Design and Implementation of an Open Source Indexing Solution for a Large Set of Radiological Reports and Images

This paper hopes to share the insights we experienced during designing, building, and running an indexing solution for a large set of radiological reports and images in a production environment for more than 3 years. Several technical challenges were encountered and solved in the course of this project. One hundred four million words in 1.8 million radiological reports from 1989 to the present were indexed and became instantaneously searchable in a user-friendly fashion; the median query duration is only 31 ms. Currently, our highly tuned index holds 332,088 unique words in four languages. The indexing system is feature-rich and language-independent and allows for making complex queries. For research and training purposes it certainly is a valuable and convenient addition to our radiology informatics toolbox. Extended use of open-source technology dramatically reduced both implementation time and cost. All software we developed related to the indexing project has been made available to the open-source community covered by an unrestricted Berkeley Software Distribution-style license

The Importance of DNA Repair in Tumor Suppression

The transition from a normal to cancerous cell requires a number of highly specific mutations that affect cell cycle regulation, apoptosis, differentiation, and many other cell functions. One hallmark of cancerous genomes is genomic instability, with mutation rates far greater than those of normal cells. In microsatellite instability (MIN tumors), these are often caused by damage to mismatch repair genes, allowing further mutation of the genome and tumor progression. These mutation rates may lie near the error catastrophe found in the quasispecies model of adaptive RNA genomes, suggesting that further increasing mutation rates will destroy cancerous genomes. However, recent results have demonstrated that DNA genomes exhibit an error threshold at mutation rates far lower than their conservative counterparts. Furthermore, while the maximum viable mutation rate in conservative systems increases indefinitely with increasing master sequence fitness, the semiconservative threshold plateaus at a relatively low value. This implies a paradox, wherein inaccessible mutation rates are found in viable tumor cells. In this paper, we address this paradox, demonstrating an isomorphism between the conservatively replicating (RNA) quasispecies model and the semiconservative (DNA) model with post-methylation DNA repair mechanisms impaired. Thus, as DNA repair becomes inactivated, the maximum viable mutation rate increases smoothly to that of a conservatively replicating system on a transformed landscape, with an upper bound that is dependent on replication rates. We postulate that inactivation of post-methylation repair mechanisms are fundamental to the progression of a tumor cell and hence these mechanisms act as a method for prevention and destruction of cancerous genomes.Comment: 7 pages, 5 figures; Approximation replaced with exact calculation; Minor error corrected; Minor changes to model syste

Ab initio study of alanine polypeptide chains twisting

We have investigated the potential energy surfaces for alanine chains consisting of three and six amino acids. For these molecules we have calculated potential energy surfaces as a function of the Ramachandran angles Phi and Psi, which are widely used for the characterization of the polypeptide chains. These particular degrees of freedom are essential for the characterization of proteins folding process. Calculations have been carried out within ab initio theoretical framework based on the density functional theory and accounting for all the electrons in the system. We have determined stable conformations and calculated the energy barriers for transitions between them. Using a thermodynamic approach, we have estimated the times of characteristic transitions between these conformations. The results of our calculations have been compared with those obtained by other theoretical methods and with the available experimental data extracted from the Protein Data Base. This comparison demonstrates a reasonable correspondence of the most prominent minima on the calculated potential energy surfaces to the experimentally measured angles Phi and Psi for alanine chains appearing in native proteins. We have also investigated the influence of the secondary structure of polypeptide chains on the formation of the potential energy landscape. This analysis has been performed for the sheet and the helix conformations of chains of six amino acids.Comment: 24 pages, 10 figure

Exploring multivariate clinical chemical routine data concerning three major disease groups

In preparation for multivariate analysis, an exploratory study has been undertaken to investigate the relative position, separability, homogeneity and shape of three major disease groups, using data from a clinical chemical routine package

What’s in it for others? The relationship between prosocial motivation and commitment to change among youth care professionals.

This study assesses the relationship between prosocial motivation and commitment to change among youth care professionals. We draw on person–environment fit theory to propose that this relationship is conditional on employees’ perceived meaningfulness of the change for society and clients. Our results confirm the expected positive relationship between prosocial motivation and commitment to change. Our analysis suggests that the moderating relationship between prosocial motivation, client meaningfulness and commitment to change should be understood as a substitutive relationship: both prosocial motivation and client meaningfulness are sufficient conditions, but the presence of both is not a necessary condition for commitment to change.The politics and administration of institutional chang

Identification of Low Allele Frequency Mosaic Mutations in Alzheimer Disease

Germline mutations ofAPP,PSEN1, andPSEN2 genes cause autosomal dominant Alzheimer disease (AD). Somatic variants of the same genes may underlie pathogenesis in sporadic AD, which is the most prevalent form of the disease. Importantly, such somatic variants may be present at very low allelic frequency, confined to the brain, and are thus very difficult or impossible to detect in blood-derived DNA. Ever-refined methodologies to identify mutations present in a fraction of the DNA of the original tissue are rapidly transforming our understanding of DNA mutation and their role in complex pathologies such as tumors. These methods stand poised to test to what extend somatic variants may play a role in AD and other neurodegenerative diseases

Photopolymer Resins with Biobased Methacrylates Based on Soybean Oil for Stereolithography

The accessibility of renewable materials that are both sustainable and competitive is essential to accommodate the rapid growth in consumption of 3D printing materials. We have developed biobased photopolymer resins based on modified soybean oil for application in commercial stereolithography printers. First, soybean oil methacrylates with various functionalities were successfully synthesized from epoxidized soybean oil as an alternative to commercially available soybean oil acrylate. A library of photoresins was created by mixing up to 80% of the biobased (meth)acrylate oligomers with biobased diluents and a photoinitiator. The resin composition was optimized to achieve a maximum biobased content and a low viscosity. The manufactured parts demonstrated complete layer fusion and accurate print quality. Stiffness and toughness can be tuned by altering the chemical composition or the number of functional groups per oligomer. These biobased materials can be employed to reduce the environmental impact of additive manufacturing while being competitive with current fossil-based resins from commercial manufacturers

Pacific abyssal transport and mixing: Through the Samoan Passage versus around the Manihiki Plateau

Author Posting. © American Meteorological Society, 2019. This article is posted here by permission of American Meteorological Society for personal use, not for redistribution. The definitive version was published in Journal of Physical Oceanography 49(6), (2019): 1577-1592, doi:10.1175/JPO-D-18-0124.1.The main source feeding the abyssal circulation of the North Pacific is the deep, northward flow of 5–6 Sverdrups (Sv; 1 Sv ≡ 106 m3 s−1) through the Samoan Passage. A recent field campaign has shown that this flow is hydraulically controlled and that it experiences hydraulic jumps accompanied by strong mixing and dissipation concentrated near several deep sills. By our estimates, the diapycnal density flux associated with this mixing is considerably larger than the diapycnal flux across a typical isopycnal surface extending over the abyssal North Pacific. According to historical hydrographic observations, a second source of abyssal water for the North Pacific is 2.3–2.8 Sv of the dense flow that is diverted around the Manihiki Plateau to the east, bypassing the Samoan Passage. This bypass flow is not confined to a channel and is therefore less likely to experience the strong mixing that is associated with hydraulic transitions. The partitioning of flux between the two branches of the deep flow could therefore be relevant to the distribution of Pacific abyssal mixing. To gain insight into the factors that control the partitioning between these two branches, we develop an abyssal and equator-proximal extension of the “island rule.” Novel features include provisions for the presence of hydraulic jumps as well as identification of an appropriate integration circuit for an abyssal layer to the east of the island. Evaluation of the corresponding circulation integral leads to a prediction of 0.4–2.4 Sv of bypass flow. The circulation integral clearly identifies dissipation and frictional drag effects within the Samoan Passage as crucial elements in partitioning the flow.This work was supported by the National Science Foundation under Grants OCE-1029268, OCE-1029483, OCE-1657264, OCE-1657870, OCE-1658027, and OCE-1657795. We thank the captain, crew, and engineers at APL/UW for their hard work and skill.2020-06-1

Transitioning to low-carbon residential heating: the impacts of material-related emissions

To achieve climate neutrality, future urban heating systems will need to use a variety of low-carbon heating technologies. The transition toward low-carbon heating technologies necessitates a complete restructuring of the heating system, with significant associated material requirements. However, little research has been done into the quantity and environmental impact of the required materials for this system change. We analyzed the material demand and the environmental impact of the transition toward low-carbon heating in the Netherlands across three scenarios based on the local availability and capacity for sources of low-carbon heat. A wide range of materials are included, covering aggregates, construction materials, metals, plastics, and critical materials. We find that while the Dutch policy goal of reducing GHG emissions by 90% before 2050 can be achieved if only direct emissions from the heating system are considered, this is no longer the case when the cradle-to-gate emissions from the additional materials, especially insulation materials, are taken into account. The implementation of these technologies will require 59–63 megatons of materials in the period of 2021–2050, leading to a maximum reduction of 62%.Industrial Ecolog