The presence of trehalose enhances the rate of glucose-6-phosphate hydrolysis in extracts of fat body and other tissues of adult Phormia regina Meigen. The activation appears to be specific, and increasing the concentration of trehalose changes both Vmax and Km for glucose-6-phosphate. There is, however, no easily recognizable phosphotransferase in the extract.


Abstract: In this paper I explore the relationship between insects, technoscience and sustainability culture made possible by recent developments in fabrication, micro-robotics, and design. I define the resulting scenario as "Insect Industry". This emerging agglomerate of practices and technological developments is comprised of practices and applications that promote, exploit and manipulate insects for their sustainable potentials. Among these practices is the flourishing of visionary micro-farming enclosures and experimental food-design, contributing to the urge to produce sustainable sources of food; the re-making of insects in micro-robotics; and the design of GM insects to help fight devastating diseases such as Dengue Fever. Although engaging with distinct fields of research and forms of creative entrepreneurship, these endeavors use very similar strategies and discursive patterns to promote innovation and sustainability, and the promise to fix the world. In illustrating a variety of examples in microrobotics, fabrication, and bioengineering, I ask: is this recent trend really marking the beginning of a new phase in sustainable innovation based on Humans/animals balanced coexistence or it rather constitutes another (maybe more acceptable or more palatable) form of exploitation of the non-human? Is this newly emerging "insect industry" obeying or rather contradicting the imperatives  of economic growth and the principles of technological innovation supported by Western Culture? Keywords: sustainable innovation; interspecies relation; anthropocentrism; biomimicry; solutionism.


By means of the enrichment culture technique, a mixed population of microorganisms was obtained which catalyzed the dispersion of crude oil in supplemented sea water. From this enrichment culture, eight pure cultures were isolated and studied. Only one of the isolates (RAG-1) brought about a significant dispersion of crude oil. RAG-1 has been tentatively characterized as a member of the genus Arthrobacter. The other seven isolates gave rise to colonies on supplemented oil agar, but were neither able to disperse oil nor to stimulate the dispersion catalyzed by RAG-1. The dispersion of crude oil by either RAG-1 or the enrichment culture was absolutely dependent on exogenous sources of nitrogen and phosphorous and completely inhibited by 10−2m azide. The increase in cell number of RAG-1 was directly proportional to the concentration of crude oil added to the medium over the range 0.05 to 1.0 mg/ml. Within this linear region, 1.0 mg of crude oil yielded 9 × 107 cells and approximately 65% of the oil was converted into a nonbenzene extractable form. Accompanying the emulsification was a decrease in the pH from 7.6 to 5.0. Acidic conditions, however, were neither necessary nor sufficient for oil dispersion. When sea water was supplemented with 0.029 mm K2HPO4 and 3.8 mm (NH4)2SO4 and inoculated with RAG-1, oil dispersion occurred within 1 day. This dispersion could also be brought about by the supernatant following separation of the cells from the medium. Similarly, the supernatant obtained following growth of RAG-1 on hexadecane was capable of emulsifying crude oil in 60 min.


Previous in vivo studies have demonstrated that type I receptors in the rat kidney are aldosterone selective, whereas those in the hippocampus do not appear to discriminate between aldosterone and corticosterone. We have injected mature rats with [3H]aldosterone or [3H]corticosterone plus 100-fold excess of RU 28362, with or without unlabeled aldosterone or corticosterone, and compared type I receptor occupancy in two classic mineralocorticoid target tissues (parotid and colon) and in the pituitary. Mature rats were killed 10-180 min after tracer administration; [3H]aldosterone was well taken up and retained in all tissues, whereas [3H]corticosterone was significantly retained only in the pituitary 10 min after tracer administration. To assess a possible role for corticosterone-binding globulin (CBG) in conferring aldosterone specificity on type I receptors, 10-day-old rats (with very low levels of CBG) were similarly injected. In the colon and parotid, [3H]aldosterone binding was at least an order of magnitude higher than that of corticosterone; in the pituitary aldosterone binding was approximately three times that of corticosterone. We interpret these data as evidence that in the parotid and colon type I receptors are aldosterone selective by a non-CBG-requiring mechanism, whereas in the pituitary there appear to be both aldosterone-selective and nonselective type I sites.


Turner Syndrome (TS) is a sex-chromosome disorder occurring in approximately 1 in
2,500 female births. The main features are short stature and dysfunctional gonads,
resulting in a lack of sex hormones, delayed puberty and infertility. Physical
characteristics associated with TS include webbed neck and pigmented moles.
Women with TS have a high risk of developing chronic ill health and require ongoing
medical monitoring. This qualitative study aims to develop an understanding of the
psychosocial impact of living with TS during adulthood, with particular reference to
chronic ill health, body-image and infertility. Ten women were interviewed and data
were analysed using Interpretative Phenomenological Analysis. Two superordinate
themes were developed: 'Living with an Evolving Condition' and 'Oscillating
between a Positive and Negative Identity'. The meaning of TS changed for
participants depending on their life stage and they described living with uncertainty
and difficulty in differentiating themselves from the manifestations of TS. Various
consequences of TS impacted upon participants' struggles to establish a coherent and
positive identity, including dissatisfaction with their appearance, receiving differential
treatment and their medical care. Infertility was a particularly important aspect of
participants' experiences of TS across the life stage and challenged their
establishment of a positive identity. A limited version of Foucauldian Discourse
Analysis was adopted to understand the influence of the socio-cultural (pronatalist)
context on being infertile and provided a 'material-discursive' approach to the
experience of infertility. Participants' struggles to maintain a positive identity were
related to a lack of available, positive discursive resources to define themselves as
(infertile) women. The participants also constructed their infertility as a 'dis-ability'
and a 'reproductive impairment', placing them in positions of deficit and dysfunction.
Potential clinical implications are discussed.


This ethically approved, novel study emphasizes an important aspect of Information and communication flow (ICF) that underpins the transport systems' activities under disasters (e.g. search, rescue, relief operations and emergency related travel activities). Multi perspectives of ICF, based on numerous ICT and ITS technologies, are investigated in detail by employing various analysis techniques and methods.
Two scenarios were developed for three case studies from developed and developing countries (one in UK and two in Pakistan). The effectiveness and choice making process regarding use of ITS technologies by the transport-disaster managers (scenario1) and people affected (scenario 2) were investigated for three phases (pre, during, post) of two different disasters (floods and earthquakes). Participants for both scenarios were recruited and data collected and analysed using different data collection and analysis methods.
The study contributes a new data collection and analysis technique named as the Q-Likert methodology, which was developed and used to identify those factors (relating to ITS deployment plans, policies, ICF within and among other authorities and availability of resources, expertise and liberty to practice) that limit the scope of ITS technologies during disasters. An evaluation of the effectiveness of each ITS technology under both scenarios and for three phases of disasters is reported. A range of variables (e.g. personal characteristics of people, prevailing situations and facilities) and their influence on the use of ITS technologies was tested. Many aspects relating to transport-disaster affected communities are revealed. The results are fused and validated through data fusion technique to get maximum information regarding the multidimensional issues of transport-disasters ICF.
Based on the evidence found, an integrated framework is proposed covering ITS technologies, transport and disasters systems. The framework focuses on the provision of an un-interrupted ICF along with cooperation, coordination and exchange of information and resources between all stakeholders.


To attain agricultural sustainability, use of soil resources and tillage requires equal consideration for chemical and physical components of soil fertility. We assessed responses of selected soil physical and chemical properties to tillage and soil fertility amending resources. The study was carried out in Meru South and Kandara sub-counties located in the Central Highlands of Kenya for four cropping seasons. The experimental design was split-plot with tillage as the main factor conventional (D15) and minimum (D0) tillage and soil fertility resources (SFR) as sub-factors mineral fertilizer (F), crop residues + fertilizer (RF), residues + fertilizer + animal manure (RFM), residues + Tithonia diversifolia + manure (RTiM), residues + Tithonia diversifolia + phosphate rock (Minjingu) (RTiP), residues + manure + legume intercrop (RML) and control (no input). Compared with control, aggregate stability was significantly higher on average under SFRs with sole organics by 19% in Meru South. Total N and available P were higher under integration of fertilizer and organics in both sites. Calcium increased under sole organic or integration with fertilizer in Meru South and under sole organics in Kandara. Magnesium significantly increased under all SFRs compared with control in Kandara. Soil organic carbon significantly (P=0.02) increased under D0 by 6% compared to D15 in 0-5 cm depth in Kandara. Application of RTiM had the highest SOC in all depths' at Meru South. SOC significantly increased under RTiP and RML by 11% in 0-5 cm depth and under RML by 13% in 5-10 cm depth at Kandara. Mineral-N (NO3–-N and NH4+-N) was higher under D0 at planting compared with D15 in Meru South. In Kandara, NO3–-N and NH4+-N were significantly higher by 17% and 30%, respectively under D0 compared with D15 at planting during SR16 season. Higher mineral N was recorded under F application on the 30th and 45th days in both sites. The highest mineral-N content was on the 45th day after planting during SR16 season and on the 30th day during LR17 season at Meru South. In Kandara, NO3–-N and NH4+-N were highest on the 45th day and 30th day, respectively, during SR16 season. During LR17 season, mineral-N was highest on the 30th day in Kandara. The study highlights that minimal soil disturbance and organic inputs use or integration with fertilizers are feasible alternatives for improving soil fertility in the Nitisols of Central Highlands of Kenya.


Previous classifications dealing with the cytogenesis of neuroglia have formed a working basis for the study of the neoplasms of the glioma group. With the ever increasing interest in the field of neuro-pathology, largely owing to the advent of metallic staining methods, it will be necessary to modify these classifications from time to time in order to clarify the relationship between the embryonic and the pathologic cell types. In the evolution of primitive spongioblasts to adult autonomous neuroglia can be distinguished cell types comparable to those constituting the various neoplasms arising from these cells. A review of the literature on the phylogenetic development of neuroglia, in association with an ontogenetic study of their evolution in mammals, has suggested a possible simplification of the existing classifications. The term neuroglia, as now used, applies first to the so-called classic neuroglia; this term includes the fibrous and protoplasmic astrocytes which differ only in


Since at least 1989, courts and commentators have debated whether 28 U.S.C. § 1782, which allows parties to a proceeding before a "foreign or international tribunal" to request assistance from U.S. district courts in obtaining evidence, is available in a private arbitration. The main disputed questions have been (a) whether assistance for private arbitration is contemplated by the term "foreign or international tribunal" and § 1782's legislative history; and (b) whether § 1782 helps or hinders international arbitration in light of (i) the possibility that parties will apply for assistance without the arbitrators' approval and (ii) the differences between disclosure in U.S. courts and in international arbitration. These issues are now before the United States Court of Appeals for the first time since the Supreme Court's 2004 decision that sparked the latest round of the debate, Intel Corp. v. Advanced Micro Devices, Inc. This article attempts to contribute to a resolution of the controversy by arguing as follows: Judicial assistance in obtaining evidence is needed in order for international arbitration to be effective. Section 1782, as applied by some courts, offers the necessary assistance, but also threatens to disrupt arbitral proceedings by allowing parties to request assistance without the arbitrators' approval. Also, the unresolved questions about § 1782's applicability to private arbitration create a risk that if arbitrators prevent assistance under § 1782, enforcement of the arbitral award will be refused on the ground that the party that requested disclosure in the United States was denied the right to present its case in the arbitration. Therefore, the question of § 1782's applicability to private arbitration needs to be resolved. (Section II) The language and legislative history of § 1782 suggest that it was not intended to be used for private arbitration. (Section III.A) The absence of such intent is


High rate of anemia and stress is reported in medical students. Experimental studies in animals have indicated
that psychological stress may lead to iron deficiency anemia. Therefore we investigated the association between
perceived stress and hemoglobin concentration in medical students. 84 medical students aged between 19-21
years were studied. The main parameters measured were hemoglobin concentration, perceived stress and diet.
The perceived stress was measured using Cohen's perceived stress scale. Diet was estimated by a dietician's
questionnaire. Hemoglobin was measured by digital hemoglobin meter using capillary blood. In male subjects,
hemoglobin concentration below 13.5 gm% and in female subjects below 11.5 gm% was taken as low (group A)
and the rest were considered as with normal hemoglobin (group B). Data analysis included unpaired t test,
Mann- Whitney U test and Chi-square test. Level of significance was taken at p value less than 0.05.
Hemoglobin concentration was negatively correlating with perceived stress score and positively correlating with
diet score (r = - 0. 26, p = 0.015; r = 0.25, p = 0.018 respectively). Mean perceived stress score of group A was
higher compared to group B (Mann-Whitney U-statistic = 614.00, p = 0.0376). Frequency of subjects with high
perceived stress score in group A was higher compared to group B (Chi-square = 8.0188, p = 0.00463). The
diet score did not differ significantly between group A and group B. High perceived stress may contribute to
development of iron deficiency anemia in undergraduate medical students.


A spectrum of disease severity has been observed in patients with Lyme disease, with approximately 60% of untreated individuals developing arthritis. The murine model of Lyme disease has provided strong evidence that the genetic composition of the host influences the severity of arthritis following infection with Borrelia burgdorferi: infected C3H mice develop severe arthritis while infected C57BL/6N mice develop mild arthritis. Regions of the mouse genome controlling arthritis severity and humoral responses during B. burgdorferi infection were identified in the F2 intercross generation of C3H/HeNCr and C57BL/6NCr mice. Rear ankle swelling measurements identified quantitative trait loci (QTL) on chromosomes 4 and 5, while histopathological scoring identified QTL on a unique region of chromosome 5 and on chromosome 11. The identification of QTL unique for ankle swelling or histopathological severity suggests that processes under distinct genetic control are responsible for these two manifestations of Lyme arthritis. Additional QTL that control the levels of circulating Igs induced by B. burgdorferi infection were identified on chromosomes 6, 9, 11, 12, and 17. Interestingly, the magnitude of the humoral response was not correlated with the severity of arthritis in infected F2 mice. This work defines several genetic loci that regulate either the severity of arthritis or the magnitude of humoral responses to B. burgdorferi infection in mice, with implications toward understanding the host-pathogen interactions involved in disease development.


Women with preeclampsia produce AT1-AA (agonistic autoantibodies to the angiotensin II type 1 receptor), which stimulate reactive oxygen species, inflammatory factors, and hypertensive mechanisms (ET [endothelin] and sFlt-1 [soluble fms-like tyrosine kinase-1]) in rodent models of preeclampsia. The placental ischemic reduced uterine perfusion pressure (RUPP) rat model of preeclampsia exhibits many of these features. In this study, we examined the maternal outcomes of AT1-AA inhibition (‵n7AAc′) in RUPP rats. Blood pressure was higher in RUPP rats versus normal pregnant (NP) rats (123±2 versus 99±2 mm Hg, P<0.05), which was reduced in RUPP+‵n7AAc′ (105±3 versus 123±2 mm Hg, P<0.05 versus RUPP). Uterine artery resistant index was increased in RUPP versus NP rats (0.71±0.02 versus 0.49±0.02, P<0.05) and normalized in RUPP+‵n7AAc′ rats (0.55±0.03). Antiangiogenic factor sFlt-1 was elevated in RUPP versus NP rats (176±37 versus 77±15 pg/mL, P<0.05) but normalized in RUPP+‵n7AAc′ (86±9, P=0.05 versus RUPP). Plasma nitrate and nitrite were decreased (14±1 versus 20±1 µMNO3, P<0.05) and isoprostanes were elevated (20 117±6304 versus 2809±1375 pg/mL, P<0.05) in RUPP versus NP rats; and normalized in RUPP+‵n7AAc′ rats; (18±2 µMNO3; 4311±1 pg/mL). PPET-1 (preproendothelin-1) expression increased 4-fold in RUPP versus NP rats which were prevented with ‵n7AAc′. Importantly, placental cytolytic natural killer cells were elevated in RUPP versus NP rats (8±2% versus 2±2% gated, P<0.05), which was prevented in RUPP+‵n7AAc′ total (3±1% gated, P<0.05) In conclusion, AT1-AA inhibition prevents the rise in maternal blood pressure and several pathophysiological factors associated with preeclampsia in RUPP rats and could be a potential therapy for preeclampsia.


Aim: To determine the experience of people with COPD to Tai Chi. Methods: Participants, who finished 12 week short-form Sun-style Tai Chi (SSTC) training program, completed a survey of eight questions. Each question was answered by putting a stroke on a 10 cm Visual Analogue Scale with anchors at either end, ranging from the negative of the question on the left to the positive of the question on the right. The number of supervised training sessions attended and the number of days unsupervised home training practised was reported. Results: Twenty-three participants completed the survey, mean (SD) age 74 (8) years, mean FEV1% predicted 59 (17)%. Participants attended 21 (2) supervised training sessions out of a possible 24 sessions and performed 4 (1) days per week of unsupervised home training. The Table below indicates the results of four survey questions. Conclusion: Participants reported that SSTC was a highly enjoyable exercise which they perceived improved their physical fitness, balance and shortness of breath. Compliance with supervised and unsupervised training was high. Importantly, participants indicated that they would continue Tai Chi as their regular exercise regimen.

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PURPOSE: Patients with unstable angina or non-ST-segment elevation myocardial infarction (MI) may be managed with either an "invasive" or "conservative" strategy. It is unclear which of these strategies is superior. METHODS: We identified studies with MEDLINE and EMBASE searches (1966–September 2003) and by reviewing reference lists. Studies were included if they were randomized controlled trials comparing management strategies for patients in the early post-unstable angina/non-ST-segment elevation MI period and had follow-up data for at least 3 months. RESULTS: Seven trials that randomized a total of 9212 patients were included. The pooled odds ratio (OR) for all-cause mortality was 0.96 (95% confidence interval [CI]: 0.72 to 1.27). The occurrence of fatal or nonfatal re-infarction was reduced with an invasive strategy (OR 0.73; 95% CI: 0.61 to 0.88) as was readmission to hospital (OR 0.67; 95% CI: 0.48 to 0.94). The endpoints of nonfatal MI and the composite of death or nonfatal MI showed nonsignificant trends favoring an invasive strategy. Trials that included a higher proportion of patients with ST-segment depression on admission and trials in which a larger proportion of patients underwent revascularization showed a greater magnitude of benefit for an invasive strategy. CONCLUSION: For patients with unstable angina/non-ST-segment elevation MI, an invasive strategy reduces rates of fatal or nonfatal re-infarction and hospital readmission, but not all-cause mortality, when compared with a noninvasive strategy. These results suggest that an invasive management strategy should be considered for all patients with unstable angina/non-ST-segment elevation MI and perhaps in particular those with ST-segment depression. © 2005 Elsevier Inc. All rights reserved.


Water-deficit stress is a major environmental factor that limits agricultural productivity worldwide. Recent episodes of extreme drought have severely affected cotton production in the Southwestern USA. There is a pressing need to develop cotton varieties with improved tolerance to water-deficit stress for sustainable production in water-limited regions. One approach to engineer drought tolerance is by delaying drought-induced senescence via up-regulation of cytokinin biosynthesis. The isopentenyltransferase gene (IPT) that encodes a rate limiting enzyme in cytokinin biosynthesis, under the control of a water-deficit responsive and maturation specific promoter PSARK was introduced into cotton and the performance of the PSARK::IPT transgenic cotton plants was analyzed in the greenhouse and growth chamber conditions. The data indicate that PSARK::IPT-transgenic cotton plants displayed delayed senescence under water deficit conditions in the greenhouse. These plants produced more root and shoot biomass, dropped fewer flowers, maintained higher chlorophyll content, and higher photosynthetic rates under reduced irrigation conditions in comparison to wild-type and segregated non-transgenic lines. Furthermore, PSARK::IPT-transgenic cotton plants grown in growth chamber condition also displayed greater drought tolerance. These results indicate that water-deficit induced expression of an isopentenyltransferase gene in cotton could significantly improve drought tolerance.


With the aim of characterizing the functional and pharmacological properties of the different voltage-dependent Ca2+ channels expressed in a given type of CNS neuron, we obtained single Ca2+ channel recordings from rat cerebellar granule cells in primary culture. Our data show that three novel classes of voltage-dependent Ca2+ channels are coexpressed in cerebellar granule cells. They are pharmacologically distinct from dihydropyridine-sensitive L-type and omega-conotoxin- sensitive N-type channels, and their functional properties are different from those of P- and T-type channels. The three novel 21 pS G1-, 15 pS G2-, and 20 pS G3-type Ca2+ channels have similar inactivation properties. They show complete steady-state inactivation at -40 mV and their single-channel average currents have both sustained and decaying components. They differ in activation threshold (-40 mV for G2, -30 mV for G3, and -10 mV for G1, with 90 mM Ba2+ as charge carrier), mean open time (1.2 msec for G2, 1 msec for G3, 0.8 msec for G1), and single-channel currents (at 0 mV: 0.5 pA for G2, 0.8 pA for G3, and 1.4 pA for G1). Together with the previously characterized multiple L-type Ca2+ channels (Forti and Pietrobon, 1993), G1-, G2-, and G3-type channels constitute the large majority of Ca2+ channels of cerebellar granule cells in culture. The low activation threshold of G2- type channels and their inactivation properties suggest that they might be native counterparts of the recently expressed rat brain clone rbE-II (Soong et al., 1993).


Neurotrophic factors and their signaling pathways have been implicated in the neurobiological adaptations in response to stress and the regulation of mood-related behaviors. A candidate signaling molecule implicated in mediating these cellular responses is the extracellular signal-regulated kinase (ERK1/2), although its functional role in mood regulation remains to be fully elucidated. Here we show that acute (1 d) or chronic (4 weeks) exposure to unpredictable stress increases phosphorylation of ERK1/2 and of two downstream targets (ribosomal S6 kinase and mitogen- and stress-activated protein kinase 1) within the ventral tegmental area (VTA), an important substrate for motivated behavior and mood regulation. Using herpes simplex virus-mediated gene transfer to assess the functional significance of this ERK induction, we show that overexpressing ERK2 within the VTA increases susceptibility to stress as measured in the forced swim test, responses to unconditioned nociceptive stimuli, and elevated plus maze in Sprague Dawley male rats, and in the tail suspension test and chronic social defeat stress procedure in C57BL/6 male mice. In contrast, blocking ERK2 activity in the VTA produces stress-resistant behavioral responses in these same assays and also blocks a chronic stress-induced reduction in sucrose preference. The effects induced by ERK2 blockade were accompanied by decreases in the firing frequency of VTA dopamine neurons, an important electrophysiological hallmark of resilient-like behavior. Together, these results strongly implicate a role for ERK2 signaling in the VTA as a key modulator of responsiveness to stress and mood-related behaviors.


Aim The aim of this study was to describe district nurses' (DNs') experiences of their knowledge development in wound management when treating patients with different types of wounds at healthcare centers. Background In primary healthcare, DNs are mainly responsible for wound management. Previous research has focused on DNs' level of expertise regarding wound management, mostly based on quantitative studies. An unanswered question concerns DNs' knowledge development in wound management. The present study therefore intends to broaden understanding and to provide deeper knowledge in regard to the DNs' experiences of their knowledge development when treating patients with wounds. Methods A qualitative descriptive design was used. Subjects were a purposeful sample of 16 DNs from eight healthcare centers in a metropolitan area in Stockholm, Sweden. The study was conducted with qualitative interviews and qualitative content analysis was used to analyze the data. Results The content analysis resulted in three categories and 11 sub-categories. The first category, 'ongoing learning by experience,' was based on experiences of learning alongside clinical practice. The second category 'searching for information,' consisted of various channels for obtaining information. The third category, 'lacking organizational support,' consisted of experiences related to the DNs' work organization, which hindered their development in wound care knowledge. Conclusions The DNs experienced that they were in a constant state of learning and obtained their wound care knowledge to a great extent through practical work, from their colleagues as well as from various companies. A lack of organizational structures and support from staff management made it difficult for DNs to develop their knowledge and skills in wound management, which can lead to inadequate wound management.


Background: Although the use of contraceptive hormones is a risk factor for development of breast cancer, level of risk is unknown; thus the current research was conducted to investigate the effect of factors related to fertility and hormone use on risk of breast cancer in women aged under 50 years old in the west of Iran. Methods: In this case-control study, all incidence cases of breast cancer aged between 25 – 49 years old (n=212) were selected. Twice as many as the case group, the individuals referred to other outpatient sections of the same hospital at the time of study and up to 2 years after the follow-up not diagnosed with breast or other cancers were selected as a control group. The data were collected using healthy fertility program and middle-aged periodical care forms developed by Iran ' s Ministry of Health (MOH). Results: After controlling for confounding variables, history of hormonal use for contraception (OR=2.02, 95% CI=1.2 – 3.3) and hormone therapies (OR=1.9, 95% CI=1.2 – 3.04) were identi fi ed as factors increasing the risk of breast cancer. Dose-response relationships between breast cancer and the use of hormones for contraception and hormone therapy indicated that these factors increased the risk of breast cancer. The risk was found to be higher in women who had been under hormone therapy for more than 120 months. With an increase in the age of the fi rst menstruation, risk of breast cancer increased linearly, but with an increase in the age of the fi rst pregnancy, risk of breast cancer increased exponen-tially. After 20 years of age, the risk increased with a steeper slope. Conclusion: Considering the effect of hormone therapy and fertility factors on breast cancer and changeability of listed risk factors, the researchers suggest planning for sensitizing, increasing the awareness, and educating women and professionals regarding the in fl uence of fertility and hormonal factors including pregnancy at lower ages, minimizing the use of hormones for contraception, and hormone therapy.


It is well known that heterogeneities in carbonate reservoirs impact fluid flow during production. However, few studies have examined the impact of the same heterogeneities on flow behaviour with different fluid properties and production scenarios. We use integrated flow simulation and experimental design techniques to investigate the relative, first-order impact of stratigraphic and sedimentological heterogeneities on simulated recovery in carbonate ramp reservoirs. Two production strategies are compared, which promote dominance of either horizontal or vertical flow. We find that the modelled geology is more important than the simulated fluid properties and production scenarios over the ranges tested. Of the heterogeneities modelled here, rock properties and stratigraphic heterogeneities that control reservoir architecture and the spatial distribution of environment of deposition (EOD) belts are important controls on recovery regardless of the production strategy. The presence of cemented hardground surfaces becomes the key control on oil recovery in displacements dominated by vertical flow. Permeability anisotropy is of low importance for all production strategies. The impacts of stratigraphic heterogeneities on recovery factor and water breakthrough are more strongly influenced by fluid properties and well spacing in displacements dominated by vertical flow. These results help to streamline the reservoir modelling process, by identifying key heterogeneities, and to optimize production strategies. 2013-014research-articlethematic set: [Fundamental controls on Flow in carbonates]XXX10.1144/petgeo2013-014P. J. R. FitchInteraction of carbonate heterogeneities with flow 2014 at Imperial College London on February 24, 2014 http://pg.lyellcollection.org/ Downloaded from


Heavy Haul trains are a very efficient way to transport bulk material over land. One way to increase network capacity and reduce operating costs is to use longer and heavier trains. Worldwide, railway operators are increasing the length and weight of heavy haul trains. However, longer trains tend to exhibit larger steady state and dynamic longitudinal coupler forces. Large coupler forces can increase the probability of derailments, and cause increased wear and damage to coupling components. Driving strategies need to be determined to ensure that the train is operated efficiently, safely, without excessive wear and in a timely manner. Improved driving strategies can be created by using experienced drivers, field tests and simulator trials. Recently some computer based optimisations methods have been developed to also improve driving strategies. Computer based optimisation methods have the advantage that they can be used to more easily assess the effect of changing train configurations, track topography or speed restrictions. Current computer based optimisations are good at optimising energy and time but there is a lack of optimisation methods that also consider longitudinal train forces. Research conducted at the Centre for Railway Engineering is investigating the use of computational techniques such as genetic algorithms to determine driving strategies of long trains. This paper presents a review of current optimisation methods and the progress in using genetic algorithms.


Objective Trichomonas vaginalis (TV) is common in HIV+ women, and host factors may play a role in TV treatment outcomes. The purpose of this study was to examine the influence of bacterial vaginosis (BV) on the response to TV treatment among HIV+ women. Methods A secondary analysis was conducted of a clinical trial which randomised HIV+/TV+ women to metronidazole (MTZ) treatment: 2 g (single-dose) versus 7 day 500 mg twice daily (multidose). BV was classified using Nugent scores from baseline Gram stains. Women were recultured for TV at test-of-cure (TOC) and again at 3 months if TV-negative at TOC. Repeat TV infection rates were compared for women with a baseline TV/BV coinfection versus baseline TV infection only, and stratified by treatment arm. Results Among 244 HIV+/TV+ women (mean age=40.3, ±9.5; 92.2% African–American), the rate of BV was 66.8%. Women with BV were more likely to report douching and ≥1 recent sex partners. HIV+ women with baseline TV/BV coinfection were more likely to be TV-positive at TOC than women with baseline TV infection only (RR 2.42 (95% CI 0.96 to 6.07; p=0.05)). When stratified by treatment arm, the association was only found in the single-dose arm (p=0.02) and not in the multidose arm (p=0.92). This interaction did not persist at 3 months. Conclusions For HIV+/TV+ women, the rate of BV was high, and BV was associated with early failure of the MTZ single-dose treatment for TV. Biological explanations require further investigation.


We have developed a FRET-based assay for the fingers-closing conformational transition that occurs when a binary complex of DNA polymerase I (Klenow fragment) with a primer-template binds a complementary dNTP and have used this and other fluorescence assays to place the fingers-closing step within the reaction pathway. Because the rate of fingers-closing was substantially faster than the rate of nucleotide incorporation measured in chemical quench experiments, fingers-closing cannot be the rate-limiting prechemistry step defined by earlier kinetic studies. Experiments using Ca (2+) instead of Mg (2+) as the metal cofactor suggest instead that the prechemistry step may involve a change in metal ion occupancy at the polymerase active site. The use of ribonucleotide substrates shows there is a base discriminating step that precedes fingers-closing. This earlier step, detected by 2-AP fluorescence, is promoted by complementary nucleotides (ribo- as well as deoxyribo-) but is blocked by mismatches. The complementary rNTP blocks the subsequent fingers-closing step. Thus, discrimination against rNTPs occurs during the transition from open to closed conformations, whereas selection against mismatched bases is initiated earlier in the pathway, in the open complex. Mismatched dNTPs accelerate DNA release from the polymerase, suggesting the existence of an early intermediate in which DNA binding is destabilized relative to the binary complex; this could correspond to a conformation that allows an incoming dNTP to preview the template base. The early kinetic checkpoints identified by this study provide an efficient mechanism for the rejection of mismatched bases and ribose sugars and thus enhance polymerase throughput.


Aim: This study was aimed to investigate the immunomodulatory activity of water soluble polysaccharides isolated from Metroxylon sagu (PSMS) by dilute acid extraction, ethanol precipitation in rats by using three different in-vivo experimental models of immunosuppression. Methodology: Three models of immunosuppression include metronidazole (MTZ) induced immunosuppression, pyrogallol induced immunosuppression and Ethanol-induced immunosuppression. Immunological indices like humoral antibody titer values, cellular immune response, percent change in phagocytosis, serum immunoglobulins were estimated. Histopathology of spleen was done in all control and treated groups. The doses of 500 and 250 mg/kg of PSMS were administered orally to evaluate the immunomodulatory activity. Results: Though PSMS was demonstrated to have immunostimulatory activity in almost all three models of immunosuppression, PSMS was found to be more effi cacious against ethanol-induced immunosuppression when compared with pyrogallol induced immunosuppression and MTZ induced immunosuppression. However, dose-dependent improvement in immunological indices was evident in all three models. Conclusion: In summary, water soluble polysaccharides isolated from M. sagu stimulate the immunity in the animal models of immunosuppression.


Dijkstra's algorithm for the Single-Source Shortest Path (SSSP) problem is notoriously hard to parallelize in $o(n)$ depth, $n$ being the number of vertices in the input graph, without increasing the required parallel work unreasonably. Crauser et al.\ (1998) presented observations that allow to identify more than a single vertex at a time as correct and correspondingly more edges to be relaxed simultaneously. Their algorithm runs in parallel phases, and for certain random graphs they showed that the number of phases is $O(n^{1/3})$ with high probability. A work-efficient CRCW PRAM with this depth was given, but no implementation on a real, parallel system.
In this paper we strengthen the criteria of Crauser et al., and discuss tradeoffs between work and number of phases in their implementation. We present simulation results with a range of common input graphs for the depth that an ideal parallel algorithm that can apply the criteria at no cost and parallelize relaxations without conflicts can achieve. These results show that the number of phases is indeed a small root of $n$, but still off from the shortest path length lower bound that can also be computed.
We give a shared-memory parallel implementation of the most work-efficient version of a Dijkstra's algorithm running in parallel phases, which we compare to an own implementation of the well-known $\Delta$-stepping algorithm. We can show that the work-efficient SSSP algorithm applying the criteria of Crauser et al. is competitive to and often better than $\Delta$-stepping on our chosen input graphs. Despite not providing an $o(n)$ guarantee on the number of required phases, criteria allowing concurrent relaxation of many correct vertices may be a viable approach to practically fast, parallel SSSP implementations.


An artificial climate room plays an important role in the research of an apparatus test and indoor/outdoor environment simulation. Generally, the refrigerator is used to decrease temperature to simulate outdoor environment, while a heater is used to increase the temperature to simulate the indoor environment. It would result in large waste if the temperature control method of artificial climate room is unreasonable. It causes energy waste because it takes too much time for control process stability, which is caused by the characteristics of controlled objects such as lagging, inertia and uncertainty. Thus it is necessary to design more reasonable control methods for energy conservation. The cooling capacity for simulating outdoor temperature varies widely, so multiform controlling means is adopted, such as frequency control for the refrigerator, on/off control and auxiliary heater. While the thermal chamber which is used for simulating indoor temperature is on a long-time delay, large inertia (forced disturb is not allowed), and a new type of immune controller is designed by learning from the functions of self-adjustment, antigen memory and immunity response in biology immunity systems. By the control method, it gets a smaller overshoot and a quicker response speed in the practical process of temperature control of an artificial climate room; thus it is considered to be an optimum energy conservation method. The control method can be widely popularized


Objectives
We aimed to estimate the potential effects, costs, and cost-effectiveness of a programmatic transition from distribution of iron-folic acid (IFA) tablets to distribution of multiple micronutrient supplements (MMS) to pregnant woman, using Bangladesh and Burkina Faso as case studies.

Methods
For each country, we developed an 11-year predictive model using baseline demographic information from the Lives Saved Tool and effect sizes from a recent meta-analysis of trials of MMS compared to IFA supplementation during pregnancy. We predicted the number of cases of stillbirth, infant mortality, and adverse birth outcomes (low birth weight, small-for-gestational age, and preterm birth) and DALYs averted by replacing IFA with MMS at current levels of IFA coverage (∼50% nationally in Bangladesh; ∼10% in Burkina Faso). We estimated initial program transition costs and the annual marginal cost of MMS compared to IFA supplements, and calculated cost-effectiveness measures for scenarios with varied numbers of tablets received and consumed by pregnant women.

Results
In Bangladesh, immediate replacement of IFA with MMS at current coverage (assuming all covered pregnancies receive 180 tablets) was predicted to avert >73,800 deaths and >178,500 cases of preterm birth over 11 years at a cost of $5.0 to $14.2 per DALY averted; costs would increase by ∼9% with the addition of programmatic transition costs. In Burkina Faso, the same scenario would avert >5700 deaths and >6600 cases of preterm birth over 11 years at a cost of $3.6 to $15.5 per DALY averted. Assuming that benefits of supplementation accrue only above a given threshold (e.g., 180 tablets per pregnancy), accounting for supplement consumption above or below this threshold (e.g., consumption of 30 tablets or 270 tablets) could substantially reduce the cost-effectiveness of the IFA-MMS switch in comparison with a scenario in which all covered pregnancies consume exactly 180 tablets, although cost per DALY averted remained below $105 in all scenarios.

Conclusions
This modeling analysis suggests that the cost per DALY averted by transitioning from IFA to MMS is low relative to other prenatal interventions designed to save lives. Improvements in program delivery and supplement adherence would improve the cost-effectiveness of replacing IFA with MMS.

Funding Sources
Sight and Life; Sackler Institute for Nutrition Science.


Prefetching is a widely used technique in modern data storage systems. We study the most widely used class of prefetching algorithms known as sequential prefetching. There are two problems that plague the state-of-the-art sequential prefetching algorithms: (i) cache pollution, which occurs when prefetched data replaces more useful prefetched or demand-paged data, and (ii) prefetch wastage, which happens when prefetched data is evicted from the cache before it can be used.

A sequential prefetching algorithm can have a fixed or adaptive degree of prefetch and can be either synchronous (when it can prefetch only on a miss), or asynchronous (when it can also prefetch on a hit). To capture these distinctions we define four classes of prefetching algorithms: Fixed Synchronous (FS), Fixed Asynchronous (FA), Adaptive Synchronous (AS), and Adaptive Asynchronous (AA). We find that the relatively unexplored class of AA algorithms is in fact the most promising for sequential prefetching. We provide a first formal analysis of the criteria necessary for optimal throughput when using an AA algorithm in a cache shared by multiple steady sequential streams. We then provide a simple implementation called AMP, which adapts accordingly leading to near optimal performance for any kind of sequential workload and cache size.

Our experimental set-up consisted of an IBM xSeries 345 dual processor server running Linux using five SCSI disks. We observe that AMP convincingly outperforms all the contending members of the FA, FS, and AS classes for any number of streams, and over all cache sizes. As anecdotal evidence, in an experiment with 100 concurrent sequential streams and varying cache sizes, AMP beats the FA, FS, and AS algorithms by 29-172%, 12-24%, and 21-210% respectively while outperforming OBL by a factor of 8. Even for complex workloads like SPC1-Read, AMP is consistently the best performing algorithm. For the SPC2 Video-on-Demand workload, AMP can sustain at least 25% more streams than the next best algorithm. Finally, for a workload consisting of short sequences, where optimality is more elusive, AMP is able to outperform all the other contenders in overall performance.


The rise in antibiotic resistance in bacteria has spawned new technological approaches for identifying novel antimicrobials with narrow specificity. Current antibiotic treatment regimens and antituberculosis drugs are not effective in treating Mycobacterium abscessus. Meanwhile, antimicrobial peptides are gaining prominence as alternative antimicrobials due to their specificity toward anionic bacterial membranes, rapid action, and limited development of resistance. To rapidly identify antimicrobial peptide candidates, our group has developed a high-density peptide microarray consisting of 125,000 random synthetic peptides screened for interaction with the mycobacterial cell surface of M. abscessus morphotypes. From the array screening, peptides positive for interaction were synthesized and their antimicrobial activity was validated. Overall, six peptides inhibited the M. abscessus smooth morphotype (IC50 = 1.7 μM for all peptides) and had reduced activity against the M. abscessus rough morphotype (IC50 range: 13–82 μM). Peptides ASU2056 and ASU2060 had minimum inhibitory concentration values of 32 and 8 μM, respectively, against the M. abscessus smooth morphotype. Additionally, ASU2060 (8 μM) was active against Escherichia coli, including multidrug-resistant E. coli clinical isolates, Pseudomonas aeruginosa, and methicillin-resistant Staphylococcus aureus. ASU2056 and ASU2060 exhibited no significant hemolytic activity at biologically relevant concentrations, further supporting these peptides as promising therapeutic candidates. Moreover, ASU2060 retained antibacterial activity after preincubation in human serum for 24 h. With antimicrobial resistance on the rise, methods such as those presented here will streamline the peptide discovery process for targeted antimicrobial peptides.


Significant amounts of sugar were found in 22% of 180 faecal samples from 135 children with acute or chronic diarrhoea. The methods used were the Clinitest method and paper chromatography. There was very good correlation between the results of these methods. Screening by Ph was less reliable. Various di- and monosaccharides were found. However, a disaccharide was never found without the simultaneous finding of its component monosaccharides. In vitro studies showed that the faecal flora has the ability to split disaccharides very rapidly. Within a few minutes much of the disaccharide had been split and no traces could be found after 30 minutes. Since the same process is assumed to take place in the lower gut, children with disacchardase deficency cannot be expected to excrete disaccharide alone in their faeces without the corresponding monosaccharides. The lack of a disaccharide in the faeces does not exclude the possibility of disaccharidase deficiency. Acid hydrolysis of faecal samples in cases of suspected sucrase deficiency seems not to be necessary.


In this thesis, we discuss quantum phase transitions in low-dimensional optical lattices, namely one- and two-dimensional lattices. The dimensional confinement is realized in experiments by suppressing the hopping in the extra dimensions through a deep potential barrier that prevents the atoms to tunnel across dimensions. The dimensionality considerably affects the physical behavior of the system. For instance, in one dimension, the celebrated Fermi-liquid theory does not describe the many-body behavior of a fermionic system. There are no single particle excitations, but instead collective behavior, and spin and charge degrees of freedom are decoupled . In the first part of this thesis, we consider one-dimensional fermionic gases under the effect of time-dependent driving forces. First, we describe a proposal to realize non-standard Hubbard models that display correlated-hopping terms by modulating interactions through a time-dependent magnetic field. The extra terms describe hopping processes that depend on the particle-density difference in neighboring sites. The effective model is obtained in arbitrary spatial dimensions, but only in one-dimension it is known to be exactly solvable for specific values of the parameters. Moreover, an SU(2) symmetry in the charge sector allows to construct non-trivial superconducting eigenstates (eta-states), discovered by Yang as excited states of the Hubbard model. Then, we study a one-dimensional bipartite optical lattice with fermionic atoms at half-filling. The lattice potential barriers have heights alternating in magnitude. As a consequence, the hopping amplitudes also alternate in magnitude and the elementary unit cell has two sites. This system is known to display Peierls dimerization at half-filling: the fermions form dimers in neighboring sites that inhibit transport and open a gap in the spectrum. After applying shaking on this system we discover that one can dynamically induce a phase transition to an unconventional metallic state with four Fermi-points. The second part of this thesis describes bosonic systems in two-dimensional optical lattices. First, we consider a square optical lattice with alternating deep-shallow wells arranged in a checkerboard pattern. This lattice is realized in the experimental laboratory of Prof. Hemmerich in Hamburg. In the experiment, the visibility is extracted from the time-of-flight imaging to quantify the phase coherence of the bosonic gas. We develop a mean-field theory and determine the phase diagram of this model. We interpret the experimental data by assuming that at large detuning, only the deeper wells are populated and form an imbalanced Mott insulator with empty shallow wells and integer density on the deeper wells. We support this hypothesis by large-scale Gutzwiller calculations. Then, we investigate a system of bosons in the Lieb lattice, which is the lattice geometry of the Cu-O plane in cuprates . We consider configurations of the optical potential where s and p orbitals sitting on neighboring wells become resonant and hybridize. The interest in this problem comes from the possibility to realize time-reversal broken phases, usually known as Varma phases for electronic systems, which have been proposed to explain the pseudo-gap regime of cuprate superconductors. We show the conditions under which the symmetry breaking in a four-band model can lead to states with loop currents. Moreover, the lowest branch of the excitation spectrum has a non-vanishing Chern number and therefore supports topological excitations.


Background: The credibility of modern science is grounded on the perception of the objectivity of its scientists, but that credibility can be undermined by financial conflicts of interest. The US Public Health Service and the National Science Foundation issued regulations effective October 1, 1995, regarding the disclosure of financial interests in the submission of grant proposals. Several scientific journals have also established pertinent policies for authors and editors. The objectives of this study were: (1) to select a set of published articles and observe the degree to which a sample of authors hold a financial interest in areas related to their research that are reportable under current standards, and (2) to examine the hypothesis that significant numbers of authors of articles in life science and biomedical journals have verifiable financial interests that might be important for journal editors and readers to know. This paper measures the frequency of selected financial interests held among lead authors of certain types of scientific publications and assesses disclosure practices of authors and journals. Method: These objectives were applied to a pilot study of Massachusetts academic scientists who were cited as first or last author in at least one article published in 1992 in 14 leading journals of cell or molecular biology and medicine. We created a database of every original article published in 1992 by 14 leading life science and biomedical journals, supplemented by data sets consisting of (1) Massachusetts biotechnology firms, including their officers and scientific advisory boards, and (2) scientists listed as inventors on patents or patent applications registered with the World Intellectual Property Organization. Results: We examined 1,105 university authors (first and last cited) from Massachusetts institutions whose 789 articles, published in 1992, appeared in 14 scientific and medical journals. Authors are said to 'possess a financial interest' if they are listed as inventors in a patent or patent application closely related to their published work; serve on a scientific advisory board of a biotechnology company; or are officers, directors, or major shareholders (beneficial owner of 10% or more of stock issued) in a firm that has commercial interests related to their research. Applying the criteria to the reference population of journals and Massachusetts academic authors, we measured the following frequencies for lead authors: 0.20 for serving on a scientific advisory board; 0.07 for being an officer, director, or major shareholder in a biotechnology firm, and 0.22 for being listed as an inventor in a related patent or patent application. The joint frequency of articles in the journals reviewed with a lead author that meets one of the three conditions is 0.34. Conclusions: One of every three articles in our sample has at least one Massachusetts-based author with a financial interest, and 15% of the authors in our sample have a financial interest relevant to one of their publications. For the year 1992, the rate of published voluntary disclosures of financial interest (as defined in our study) is virtually zero, but relatively few scientific and biomedical journals at that time required any such disclosure to journal editors and reviewers. Further research is needed to determine the effectiveness of mandatory disclosure requirements by some journals.


Concrete strength is fairly sensitive to environmental effects. Extreme weather conditions and changes in humidity rates significantly affect the concrete compressive strength development. Concrete as one of the substantial material used in residential buildings and infrastructures is subjected to a massive strength change under extreme weather conditions. For understanding, the different concrete's behavioral aspects, various commercial cement types under different temperatures, and humidity rates are investigated in this chapter. The experiments are aimed to investigate the concrete strength development over time when the material is cast at lower to mild temperatures and different humidity index rates. Results show that reducing the curing temperature more than 15° could result in 20% reduction in total compressive strength, while decreasing humidity rates by 50% leads to less than 10% drop in ultimate strength. To understand the strength developing process, maturity tests are conducted. It is shown that concrete is not able to reach to the expected ultimate strength if the temperature is significantly low regardless of curing time. The effect of temperature change during the curing process is more tangible on strength development compared to cement type and humidity rate values.


: Objective: Anticoagulation reversal, intensive blood pressure lowering, neurosurgery and access to critical care might all be beneficial in acute intracerebral hemorrhage (ICH). We combined and implemented these as the 'ABC' hyperacute care bundle and sought to determine whether the implementation was associated with lower case fatality. Methods: The ABC bundle was implemented from 1 June 2015 to 31 May 2016. Key process targets were set and a registry captured consecutive patients. We compared 30-day case fatality before, during and after bundle implementation with multivariable logistic regression and used mediation analysis to determine which care process measures mediated any association. Difference-in-difference analysis compared 30-day case fatality with 32,295 patients with ICH from 214 other hospitals in England and Wales using Sentinel Stroke National Audit Programme data. Results: 973 ICH patients were admitted in the study period. Compared to before implementation, the adjusted odds of death by 30 days were lower in the implementation period (odds ratio [OR] 0·62; 95% confidence interval [CI] 0·38 to 0·97; p=0·03) and this was sustained after implementation (OR 0·40; 95%CI: 0·24 to 0·61; p<0·0001). Implementation of the bundle was associated with a 10·8 pp (95%CI -17·9 to -3·7; p=0·003) reduction in 30-day case fatality in difference-in-difference analysis. The total effect of the care bundle was mediated by a reduction in do-not-resuscitate orders within 24 h (52·8%) and increased admission to critical care (11·1%). Interpretation: Implementation of the ABC care bundle was significantly associated with lower 30-day case fatality after ICH.


Bacillus subtilis possesses a secondary transporter CitM that is specific for the complex of citrate and Mg but is also capable of transporting citrate in complex with the heavy metal ions Zn, Ni and Co. We report on the impact of CitM activity on the toxicity of the heavy metals Zn, Ni and Co + in B. subtilis. In a CitM deletion mutant or under conditions when CitM is not expressed, the toxic effects of the metals were reduced by the presence of citrate in the medium. In contrast, the presence of citrate dramatically enhanced toxicity when the Mgcitrate transporter was present in the membrane. It is demonstrated that the complex of Ni and citrate is transported into the cell and that the uptake is responsible for the enhanced toxicity. At toxic concentrations of the metal ions, the cultures adapted by developing resistance against these ions. Resistant cells isolated by exposure to one of the metal ions remained resistant after growth in the absence of toxic metal ions, and were cross-resistant against the other two toxic ions. Resistant strains were shown to contain point mutations in the citM gene, which resulted in premature termination of translation.


BACKGROUND
Acute renal failure after major surgery is associated with significant mortality and morbidity that theoretically may be attenuated by N-acetylcysteine.

DESIGN
Meta-analysis of relevant studies sourced from the Cochrane Controlled Trial Register (2007 issue 4), EMBASE, and MEDLINE databases (1966 to February 1, 2008) without language restriction.

SETTING & POPULATION
Adult patients undergoing major surgery without the use of radiocontrast.

SELECTION CRITERIA FOR STUDIES
Randomized controlled studies comparing N-acetylcysteine with a placebo perioperatively.

DATA ANALYSIS
Categorical variables are reported as odds ratio (OR) with 95% confidence interval (CI), and continuous variables are reported as weighted-mean-difference (WMD) with 95% CI.

OUTCOME MEASURES
Effects of N-acetylcysteine on mortality and acute renal failure requiring dialysis were the main outcomes of interest. Additional outcome measures included an incremental increase in serum creatinine concentration greater than 25% above baseline, surgical reexploration for bleeding, amount of allogeneic blood transfusion, and length of intensive care unit stay.

RESULTS
10 studies involving a total of 1,193 adult patients undergoing major surgery were considered. N-Acetylcysteine use was not associated with a decrease in mortality (OR, 1.05; 95% CI, 0.58 to 1.92), acute renal failure requiring dialysis (OR, 1.04; 95% CI, 0.45 to 2.37), incremental increase in serum creatinine concentration greater than 25% above baseline (OR, 0.84; 95% CI, 0.64 to 1.11), or length of intensive care unit stay (WMD in days, 0.46; 95% CI, -0.43 to 1.36). N-acetylcysteine did not appear to increase the risk of surgical reexploration for bleeding (OR, 1.16; 95% CI, 0.57 to 2.38) or amount of allogeneic blood transfusion required (WMD in units, 0.31; 95% CI, -0.21 to 0.84).

LIMITATIONS
Most studied patients had cardiac surgery and normal renal function preoperatively.

CONCLUSIONS
There is no current evidence that N-acetylcysteine used perioperatively can alter mortality or renal outcomes when radiocontrast is not used.


Several geometrical modifications for passive flow control applied to a railroad tank wagon were investigated for the purpose of assessing the potential for the aerodynamic optimization of freight trains. The modifications were designed in accordance with applicable requirements and regulations. Four different modifications were investigated in the wind tunnel of the TU Berlin with 1:25 scaled wagon models: face radius, side skirts, fairing of the roof platform, and the newly introduced inter-wagon discs. In order to simulate the positions of the tested wagon at the end of a long train, the boundary layer on the train model setup was artificially thickened by spires. The Reynolds number was in the range of 0.4 × 106. The results of the experiments show that the proposed measures can reduce the aerodynamic drag of the individual wagon by up to 29%, depending on the location in the train consist. It was also shown that by combining different measures, the individual drag reductions add up. The device with the highest drag reduction was found to be the inter-wagon disc. Three different diameters of the inter-wagon disc were investigated. The largest diameter performed best and was less sensitive to the moving direction of the wagon in comparison to the smaller diameters.


Huntington's disease features the loss of striatal neurons that stems from a disease process that is initiated by mutant huntingtin. Early events in the disease cascade, which predate overt pathology in Hdh CAG knock-in mouse striatum, implicate enhanced N-methyl-d-aspartate (NMDA) receptor activation, with excitotoxity caused by aberrant Ca2+ influx. Here we demonstrate in precise genetic Huntington's disease mouse and striatal cell models that these early phenotypes are associated with activation of the Akt pro-survival signaling pathway. Elevated levels of activated Ser(P)473-Akt are detected in extracts of HdhQ111/Q111 striatum and cultured mutant STHdhQ111/Q111 striatal cells, compared with their wild type counterparts. Akt activation in mutant striatal cells is associated with increased Akt signaling via phosphorylation of GSK3β at Ser9. Consequent decreased turnover of transcription co-factor β-catenin leads to increased levels of β-catenin target gene cyclin D1. Akt activation is phosphatidylinositol 3-kinase dependent, as demonstrated by increased levels of Ser(P)241-PDK1 kinase and decreased Ser(P)380-PTEN phosphatase. Moreover, Akt activation can be normally stimulated by treatment with insulin growth factor-1 and blocked by treatment with the phosphatidylinositol 3-kinase inhibitor LY294002. However, in contrast to wild type cells, Akt activation in mutant striatal cells can be blocked by the addition of the NMDA receptor antagonist MK-801. Akt activation in mutant striatal cells is Ca2+-dependent, because treatment with EGTA reduces levels of Ser(P)473-Akt. Thus, consistent with excitotoxicity early in the disease process, activation of the Akt pro-survival pathway in mutant knock-in striatal cells predates overt pathology and reflects mitochondrial dysfunction and enhanced NMDA receptor signaling.


eGovernment promises more efficient services and a more responsive government. Despite substantial investment, increasing failure rates have prompted critics to argue that policy makers are not achieving this vision. Surprisingly, there is very little research on what citizens define as important in eGovernment services and how aspects of government web sites affect that perception. The inclusion of the citizen perspective has largely been absent, denying a deeper understanding of the factors that drive usage. This research proposes an important and unique development of the D&M IS Success Model. By combining elements from public administration research and eGovernment success, this study constructs a comprehensive model of Net Benefits centred on the perspective of the citizen. The novel paradigm of Public Value is used to create a balanced success model, tailored for the public sector and is situated within the D&M IS Success Model. This research therefore aims to understand what citizens regard as important in the success of eGovernment services and what aspects of IT Quality affect eGovernment success.


Elevated SNSA induces dysglycemia by enhancing adipose lipolysis and stimulating hepatic glucose production. It also promotes cardiovascular disease (CVD) by multiple mechanisms including augmenting systemic and vascular reactive oxygen and nitrogen species (ROS, RNS) generation. Elevated plasma prolactin (subclinical hyperprolactinemia) has also been associated with systemic inflammation, which can potentiate dysglycemia and CVD. BQR, the only dopamine agonist approved for treatment of T2D, improves postprandial dysglycemia and reduces CVD events. To evaluate mechanisms for the glucose lowering and CVD protective effects of BQR, we evaluated BQR's effect on plasma markers of SNSA and ROS/RNS and plasma prolactin and leptin from a mechanistic study in which BQR added to 15 T2D subjects (HbA1c 8.3%) treated with a GLP-1 RA significantly improved HbA1c (-0.6%), postprandial hyperglycemia (by 22%) and endothelial dysfunction (by 36%). Plasma norepinephrine (NE), normetanephrine (NM), TBAR (a marker of systemic OS), nitrotyrosine (NT, a marker of systemic oxidative/nitrosative stress), prolactin and leptin were measured at baseline and after 4 months of BQR add-on therapy (3.2 mg/day). Plasma NE, NM, TBAR, NT and prolactin levels were elevated at baseline and decreased significantly with BQR [NE by 33% (2.95 to 1.95 ng/mL, p 20 ng/dl, N=7) at baseline. Conclusion: Bromocriptine-QR is the only T2D therapy known to simultaneously reduce elevated plasma NE, NM, prolactin and OS and such actions may be important for the drug's glucose lowering and CVD protective effects. Disclosure B. Chamarthi: Employee; Self; VeroScience LLC. E. Cersosimo: None. J.M. Adams: None. M. Alatrach: None. C. Agyin: None. C.L. Triplitt: Consultant; Self; Abbott. Speaker9s Bureau; Self; AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Eli Lilly and Company, Janssen Pharmaceuticals, Inc. M. Ezrokhi: Employee; Self; VeroScience LLC. S. Luo: Employee; Self; VeroScience LLC. E. Duvallet: Employee; Self; VeroScience LLC. A.H. Cincotta: Employee; Self; VeroScience LLC. R.A. DeFronzo: Advisory Panel; Self; AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Elcelyx Therapeutics, Inc., Intarcia Therapeutics, Inc., Janssen Pharmaceuticals, Inc., Novo Nordisk Inc. Research Support; Self; AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Janssen Pharmaceuticals, Inc., Merck & Co., Inc. Speaker9s Bureau; Self; AstraZeneca, Novo Nordisk Inc.


Silver PMMA Nanocomposite Thin Films Deposited on Glass Substrates by in-situ aerosol assisted plasma jet polymerization at atmospheric pressure and room temperature, from MMA monomer in the presence of 7wt% concentrations of Ag nanoparticles. The effects of argon gas flow rate on the linear and nonlinear optical properties of Ag/PMMA nanocomposite films are studied. It is shown that the changed in gas flow rate does not affect the linear properties while the nonlinear properties have an arbitrary changes with gas flow rate increase. The prepared thin films are characterized by UV-Visible, XRD, FT-IR, AFM, the nonlinear optical properties are measured by Z-scan technique using second harmonic of pulsed Nd:YAG laser 532nm and pulse duration of 30ns, the third order nonlinearity are determined the nonlinear refractive index n2, nonlinear absorption coefficient , as well as the real and imaginary parts of third order susceptibility X3 all are changed due to effect of plasma and gas flow rate.


Recently, the QoS architecture in the beyond 3rd generation mobile communication system is becoming a hot topic in the area of computer networks and telecommunications. In this paper, the state-of-the-art QoS architectures are presented. By analyzing and comparing the key projects and papers published abroad, it is concluded that QoS architecture in B3G (beyond 3rd generation) system should be an all-IP, hierarchical and end-to-end framework. The main characteristics include scalability, controllable, self-adaptation and dynamic resource management. Finally, the design principals are proposed, and future works are summarized as well.


Florida has a long association with citrus (Citrus sp.) production. However, the citrus industry in Florida has been devastated by Huanglongbing (HLB) or citrus greening disease (Candidatus Liberibacter asiaticus). HLB affects the citrus tree phloem and eventually causes tree death. Cover crops, or noncash crops, have traditionally been used in row crop production to improve soil organic matter, for nitrogen fixing, and for weed control. Citrus growers may benefit from adopting cover crops because healthier soils could improve yields and fruit quality of citrus trees. However, growers are uncertain about the costs and benefits associated with cover crop investments. The objective of our study was to analyze whether cover crops represent an economically feasible option for Florida citrus growers. We calculated the break-even prices for 'Valencia' and non-'Valencia' oranges (Citrus sinensis) in terms of price per box (equivalent to 90 lb of oranges in Florida) and price per pound solids per box (amount of soluble solids per box of oranges) by considering additional costs and short-term savings from using cover crops across various yield and quality scenarios based on the past 10 years of data. Considering the short-term savings from adopting cover crops, the per-acre cost of production increased by $107.3/acre or by 5.73% and constituted 5.42% of the total production cost during the first year of adoption. After the 2018–19 peak, the yield and quality for both 'Valencia' and non-'Valencia' oranges have decreased steadily. Adopting cover crops in the current yield–quality scenario will not be profitable for either 'Valencia' or non-'Valencia' oranges. However, for 'Valencia' oranges, at the median yield and quality levels of 193.5 boxes/acre and 6.08 lb solids/box, respectively, cover crop adoption would be profitable because the break-even price of $2.25/lb solids would be comparable to the market prices of the past 5 years.


Radiation-induced lung injury (RILI) is a common and potentially serious complication from radiotherapy to the thoracic region. In the current study, we examined the potential protective effects of URB937, an inhibitor of fatty acid amide hydrolase in a mouse model of RILI. Here we challenged male C57BL/6 mice with irradiation (16Gy to the thoracic region), and then injected intraperitonealy either URB937 (1 mg/kg) or vehicle three times a week for 30 days. Mice were sacrificed at either the end of treatment or120 days from irradiation to evaluate the extent of RILI and mice survival. Potential effects of URB937 on irradiation induced tumor growth inhibition were also evaluated. We found URB937 increased endocannabinoids in the lungs, attenuated the extent of RILI, prolonged the survival,inhibited mice developed pathological alterations of pneumonitis and lung fibrosis. Irradiation-induced increases of proinflammatory and profibrotic cytokines were decreased, including interleukin-1β, interleukin-6, tumor necrosis factor-α, transforming growth factor-β1 in plasma and lung tissue. Moreover, malondialdehyde in plasma and inflammation cells in bronchoalveolar lavage fluid were lower in mice treated with irradiation plus URB937. URB937 did not affect tumor growth inhibition caused by irradiation. These results suggested that inhibiting fatty acid amide hydrolase through URB937 could ameliorate the RILI, without affecting the efficacy of irradiation on tumor control. Note: This abstract was not presented at the meeting. Citation Format: Rui Li, Jianxin Xue, You Lu. The fatty acid amide hydrolase inhibitor URB937 ameliorates radiation-induced lung injury in a mouse model [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 2233. doi:10.1158/1538-7445.AM2017-2233


Abstract. Sources and propagation characteristics of high-frequency gravity waves observed in the mesosphere using airglow emissions from Gadanki (13.5° N, 79.2° E) and Hyderabad (17.5° N, 78.5° E) are investigated using reverse ray tracing. Wave amplitudes are also traced back, including both radiative and diffusive damping. The ray tracing is performed using background temperature and wind data obtained from the MSISE-90 and HWM-07 models, respectively. For the Gadanki region, the suitability of these models is tested. Further, a climatological model of the background atmosphere for the Gadanki region has been developed using nearly 30 years of observations available from a variety of ground-based (MST radar, radiosondes, MF radar) and rocket- and satellite-borne measurements. ERA-Interim products are utilized for constructing background parameters corresponding to the meteorological conditions of the observations. With the reverse ray-tracing method, the source locations for nine wave events could be identified to be in the upper troposphere, whereas for five other events the waves terminated in the mesosphere itself. Uncertainty in locating the terminal points of wave events in the horizontal direction is estimated to be within 50–100 km and 150–300 km for Gadanki and Hyderabad wave events, respectively. This uncertainty arises mainly due to non-consideration of the day-to-day variability in the tidal amplitudes. Prevailing conditions at the terminal points for each of the 14 events are provided. As no convection in and around the terminal points is noticed, convection is unlikely to be the source. Interestingly, large (~9 m s−1km−1) vertical shears in the horizontal wind are noticed near the ray terminal points (at 10–12 km altitude) and are thus identified to be the source for generating the observed high-phase-speed, high-frequency gravity waves.


In this study, we performed thermal stress analyses on a ventilated disk brake with a 3D model for two cases (whether the pressure distribution on a contact surface is uniform or not). A pressure distribution analysis was performed to determine the pressure distribution on the contact surface. Then, by using the results that were obtained from the pressure distribution analyses, we performed thermal stress analyses. Finally, we have found the spots where the maximum thermal stresses occur. Also, for the life evaluation of a disk brake, we have conducted the fatigue test and obtained the S-N curve. From those results, we evaluated the life of a disk brake.


The carrier frequency estimation algorithm based on high-order cyclic cumulants does not need a training sequence. Due to the fact that the high-order cycle can suppress the stationary and non-stationary Gaussian noise, the algorithm is tolerant to the noise mentioned above. The computation of the algorithm is deduced in this paper. It shows that if large searching range of carrier frequency and high frequency resolution are required, the computation will be great. In order to reduce the computation, a 3-order iterative carrier frequency estimation algorithm based on high-order cyclic cumulants is introduced in this paper and the relationship between frequency resolution and computation is deduced. The simulations show that the algorithm proposed in this paper can reduce the computation significantly.


The sweet chestnut ( Castanea sativa Mill.) is one of the most important starchy foods worldwide due to its low fat content and high nutritional value. This study is the first analysis of the sweet chestnut fruit in forest plantations where the morphological properties are characterized, in terms of caliber, size, shape, and internal cracking, damage, and cavities. The study was based in three sites in Chile, Los Rios Region (39°S), where most of the forest chestnut plantations are located. Scott and Knott test of variance and contingency tables were used as statistical methods for site comparisons. In general, no significant differences in size were found among sites. Moreover, the Chilean forest sweet chestnut can be defined as a small-caliber fruit with slight internal cracking and internal damage and almost no cavities. Therefore, due to its morphological characteristic (especially caliber), it has the potential to be used for secondary food products.


To the Editor.— We wish to comment on the recent article by Odukoya and Shklar that appeared in the September 1985 issue of theArchives 1 . In our opinion, their article demonstrates the classic error made by those who claim that lichen planus has significant premalignant potential. The misconception rests on the fact that, in cases selected for study, the original diagnoses of lichen planus are either incorrect or unsubstantiated by histomorphologic documentation. With specific reference to their article, the authors state that they selected for study "cases histologically diagnosed as lichen planus." Published photomicrographs, however, fail to satisfy the diagnostic criteria of lichen planus and, on the contrary, show dysplasia with lichenoid features (eg, lichenoid dysplasia). Thus, in all probability, lesions cited in this study bear no relation to lichen planus other than that they share with lichen planus some rather nonspecific clinical and histologic features seen in a


Hypoxia inducible factor (HIF) is important in cancer, as it regulates various oncogenic genes as well as genes involved in cell survival, proliferation, and migration. Elevated HIF-1 protein promotes a more aggressive tumor phenotype, and greater HIF-1 expression has been demonstrated to correlate with poorer prognosis, increased risk of metastasis and increased mortality. Recent reports suggest that HIF-1 activates autophagy, a lysosomal degradation pathway which may promote tumor cell survival. We show here that HIF-1α is constitutively active in multiple diffuse large B cell lymphoma (DLBCL) cell lines under normoxia and it is regulated by the PI3K/AKT pathway. PCI-24781, a pan histone deacetylase inhibitor (HDACI), enhanced accumulation of HIF-1α and induced autophagy initially, while extended incubation with the drug resulted in inhibition of HIF-1α. We tested the hypothesis that PCI-24781- induced autophagy is mediated by HIF-1α and that inhibition of HIF-1α in these cells results in attenuation of autophagy and decreased survival. We also provide evidence that autophagy serves as a survival pathway in DLBCL cells treated with PCI-24781 which suggest that the use of autophagy inhibitors such as chloroquine or 3-methyl adenine in combination with PCI-24781 may enhance apoptosis in lymphoma cells.

Citation Information: Mol Cancer Ther 2013;12(11 Suppl):B201.

Citation Format: Savita Bhalla, Andrew M. Evens, Sheila Prachand, Paul T. Schumacker, Leo I. Gordon. Targeting HIF-1α in diffuse large B cell lymphoma: Role for HDAC inhibitors. [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2013 Oct 19-23; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2013;12(11 Suppl):Abstract nr B201.


Background: The European Association of Endoscopic Surgery (EAES) initiated a consensus development conference on the laparoscopic resection of colon cancer during the annual congress in Lisbon, Portugal, in June 2002. Methods: Asystematic review of the current literature was combined with the opinions, of experts in the field of colon cancer surgery to formulate evidence-based statements and recommendations on the laparoscopic resection of colon cancer. Results: Advanced age, obesity, and previous abdominal operations are not considered absolute contraindications for laparoscopic colon cancer surgery. The most common cause for conversion is the presence of bulky or invasive tumors. Laparoscopic operation takes longer to perform than the open counterpart, but the outcome is similar in terms of specimen size and pathological examination. Immediate postoperative morbidity and mortality are comparable for laparoscopic and open colonic cancer surgery. The laparoscopically operated patients had less postoperative pain, better-preserved pulmonary function, earlier restoration of gastrointestinal function, and an earlier discharge from the hospital. The postoperative stress response is lower after laparoscopic colectomy. The incidence of port site metastases is <1%. Survival after laparoscopic resection of colon cancer appears to be at least equal to survival after open resection. The costs of laparoscopic surgery for colon cancer are higher than those for open surgery. Conclusion: Laparoscopic resection of colon cancer is a safe and feasible procedure that improves short-term outcome. Results regarding the long-term survival of patients enrolled in large multicenter trials will determine its role in general surgery.


This paper describes a structured programming and teaching system for a robot manipuLator where stress is Laid on the consistent integration of programming and teaching. Tn the PAL programming system being developed at Purdue, tasks are represented in terms of structured Cartesian coordinates. Every motion statement is a request to position and orient the manipulator such that a position equation, representing a closed kinematic chain of homogeneous transformations, is satisfied. In the teaching process, the transformation which represents the position of the end of the manipulator is defined using the manipulator itself, and an equation relating any undefined transformations is obtained. By defining these equations during the interpretation of the task program and progressive by solving them, the task is taught. The method is applicabLe both to practical industrial robot control and to intelligent robot control.


This review traces the efforts of different fields of thermoregulatory modeling. The aims of the three diverging branches can be characterized by (i) insight into functional physiological mechanisms and prediction of physiological phenomena, (ii) prediction of human performance for the protection of industrial workers or military personnel, and (iii) prediction of the impact of accidents, diseases, and clinical treatments. Common current and future efforts may be recognized which improve the physiological quality of the models for purposes either of physiological research itself or of promotion of the field of application, namely, (i) to approach the models to real geometry and anatomy of the human body, (ii) to simulate more adequately heat transport processes induced by the circulating blood, (iii) to implement more sophisticated regulatory concepts, (iv) to take into account interaction with other regulatory systems. "Environmental Ergonomics" should be an adequate forum for linking these diversified fields together.


Background The rise in obesity is leading to an increasing rate of type 2 diabetes in those aged younger than 40. Management of hyperglycaemia and cardiovascular disease (CVD) in this age profile is complicated by higher insulin requirements and contraindications to certain CVD agents, yet few studies to date have focussed on the primary care setting. The aims of this study were to: 1) characterise antidiabetic drug utilisation including non-persistence, treatment addition and switching, 2) investigate factors associated with insulin use, 3) characterise the use of and factors associated with CVD agents in early onset diabetes. Methods A population-based retrospective cohort study from 2008–2011 was conducted using the Irish national pharmacy claims database. Subjects aged 15–39 were analysed for use of antidiabetic therapy and any co-prescription of cardiovascular agents. Cox proportional-hazards regression and logistic regression were used to examine associations of socio-demographic and treatment factors on treatment patterns, including non-persistence (among males), initiation of insulin and use of cardiovascular agents. Hazard ratios (HR), odds ratios (OR) and 95% confidence intervals (CI) are presented. Results From 2008–2011 there were 5284 individuals initiated on antidiabetic agents. Most were initiated on metformin (88%) and 26% of those with a treatment addition or switching received insulin. A total of 62% of males were persistent with their initial antidiabetic agent. Over 40% of subjects were initiated on cardiovascular agents. The likelihood of non-persistence was significantly higher in males aged 15–29 years (HR 1.97 [CI 1.58–2.45]) and those on sulphonylureas (HR 1.79 [CI 1.35–2.37]). Females and those aged 15–29 years were more likely to receive insulin (HR 1.61[CI 1.19–2.19] and HR 1.51 [CI 1.10–2.09] respectively), and less likely to receive cardiovascular agents (HR 0.50 [CI 0.42–0.83] and HR 0.46 [CI 0.37–0.57] respectively). Conclusion Early onset type 2 diabetes has been shown to be a complex condition associated with high levels of treatment non-persistence, use of insulin and of CVD agents in certain sub-groups. Treatment patterns differ between those aged 15–29 years compared to those aged 30–39 years as well as by gender. The choice of initial agent affects future treatment use and prescribers should thoroughly assess the suitability of a sulphonylurea as the initial agent. Given that diabetes is a chronic, progressive condition that is increasingly occurring in younger populations, it is essential that health professionals and policy makers address the selection of, and persistence with medicines in each of the sub-groups identified in this study.


The natural dihydrate form of calcium sulphate, CaSO 4 .2H 2 O (gypsum), particularly found in gypsiferous soils and in certain building constructions, was found to be effectively solubilized by both Aspergillus niger and Serpula himantioides . When the fungi were grown on malt extract agar (MEA) medium amended with up to 1% (w/v) of gypsum, solubilization activity was evident by the appearance of a clear zone (haol) around and/or under the growing colonies. The haloes were found subsequently to enclose concentric rings of newly formed crystalline precipitate. The pH profile of the medium underneath the growing mycelium of A. niger was not affected by the presence of gypsum, while the S. himantioides pH profile displayed a slight reduction in pH values when grown on gypsum-containing media compared with the control. Electron microscopy and X-ray microanalysis of the crystals revealed the formation of calcium-containing crystals with the characteristic morphology typical of different forms of calcium oxalate. The complexing activity of fungal-produced organic acids with calcium was suggested to be the prevalent mechanism of solubilization with the production of oxalic acid resulting in precipitation of oxalate. Such activity resulted in the release of available sulphate which increased over the incubation period. The concentrations of sulphate released from 0.5% (w/v) gypsum after growth of A. niger and S. himantioides for 8 d were 14·7±0·7 and 7·4±0·9 μmol cm -3 respectively. These results are discussed in the light of their relevance to land reclamation and plant nutrition, as well as the weathering of building materials containing gypsum.


THE BEHAVIOUR OF IODINE AND XENON IN THE FIRST ASTEROIDSJennifer Louise ClaydonThe University of Manchestersubmitted for the degree of Doctor of Philosophy, September 2012.Results of I-Xe analyses have been obtained from meteorite samples that experienced different extents of thermal processing in the early Solar System in order to help characterise the movements of iodine and xenon in the early Solar System and constrain the timing of these movements using the I-Xe chronometer. Samples were irradiated to convert 127I to 128Xe* and allow simultaneous measurements of iodine and xenon isotopes. Xe isotopes were measuring using the RELAX mass spectrometer.I-Xe ages of material of different metamorphic grade from R-chondrites NWA 6492, NWA 830 and NWA 3364 suggest a link between the time of closure to Xe-loss and extent of metamorphism on the R-chondrite parent body. However, further I-Xe analyses of R5 material from NWA 6492 and R4 and R6 material from other R-chondrites are needed to confirm this. The most primitive material analysed give I? Xe ages between 4559 ? 4554 Myr, slightly later than reported Mn-Cr ages. This may support the ideal of radial heterogeneity of 53Mn in the early Solar System. However differences could also be due to variations in the samples analysed. Future analyses of I-Xe and Mn-Cr ages in mineral separates from the same R-chondrite are recommended in order to investigate this hypothesis. Closure to Xe-loss in chondrules on the R-chondrite parent body appears to have occurred ~5 ? 10 Myr later than on the ordinary and enstatite parent bodies. This implies either later accumulation of material or slower cooling in a larger body.Comparisons of I-Xe systematics in anomalous eucrites Bunburra Rockhole and Ibitira and ?nomalous? eucrites Juvinas and B�r�ba show lower 129I/244Pu ratios in the ?nomalous? eucrites. This is not due to formation on a less volatile-rich body but instead reflects extended loss of Xe on 4 Vesta. 129I/244Pu ratios indicate igneous processing continued on 4 Vesta for ~50-100 Myr after geological activity had ceased on the anomalous eucrites parent bodies. The extended processing seen in Juvinas and B�r�ba is attributed to formation on a larger body that retained heat for longer. If, as the data suggest, the anomalous eucrites formed on a separate parent body it must have been catastrophically disrupted as Vesta is thought to be the only remaining differentiated asteroid. The larger size of Vesta may explain why it has uniquely survived the impacts that destroyed its siblings. Analyses of the unique achondrite GRA 06129 show that the I-Xe system in this meteorite has no chronological significance. The data instead suggest that iodine-bearing plagioclase formed early but thermal metamorphism resulted in loss of 129Xe* from iodine bearing sites. Uranium-bearing apatite appears to be a secondary mineral that incorporated parentless 129Xe* and 129Xe*that had been redistributed during earlier metamorphism. A trapped-Xe component released at high-temperatures may be a primitive component such as Q-Xe, though terrestrial?Xe acquired during weathering cannot be ruled out by this study. If Q-Xe is present, it is most likely hosted in a primary phase other than plagioclase. During its terrestrial residence time GRA 06129 acquired iodine via Antarctic weathering. I-Xe analyses on Antarctic meteorites should therefore be carried out with caution. Further Xe analyses of mineral separates from GRA 06129 would help constrain the host phase of the trapped Xe. That the I-Xe system of the plagioclase has been completely reset make it a good candidate mineral for I-Xe dating of primary processes whereas I-Xe dating of apatite appears more problematic.


Vascular smooth muscle (VSM) cell proliferation and migration are the hallmark of atherosclerosis and re-stenosis. In this study, we have investigated the role of mitochondrial bioactivity in determining the content of exosomes released by vascular smooth muscle cells and the biological effect these exosomes have on vascular smooth muscle (VSM) cell proliferation and migration. VSM cells were isolated from 12 week old male Sprague-Dawley rats. Experiments were undertaken using day zero isolated (contractile phenotype), 21 day cultured (synthetic phenotype) and 21 day mitochondrial incompetent (synthetic phenotype- Rho cell). The effect of balloon angioplasty on rat aorta structural remodelling was also studied. Inhibition of mitochondrial network formation with the DRP1 inhibitor MDivi (10 uM) inhibited angioplasty-dependent remodelling. This observation was confirmed in VSM cell cultures where MDivi significantly reduced proliferation and migration. Total exosomal release was significantly greater in the 21 day cultured cells when compared with quiesced non-proliferating cells and 21 day cultured Rho cells (480±20 ng, 520±10 ng and 420±10 ng per ml respectively) and total exosomal RNA yield was 70.2±10.2 ng/ul, 118.7±2.4 ng/ul and 70.8±4.7 ng/ul respectively. Mitochondrial function significantly influenced miRNA and mRNA measured in exosomes. When compared with the hyperproliferative synthetic VSM cell miR-21 expression was reduced by 88±12.1% and miR-145 expression increased by 73±19.8%. We also measured a 7-fold decrease and 6.6-fold decrease mTOR, PI3K and 4EBP1 respectively. A significant increase expression of P53, cdkn2a and ROS scavenging proteins including SOD1 and SOD2 were measured in 21 day cultured Rho cells vs. 21 day hyperproliferative VSM cells. In this study we have further correlated VSM cell hyperproliferative phenotype with mitochondrial function. Moreover, further demonstrated mitochondrial function/VSM cell phenotype with exosomal release and cargo that potentially drives the hyperproliferative/migratory phenotype central to atherosclerosis and re-stenosis.


BACKGROUND The prevalence of childhood asthma is increasing but few studies have investigated trends in asthma severity. We investigated trends in asthma diagnosis and symptom morbidity between an eight year time period in a paired prevalence study. METHODS All children in one single school year aged 8–9 years in the city of Sheffield were given a parent respondent questionnaire in 1991 and 1999 based on questions from the International Survey of Asthma and Allergy in Children (ISAAC). Data were obtained regarding the prevalence of asthma and wheeze and current (12 month) prevalences of wheeze attacks, speech limiting wheeze, nocturnal cough and wheeze, and exertional symptoms. RESULTS The response rates in 1991 and 1999 were 4580/5321 (85.3%) and 5011/6021 (83.2%), respectively. There were significant increases between the two surveys in the prevalence of asthma ever (19.9%v 29.7%, mean difference 11.9%, 95% confidence interval (CI) 10.16 to 13.57, p<0.001), current asthma (10.3% v 13.0%, mean difference 2.7%, 95% CI 1.44 to 4.03, p<0.001), wheeze ever (30.3%v 35.8%, mean difference 5.7%, 95% CI 3.76 to 7.56, p<0.001), wheeze in the previous 12 months (17.0%v 19.4%, mean difference 2.5, 95% CI 0.95 to 4.07, p<0.01), and reporting of medication use (16.9%v 20%, mean difference 3.0%, 95% CI 1.46 to 4.62, p<0.001). There were also significant increases in reported hayfever and eczema diagnoses. CONCLUSIONS Diagnostic labelling of asthma and lifetime prevalence of wheeze has increased. The current 12 month point prevalence of wheeze has increased but this is confined to occasional symptoms. The increased medication rate may be responsible for the static prevalence of severe asthma symptoms. The significant proportion of children receiving medication but reporting no asthma symptoms identified from our 1999 survey suggests that some children are being inappropriately treated or overtreated.