α_1L-adrenoceptors mediate contraction of human erectile tissue

α1-adrenoceptor antagonists can impact upon sexual function and have potential in the treatment of erectile dysfunction. Human erectile tissue contains predominantly α1A-adrenoceptors, and here we examined whether contractions of this tissue are mediated by the functional phenotype, the α1L-adrenoceptor. Functional experiments using subtype selective agonists and antagonists, along with radioligand ([3H]tamsulosin) binding assays, were used to determine the α1-adrenoceptor population. A61603, a α1A-adrenoceptor agonist, was a full agonist with a potency 21-fold greater than that of noradrenaline. The α1A- and α1D-adrenoceptor antagonist tamsulosin antagonized noradrenaline responses with high affinity (pKD = 9.7 ± 0.3), whilst BMY7378 (100 nM) (α1D-adrenoceptor antagonist) failed to antagonize responses. In contrast, relatively low affinity estimates were obtained for both prazosin (pKD = 8.2 ± 0.1) and RS17053 (pKD = 6.9 ± 0.2), antagonists which discriminate between the α1A- and α1L-adrenoceptors. [3H]Tamsulosin bound with high affinity to the receptors of human erectile tissue (pKD = 10.3 ± 0.1) with a receptor density of 28.1 ± 1.4 fmol mg−1 protein. Prazosin displacement of [3H]tamsulosin binding revealed a single homogenous population of binding sites with a relatively low affinity for prazosin (pKi = 8.9). Taken together these data confirm that the receptor mediating contraction in human erectile tissue has the pharmacological properties of the α1L-adrenoceptor. Keywords: Erectile tissue, α1-adrenoceptor subtypes, α1L-adrenoceptor, Tamsulosin, Prazosi

D’Agents: Security in a Multiple-Language, Mobile-Agent System

Abstract. Mobile-agent systems must address three security issues: protecting an individual machine, protecting a group of machines, and protecting an agent. In this chapter, we discuss these three issues in the context of D’Agents, a mobile-agent system whose agents can be written in Tcl, Java and Scheme. (D’Agents was formerly known as Agent Tcl.) First we discuss mechanisms existing in D’Agents for protecting an individual machine: (1) cryptographic authentication of the agent’s owner, (2) resource managers that make policy decisions based on the owner’s identity, and (3) secure execution environments for each language that enforce the decisions of the resource managers. Then we discuss our planned market-based approach for protecting machine groups. Finally we consider several (partial) solutions for protecting an agent from a malicious machine.

What Developers Want and Need from Program Analysis: An Empirical Study

Program Analysis has been a rich and fruitful field of research for many decades, and countless high quality program analysis tools have been produced by academia. Though there are some well-known examples of tools that have found their way into routine use by practitioners, a common challenge faced by researchers is knowing how to achieve broad and lasting adoption of their tools. In an effort to understand what makes a program analyzer most attractive to developers, we mounted a multi-method investigation at Microsoft. Through interviews and surveys of developers as well as analysis of defect data, we provide insight and answers to four high level research questions that can help researchers design program analyzers meeting the needs of software developers. First, we explore what barriers hinder the adoption of program analyzers, like poorly expressed warning messages. Second, we shed light on what functionality developers want from analyzers, including the types of code issues that developers care about. Next, we answer what non-functional characteristics an analyzer should have to be widely used, how the analyzer should fit into the development process, and how its results should be reported. Finally, we investigate defects in one of Microsoft's flagship software services, to understand what types of code issues are most important to minimize, potentially through program analysis

Development of parent- and teacher-reported emotional and behavioural problems in young people with intellectual disabilities: Does level of ID matter?

This study described similarities and differences in the 5-year stability and change of problem behaviour between youths attending schools for children with mild to borderline (MiID) versus moderate intellectual disabilities (MoID). A two-wave multiple-birth-cohort sample of 6 to 18-year-old was assessed twice across a 5-year interval using the Developmental Behaviour Checklist Primary Carer version (n = 718) and Teacher version (n = 313). For most types of problem behaviour youths with MiID and MoID showed similar levels of stability of individual differences, persistence and onset of psychopathology. Whenever differences were found, youths with MoID showed the highest level of stability, persistence and onset across informants. Mean levels of parent-reported, but not teacher-reported, problem behaviour, regardless of level of intellectual disability, decreased during the 5-year follow-up period. Youths with MoID and MiID are at risk for persistent psychopathology to a similar degree. Different informants showed to have a different evaluation of the level and the amount of change of problem behaviour, and should be considered complementary in the diagnostic process. © 2007 BILD Publications

Zinc-Rich Paint As Anode for Cathodic Protection of Steel in Concrete

This paper describes the findings of the experimental works undertaken to investigate the performance of zinc-rich paint (ZRP) to provide cathodic protection to chloride-contaminated RC structures. The program of experimental works was designed and conducted to assess four principal properties, viz (1) conductivity, (2) adhesion with concrete (short term and long term), (3) durability, and (4) electrochemical polarization. These properties considered together define the ability and effectiveness of the materials to act as an anode for impressed current cathodic protection. The research findings indicated that a specific proprietary ZRP product showed that optimum conductance was obtained with three coats producing a 280-320 μm thickness, with good adhesion to the concrete substrate, in which values obtained ranged between 1.65 and 3.5 MPa with and without applied current. It was capable of withstanding/supporting high levels of current, i.e., more than 300 mA/m2, and the service life of the ZRP coating was estimated to be well in excess of 20 years at an applied current density of 10 mA/m2

Ready ... Go: Amplitude of the fMRI Signal Encodes Expectation of Cue Arrival Time

What happens when the brain awaits a signal of uncertain arrival time, as when a sprinter waits for the starting pistol? And what happens just after the starting pistol fires? Using functional magnetic resonance imaging (fMRI), we have discovered a novel correlate of temporal expectations in several brain regions, most prominently in the supplementary motor area (SMA). Contrary to expectations, we found little fMRI activity during the waiting period; however, a large signal appears after the “go” signal, the amplitude of which reflects learned expectations about the distribution of possible waiting times. Specifically, the amplitude of the fMRI signal appears to encode a cumulative conditional probability, also known as the cumulative hazard function. The fMRI signal loses its dependence on waiting time in a “countdown” condition in which the arrival time of the go cue is known in advance, suggesting that the signal encodes temporal probabilities rather than simply elapsed time. The dependence of the signal on temporal expectation is present in “no-go” conditions, demonstrating that the effect is not a consequence of motor output. Finally, the encoding is not dependent on modality, operating in the same manner with auditory or visual signals. This finding extends our understanding of the relationship between temporal expectancy and measurable neural signals

Clastic Sediments in the Butler Cave – Sinking Creek System, Virginia, USA

The Butler Cave - Sinking Creek System in Bath County, Virginia, consists of a master trunk passage along the axis of a syncline with a trellis arrangement of dip-oriented side caves. The western set of dip passages contain a sequence of massively and chaotically bedded sand and cobble sediments. Massive cobble fills also occur in the strike-oriented trunk passage. Cave passages on the eastern side of the syncline contain mostly sand and silt. The light fraction of the sediments consists predominantly of quartz and rock fragments. The sediments contain several percent heavy minerals composed of iron oxides, zircon, rutile, tourmaline and other minerals. Measurement of the visible and near infrared diffuse reflectance spectra shows at least three populations of sediments to be present: an iron-rich, clay-poor group; a clay-rich group; and a gypsiferous sediment. The iron minerals provided a paleomagnetic signal. Sediments from the trunk passage, deposited by recent underground drainage, contained a normal pole direction. Sediments from the dip passages were paleomagnetically reversed, showing the deposition dates from prior to 780,000 years. In one instance reversed polarity deposits overlie normal polarity, implying a minimum age of 990,000 years for the reversed sediments.   

Human neutrophil clearance of bacterial pathogens triggers anti-microbial gamma delta T cell responses in early infection

Human blood Vc9/Vd2 T cells, monocytes and neutrophils share a responsiveness toward inflammatory chemokines and are rapidly recruited to sites of infection. Studying their interaction in vitro and relating these findings to in vivo observations in patients may therefore provide crucial insight into inflammatory events. Our present data demonstrate that Vc9/Vd2 T cells provide potent survival signals resulting in neutrophil activation and the release of the neutrophil chemoattractant CXCL8 (IL-8). In turn, Vc9/Vd2 T cells readily respond to neutrophils harboring phagocytosed bacteria, as evidenced by expression of CD69, interferon (IFN)-c and tumor necrosis factor (TNF)-a. This response is dependent on the ability of these bacteria to produce the microbial metabolite (E)-4-hydroxy-3-methyl-but-2-enyl pyrophosphate (HMB-PP), requires cell-cell contact of Vc9/Vd2 T cells with accessory monocytes through lymphocyte function-associated antigen-1 (LFA-1), and results in a TNF-a dependent proliferation of Vc9/Vd2 T cells. The antibiotic fosmidomycin, which targets the HMB-PP biosynthesis pathway, not only has a direct antibacterial effect on most HMB-PP producing bacteria but also possesses rapid anti-inflammatory properties by inhibiting cd T cell responses in vitro. Patients with acute peritoneal-dialysis (PD)-associated bacterial peritonitis – characterized by an excessive influx of neutrophils and monocytes into the peritoneal cavity – show a selective activation of local Vc9/Vd2 T cells by HMB-PP producing but not by HMB-PP deficient bacterial pathogens. The cd T celldriven perpetuation of inflammatory responses during acute peritonitis is associated with elevated peritoneal levels of cd T cells and TNF-a and detrimental clinical outcomes in infections caused by HMB-PP positive microorganisms. Taken together, our findings indicate a direct link between invading pathogens, neutrophils, monocytes and microbe-responsive cd T cells in early infection and suggest novel diagnostic and therapeutic approaches.Martin S. Davey, Chan-Yu Lin, Gareth W. Roberts, Sinéad Heuston, Amanda C. Brown, James A. Chess, Mark A. Toleman, Cormac G.M. Gahan, Colin Hill, Tanya Parish, John D. Williams, Simon J. Davies, David W. Johnson, Nicholas Topley, Bernhard Moser and Matthias Eber

Farm Production Analysis Training for Small Farmers

A partnership between Penn State Cooperative Extension and the Farm Service Agency has developed a successful production training program for more than 367 farmers. Farmers received training in producing planning and budgets, partial budgeting, and livestock and agronomic basics. Significant gains in knowledge occurred in multi-year planning, enterprise budgeting, and use of the Penn State Agronomy Guide. Designing workshop material for low-producing farmers proved difficult because most participants, while finding the topics helpful, also found the material too advanced. Future focus will encourage greater involvement with private-sector institutions and coordination between production and management Extension specialists

Farm Production Analysis Training for Small Farmers

A partnership between Penn State Cooperative Extension and the Farm Service Agency has developed a successful production training program for more than 367 farmers. Farmers received training in producing planning and budgets, partial budgeting, and livestock and agronomic basics. Significant gains in knowledge occurred in multi-year planning, enterprise budgeting, and use of the Penn State Agronomy Guide. Designing workshop material for low-producing farmers proved difficult because most participants, while finding the topics helpful, also found the material too advanced. Future focus will encourage greater involvement with private-sector institutions and coordination between production and management Extension specialists