American String Trio Recital: Lucinda Marvin, Violin; Donna Lively Clark, Violin; Dennis McCafferty, Cello; Sylvia Morehead, Piano; November 21, 1975

Centennial East Recital HallFriday EveningNovember 21, 19758:15 p.m

Cooperazione interistituzionale nelle Pubbliche Amministrazioni: l'Ufficio intercomunale

Nell'ambito dello scenario istituzionale caratterizzato da profonde trasformazioni (si pensi ad esempio alla riforma del titolo V della Costituzione), l'innovazione nella pubblica amministrazione risulta assumere un importanza rilevante. Gli Enti Locali dovranno prepararsi ed adeguarsi a ricevere le funzioni e le responsabilita' derivanti dall'attuazione della riforma. In questo quadro di riferimento si inserisce il presente progetto che individua come idea forza la collaborazione inter-istituzionale come fattore decisivo nella valorizzazione e nell'uso strategico delle risorse turistico culturali del territorio preso in esame. L'area analizzata e' quella dell'alto Casertano, nello specifico i nove Comuni che hanno dimostrato una buona propensione alla collaborazione: Alife, Castello del Matese, Gallo Matese, Letino, Piedimonte Matese, San Gregorio Matese, San Potito Sannitico, Sant'Angelo d'Alife e Valle Agricola. L'idea progetto consiste nella stipulazione di una convenzione tra questi Comuni al fine di istituire un ufficio intercomunale per la gestione associata di diverse funzioni che risultano essere fondamentali per un maggiore coordinamento istituzionale. Il progetto e' strutturato secondo il seguente schema: analisi del cambiamento istituzionale risorse culturali come fattore di sviluppo analisi del quadro di riferimento territoriale analisi swot formulazione della strategia e degli obiettivi idea forza idea progetto aspetti tecnic

Targeting DNA Damage Response and Replication Stress in Pancreatic Cancer

Background and aims: Continuing recalcitrance to therapy cements pancreatic cancer (PC) as the most lethal malignancy, which is set to become the second leading cause of cancer death in our society. The study aim was to investigate the association between DNA damage response (DDR), replication stress and novel therapeutic response in PC to develop a biomarker driven therapeutic strategy targeting DDR and replication stress in PC. Methods: We interrogated the transcriptome, genome, proteome and functional characteristics of 61 novel PC patient-derived cell lines to define novel therapeutic strategies targeting DDR and replication stress. Validation was done in patient derived xenografts and human PC organoids. Results: Patient-derived cell lines faithfully recapitulate the epithelial component of pancreatic tumors including previously described molecular subtypes. Biomarkers of DDR deficiency, including a novel signature of homologous recombination deficiency, co-segregates with response to platinum (P < 0.001) and PARP inhibitor therapy (P < 0.001) in vitro and in vivo. We generated a novel signature of replication stress with which predicts response to ATR (P < 0.018) and WEE1 inhibitor (P < 0.029) treatment in both cell lines and human PC organoids. Replication stress was enriched in the squamous subtype of PC (P < 0.001) but not associated with DDR deficiency. Conclusions: Replication stress and DDR deficiency are independent of each other, creating opportunities for therapy in DDR proficient PC, and post-platinum therapy

The 2021 WHO catalogue of Mycobacterium tuberculosis complex mutations associated with drug resistance: a genotypic analysis.

Background: Molecular diagnostics are considered the most promising route to achievement of rapid, universal drug susceptibility testing for Mycobacterium tuberculosis complex (MTBC). We aimed to generate a WHO-endorsed catalogue of mutations to serve as a global standard for interpreting molecular information for drug resistance prediction. Methods: In this systematic analysis, we used a candidate gene approach to identify mutations associated with resistance or consistent with susceptibility for 13 WHO-endorsed antituberculosis drugs. We collected existing worldwide MTBC whole-genome sequencing data and phenotypic data from academic groups and consortia, reference laboratories, public health organisations, and published literature. We categorised phenotypes as follows: methods and critical concentrations currently endorsed by WHO (category 1); critical concentrations previously endorsed by WHO for those methods (category 2); methods or critical concentrations not currently endorsed by WHO (category 3). For each mutation, we used a contingency table of binary phenotypes and presence or absence of the mutation to compute positive predictive value, and we used Fisher's exact tests to generate odds ratios and Benjamini-Hochberg corrected p values. Mutations were graded as associated with resistance if present in at least five isolates, if the odds ratio was more than 1 with a statistically significant corrected p value, and if the lower bound of the 95% CI on the positive predictive value for phenotypic resistance was greater than 25%. A series of expert rules were applied for final confidence grading of each mutation. Findings: We analysed 41 137 MTBC isolates with phenotypic and whole-genome sequencing data from 45 countries. 38 215 MTBC isolates passed quality control steps and were included in the final analysis. 15 667 associations were computed for 13 211 unique mutations linked to one or more drugs. 1149 (7·3%) of 15 667 mutations were classified as associated with phenotypic resistance and 107 (0·7%) were deemed consistent with susceptibility. For rifampicin, isoniazid, ethambutol, fluoroquinolones, and streptomycin, the mutations' pooled sensitivity was more than 80%. Specificity was over 95% for all drugs except ethionamide (91·4%), moxifloxacin (91·6%) and ethambutol (93·3%). Only two resistance mutations were identified for bedaquiline, delamanid, clofazimine, and linezolid as prevalence of phenotypic resistance was low for these drugs. Interpretation: We present the first WHO-endorsed catalogue of molecular targets for MTBC drug susceptibility testing, which is intended to provide a global standard for resistance interpretation. The existence of this catalogue should encourage the implementation of molecular diagnostics by national tuberculosis programmes. Funding: Unitaid, Wellcome Trust, UK Medical Research Council, and Bill and Melinda Gates Foundation

Expanded Craters on Mars: Implications for Shallow, Mid-Latitude Excess Ice

Understanding the age and distribution of shallow ice on Mars is valuable for interpreting past and present climate conditions, and has implications on habitability and future in situ resource utilization. Many ice-related features, such as lobate debris aprons and concentric crater fill, have been studied using a range of remote sensing techniques. Here, I explore the distribution of expanded craters, a form of sublimation thermokarst where shallow, excess ice has been destabilized and sublimated following an impact event. This leads to the collapse of the overlying dry regolith to produce the appearance of diameter widening. The modern presence of these features suggests that excess ice has remained preserved in the terrain immediately surrounding the craters since the time of their formation in order to maintain the surface. High-resolution imagery is ideal for observing thermokarst features, and much of the work described here will utilize data from the Context Camera (CTX) and High Resolution Imaging Science Experiment (HiRISE) on the Mars Reconnaissance Orbiter (MRO). Expanded craters tend to be found in clusters that emanate radially from at least four primary craters in Arcadia Planitia, and are interpreted as secondary craters that formed nearly simultaneously with their primaries. Crater age dates of the primaries indicate that the expanded secondaries, as well as the ice layer into which they impacted, must be at least tens of millions of years old. Older double-layer ejecta craters in Arcadia Planitia commonly have expanded craters superposed on their ejecta – and they tend to be more expanded (with larger diameters) in the inner ejecta layer. This has implications on the formation mechanisms for craters with this unique ejecta morphology. Finally, I explore the distribution of expanded craters south of Arcadia Planitia and across the southern mid-latitudes, along with scalloped depressions (another form of sublimation thermokarst), in order to identify the modern excess ice boundary in this region and any longitudinal variations. This study identifies some potential low-latitude locations with patchy excess ice, possibly preserved during a past climate. Through these studies, I will infer regions that contain abundant ice today and consider the implications that this ice has on both the martian climate and future exploration