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The Xindian culture of northwest China has been seen as a prototypical example of a transition toward pastoralism, resulting in part from environmental changes that started around 4000 years ago. To date, there has been little available residential data to document how and whether subsistence strategies and community organization in northwest China changed following or in association with documented environmental changes. The Tao River Archaeology Project is a collaborative effort aimed at gathering robust archaeological information to solidify our baseline understanding of economic, technological, and social practices in the third through early first millennia BC. Here we present data from two Xindian culture residential sites, and propose that rather than a total transition to nomadic pastoralism—as it is often reconstructed—the Xindian culture reflects a prolonged period of complex transition in cultural traditions and subsistence practices. In fact, communities maintained elements of earlier cultivation and animal-foddering systems, selectively incorporating new plants and animals into their repertoire. These locally-specific strategies were employed to negotiate ever-changing environmental and social conditions in the region of developing ‘proto-Silk Road’ interregional interactions.

SummaryMalignant melanoma (MM) develops from the melanocytes and in its advanced stage is the most aggressive type of skin cancer. Here we report a comprehensive analysis on a prospective cohort study, including non-tumor, primary and metastasis tissues (n=77) with the corresponding plasma samples (n=56) from patients with malignant melanoma. The tumors and surrounding tissues were characterized with a combination of high-throughput analyses including quantitative proteomics, phosphoproteomics, acetylomics, and whole exome sequencing (WES) combined with in-depth histopathology analysis. Melanoma cell proliferation highly correlates with dysregulation at the proteome, at the posttranslational- and at the transcriptome level. Some of the changes were also verified in the plasma proteome. The metabolic reprogramming in melanoma includes upregulation of the glycolysis and the oxidative phosphorylation, and an increase in glutamine consumption, while downregulated proteins involved in the degradation of amino acids, fatty acids, and the extracellular matrix (ECM) receptor interaction. The pathways most dysregulated in MM including the MAP kinases-, the PI3K-AKT signaling, and the calcium homeostasis, are among the most affected by mutations, thus, dysregulation in these pathways can be manifested as drivers in melanoma development and progression.The phosphoproteome analysis combined with target-based prediction mapped 75% of the human kinome. Melanoma cell proliferation was driven by two key factors: i) metabolic reprogramming leading to upregulation of the glycolysis and oxidative phosphorylation, supported by HIF-1 signaling pathway and mitochondrial translation; and ii) a dysregulation of the immune system response, which was mirrored by immune system processes in the plasma proteome. Regulation of the melanoma acetylome and expression of deacetylase enzymes discriminated between groups based on tissue origin and proliferation, indicating a way to guide the successful use of HDAC inhibitors in melanoma. The disease progression toward metastasis is driven by the downregulation of the immune system response, including MHC class I and II, which allows tumors to evade immune surveillance. Altogether, new evidence is provided at different molecular levels to allow improved understanding of the melanoma progression, ultimately contributing to better treatment strategies.TOC figure

The Information Technology sector has been using proximity offshoring (near-shoring) as common practice over the past 2 decades, mainly for software development projects. Using a large business transformation project from a global consumer goods company as a single case study, the present paper analyses the benefits and key challenges of incorporating such delivery models in these types of projects, focusing its attention mainly on the financial and quality aspects. The analysis suggests that, when compared to traditional services delivery (on-site consultants), near-shoring practices can have a very positive financial impact for the vendor and the customer, translating into an increase on the Return on Investment (ROI) without a significant increase of risks or losses in quality – The project’s cost can have a significant reduction on the vendor side, with a consequent reduction to the end client. Regardless these benefits, it is suggested that traditional consulting still plays an un-replaceable role in these types of projects. Furthermore, it is suggested that it is equally important the commitment from top management for such initiatives. info:eu-repo/semantics/publishedVersion

Background: Glioblastomas are the most common and lethal primary brain tumors. Microglia, the resident immune cells of the brain, survey their environment and respond to pathogens, toxins, and tumors. Glioblastoma cells communicate with microglia, in part by releasing extracellular vesicles (EVs). Despite the presence of large numbers of microglia in glioblastoma, the tumors continue to grow, and these neuroimmune cells appear incapable of keeping the tumor in check. To understand this process, we analyzed gene expression in microglia interacting with glioblastoma cells.Methods: We used RNASeq of isolated microglia to analyze the expression patterns of genes involved in key microglial functions in mice with glioblastoma. We focused on microglia that had taken up tumor-derived EVs and therefore were within and immediately adjacent to the tumor.Results: We show that these microglia have downregulated expression of genes involved in sensing tumor cells and tumor-derived danger signals, as well as genes used for tumor killing. In contrast, expression of genes involved in facilitating tumor spread was upregulated. These changes appear to be in part EV-mediated, since intracranial injection of EVs in normal mice led to similar transcriptional changes in microglia. We observed a similar microglial transcriptomic signature when we analyzed datasets from human patients with glioblastoma.Conclusion: Our data define a microgliaGlioblastoma specific phenotype, whereby glioblastomas have hijacked gene expression in the neuroimmune system to favor avoiding tumor sensing, suppressing the immune response, clearing a path for invasion, and enhancing tumor propagation. For further exploration, we developed an interactive online tool at http://www.glioma-microglia.com with all expression data and additional functional and pathway information for each gene.

Recently, bone tissue engineering (TE) has seen new developments, with triply periodic minimal surfaces (TPMSs) being used to develop new porosity-controlled sca olds to interface new tissue growth. The process of choosing the best geometry to a specific application still lacks research, so the goal for this work is to propose a new method of sca old selection, based on assessing the tortuosity inside these symmetric TPMS-based structures. Additionally, computer fluid dynamic (CFD) simulations were conducted to validate this method. The comparison between tortuosity and CFD outputs suggests that an analysis of the tortuosity could be used as an early indicator of the sca old’s viability for specific applications, favouring sca olds with more intricate and curvature-dependent streamlines.

Atualmente, o setor termal encontra-se em forte crescimento. Ao longo do tempo, a sua atividade deixou de ser meramente terapêutica e de bem-estar e passou a ter uma ligação com as energias renováveis. Em Portugal Continental, é conhecida a utilização deste recurso para geotermia, apesar de todas as ocorrências geotérmicas possuírem uma temperatura inferior a 150º C, sendo classificadas de baixa entalpia. Com o aumento da importância das águas termais, torna-se fundamental o conhecimento detalhado dos sistemas hidrogeológicos associados, pois um melhor conhecimento da ocorrência geotermal, permitirá uma maior eficiência da sua exploração e monitorização, em situações de contaminação ou sobre-exploração. No norte de Portugal ocorrem diversas zonas termais, como é o caso das Termas do Eirogo, distrito de Braga, concelho de Barcelos (Galegos de Santa Maria). Geologicamente, ocorre em granodioritos, de idade Varisca, com rochas básicas associadas, correspondentes à série tardia do domínio estrutural da Zona de Cisalhamento de Vigo - Régua. Estas formações litológicas são intrusivas nos metassedimentos, de idade Silúrica, pertencentes à unidade parautóctone do Minho Central e Ocidental. A orientação do ribeiro de Eirogo e a ocorrência da falha, como orientação N32ºE, sugerem uma estreita relação com o circuito ascendente da água mineral. Atualmente, a atividade termal nas termas do Eirogo encontra-se suspensa, embora existam registos da sua utilização na década de noventa. A água é fracamente mineralizada com uma fácies sulfúrea-sódica dominante. A característica sulfúrea torna-a adequada no tratamento de doenças do aparelho respiratório, doenças de pele, aparelho músculo esquelético e ginecológicas. Com este trabalho, pretende-se um estudo detalhado do enquadramento geológico e hidrogeológico nesta área termal e posterior proposta de um modelo hidrogeológico concetual para a sua ocorrência. Para tal, é seguida a metodologia: - Estudos geológicos e estruturais com imagens de satélite e reconhecimento “in situ”; - Caraterização geográfica, hidrológica e hidrogeológica na envolvente das Termas do Eirogo; - Caraterização da captação e da água termal; - Integração de dados geofísicos; - Proposta de um modelo hidrogeológico., European Regional Development Fund (EU), COMPETE 2020 120 - project ICT (UID/GEO/04683/2013) with reference POCI-01-0145-FEDER-007690 and pro121 ject Nano-MINENV 029259.