The actual Co-occurrence regarding Self-Harm and Violence: A Cognitive-Emotional Style of Dual-Harm.

Ex-vivo tumor tissue culture systems are used as models to test specific anti-cancer drugs. Their main advantage is that they are closely comparable with the in vivo tumor in their host organism. We previously reported that precision-cut organotypic tissue slices of pancreatic ductal adenocarcinoma (PDAC) can be successfully cultured ex-vivo for at least 4 days. In order to study how culturing might affect transcription patterns, we now performed genome-wide transcriptome profiling of both baseline (0 h) and explanted tumors at daily intervals (24, 48 and 72 h) after start of culturing. The total-RNA from five samples of surgically resected human PDAC tumors at baseline and at different time points in culture was sequenced. Differential gene expression analysis of the whole transcriptome, testing 58,713 genes and over 206,000 transcripts, found that only a small number of genes showed significant changes in expression between baseline and cultured samples. The cultured tumor slices showed upregulation of a median of 12, 10 and 15 genes and downregulation of a median of 15, 12 and 25 genes at 24, 48 and 72 h in culture, respectively. One sample had morphologically increasing loss of tissue viability (range 0-18%). The vascular endothelial growth factor A (VEGFA) was significantly upregulated during the entire culture period in this case. Pathway over-representation analysis suggested that VEGFA together with the PTGS2 gene were upregulated at the same time as HIF-1-triggered cell apoptosis via NF-ĸB and the AP-1 activating factor was induced. Indeed, increased areas of apoptotic lesions were visible in this sample after 24 hours of culture. In conclusion, genome-wide transcriptome analysis supports that ex-vivo cultured tissue slices of PDAC may be a representative model of the original tumor. Tanespimycin Transcriptome analysis was found to be a valuable complement to morphology for evaluation of ex-vivo cultures of PDAC.High dose-rate radiotherapy, known as FLASH, has been shown to increase the differential response between healthy and tumour tissue. Moreover, Very High Energy Electrons (VHEEs) provide more favourable dose distributions than conventional radiotherapy electron and photon beams. Plane-parallel ionisation chambers are the recommended secondary standard systems for clinical reference dosimetry of electrons, therefore chamber response to these high energy and high dose-per-pulse beams must be well understood. Graphite calorimetry, the UK primary standard, has been employed to measure the dose delivered from a 200 MeV pulsed electron beam. This was compared to the charge measurements of a plane-parallel ionisation chamber to determine the absolute collection efficiency and infer the ion recombination factor. The dose-per-pulse measured by the calorimeter ranged between 0.03 Gy/pulse and 5.26 Gy/pulse, corresponding to collection efficiencies between 97% and 4%, respectively. Multiple recombination models currently available have been compared with experimental results. This work is directly applicable to the development of standard dosimetry protocols for VHEE radiotherapy, FLASH radiotherapy and other high dose-rate modalities. However, the use of secondary standard ionisation chambers for the dosimetry of high dose-per-pulse VHEEs has been shown to require large corrections for charge collection inefficiency.Immunotherapy, by enhancing the endogenous anti-tumor immune responses, is showing promising results for the treatment of numerous cancers refractory to conventional therapies. However, its effectiveness for advanced castration-resistant prostate cancer remains unsatisfactory and new therapeutic strategies need to be developed. To this end, systems pharmacology modeling provides a quantitative framework to test in silico the efficacy of new treatments and combination therapies. In this paper we present a new Quantitative Systems Pharmacology (QSP) model of prostate cancer immunotherapy, calibrated using data from pre-clinical experiments in prostate cancer mouse models. We developed the model by using Ordinary Differential Equations (ODEs) describing the tumor, key components of the immune system, and seven treatments. Numerous combination therapies were evaluated considering both the degree of tumor inhibition and the predicted synergistic effects, integrated into a decision tree. Our simulations predicted cancer vaccine combined with immune checkpoint blockade as the most effective dual-drug combination immunotherapy for subjects treated with androgen-deprivation therapy that developed resistance. Overall, the model presented here serves as a computational framework to support drug development, by generating hypotheses that can be tested experimentally in pre-clinical models.Currently, lead (Pb) has become a severe environmental pollutant and fungi hold a promising potential for the remediation of Pb-containing wastewater. The present study showed that Penicillium polonicum was able to tolerate 4 mmol/L Pb(II), and remove 90.3% of them in 12 days through three mechanisms extracellular immobilization, cell wall adsorption, and intracellular bioaccumulation. In this paper. the three mechanisms were studied by Raman, X-ray diffraction analysis (XRD), scanning electron microscopy (SEM), Fourier transform infrared spectroscopy (FTIR) and transmission electron microscopy (TEM). The results indicated that Pb(II) was immobilized as lead oxalate outside the fungal cell, bound with phosphate, nitro, halide, hydroxyl, amino, and carboxyl groups on the cell wall, precipitated as pyromorphite [Pb5(PO4)3Cl] on the cell wall, and reduced to Pb(0) inside the cell. These combined results provide a basis for additionally understanding the mechanisms of Pb(II) removal by P. polonicum and developing remediation strategies using this fungus for lead-polluted water.Some human fronts spread faster than expected by models based on dispersal and reproduction. The only explanation proposed so far assumes that some autochthonous individuals are incorporated by the expanding populations, leading to faster front speeds. Here we show that simple models without this effect are also consistent with the observed speeds of two fronts (a Khoi-khoi expansion of herders and a Bantu expansion of farmers), provided that the dispersal of individuals is biased (i.e., more probable) in directions closer to the front propagation direction. The physical models presented may also be applied to other kinds of social phenomena, including innovation diffusion, rumor propagation, linguistic fronts, epidemic spread, diffusion in economic space and the evolution of cooperation in spatial systems. They can be also adapted to non-human systems with biased dispersal, including biological invasions, cancer tumors and virus treatment of tumors.Tanespimycin