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Bioethanol has been successfully produced from sorghum (Sorghum bicolor L.) seed dregs as a biofuel to replace fossil fuels. The goal of this study is to find out what sulfuric acid concentration produces sugar content during hydrolysis utilizing microwave and an autoclave. The concentrations of sulfuric acid used in this experiment were 0.5, 1, 2, and 5%. The hydrolysis of sorghum brans is suspended with a sulfuric acid solution, then in the hydrolysis using microwave (temperature 150°C for 30 minutes) and autoclave (pressurized 1 atm temperature 121 °C for 30 minutes). The fermentation using yeast saccharomyces cerevisiae for 5 days. The analyzed through reducing sugar content using UV-VIS, then morphology of sorghum brans using SEM, the density of ethanol using pycnometer, and analysis ethanol levels using GC. The analysis used SEM is sulfuric acid was able to damage the surface structure of sorghum brans. Produced the optimum reducing glucose occurred in hydrolysis using a microwave with a sulfuric acid concentration of 1% is 44,97 gr/L, then using methods autoclave produced the optimum glucose reducing with a sulfuric acid concentration of 5 % is 30,86 g/L. The analysis ethanol used pycnometer is 1,96%. and gas chromatography converting of ethanol was 15.76%.

One of the most urgent challenges for European academic and cultural institutions is to promote an intelligent use of materials and resources available on the web, by implementing best practices of web archiving, and building scientifically valid databases which can have a positive social impact. This paper will present the theoretical and methodological framework of Eredità Culturali, an ongoing project that aims at answering this challenge by focusing on the Florentine cultural heritage. The first stage of Eredità Culturali consisted in surveying similar initiatives within the European research landscape and examining national and international cataloguing models and standards to build a data entry prototype that interacts with other systems. Hence, a flexible and open-access web platform has been designed to validate, preserve and consult cultural information from disparate data sets into a single archive. A geo-referenced information system has also been developed, in which four databases designed by the Department's research groups of Geography, Archaeology, Performing Arts and History of the Book will converge and make sound data available for both non-academic and professional audiences. The analytical investigation is integrated with original ways of dissemination that will facilitate historical connections between different cultural heritages and legacies., Umanistica Digitale, No. 15 (2023)

PURPOSE Nivolumab and relatlimab activity in advanced melanoma with prior progression on anti–programmed death-1/programmed death ligand 1 (PD-(L)1)-containing regimens is under investigation. RELATIVITY-047 demonstrated significantly improved progression-free survival (PFS) for nivolumab and relatlimab over nivolumab in previously untreated advanced melanoma. METHODS The phase I/IIa, open-label RELATIVITY-020 trial part D assessed efficacy and safety of nivolumab and relatlimab in advanced melanoma with progression during, or within 3 months of, 1 (D1) or ≥ 1 (D2) anti–PD-(L)1-containing regimens. Safety was a primary end point. Objective response rate (coprimary end point) and PFS by blinded independent central review (BICR) were assessed. RESULTS Five hundred eighteen patients (D1 = 354; D2 = 164) received nivolumab and relatlimab. Among evaluable patients, the objective response rate by BICR was 12.0% (95% CI, 8.8 to 15.8) in D1 (n = 351) and 9.2% (95% CI, 5.2 to 14.7) in D2 (n = 163). Responses appeared to be enriched among patients with tumors expressing programmed death ligand 1 or lymphocyte activation gene 3; however, responses were observed regardless of programmed death ligand 1 and lymphocyte activation gene 3 expression (1%). The median duration of response was not reached (95% CI, 12.9 to not reached) in D1 and 12.8 months (95% CI, 6.9 to 12.9) in D2. The median PFS by BICR was 2.1 months (95% CI, 1.9 to 3.5) in D1 and 3.2 months (95% CI, 1.9 to 3.6) in D2; the 6-month PFS rate was 29.1% (95% CI, 24.2 to 34.1) and 27.7% (95% CI, 20.5 to 35.4), respectively. The grade 3-4 treatment-related adverse event incidence was 15.0% in D1 and 12.8% in D2. One case of grade 3 myocarditis and no treatment-related deaths occurred across part D. CONCLUSION Nivolumab and relatlimab had a manageable safety profile and demonstrated durable clinical activity in a proportion of patients with heavily pretreated advanced melanoma with prior progression on anti–PD-(L)1-containing regimens. [Media: see text]

DATA SUPPLEMENT Adjuvant Nivolumab Versus Ipilimumab in Resected Stage III/IV Melanoma: 5-Year Efficacy and Biomarker Results From CheckMate 238

Purpose:In the phase III CheckMate 238 study, adjuvant nivolumab significantly improved recurrence-free survival (RFS) and distant metastasis-free survival versus ipilimumab in patients with resected stage IIIB–C or stage IV melanoma, with benefit sustained at 4 years. We report updated 5-year efficacy and biomarker findings.Patients and Methods:Patients with resected stage IIIB–C/IV melanoma were stratified by stage and baseline programmed death cell ligand 1 (PD-L1) expression and received nivolumab 3 mg/kg every 2 weeks or ipilimumab 10 mg/kg every 3 weeks for four doses and then every 12 weeks, both intravenously for 1 year until disease recurrence, unacceptable toxicity, or withdrawal of consent. The primary endpoint was RFS.Results:At a minimum follow-up of 62 months, RFS with nivolumab remained superior to ipilimumab (HR = 0.72; 95% confidence interval, 0.60–0.86; 5-year rates of 50% vs. 39%). Five-year distant metastasis-free survival (DMFS) rates were 58% with nivolumab versus 51% with ipilimumab. Five-year overall survival (OS) rates were 76% with nivolumab and 72% with ipilimumab (75% data maturity: 228 of 302 planned events). Higher levels of tumor mutational burden (TMB), tumor PD-L1, intratumoral CD8+ T cells and IFNγ-associated gene expression signature, and lower levels of peripheral serum C-reactive protein were associated with improved RFS and OS with both nivolumab and ipilimumab, albeit with limited clinically meaningful predictive value.Conclusions:Nivolumab is a proven adjuvant treatment for resected melanoma at high risk of recurrence, with sustained, long-term improvement in RFS and DMFS compared with ipilimumab and high OS rates. Identification of additional biomarkers is needed to better predict treatment outcome.

NLR family, apoptosis inhibitory proteins (NAIPs) detect bacterial flagellin and structurally related components of bacterial type III secretion systems (T3SS), and recruit NLR family, CARD domain containing protein 4 (NLRC4) and caspase-1 into an inflammasome complex that induces pyroptosis. NAIP/NLRC4 inflammasome assembly is initiated by the binding of a single NAIP to its cognate ligand, but a subset of bacterial flagellins or T3SS structural proteins are thought to evade NAIP/NLRC4 inflammasome sensing by not binding to their cognate NAIPs. Unlike other inflammasome components such as NLRP3, AIM2, or some NAIPs, NLRC4 is constitutively present in resting macrophages, and not thought to be regulated by inflammatory signals. Here, we demonstrate that Toll-like receptor (TLR) stimulation upregulates NLRC4 transcription and protein expression in murine macrophages, which licenses NAIP detection of evasive ligands. TLR-induced NLRC4 upregulation and NAIP detection of evasive ligands required p38 MAPK signaling. In contrast, TLR priming in human macrophages did not upregulate NLRC4 expression, and human macrophages remained unable to detect NAIP-evasive ligands even following priming. Critically, ectopic expression of either murine or human NLRC4 was sufficient to induce pyroptosis in response to immunoevasive NAIP ligands, indicating that increased levels of NLRC4 enable the NAIP/NLRC4 inflammasome to detect these normally evasive ligands. Altogether, our data reveal that TLR priming tunes the threshold for NAIP/NLRC4 inflammasome activation and enables inflammasome responses against immunoevasive or suboptimal NAIP ligands.Significance StatementCytosolic receptors in the neuronal apoptosis inhibitor protein (NAIP) family detect bacterial flagellin and components of the type III secretion system (T3SS). NAIP binding to its cognate ligand engages the adaptor molecule NLRC4 to form NAIP/NLRC4 inflammasomes culminating in inflammatory cell death. However, some bacterial pathogens evade NAIP/NLRC4 inflammasome detection, thus bypassing a crucial barrier of the immune system. Here, we find that, in murine macrophages, TLR-dependent p38 MAPK signaling increases NLRC4 expression, thereby lowering the threshold for NAIP/NLRC4 inflammasome activation in response to immunoevasive NAIP ligands. Human macrophages were unable to undergo priming-induced upregulation of NLRC4 and could not detect immunoevasive NAIP ligands. These findings provide a new insight into species-specific regulation of the NAIP/NLRC4 inflammasome.

Let $G$ be a finite group. Denoting by ${\rm{cd}}(G)$ the set of the degrees of the irreducible complex characters of $G$, we consider the {\it character degree graph} of $G$: this is the (simple, undirected) graph whose vertices are the prime divisors of the numbers in ${\rm{cd}}(G)$, and two distinct vertices $p$, $q$ are adjacent if and only if $pq$ divides some number in ${\rm{cd}}(G)$. This paper completes the classification, started in [5] and [6], of the finite non-solvable groups whose character degree graph has a {\it cut-vertex}, i.e. a vertex whose removal increases the number of connected components of the graph. More specifically, it was proved in [6] that these groups have a unique non-solvable composition factor $S$, and that $S$ is isomorphic to a group belonging to a restricted list of non-abelian simple groups. In [5] and [6] all isomorphism types for $S$ were treated, except the case \(S\cong{\rm{PSL}}_2(2^a)\) for some integer $a\geq 2$; the remaining case is addressed in the present paper., arXiv admin note: text overlap with arXiv:2208.03519