Could Protons and Carbon Ions Be the Silver Bullets Against Pancreatic Cancer?

Pancreatic cancer is a very aggressive cancer type associated with one of the poorest prognostics. Despite several clinical trials to combine different types of therapies, none of them resulted in significant improvements for patient survival. Pancreatic cancers demonstrate a very broad panel of resistance mechanisms due to their biological properties but also their ability to remodel the tumour microenvironment. Radiotherapy is one of the most widely used treatments against cancer but, up to now, its impact remains limited in the context of pancreatic cancer. The modern era of radiotherapy proposes new approaches with increasing conformation but also more efficient effects on tumours in the case of charged particles. In this review, we highlight the interest in using charged particles in the context of pancreatic cancer therapy and the impact of this alternative to counteract resistance mechanisms

Responsible innovation: exploring how Malaysia small-medium enterprises (SMEs) co-create value with external stakeholders in different industries

It is said that a sustainable business model can responsibly innovate to affect society, the environment, and the economy. Several scholars are interested in co-creation, one of the facets of responsible innovation. There is now a wealth of literature examining the many forms of co-creation as well as the benefits and effects of doing so in a business-to-consumer setting. Research on how SMEs collaborate with outside parties to accomplish responsible innovation in the context of B2C and B2B, however, is woefully inadequate, particularly in Malaysia. This study fills that gap. This study aims to explore (i) how Malaysian SMEs undergo responsible innovation in terms of co-creation with external stakeholders (ii) who are the external stakeholders involved in co-creating with Malaysian SMEs, and (iii) what are the co-creation impacts/outcomes in terms of responsible innovation for SMEs and end users? Using purposive sampling, which is extremely popular in a qualitative study, this research effort focuses on four Malaysian SMEs from diverse industries, providing us insights into the co-creation processes of B2B and B2C. Primary data was obtained via in-depth, semi-structured interviews with the senior management and founders of SMEs. Meanwhile, secondary data was obtained from publications such as financial reports, news articles, and corporate social reports (CSR). The study findings provide detailed information on SMEs' innovative processes, especially the different stakeholders and the roles played in multiple stages of business operation. A theoretical framework was developed to explain how SMEs with certain characteristics affect responsible innovation processes in terms of co-creation with their external stakeholders. Besides that, the framework also identified the roles of the external stakeholders, which leads to different responsible innovation impacts. At the end of the research effort, future directions were suggested, where research on the relationship between founders' personalities and characteristics and responsible innovation processes could provide useful insights into whether entrepreneurship and activism characteristics are the factors behind all innovation

NeuralStory: an Interactive Multimedia System for Video Indexing and Re-use

In the last years video has been swamping the Internet: websites, social networks, and business multimedia systems are adopting video as the most important form of communication and information. Video are normally accessed as a whole and are not indexed in the visual content. Thus, they are often uploaded as short, manually cut clips with user-provided annotations, keywords and tags for retrieval. In this paper, we propose a prototype multimedia system which addresses these two limitations: it overcomes the need of human intervention in the video setting, thanks to fully deep learning-based solutions, and decomposes the storytelling structure of the video into coherent parts. These parts can be shots, key-frames, scenes and semantically related stories, and are exploited to provide an automatic annotation of the visual content, so that parts of video can be easily retrieved. This also allows a principled re-use of the video itself: users of the platform can indeed produce new storytelling by means of multi-modal presentations, add text and other media, and propose a different visual organization of the content. We present the overall solution, and some experiments on the re-use capability of our platform in edutainment by conducting an extensive user valuation %with students from primary schools

Teen Culture, Technology and Literacy Instruction: Urban Adolescent Students’ Perspectives

Modern teens have pervasively integrated new technologies into their lives, and technology has become an important component of teen popular culture. Educators have pointed out the promise of exploiting technology to enhance students’ language and literacy skills and general academic success. However, there is no consensus on the effect of technology on teens, and scant literature is available that incorporates the perspective of urban and linguistically diverse students on the feasibility of applying new technologies in teaching and learning literacy in intact classrooms. This paper reports urban adolescents’ perspectives on the use of technology within teen culture, for learning in general and for literacy instruction in particular. Focus group interviews were conducted among linguistically diverse urban students in grades 6, 7 and 8 in a lower income neighborhood in the Northeastern region of the United States. The major findings of the study were that 1) urban teens primarily and almost exclusively used social media and technology devices for peer socializing, 2) they were interested in using technology to improve their literacy skills, but did not appear to voluntarily or independently integrate technology into learning, and 3) 8th graders were considerably more sophisticated in their use of technology and their suggestions for application of technology to literacy learning than 6th and 7th graders. These findings lead to suggestions for developing effective literacy instruction using new technologies

Characterisation of two quorum sensing systems in the endophytic Serratia plymuthica strain G3: differential control of motility and biofilm formation according to life-style

<p>Abstract</p> <p>Background</p> <p><it>N</it>-acylhomoserine lactone (AHL)-based quorum sensing (QS) systems have been described in many plant-associated Gram-negative bacteria to control certain beneficial phenotypic traits, such as production of biocontrol factors and plant growth promotion. However, the role of AHL-mediated signalling in the endophytic strains of plant-associated <it>Serratia </it>is still poorly understood. An endophytic <it>Serratia </it>sp. G3 with biocontrol potential and high levels of AHL signal production was isolated from the stems of wheat and the role of QS in this isolate was determined.</p> <p>Results</p> <p>Strain G3 classified as <it>Serratia plymuthica </it>based on 16S rRNA was subjected to phylogenetic analysis. Using primers to conserved sequences of <it>luxIR </it>homologues from the <it>Serratia </it>genus, <it>splIR </it>and <it>spsIR </it>from the chromosome of strain G3 were cloned and sequenced. AHL profiles from strain G3 and <it>Escherichia coli </it>DH5α expressing <it>splI </it>or <it>spsI </it>from recombinant plasmids were identified by liquid chromatography-tandem mass spectrometry. This revealed that the most abundant AHL signals produced by SplI in <it>E. coli </it>were <it>N</it>-3-oxo-hexanoylhomoserine lactone (3-oxo-C6-HSL), <it>N</it>-3-oxo-heptanoylhomoserine lactone (3-oxo-C7-HSL), <it>N</it>-3-hydroxy-hexanoylhomoserine lactone (3-hydroxy-C6-HSL), <it>N</it>-hexanoylhomoserine lactone (C6-HSL), and <it>N</it>-heptanoyl homoserine lactone (C7-HSL); whereas SpsI was primarily responsible for the synthesis of <it>N</it>-butyrylhomoserine lactone (C4-HSL) and <it>N</it>-pentanoylhomoserine lactone (C5-HSL). Furthermore, a quorum quenching analysis by heterologous expression of the <it>Bacillus </it>A24 AiiA lactonase in strain G3 enabled the identification of the AHL-regulated biocontrol-related traits. Depletion of AHLs with this lactonase resulted in altered adhesion and biofilm formation using a microtiter plate assay and flow cells coupled with confocal laser scanning microscopy respectively. This was different from the closely related <it>S. plymuthica </it>strains HRO-C48 and RVH1, where biofilm formation for both strains is AHL-independent. In addition, QS in G3 positively regulated antifungal activity, production of exoenzymes, but negatively regulated production of indol-3-acetic acid (IAA), which is in agreement with previous reports in strain HRO-C48. However, in contrast to HRO-C48, swimming motility was not controlled by AHL-mediated QS.</p> <p>Conclusions</p> <p>This is the first report of the characterisation of two AHL-based quorum sensing systems in the same isolate of the genus <it>Serratia</it>. Our results show that the QS network is involved in the global regulation of biocontrol-related traits in the endophytic strain G3. However, although free-living and endophytic <it>S. plymuthica </it>share some conservation on QS phenotypic regulation, the control of motility and biofilm formation seems to be strain-specific and possible linked to the life-style of this organism.</p

Sex- and isoform-specific mechanism of neuroprotection by transgenic expression of P450 epoxygenase in vascular endothelium

Cytochrome P450 epoxygenases (CYP) metabolize arachidonic acid to epoxyeicosatrienoic acids (EETs), which exhibit vasodilatory, anti-inflammatory and neuroprotective actions in experimental cerebral ischemia. We evaluated the effect of endothelial-specific CYP overexpression on cerebral blood flow, inflammatory cytokine expression and tissue infarction after focal cerebral ischemia in transgenic mice

A machine learning approach enables quantitative measurement of liver histology and disease monitoring in NASH

BACKGROUND AND AIMS: Manual histological assessment is currently the accepted standard for diagnosing and monitoring disease progression in NASH, but is limited by variability in interpretation and insensitivity to change. Thus, there is a critical need for improved tools to assess liver pathology in order to risk stratify NASH patients and monitor treatment response. APP ROA CH AND RESULT S: Here, we describe a machine learning (ML)-based approach to liver histology assessment, which accurately characterizes disease severity and heterogeneity, and sensitively quantifies treatment response in NASH. We use samples from three randomized controlled trials to build and then validate deep convolutional neural networks to measure key histological features in NASH, including steatosis, inflammation, hepatocellular ballooning, and fibrosis. The ML-based predictions showed strong correlations with expert pathologists and were prognostic of progression to cirrhosis and liver-related clinical events. We developed a heterogeneity-sensitive metric of fibrosis response, the Deep Learning Treatment Assessment Liver Fibrosis score, which measured antifibrotic treatment effects that went undetected by manual pathological staging and was concordant with histological disease progression. CONCLUSIONS: Our ML method has shown reproducibility and sensitivity and was prognostic for disease progression, demonstrating the power of ML to advance our understanding of disease heterogeneity in NASH, risk stratify affected patients, and facilitate the development of therapies. (Hepatology 2021;74:133-147)

Characterization of the role of TMEM45A in cancer cell sensitivity to cisplatin

TMEM45A is a transmembrane protein involved in tumor progression and cancer resistance to chemotherapeutic agents in hypoxic condition. It is correlated to a low breast cancer patient overall survival. However, little is known about this protein, in particular the mechanisms by which TMEM45A modulates cancer cell chemosensitivity. In this work, the messenger RNA expression of TMEM45A was assessed in head and neck squamous cell carcinoma (HNSCC) and renal cell carcinoma (RCC) biopsies. TMEM45A was upregulated in patients diagnosed for head and neck or renal cancer. Then, the implication of this protein in cisplatin sensitivity was explored in SQD9 and RCC4 + pVHL cells. TMEM45A inactivation decreased cell proliferation and modulated cell responses to cisplatin. Indeed, TMEM45A inactivation increased the sensitivity of SQD9 cells to cisplatin, whereas it rendered RCC4 + pVHL cells resistant to this anticancer agent. Through RNA-sequencing analysis, we identified several deregulated pathways that indicated that the impact on cisplatin sensitivity may be associated to the inhibition of DNA damage repair and to UPR pathway activation. This study demonstrated, for the first time, an anti or a pro-apoptotic role of this protein depending on the cancer type and highlighted the role of TMEM45A in modulating patient responses to treatment