Elucidating the role of matrix porosity and rigidity in glioblastoma type IV progression

The highly infiltrating nature of glioma cells is the major cause for the poor prognosis of brain malignancies. Motility, proliferation, and gene expression of cells in natural and synthetic gels have been analyzed by several authors, yet quantitative studies elucidating the role of matrix porosity and rigidity in the development of whole malignant masses are missing. Here, an experimental\u2010computational framework is introduced to analyze the behavior of U87\u2010MG cells and spheroids in compact hyaluronic acid gels (HA), replicating the brain parenchyma; and fibrous collagen gels (COL), resembling the organized structures of the brain. Experimentally it was observed that individual U87\u2010MG cells in COL assumed an elongated morphology within a few hours post inclusion (p.i.) and travelled longer distances than in HA. As spheroids, U87\u2010MG cells rapidly dispersed into COL resulting in infiltrating regions as large as tumor cores ( 48600 \u3bcm, at 8 days p.i.). Conversely, cells in HA originated smaller and denser infiltrating regions ( 48300 \u3bcm, at 8 days p.i.). Notably, COL tumor core size was only 20% larger than in HA, at longer time points. Computationally, by introducing for the first time the effects of matrix heterogeneity in our numerical simulations, the results confirmed that matrix porosity and its spatial organization are key factors in priming the infiltrating potential of these malignant cells. The experimental\u2010numerical synergy can be used to predict the behavior of neoplastic masses under diverse conditions and the efficacy of combination therapies simultaneously aiming at killing cancer cells and modulating the tumor microenvironment

A parametric study of a multiphase porous media model for tumor spheroids and environment interactions

Computational models for tumor growth provide an effective in silico tool to investigate the different stages of cancer growth. Recently, a series of computational models based on porous media theory has been proposed to predict tumor evolution and its interactions with the host tissue. In addition, a specialization of the original models, adapted for tumor spheroids, has been proposed and validated experimentally. However, due to the complexity of the modeling framework, a systematic understanding of the role of the parameters governing the equations is still lacking. In this work, we perform a parametric analysis on a set of fundamental parameters appearing in the model equations. We investigate the effects of a variation of these coefficients on the spheroid growth curves and, in particular, on the final radii reached by the cell aggregates in the growth saturation stage. Finally, we provide a discussion of the results and give a brief summary of our findings

Firm resilience, stressors, and entrepreneurial well-being: insights from women entrepreneurs in Ghana

Purpose This study draws on the conservation of resources logic to theorize the role of firm resilience in explaining variations in entrepreneurial well-being under varying conditions of supply chain disruption and dependency ratio. Design/methodology/approach The study uses ex-post survey data from 373 women entrepreneurs in diverse agricultural supply chains in Ghana, a sub-Saharan African country. Moderated regression analysis is employed to test the research hypotheses. Findings The results indicate that firm resilience has both positive and negative relationships with economic and subjective well-being, depending on the level of supply chain disruption and dependency ratio women entrepreneurs face. Notably, the findings suggest that firm resilience contributes more to economic and subjective well-being of women entrepreneurs when dependency ratio is low and supply chain disruption is high. Originality/value The study integrates firm resilience research and entrepreneurial well-being literature to provide new insights into theorizing and analyzing the benefit of firm resilience for women entrepreneurs’ well-being

Optimisation of ITER Nb3Sn CICCs for coupling loss, transverse electromagnetic load and axial thermal contraction

The ITER cable-in-conduit conductors (CICCs) are built up from sub-cable bundles, wound in different stages, which are twisted to counter coupling loss caused by time-changing external magnet fields. The selection of the twist pitch lengths has major implications for the performance of the cable in the case of strain sensitive superconductors, i.e. Nb3Sn, as the electromagnetic and thermal contraction loads are large but also for the heat load from the AC coupling loss. Reduction of the transverse load and warm-up cool-down degradation can be reached by applying longer twist pitches in a particular sequence for the sub-stages, offering a large cable transverse stiffness, adequate axial flexibility and maximum allowed lateral strand support. Analysis of short sample (TF conductor) data reveals that increasing the twist pitch can lead to a gain of the effective axial compressive strain of more than 0.3 % with practically no degradation from bending. For reduction of the coupling loss, specific choices of the cabling twist sequence are needed with the aim to minimize the area of linked strands and bundles that are coupled and form loops with the applied changing magnetic field, instead of simply avoiding longer pitches. In addition we recommend increasing the wrap coverage of the CS conductor from 50 % to at least 70 %. The models predict significant improvement against strain sensitivity and substantial decrease of the AC coupling loss in Nb3Sn CICCs, but also for NbTi CICCs minimization of the coupling loss can be achieved. Although the success of long pitches to transverse load degradation was already demonstrated, the prediction of the combination with low coupling loss needs to be validated by a short sample test.Comment: to be published in Supercond Sci Techno

The predictive and prognostic potential of plasma telomerase reverse transcriptase (TERT) RNA in rectal cancer patients

Background: Preoperative chemoradiotherapy (CRT) followed by surgery is the standard care for locally advanced rectal cancer, but tumour response to CRT and disease outcome are variable. The current study aimed to investigate the effectiveness of plasma telomerase reverse transcriptase (TERT) levels in predicting tumour response and clinical outcome. Methods: 176 rectal cancer patients were included. Plasma samples were collected at baseline (before CRT\ubcT0), 2 weeks after CRT was initiated (T1), post-CRT and before surgery (T2), and 4\u20138 months after surgery (T3) time points. Plasma TERT mRNA levels and total cell-free RNA were determined using real-time PCR. Results: Plasma levels of TERT were significantly lower at T2 (Po0.0001) in responders than in non-responders. Post-CRT TERT levels and the differences between pre- and post-CRT TERT levels independently predicted tumour response, and the prediction model had an area under curve of 0.80 (95% confidence interval (CI) 0.73\u20130.87). Multiple analysis demonstrated that patients with detectable TERT levels at T2 and T3 time points had a risk of disease progression 2.13 (95% CI 1.10\u20134.11)-fold and 4.55 (95% CI 1.48\u201313.95)-fold higher, respectively, than those with undetectable plasma TERT levels. Conclusions: Plasma TERT levels are independent markers of tumour response and are prognostic of disease progression in rectal cancer patients who undergo neoadjuvant therapy

Allogenic tissue-specific decellularized scaffolds promote long-term muscle innervation and functional recovery in a surgical diaphragmatic hernia model

Congenital diaphragmatic hernia (CDH) is a neonatal defect in which the diaphragm muscle does not develop properly, thereby raising abdominal organs into the thoracic cavity and impeding lung development and function. Large diaphragmatic defects require correction with prosthetic patches to close the malformation. This treatment leads to a consequent generation of unwelcomed mechanical stress in the repaired diaphragm and hernia recurrences, thereby resulting in high morbidity and significant mortality rates. We proposed a specific diaphragm-derived extracellular matrix (ECM) as a scaffold for the treatment of CDH. To address this strategy, we developed a new surgical CDH mouse model to test the ability of our tissue-specific patch to regenerate damaged diaphragms. Implantation of decellularized diaphragmatic ECM-derived patches demonstrated absence of rejection or hernia recurrence, in contrast to the performance of a commercially available synthetic material. Diaphragm-derived ECM was able to promote the generation of new blood vessels, boost long-term muscle regeneration, and recover host diaphragmatic function. In addition, using a GFP + Schwann cell mouse model, we identified re-innervation of implanted patches. These results demonstrated for the first time that implantation of a tissue-specific biologic scaffold is able to promote a regenerating diaphragm muscle and overcome issues commonly related to the standard use of prosthetic materials

Beta decay of the Tz=-2 nucleus 64Se and its descendants

International audience; The beta decay of the Tz=-2 nucleus 64Se has been studied in a fragmentation reaction at RIKEN-Nishina Center. 64Se is the heavies Tz=-2 nucleus that decays to bound states in the daughter nucleus and the heaviest case where the mirror reaction 64Zn(3He,t)64Ga on the Tz=+2 64Zn stable target exists and can be compared. Beta-delayed gamma and proton radiation is reported for the 64Se and 64As cases. New levels have been observed in 64As, 64Ge (N=Z), 63Ge and 63Ga. The associated T1/2 values have been obtained

The initial characterization of the iron environment in lipoxygenase by MÖssbauer spectroscopy

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/65879/1/j.1432-1033.1990.tb15616.x.pd