The Emergence of Canalization and Evolvability in an Open-Ended, Interactive Evolutionary System

Natural evolution has produced a tremendous diversity of functional organisms. Many believe an essential component of this process was the evolution of evolvability, whereby evolution speeds up its ability to innovate by generating a more adaptive pool of offspring. One hypothesized mechanism for evolvability is developmental canalization, wherein certain dimensions of variation become more likely to be traversed and others are prevented from being explored (e.g. offspring tend to have similarly sized legs, and mutations affect the length of both legs, not each leg individually). While ubiquitous in nature, canalization almost never evolves in computational simulations of evolution. Not only does that deprive us of in silico models in which to study the evolution of evolvability, but it also raises the question of which conditions give rise to this form of evolvability. Answering this question would shed light on why such evolvability emerged naturally and could accelerate engineering efforts to harness evolution to solve important engineering challenges. In this paper we reveal a unique system in which canalization did emerge in computational evolution. We document that genomes entrench certain dimensions of variation that were frequently explored during their evolutionary history. The genetic representation of these organisms also evolved to be highly modular and hierarchical, and we show that these organizational properties correlate with increased fitness. Interestingly, the type of computational evolutionary experiment that produced this evolvability was very different from traditional digital evolution in that there was no objective, suggesting that open-ended, divergent evolutionary processes may be necessary for the evolution of evolvability.Comment: SI can be found at: http://www.evolvingai.org/files/SI_0.zi

The Formative Years of the Modern Corporation: The Dutch East India Company VOC, 1602-1623

With their legal personhood, permanent capital with transferable shares, separation of ownership and management, and limited liability for both shareholders and managers, the Dutch East India Company (VOC) and subsequently the English East India Company (EIC) are generally considered a major institutional breakthrough. Our analysis of the business operations and notably the financial policy of the VOC during the company’s first two decades in existence shows that its c

An Admiralty for Asia: Isaac le Maire and conflicting conceptions about the corporate governance of the VOC

The Dutch East India Company or VOC in 1602 showed many characteristics of modern corporations, including limited liability, freely transferable shares, and well-defined managerial functions. However, we challenge the notion of the VOC as the precursor of modern corporations to argue that the company was a hybrid, combining elements from traditional partnerships with a governance structure modeled on existing public-private partnerships. The company’s charter r

Gastroparesis in patients with inactive Crohn's disease: a case series

BACKGROUND: Few studies have described patients with foregut dysmotility in inflammatory bowel disease. The aim of this case series was to evaluate clinical characteristics of 5 patients with inflammatory bowel disease and symptoms and signs of upper gut dysmotility. CASE PRESENTATIONS: We describe a series of four patients with Crohn's disease and one with indeterminate colitis who presented with severe symptoms and signs of gastroparesis. We reviewed medical records of all cases. Gastric emptying of a solid meal was assessed by scintigraphy. Small bowel enteroclysis, gastroduodenoscopy and colonoscopy with biopsies were performed to estimate the activity of the disease and to exclude organic obstruction. None of the patients had any signs of active inflammation or stricture. All of the patients had markedly delayed gastric emptying with a mean t 1/2 of 234 minutes (range 110–380 minutes; normal values 54–94 minutes). CONCLUSION: Clinicians should consider impaired gastric emptying when evaluating patients with Crohn's disease and severe symptoms of upper gut dysmotility, which cannot be attributed to active inflammation or organic obstruction of the digestive tract. Symptoms in these patients are refractory to various therapeutic interventions including tube feeding and gastric surgery

Vascular Endothelial Growth Factor in the Circulation in Cancer Patients May Not Be a Relevant Biomarker

Levels of circulating vascular endothelial growth factor (VEGF) have widely been used as biomarker for angiogenic activity in cancer. For this purpose, non-standardized measurements in plasma and serum were used, without correction for artificial VEGF release by platelets activated ex vivo. We hypothesize that "true" circulating (c)VEGF levels in most cancer patients are low and unrelated to cancer load or tumour angiogenesis. We determined VEGF levels in PECT, a medium that contains platelet activation inhibitors, in citrate plasma, and in isolated platelets in 16 healthy subjects, 18 patients with metastatic non-renal cancer (non-RCC) and 12 patients with renal cell carcinoma (RCC). In non-RCC patients, circulating plasma VEGF levels were low and similar to VEGF levels in controls if platelet activation was minimized during the harvest procedure by PECT medium. In citrate plasma, VEGF levels were elevated in non-RCC patients, but this could be explained by a combination of increased platelet activation during blood harvesting, and by a two-fold increase in VEGF content of individual platelets (controls: 3.4 IU/10(6), non-RCC: 6.2 IU/10(6) platelets, p = 0.001). In contrast, cVEGF levels in RCC patients were elevated (PECT plasma: 64 pg/ml vs. 21 pg/ml, RCC vs. non-RCC, p<0.0001), and not related to platelet VEGF concentration. Our findings suggest that "true" freely cVEGF levels are not elevated in the majority of cancer patients. Previously reported elevated plasma VEGF levels in cancer appear to be due to artificial release from activated platelets, which in cancer have an increased VEGF content, during the blood harvest procedure. Only in patients with RCC, which is characterized by excessive VEGF production due to a specific genetic defect, were cVEGF levels elevated. This observation may be related to limited and selective success of anti-VEGF agents, such as bevacizumab and sorafenib, as monotherapy in RCC compared to other forms of cance

High-level algorithm prototyping: An example extending the TVR-DART algorithm

Operator Discretization Library (ODL) is an open-source Python library for prototyping reconstruction methods for inverse problems, and ASTRA is a high-performance Matlab/Python toolbox for large-scale tomographic reconstruction. The paper demonstrates the feasibility of combining ODL with ASTRA to prototype complex reconstruction methods for discrete tomography. As a case in point, we consider the total-variation regularized discrete algebraic reconstruction technique (TVR-DART). TVR-DART assumes that the object to be imaged consists of a limited number of distinct materials. The ODL/ASTRA implementation of this algorithm makes use of standardized building blocks, that can be combined in a plug-and-play manner. Thus, this implementation of TVR-DART can easily be adapted to account for application specific aspects, such as various noise statistics that come with different imaging modalities

Smooth Muscle Progenitor Cells: Friend or Foe in Vascular Disease?

The origin of vascular smooth muscle cells that accumulate in the neointima in vascular diseases such as transplant arteriosclerosis, atherosclerosis and restenosis remains subject to much debate. Smooth muscle cells are a highly heterogeneous cell population with different characteristics and markers, and distinct phenotypes in physiological and pathological conditions. Several studies have reported a role for bone marrow-derived progenitor cells in vascular maintenance and repair. Moreover, bone marrow-derived smooth muscle progenitor cells have been detected in human atherosclerotic tissue as well as in in vivo mouse models of vascular disease. However, it is not clear whether smooth muscle progenitor cells can be regarded as a ‘friend’ or ‘foe’ in neointima formation. In this review we will discuss the heterogeneity of smooth muscle cells, the role of smooth muscle progenitor cells in vascular disease, potential mechanisms that could regulate smooth muscle progenitor cell contribution and the implications this may have on designing novel therapeutic tools to prevent development and progression of vascular disease