EVALUATION OF CURRENT CLINICAL CRITERIA FOR LI-FRAUMENI SYNDROME IN A DIVERSE SAMPLE OF TP53 MUTATION CARRIERS

Li-Fraumeni syndrome (LFS) is a hereditary cancer predisposition syndrome caused by heterozyogous germline mutations in the TP53 gene and characterized by an excess of early-onset cancers, high lifetime risk of cancer, and a wide range of tumor types. Recent studies suggesting a benefit in comprehensive screening protocols for both children and adults make the timely identification of individuals with LFS increasingly important. A number of criteria have been proposed to identify patients with LFS. The National Comprehensive Cancer Network (NCCN) combines several in its Clinical Practice Guidelines for TP53 genetic testing. Prior studies have shown that the cumulative sensitivity of criteria included in these guidelines approaches 100% in populations referred for testing due to clinical suspicion based on personal and family histories at the time of test requisition. Because NCCN guidelines are created and revised by panels of experts and are commonly utilized by both providers and insurance companies, we choose to evaluate these guidelines in order to assess the performance of current of TP53 genetic testing criteria. By retrospectively analyzing the cancer histories of positive and negative families within the M.D. Anderson Cancer Center TP53 Research database, estimates of the individual and cumulative sensitivities and specificities of criteria schemes included in the NCCN guidelines were made at the time of the index patient’s initial cancer diagnosis and again at the time of last contact with each family. Out of 122 TP53 positive families in our sample, 22% (27/122) were missed by NCCN guidelines at the time of the index patient’s initial cancer diagnosis. ‘De novo’ mutations and inherited mutations exhibiting incomplete penetrance were particularly likely to be missed, indicating a need for additional criteria able to identify TP53 mutation carriers in the absence of significant family history. Interestingly, in 22 of the 27 families missed by NCCN guidelines, the index patient had sarcoma diagnosed diagnosis, suggesting that TP53 genetic testing should be considered in any individual with early-onset sarcoma, regardless of family history

The impact of mutation and gene conversion on the local diversification of antigen genes in African trypanosomes

Patterns of genetic diversity in parasite antigen gene families hold important information about their potential to generate antigenic variation within and between hosts. The evolution of such gene families is typically driven by gene duplication, followed by point mutation and gene conversion. There is great interest in estimating the rates of these processes from molecular sequences for understanding the evolution of the pathogen and its significance for infection processes. In this study, a series of models are constructed to investigate hypotheses about the nucleotide diversity patterns between closely related gene sequences from the antigen gene archive of the African trypanosome, the protozoan parasite causative of human sleeping sickness in Equatorial Africa. We use a hidden Markov model approach to identify two scales of diversification: clustering of sequence mismatches, a putative indicator of gene conversion events with other lower-identity donor genes in the archive, and at a sparser scale, isolated mismatches, likely arising from independent point mutations. In addition to quantifying the respective probabilities of occurrence of these two processes, our approach yields estimates for the gene conversion tract length distribution and the average diversity contributed locally by conversion events. Model fitting is conducted using a Bayesian framework. We find that diversifying gene conversion events with lower-identity partners occur at least five times less frequently than point mutations on variant surface glycoprotein (VSG) pairs, and the average imported conversion tract is between 14 and 25 nucleotides long. However, because of the high diversity introduced by gene conversion, the two processes have almost equal impact on the per-nucleotide rate of sequence diversification between VSG subfamily members. We are able to disentangle the most likely locations of point mutations and conversions on each aligned gene pair

Crystallinity And Ultrastructure Of Ammoniated Wood Part II. Ultrastructure

Cell-wall layering, pits, and lumen surfaces of loblolly pine wood were examined in the electron microscope for changes due to ammonia treatment. Both normal and compression wood cell walls were crimped circumferentially after ammoniation as evidenced by deformations in the S3 and/or S1 layers. Such crimping would imply a cell-wall consolidation due to shrinkage in the S2, and the overall phenomenon was probably responsible for the increase in X-ray crystallinity of the same material. Other ultrastructural changes included definite pit aspiration and the deposition of an incmstant-like substance onto both pit structure and lumen surfaces. This incrustant was probably some residual wood extractive or other wall constituent partially solubilized by condensed ammonia in the cell

Green Computer and Video Games: An Introduction

Whether framed as environmental communication, ’sustainable media’, ‘eco-media’, or ‘green popular culture’ environmental media and cultural studies constitutes an embryonic but rapidly developing body of research. The vibrant, multi-layered engagements of the eight essays collected here demonstrate not only that green gaming engages with all of the issues addressed in that research but also that games and game studies can expand the range of this incipient green media and cultural studies. This volume of Ecozon@is the first collection of essays to focus exclusively on the topic of ‘Green Computer and Video Games’. Working from these essays, we will demonstrate in Part I of this introduction how attributes specific to gaming might address and expand our understanding of environments and ecological relations; and, in Part II, how these essays might help develop green game studies itself

Isolation of 39 polymorphic microsatellite loci and the development of a fluorescently labelled marker set for the Eurasian badger

We have isolated 78 microsatellite loci from the Eurasian badger (Meles meles). Of the 52 loci characterized, 39 were found to be polymorphic. A fluorescently labelled primer set was developed to enable individual-specific 17-locus genotypes to be obtained efficiently

Influence of the underneath cavity on buoyant-forced cooling of the integrated photovoltaic panels in building roof: a thermography study

Airflow around building-integrated photovoltaics (BIPV) has a significant impact on their hygrothermal behavior and degradation. The potential of reducing the temperature of BIPV using an underneath cavity is experimentally and numerically investigated in literature. Most of the models are oversimplified in terms of modeling the impact of 3D flow over/underneath of PV modules, which can result in a non-uniform surface temperature and consequently a non-homogenous thermal degradation. Moreover, the simultaneous presence of radiation and convection related to upstream wind, in addition to the combined impact of back-ventilation and surface convection, is barely addressed in literature. However, these simplifications can result in the unrealistic loading climate conditions. This paper aims to present a unique experimental setup to provide more realistic climate conditions for investigating the ventilation potential of the underneath. The setup consists of a solar simulator and a building prototype with installed PV, placed inside an atmospheric wind tunnel to control upstream wind velocity. Thermography is performed using an infrared camera to monitor the surface temperature of the BIPV. The potential of an underneath cavity with various cavity heights and PV arrangement is further investigated in this paper. The outcome would be eventually useful in the development of practical guidelines for BIPV installation. Copyright © 2013 John Wiley & Sons, Ltd

Validation of a Climatic CFD Model to Predict the Surface Temperature of Building Integrated Photovoltaics

AbstractThe current market of the photovoltaic (PV) industry is dominated by silicon-based modules, which are malfunctioned and degraded in higher temperatures mainly above 25°C. Consequently, one of the challenges for such modules is finding a more efficient way in their integration into the buildings in order to reduce the mentioned temperature. The present work is a part of a comprehensive framework toward the investigation of the lifetime durability of the BIPV modules. Therefore, this paper explain the development and validation of a computational fluid dynamics (CFD) model to be later utilized to evaluate the temperature distribution of BIPV's surfaces under different arrangements and climate loadings. For this purpose, a high resolution 3D CFD model is firstly developed by generation of about 3 million cells. Then, the model is validated with a velocimetry experimental dataset from the same model tested in a wind tunnel experiment by [6]. Furthermore, the solar radiation is added into simulation to model the non-isothermal condition of the BIPV module. The non-isothermal case is further validated with a thermography observation conducted by [5] where a solar simulator is installed inside the tunnel. The simulation results show that the developed model can accurately simulate the impact of 3D flow over/underneath the PV modules

Integrated sub-regional planning informed by weighted spatial network models: The case of Jeddah sub-regional system

Existing Space Syntax methodologies provide the tools to measure the impact of proposed spatial changes, but are strongly dependant on the quality and availability of the spatial data. This becomes particularly more complex when major land use changes or development projects are proposed in a large region and there is no or vey little spatial layout data available for them. To counter this problem it is suggested that an 'integrated urban model' can be developed by using land use and demographic data to supplement the lack of spatial layout data and create a more realistic model for evaluating planning decisions. This paper explores the use of a 'weighted space syntax' model to contribute to the process of integrated urban planning for a large urban region in a major planning exercise in Jeddah, Saudi Arabia. The study aims at identifying the growth pattern and development potentials of the Jeddah Sub-regional system along with testing planning proposals for its growth over the next twenty years. The method for allocating the weighting to the segments of spatial networks by dividing the city into 'superblocks', identified by the foreground network and morphological similarities or spatial conditions such as existing municipal districts and major development boundaries. The weighting is then applied to the segments per unit length since longer segments have a higher probability of having a higher number of plots. The output is a spatial analysis impacted by the land use distribution, which adds the attraction or repulsion to movement generated by certain land uses to the spatial configuration and provides an accurate depiction of the functioning of the city. With this methodology we are able to estimate the impact of any number of projects of varying scales, at different time periods. This model has been integrated into the planning process through working with the lead planners in Jeddah at different stages of the project in both informative and evaluative modes. The result is an iterative, evidence-based approach and a collaborative framework for the planning and decision making, which could be adopted in future planning for Jeddah or elsewhere

Simplified model to predict the thermal demand profile of districts

Extensive research works have been carried out over the past few decades in the development of simulation tools to predict the thermal performance of buildings. These validated tools have been used in the design of the building and its components. However, limited simulation tools have been developed for modeling of district energy systems, which can potentially be a very laborious and time-consuming process. Besides many associated limitations, providing a realistic demand profile of the district energy systems is not a straightforward task due to high number of parameters involved in predicting a detail demand profile. This paper reports the development of a simplified model for predicting the thermal demand profile of a district heating system. The paper describes the method used to develop two types of simplified models to predict the thermal load of a variety of buildings (residential, office, attached, detached, etc.). The predictions were also compared with those made by the detailed simulation models. The simplified model was then utilized to predict the energy demand of a variety of districts types (residential, commercial or mix), and its prediction accuracy was compared with those made by detailed model: good agreement was observed between the results