Modeling the isothermal inactivation curves of Listeria innocua CECT 910 in a vegetable beverage under low-temperature treatments and different pH levels

Thermal inactivation kinetics of Listeria innocua CECT 910 inoculated in a vegetable beverage at three pH conditions (4.25, 4.75, and 5.20), four levels of temperature (50, 55, 60, 65℃), and different treatment times (0–75 min) were obtained. Survival curves did not follow a log-linear relationship and consequently were fitted to various mathematical models: Weibull, Geeraerd, Cerf with shoulder, and the modified Gompertz equation. Results indicated that the best model for the treatment conditions was the modified Gompertz equation, which provides the best goodness-of-fit and the lowest Akaike information criterion value. Sensitivity analysis indicated that the most influential factors affecting the final microbial load were temperature and time in the case of the higher temperature level (65℃) and time in the case of the lower temperature level (50℃).This paper has been partially supported by research grants MTM2013-42323-P and AGL2013-48993-C2-2-R from the Spanish Ministry of Economy and Competiveness.Peer reviewe

Benchmarking Digital-Analog Quantum Computation

Digital-Analog Quantum Computation (DAQC) has recently been proposed as an alternative to the standard paradigm of digital quantum computation. DAQC creates entanglement through a continuous or analog evolution of the whole device, rather than by applying two-qubit gates. This manuscript describes an in-depth analysis of DAQC by extending its implementation to arbitrary connectivities and by performing the first systematic study of its scaling properties. We specify the analysis for three examples of quantum algorithms, showing that except for a few specific cases, DAQC is in fact disadvantageous with respect to the digital case.Comment: 16+5 pages, 11 figure

Early imaging and molecular changes with neoadjuvant bevacizumab in stage ii/iii breast cancer

This prospective, phase II study evaluated novel biomarkers as predictors of response to bevacizumab in patients with breast cancer (BC), using serial imaging methods and gene expression analysis. Patients with primary stage II/III BC received bevacizumab 15 mg/kg (cycle 1; C1), then four cycles of neoadjuvant docetaxel doxorubicin, and bevacizumab every 3 weeks (C2–C5). Tumour proliferation and hypoxic status were evaluated using18F-fluoro-3'-deoxy-3'-L-fluorothymidine (FLT)-and18F-fluoromisonidazole (FMISO)-positron emission tomography (PET) at baseline, and during C1 and C5. Pre-and post-bevacizumab vascular changes were evaluated using dynamic contrastenhanced magnetic resonance imaging (DCE-MRI). Molecular biomarkers were assessed using microarray analysis. A total of 70 patients were assessed for treatment efficacy. Significant decreases from baseline in tumour proliferation (FLT-PET), vascularity, and perfusion (DCE-MRI) were observed during C1 (p = 0.001), independent of tumour subtype. Bevacizumab treatment did not affect hypoxic tumour status (FMISO-PET). Significant changes in the expression of 28 genes were observed after C1. Changes in vascular endothelial growth factor receptor (VEGFR)-2p levels were observed in 65 patients, with a > 20% decrease in VEGFR-2p observed in 13/65. Serial imaging techniques. © 2021 by the authors. Licensee MDPI, Basel, Switzerland

Colorectal cancer promoter methylation alteration affects the expression of glutamate ionotropic receptor AMPA type subunit 4 alternative isoforms potentially relevant in colon tissue

DNA methylation alterations are early events during tumourigenesis, affecting genes involved in the crosstalk between cells and surroundings in colorectal cancer (CRC). Among these genes, GRIA4, Glutamate Ionotropic Receptor AMPA Type Subunit 4, displays hypermethylation in the promoter region, and is an early diagnostic biomarker. It is well known that methylation can also affect alternative transcription. The purpose of this study is to evaluate the expression, at transcript and protein level, of GRIA4 main isoforms (the canonical one and a short variant) in 23 CRC and matched normal samples, of which we previously verified the methylation status. We further predicted miRNA/transcript target interactions as a possible post-transcriptional regulation using bioinformatics tools. As expected, downregulation of both variants has been observed in tumours. Interestingly, in contrast to what observed at transcriptional level, the GluR4 protein short isoform displayed higher expression than the canonical one either in normal or tumoural tissues. This may be explained by miRNA specifically targeting the canonical isoform. Our study is the first one that shows the expression of both isoforms in colon tissues. To note, the evident expression of the short isoform suggests a functional role in intestinal cell biology

La transición hacia la Universidad: un reto para no caer en el vacío

La importancia que la transición educativa alcanza en el acceso a la Universidad precisa de un trabajo de regulación que en estos momentos no existe. En base a la información previa obtenida de los centros de secundaria sobre la transición primaria – secundaria, y sobre las actividades que se realizan dentro del Plan de Acción Tutorial, se elabora una propuesta sobre la que generar un programa de transición secundaria – universidad. Contamos como recursos, con un centro de secundaria piloto, y el Programa de Acción Tutorial de la Universidad de Alicante. El Programa de Transición Universitaria establece una serie de actividades en coordinación, y recoge además actividades de intervención directa con el alumnado de secundaria. Una de ellas sería plan de intervención integral que incluye, además de los aspectos técnicos necesarios, aspectos personales. Se delimitan los contenidos, la metodología, los recursos, el calendario de aplicación y los responsables, y esta actividad generada desde la Universidad, estará incluida en el Plan de Acción Tutorial del Instituto

Co-Design quantum simulation of nanoscale NMR

Quantum computers have the potential to efficiently simulate the dynamics of nanoscale NMR systems. In this work, we demonstrate that a noisy intermediate-scale quantum computer can be used to simulate and predict nanoscale NMR resonances. In order to minimize the required gate fidelities, we propose a superconducting application-specific Co-Design quantum processor that reduces the number of SWAP gates by over 90% for chips with more than 20 qubits. The processor consists of transmon qubits capacitively coupled via tunable couplers to a central co-planar waveguide resonator with a quantum circuit refrigerator (QCR) for fast resonator reset. The QCR implements the nonunitary quantum operations required to simulate nuclear hyperpolarization scenarios.The authors would like to thank Caspar Ockeloen-Korppi, Alessandro Landra, and Johannes Heinsoo for their help in de- veloping the idea of the star-architecture chip, Jani Tuorila for his support in developing the gate theory, Amin Hosseinkhani and Tianhan Liu for reviewing the manuscript, and Hen- rikki Mäkynen and Hoang-Mai Nguyen for graphic design. J.C. additionally acknowledges the Ramón y Cajal program (RYC2018-025197-I). We further acknowledge support from Atos with the Quantum Learning Machine (QLM). Finally, the authors acknowledge financial support to BMBF through the Q-Exa Project No. FZK: 13N16062

NKG2D-CAR-transduced natural killer cells efficiently target multiple myeloma

CAR-T-cell therapy against MM currently shows promising results, but usually with serious toxicities. CAR-NK cells may exert less toxicity when redirected against resistant myeloma cells. CARs can be designed through the use of receptors, such as NKG2D, which recognizes a wide range of ligands to provide broad target specificity. Here, we test this approach by analyzing the antitumor activity of activated and expanded NK cells (NKAE) and CD45RA− T cells from MM patients that were engineered to express an NKG2D-based CAR. NKAE cells were cultured with irradiated Clone9.mbIL21 cells. Then, cells were transduced with an NKG2D-4-1BB-CD3z-CAR. CAR-NKAE cells exhibited no evidence of genetic abnormalities. Although memory T cells were more stably transduced, CAR-NKAE cells exhibited greater in vitro cytotoxicity against MM cells, while showing minimal activity against healthy cells. In vivo, CAR-NKAE cells mediated highly efficient abrogation of MM growth, and 25% of the treated mice remained disease free. Overall, these results demonstrate that it is feasible to modify autologous NKAE cells from MM patients to safely express a NKG2D-CAR. Additionally, autologous CAR-NKAE cells display enhanced antimyeloma activity demonstrating that they could be an effective strategy against MM supporting the development of NKG2D-CAR-NK-cell therapy for MM.This study was supported by a grant from the Spanish Society for Hematology and Hemotherapy to Alejandra Leivas, the CRIS Foundation to Beat Cancer and the Instituto de Salud Carlos III (PI18/01519)

Distinct Differences in Chromatin Structure at Subtelomeric X and Y' Elements in Budding Yeast

In Saccharomyces cerevisiae, all ends of telomeric DNA contain telomeric repeats of (TG1–3), but the number and position of subtelomeric X and Y' repeat elements vary. Using chromatin immunoprecipitation and genome-wide analyses, we here demonstrate that the subtelomeric X and Y' elements have distinct structural and functional properties. Y' elements are transcriptionally active and highly enriched in nucleosomes, whereas X elements are repressed and devoid of nucleosomes. In contrast to X elements, the Y' elements also lack the classical hallmarks of heterochromatin, such as high Sir3 and Rap1 occupancy as well as low levels of histone H4 lysine 16 acetylation. Our analyses suggest that the presence of X and Y' elements govern chromatin structure and transcription activity at individual chromosome ends