What we know and how we know it: Cartesian meditations on some hard problems at the interface of science and empiricist philosophy.

Laboratory science is our only source of knowledge about the world as it is apart from our perceptions of the world. Empiricist philosophy, relying on evidence consisting in human perceptions, can only give us knowledge of phenomena making up the world-perceived, which recent neuroscience tells us is wholly and entirely constructed by our neuron-based human perceptual apparatus. In this light, empiricist philosophy should explicitly and fundamentally be reconceived as a method of thinking critically about phenomena, i.e. as a stripped down, fallibilist, non-foundationalist version of “phenomenology”. I also describe implications of these proposals for thinking critically about and conceptualizing phenomena like the Cartesian “I”-that-thinks, consciousness, mind, personal identity, free will, and causal relationships between the brain and the conscious “I.

Broken chocolate:biomarkers as a method for delivering cocoa supply chain visibility

Purpose: This paper examines the potential of “biomarkers” to provide immutable identification for food products (chocolate), providing traceability and visibility in the supply chain from retail product back to farm. Design/methodology/approach: This research uses qualitative data collection, including fieldwork at cocoa farms and chocolate manufacturers in Ecuador and the Netherlands and semi-structured interviews with industry professionals to identify challenges and create a supply chain map from cocoa plant to retailer, validated by area experts. A library of biomarkers is created using DNA collected from fieldwork and the International Cocoa Quarantine Centre, holders of cocoa varieties from known locations around the world. Matching sample biomarkers with those in the library enables identification of origins of cocoa used in a product, even when it comes from multiple different sources and has been processed. Findings: Supply chain mapping and interviews identify areas of the cocoa supply chain that lack the visibility required for management to guarantee sustainability and quality. A decoupling point, where smaller farms/traders’ goods are combined to create larger economic units, obscures product origins and limits visibility. These factors underpin a potential boundary condition to institutional theory in the industry’s fatalism to environmental and human abuses in the face of rising institutional pressures. Biomarkers reliably identify product origin, including specific farms and (fermentation) processing locations, providing visibility and facilitating control and trust when purchasing cocoa. Research limitations/implications: The biomarker “meta-barcoding” of cocoa beans used in chocolate manufacturing accurately identifies the farm, production facility or cooperative, where a cocoa product came from. A controlled data set of biomarkers of registered locations is required for audit to link chocolate products to origin. Practical implications: Where biomarkers can be produced from organic products, they offer a method for closing visibility gaps, enabling responsible sourcing. Labels (QR codes, barcodes, etc.) can be swapped and products tampered with, but biological markers reduce reliance on physical tags, diminishing the potential for fraud. Biomarkers identify product composition, pinpointing specific farm(s) of origin for cocoa in chocolate, allowing targeted audits of suppliers and identifying if cocoa of unknown origin is present. Labour and environmental abuses exist in many supply chains and enabling upstream visibility may help firms address these challenges. Social implications: By describing a method for firms in cocoa supply chains to scientifically track their cocoa back to the farm level, the research shows that organizations can conduct social audits for child labour and environmental abuses at specific farms proven to be in their supply chains. This provides a method for delivering supply chain visibility (SCV) for firms serious about tackling such problems. Originality/value: This paper provides one of the very first examples of biomarkers for agricultural SCV. An in-depth study of stakeholders from the cocoa and chocolate industry elucidates problematic areas in cocoa supply chains. Biomarkers provide a unique biological product identifier. Biomarkers can support efforts to address environmental and social sustainability issues such as child labour, modern slavery and deforestation by providing visibility into previously hidden areas of the supply chain

Overcoming Adaptive Resistance to Anti-vegf Therapy by Targeting CD5L

Antiangiogenic treatment targeting the vascular endothelial growth factor (VEGF) pathway is a powerful tool to combat tumor growth and progression; however, drug resistance frequently emerges. We identify CD5L (CD5 antigen-like precursor) as an important gene upregulated in response to antiangiogenic therapy leading to the emergence of adaptive resistance. By using both an RNA-aptamer and a monoclonal antibody targeting CD5L, we are able to abate the pro-angiogenic effects of CD5L overexpression in both in vitro and in vivo settings. In addition, we find that increased expression of vascular CD5L in cancer patients is associated with bevacizumab resistance and worse overall survival. These findings implicate CD5L as an important factor in adaptive resistance to antiangiogenic therapy and suggest that modalities to target CD5L have potentially important clinical utility

A Mississippian black shale record of redox oscillation in the Craven Basin, UK

Early diagenetic redox oscillation processes have been rarely recognised in the ancient rock record but potentially exert an important control on mineral authigenesis, hydrocarbon prospectivity and supply of metals and/or reduced S as part of associated mineral systems. The upper unit of the Mississippian Bowland Shale Formation is a candidate record of diagenetic redox oscillation processes because it was deposited under a relatively high sediment accumulation rate linked to a large delta system, and under dominantly anoxic and intermittently sulphidic bottom-water conditions. In order to characterise the syngenetic and early diagenetic processes, sedimentological and geochemical data were integrated through the Upper Bowland Shale at three sites in the Craven Basin (Lancashire, UK). Organic matter (OM) comprises a mixture of Type II, II-S, II/III and III OM. ‘Redox zones’ are defined by patterns of Fe-speciation and redox-sensitive trace element enrichment and split into two groups. ‘Sulphidic’ zones (EUX, AN-III, AN-I and AN-IT) represent sediments deposited under conditions of at least intermittently active sulphate-reduction in bottom-waters. ‘Non-sulphidic’ zones (OX-RX, OX-F and OX) represent sediments deposited under non-sulphidic (oxic to ferruginous anoxic) bottom-waters. Operation of a shelf-to-basin ‘reactive Fe’ (FeHR) shuttle, moderated by sea level fluctuation and delta proximity, controlled the position and stability of redoxclines between zones of Fe and sulphate reduction, and methanogenesis. Early diagenetic redoxclines were capable of migration through the shallow sediment column relatively quickly, in response to sea level fluctuation. Preservation of syngenetic and early diagenetic geochemical signals shows redoxclines between Fe and sulphate reduction, and the upper boundary of sulphate-methane transition zone, were positioned within decimetres (i.e., 10 s cm) of seabed. Falling sea level and increasing FeHR supply is recognised as a switch from zones EUX (high sea level), AN-III and ultimately AN-I and AN-IT (low sea level). Zone AN-I defines the operation of ‘redox oscillation’, between zones of Fe and sulphate reduction in shallow porewaters, associated with enhanced degradation of OM and complete dissolution of primary carbonate. Preservation of OM and carbonate, in this system, was a function of changing bottom and pore water redox processes. Redox oscillation operated in a siliciclastic, prodeltaic environment associated with a relatively high sediment accumulation rate and high loadings of labile organic matter and metal oxides. These findings are important for understanding Late Palaeozoic black shales in the context of hydrocarbon and mineral systems

SOX2 is an amplified lineage-survival oncogene in lung and esophageal squamous cell carcinomas

Lineage survival oncogenes are activated by somatic DNA alterations in cancers arising from the cell lineages in which these genes play a role in normal development.1,2 Here we show that a peak of genomic amplification on chromosome 3q26.33, found in squamous cell carcinomas (SCCs) of the lung and esophagus, contains the transcription factor gene SOX2—which is mutated in hereditary human esophageal malformations3 and necessary for normal esophageal squamous development4, promotes differentiation and proliferation of basal tracheal cells5 and co-operates in induction of pluripotent stem cells.6,7,8 SOX2 expression is required for proliferation and anchorage-independent growth of lung and esophageal cell lines, as shown by RNA interference experiments. Furthermore, ectopic expression of SOX2 cooperated with FOXE1 or FGFR2 to transform immortalized tracheobronchial epithelial cells. SOX2-driven tumors show expression of markers of both squamous differentiation and pluripotency. These observations identify SOX2 as a novel lineage survival oncogene in lung and esophageal SCC

Some Foundations for a radically pluralist but genuinely critical theory of religions

This article argues (against John Hick and Huston Smith) that different religions teach truths that are different even at the most fundamental level. Nevertheless these are genuine axiological truth claims that can be subject to rational evaluation, differentiating well-founded interpretations of a given religion from interpretations that are not well-founded