Constraints on Fluctuations in Sparsely Characterized Biological Systems.

Biochemical processes are inherently stochastic, creating molecular fluctuations in otherwise identical cells. Such "noise" is widespread but has proven difficult to analyze because most systems are sparsely characterized at the single cell level and because nonlinear stochastic models are analytically intractable. Here, we exactly relate average abundances, lifetimes, step sizes, and covariances for any pair of components in complex stochastic reaction systems even when the dynamics of other components are left unspecified. Using basic mathematical inequalities, we then establish bounds for whole classes of systems. These bounds highlight fundamental trade-offs that show how efficient assembly processes must invariably exhibit large fluctuations in subunit levels and how eliminating fluctuations in one cellular component requires creating heterogeneity in another.The work was supported by grant 1137676 from the Division of Mathematical Sciences at the National Science Foundation, and grant GM081563 from the National Institutes of Health.This is the final version of the article. It first appeared from the American Physical Society via http://dx.doi.org/10.1103/PhysRevLett.116.05810

Efficacy of a progressive walking program and glucosamine sulphate supplementation on osteoarthritic symptoms of the hip and knee: a feasibility trial

Introduction: Management of osteoarthritis (OA) includes the use of non-pharmacological and pharmacological therapies. Although walking is commonly recommended for reducing pain and increasing physical function in people with OA, glucosamine sulphate has also been used to alleviate pain and slow the progression of OA. This study evaluated the effects of a progressive walking program and glucosamine sulphate intake on OA symptoms and physical activity participation in people with mild to moderate hip or knee OA. Methods: Thirty-six low active participants (aged 42 to 73 years) were provided with 1500 mg glucosamine sulphate per day for 6 weeks, after which they began a 12-week progressive walking program, while continuing to take glucosamine. They were randomized to walk 3 or 5 days per week and given a pedometer to monitor step counts. For both groups, step level of walking was gradually increased to 3000 steps/day during the first 6 weeks of walking, and to 6000 steps/day for the next 6 weeks. Primary outcomes included physical activity levels, physical function (self-paced step test), and the WOMAC Osteoarthritis Index for pain, stiffness and physical function. Assessments were conducted at baseline and at 6-, 12-, 18-, and 24-week follow-ups. The Mann Whitney Test was used to examine differences in outcome measures between groups at each assessment, and the Wilcoxon Signed Ranks Test was used to examine differences in outcome measures between assessments. Results: During the first 6 weeks of the study (glucosamine supplementation only), physical activity levels, physical function, and total WOMAC scores improved (P<0.05). Between the start of the walking program (Week 6) and the final follow-up (Week 24), further improvements were seen in these outcomes (P<0.05) although most improvements were seen between Weeks 6 and 12. No significant differences were found between walking groups. Conclusions: In people with hip or knee OA, walking a minimum of 3000 steps (~30 minutes), at least 3 days/week, in combination with glucosamine sulphate, may reduce OA symptoms. A more robust study with a larger sample is needed to support these preliminary findings. Trial Registration: Australian Clinical Trials Registry ACTRN012607000159459

Molecular Gas in Spiral Galaxies

In this review, I highlight a number of recent surveys of molecular gas in nearby spiral galaxies. Through such surveys, more complete observations of the distribution and kinematics of molecular gas have become available for galaxies with a wider range of properties (e.g., brightness, Hubble type, strength of spiral or bar structure). These studies show the promise of both interferometers and single-dish telescopes in advancing our general understanding of molecular gas in spiral galaxies. In particular, I highlight the contributions of the recent BIMA Survey of Nearby Galaxies (SONG).Comment: 8 pages, 1 figure. To appear in the proceedings of the 4th Cologne-Bonn-Zermatt-Symposium, "The Dense Interstellar Medium in Galaxies", which was held in Zermatt, Switzerland in September 200

Does self-monitoring of blood glucose improve outcome in type 2 diabetes? The Fremantle Diabetes Study

AIMS/HYPOTHESIS: To assess whether self-monitoring of blood glucose (SMBG) is an independent predictor of improved outcome in a community-based cohort of type 2 diabetic patients. MATERIALS AND METHODS: We used longitudinal data from (1) 1,280 type 2 diabetic participants in the observational Fremantle Diabetes Study (FDS) who reported SMBG and diabetes treatment status at study entry (1993–1996), and (2) a subset of 531 participants who attended six or more annual assessments (referred to as the 5-year cohort). Diabetes-related morbidity, cardiac death and all-cause mortality were ascertained at each assessment, supplemented by linkage to the Western Australian Data Linkage System. RESULTS: At baseline, 70.2% (898 out of 1,280) of type 2 patients used SMBG. During 12,491 patient-years of follow-up (mean 9.8 ± 3.5 years), 486 (38.0%) type 2 participants died (196 [15.3%] from cardiac causes). SMBG was significantly less prevalent in those who died during follow-up than in those who were still alive at the end of June 2006 (65.4 vs 73.0%, p = 0.005). In Cox proportional hazards modelling, after adjustment for confounding and explanatory variables, SMBG was not independently associated with all-cause mortality, but was associated with a 79% increased risk of cardiovascular mortality in patients not treated with insulin. For the 5-year cohort, time-dependent SMBG was independently associated with a 48% reduced risk of retinopathy. CONCLUSIONS/INTERPRETATION: SMBG was not independently associated with improved survival. Inconsistent findings relating to the association of SMBG with cardiac death and retinopathy may be due to confounding, incomplete covariate adjustment or chance

Positive words carry less information than negative words

We show that the frequency of word use is not only determined by the word length \cite{Zipf1935} and the average information content \cite{Piantadosi2011}, but also by its emotional content. We have analyzed three established lexica of affective word usage in English, German, and Spanish, to verify that these lexica have a neutral, unbiased, emotional content. Taking into account the frequency of word usage, we find that words with a positive emotional content are more frequently used. This lends support to Pollyanna hypothesis \cite{Boucher1969} that there should be a positive bias in human expression. We also find that negative words contain more information than positive words, as the informativeness of a word increases uniformly with its valence decrease. Our findings support earlier conjectures about (i) the relation between word frequency and information content, and (ii) the impact of positive emotions on communication and social links.Comment: 16 pages, 3 figures, 3 table

Access route selection for percutaneous coronary intervention among Vietnamese patients: Implications for in-hospital costs and outcomes

Background:Little is known about rates of access site (transradial (TRI) or transfemoral (TFI)) preference for percutaneous coronary intervention (PCI) and in-hospital costs of patients undergoing these procedures in lower-and middle-countries. Here, we report on access site use, in-hospital costs and outcomes of patients undergoing PCI in Vietnam.Methods:Information from 868 patients were included in the cohort of 1022 patients recruited into the first PCI registry in Vietnam. The total hospital costs and in-hospital outcomes of patients undergoing TRI and TFI were compared. Hospital costs were obtained from the hospital admission system, and major adverse cardiac events, major bleeding events and length of stay were identified through review of medical records.Findings:TRI was the dominant access site for interventionists (694/868 patients). The TFI group reported more lesions of the left main artery, more previous coronary artery bypass grafts and previous PCI in comparison with the TRI group (all p Interpretations:Among patients undergoing PCI, TRI was associated with lower costs and favourable clinical outcomes relative to TFI

Large Isoforms of UNC-89 (Obscurin) Are Required for Muscle Cell Architecture and Optimal Calcium Release in Caenorhabditis elegans

Calcium, a ubiquitous intracellular signaling molecule, controls a diverse array of cellular processes. Consequently, cells have developed strategies to modulate the shape of calcium signals in space and time. The force generating machinery in muscle is regulated by the influx and efflux of calcium ions into the muscle cytoplasm. In order for efficient and effective muscle contraction to occur, calcium needs to be rapidly, accurately and reliably regulated. The mechanisms underlying this highly regulated process are not fully understood. Here, we show that the Caenorhabditis elegans homolog of the giant muscle protein obscurin, UNC-89, is required for normal muscle cell architecture. The large immunoglobulin domain-rich isoforms of UNC-89 are critical for sarcomere and sarcoplasmic reticulum organization. Furthermore, we have found evidence that this structural organization is crucial for excitation-contraction coupling in the body wall muscle, through the coordination of calcium signaling. Thus, our data implicates UNC-89 in maintaining muscle cell architecture and that this precise organization is essential for optimal calcium mobilization and efficient and effective muscle contraction

FILTWAM and Voice Emotion Recognition

This paper introduces the voice emotion recognition part of our framework for improving learning through webcams and microphones (FILTWAM). This framework enables multimodal emotion recognition of learners during game-based learning. The main goal of this study is to validate the use of microphone data for a real-time and adequate interpretation of vocal expressions into emotional states were the software is calibrated with end users. FILTWAM already incorporates a valid face emotion recognition module and is extended with a voice emotion recognition module. This extension aims to provide relevant and timely feedback based upon learner's vocal intonations. The feedback is expected to enhance learner’s awareness of his or her own behavior. Six test persons received the same computer-based tasks in which they were requested to mimic specific vocal expressions. Each test person mimicked 82 emotions, which led to a dataset of 492 emotions. All sessions were recorded on video. An overall accuracy of our software based on the requested emotions and the recognized emotions is a pretty good 74.6% for the emotions happy and neutral emotions; but will be improved for the lower values of an extended set of emotions. In contrast with existing software our solution allows to continuously and unobtrusively monitor learners’ intonations and convert these intonations into emotional states. This paves the way for enhancing the quality and efficacy of game-based learning by including the learner's emotional states, and links these to pedagogical scaffolding.The Netherlands Laboratory for Lifelong Learning (NELLL) of the Open University of the Netherlands

An e-learning reproductive health module to support improved student learning and interaction: a prospective interventional study at a medical school in Egypt

<p>Abstract</p> <p>Background</p> <p>The Public Health (PH) course at the medical college of Cairo University is based on traditional lectures. Large enrollment limits students' discussions and interactions with instructors.</p> <p>Aim</p> <p>Evaluate students' learning outcomes as measured by improved knowledge acquisition and opinions of redesigning the Reproductive Health (RH) section of the PH course into e-learning and assessing e-course utilization.</p> <p>Methods</p> <p>This prospective interventional study started with development of an e-learning course covering the RH section, with visual and interactive emphasis, to satisfy students' diverse learning styles. Two student groups participated in this study. The first group received traditional lecturing, while the second volunteered to enroll in the e-learning course, taking online course quizzes. Both groups answered knowledge and course evaluation questionnaires and were invited to group discussions. Additionally, the first group answered another questionnaire about reasons for non-participation.</p> <p>Results</p> <p>Students participating in the e-learning course showed significantly better results, than those receiving traditional tutoring. Students who originally shunned the e-course expressed eagerness to access the course before the end of the academic year. Overall, students using the redesigned e-course reported better learning experiences.</p> <p>Conclusions</p> <p>An online course with interactivities and interaction, can overcome many educational drawbacks of large enrolment classes, enhance student's learning and complement pit-falls of large enrollment traditional tutoring.</p