Information flow and optimization in transcriptional control

In the simplest view of transcriptional regulation, the expression of a gene is turned on or off by changes in the concentration of a transcription factor (TF). We use recent data on noise levels in gene expression to show that it should be possible to transmit much more than just one regulatory bit. Realizing this optimal information capacity would require that the dynamic range of TF concentrations used by the cell, the input/output relation of the regulatory module, and the noise levels of binding and transcription satisfy certain matching relations. This parameter-free prediction is in good agreement with recent experiments on the Bicoid/Hunchback system in the early Drosophila embryo, and this system achieves ~90% of its theoretical maximum information transmission.Comment: 5 pages, 4 figure

Handleiding Paprika model “Cultivista” - Project Topmodel4all / 2010-2011

Abstract NL Deze handleiding is bedoeld voor telers die aan de slag willen met het paprika model “Cultivista”. Er wordt uitgelegd hoe met het interactieve paprika model “Cultivista” kan worden gewerkt. De installatie van het model en de verschillende in te voeren gegevens (inputs) van het model worden besproken. Vervolgens worden de werking van het model en de onderdelen van de interface besproken. Tevens worden de voorwaarden voor mogelijke automatisering van de inputs en het oplossen van de meest voorkomende problemen besproken. Abstract UK This manual is meant for growers who would like to work with the sweet pepper growth model “Cultivista”. This manual explains how the model works, how to install the model and which inputs are used. Furthermore, the different parts of the interface are explained. Finally, the conditions for automation of the inputs and troubleshooting of the most common problems are discussed

The Role of Regulated mRNA Stability in Establishing Bicoid Morphogen Gradient in Drosophila Embryonic Development

The Bicoid morphogen is amongst the earliest triggers of differential spatial pattern of gene expression and subsequent cell fate determination in the embryonic development of Drosophila. This maternally deposited morphogen is thought to diffuse in the embryo, establishing a concentration gradient which is sensed by downstream genes. In most model based analyses of this process, the translation of the bicoid mRNA is thought to take place at a fixed rate from the anterior pole of the embryo and a supply of the resulting protein at a constant rate is assumed. Is this process of morphogen generation a passive one as assumed in the modelling literature so far, or would available data support an alternate hypothesis that the stability of the mRNA is regulated by active processes? We introduce a model in which the stability of the maternal mRNA is regulated by being held constant for a length of time, followed by rapid degradation. With this more realistic model of the source, we have analysed three computational models of spatial morphogen propagation along the anterior-posterior axis: (a) passive diffusion modelled as a deterministic differential equation, (b) diffusion enhanced by a cytoplasmic flow term; and (c) diffusion modelled by stochastic simulation of the corresponding chemical reactions. Parameter estimation on these models by matching to publicly available data on spatio-temporal Bicoid profiles suggests strong support for regulated stability over either a constant supply rate or one where the maternal mRNA is permitted to degrade in a passive manner

Near infrared few-cycle pulses for high harmonic generation

We report on the development of tunable few-cycle pulses with central wavelengths from 1.6 um to 2 um. Theses pulses were used as a proof of principle for high harmonic generation in atomic and molecular targets. In order to generate such pulses we produced a filament in a 4 bar krypton cell. Spectral broadening by a factor of 2 to 3 of a 40 fs near infrared input pulse was achieved. The spectrally broadened output pulses were then compressed by fused silica plates down to the few-cycle regime close to the Fourier limit. The auto-correlation of these pulses revealed durations of about 3 cycles for all investigated central wavelengths. Pulses with a central wavelength of 1.7 um and up to 430 uJ energy per pulse were employed to generate high order harmonics in Xe, Ar and N2. Moving to near infrared few-cycle pulses opens the possibility to operate deeply in the non-perturbative regime with a Keldysh parameter smaller than 1. Hence, this source is suitable for the study of the non-adiabatic tunneling regime in most generating systems used for high order harmonic generation and attoscience.Comment: 12 pages, 4 figure

Natural History of Pediatric Low-Grade Glioma Disease – First Multi-State Model Analysis

Background: Pediatric low-grade glioma [PLGG] is often a chronic progressive disease requiring multiple treatments, i.e. surgery, chemotherapy and irradiation. The multi-state model [MSM] allows an extended analysis of disease-states, that patients may undergo, incorporating competing risks over the course of time. Purpose: We studied disease-state-probabilities of the German SIOP-LGG 2004 cohort from the initial state "diagnosis" to the final state "death". Transient "disease-states" incorporated successive surgical and non-surgical treatments. We evaluated clinical risk factors for highly progressive disease requiring multiple interventions and death. Results: We identified 22 states within 1587 patients (median follow-up 6.3 years). For robust statistical calculation, we reduced the model to 7 states and eventually to three levels of disease-progressiveness: non, low and highly progressive. Five years after diagnosis state-probabilities were: 0.11 no therapy, 0.49 one and 0.11 two or more surgeries only, 0.19 one and 0.06 two or more non-surgical interventions with or without prior surgery. At this time point higher probability for highly progressive disease was found in infants (0.30), supratentorial-midline location (0.17) and diffuse astrocytoma WHO-grade II (0.12). Neurofibromatosis type-1 patients were most likely not to be treated (0.36) or to have received only non-surgical therapy (0.45). Two years after diagnosis 3-year predictions for highly progressive disease and death increased with the number of interventions patients underwent in the first 2 years after diagnosis. Conclusion: In this first MSM analysis we delineated a refined description of PLGG disease course over time, identifying three levels of progressiveness. Growth behavior in the first two years predicted future progressiveness and death

Portal vein thrombosis and hemostatic alterations in patients with advanced liver diseases

In patients with liver diseases, the liver has a reduced capacity to produce pro- and antihemostatic proteins. This results in a rebalanced hemostatic system, which remains stable in patients with stable liver diseases but can be fragile in those with additional disease complications, such as inflammation or renal failure. Although liver diseases were long associated with an increased risk of bleeding, hemostasis-related bleeding is rare in patients with liver diseases. With increasing insights, it becomes evident that patients with liver diseases have an elevated risk of thrombotic complications, with portal vein thrombosis being the primary concern. The pathophysiology of portal vein thrombosis is not fully understood. The studies described in this thesis aimed to gain more insights into the development of portal vein thrombosis in patients with chronic liver diseases. The results showed that, in most patients with portal vein thrombosis, there is no classical thrombus consisting of fibrin, platelets, and red blood cells. Instead, the obstruction of the portal vein is caused by thickening of the vessel wall. Portal vein thrombosis may therefore be a misnomer and might be more accurately termed as 'portal vein stenosis' or 'portal vein intima hyperplasia.' Additionally, we investigated whether blood in the portal vein of liver patients has locally elevated levels of markers of activation of coagulation or inflammation, due to drainage from the intestines. This could potentially lead to a locally increased risk of thrombosis. However, no differences were found in samples taken from the systemic circulation and the portal vein. Furthermore, there was no correlation between elevated levels of markers of activation of coagulation or inflammation in the systemic circulation and the development of portal vein thrombosis in patients with chronic liver diseases. Factors related to the development of portal vein thrombosis were factors that are associated with portal hypertension and changes in portal blood flow. The findings described may explain why treatment with anticoagulants is not always effective in the treatment of portal vein thrombosis in cirrhosis. The insights described in this thesis pave the way for exploring new treatment strategies. Future studies should focus on investigating safe and effective pharmacotherapeutic interventions for the prevention and treatment of portal vein thrombosis or portal vein intima hyperplasia in patients with chronic liver diseases

Phenotyping of field-grown wheat in the UK highlights contribution of light response of photosynthesis and flag leaf longevity to grain yield

Improving photosynthesis is a major target for increasing crop yields and ensuring food security. Phenotyping of photosynthesis in the field is critical to understand the limits to crop performance in agricultural settings. Yet, detailed phenotyping of photosynthetic traits is relatively scarce in field-grown wheat, with previous studies focusing on narrow germplasm selections. Flag leaf photosynthetic traits, crop development, and yield traits were compared in 64 field-grown wheat cultivars in the UK. Pre-anthesis and post-anthesis photosynthetic traits correlated significantly and positively with grain yield and harvest index (HI). These traits included net CO2 assimilation measured at ambient CO2 concentrations and a range of photosynthetic photon flux densities, and traits associated with the light response of photosynthesis. In most cultivars, photosynthesis decreased post-anthesis compared with pre-anthesis, and this was associated with decreased Rubisco activity and abundance. Heritability of photosynthetic traits suggests that phenotypic variation can be used to inform breeding programmes. Specific cultivars were identified with traits relevant to breeding for increased crop yields in the UK: pre-anthesis photosynthesis, post-anthesis photosynthesis, light response of photosynthesis, and Rubisco amounts. The results indicate that flag leaf longevity and operating photosynthetic activity in the canopy can be further exploited to maximize grain filling in UK bread wheat

Demographic and Census Trends of Latinos in the Kansas City Area

Presentation made at Latinos in Missouri (2nd : 2007 : Kansas City, Mo.) and published in the annual conference proceedings

Shared decision making in hospital care:what happens in practice

Shared decision making (SDM) is presented by the government, and by patient and healthcare organizations, as the preferred model of decision making in medical consultations. SDM can improve therapy adherence and patient outcomes. SDM allows the physician’s medical expertise to be coupled to the patient’s unique situation, views and preferences.Most healthcare providers and patients want to make decisions about diagnostics and treatment together with each other. This thesis examines how doctors think about SDM, and how they apply it in daily clinical practice. We videotaped 781 consultations between hospital-based consultants and their patients, and analyzed the decision-making process. In these consultations, doctors applied less SDM than they prefer and they thought they did. They presented different options, then made a proposal and asked the patient to consent with this treatment. However, they skipped a key SDM step: choice awareness. Making it clear that a choice has to be made, and that the physician and patient decide together, as a team, which option best fits the patient’s current situation.Our studies show that doctors need to be made aware of their own decision-making behavior, as they do not apply as much SDM as they think they do. In addition, skills training is required to support doctors to apply all SDM steps. In this dissertation, we propose an SDM training model to promote that doctors make decisions with their patients instead of for their patients

Food chain inefficiency (FCI) : accounting conversion efficiencies across entire food supply chains to re-define food loss and waste

Achieving global food security requires a new approach that integrates not only all aspects of the growing, harvesting and processing of food (necessary to ensure sufficient affordable and sustainable production to alleviate hunger) but also the complexities associated with food consumption including deterring unhealthy overconsumption. Inefficiencies occur at various points along the agri-food supply chain but at present they are inadequately conceptualized via separate accounts of food loss, food waste, supply chain management, and public health. Here we re-define food loss and waste through the concept of conversion efficiency applied to the entire system, an approach up to now only applied to the primary processes of crop productivity. Nine conversion efficiencies are defined: sunlight capture efficiency; photosynthesis use efficiency; biomass allocation efficiency; harvesting efficiency; storage and distribution efficiency; processing efficiency; retailing efficiency; consumption efficiency; and dietary efficiency. Using the production and consumption of bread in the UK as an example, we demonstrate how efficiencies may be estimated and thus where the main inefficiencies lie, so indicating where the most significant improvements could be made. We suggest that our approach, which introduces the term Food Chain Inefficiency (FCI) to re-define food loss and waste, provides a rational and effective way to devise the practical interventions and policies needed to deliver a sustainable agri-food system