Positive chronotropic actions of parathyroid hormone and parathyroid hormone-related peptide are associated with increases in the current, I(f), and the slope of the pacemaker potential

BACKGROUND: The classic calciotropic hormone parathyroid hormone (PTH) and its paracrine factor parathyroid hormone-related protein (PTHrP) both increase heart rate. METHODS AND RESULTS: We used standard electrophysiological techniques to study the effects of PTH and PTHrP on isolated rabbit sinus node, isolated canine Purkinje fibers, and disaggregated rabbit sinus node myocytes. Sinus node maximum diastolic potential, activation voltage, and amplitude were unchanged by PTH or PTHrP (P>.05). However, the slope of phase 4 and the automatic rate were increased at PTH and PTHrP > or = 10 nmol/L (P<.05). Comparable results were seen in canine Purkinje fibers. We then used the perforated-patch technique to study the I(f) pacemaker current in sinus node. PTH 12.5 nmol/L and PTHrP 12.5 to 18 nmol/L increased I(f) at -65 mV by 68+/-41% (n=5) and 69+/-50% (n=5), respectively. Actions of both agents were reversible. The increase in I(f) appeared to result from a change in maximal conductance and not a shift in the voltage dependence of activation. CONCLUSIONS: These observations provide, for the first time, direct electrophysiological support for the chronotropic actions of PTH and PTHrP. They suggest that classic hormones and paracrine factors can have multiple functions and that in the case of PTH and PTHrP, a newly recognized action is to alter automaticity directly.     

Reasoning about Textual Similarity in a Web-Based Information Access System

The degree to which information sources are pre-processed by Web-based information systems varies greatly. In search engines like Altavista, little pre-processing is done, while in knowledge integration systems, complex site-specific wrappers are used to integrate different information sources into a common database representation. In this paper we describe an intermediate point between these two models. In our system, information sources are converted into a highly structured collection of small fragments of text. Database-like queries to this structured collection of text fragments are approximated using a novel logic called WHIRL, which combines inference in the style of deductive databases with ranked retrieval methods from information retrieval (IR). WHIRL allows queries that integrate information from multiple Web sites, without requiring the extraction and normalization of object identifiers that can be used as keys; instead, operations that in conventional databases require equality tests on keys are approximated using IR similarity metrics for text. This leads to a reduction in the amount of human engineering required to field a knowledge integration system. Experimental evidence is given showing that many information sources can be easily modeled with WHIRL, and that inferences in the logic are both accurate and efficient.     

An efficient and robust method for Lagrangian magnetic particle tracking in fluid flow simulations on unstructured grids

In this paper we report on a newly developed particle tracking scheme for fluid flow simulations on 3D unstructured grids, aiming to provide detailed insights in the particle behaviour in complex geometries. A possible field of applications is the magnetic drug targeting (MDT) technique, on which this paper will be focused. MDT is a promising medical technique that uses locally applied magnetic fields to capture magnetic drug carriers at the desired locations in the human body, strongly increasing the efficiency of medical drugs. The new particle tracking scheme combines the advantages of existing methods and is easy for implementation in a generic numerical code. The scheme is tested and validated for simple MDT cases that include effects of a non-homogeneous magnetic field on deposition of magnetic particles in laminar flow. The first test case is a validation study of the magnetic particle trajectories released in a horizontal circular pipe flow with a current-carrying wire parallel to the flow, for which analytical solutions are reported in literature. The second test case involves particle capture efficiencies in a 90° bent tube for different configurations of the imposed magnetic field. This configuration corresponds more closely to the conditions inside blood vessels, because of the presence of secondary motions. These results are compared with numerical studies from literature too. The obtained results demonstrate that the developed particle tracking scheme is a very robust, efficient and accurate method, which can give detailed insights in particle behaviour in complex geometries. As such it is a good candidate for future applications and optimisations of MDT technique for loco-regional cancer treatment or treatment of cardiovascular diseases.     

Venom Peptide Toxins Targeting the Outer Pore Region of Transient Receptor Potential Vanilloid 1 in Pain: Implications for Analgesic Drug Development

The transient receptor potential vanilloid 1 (TRPV1) ion channel plays an important role in the peripheral nociceptive pathway. TRPV1 is a polymodal receptor that can be activated by multiple types of ligands and painful stimuli, such as noxious heat and protons, and contributes to various acute and chronic pain conditions. Therefore, TRPV1 is emerging as a novel therapeutic target for the treatment of various pain conditions. Notably, various peptides isolated from venomous animals potently and selectively control the activation and inhibition of TRPV1 by binding to its outer pore region. This review will focus on the mechanisms by which venom-derived peptides interact with this portion of TRPV1 to control receptor functions and how these mechanisms can drive the development of new types of analgesics.     

Transformation of c-oriented nanowall network to a flat morphology in GaN films on c-plane sapphire

The work significantly optimizes growth parameters for nanostructured and flat GaN film in the 480–830 °C temperature range. The growth of ordered, high quality GaN nanowall hexagonal honeycomb like network on c-plane sapphire under nitrogen rich (N/Ga ratio of 100) conditions at temperatures below 700 °C is demonstrated. The walls are c-oriented wurtzite structures 200 nm wide at base and taper to 10 nm at apex, manifesting electron confinement effects to tune optoelectronic properties. For substrate temperatures above 700 °C the nanowalls thicken to a flat morphology with a dislocation density of 10¹⁰/cm². The role of misfit dislocations in the GaN overlayer evolution is discussed in terms of growth kinetics being influenced by adatom diffusion, interactions and bonding at different temperatures. The GaN films are characterized by reflection high energy electron diffraction (RHEED), field emission scanning electron (FESEM), high resolution X-ray diffraction (HRXRD) and cathodoluminescence (CL).     

Understanding Viruses Bio-logically

Networks dominate today’s computing landscape and commercial, technical protection is lagging behind attack technology. As a result, protection program success depends more on prudent management decisions than on the selection of technical safeguards. Managing Network Security takes a management view of protection and seeks to reconcile the need for security with the limitations of technology.     

Example Based Everyting

The magic of computer graphics as seen in many current movies and computer games comes at a cost. Creating the geometric forms with which to generate synthetic characters and animating the characters to bring them to life require either highly skilled artists and/or sophisticated capture devices. Both are expensive and, in the case of highly skilled artists, rare.     

Constance Kamii's research and recent math reforms

Constance Kamii. (1990). Multiplication of two‐digit numbers: Two teachers using Piaget's theory. [Videotape.] New York: Teachers College Press. ISBN 0–8077–3086–6, Cdn $86.