Brauer-Thrall for totally reflexive modules over local rings of higher dimension

Let $R$ be a commutative Noetherian local ring. Assume that $R$ has a pair $\{x,y\}$ of exact zerodivisors such that $\dim R/(x,y)\ge2$ and all totally reflexive $R/(x)$-modules are free. We show that the first and second Brauer--Thrall type theorems hold for the category of totally reflexive $R$-modules. More precisely, we prove that, for infinitely many integers $n$, there exists an indecomposable totally reflexive $R$-module of multiplicity $n$. Moreover, if the residue field of $R$ is infinite, we prove that there exist infinitely many isomorphism classes of indecomposable totally reflexive $R$-modules of multiplicity $n$.Comment: to appear in Algebras and Representation Theor

The lung cancer exercise training study: a randomized trial of aerobic training, resistance training, or both in postsurgical lung cancer patients: rationale and design

<p>Abstract</p> <p>Background</p> <p>The Lung Cancer Exercise Training Study (LUNGEVITY) is a randomized trial to investigate the efficacy of different types of exercise training on cardiorespiratory fitness (VO_2peak), patient-reported outcomes, and the organ components that govern VO_2peakin post-operative non-small cell lung cancer (NSCLC) patients.</p> <p>Methods/Design</p> <p>Using a single-center, randomized design, 160 subjects (40 patients/study arm) with histologically confirmed stage I-IIIA NSCLC following curative-intent complete surgical resection at Duke University Medical Center (DUMC) will be potentially eligible for this trial. Following baseline assessments, eligible participants will be randomly assigned to one of four conditions: (1) aerobic training alone, (2) resistance training alone, (3) the combination of aerobic and resistance training, or (4) attention-control (progressive stretching). The ultimate goal for all exercise training groups will be 3 supervised exercise sessions per week an intensity above 70% of the individually determined VO_2peakfor aerobic training and an intensity between 60 and 80% of one-repetition maximum for resistance training, for 30-45 minutes/session. Progressive stretching will be matched to the exercise groups in terms of program length (i.e., 16 weeks), social interaction (participants will receive one-on-one instruction), and duration (30-45 mins/session). The primary study endpoint is VO_2peak. Secondary endpoints include: patient-reported outcomes (PROs) (e.g., quality of life, fatigue, depression, etc.) and organ components of the oxygen cascade (i.e., pulmonary function, cardiac function, skeletal muscle function). All endpoints will be assessed at baseline and postintervention (16 weeks). Substudies will include genetic studies regarding individual responses to an exercise stimulus, theoretical determinants of exercise adherence, examination of the psychological mediators of the exercise - PRO relationship, and exercise-induced changes in gene expression.</p> <p>Discussion</p> <p>VO_2peakis becoming increasingly recognized as an outcome of major importance in NSCLC. LUNGEVITY will identify the optimal form of exercise training for NSCLC survivors as well as provide insight into the physiological mechanisms underlying this effect. Overall, this study will contribute to the establishment of clinical exercise therapy rehabilitation guidelines for patients across the entire NSCLC continuum.</p> <p>Trial Registration</p> <p>NCT00018255</p

On the conservation of the slow conformational dynamics within the amino acid kinase family: NAGK the paradigm

N-Acetyl-L-Glutamate Kinase (NAGK) is the structural paradigm for examining the catalytic mechanisms and dynamics of amino acid kinase family members. Given that the slow conformational dynamics of the NAGK (at the microseconds time scale or slower) may be rate-limiting, it is of importance to assess the mechanisms of the most cooperative modes of motion intrinsically accessible to this enzyme. Here, we present the results from normal mode analysis using an elastic network model representation, which shows that the conformational mechanisms for substrate binding by NAGK strongly correlate with the intrinsic dynamics of the enzyme in the unbound form. We further analyzed the potential mechanisms of allosteric signalling within NAGK using a Markov model for network communication. Comparative analysis of the dynamics of family members strongly suggests that the low-frequency modes of motion and the associated intramolecular couplings that establish signal transduction are highly conserved among family members, in support of the paradigm sequence→structure→dynamics→function © 2010 Marcos et al

Headache and musculoskeletal complaints among subjects with self reported whiplash injury. The HUNT-2 study

<p>Abstract</p> <p>Background</p> <p>To evaluate the life-time prevalence of self reported whiplash injury and the relationship to chronic musculoskeletal complaints (MSCs) and headache in a large unselected adult population.</p> <p>Methods</p> <p>Between 1995 and 1997, all inhabitants 20 years and older in Nord-Trondelag county in Norway were invited to a comprehensive health survey. Out of 92,936 eligible for participation, a total of 59,104 individuals (63.6%) answered the question about whiplash injury (whiplash). Among these, 46,895 (79.3%) responded to the questions of musculoskeletal complaints and headache.</p> <p>Results</p> <p>The total life-time prevalence of self reported whiplash injury was 2.9%, for women 2.7% and for men 3.0%. There was a significant association between self reported whiplash injury and headache (OR = 2.1; 95% CI 1.8-2.4), and chronic MSCs (OR = 3.3; 95% CI 2.8-3.8), evident for all ten anatomical sites investigated. The association was most pronounced for those with a combination of headache and chronic MSC for both men (OR = 4.8; 95% CI 3.6-6.2) and women (OR = 5.2; 95% CI 3.7-7.1).</p> <p>Conclusions</p> <p>Subjects with self reported whiplash injury had significantly more headache and musculoskeletal complaints than those without, and may in part be due to selective reporting. The causal mechanism remains unclear and cannot be addressed in the present study design.</p

The Use of Experimental Structures to Model Protein Dynamics

The number of solved protein structures submitted in the Protein Data Bank (PDB) has increased dramatically in recent years. For some specific proteins, this number is very high—for example, there are over 550 solved structures for HIV-1 protease, one protein that is essential for the life cycle of human immunodeficiency virus (HIV) which causes acquired immunodeficiency syndrome (AIDS) in humans. The large number of structures for the same protein and its variants include a sample of different conformational states of the protein. A rich set of structures solved experimentally for the same protein has information buried within the dataset that can explain the functional dynamics and structural mechanism of the protein. To extract the dynamics information and functional mechanism from the experimental structures, this chapter focuses on two methods—Principal Component Analysis (PCA) and Elastic Network Models (ENM). PCA is a widely used statistical dimensionality reduction technique to classify and visualize high-dimensional data. On the other hand, ENMs are well-established simple biophysical method for modeling the functionally important global motions of proteins. This chapter covers the basics of these two. Moreover, an improved ENM version that utilizes the variations found within a given set of structures for a protein is described. As a practical example, we have extracted the functional dynamics and mechanism of HIV-1 protease dimeric structure by using a set of 329 PDB structures of this protein. We have described, step by step, how to select a set of protein structures, how to extract the needed information from the PDB files for PCA, how to extract the dynamics information using PCA, how to calculate ENM modes, how to measure the congruency between the dynamics computed from the principal components (PCs) and the ENM modes, and how to compute entropies using the PCs. We provide the computer programs or references to software tools to accomplish each step and show how to use these programs and tools. We also include computer programs to generate movies based on PCs and ENM modes and describe how to visualize them

Pit and fissure sealants in dental public health – application criteria and general policy in Finland

<p>Abstract</p> <p>Background</p> <p>Pit and fissure sealants (sealants) are widely used as a non-operative preventive method in public dental health in Finland. Most children under 19 years of age attend the community-organized dental health services free of charge. The aims of this study were to find out to what extent sealants were applied, what the attitudes of dental professionals towards sealant application were, and whether any existing sealant policies could be detected among the health centres or among the respondents in general. The study evaluated changes that had taken place in the policies used during a ten year period (1991–2001).</p> <p>Methods</p> <p>A questionnaire was mailed to each chief dental officer (CDO) of the 265 public dental health centres in Finland, and to a group of general dentists (GDP) applying sealants in these health centres, giving a total of 434 questionnaires with 22 questions. The response rate was 80% (N = 342).</p> <p>Results</p> <p>A majority of the respondents reported to application of sealants on a systematic basis for children with increased caries risk. The criteria for applying sealants and the actual strategies seemed to vary locally between the dentists within the health centres and between the health centres nationwide. The majority of respondents believed sealants had short- and long-term effects. The overall use of sealants decreased towards the end of the ten year period. The health centres (N = 28) choosing criteria to seal over detected or suspected enamel caries lesion had a DMFT value of 1.0 (SD ± 0.49) at age 12 (year 2000) compared to a value of 1.2 (SD ± 0.47) for those health centres (N = 177) applying sealants by alternative criteria (t-test, p < 0.05).</p> <p>Conclusion</p> <p>There seems to be a need for defined guidelines for sealant application criteria and policy both locally and nationwide. Occlusal caries management may be improved by shifting the sealant policy from the traditional approach of prevention to interception, i.e. applying the sealants over detected or suspected enamel caries lesions instead of sealing sound teeth.</p

Elevated [11C]-D-Deprenyl Uptake in Chronic Whiplash Associated Disorder Suggests Persistent Musculoskeletal Inflammation

There are few diagnostic tools for chronic musculoskeletal pain as structural imaging methods seldom reveal pathological alterations. This is especially true for Whiplash Associated Disorder, for which physical signs of persistent injuries to the neck have yet to be established. Here, we sought to visualize inflammatory processes in the neck region by means Positron Emission Tomography using the tracer 11C-D-deprenyl, a potential marker for inflammation. Twenty-two patients with enduring pain after a rear impact car accident (Whiplash Associated Disorder grade II) and 14 healthy controls were investigated. Patients displayed significantly elevated tracer uptake in the neck, particularly in regions around the spineous process of the second cervical vertebra. This suggests that whiplash patients have signs of local persistent peripheral tissue inflammation, which may potentially serve as a diagnostic biomarker. The present investigation demonstrates that painful processes in the periphery can be objectively visualized and quantified with PET and that 11C-D-deprenyl is a promising tracer for these purposes

Genetic association study of QT interval highlights role for calcium signaling pathways in myocardial repolarization.

The QT interval, an electrocardiographic measure reflecting myocardial repolarization, is a heritable trait. QT prolongation is a risk factor for ventricular arrhythmias and sudden cardiac death (SCD) and could indicate the presence of the potentially lethal mendelian long-QT syndrome (LQTS). Using a genome-wide association and replication study in up to 100,000 individuals, we identified 35 common variant loci associated with QT interval that collectively explain ∼8-10% of QT-interval variation and highlight the importance of calcium regulation in myocardial repolarization. Rare variant analysis of 6 new QT interval-associated loci in 298 unrelated probands with LQTS identified coding variants not found in controls but of uncertain causality and therefore requiring validation. Several newly identified loci encode proteins that physically interact with other recognized repolarization proteins. Our integration of common variant association, expression and orthogonal protein-protein interaction screens provides new insights into cardiac electrophysiology and identifies new candidate genes for ventricular arrhythmias, LQTS and SCD