IGF-II/mannose 6-phosphate receptor activation induces metalloproteinase-9 matrix activity and increases plasminogen activator expression in H9c2 cardiomyoblast cells

[[abstract]]The IGF-II/mannose 6-phosphate receptor (IGF2R) function in extracellular matrix (ECM) remodeling is known to occur as a result of transforming growth factor-beta (TgF-beta) activation and plasmin in the proteolytic cleavage level caused by the interaction between latent TGF-13 and urokinase plasminogen activator receptor (uPAR) respectively. In one of our previous studies, we found IGF-II and IGF2R dose-dependently correlated with the progression of pathological hypertrophy remodeling following complete abdominal aorta ligation. However, how this IGF2R signaling pathway responds specifically to IGF-II and regulates the myocardial ECM remodeling process is unclear. We found that IGF2R was aberrantly expressed in myocardial infarction scars. The matrix metalloproteinase-9 (MMP-9) zymographic activity was elevated in H9c2 cardiomyoblast cells treated with IGF-II, but not IGF-I Treatment with Leu271GF-II, an IGF2R specifically binding IGF-II analog, resulted in significant time-dependent increases in the MMP-9, tissue-type plasminogen activator (tPA), and urokinase plasminogen activator (uPA); and a reduction in the tissue inhibitor of matrix metalloproteinases-2 (TIMP-2) protein expression. Furthermore, IGF2R expression inhibition by siRNA blocked the IGF-II-induced MMP-9 activity. We hypothesize that after IGF-II is bound with IGF2R, the resulting signal disrupts the balance in the MMP-9/TIMP-2 expression level and increases plasminogen activator (PAS) expression involved in the development of myocardial remodeling. If so, IGF2R signaling inhibition may have potential use in the development of therapies preventing heart fibrosis progression

Aerial dissemination of Clostridium difficile spores

Background: Clostridium difficile-associated diarrhoea (CDAD) is a frequently occurring healthcare-associated infection, which is responsible for significant morbidity and mortality amongst elderly patients in healthcare facilities. Environmental contamination is known to play an important contributory role in the spread of CDAD and it is suspected that contamination might be occurring as a result of aerial dissemination of C. difficile spores. However previous studies have failed to isolate C. difficile from air in hospitals. In an attempt to clarify this issue we undertook a short controlled pilot study in an elderly care ward with the aim of culturing C. difficile from the air. Methods: In a survey undertaken during February (two days) 2006 and March (two days) 2007, air samples were collected using a portable cyclone sampler and surface samples collected using contact plates in a UK hospital. Sampling took place in a six bedded elderly care bay (Study) during February 2006 and in March 2007 both the study bay and a four bedded orthopaedic bay (Control). Particulate material from the air was collected in Ringer's solution, alcohol shocked and plated out in triplicate onto Brazier's CCEY agar without egg yolk, but supplemented with 5 mg/L of lysozyme. After incubation, the identity of isolates was confirmed by standard techniques. Ribotyping and REP-PCR fingerprinting were used to further characterise isolates. Results: On both days in February 2006, C. difficile was cultured from the air with 23 samples yielding the bacterium (mean counts 53 – 426 cfu/m3 of air). One representative isolate from each of these was characterized further. Of the 23 isolates, 22 were ribotype 001 and were indistinguishable on REP-PCR typing. C. difficile was not cultured from the air or surfaces of either hospital bay during the two days in March 2007. Conclusion: This pilot study produced clear evidence of sporadic aerial dissemination of spores of a clone of C. difficile, a finding which may help to explain why CDAD is so persistent within hospitals and difficult to eradicate. Although preliminary, the findings reinforce concerns that current C. difficile control measures may be inadequate and suggest that improved ward ventilation may help to reduce the spread of CDAD in healthcare facilities

Flood impact assessment under climate change scenarios in central Taipei area, Taiwan

Providing effective information regarding flood control for responding climate change is essential to future flood risk management for cities. This study simulated and assessed the impacts of flooding for future climate change scenarios in Taipei city, Taiwan. We modelled rainfall events, generated by general circulation models, with different return periods. The flood extents and damage in the Central Taipei Area for the A1B climate change scenarios were compared to the ones, caused by the rainfall events with same return periods, without climate change (baseline scenario). The proposed approach provides potential flooding maps and flood damage assessment for climate change scenarios as useful information for flood risk management in urban areas.The work is supported by the National Science Council, Taiwan (NSC 99-2915-I-002-120) and the CORFU project, funded by the European Commission through Framework Programme 7, Grant Number 244047

Static behaviour of two-tiered Dou-Gong system reinforced by super-elastic alloy

Dou-Gong system in Asian timber structures play an important role in resisting seismic action. Traditional carpentry in Asia uses timber pegs to connect components which enables relative movement between components, and hence provide friction to dissipate energy in an earthquake. This method however has some short falls such as inadequate stiffness to resist large lateral force and therefore the structures tend to exhibit permanent deformation after the earthquakes. This study proposes a new technique by using super-elastic alloy bars to replace the conventional wooden peg connections to enhance the seismic performance of the structures. Static push-over experiments were conducted on full scaled two-tiered Dou-Gong systems and the high-strength steel and conventional wood pegs as benchmarks. The ultimate stiffness of Dou-Gong system has shown increase by using both high-strength steel and super-elastic alloy bars, but only super-elastic alloy can provide a consistent high damping ratio. This technique also involves pre-strain the super-elastic alloy and the outcomes of this series of experiments have shown that pre-strain in the super-elastic alloy can significantly increase the damping ratio in the structure and hence more energy is dissipated. The results of this paper can be used in the projects of timber structures with Dou-Gong system

Measuring decision quality: psychometric evaluation of a new instrument for breast cancer chemotherapy

Background: Women diagnosed with early stage (I or II) breast cancer face a highly challenging decision – whether or not to undergo adjuvant chemotherapy. We developed a decision quality instrument for chemotherapy for early stage breast cancer and sought to evaluate its performance. Methods: Cross-sectional, mailed survey of recent breast cancer survivors, providers, and healthy controls and a retest survey of survivors. The decision quality instrument includes questions on knowledge and personal goals. It results in a knowledge score and concordance score, which reflects the percentage of patients who received treatments that match their goals. Hypotheses related to acceptability, feasibility, validity, and reliability of the survey instrument were examined. Results: Responses were received from 352 patients, 89 providers and 35 healthy controls. The decision quality instrument was feasible to implement with few missing data. The knowledge scores had good retest reliability (intraclass correlation coefficient (ICC) =0.75). Knowledge scores discriminated between providers and patients (mean difference 31.1%, 95% CI 26.9, 35.3) and between patients and healthy controls (mean difference 11.2, 95% CI 5.4, 17.1). Most providers reported that the knowledge items covered essential content. Two of the five goal items had a ceiling effect, and one goal had low content validity. The goal items had moderate retest reliability (ICC’s 0.57 to 0.78). In the multivariable model of treatment, none of the patient goals was associated with receipt of chemotherapy. Age and hormone receptor status were the only variables independently associated with chemotherapy. Most patients (77.6%) had treatment concordant with that predicted by the model. Patients who had concordant treatment had similar levels of confidence and regret as those who did not. Conclusions: The Decision Quality Instrument is a reliable and valid measure of patient knowledge about chemotherapy, but its ability to measure concordance with patient goals is limited. In this sample, patient goals were not associated with treatment, and most patients reported they were not asked their preference, suggesting that goals were not adequately considered in decision making

Impaired flush response to niacin skin patch among schizophrenia patients and their nonpsychotic relatives: The effect of genetic loading

We previously reported familial aggregation in flush response to niacin skin patch among schizophrenia patients and their nonpsychotic relatives. However, little is known about whether this abnormal skin response is associated with genetic loading for schizophrenia. This study compared the niacin flush response in subjects from families with only one member affected with schizophrenia (simplex families) with those from families having a sib-pair with schizophrenia (multiplex families). Subjects were patients with schizophrenia and their nonpsychotic first-degree relatives from simplex families (176 probands, 260 parents, and 80 siblings) and multiplex families (311 probands, 180 parents, and 52 siblings) as well as 94 healthy controls. Niacin patches of 3 concentrations (0.001M, 0.01M, and 0.1M) were applied to forearm skin, and the flush response was rated at 5, 10, and 15 minutes, respectively, with a 4-point scale. More attenuated flush response to topical niacin was shown in schizophrenia probands and their relatives from multiplex families than in their counterparts from simplex families, and the differentiation was better revealed using 0.1M concentration of niacin than 0.01M or 0.001M. For the highest concentration of 0.1M and the longest time lag of 15 minutes, a subgroup of probands (23%), parents (27%), and siblings (19%) still exhibited nonflush response. Flush response to niacin skin patch is more impaired in schizophrenia patients and their relatives from families with higher genetic loading for schizophrenia, and this finding has implications for future genetic dissection of schizophrenia. © 2008 The Authors.published_or_final_versio

A new potential energy surface for OH(A 2Σ+)–Kr: The van der Waals complex and inelastic scattering

New ab initio studies of the OH(A(2)Σ(+))-Kr system reveal significantly deeper potential energy wells than previously believed, particularly for the linear configuration in which Kr is bound to the oxygen atom side of OH(A(2)Σ(+)). In spite of this difference with previous work, bound state calculations based on a new RCCSD(T) potential energy surface yield an energy level structure in reasonable accord with previous studies. However, the new calculations suggest the need for a reassignment of the vibrational levels of the electronically excited complex. Quantum mechanical and quasi-classical trajectory scattering calculations are also performed on the new potential energy surface. New experimental measurements of rotational inelastic scattering cross sections are reported, obtained using Zeeman quantum beat spectroscopy. The values of the rotational energy transfer cross sections measured experimentally are in good agreement with those derived from the dynamical calculations on the new adiabatic potential energy surface

Compressibility of titanosilicate melts

The effect of composition on the relaxed adiabatic bulk modulus (K0) of a range of alkali- and alkaline earth-titanosilicate [X 2 n/n+ TiSiO5 (X=Li, Na, K, Rb, Cs, Ca, Sr, Ba)] melts has been investigated. The relaxed bulk moduli of these melts have been measured using ultrasonic interferometric methods at frequencies of 3, 5 and 7 MHz in the temperature range of 950 to 1600°C (0.02 Pa s < s < 5 Pa s). The bulk moduli of these melts decrease with increasing cation size from Li to Cs and Ca to Ba, and with increasing temperature. The bulk moduli of the Li-, Na-, Ca- and Ba-bearing metasilicate melts decrease with the addition of both TiO2 and SiO2 whereas those of the K-, Rb- and Cs-bearing melts increase. Linear fits to the bulk modulus versus volume fraction of TiO2 do not converge to a common compressibility of the TiO2 component, indicating that the structural role of TiO2 in these melts is dependent on the identity of the cation. This proposition is supported by a number of other property data for these and related melt compositions including heat capacity and density, as well as structural inferences from X-ray absorption spectroscopy (XANES). The compositional dependence of the compressibility of the TiO2 component in these melts explains the difficulty incurred in previous attempts to incorporate TiO2 in calculation schemes for melt compressibility. The empirical relationship KV-4/3 for isostructural materials has been used to evaluate the compressibility-related structural changes occurring in these melts. The alkali metasilicate and disilicate melts are isostructural, independent of the cation. The addition of Ti to the metasilicate composition (i.e. X2TiSiO5), however, results in a series of melts which are not isostructural. The alkaline-earth metasilicate and disilicate compositions are not isostructural, but the addition of Ti to the metasilicate compositions (i.e. XTiSiO5) would appear, on the basis of modulus-volume systematics, to result in the melts becoming isostructural with respect to compressibility

Cooperative coupling of ultracold atoms and surface plasmons

Cooperative coupling between optical emitters and light fields is one of the outstanding goals in quantum technology. It is both fundamentally interesting for the extraordinary radiation properties of the participating emitters and has many potential applications in photonics. While this goal has been achieved using high-finesse optical cavities, cavity-free approaches that are broadband and easy to build have attracted much attention recently. Here we demonstrate cooperative coupling of ultracold atoms with surface plasmons propagating on a plane gold surface. While the atoms are moving towards the surface they are excited by an external laser pulse. Excited surface plasmons are detected via leakage radiation into the substrate of the gold layer. A maximum Purcell factor of $\eta_\mathrm{P}=4.9$ is reached at an optimum distance of $z=250~\mathrm{nm}$ from the surface. The coupling leads to the observation of a Fano-like resonance in the spectrum.Comment: 9 pages, 4 figure