Amino acid classes and the protein folding problem

We present and implement a distance-based clustering of amino acids within the framework of a statistically derived interaction matrix and show that the resulting groups faithfully reproduce, for well-designed sequences, thermodynamic stability in and kinetic accessibility to the native state. A simple interpretation of the groups is obtained by eigenanalysis of the interaction matrix.Comment: REVTeX, 11 pages, 4 figures, To appear in J. Chem. Phy

Two satellite study of substorm expansion near geosynchronous orbit

During several time intervals in 1979–1980 the satellites GEOS-2 and SCATHA were situated relatively close on the nightside of the Earth at geosynchronous distances. Several substorm events were identified during these periods. The event considered in this paper was recorded on 22 May 1979, when the satellites were separated by less than 30min in local time around 21:00 LT. The observed 45 to 60 s delay of magnetic signatures observed at the two s/c indicates a westward expansion of ~7.7°/min. At the two s/c, the magnetic signatures are, in particular for the azimuthal magnetic field components, quite different. At GEOS-2, being close to the magnetic equator, the dominant feature is a dipolarization with a weak field-aligned current signature corresponding to a symmetric current which cancels at the equator. On SCATHA, however, being close to the current sheet boundary, the azimuthal magnetic field indicates a strong field-aligned Birkeland current structure. On both s/c the first indication of an approaching substorm was an increase in the high energy ion flux followed by a reduction in the flux intensity of energetic electrons and a further tailward stretching of the magnetic field, starting ~2min before the onset of the magnetic field dipolarization. The tailward stretching, the observed variations of the magnetic field components, and the subsequent dipolarization are interpreted in terms of an azimuthally tilted field-aligned current system passing the s/c on the tailward side from east to west. The westward expansion and dipolarization observed at the two s/c are consistent with the propagation of a Rayleigh-Taylor type instability. The increased radial ion flux corresponds to the <i><b>E</b></i>x<i><b>B</b></i>-drift due to the substorm associated electric field.<br><br> <b>Key words.</b> Magnetospheric physics (storms and substorms; plasma waves and instabilities; current systems

Getting Change-Space: A Grounded Theory Study of Automated eHealth Therapy

A promising tool for bettering people’s health is eHealth (or “mHealth”) programs: fully automated, web-based health interventions. However, we know surprisingly little about eHealth’s working mechanisms. One possible working mechanism is that program users benefit from a collaborative “relationship”—a “working alliance”—with the program. Although evidence support the existence of a person-to-program alliance it is unclear if and how it influences change. Therefore, we conducted a grounded theory study of how relating to an eHealth program for quitting smoking influenced the participants’ change processes. The ensuing model focuses on how participants got change-space—feeling free from social forcing and able to work constructively on changing—and how the relational processes “making come-alive” and “keeping un-alive” were instrumental in this process. By presenting evidence that relating may influence change in automated therapy, this study supports the person-to-program alliance as a working mechanism in eHealth

Technology, Safety and Costs of Decommissioning a Reference Low-Level Waste Burial Ground. Main Report

Safety and cost information are developed for the conceptual decommissioning of commercial low-level waste (LLW) burial grounds. Two generic burial grounds, one located on an arid western site and the other located on a humid eastern site, are used as reference facilities for the study. The two burial grounds are assumed to have the same site capacity for waste, the same radioactive waste inventory, and similar trench characteristics and operating procedures. The climate, geology. and hydrology of the two sites are chosen to be typical of real western and eastern sites. Volume 1 (Main Report) contains background information and study results in summary form

Exome sequencing identifies nonsegregating nonsense ATM and PALB2 variants in familial pancreatic cancer.

We sequenced 11 germline exomes from five families with familial pancreatic cancer (FPC). One proband had a germline nonsense variant in ATM with somatic loss of the variant allele. Another proband had a nonsense variant in PALB2 with somatic loss of the variant allele. Both variants were absent in a relative with FPC. These findings question the causal mechanisms of ATM and PALB2 in these families and highlight challenges in identifying the causes of familial cancer syndromes using exome sequencing

Macro material flow modeling for analyzing solid waste management options

A Macro Material Flow Modeling (MMFM) concept and approach are being adopted to develop a predictive modeling capability. This capability is intended to provide part of the basis for evaluating potential impacts from various solid waste management system configurations and operating scenarios, as well as evaluating the impacts of various policies on solid waste quantities and compositions. The MMFM capability, as part of a broader Solid Waste Initiative at Pacific Northwest Laboratory, is intended to provide an increased understanding of solid waste as a disposal, energy, and resource problem on a national and global scale, particularly over the long term. This model is a macro-level simulation of the flows of the various materials through the solid waste management system, and also through the associated materials production and use system. Inclusion of materials production and use within the modeling context allows a systems approach to be used, providing a much more complete understanding of the origins of the solid waste materials and also of possible options for materials recovery and reuse than if a more traditional end-of-pipe'' view of solid waste is adopted. The MMFM is expected to be useful in evaluating longer-term, broader-ranging solid waste impacts than are traditionally evaluated by decision-makers involved in implementing solutions to local or regional solid waste management problems. This paper discusses the types of questions of interest in evaluating long-term, broad-range impacts from solid waste. It then identifies the basic needs for predictive modeling capabilities like the MMFM, and provides a basic description of the conceptual framework for the model and the associated data. Status of the MMFM implementation is also discussed

Grouping time series by pairwise measures of redundancy

A novel approach is proposed to group redundant time series in the frame of causality. It assumes that (i) the dynamics of the system can be described using just a small number of characteristic modes, and that (ii) a pairwise measure of redundancy is sufficient to elicit the presence of correlated degrees of freedom. We show the application of the proposed approach on fMRI data from a resting human brain and gene expression profiles from HeLa cell culture.Comment: 4 pages, 8 figure

A Coding System to Measure Elements of Shared Decision Making During Psychiatric Visits

Objective: Shared decision making is widely recognized to facilitate effective health care. The purpose of this study was to assess the applicability and usefulness of a scale to measure the presence and extent of shared decision making in clinical decisions in psychiatric practice. Methods: A coding scheme assessing shared decision making in general medical settings was adapted to mental health settings, and a manual for using the scheme was created. Trained raters used the adapted scale to analyze 170 audio-recordings of medication check-up visits with either psychiatrists or nurse practitioners. The scale assessed the level of shared decision making based on the presence of nine specific elements. Interrater reliability was examined, and the frequency with which elements of shared decision making were observed was documented. The association between visit length and extent of shared decision making was also examined. Results: Interrater reliability among three raters on a subset of 20 recordings ranged from 67% to 100% agreement for the presence of each of the nine elements of shared decision making and 100% for the agreement between provider and consumer on decisions made. Of the 170 sessions, 128 (75%) included a clinical decision. Just over half of the decisions (53%) met minimum criteria for shared decision making. Shared decision making was not related to visit length after the analysis controlled for the complexity of the decision. Conclusions: The rating scale appears to reliably assess shared decision making in psychiatric practice and could be helpful for future research, training, and implementation efforts

Peripheral blood marker of residual acute leukemia after hematopoietic cell transplantation using multi-plex digital droplet PCR

BACKGROUND Relapse remains the primary cause of death after hematopoietic cell transplantation (HCT) for acute leukemia. The ability to identify minimal/measurable residual disease (MRD) via the blood could identify patients earlier when immunologic interventions may be more successful. We evaluated a new test that could quantify blood tumor mRNA as leukemia MRD surveillance using droplet digital PCR (ddPCR). METHODS The multiplex ddPCR assay was developed using tumor cell lines positive for the tumor associated antigens (TAA: WT1, PRAME, BIRC5), with homeostatic ABL1. On IRB-approved protocols, RNA was isolated from mononuclear cells from acute leukemia patients after HCT (n = 31 subjects; n = 91 specimens) and healthy donors (n = 20). ddPCR simultaneously quantitated mRNA expression of WT1, PRAME, BIRC5, and ABL1 and the TAA/ABL1 blood ratio was measured in patients with and without active leukemia after HCT. RESULTS Tumor cell lines confirmed quantitation of TAAs. In patients with active acute leukemia after HCT (MRD+ or relapse; n=19), the blood levels of WT1/ABL1, PRAME/ABL1, and BIRC5/ABL1 exceeded healthy donors (p<0.0001, p=0.0286, and p=0.0064 respectively). Active disease status was associated with TAA positivity (1+ TAA vs 0 TAA) with an odds ratio=10.67, (p=0.0070, 95% confidence interval 1.91 - 59.62). The area under the curve is 0.7544. Changes in ddPCR correlated with disease response captured on standard of care tests, accurately denoting positive or negative disease burden in 15/16 (95%). Of patients with MRD+ or relapsed leukemia after HCT, 84% were positive for at least one TAA/ABL1 in the peripheral blood. In summary, we have developed a new method for blood MRD monitoring of leukemia after HCT and present preliminary data that the TAA/ABL1 ratio may may serve as a novel surrogate biomarker for relapse of acute leukemia after HCT

Construct dimensionality and properties of the categories in the ICF Core Set for low back pain

Objective: The aim of this study was to explore by Rasch analysis whether the Comprehensive International Classification of Functioning, Disability and Health (ICF) Core Set might represent a future clinical tool for measuring functioning of patients with low back pain. Material and methods: The Comprehensive ICF Core Set for low back pain was scored by health professionals for 118 patients with low back pain. Qualifier levels, invariance, construct validity and ordering of the categories in the components of Body function, Body structure, Activities and participation and Environmental factors were explored by Rasch analysis. Results: The number of qualifier levels had to be reduced. Categories within Body functions and within Environmental factors reflected a single underlying construct. The categories within the component of Activities and Participation did not meet the requirements of a single underlying construct in the present population. Few categories covered the problems reported by patients with a relatively high level of function.Conclusion: Rasch analysis indicated that the Comprehensive ICF Core Set for low back pain may be used with some modification of categories as a common tool for assessing problems within the components Body functions, and Activity and Participation. However, detecting ICF categories that reflect the higher functional levels in patients with low back pain, and revision of the qualifier levels may be necessary