Pretreatment Tissue TCR Repertoire Evenness Is Associated with Complete Pathologic Response in Patients with NSCLC Receiving Neoadjuvant Chemoimmunotherapy

Neoadjuvant Chemoimmunotherapy; Lung cancer; T-cell receptorQuimioimmunoteràpia neoadjuvant; Càncer de pulmó; Receptor de cèl·lules TQuimioinmunoterapia neoadyuvante; Cáncer de pulmón; Receptor de células TPurpose: Characterization of the T-cell receptor (TCR) repertoire may be a promising source for predictive biomarkers of pathologic response to immunotherapy in locally advanced non–small cell lung cancer (NSCLC). Experimental Design: In this study, next-generation TCR sequencing was performed in peripheral blood and tissue samples of 40 patients with NSCLC, before and after neoadjuvant chemoimmunotherapy (NADIM clinical trial, NCT03081689), considering their complete pathologic response (CPR) or non-CPR. Beyond TCR metrics, tissue clones were ranked by their frequency and spatiotemporal evolution of top 1% clones was determined. Results: We have found a positive association between an uneven TCR repertoire in tissue samples at diagnosis and CPR at surgery. Moreover, TCR most frequently ranked clones (top 1%) present in diagnostic biopsies occupied greater frequency in the total clonal space of CPR patients, achieving an AUC ROC to identify CPR patients of 0.967 (95% confidence interval, 0.897–1.000; P = 0.001), and improving the results of PD-L1 tumor proportion score (TPS; AUC = 0.767; P = 0.026) or tumor mutational burden (TMB; AUC = 0.550; P = 0.687). Furthermore, tumors with high pretreatment top 1% clonal space showed similar immune cell populations but a higher immune reactive gene expression profile. Finally, the selective expansion of pretreatment tissue top 1% clones in peripheral blood of CPR patients suggests also a peripheral immunosurveillance, which could explain the high survival rate of these patients. Conclusions: We have identified two parameters derived from TCR repertoire analysis that could outperform PD-L1 TPS and TMB as predictive biomarkers of CPR after neoadjuvant chemoimmunotherapy, and unraveled possible mechanisms of CPR involving enhanced tumor immunogenicity and peripheral immunosurveillance

Spartan Daily, September 27, 1972

Volume 60, Issue 6https://scholarworks.sjsu.edu/spartandaily/5641/thumbnail.jp

Star formation laws and thresholds from ISM structure and turbulence

We present an analytical model of the relation between the surface density of gas and star formation rate in galaxies and clouds, as a function of the presence of supersonic turbulence and the associated structure of the interstellar medium. The model predicts a power-law relation of index 3/2, flattened under the effects of stellar feedback at high densities or in very turbulent media, and a break at low surface densities when ISM turbulence becomes too weak to induce strong compression. This model explains the diversity of star formation laws and thresholds observed in nearby spirals and their resolved regions, the Small Magellanic Cloud, high-redshift disks and starbursting mergers, as well as Galactic molecular clouds. While other models have proposed interstellar dust content and molecule formation to be key ingredients to the observed variations of the star formation efficiency, we demonstrate instead that these variations can be explained by interstellar medium turbulence and structure in various types of galaxies.Comment: 6 pages, re-submitted to ApJL after referee repor

War and Insurgency in the Western Sahara

Home to the largest functional military barrier in the world, the Western Sahara has a long history of colonial conquest and resistance, guerrilla warfare and counterinsurgency, and evolving strategic thought. This monograph explores the past, present, and future of the region, including its relationship to developments in Morocco, Algeria, and elsewhere in North Africa. At a crucial crossroads between Africa and Europe, the Mediterranean and the Atlantic, and the Arab World and the West, Morocco has long had a special place in U.S. diplomacy and strategic planning. Since September 11, 2001, Morocco\u27s importance to the United States has only increased, and the more recent uncertainties of the Arab Spring and Islamist extremism have further increased the value of the Moroccan-American alliance. Yet one of the pillars of the legitimacy of the Moroccan monarchy, its claim to the Western Sahara, remains a point of violent contention. Home to the largest functional military barrier in the world, the Western Sahara has a long history of colonial conquest and resistance, guerrilla warfare and counterinsurgency, and evolving strategic thought, and its future may prove critical to U.S. interests in the region.https://press.armywarcollege.edu/monographs/1525/thumbnail.jp

El conde D. Garci-Sanchez de Castilla : tragedia : en cinco actos

Precede al tit.: "N.99"Copia digital. Valladolid : Junta de Castilla y León. Consejería de Cultura y Turismo, 2009-2010Según el "Catálogo de autores teatrales del siglo XVIII" de J. Herrera Navarro, p.481, esta obra es de Lorenzo María de Villarroel y Velazquez y se imprimió por primera vez en 1778Pi de imp. tomado de colofónEl impresor trabajó en Barcelona entre 1775 y 179

Innovative Techniques for Landscape Recovery after Clay Mining under Mediterranean Conditions

Open-pit mining results in profound modifications at different environmental scales that may persist for very long time periods, or even indefinitely. Considerable research efforts in mine reclamation strategies have been made, although reclamation failures are still common. In dry climates, such as in the Mediterranean Basin, successful actions may depend on features related to proper species selection and restoration techniques, which may substantially contribute to provide substrate stability and facilitate the regeneration of the main ecological processes. In this context, we developed the TECMINE case-study aimed to evaluate the feasibility and suitability of innovative restoration practices applied to clay-mine reclamation under Mediterranean conditions. The restoration strategy was designed at the landscape level with two main approaches: the recovery of natural geomorphology shapes and ecological restoration, including vegetation recovery and soil quality, based on proper reference ecosystems. After the geomorphological land remodeling, a combination of several innovative restoration techniques was implemented to reclaim plant communities and ecosystem functioning. These techniques involved: (i) accurate species selection according to microhabitat characteristics; (ii) high-quality plant production; (iii) surface remodeling to improve substrate stabilization; and (iv) implementing rainfall collection to enhance resources availability, soil fertility improvement and the amelioration of abiotic conditions for seedlings. Finally, we developed a monitoring program to assess the success of the implemented restoration techniques over time. The application of these innovative techniques has reported interesting results and represents a step forward in the improvement of mine restoration under Mediterranean climate.The study was funded by the LIFE TECMINE Project (LIFE16 ENV/ES/000159) from the European Programme for the Environment and Climate Action (2014–2020)*. L.M. was supported by the Spanish MICINN (PTA2019-018094). The CEAM foundation is funded by the Generalitat Valenciana

Higher expression of the strawberry xyloglucan endotransglucosylase/hydrolase genes FvXTH9 and FvXTH6 accelerates fruit ripening

Fruit softening in Fragaria (strawberry) is proposed to be associated with the modification of cell wall components such as xyloglucan by the action of cell wall‐modifying enzymes. This study focuses on the in vitro and in vivo characterization of two recombinant xyloglucan endotransglucosylase/hydrolases (XTHs) from Fragaria vesca, FvXTH9 and FvXTH6. Mining of the publicly available F. vesca genome sequence yielded 28 putative XTH genes. FvXTH9 showed the highest expression level of all FvXTHs in a fruit transcriptome data set and was selected with the closely related FvXTH6 for further analysis. To investigate their role in fruit ripening in more detail, the coding sequences of FvXTH9 and FvXTH6 were cloned into the vector pYES2 and expressed in Saccharomyces cerevisiae. FvXTH9 and FvXTH6 displayed xyloglucan endotransglucosylase (XET) activity towards various acceptor substrates using xyloglucan as the donor substrate. Interestingly, FvXTH9 showed activity of mixed‐linkage glucan:xyloglucan endotransglucosylase (MXE) and cellulose:xyloglucan endotransglucosylase (CXE). The optimum pH of both FvXTH9 and FvXTH6 was 6.5. The prediction of subcellular localization suggested localization to the secretory pathway, which was confirmed by localization studies in Nicotiana tabacum. Overexpression showed that Fragaria × ananassa fruits infiltrated with FvXTH9 and FvXTH6 ripened faster and showed decreased firmness compared with the empty vector control pBI121. Thus FvXTH9 and also FvXTH6 might promote strawberry fruit ripening by the modification of cell wall components

Spartan Daily, June 3, 1938

Volume 26, Issue 147https://scholarworks.sjsu.edu/spartandaily/2784/thumbnail.jp

Field campaign on pressure on the crown wall at the outer port of Punta Langosteira breakwater

[Abstract:] Punta Langosteira port, located in A Coruña (Spain), was monitored during the winters of 2017 and 2018, measuring wave pressure in the crown wall structure. Furthermore, the metocean variables were measured on a buoy located very close to the breakwater. This paper presents the real pressures measured at the crown wall of the breakwater during different storm events. These values are compared with the results of the application of state-of-the-art equations for the calculation of pressures on crown walls. The results obtained show the behaviour of the pressures with a crown wall fully protected by the armour, as is the case of Langosteira breakwater. Finally, several conclusions are made on the methodology for measuring the pressures using physical models and the relevance of the armour roughness.Fundação para a Ciência e a Tecnologia (FCT); PTDC/ECI-EGC/31090/201