Report of the panel on plate motion and deformation, section 2

Given here is a panel report on the goals and objectives, requirements and recommendations for the investigation of plate motion and deformation. The goals are to refine our knowledge of plate motions, study regional and local deformation, and contribute to the solution of important societal problems. The requirements include basic space-positioning measurements, the use of global and regional data sets obtained with space-based techniques, topographic and geoid data to help characterize the internal processes that shape the planet, gravity data to study the density structure at depth and help determine the driving mechanisms for plate tectonics, and satellite images to map lithology, structure and morphology. The most important recommendation of the panel is for the implementation of a world-wide space-geodetic fiducial network to provide a systematic and uniform measure of global strain

P-624: Changes in plasma renin match the antihypertensive effects of aliskiren in patients with hypertension: Placebo/irbesartan-controlled trial with the orally active renin inhibitor aliskiren

For several decades, the lack of oral availability and poor antihypertensive effects of renin inhibitors (RI), despite seemingly powerful inhibition of conventionally measured plasma renin activity (PRA), have discredited RI as cardiovascular drugs. Aliskiren is a novel orally effective RI with antihypertensive potency comparable to losartan or irbesartan. The present study investigated the effects of aliskiren and irbesartan on PRA, measured by the reliable antibody trapping technique, as well as on plasma active renin concentration (ARC) and sitting systolic blood pressure (SBP). In 569 patients with mild to moderate hypertension (baseline sphygmomanometric sitting blood pressure 152±12/99±4 mmHg, mean±SD), PRA and ARC, as well as SBP were measured before and after 8 weeks of treatment with once daily oral doses of aliskiren (150, 300 or 600mg), irbesartan 150mg or placebo. The effects of study treatments on PRA, ARC and SBP are summarized in the Table. Treatment N PRA (ng/mL/h) ARC (pg/mL) SBP (mmHg) Baseline Week 8 Baseline Week 8 Baseline Week 8 Placebo 111 0.72 0.64 6.2 5.6 152 ± 12 147 ± 18 Aliskiren 150mg 112 0.66 0.20 6.0 15.3 151 ± 11 140 ± 14 Aliskiren 300mg 115 0.59 0.17 6.1 21.0 152 ± 10 137 ± 14 Aliskiren 600mg 113 0.64 0.16 5.8 34.9 153 ± 12 137 ± 16 Irbesartan 150mg 118 0.64 1.33 5.5 11.3 153 ± 11 140 ± 16 PRA and ARC values are geometric means; SBP values are mean ± SD Aliskiren reduced PRA by 69%, 71% and 75% at 150, 300 and 600mg respectively, while irbesartan doubled PRA. Most of the antihypertensive effect of aliskiren was obtained with the lowest dose, but higher doses slightly further decreased SBP. Aliskiren 150mg and irbesartan 150mg provided similar increases in ARC and hence comparably blocked the renin-angiotensin system (RAS), and the achieved SBP was also the same. Aliskiren 300mg and 600mg caused greater increases in ARC compared with irbesartan 150mg (p<0.05), and further decreases in SBP. The dose-dependent increases in ARC observed with aliskiren document increasing blockade of the RAS. In conclusion, aliskiren provides a parallel reduction in PRA and SBP, a dose-dependent blockade of the RAS and is at least as effective as irbesartan at comparable dosages (150mg

An Expert Consensus Framework for Asthma Remission as a Treatment Goal

With novel therapies in development, there is an opportunity to consider asthma remission as a treatment goal. In this Rostrum, we present a generalized framework for clinical and complete remission in asthma, on and off treatment, developed on the basis of medical literature and expert consensus. A modified Delphi survey approach was used to ascertain expert consensus on core components of asthma remission as a treatment target. Phase 1 identified other chronic inflammatory diseases with remission definitions. Phase 2 evaluated components of those definitions as well as published definitions of spontaneous asthma remission. Phase 3 evaluated a remission framework created using consensus findings. Clinical remission comprised 12 or more months with (1) absence of significant symptoms by validated instrument, (2) lung function optimization/stabilization, (3) patient/provider agreement regarding remission, and (4) no use of systemic corticosteroids. Complete remission was defined as clinical remission plus objective resolution of asthma-related inflammation and, if appropriate, negative bronchial hyperresponsiveness. Remission off treatment required no asthma treatment for 12 or more months. The proposed framework is a first step toward developing asthma remission as a treatment target and should be refined through future research, patient input, and clinical study

Ontogeny of Toll-Like and NOD-Like Receptor-Mediated Innate Immune Responses in Papua New Guinean Infants

Studies addressing the ontogeny of the innate immune system in early life have reported mainly on Toll-like receptor (TLR) responses in infants living in high-income countries, with little or even no information on other pattern recognition receptors or on early life innate immune responses in children living under very different environmental conditions in less-developed parts of the world. In this study, we describe whole blood innate immune responses to both Toll-like and nucleotide-binding oligomerization domain (NOD)-like receptor agonists including the widely used vaccine adjuvant ‘alum’ in a group of Papua New Guinean infants aged 1–3 (n = 18), 4–6 (n = 18), 7–12 (n = 21) and 13–18 (n = 10) months old. Depending on the ligands and cytokines studied, different age-related patterns were found: alum-induced IL-1β and CXCL8 responses were found to significantly decline with increasing age; inflammatory (IL-6, IL-1β, IFN-γ) responses to TLR2 and TLR3 agonists increased; and IL-10 responses remained constant or increased during infancy, while TNF-α responses either declined or remained the same. We report for the first time that whole blood innate immune responses to the vaccine adjuvant alum decrease with age in infancy; a finding that may imply that the adjuvant effect of alum in pediatric vaccines could be age-related. Our findings further suggest that patterns of innate immune development may vary between geographically diverse populations, which in line with the ‘hygiene hypothesis’ particularly involves persistence of innate IL-10 responses in populations experiencing higher infectious pressure

Effect of heparin and heparan sulphate on open promoter complex formation for a simple tandem gene model using ex situ atomic force microscopy

The influence of heparin and heparan sulphate (HepS) on the appearance and analysis of open promoter complex (RPo) formation by E. coli RNA polymerase (RNAP) holoenzyme (σ70RNAP) on linear DNA using ex situ imaging by atomic force microscopy (AFM) has been investigated. Introducing heparin or HepS into the reaction mix significantly reduces non-specific interactions of the σ70RNAP and RNAP after RPo formation allowing for better interpretation of complexes shown within AFM images, particularly on DNA templates containing more than one promoter. Previous expectation was that negatively charged polysaccharides, often used as competitive inhibitors of σRNAP binding and RPo formation, would also inhibit binding of the DNA template to the mica support surface and thereby lower the imaging yield of active RNAP-DNA complexes. We found that the reverse of this was true, and that the yield of RPo formation detected by AFM, for a simple tandem gene model containing two λPR promoters, increased. Moreover and unexpectedly, HepS was more efficient than heparin, with both of them having a dispersive effect on the sample, minimising unwanted RNAP-RNAP interactions as well as non-specific interactions between the RNAP and DNA template. The success of this method relied on the observation that E. coli RNAP has the highest affinity for the mica surface of all the molecular components. For our system, the affinity of the three constituent biopolymers to muscovite mica was RNAP > Heparin or HepS > DNA. While we observed that heparin and HepS can inhibit DNA binding to the mica, the presence of E. coli RNAP overcomes this effect allowing a greater yield of RPos for AFM analysis. This method can be extended to other DNA binding proteins and enzymes, which have an affinity to mica higher than DNA, to improve sample preparation for AFM studies

High-resolution image of Calaveras Fault seismicity

By measuring relative earthquake arrival times using waveform cross correlation and locating earthquakes using the double difference technique, we are able to reduce hypocentral errors by 1 to 2 orders of magnitude over routine locations for nearly 8000 events along a 35-km section of the Calaveras Fault. This represents ∼92% of all seismicity since 1984 and includes the rupture zone of the M 6.2 1984 Morgan Hill, California, earthquake. The relocated seismicity forms highly organized structures that were previously obscured by location errors. There are abundant repeating earthquake sequences as well as linear clusters of earthquakes. Large voids in seismicity appear with dimensions of kilometers that have been aseismic over the 30-year time interval, suggesting that these portions of the fault are either locked or creeping. The area of greatest slip in the Morgan Hill main shock coincides with the most prominent of these voids, suggesting that this part of the fault may be locked between large earthquakes. We find that the Calaveras Fault at depth is extremely thin, with an average upper bound on fault zone width of 75 m. Given the location error, however, this width is not resolvably different from zero. The relocations reveal active secondary faults, which we use to solve for the stress field in the immediate vicinity of the Calaveras Fault. We find that the maximum compressive stress is at a high angle, only 13° from the fault normal, supporting previous interpretations that this fault is weak

Collision events between RNA polymerases in convergent transcription studied by atomic force microscopy

Atomic force microscopy (AFM) has been used to image, at single molecule resolution, transcription events by Escherichia coli RNA polymerase (RNAP) on a linear DNA template with two convergently aligned λ(pr) promoters. For the first time experimentally, the outcome of collision events during convergent transcription by two identical RNAP has been studied. Measurement of the positions of the RNAP on the DNA, allows distinction of open promoter complexes (OPCs) and elongating complexes (EC) and collided complexes (CC). This discontinuous time-course enables subsequent analysis of collision events where both RNAP remain bound on the DNA. After collision, the elongating RNAP has caused the other (usually stalled) RNAP to back-track along the template. The final positions of the two RNAP indicate that these are collisions between an EC and a stalled EC (SEC) or OPC (previously referred to as sitting-ducks). Interestingly, the distances between the two RNAP show that they are not always at closest approach after ‘collision’ has caused their arrest

Malaria in HIV-Infected Children Receiving HIV Protease-Inhibitor- Compared with Non-Nucleoside Reverse Transcriptase Inhibitor-Based Antiretroviral Therapy, IMPAACT P1068s, Substudy to P1060

HIV and malaria geographically overlap. HIV protease inhibitors kill malaria parasites in vitro and in vivo, but further evaluation in clinical studies is needed

Study of Gluon versus Quark Fragmentation in Υ→ggγ\Upsilon\to gg\gamma and e+e−→qqˉγe^{+}e^{-}\to q\bar{q}\gamma Events at \sqrt{s}=10 GeV

Using data collected with the CLEO II detector at the Cornell Electron Storage Ring, we determine the ratio R(chrg) for the mean charged multiplicity observed in Upsilon(1S)->gggamma events, to the mean charged multiplicity observed in e+e- -> qqbar gamma events. We find R(chrg)=1.04+/-0.02+/-0.05 for jet-jet masses less than 7 GeV.Comment: 15 pages, postscript file also available through http://w4.lns.cornell.edu/public/CLN