1,024 research outputs found

    Cargo dwell time in Durban : lessons for Sub-Saharan African ports

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    Based on quantitative and qualitative data, this paper attempts to identify the main reasons why cargo dwell time in Durban port has dramatically reduced in the past decade to a current average of 3-4 days. A major customs reform; changes in port storage tariffs coupled with strict enforcement; massive investments in infrastructure and equipment; and changing customer behavior through contractualization between the port operator and shipping lines or between customs, importers, and brokers have all played a major role. The main lesson for Sub-Saharan Africa that can be drawn from Durban is that cargo dwell time is mainly a function of the characteristics of the private sector, but it is the onus of public sector players, such as customs and the port authority, to put pressure on the private sector to make more efficient use of the port and reduce cargo dwell time.Transport Economics Policy&Planning,Transport and Trade Logistics,Common Carriers Industry,Ports&Waterways,Airports and Air Services

    Pan-urologic cancer genomic subtypes that transcend tissue of origin

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    AbstractUrologic cancers include cancers of the bladder, kidney, prostate, and testes, with common molecular features spanning different types. Here, we show that 1954 urologic cancers can be classified into nine major genomic subtypes, on the basis of multidimensional and comprehensive molecular characterization (including DNA methylation and copy number, and RNA and protein expression). Tissue dominant effects are first removed computationally in order to define these subtypes, which reveal common processes—reflecting in part tumor microenvironmental influences—driving cellular behavior across tumor lineages. Six of the subtypes feature a mixture of represented cancer types as defined by tissue or cell of origin. Differences in patient survival and in the manifestation of specific pathways—including hypoxia, metabolism, NRF2-ARE, Hippo, and immune checkpoint—can further distinguish the subtypes. Immune checkpoint markers and molecular signatures of macrophages and T cell infiltrates are relatively high within distinct subsets of each cancer type studied. The pan-urologic cancer genomic subtypes would facilitate information sharing involving therapeutic implications between tissue-oriented domains.</jats:p

    Neuroblastoma patient outcomes, tumor differentiation, and ERK activation are correlated with expression levels of the ubiquitin ligase UBE4B.

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    BackgroundUBE4B is an E3/E4 ubiquitin ligase whose gene is located in chromosome 1p36.22. We analyzed the associations of UBE4B gene and protein expression with neuroblastoma patient outcomes and with tumor prognostic features and histology.MethodsWe evaluated the association of UBE4B gene expression with neuroblastoma patient outcomes using the R2 Platform. We screened neuroblastoma tumor samples for UBE4B protein expression using immunohistochemistry. FISH for UBE4B and 1p36 deletion was performed on tumor samples. We then evaluated UBE4B expression for associations with prognostic factors and with levels of phosphorylated ERK in neuroblastoma tumors and cell lines.ResultsLow UBE4B gene expression is associated with poor outcomes in patients with neuroblastoma and with worse outcomes in all patient subgroups. UBE4B protein expression was associated with neuroblastoma tumor differentiation, and decreased UBE4B protein levels were associated with high-risk features. UBE4B protein levels were also associated with levels of phosphorylated ERK.ConclusionsWe have demonstrated associations between UBE4B gene expression and neuroblastoma patient outcomes and prognostic features. Reduced UBE4B protein expression in neuroblastoma tumors was associated with high-risk features, a lack of differentiation, and with ERK activation. These results suggest UBE4B may contribute to the poor prognosis of neuroblastoma tumors with 1p36 deletions and that UBE4B expression may mediate neuroblastoma differentiation

    Liability of the Structural Engineer: Establishing, Quantifying, and Managing Risks

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    Liability is an important topic to all practicing professionals—including practicing engineers. However, the topic of liability does not receive the necessary attention required relative to other professions. Further, engineers that desire to learn more about liability in relation to their practice do not have many university options within an engineering curriculum or from outside materials available to a non-legally trained engineer. The goal of the study is to provide a comprehensive overview of liability directed towards an intelligent practicing engineer, while avoiding unnecessary over-simplification of the material. This study initially provides an in depth survey of the legal standard of care for a structural engineer – i.e. a major factor in determining whether liability is established in a case involving engineering fault. Next, the study reviews the extent to which an engineer can be personally liable if conduct giving rise to liability is established. This study examines the personal liability of an engineer in several different forms of practice, as well as reviewing the implications (or lack thereof) for sealing or failing to properly seal plans. Finally, this study provides an in-depth examination of a common technique used to manage risk through contract terms and conditions. This technique is negotiating a clause into the service agreement which limits liability. Courts will generally enforce these limitation of liability clauses, but there are many circumstances in which they will be deemed void

    Private–public partnerships: A mechanism for freight transport infrastructure delivery?

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    Abstract: Freight transport infrastructure is an indispensable requirement for economic growth, development and prosperity. Public–private partnerships (PPPs), as a mechanism to fund and construct freight transport infrastructure, have been suggested by many in private and public sectors. Objectives: The concept of PPPs is dealt with, and the relevance of this mechanism is expanded upon. It is clear that PPPs in the rail environment present huge challenges and complexities. The objective was to determine whether PPPs are a viable mechanism to fund freight transport infrastructure in South Africa. Method: Experiences with rail PPPs worldwide have shown that many failures occurred implementing these. The challenges and complexities of PPPs, in the freight rail environment, are highlighted together with the benefits, risks and best practices of PPPs. It is shown that suitable policies, legislation and regulations concerning PPPs are in place in South Africa. Results: A proper framework and methodology to proceed should be in place. PPPs take time and are complex. Government involvement remains essential. Firm contractual agreements between parties are essential. Risk handling, risk sharing and the magnitude of risks should be clarified with agreement on where the risks reside. Financial viability, with value for money (VfM) and financial benefits for private sector role players are non-negotiable. Conclusion: Appropriate legislation for implementing PPPs must be in place while two further important elements are economic circumstances and proper project execution. Taking all these factors into consideration, the freight transport sector can only benefit from successfully negotiated and implemented PPPs

    Pan-cancer Alterations of the MYC Oncogene and Its Proximal Network across the Cancer Genome Atlas

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    Although theMYConcogene has been implicated incancer, a systematic assessment of alterations ofMYC, related transcription factors, and co-regulatoryproteins, forming the proximal MYC network (PMN),across human cancers is lacking. Using computa-tional approaches, we define genomic and proteo-mic features associated with MYC and the PMNacross the 33 cancers of The Cancer Genome Atlas.Pan-cancer, 28% of all samples had at least one ofthe MYC paralogs amplified. In contrast, the MYCantagonists MGA and MNT were the most frequentlymutated or deleted members, proposing a roleas tumor suppressors.MYCalterations were mutu-ally exclusive withPIK3CA,PTEN,APC,orBRAFalterations, suggesting that MYC is a distinct onco-genic driver. Expression analysis revealed MYC-associated pathways in tumor subtypes, such asimmune response and growth factor signaling; chro-matin, translation, and DNA replication/repair wereconserved pan-cancer. This analysis reveals insightsinto MYC biology and is a reference for biomarkersand therapeutics for cancers with alterations ofMYC or the PMN

    Retrospective value analysis of decision support benefits from a production planning system for a brewery

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    A decision support system for production planning in a brewing company was developed to assist with the planning of brewing, packaging and distribution of beer and to minimise production costs. Having been in operation for some time, the system has changed and adapted in a very dynamic environment. The system's present form and current use are discussed. Initial management approval for system development was based on faith rather than proper cost-benefit and value analyses. This paper aims at retrospectively highlighting these values and benefits with regard to supporting decision-making in the company

    Pan-Cancer Analysis of lncRNA Regulation Supports Their Targeting of Cancer Genes in Each Tumor Context

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    Long noncoding RNAs (lncRNAs) are commonly dys-regulated in tumors, but only a handful are known toplay pathophysiological roles in cancer. We inferredlncRNAs that dysregulate cancer pathways, onco-genes, and tumor suppressors (cancer genes) bymodeling their effects on the activity of transcriptionfactors, RNA-binding proteins, and microRNAs in5,185 TCGA tumors and 1,019 ENCODE assays.Our predictions included hundreds of candidateonco- and tumor-suppressor lncRNAs (cancerlncRNAs) whose somatic alterations account for thedysregulation of dozens of cancer genes and path-ways in each of 14 tumor contexts. To demonstrateproof of concept, we showed that perturbations tar-geting OIP5-AS1 (an inferred tumor suppressor) andTUG1 and WT1-AS (inferred onco-lncRNAs) dysre-gulated cancer genes and altered proliferation ofbreast and gynecologic cancer cells. Our analysis in-dicates that, although most lncRNAs are dysregu-lated in a tumor-specific manner, some, includingOIP5-AS1, TUG1, NEAT1, MEG3, and TSIX, synergis-tically dysregulate cancer pathways in multiple tumorcontexts

    Genomic, Pathway Network, and Immunologic Features Distinguishing Squamous Carcinomas

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    This integrated, multiplatform PanCancer Atlas study co-mapped and identified distinguishing molecular features of squamous cell carcinomas (SCCs) from five sites associated with smokin

    Spatial Organization and Molecular Correlation of Tumor-Infiltrating Lymphocytes Using Deep Learning on Pathology Images

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    Beyond sample curation and basic pathologic characterization, the digitized H&E-stained images of TCGA samples remain underutilized. To highlight this resource, we present mappings of tumorinfiltrating lymphocytes (TILs) based on H&E images from 13 TCGA tumor types. These TIL maps are derived through computational staining using a convolutional neural network trained to classify patches of images. Affinity propagation revealed local spatial structure in TIL patterns and correlation with overall survival. TIL map structural patterns were grouped using standard histopathological parameters. These patterns are enriched in particular T cell subpopulations derived from molecular measures. TIL densities and spatial structure were differentially enriched among tumor types, immune subtypes, and tumor molecular subtypes, implying that spatial infiltrate state could reflect particular tumor cell aberration states. Obtaining spatial lymphocytic patterns linked to the rich genomic characterization of TCGA samples demonstrates one use for the TCGA image archives with insights into the tumor-immune microenvironment
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