A quasi-static nonlinear analysis for assessing the fire resistance of 3d frames exploiting time-dependent yield surface

In this work an automatic procedure for evaluating the axial force-biaxial bending yield surface of reinforced concrete sections in fire is proposed. It provides an accurate time-dependent expression of the yield condition by a section analysis carried out once and for all, accounting for the strength reduction of the materials, which is a function of the fire duration. The equilibrium state of 3D frames with such yield conditions, once discretized using beam finite elements, is formulated as a nonlinear vectorial equation defining a curve in the hyperspace of the discrete variables and the fire duration. A generalized path-following strategy is proposed for tracing this curve and evaluating, if it exists, the limit fire duration, that is the time of exposure which leads to structural collapse. Compared to the previous proposals on the topic, which are limited to local sectional checks, this work is the first to present a global analysis for assessing the fire resistance of 3D frames, providing a time history of the fire event and taking account of the stress redistribution. Numerical examples are given to illustrate and validate the proposal

Co-transport-induced instability of membrane voltage in tip-growing cells

A salient feature of stationary patterns in tip-growing cells is the key role played by the symports and antiports, membrane proteins that translocate two ionic species at the same time. It is shown that these co-transporters destabilize generically the membrane voltage if the two translocated ions diffuse differently and carry a charge of opposite (same) sign for symports (antiports). Orders of magnitude obtained for the time and lengthscale are in agreement with experiments. A weakly nonlinear analysis characterizes the bifurcation

Optical amplification enhancement in photonic crystals

Improving and controlling the efficiency of a gain medium is one of the most challenging problems of laser research. By measuring the gain length in an opal based photonic crystal doped with laser dye, we demonstrate that optical amplification is more than twenty-fold enhanced along the Gamma-K symmetry directions of the face centered cubic photonic crystal. These results are theoretically explained by directional variations of the density of states, providing a quantitative connection between density of the states and light amplification

Modulating Tumor Microenvironment: A Review on STK11 Immune Properties and Predictive vs Prognostic Role for Non-small-cell Lung Cancer Immunotherapy

The quest for immunotherapy (IT) biomarkers is an element of highest clinical interest in both solid and hematologic tumors. In non-small-cell lung cancer (NSCLC) patients, besides PD-L1 expression evaluation with its intrinsic limitations, tissue and circulating parameters, likely portraying the tumor and its stromal/immune counterparts, have been proposed as potential predictors of IT responsiveness. STK11 mutations have been globally labeled as markers of IT resistance. After a thorough literature review, STK11 mutations condition the prognosis of NSCLC patients receiving ICI-containing regimens, implying a relevant biological and clinical significance. On the other hand, waiting for prospective and solid data, the putative negative predictive value of STK11 inactivation towards IT is sustained by less evidence. The physiologic regulation of multiple cellular pathways performed by STK11 likely explains the multifaceted modifications in tumor cells, stroma, and tumor immune microenvironment (TIME) observed in STK11 mutant lung cancer, particularly explored in the molecular subgroup of KRAS co-mutation. IT approaches available thus far in NSCLC, mainly represented by anti-PD-1/PD-L1 inhibitors, are not promising in the case of STK11 inactivation. Perceptive strategies aimed at modulating the TIME, regardless of STK11 status or specifically addressed to STK11-mutated cases, will hopefully provide valid therapeutic options to be adopted in the clinical practice

Enhancing the Sensitivity of Biotinylated Surfaces by Tailoring the Design of the Mixed Self-Assembled Monolayer Synthesis

Thiolated self-assembled monolayers (SAMs) are typically used to anchor on a gold surface biomolecules serving as recognition elements for biosensor applications. Here, the design and synthesis of N-(2-hydroxyethyl)-3-mercaptopropanamide (NMPA) in biotinylated mixed SAMs is proposed as an alternative strategy with respect to on-site multistep functionalization of SAMs prepared from solutions of commercially available thiols. In this study, the mixed SAM deposited from a 10:1 solution of 3-mercaptopropionic acid (3MPA) and 11-mercaptoundecanoic acid (11MUA) is compared to that resulting from a 10:1 solution of NMPA:11MUA. To this end, surface plasmon resonance (SPR) and attenuated total reflectance infrared (ATR-IR) experiments have been carried out on both mixed SAMs after biotinylation. The study demonstrated how the fine tuning of the SAM features impacts directly on both the biofunctionalization steps, i.e., the biotin anchoring, and the biorecognition properties evaluated upon exposure to streptavidin analyte. Higher affinity for the target analyte with reduced nonspecific binding and lower detection limit has been demonstrated when NMPA is chosen as the more abundant starting thiol. Molecular dynamics simulations complemented the experimental findings providing a molecular rationale behind the performance of the biotinylated mixed SAMs. The present study confirms the importance of the functionalization design for the development of a highly performing biosensor

Influence of MLH1 on colon cancer sensitivity to poly(ADP-ribose) polymerase inhibitor combined with irinotecan

Poly(ADP-ribose) polymerase inhibitors (PARPi) are currently evaluated in clinical trials in combination with topoisomerase I (Top1) inhibitors against a variety of cancers, including colon carcinoma. Since the mismatch repair component MLH1 is defective in 10-15% of colorectal cancers we have investigated whether MLH1 affects response to the Top1 inhibitor irinotecan, alone or in combination with PARPi. To this end, the colon cancer cell lines HCT116, carrying MLH1 mutations on chromosome 3 and HCT116 in which the wildtype MLH1 gene was replaced via chromosomal transfer (HCT116+3) or by transfection of the corresponding MLH1 cDNA (HCT116 1-2) were used. HCT116 cells or HCT116+3 cells stably silenced for PARP-1 expression were also analysed. The results of in vitro and in vivo experiments indicated that MLH1, together with low levels of Top1, contributed to colon cancer resistance to irinotecan. In the MLH1-proficient cells SN-38, the active metabolite of irinotecan, induced lower levels of DNA damage than in MLH1-deficient cells, as shown by the weaker induction of γ-H2AX and p53 phosphorylation. The presence of MLH1 contributed to induce of prompt Chk1 phosphorylation, restoring G2/M cell cycle checkpoint and repair of DNA damage. On the contrary, in the absence of MLH1, HCT116 cells showed minor Chk1 phosphorylation and underwent apoptosis. Remarkably, inhibition of PARP function by PARPi or by PARP-1 gene silencing always increased the antitumor activity of irinotecan, even in the presence of low PARP-1 expression

Effects of the COVID-19 lockdown on glycaemic control in subjects with type 2 diabetes: the glycalock study

Aim: To assess the effect of the coronavirus disease 2019 (COVID-19) lockdown on glycaemic control in subjects with type 2 diabetes (T2D). Materials and Methods: In this observational, multicentre, retrospective study conducted in the Lazio region, Italy, we compared the differences in the HbA1c levels of 141 subjects with T2D exposed to lockdown with 123 matched controls with T2D who attended the study centres 1 year before. Basal data were collected from 9 December to 9 March and follow-up data from 3 June to 10 July in 2020 for the lockdown group, and during the same timeframes in 2019 for the control groups. Changes in HbA1c (ΔHbA1c) and body mass index (ΔBMI) during lockdown were compared among patients with different psychological well-being, as evaluated by tertiles of the Psychological General Well-Being Index (PGWBS). Results: No difference in ΔHbA1c was found between the lockdown and control groups (lockdown group −0.1% [−0.5%−0.3%] vs. control group −0.1% [−0.4%−0.2%]; p =.482). Also, no difference was found in ΔBMI (p =.316) or ΔGlucose (p =.538). In the lockdown group, subjects with worse PGWBS showed a worsening of HbA1c (p =.041 for the trend among PGWBS tertiles) and BMI (p =.022). Conclusions: The COVID-19 lockdown did not significantly impact glycaemic control in people with T2D. People with poor psychological well-being may experience a worsening a glycaemic control because of restrictions resulting from lockdown. These findings may aid healthcare providers in diabetes management once the second wave of COVID-19 has ended

Avaliação de temperaturas hibernais na brotação de gemas de macieira utilizando ramos enxertados.

bitstream/item/105140/1/ADM14001.pd

Granzyme B expression in visceral adipose tissue associates with local inflammation and glyco-metabolic alterations in obesity

Granzyme B (GrB) is a serine protease produced by immune and non-immune cells, able to promote multiple processes, like apoptosis, inflammation, extracellular matrix remodeling and fibrosis. GrB expression in visceral adipose tissue (VAT) was associated with tissue damage, local inflammation and insulin resistance in obesity murine model, but there is no data in humans. Aim of this study was to explore the expression of GrB in VAT from obese subjects in relation to adipose tissue injury, inflammation, metabolic alterations and GrB circulating levels. For this purpose, 85 obese individuals undergoing bariatric surgery and 35 healthy subjects (as control) were recruited at Sapienza University, Rome, Italy. Study participants underwent clinical work-up and routine biochemistry. mRNA expression of GrB in VAT and of a panel of VAT inflammatory markers was analyzed by real-time PCR. Serum GrB levels were measured by Elisa Affymetrix EBIO. We observed that 80% of obese patients expressed GrB mRNA in VAT, and GrB VAT expression was associated with the presence of local inflammation and glucose homeostasis alterations. Moreover, GrB serum levels, which were higher in obese subjects compared to non-obese healthy individuals, were associated with GrB expression in VAT and glyco-metabolic impairment. Our data show, for the first time in humans, that obese subjects with “sick” fat and altered glucose tolerance exhibit GrB expression in VAT, and suggest that GrB might contribute to obesity-related VAT inflammatory remodeling and glucose homeostasis dysregulation. Moreover, increased circulating GrB levels might represent a possible peripheral marker of VAT dysfunction in metabolic diseases