamente. Da qui, segue la definizione di curve ellittiche e uno studio più dettagliato delle loro pricipali proprietà, quali la possibilità di definirle tramite un'equazione affine nota come equazione di Weierstrass e la loro struttura intrinseca di gruppo abeliano. Si fornisce quindi un'ulteriore classificazione delle cubiche lisce, totalmente differente da quella precedente, che si basa invece sul modulo della cubica, invariante per trasformazioni proiettive. Infine, si considera un aspetto computazionale delle curve ellittiche, ovvero la loro applicazione nel campo della Crittografia. Grazie alla struttura che esse assumono sui campi finiti, sotto opportune ipotesi, i crittosistemi a chiave pubblica basati sul problema del logaritmo discreto definiti sulle curve ellittiche, a parità di sicurezza rispetto ai crittosistemi classici, permettono l'utilizzo di chiavi più corte, e quindi meno costose computazionalmente. Si forniscono quindi le definizioni di problema del logaritmo discreto classico e sulle curve ellittiche, ed alcuni esempi di algoritmi crittografici classici definiti su quest'ultime

FINCH: A Blueprint for Accessible and Scientifically Valuable Remote Sensing Satellite Missions

Satellite remote sensing missions have grown in popularity over the past fifteen years due to their ability to cover large swaths of land at regular time intervals, making them suitable for monitoring environmental trends such as greenhouse gas emissions and agricultural practices. As environmental monitoring becomes central in global efforts to combat climate change, accessible platforms for contributing to this research are critical. Many remote sensing missions demand high performance of payloads, restricting research and development to organizations with sufficient resources to address these challenges. Atmospheric remote sensing missions, for example, require extremely high spatial and spectral resolutions to generate scientifically useful results. As an undergraduate-led design team, the University of Toronto Aerospace Team’s Space Systems Division has performed an extensive mission selection process to find a feasible and impactful mission focusing on crop residue mapping. This mission profile provides the data needed to improve crop residue retention practices and reduce greenhouse gas emissions from soil, while relaxing performance requirements relative to many active atmospheric sensing missions. This is accompanied by the design of FINCH, a 3U CubeSat with a hyperspectral camera composed of custom and commercial off-the-shelf components. The team’s custom composite payload, the FINCH Eye, strives to advance performance achieved at this form factor by leveraging novel technologies while keeping design feasibility for a student team a priority. Optical and mechanical design decisions and performance are detailed, as well as assembly, integration, and testing considerations. Beyond its design, the FINCH Eye is examined from operational, timeline, and financial perspectives, and a discussion of the supporting firmware, data processing, and attitude control systems is included. Insight is provided into open-source tools that the team has developed to aid in the design process, including a linear error analysis tool for assessing scientific performance, an optical system tradeoff analysis tool, and data processing algorithms. Ultimately, the team presents a comprehensive case study of an accessible and impactful satellite optical payload design process, in hopes of serving as a blueprint for future design teams seeking to contribute to remote sensing research

Octyl itaconate enhances VSVΔ51 oncolytic virotherapy by multitarget inhibition of antiviral and inflammatory pathways

The presence of heterogeneity in responses to oncolytic virotherapy poses a barrier to clinical effectiveness, as resistance to this treatment can occur through the inhibition of viral spread within the tumor, potentially leading to treatment failures. Here we show that 4-octyl itaconate (4-OI), a chemical derivative of the Krebs cycle-derived metabolite itaconate, enhances oncolytic virotherapy with VSVΔ51 in various models including human and murine resistant cancer cell lines, three-dimensional (3D) patient-derived colon tumoroids and organotypic brain tumor slices. Furthermore, 4-OI in combination with VSVΔ51 improves therapeutic outcomes in a resistant murine colon tumor model. Mechanistically, we find that 4-OI suppresses antiviral immunity in cancer cells through the modification of cysteine residues in MAVS and IKKβ independently of the NRF2/KEAP1 axis. We propose that the combination of a metabolite-derived drug with an oncolytic virus agent can greatly improve anticancer therapeutic outcomes by direct interference with the type I IFN and NF-κB-mediated antiviral responses.</p

Octyl itaconate enhances VSVΔ51 oncolytic virotherapy by multitarget inhibition of antiviral and inflammatory pathways

The presence of heterogeneity in responses to oncolytic virotherapy poses a barrier to clinical effectiveness, as resistance to this treatment can occur through the inhibition of viral spread within the tumor, potentially leading to treatment failures. Here we show that 4-octyl itaconate (4-OI), a chemical derivative of the Krebs cycle-derived metabolite itaconate, enhances oncolytic virotherapy with VSVΔ51 in various models including human and murine resistant cancer cell lines, three-dimensional (3D) patient-derived colon tumoroids and organotypic brain tumor slices. Furthermore, 4-OI in combination with VSVΔ51 improves therapeutic outcomes in a resistant murine colon tumor model. Mechanistically, we find that 4-OI suppresses antiviral immunity in cancer cells through the modification of cysteine residues in MAVS and IKKβ independently of the NRF2/KEAP1 axis. We propose that the combination of a metabolite-derived drug with an oncolytic virus agent can greatly improve anticancer therapeutic outcomes by direct interference with the type I IFN and NF-κB-mediated antiviral responses.</p

BLOOM: A 176B-Parameter Open-Access Multilingual Language Model

Large language models (LLMs) have been shown to be able to perform new tasks based on a few demonstrations or natural language instructions. While these capabilities have led to widespread adoption, most LLMs are developed by resource-rich organizations and are frequently kept from the public. As a step towards democratizing this powerful technology, we present BLOOM, a 176B-parameter open-access language model designed and built thanks to a collaboration of hundreds of researchers. BLOOM is a decoder-only Transformer language model that was trained on the ROOTS corpus, a dataset comprising hundreds of sources in 46 natural and 13 programming languages (59 in total). We find that BLOOM achieves competitive performance on a wide variety of benchmarks, with stronger results after undergoing multitask prompted finetuning. To facilitate future research and applications using LLMs, we publicly release our models and code under the Responsible AI License

Canagliflozin and renal outcomes in type 2 diabetes and nephropathy

BACKGROUND Type 2 diabetes mellitus is the leading cause of kidney failure worldwide, but few effective long-term treatments are available. In cardiovascular trials of inhibitors of sodium–glucose cotransporter 2 (SGLT2), exploratory results have suggested that such drugs may improve renal outcomes in patients with type 2 diabetes. METHODS In this double-blind, randomized trial, we assigned patients with type 2 diabetes and albuminuric chronic kidney disease to receive canagliflozin, an oral SGLT2 inhibitor, at a dose of 100 mg daily or placebo. All the patients had an estimated glomerular filtration rate (GFR) of 30 to &lt;90 ml per minute per 1.73 m2 of body-surface area and albuminuria (ratio of albumin [mg] to creatinine [g], &gt;300 to 5000) and were treated with renin–angiotensin system blockade. The primary outcome was a composite of end-stage kidney disease (dialysis, transplantation, or a sustained estimated GFR of &lt;15 ml per minute per 1.73 m2), a doubling of the serum creatinine level, or death from renal or cardiovascular causes. Prespecified secondary outcomes were tested hierarchically. RESULTS The trial was stopped early after a planned interim analysis on the recommendation of the data and safety monitoring committee. At that time, 4401 patients had undergone randomization, with a median follow-up of 2.62 years. The relative risk of the primary outcome was 30% lower in the canagliflozin group than in the placebo group, with event rates of 43.2 and 61.2 per 1000 patient-years, respectively (hazard ratio, 0.70; 95% confidence interval [CI], 0.59 to 0.82; P=0.00001). The relative risk of the renal-specific composite of end-stage kidney disease, a doubling of the creatinine level, or death from renal causes was lower by 34% (hazard ratio, 0.66; 95% CI, 0.53 to 0.81; P&lt;0.001), and the relative risk of end-stage kidney disease was lower by 32% (hazard ratio, 0.68; 95% CI, 0.54 to 0.86; P=0.002). The canagliflozin group also had a lower risk of cardiovascular death, myocardial infarction, or stroke (hazard ratio, 0.80; 95% CI, 0.67 to 0.95; P=0.01) and hospitalization for heart failure (hazard ratio, 0.61; 95% CI, 0.47 to 0.80; P&lt;0.001). There were no significant differences in rates of amputation or fracture. CONCLUSIONS In patients with type 2 diabetes and kidney disease, the risk of kidney failure and cardiovascular events was lower in the canagliflozin group than in the placebo group at a median follow-up of 2.62 years

The SIB Swiss Institute of Bioinformatics' resources: focus on curated databases

The SIB Swiss Institute of Bioinformatics (www.isb-sib.ch) provides world-class bioinformatics databases, software tools, services and training to the international life science community in academia and industry. These solutions allow life scientists to turn the exponentially growing amount of data into knowledge. Here, we provide an overview of SIB's resources and competence areas, with a strong focus on curated databases and SIB's most popular and widely used resources. In particular, SIB's Bioinformatics resource portal ExPASy features over 150 resources, including UniProtKB/Swiss-Prot, ENZYME, PROSITE, neXtProt, STRING, UniCarbKB, SugarBindDB, SwissRegulon, EPD, arrayMap, Bgee, SWISS-MODEL Repository, OMA, OrthoDB and other databases, which are briefly described in this article