Genes for blood pressure: an opportunity to understand hypertension

Hypertension (HTN) is quantitatively the major cardiovascular risk factor and responsible for ∼50% of cardiovascular morbidity and mortality. Blood pressure (BP) is also a classical complex genetic trait with heritability estimates of 30-50%. Although much is known about BP regulation, the intrinsic origin of essential HTN remains obscure although many environmental factors are known. Analyses of rare monogenic syndromes of HTN have focused attention on pathways that involve renal sodium handling, and steroid hormone metabolism including the mineralocorticoid receptor activity. The genetic basis of common essential HTN on the other hand is only just becoming accessible through high-throughput approaches. Unbiased genome-wide analyses of BP genomics have identified 43 genetic variants associated with systolic, diastolic BP, and HTN. It is highly likely based on current findings that there are hundreds of such loci with small effects on BP, opening a perspective on the genetic architecture of BP that was unknown before. It is our hope that the knowledge of these and further loci will lead to improved understanding of BP pathophysiology and to the identification of new targets for drug therap

STUDIES ON PROTEIN UPTAKE BY ISOLATED TUMOR CELLS : I. Electron Microscopic Evidence of Ferritin Uptake by Ehrlich Ascites Tumor Cells

Ferritin, added to the incubation medium of ascites tumor cells, was used as an electron microscopic marker to study the uptake of large protein molecules by morphologically intact cells. A definite uptake could be detected after 1 hour of incubation in Tyrode bicarbonate solution containing 0.04 to 13.3 mg ferritin/ml. Ferritin was found in a variety of membrane-surrounded structures, suggesting that pinocytesis and related membrane movements are occurring under physiological conditions and can account for the penetration of intact macromolecules into isolated tumor cells. Supplementation of the medium with serum albumin (33 mg/ml) increased the average amount of ferritin per cell and per pinocytotic structure. Ferritin was strongly adsorbed by fragments of lysed cells, which were readily taken up by intact cells. Besides its role as carrier, this debris appeared to stimulate membrane movements. Only rare examples were found to suggest the release of ferritin from the pinocytotic structures into the cytoplasm. Thus, the disintegration of such structures cannot be considered an obvious step towards a rapid metabolic utilization of protein by the cell. Particles of colloidal gold presented to the cell under the same conditions were not taken up to any significant extent, thus providing good evidence for a selective ingestion of particles of comparable sizes

STUDIES ON PROTEIN UPTAKE BY ISOLATED TUMOR CELLS : II. Quantitative Data on the Adsorption and Uptake of I131-Serum Albumin by Ehrlich Ascites Tumor Cells

Surface adsorption is studied in some detail because it is believed to be a major artifact in measurements of protein uptake by mammalian cells. Adsorption increases linearly with the I131-albumin concentration between 0.001 and 300 mg/ml. After short exposure to 300 mg/ml and two cell washings, the adsorption amounts to 38 mg albumin per gm cell proteins. Further washings remove 80 per cent of this value, leaving a small irreversibly bound residue. At equilibrium, adsorbed albumin can be labeled by a simple albumin exchange. This labeling reaches a steady state within seconds and stays at constant level over 30 minutes. Significant increases above this initial level are measured over periods of 2 hours. In our experimental conditions these increases can be considered due to albumin uptake. This uptake rises linearly with the albumin concentration between 0.5 and 50.0 mg/ml, and reaches 0.2 mg/gm cell protein or 4 x 105 molecules per cell. Compared to the incorporation of free amino acids in similar conditions, this value does not appear to contribute significantly to the N-metabolism of the tumor cells. Adsorption was generally greater than uptake. Both processes are linear functions of the same variable over the whole range of concentration tested. It is suggested that albumin is taken up by pinocytosis

The angular dependent magnetoresistance in alpha-(BEDT-TTF)_2KHg(SCN)_4

In spite of extensive experimental studies of the angular dependent magnetoresistance (ADMR) of the low temperature phase (LTP) of alpha-(BEDT-TTF)_2KHg(SCN)_4 about a decade ago, the nature of LTP remains elusive. Here we present a new study of ADMR of LTP in alpha-(ET)_2 salts assuming that LTP is unconventional charge density wave (UCDW). In the presence of magnetic field the quasiparticle spectrum in UCDW is quantized, which gives rise to striking ADMR in UCDW. The present model appears to account for many existing ADMR data of alpha-(BEDT-TTF)_2KHg(SCN)_4 remarkably well.Comment: 6 pages, 4 figure

Predicting deleterious nsSNPs: an analysis of sequence and structural attributes

BACKGROUND: There has been an explosion in the number of single nucleotide polymorphisms (SNPs) within public databases. In this study we focused on non-synonymous protein coding single nucleotide polymorphisms (nsSNPs), some associated with disease and others which are thought to be neutral. We describe the distribution of both types of nsSNPs using structural and sequence based features and assess the relative value of these attributes as predictors of function using machine learning methods. We also address the common problem of balance within machine learning methods and show the effect of imbalance on nsSNP function prediction. We show that nsSNP function prediction can be significantly improved by 100% undersampling of the majority class. The learnt rules were then applied to make predictions of function on all nsSNPs within Ensembl. RESULTS: The measure of prediction success is greatly affected by the level of imbalance in the training dataset. We found the balanced dataset that included all attributes produced the best prediction. The performance as measured by the Matthews correlation coefficient (MCC) varied between 0.49 and 0.25 depending on the imbalance. As previously observed, the degree of sequence conservation at the nsSNP position is the single most useful attribute. In addition to conservation, structural predictions made using a balanced dataset can be of value. CONCLUSION: The predictions for all nsSNPs within Ensembl, based on a balanced dataset using all attributes, are available as a DAS annotation. Instructions for adding the track to Ensembl are a

Recent developments in the determination of the amplitude and phase of quantum oscillations for the linear chain of coupled orbits

De Haas-van Alphen oscillations are studied for Fermi surfaces (FS) illustrating the model proposed by Pippard in the early sixties, namely the linear chain of orbits coupled by magnetic breakdown. This FS topology is relevant for many multiband quasi-two dimensional (q-2D) organic metals such as $\kappa$-(BEDT-TTF)$_2$Cu(NCS)$_2$ and $\theta$-(BEDT-TTF)$_4$CoBr$_4$(C$_6$H$_4$Cl$_2$) which are considered in detail. Whereas the Lifshits-Kosevich model only involves a first order development of field- and temperature-dependent damping factors, second order terms may have significant contribution on the Fourier components amplitude for such q-2D systems at high magnetic field and low temperature. The strength of these second order terms depends on the relative value of the involved damping factors, which are in turns strongly dependent on parameters such as the magnetic breakdown field, effective masses and, most of all, effective Land\'{e} factors. In addition, the influence of field-dependent Onsager phase factors on the oscillation spectra is considered.Comment: arXiv admin note: text overlap with arXiv:1304.665

Characterizing the Use of Images in State-Sponsored Information Warfare Operations by {R}ussian {Tr}olls on Twitter

State-sponsored organizations are increasingly linked to efforts aimed to exploit social media for information warfare and manipulating public opinion. Typically, their activities rely on a number of social network accounts they control, aka trolls, that post and interact with other users disguised as "regular" users. These accounts often use images and memes, along with textual content, in order to increase the engagement and the credibility of their posts. In this paper, we present the first study of images shared by state-sponsored accounts by analyzing a ground truth dataset of 1.8M images posted to Twitter by accounts controlled by the Russian Internet Research Agency. First, we analyze the content of the images as well as their posting activity. Then, using Hawkes Processes, we quantify their influence on popular Web communities like Twitter, Reddit, 4chan's Politically Incorrect board (/pol/), and Gab, with respect to the dissemination of images. We find that the extensive image posting activity of Russian trolls coincides with real-world events (e.g., the Unite the Right rally in Charlottesville), and shed light on their targets as well as the content disseminated via images. Finally, we show that the trolls were more effective in disseminating politics-related imagery than other images

A USB Interfaced Motion Capture Sensor, Using Tri-Axis Magnetic/Inertial Sensors For Use In Kinematic Studies

An unobtrusive tri-axis magnetic and gravitational field transducer for use in kinematic tracking is presented. Outlined is a novel approach for using such a sensor i.e. providing a Universal Serial Bus (USB) interface, allowing the direct utilization of the logical topology of the standard, making scalable deployment possible. Furthermore design considerations; construction and performance of the sensor are analysed and discussed in detail

Unconventional charge density wave in the organic conductor alpha-(BEDT-TTF)_2KHg(SCN)_4

The low temperature phase (LTP) of alpha-(BEDT-TTF)_2KHg(SCN)_4 salt is known for its surprising angular dependent magnetoresistance (ADMR), which has been studied intensively in the last decade. However, the nature of the LTP has not been understood until now. Here we analyse theoretically ADMR in unconventional (or nodal) charge density wave (UCDW). In magnetic field the quasiparticle spectrum in UCDW is quantized, which gives rise to spectacular ADMR. The present model accounts for many striking features of ADMR data in alpha-(BEDT-TTF)_2KHg(SCN)_4.Comment: 5 pages, 6 figure

A USB Interfaced Motion Capture Sensor, Using Tri-Axis Magnetic/Inertial Sensors For Use In Kinematic Studies

An unobtrusive tri-axis magnetic and gravitational field transducer for use in kinematic tracking is presented. Outlined is a novel approach for using such a sensor i.e. providing a Universal Serial Bus (USB) interface, allowing the direct utilization of the logical topology of the standard, making scalable deployment possible. Furthermore design considerations; construction and performance of the sensor are analysed and discussed in detail