The control of calcium signaling in the heart

Work on the role of calcium in the heart began in the nineteenth century with Ringer’s demonstration that calcium is essential for cardiac contraction. This article provides a brief overview of the regulation of cardiac calcium signalling. Contraction results from the systolic rise of Ca concentration (the Ca transient). This occurs by the process of calcium induced Ca release in which Ca entry into the cell results in the opening of the sarcoplasmic reticulum Ca release channel (Ryanodine Receptor) releasing a much larger quantity of Ca into the cytoplasm. The Ca concentration in the sarcoplasmic reticulum is a major factor determining the amplitude of the Ca transient. The remainder of the article discusses how sarcoplasmic reticulum Ca content is regulated and the consequences this has for regulation of systolic Ca.Keywords: heart; calcium; sarcoplasmic reticulum, Ryanodine Recepto

Incorporating diverse data to improve genetic network alignment with IsoRank

Thesis (M. Eng.)--Massachusetts Institute of Technology, Dept. of Electrical Engineering and Computer Science, 2011.Cataloged from PDF version of thesis.Includes bibliographical references (p. 26).To more accurately predict which genes from different species have the same function (orthologs), I extend the network-alignment algorithm IsoRank to simultaneously align multiple unrelated networks over the same set of nodes. In addition to the original protein-interaction networks, I align genetic-interaction networks, gene-expression correlations, and chromosome localization data to improve the functional similarity of aligned genes. Alignments are evaluated with consistency measurements of protein function within ortholog clusters, and with an information-retrieval statistic from a small set of known orthologs. Integrating these additional types of data is shown to improve IsoRank's predictions of classes of genes that have sparse coverage in the original protein-interaction networks.by Eric David Eisner.M.Eng

Pseudoreplication in physiology:More means less

This article reviews how to analyze data from experiments designed to compare the cellular physiology of two or more groups of animals or people. This is commonly done by measuring data from several cells from each animal and using simple t tests or ANOVA to compare between groups. I use simulations to illustrate that this method can give erroneous positive results by assuming that the cells from each animal are independent of each other. This problem, which may be responsible for much of the lack of reproducibility in the literature, can be easily avoided by using a hierarchical, nested statistics approach

Support expansion C∗\mathrm C^*-algebras

We consider operators on $L^2$ spaces that expand the support of vectors in a manner controlled by some constraint function. The primary objects of study are $\mathrm C^*$-algebras that arise from suitable families of constraints, which we call support expansion $\mathrm C^*$-algebras. In the discrete setting, support expansion $\mathrm C^*$-algebras are classical uniform Roe algebras, and the continuous version featured here provides examples of "measurable" or "quantum" uniform Roe algebras as developed in a companion paper. We find that in contrast to the discrete setting, the poset of support expansion $\mathrm C^*$-algebras inside $\mathcal B(L^2(\mathbb R))$ is extremely rich, with uncountable ascending chains, descending chains, and antichains

Heart rate variability used to assess changing autonomic functionin transmissible spongiform encephalopathies

The dorsal vagal nucleus (DMNX) and nucleus ambiguus (NA) are two anatomically distinct regions of the medulla oblongata of the brainstem involved with the control of the heart on a beat to beat basis. The vagus nerve has parasympathetic cell bodies located in the DMNX and NA. The presence of the disease associated prion (PrPD) in the DMNX and NA is used in the post mortem diagnosis of transmissible spongiform encephalopathies (TSEs) in animals. It has been shown that PrPD alters the neuronal discharge properties of infected tissue (Barrow, Holmgren et al.1999; Collinge, Whittington et al. 1994). I wished to investigate whether a change in heart rate variability (HRV) influenced by the presence of PrPD deposits in brainstem areas of animals and people incubating TSEs would be detectable. Recordings from control and infected sheep, cattle and humans, consisting of three hundred-second samples of electrocardiogram (ECG) were collected from species specific healthy controls and subjects incubating TSE disease. Data were digitised at a sampling frequency of 1kHz and were translated and analysed using standard software (CED Spike2 ; IBM SPSS). Artefacts and missed beats were corrected based upon screening by eye. ECG R-wave timings were obtained in order to determine variability in the R-R intervals. An instantaneous tachogram was constructed from which power spectra were calculated. Power spectral analysis along with simpler time domain estimates of HRV, such as RMSSD, were employed to investigate differences between control and infected animals. In addition R wave variability within each breath was utilized to examine the vagal control of the heart in relation to breathing and thus investigate a change in function of the specific neurological areas of the brainstem used as diagnostic criteria for such diseases. It was found there were significant differences (p<0.05) in the HRV of infected sheep, cattle and humans incubating TSE disease compared to control samples. Repeated non-invasive longitudinal tests may provide a means to screen animals and humans for the presence of disease associated prions and may give applications in the objective assessments of putative therapeutics in addition to identifying TSE disease at a preclinical stage.EThOS - Electronic Theses Online ServiceGBUnited Kingdo

A Taxonomy of Internet Appliances

The world is evolving from one in which almost all access to the Internet comes from personal computers (PCs) to one in which so-called Internet appliances (IAs) will make up a greater share of end-user equipment. Today's PC is a general-purpose, highly configurable and extensible device ? an "intelligent end-node" of the sort the Internet's designers had in mind. As such, it allows users much freedom of choice (such as which service provider to use, which Web sites to visit, and which new software to download) in exchange for dealing with associated complexity. An IA is a device connected to the Internet, but beyond that there is little consensus on functionality and target markets. There is, however, general agreement that it reduces the level of complexity seen by the user. A variety of approaches to reducing complexity are being pursued. These fall on a spectrum from totally fixing the function of devices, to automating the configuration of more general purpose systems. In the middle are devices whose functions appear more or less fixed to the user, but which retain some limited capability for upgrade through their Internet connection

Evaluating the impact of flexible alcohol trading hours on violence: an interrupted time series analysis.

BACKGROUND: On November 24(th) 2005, the Government of England and Wales removed regulatory restrictions on the times at which licensed premises could sell alcohol. This study tests availability theory by treating the implementation of Licensing Act (2003) as a natural experiment in alcohol policy. METHODS: An interrupted time series design was employed to estimate the Act's immediate and delayed impact on violence in the City of Manchester (Population 464,200). We collected police recorded rates of violence, robbery, and total crime between the 1st of February 2004 and the 31st of December 2007. Events were aggregated by week, yielding a total of 204 observations (95 pre-, and 109 post-intervention). Secondary analysis examined changes in daily patterns of violence. Pre- and post-intervention events were separated into four three-hour segments 18∶00-20∶59, 21∶00-23.59, 00∶00-02∶59, 03∶00-05∶59. RESULTS: Analysis found no evidence that the Licensing Act (2003) affected the overall volume of violence. However, analyses of night-time violence found a gradual and permanent shift of weekend violence into later parts of the night. The results estimated an initial increase of 27.5% between 03∶00 to 06∶00 (ω = 0.2433, 95% CI = 0.06, 0.42), which increased to 36% by the end of the study period (δ = -0.897, 95% CI = -1.02, -0.77). CONCLUSIONS: This study found no evidence that a national policy increasing the physical availability of alcohol affected the overall volume of violence. There was, however, evidence suggesting that the policy may be associated with changes to patterns of violence in the early morning (3 a.m. to 6 a.m.)

TAX-Pose: Task-Specific Cross-Pose Estimation for Robot Manipulation

How do we imbue robots with the ability to efficiently manipulate unseen objects and transfer relevant skills based on demonstrations? End-to-end learning methods often fail to generalize to novel objects or unseen configurations. Instead, we focus on the task-specific pose relationship between relevant parts of interacting objects. We conjecture that this relationship is a generalizable notion of a manipulation task that can transfer to new objects in the same category; examples include the relationship between the pose of a pan relative to an oven or the pose of a mug relative to a mug rack. We call this task-specific pose relationship "cross-pose" and provide a mathematical definition of this concept. We propose a vision-based system that learns to estimate the cross-pose between two objects for a given manipulation task using learned cross-object correspondences. The estimated cross-pose is then used to guide a downstream motion planner to manipulate the objects into the desired pose relationship (placing a pan into the oven or the mug onto the mug rack). We demonstrate our method's capability to generalize to unseen objects, in some cases after training on only 10 demonstrations in the real world. Results show that our system achieves state-of-the-art performance in both simulated and real-world experiments across a number of tasks. Supplementary information and videos can be found at https://sites.google.com/view/tax-pose/home.Comment: Conference on Robot Learning (CoRL), 2022. Supplementary material is available at https://sites.google.com/view/tax-pose/hom

A Novel HDL-Mimetic Peptide HM-10/10 Protects RPE and Photoreceptors in Murine Models of Retinal Degeneration.

Age-related macular degeneration (AMD) is a leading cause of blindness in the developed world. The retinal pigment epithelium (RPE) is a critical site of pathology in AMD. Oxidative stress plays a key role in the development of AMD. We generated a chimeric high-density lipoprotein (HDL), mimetic peptide named HM-10/10, with anti-oxidant properties and investigated its potential for the treatment of retinal disease using cell culture and animal models of RPE and photoreceptor (PR) degeneration. Treatment with HM-10/10 peptide prevented human fetal RPE cell death caused by tert-Butyl hydroperoxide (tBH)-induced oxidative stress and sodium iodate (NaIO3), which causes RPE atrophy and is a model of geographic atrophy in mice. We also show that HM-10/10 peptide ameliorated photoreceptor cell death and significantly improved retinal function in a mouse model of N-methyl-N-nitrosourea (MNU)-induced PR degeneration. Our results demonstrate that HM-10/10 protects RPE and retina from oxidant injury and can serve as a potential therapeutic agent for the treatment of retinal degeneration