The global credit crisis of 2008-09 was the most serious shock to the world economy in 80 years. It was for the world what the Asian crisis of 1997-98 had been for emerging markets: a profoundly alarming wake-up call. By laying bare the fragility of global markets, it raised troubling questions about the operation of the 21st-century world economy. It cast doubt on the efficacy of light-touch financial regulation and, more generally, on the prevailing commitment to economic and financial liberalization. It challenged the managerial capacity of institutions of global governance. It augured a changing of the guard, pointing to the possibility that the economies that had been leaders in the global growth stakes in the past would no longer be leaders in the future. Given that the 2008-09 crisis was first and foremost a financial crisis, it is appropriate that analysis should start with an assessment of the causes of recent financial problems and the successes and failures of post-crisis financial reform. The author argues that the traditional separation of macroeconomic and financial policies – the "Tinbergen principle" of assigning monetary policy to the maintenance of price stability and regulatory policy to financial stability – is part of what caused the crisis, and that the development of a synthesis, which flies under the flag of "macro-prudential" or "macro-financial" policy, points the way to a solution. Another striking aspect of the crisis was the abrupt collapse of international trade, which declined even more precipitously than the production of goods and services. Why the impact on trade was so dramatic continues to be debated. Then there was the protectionist response, described in Chapter 3. A few governments responded to the crisis and recession with overtly protectionist policies, but more important was "murky protectionism" defined to include not simply import tariffs, quotas and export taxes but also subsidies, bailouts, preferential public procurement practices. The global crisis also deepened disenchantment with the structure and operation of the international monetary system. It was already a commonplace that a system in which the U.S. dollar enjoyed the "exorbitant privilege" of providing the vast majority of global foreign exchange reserves was dangerously prone to imbalances. Chapter 4 sketches likely future trajectories for the international monetary arrangements. The author is dismissive of far-reaching reforms ranging from a regime based on Special Drawing Rights on the one hand to restoration of a gold-based system on the other. But he is equally skeptical about the viability of a dollar-centric monetary system like that of the recent past. The remaining option being a system organized around several national currencies – not just the dollar but also the euro and the Chinese renminbi, the question then becomes how to ease the transition to such a system and to smooth its operation once it arrives. Among the notable long-term consequences of the crisis has been the emergence of the Group of Twenty (G20) as the de facto steering committee for the world economy, displacing earlier advanced-country-centered groupings, notably the Group of Seven/Eight (G7/8). But, institutionally, the G20 remains a work in progress. As explained in Chapter 5, it has no permanent staff or written constitution. It has no global mandate; why it includes the countries it does reflects the particular historical process out of which it emerged. The details of how the G20 will work with multilateral organizations such as the International Monetary Fund and Financial Stability Board when additional problems arise remain to be determined. As the growing prominence of the G20 reveals, another consequence of the crisis has been to enhance the weight of emerging markets in the world economy. Their economies held up best in the face of the shock, and they continue to grow robustly. Chapter 6 marshals a number of indicators showing just how fast the emerging markets have grown and how importantly they now figure in the world economy. At the same time, as the author explains, these countries face serious challenges in the post-crisis environment. Stagnation in the advanced countries is a challenge for their traditional strategy of export-led growth. Chapter 7 focuses more closely on the challenges facing the emerging markets of East Asia in particular. The global crisis of 2008-09 and, more recently, financial turmoil in Europe had relatively little impact on East Asia's fast-growing economies. The emerging markets of East Asia, it was increasingly asserted, had successfully decoupled from the advanced-country world. The authors ask in the chapter whether this will remain the case going forward. As global liquidity strains rose again in the latter part of 2011, a number of East Asian currencies weakened substantially, highlighting the region's continuing dependence on external financial conditions. But if the challenges that emerging markets will face in the new post-crisis environment will be formidable, they pale in comparison with those that will confront the advanced economies. The advanced economies as a group emerged from the crisis with large budget deficits and heavy debts. Winding down those deficits without derailing recovery and damaging the prospects for growth will not be easy. All this takes place against a gloomy demographic backdrop that implies rising old-age dependency ratios, heavy pension obligations and health care costs, and a declining share of the population participating in the labor force. Chapter 8 takes up these issues. The authors frame their analysis around a number of distinctions. Notwithstanding numerous differences among economies, medium-term fiscal challenges are daunting across the advanced-country world. Under any plausible projection of the evolution of macroeconomic variables, current policies are not sustainable. Difficult decisions are unavoidable. The global financial crisis has cast a long shadow. It has profoundly affected the advanced economies, emerging markets and the balance between them. The implications for the international trade, the monetary and financial system, and global governance are far reaching. Drawing out those implications and beginning to comprehend what they mean for the future is the task the authors take up, collectively, in this volume.


The international community has experimented with a range of strategies to conserve biodiversity and curb tropical deforestation. But new logging investments in primary tropical forests, including those made in the name of "sustainability," are likely to do more harm than good. Conservationists should instead focus on more investments in protected areas and creative ways to prevent the spread of logging in these rapidly-declining ecosystems.


Introduction: Uncontrolled hypertension in hemodialysis (HD) patients is related to a variety of causes, of which dietary salt intake plays a major role. Excessive interdialytic weight gain (IDWG) with accompanying hypertension can lead to increase cardiovascular morbidity and mortality. Materials and Methods: We conducted a cross-sectional observational study to assess the prevalence of hypertension among patients on maintenance HD (MHD) and its relationship with daily sodium intake. We included participants who were getting MHD at out tertiary care center and in whom a digital brachial blood pressure (BP) was measured. Results: Of the 118 patients studied, 73 (61.9%) were male. AVF was the access for HD in 88 (74.6%) patients, 22 (18.6%) patients were getting HD through a permcath, and the rest through a temporary central venous HD catheter. HD was being done once a week for 3 (2.5%) patients, 80 (67.8%) patients were getting HD twice a week, and the others thrice a week. The mean pre-HD BP was 151.7/80 ± 22.55/12.8 mmHg, and the mean post-HD BP was 168/90.9 ± 23.7/11.3 mmHg. An IDWG of <2 kg was seen in 32 (32.2%) patients; the remaining patients had an IDWG of >2 kg. The mean IDWG was 2.41 kg. Seventeen (14.4%) patients were not on any antihypertensive medications, 48 (40.7%) patients were taking 1–2 antihypertensive drugs, and the rest were on >3 antihypertensive drugs. A urine output of <100 ml/day was present in 45 (38.1%) patients; the rest had a daily urine output of over 100 ml up to 1000–1200 ml. Nutritional assessment by a trained dietician showed that sodium intake ranged from 1700 mg to 2200 mg/day. Conclusion: Dietary sodium intake was controlled in our HD patients with the intake of 1700–2200 mg per day. The weight gain was excessive in 67.8% of our patients, Patients were ingesting 1–5 antihypertensive drugs of different classes and 14.4% were not on any antihypertensive drugs. Dialysis was being done twice a week for 67.8% of our patients and thrice a week for 29.7% of patients. We found hypertension in 85.6% of our cohort.


This chapter examines the development of the United Nations and the changes and challenges that it has faced since it was founded in 1945. It opens with three framing questions: Does the UN succeed in reconciling traditions of great power politics and traditions of universalism? Why has the UN become more involved in matters within states and what are the limits to this involvement? What are the UN's biggest successes and challenges in its efforts to prevent and resolve conflict and to promote sustainable development? The chapter proceeds by providing a brief history of the UN and its principal organs. It also considers the UN's role in the maintenance of international peace and security, and how the UN addresses issues relating to economic and social development. Two case studies are presented: the first is about UN peacekeeping in the Congo and the second is about the 2003 intervention in Iraq.


Metastasis of rectal cancer to the penis is a very rare condition with less than 40 cases found in the literature. The prognosis is poor and life expectancy is short. The mechanism of rectal cancer metastasis spread to penis is unknown. The most popular theory is retrograde venous spread. There are several treatment options, but no single treatment option has emerged with superior results. The authors report a case of a 41 old man who was diagnosed with rectal cancer, treated with neoadjuvant radiotherapy, underwent rectal resection, had adjuvant chemotherapy, and despite that, 2 years after had penal metastasis. After diagnosis, he survived 2 months.


Between January 1, 1979, and December 21, 1982, 2564 medically and obstetrically normal patients, admitted to the hospital with intact amniotic membranes during the latent phase of labor, were matched for spontaneous or artificial rupture of the membranes at similar cervical dilations. Spontaneous rupture of the membranes occurred earlier and was more likely in the latent phase of labor than was artificial rupture of membranes, which tended to occur nearer to or in the active phase of labor, and at lower pelvic stations. When matched by cervical dilation, spontaneous membrane rupture was associated with more rapid cervical dilation. Stepwise regression analysis confirmed that membrane rupture had a significant but small effect on labor length and rate of cervical dilation. Pelvic station and maternal parity had a smaller association with labor length than did membrane rupture. Cervical dilation at the time of membrane rupture appeared to be the most important factor associated with the length of labor.


ABSTRACT Prematurity coupled with the necessary clinical management of preterm (PT) infants introduces multiple factors that can interfere with microbial colonization. This study aimed to review the perinatal, physiological, pharmacological, dietary, and environmental factors associated with gut microbiota of PT infants. A total of 587 articles were retrieved from a search of multiple databases. Sixty studies were included in the review after removing duplicates and articles that did not meet the inclusion criteria. Review of this literature revealed that evidence converged on the effect of postnatal age, mode of delivery, use of antibiotics, and consumption of human milk in the composition of gut microbiota of PT infants. Less evidence was found for associations with race, sex, use of different fortifiers, macronutrients, and other medications. Future studies with rich metadata are needed to further explore the impact of the PT exposome on the development of the microbiota in this high-risk population.


Effect of Thermal Loading on the Performance of Horizontally Curved I-Girder Bridges Kevyn C. McBride As the amount of infrastructure in the United States continues to grow and older infrastructure is replaced or updated, bridge designers are faced with increasing space and geometrical limitations. Curved bridges have become a popular design alternative to the traditional straight girder or chorded bridges as they can provide the designer a more cost effective solution to complicated geometrical limitations or site irregularities. However, the volume of research and knowledge on the behavior of curved bridges is lacking compared to straight and chorded bridges, especially in terms of their response to changing thermal conditions. In most cases, it is assumed that bearing design allows expansion and contraction of the superstructure that relieves thermal stresses, but in reality this is rarely true. Bridge curvature complicates the structures response to thermal loading as the bearing configuration must handle a larger degree of expansion and contraction in the transverse, or radial, direction. Failure to properly design bridge bearings to accommodate thermal loads will lead to unaccounted for deformations and stresses in the superstructure. This research begins with two small scale parametric studies, performed using finite element modeling, that investigate how uniform thermal loading effects web deformations and web and flange stresses of a single curved steel I-girder and also of a section consisting of two curved steel I-girders connected with cross frames. The major focus of this research is a case study on the response of the Buffalo Creek Bridge, located in Logan County, West Virginia, to changing thermal conditions prior to any in-service loading. Two detailed 3D finite element models of the bridge were created, one modeling the piers as rigid members and one modeling the piers as flexible members, and both models were subjected to uniform temperature increase and decrease. Results indicate that uniform thermal loading leads to global and local buckling along the Igirder web centerlines, lateral distortional buckling in the web cross section, and thermal stresses in the I-girder webs. Although pier flexibility is shown to reduce the magnitude of thermally induced local and lateral distortional buckling and thermal stresses, I-girders experience larger global buckling when the piers are flexible. The results indicate that the introduction of pier flexibility did not relieve all the thermal stresses in the I-girder webs. At some locations, when the piers are rigid, the I-girder stresses exceed the AASHTO web bendbuckling capacity as well as the overall stress capacity of the section. This study shows that uniform thermal loading will lead to increased out-of-plane web deformations and increased web stress levels, which will both combine to decrease the load carrying capacity of the bridge when subject to subsequent live-loading conditions. This dissertation outlines a methodology that should be utilized by bridge designers and/or owners to validate the integrity of traditional bridge designs, especially in the case of more complicated bridge structures.


mua-3 is a Caenorhabditis elegans homolog of the mammalian fibrillin1, a monogenic cause of Marfan syndrome. We identified a new mutation of mua-3 that carries an in-frame deletion of 131 amino acids in the extracellular domain, which allows the mutants to survive in a temperature-dependent manner; at the permissive temperature, the mutants grow normally without obvious phenotypes, but at the nonpermissive temperature, more than 90% die during the L4 molt due to internal organ detachment. Using the temperature-sensitive lethality, we performed unbiased genetic screens to isolate suppressors to find genetic interactors of MUA-3. From two independent screens, we isolated mutations in dpy-17 as a suppressor. RNAi of dpy-17 in mua-3 rescued the lethality, confirming dpy-17 is a suppressor. dpy-17 encodes a collagen known to genetically interact with dpy-31, a BMP-1/Tolloid-like metalloprotease required for TGFβ activation in mammals. Human fibrillin1 mutants fail to sequester TGFβ2 leading to excess TGFβ signaling, which in turn contributes to Marfan syndrome or Marfan-related syndrome. Consistent with that, RNAi of dbl-1, a TGFβ homolog, modestly rescued the lethality of mua-3 mutants, suggesting a potentially conserved interaction between MUA-3 and a TGFβ pathway in C. elegans. Our work provides genetic evidence of the interaction between TGFβ and a fibrillin homolog, and thus provides a simple yet powerful genetic model to study TGFβ function in development of Marfan pathology.


In ovo feeding (IOF), injecting nutrients into the amnion, may improve growth performance by enhancing circulating IGF's and glycogen reserves. To test this hypothesis 400 Hybrid® turkey eggs were injected into the amnion with 1.5 ml saline solutions consisting of 4 IOF formulation treatments consisting of a factorial arrangement of 2 levels of arginine (ARG 0 or 0.7%) and 2 levels of HMB (0 or 0.1%) at 23 days (d) of incubation. At hatch, poults were fed ad libitum and bodyweights (BW), organ weights, total liver and pectoralis muscle (PM) glycogen were taken at hatch 3, 7, 10, and 14 d. Additionally, hepatic glucose-6phosphatase (G6P) activity was determined at hatch and 7 d. Heparinized blood samples were taken at hatch, 3 d, 7 d and 14 d and plasma was analyzed for IGF-I and IGF-II levels using an acid-ethanol extraction method. Although arginine had no affect on BW, there were significant main effects of HMB on increased BW from hatch through 14 d. Plasma IGF-I levels were significantly enhanced at hatch, 3 and 7 d in poults in ovo fed both ARG and HMB, but not when either factor was independent. Significant ARG X HMB effects were observed on IGF-II at hatch, 3d and 7d: without ARG, IGF-II was decreased by HMB, but it increased when added with ARG. All in ovo treatments increased G6P at hatch, while, G6P was depressed by HMB or ARG alone at 7 d. Total hepatic glycogen was increased only at hatch by HMB or ARG, but their effects were not additive as indicated by a significant ARG X HMB effect. In ovo administration of HMB and arginine enhances hepatic liver reserves, which may provide the fuel needed for rapid subsequent growth during the critical post-hatch period.


On this paper, a study of robot based remote laser welding technology for manufacturing light car body was conducted. Laser welding and industrial robotic systems were used with robot-based laser welding systems. The laser system used in this study was IPG's 1.6kW fiber laser (YLR-1600), while the robot system was Hyundai Heavy Industry's HX130-02 (payload : 130kg). The robot-based laser welding system was equipped with a laser scanner system for remote laser welding. Laser patterning on the fly needs to control some parameters to accomplish the desired shape and good quality of the welded pattern. The scan path and the mark speed as two control parameters of the laser scanner are numerically computed from pattern shape and robot motion. However, time-delay in operation of the laser scanner and the robot makes unexpected geometric error between the desired pattern and the welded pattern. To efficiently compensate the geometric error by time-delay, we divide the scan path for a pattern into the forward direction and the backward direction based on the direction of robot motion, where the time-delay is estimated through experimensts. The pattern sequence and the robot path is optimized to reduce total processing time. The proposed method is tested with various patterns and robot paths, and the welded patterns are validated by measuring their geometries and positions. Finally, the experimental results show that our method is suitable for laser patterning on the fly. The welding joints of steel plate and steel plate coated with zinc were butt and lapped joints. The quality testing of the laser welding was conducted by observing the shape of the beads on the plate and the cross-section of the welded parts, analyzing the results of mechanical tensile test. The remote laser welding system with laser scanner system is used to increase the processing speed and to improve the efficiency of processes. This paper proposes the robot-based remote laser welding system as a means of resolving the limited welding speed and accuracy of conventional laser welding systems.


The transmission capacity of an ad-hoc network is the maximum density of active transmitters per unit area, given an outage constraint at each receiver for a fixed rate of transmission. Assuming that the transmitter locations are distributed as a Poisson point process, this paper derives upper and lower bounds on the transmission capacity of an ad-hoc network when each node is equipped with multiple antennas. The transmitter either uses eigen multi-mode beamforming or a subset of its antennas without channel information to transmit multiple data streams, while the receiver uses partial zero forcing to cancel certain interferers using some of its spatial receive degrees of freedom (SRDOF). The receiver either cancels the nearest interferers or those interferers that maximize the post-cancellation signal-to-interference ratio. Using the obtained bounds, the optimal number of data streams to transmit, and the optimal SRDOF to use for interference cancellation are derived that provide the best scaling of the transmission capacity with the number of antennas. With beamforming, single data stream transmission together with using all but one SRDOF for interference cancellation is optimal, while without beamforming, single data stream transmission together with using a fraction of the total SRDOF for interference cancellation is optimal.


This paper investigates how housing and public transport planning in Stockholm has been integrated during the past 20 years through multi-level collaboration. Drawing upon how Stockholm has been portrayed in the literature on transit-oriented development (TOD), that is, as a successful case of integrated land use, housing and public transport planning, this paper suggests that multi-level collaboration in Stockholm's urban transformations has had its own challenges related to de-integration and reintegration. By including an exploration of the development of the metro system since the 1960s and onwards, the more recent processes of de-integration and reintegration emerge as endemic but often marginalised aspects of achieving TOD-like urban development. The paper contributes to previous studies by proposing three modalities of integration: (1) de-integration by agreement, (2) integration by collaboration, and (3) reintegration by intervention. These modes are not evaluative but should rather be used as a point of departure for future studies empirically investigating how integrated planning is achieved in contexts where transit-oriented development is contingent on multi-level collaboration.


This study was undertaken to determine which type 1 diabetes-associated autoantibodies and what clinical characteristics are most useful to identify patients with type 1(1/2) diabetes. We studied 125 patients, recently diagnosed clinically with type 2 diabetes for the presence of islet cell antibodies (ICA), insulin autoantibodies (IAA), antibodies to glutamic acid decarboxylase(GADAb), and IA-2a (IA-2Ab). Patients with a diagnosis of type 2 diabetes who met all of the following criteria at diagnosis were studied: age > or = 30 years, no history of ketonuria or ketoacidosis, and not requiring insulin treatment. Thirty-six patients (29%) were positive for at least 1 antibody. Thirty-two (26%) were ICA positive and 20 (16%) GADAb positive. Insulin autoantibodies and IA-2Ab occurred less frequently in 2 (1.6%) and 8 (6.4%) patients, respectively. There was no significant difference in the ages at diagnosis between the Ab(+) and Ab(-) patients, age in years (range) 47.2 (32 to 64) versus 51.2 (31 to 77), respectively, P =.06. Body mass index (BMI) was different in the 2 groups, with Ab(+) patients being less obese, BMI (range) 28.3 kg/m(2) (17.6 to 54.9) versus 32.0 kg/m(2) (19.2 to 68.8), respectively, P =.01. Clinical presentation of diabetes was more commonly symptomatic with polyuria and polydipsia in Ab(+) patients, while in Ab(-) patients, diagnosis was more often incidental, P =.002. However, more than 95% of patients overlapped in both age and BMI irrespective of antibody status. Similarly, 42% of Ab(+) patients had their diabetes diagnosed incidentally, while 29% of Ab(-) patients presented with polyuria and polydipsia. We therefore conclude that screening with antibodies, mainly ICA and GAD, but not age, BMI, or clinical presentation should be used to identify type 1(1/2) diabetes.


Tissue remodeling/fibrosis is a major feature of all fibrotic diseases, including idiopathic pulmonary fibrosis (IPF). It is underpinned by accumulating extracellular matrix (ECM) proteins. Fibulin-1c (Fbln1c) is a matricellular ECM protein associated with lung fibrosis in both humans and mice, and stabilizes collagen formation. Here we discovered that Fbln1c was increased in the lung tissues of IPF patients and experimental bleomycin-induced pulmonary fibrosis. Fbln1c-deficient (-/-) mice had reduced pulmonary remodeling/fibrosis and improved lung function after bleomycin challenge. Fbln1c interacted with fibronectin, periostin and tenascin-c in collagen deposits following bleomycin challenge. In a novel mechanism of fibrosis Fbln1c bound to latent transforming growth factor (TGF)-β binding protein-1 (LTBP1) to induce TGF-β activation, and mediated downstream Smad3 phosphorylation/signaling. This process increased myofibroblast numbers and collagen deposition. Fbln1 and LTBP1 co-localized in lung tissues from IPF patients. Thus, Fbln1c may be a novel driver of TGF-β-induced fibrosis involving LTBP1 and may be an upstream therapeutic target.


Allograft acceptance can be induced in the rat by pretransplant infusion of donor blood or spleen cells. Although promoting long-term acceptance, this treatment is also associated with chronic rejection. In this study, we show that a single administration of anti-donor MHC class II alloimmune serum on the day of transplantation results in indefinite survival of a MHC-mismatched kidney graft. Long-term recipients accept a donor-type skin graft and display no histological evidence of chronic rejection. The kidney grafts of tolerant animals display an accumulation of TCR C (cid:2) , FoxP3, and IDO transcripts. Moreover, as compared with syngeneic recipients, tolerant recipients harbor a large infiltrate of MHC class II (cid:1) cells and CD103 (cid:1) cells. In vitro, splenocytes from tolerant recipients exhibit decreased donor-specific proliferation, which is restored by depletion of non-T cells and partially restored by the blockade of IDO. Finally, splenocytes from tolerant recipients, but not purified T cell splenocytes, transfer donor-specific infectious tolerance without chronic rejection, after infusion into naive recipients, over two generations. However, splenocytes depleted of T cells or splenocytes depleted of CD103 (cid:1) cells fail to transfer tolerance. Collectively, these data show that a single administration of anti-donor MHC class II alloimmune serum induces a tolerant state characterized by an infiltration of the kidney graft by regulatory T cells and CD103 (cid:1) cells. These data also show that the transfer of tolerance requires the presence of both T cells and CD103 (cid:1) dendritic cells. The precise mechanism of cooperation of these two cell subsets remains to be defined. The Journal of Immunology, 2006, 176: 3915–3922.


Dust produced on seasonal road construction sites in Alaska is both a traffic safety and environmental concern. Dust emanating from unpaved road surfaces during construction severely reduces visibility and impacts stopping sight distance, and contributes to the local burden of PM 2.5, small particulates that present an important environmental air quality concern. This research aims to assist ADOT&PF in developing safe, efficient techniques for short-term dust suppression. Experts believe applying a dust-control palliative like calcium chloride, Enviroclean, Durasoil, or EK35 to the unpaved surface during road construction will solve the dust problem. This research will gather necessary information to determine when, what type, in what concentration, and how often the dust-control palliative should be applied. The amount and size of the dust particles, the time the surface is to remain unpaved, the makeup of the unpaved road surface, local environmental conditions, and the availability and cost of the dust control palliatives are factors to consider. The project is especially valuable because measurement systems used in other states involve special equipment and/or certification of observers, neither of which may be practical in Alaska with our remote locations and short construction season.


Hybridogenetic Rana esculenta tadpoles display tolerance to extreme environmental conditions and fit criteria of the "general‐purpose" genotype. A trade‐off between generality and competitive ability is assumed to occur in asexual species, but the evidence remains unclear. The purpose of my experiment was to test the competitive ability of hemiclonal hybrid Rana esculenta tadpoles relative to the parental species Rana lessonae. Mixed and single genotype populations of R. esculenta and R. lessonae tadpoles were reared at three densities in artificial ponds. Survival of R. esculenta was higher than for R. lessonae tadpoles, but did not differ among densities. Body size at metamorphosis was the same between genotypes, but decreased with increasing density. Larval period was not affected by density, but R. esculenta tended to metamorphose earlier than R. lessonae. Percentage of individuals metamorphosing was higher for R. esculenta at both medium and high densities, but the same as R. lessonae at the low density. The difference in survival, body size, and larval period between tadpoles reared in single and mixed genotype populations was unaffected by genotype or density. The difference in the percentage of metamorphs, however, was strongly affected. The percentage of hybrids metamorphosing was 9% above the responses of single genotype populations at the highest density. Conversely, the percentage of R. lessonae metamorphosing was 12% below the responses of single genotype populations at the same density. Hybrid success in this experiment further supports the criterion of a "general‐purpose" genotype without assumptions of reduced competitive ability.


With the rapid expansion of the Internet, Web servers have played a major role in accessing the enormous mass of Web pages to find the information needed by the user. Despite the exponential growth of the WWW, a very negligible amount of research has been conducted in Web server performance analysis with a view to improve the time a Web server takes to connect, receive, and analyze a request sent by the client and then sending the answer back to client. In this paper, we propose a multi-layer analytical approach to study the web server performance. A simple client-server model is used to represent the WWW server in order to demonstrate how to apply the proposed approach. We developed a systematic, analytical methodology to quantify the communication delay and queuing overhead in a distributed web server system. The approach uses the Computation Structure Model to derive server processing time required to process a request sent from a client and queueing model to analyze the communication between the clients and the server.


The undertaken research deals with an experimental determination of drag coefficient for five car models. Experiments were run within a subsonic aspiration wind tunnel, covering an air speed up to 33m/s.Drag coefficients of 0.45, 0.39, 0.53, 0.34 and 0.68 for Mercedes SEL300, Hyundai, Toyota, Pajero, and Mini-Bus models were obtained respectively. The flow field around the pre-quoted models with a qualitative description about the flow visualization for car models using a subsonic smoke wind tunnel has been accomplished.


Objectives Subtypes A1 and B are the most prevalent HIV-1 clades in Greece. Subtype A1 epidemic is highly monophyletic and corresponds to transmissions that occurred locally. Our aim in this molecular epidemiology analysis was to investigate the role of early treatment in preventing new HIV-1 transmissions. Methods Our analysis focused on 791 subtype A1 sequences from treatment-naïve individuals in Greece. Estimation of infection dates was performed by molecular clock calculations using Bayesian methods. We estimated the time interval between (1) the infection and sampling dates (linkage to care window), (2) the sampling dates and antiretroviral therapy (ART) initiation (treatment window), and (3) the infection dates and ART initiation (transmissibility window) for the study population. We also inferred the putative source of HIV infections between individuals of different groups divided according to the length of treatment, linkage to care or transmissibility window. Results A significant decline was detected for the treatment window during 2014–2015 versus the 2 previous years (p=0.0273), while the linkage to care interval remained unchanged during the study period. Inference of the putative source of HIV infections suggested that individuals with a recent diagnosis or narrow transmissibility window (time period between HIV infection and ART initiation) were not sources of HIV infections to other groups. Contrarily, a significant number of HIV infections originated from individuals with longer transmissibility window interval. Conclusions Our findings showed that the treatment window is decreasing over time, presumably due to the updated treatment guidelines. Our study also demonstrates that people treated earlier after infection do not transmit at high rates, thus documenting the benefits of early ART initiation in preventing ongoing HIV-1 transmission.


IL-1 beta is a stimulator of hematopoietic and inflammatory systems, and also acts as a radioprotector. After whole-body exposure to sublethal doses of ionizing radiation, the IL-1 beta mRNA level in spleen cells increases for a short time prior to regeneration of the spleen. We analyzed spleen cells of C3H/He mice after whole-body irradiation with 3 Gy x-rays to determine the cause of this short-term increase in the transcription level. An increase in the level of the message in spleen cells, found by Northern blot hybridization, reached its peak 5 to 7 days after irradiation. There was a low correlation between the curves of the mRNA level and the ratio of monocyte/macrophage lineage cells; a typical source of the message. Spleen macrophages that produce a large amount of the message were found 7 days after irradiation in an in situ hybridization experiment in which heterogeneous spleen cell populations were used. In contrast, spleen cells had no detectable levels of macrophages rich in IL-1 beta mRNA before and 17 days after irradiation. Additionally, the population of message-rich cells was 9.4% of the total number of monocytes/macrophages in the spleen. These results suggest that the short-term increase in IL-1 beta mRNA is a result of the heterogeneous differentiation of a subpopulation of spleen macrophages before regeneration of the spleen.


In the present investigation, 20 crosses of pearl millet (Pennisetum glaucum L. R. Br.) and their nine parental combinations consisting of four landrace-based and five elite exotic populations were evaluated in four contrasting seasons within arid ecosystem in order to study their response pattern to a wide range of environmental conditions. In most severe drought year, the landrace-based populations outyielded other two groups by a margin of 33–72%. In favourable conditions, exotic elite populations provided significantly higher grain yield than landraces with average degree of superiority being 25–45% across two seasons. The hybridization between landrace-based and elite populations resulted into enhanced adaptation range of crosses, beyond that of their parents. Individual landraces and elite populations differed significantly in their general combining ability (gca) effects though landraces had, in general, more pronounced gcaeffects than elite populations. Landrace Jakharana and elite population ESRC provided their crosses both adaptation to stress conditions and also higher potential productivity. On the contrary, BarPop was established as an appropriate parent for producing cultivars with general adaptation giving high stover yield but with a significant penalty for grain yield. ERajPop appeared more suitable for producing grain type materials while WRajPop emerged suitable to produce dual-purpose materials. The elite populations MC and EC had effects for specific adaptation to drought conditions for grain yield productivity. The popUlations BSEC established as promising parent for grain yield but not for stover yield across environments. Results demonstrated that there are exploitable differences among landraces and elite populations for their ability to produce genetic material with a variety of combinations for grain and stover productivity and with differential adaptation pattern. Implication of these findings in pearl millet breeding for arid zone conditions is discussed.


The urban contemporary economy, led by innovation growth, is grounded on a shift from a manufacturing based to knowledge-intensive and service-based industries. The now globalised process of production highlights the growing role of knowledgeable human capital as a primary driver of growth, where Creative Industries (CI) are often considered as avenues of development of this new economy. This CI discourse was developed as a political-economic project focusing on the economic contribution of the CI associated with the development of official statistics of added-value (creative GDP) and job creation. However, in recent years, some academics have started to question CI's benefits as only being one side of the coin. Problems such as gentrification, exacerbation of inequality, dislocation, labour precariousness, ownership and wealth concentration, are being more and more associated with CI's impacts; backlashes that oppose of that claims made during its original political conception.
Creative Labour (CL) studies -a subdiscipline of cultural studies- have grown as one of the most critical approaches to the CI. Precariousness, social inequality, gender and race discrimination, informality and individualisation are some of the 'troubles' that creative workers face according to these line of theories. Interestingly, both arguments have built their argumentations taking the same Western examples. On the one hand, the policy alleges that CI are sectors that contribute to social and economic development, and on the other hand, the critics from the academia led by CL studies that questioned this same capacity of development and the CL's undesirable social impacts, both argumentations have historically centred their assumptions in case studies notoriously produced in Euro- and North American creative-hubs. These two opposing positions have taken a universalist approach assuming the status of general truth, despite being generated from regionally limited empirical evidence.
Through a combination of a theoretical review, and a qualitative and a quantitative approach to the case study in Buenos Aires, this thesis hopes to contribute to the de-Westernisation of the CL studies, as well as to the deconstruction of the CI rhetoric by focusing on the creative labour in the city of Buenos Aires. This empirical study may suggest that the global theories may actually have different socio-economic impacts in different local contexts. CI are neither critical, nor can be disregarded, for social and economic change; and a call to a more nuanced perspective is much needed both in policy and academia to understand the specific contexts in the creative sectors.


A chiral honeycomb configuration is developed with embedded piezosensors and actuators for smart sandwich panel applications. The chiral honeycomb concept is made of repeating units of cylinders and plates (ligaments), featuring an in-plane negative Poisson's ratio. Rapid Prototyping vacuum-cast and FDM (Fusion Deposition Moulding) techniques are developed to embed micro fibres composites to be used for potential structural health monitoring (SHM) applications, and microwave absorption screens for electromagnetic compatibility. Finite Element models are also developed to prototype and simulate the response, sensing and actuation capability of the honeycombs for design purposes. Dynamic tests using scanning laser vibrometers and acoustic wave propagation are carried out to assess the feasibility of the concept.


Background Migraine without aura (MwoA) is a very frequent and remarkable comorbidity in patients with idiopathic/genetic epilepsy (I/GE). Frequently in clinical practice, diagnosis of MwoA may be challenging despite the guidance of current diagnostic criteria of the International Classification of Headache Disorders 3 (ICHD-3). In this study, we aimed to disclose the diagnostic gaps in the diagnosis of comorbid MwoA, using a zone concept, in patients with I/GEs with headaches who were diagnosed by an experienced headache expert. Methods In this multicenter study including 809 consecutive patients with a diagnosis of I/GE with or without headache, 163 patients who were diagnosed by an experienced headache expert as having a comorbid MwoA were reevaluated. Eligible patients were divided into three subgroups, namely, full diagnosis, zone I, and zone II according to their status of fulfilling the ICHD-3 criteria. A Classification and Regression Tree (CART) analysis was performed to bring out the meaningful predictors when evaluating patients with I/GEs for MwoA comorbidity, using the variables that were significant in the univariate analysis. Results Longer headache duration (<4 h) followed by throbbing pain, higher visual analog scale (VAS) scores, increase of pain by physical activity, nausea/vomiting, and photophobia and/or phonophobia are the main distinguishing clinical characteristics of comorbid MwoA in patients with I/GE, for being classified in the full diagnosis group. Despite being not a part of the main ICHD-3 criteria, the presence of associated symptoms mainly osmophobia and also vertigo/dizziness had the distinguishing capability of being classified into zone subgroups. The most common epilepsy syndromes fulfilling full diagnosis criteria (n = 62) in the CART analysis were 48.39% Juvenile myoclonic epilepsy followed by 25.81% epilepsy with generalized tonic-clonic seizures alone. Conclusion Longer headache duration, throbbing pain, increase of pain by physical activity, photophobia and/or phonophobia, presence of vertigo/dizziness, osmophobia, and higher VAS scores are the main supportive associated factors when applying the ICHD-3 criteria for the comorbid MwoA diagnosis in patients with I/GEs. Evaluating these characteristics could be helpful to close the diagnostic gaps in everyday clinical practice and fasten the diagnostic process of comorbid MwoA in patients with I/GEs.


Magnetic nanoparticles are a prospective class of materials for use in biomedicine as agents for magnetic resonance imagining (MRI) and hyperthermia treatment. However, synthesis of nanoparticles with high efficacy is resource-intensive experimental work. In turn, the use of machine learning (ML) methods is becoming useful in materials design and serves as a great approach to designing nanomagnets for biomedicine. In this work, for the first time, an ML-based approach is developed for the prediction of main parameters of material efficacy, i.e., specific absorption rate (SAR) for hyperthermia and r1 /r2 relaxivities in MRI, with parameters of nanoparticles as well as experimental conditions as descriptors. For that, a unique database with more than 980 magnetic nanoparticles collected from scientific articles is assembled. Using this data, several tree-based ensemble models are trained to predict SAR, r1 and r2 relaxivity. After hyperparameter optimization, models reach performances of R2 = 0.86, R2 = 0.78, and R2 = 0.75, respectively. Testing the models on samples unseen during the training shows no performance drops. Finally, DiMag, an open access resource created to guide synthesis of novel nanosized magnets for MRI and hyperthermia treatment with machine learning and boost development of new biomedical agents, is developed.


Abstract We analyze 51 medium-sized manufacturing industry companies identified by Ali-Yrkko and Rouvinen in their earlier research in 2015. Currently, out of these 51 companies with a staff of 250–499 employees in 2013, none are using digital platforms for business network management. It is typical for digital platforms that different actors can create, provide and maintain complementary products and services to the various distribution channels and markets, within the framework of mutually agreed business and contract rules, technical bourdary resources and a predefined user experience. Only seven companies (14%) offer digitally featured products and services. Digital product and service features are charted by using 26 different Finnish and English search terms, such as 'internet of things', 'sensor', 'cloud service' and 'preventive maintenance'. Finally we consider four strategic questions for open boundary resources.


Fruit disease cause a calamitous problem and results in economic and agricultural industry loss. Earlier detection of infected fruit had done manually but now with the advancement in technology image processing techniques was developed. There are two phases; first is for training and the other is for testing. In training phases, all the data related to the infected and non-infected fruit is stored and in testing phase, it is analyzed that whether the fruit is infected or not and if yes then by which disease. In this paper, the different existing techniques used to detect the infected fruit are discussed. These techniques are proved to be beneficial for the farmers as they help in detection of fruit disease in early stages.


A simple extended Kalman filter has been designed to track targets using outputs from a forward-looking infrared (FLIR) sensor as measurements. It exploits knowledge unused by current correlation trackers ¿ size, shape, and motion characteristics of target, and atmospheric jitter spectral description ¿ to yield enhanced performance. In order to track air-to-air missiles at close range, it incorportateson-line adaptation to target shape effects, changing target motion characteristics, and maximum signal intensity. It is shown to possess considerable performance potential for highly maneuverable targets despite background clutter.


Although imatinib therapy of chronic myelogenous leukemia is effective, the resistance to imatinib challenges the treatment of this disease. Therefore, search of novel drugs to overcome imatinib resistance is a critical issue in clinic. Withaferin A (WA), an extract of Withania somniferia, exhibits anticancer activity on a number of solid tumors. In this study, we investigate the effect of WA on imatinib-sensitive and -resistant CML cells. WA at low concentrations induces autophagy in imatinib- sensitive K562 cells. Co-treatment of chloroquine suppresses autophagy and switches WA-treated K562 cells to apoptosis. This data indicates that autophagy protects K562 cells from apoptosis induced by WA. However, we find that WA triggers caspase activation and apoptosis in imatinib-resistant T315I-positive cells and this effect is associated with downregulation of Akt activity. Treatment of the AKT inhibitor LY294002 also causes apoptosis in imatinib-resistant T315I- positive cells. Ectopic expression of constitutively active Akt reverses WA-induced apoptosis and caspase activation in imatinib-resistant T315I-positive cells. Molecular study demonstrates that WA represses the Akt signaling pathway by decreasing Akt expression. We find that WA causes Akt degradation through the ubiquitin- and proteasome-dependent pathway. More importantly, WA also induces AKT downregulation and apoptosis in primary CML cells. Taken together, our results suggest that imatinib-resistant T315I-positive cells are more addicted to Akt-dependent survival pathway and are more sensitive to WA. Therefore, WA can be useful for the treatment of imatinib-resistant CML. Citation Information: Clin Cancer Res 2010;16(14 Suppl):A4.


Microplastics (MPs) are small plastic particles released directly from the use of cosmetic products, or indirectly through the degradation of large plastic items under environmental conditions. Microplastics have been found in marine and freshwater environments around the world, raising concerns about the long term impact on animals and ecosystems in addition to recent discoveries of MPs entering the human food chain. The impacts of MP pollution on ecosystems and their functioning remain poorly quantified and there is a paucity of information on the impacts of MPs in freshwater ecosystems, despite the broad range of pathways through which MPs can proliferate and the extensive range of species which actively ingest MPs in these systems. This thesis aims to obtain key data on the uptake, fate and ecotoxicological impact of MPs on freshwater invertebrates. Initially, MP uptake and chronic toxicity tests were gathered by exposing the crustacean water flea Daphnia magna Straus 1820 (Cladocera) to polystyrene MPs of sizes 2 and 15 µm. The endpoints were mortality, growth and number of offspring. The results indicate that D. magna selectively uptake food particles over MPs, and that the toxicity was mainly linked to the availability of food. Moreover, a significant size dependent increase of toxicity was observed, with exposures to 2 µm sized particles being more toxic than 15 µm sized particles. Uptake, fate and toxicity of MPs were also studied in a holometabolous insect by exposing the common house mosquito Cu/ex pipiens Linnaeus 1758 (Diptera) to polystyrene MPs of sizes 2 and 15 µm. Results showed both particle sizes were readily taken up by larval mosquitoes then transferred to the adults via pupae. There were more transfer of MPs size 2 µm compare it to 15 µm without any effecting on mortality and weight of adults. This work is the first to demonstrate that MPs can be transferred ontogenically through organisms with complex life histories, presenting a potential pathway for dispersal of MPs into terrestrial environments. Laboratory studies were followed up with a field study exposing a small freshwater pond community to 15 µm polystyrene MPs. The results show that a high proportion of MPs accumulated in the sediment while only a small amount remained in the water column, with a significant correlation between the number of MPs in the water and the freshwater invertebrate. The presence of MPs had no real impact on the freshwater community, with season being a more important variable. Finally, the predatory ability of non-biting midge larvae, Chaoborus flavicans, towards larvae of C. pipiens mosquitoes loaded with 2 µm was quantitatively examined by linking MP trophic transfer with predation rates in a functional response framework. Results demonstrated a lack of effect of MPs on predation rates and correlation number of MPs transferred through predation.


The differentiation of cardiac fibroblasts (CFs) into myofibroblasts and the subsequent deposition of the extracellular matrix is associated with myocardial fibrosis following various types of myocardial injury. In the present study, the effect of curcumin, which is a pharmacologically-safe natural compound from the Curcuma longa herb, on transforming growth factor (TGF)-β1-induced CFs was investigated, and the underlying molecular mechanisms were examined. The expression levels of α-smooth muscle actin (SMA) stress fibers were investigated using western blotting and immunofluorescence in cultured neonatal rat CFs. Protein and mRNA expression levels of α-SMA and collagen type I (ColI) were determined by western blotting and reverse transcription-quantitative polymerase chain reaction. In addition, the activation of Smad2 and p38 was examined using western blotting. Curcumin, SB431542 (a TGF-βR-Smad2 inhibitor) and SB203580 (a p38 inhibitor) were used to inhibit the stimulation by TGF-β1. The results demonstrated that the TGF-β1-induced expression of α-SMA and ColI was suppressed by curcumin at the mRNA and protein levels, while SB431542 and SB203580 induced similar effects. Furthermore, phosphorylated Smad-2 and p38 were upregulated in TGF-β1-induced CFs, and these effects were substantially inhibited by curcumin administration. In conclusion, the results of the present study demonstrated that treatment with curcumin effectively suppresses TGF-β1-induced CF differentiation via Smad-2 and p38 signaling pathways. Thus, curcumin may be a potential therapeutic agent for the treatment of cardiac fibrosis.


Summary
• The enzymatic separation of physiologically active intraradical hyphae of arbuscular mycorrhiza (AM) fungi from host tissue is an effective way to analyse the physiological characteristics of intraradical hyphae.
• Applying this technique, first, both biomass and phosphorus (P) distribution were quantified in the intraradical and extraradical part of Gigaspora margarita colonizing onion. Second, the separated intraradical hyphae were incubated in vitro; efflux of phosphate from the hyphae and the hyphal polyphosphate (poly P) content were determined.
• A substantial proportion of P in mycorrhizal roots was fungal P, while the proportion of fungal biomass to root biomass was < 2%. Phosphate efflux and the decrease in poly-P content in the hyphae were both enhanced by the addition of glucose and 2-deoxyglucose, an analogue of glucose. The degrees of enhancement for phosphate efflux and poly-P decrease were comparable, suggesting that P efflux from intraradical hyphae was coupled with poly-P hydrolysis.
• Based on these findings, the translocation of P from fungus to host was estimated in relation to the distribution of hyphal P in extraradical and intraradical parts of the AM fungus.


This article reflects stories between us, four academics working in the fields of crafts and dance education. The unexpected encounters of our worlds and thoughts have given birth to these shared lines of inquiry. We fumble towards collaborative and embodied practices within academia. Drawing from some of the principles and ideas of the late 20th century French philosopher Gilles Deleuze, our collaboration has moved us to consider the indeterminate and continually shifting, nomadic process of not-knowing in the midst of sometimes striated academic (writing and presenting) practices. We have approached this process by putting into play simultaneously our multiple experiences, accounts, stories on be(com)ing academics in crafts and dance education. These fold in and back on one another and ripple into diverse (theoretical) discourses as well as (scholarly and artistic) practices. This, we believe, disrupts the comfortable, taken-for-granted (striated) academic spaces of reading, thinking, and knowing.


We present an active measurement study of the routing dynamics induced by AS-path prepending, a common method for controlling the inbound traffic of a multi-homed ISP. Unlike other inter-domain inbound traffic engineering methods, AS-path prepending not only provides network resilience but does not increase routing table size. Unfortunately, ISPs often perform prepending on a trail-and-error basis, which can lead to suboptimal results and to a large amount of network churn. We study these effects by actively injecting prepended routes into the Internet routing system using the RIPE NCC RIS route collectors and observing the resulting changes from almost 200 publicly-accessible sources of BGP information. Our results show that our prepending methods are simple and effective and that a small number of ASes is often responsible for large amounts of the route changes caused by prepending. Furthermore, we show that our methods are able to reveal hidden prepending policies to prepending and tie-breaking decisions made by ASes; this is useful for further predicting the behavior of prepending.1


Purpose

The purpose of this paper is to examine the significance of TripAdvisor on reputation within the hotel industry. TripAdvisor encapsulates key themes in establishing an online reputation strategy in an evolving digital landscape.

Design/methodology/approach

Through the use of an exploratory case study, data were gathered primarily by means of a series of expert interviews within the hotel industry in Cyprus, today a mature holiday destination in Europe. Further data collection included a document search of presentations, annual reports, past surveys and sales and marketing literature from the examined industry.

Findings

Hotel communication practitioners are fully aware of the impact of social media in managing reputation. Constant monitoring, prompt responses, training and transparency were identified as key factors. Online reputation management needs to be taken into consideration when designing a comprehensive integrated communication strategy.

Research limitations/implications

Congruence amongst interviewees in certain areas could be on account of the homogeneity of practitioners, of their background and training and of similar organisational cultures across the locale of study. This leads to limits in the generalisations from this study's findings.

Practical implications

Encouragement and training of employees were amongst the primary suggestions that emerged. An internal and external environmental scan, recognising possible strengths, weaknesses, opportunities and threats, which could assist in the effective engagement and monitoring of the organisation's online presence, were also suggested.

Originality/value

The uniqueness of the study lies in its exploration of reputation management of a well-known traveller's platform by addressing social media content in both a proactive and reactive manner.


Inverse kinematics algorithms are commonly used in robotic systems to achieve desired behavior, and several methods exist to ensure the achievement of numerous tasks simultaneously. The multiple task-priority inverse kinematics framework allows a consideration of tasks in a prioritized order by projecting task velocities through the null-spaces of higher priority tasks. Recent results have extended this framework from equality tasks to also handling set-based tasks, i.e. tasks that have an interval of valid values. The purpose of this paper is to further investigate and experimentally validate this algorithm and its properties. In particular, this paper presents experimental results where a number of both set-based and equality tasks have been implemented on the 6 Degree of Freedom UR5 which is an industrial robotic arm from Universal Robots. The experiments validate the theoretical results.


Angiogenesis is required for the development and biologic progression of glioblastoma multiforme (GBM), which is the most malignant infiltrative astrocytoma. Vascular endothelial growth factor (VEGF) plays a predominant role in the increased vascularity and endothelial cell proliferation in GBMs driven by the expression of pro-angiogenic cytokines. In this study, we employed a vector-encoded VEGF siRNA to impair VEGF secretion from U87 human glioblastoma cells. The direct intra-tumor injection of siRNA-encoding plasmid complexed with linear polyethylenimine (PEI) efficiently reduced the vascularization of treated tumors in xenografts established in SCID mice by subcutaneous inoculation of U87 cells, but was not able to reduce tumor growth. We then sought to strengthen the in vivo action of our siRNA by coupling it to a well known direct antiangiogenic agent, mouse interleukin 4 (mIL4). We infected U87 cells with a retroviral vector co-expressing the VEGF siRNA and mIL4 and produced stable cell lines that we used for an in vivo experiment of subcutaneous injection in SCID mice. In this setting, the concomitant expression of mIL4 and siRNA totally abolished the growth of subcutaneous tumors. These results suggest that our retroviral vector might be employed as a potential tool in future antiangiogenic gene therapy trials for glioblastoma.


Vegetables are grown worldwide and play an important role in human diets because they provide vitamins, minerals, dietary fiber, and phytochemicals. Vegetables are also associated with improvement of gastrointestinal health, good vision, and reduced risk of heart disease, stroke, chronic diseases such as diabetes, and some forms of cancer. The consumption and caloric contribution of vegetables to the diet vary widely with geographical region, nationality, local customs, and cuisine. Vegetable production suffers from many biotic stresses caused by pathogens, pests, and weeds and requires high amounts of plant protection products per hectare. US vegetables farmers are benefiting from growing transgenic squash cultivars resistant to Zucchini yellow mosaic virus, Watermelon mosaic virus, and Cucumber mosaic virus, which were deregulated and commercialized since the mid-1990s. Bt-sweet corn has also proven effective for control of some lepidopteran species and continues to be accepted in the fresh market in the United States, and Bt-fresh-market hybrids are released each year. Likewise, transgenic Bt-eggplant was bred to reduce pesticide use and hopefully will soon be grown by farmers in Asia. There are other vegetable crops in the pipeline that have been genetically modified to enhance their host plant resistance to insects and plant pathogens (including viruses), to show herbicide tolerance, and to improve features such as slow ripening that extends the shelf-life of the produce, high nutritional status, seedless fruit, and increased sweetness. Transgenic plant breeding therefore provides genetically enhanced seed embedded technology that contributes to integrated pest management in vegetable production by reducing pesticide sprays as well as improving food safety by minimizing pesticide residues. Furthermore, herbicide-tolerant transgenic crops can help reducing plough in fields, thereby saving fuel because of less tractor use, which also protects the structure of the soil by reducing its erosion. Transgenic vegetable crops could make important contributions to sustainable vegetable production in this 21st century. However, countries vary in their market standards of acceptance of transgenic crops. Biotechnology products will be successful if clear advantages and safety are demonstrated to both growers and consumers.


The current thesis presents fundamental studies of phthalocyanines (Pcs), a group of organic macro-cycle molecules. The use of phthalocyanine molecular films in devices with a variety of possible technological applications has been the reason of the many studies dedicated to such molecules during the last decades.Core and valence photoelectron spectroscopies (PES), X-ray absorption spectroscopy (XAS) and scanning tunneling microscopy (STM) techniques are used to study phthalocyanine molecules in gas phase and adsorbed on gold (111) and silicon Si(100)-2x1 substrates. Density functional theory (DFT) is used to obtain further insights in the electronic structure of the phthalocyanines.The aim of our studies is to get a deeper understanding into the molecule-molecule and molecule-substrate interactions, a fundamental requirement for improving the devices based on such molecular materials.Gas phase PES and XAS studies and single molecule DFT calculations are performed on the valence band (VB) of iron phthalocyanine (FePc), manganese phthalocyanine (MnPc) and metal-free phthalocyanine (H2Pc). The VB simulations have shown how the metal atom of the Pc influences the inner valence states of the molecules. The HOMO of the H2Pc and FePc is formed by mostly C2p states, whereas the HOMO of MnPc has mainly Mn3d character.PES studies of H2Pc on Au(111) have revealed the influence of the surface on the adsorption of the monolayer. XAS studies indicate formation of ordered monolayer with the Pc ligands parallel to the surface and the change of the molecular tilt angle with increasing thicknesses. For LuPc2 adsorbed on Au(111), STM study demonstrates a formation of bilayer instead of a monolayer.A comparison between the results of LuPc2 adsorbed on pristine or passivated Si(100)-2x1 confirmes the different reactivities of these surfaces: LuPc2 retains many molecular-like characters, when adsorbed on the innert passivated Si. Instead, on the more reactive pristine Si surface, the spectroscopic results have indicated a more significant interaction, possible hybridization and charge redistribution between the molecules and the surface. Moreover, STM images show a modification of the geometrical shape of the molecules, which are proposed to adsorb in two different geometries on the pristine Si surface.


Onions (Allium cepa L.) are the rich source of flavonoids, consisting mainly quercetin-3,4´-O-diglucoside (QDG) and quercetin-4´-O-monoglucoside (QMG), as major flavonoids. In the present study, we report the in vitro protective effect of different layers of onion extract on biomarkers of oxidative stress and on free radical induced oxidative hemolysis in erythrocytes. Results show a significant protection of oxidative stress by onion extract on erythrocyte subjected to tert-butyl hydroperoxide (t-BHP) treatment, as evidenced by the decrease in malondialdehyde (MDA) and increase in reduced glutathione (GSH) content. Onion extracts also showed significant protection of the erythrocyte from oxidative hemolysis. Quercetin (at micromolar concentration) showed significant antioxidant effect in protecting erythrocytes from t-BHP induced oxidative changes. The results are more pronounced for outer layers as compared to inner layers, suggesting that the outermost living layers had higher antioxidant activities compared to innermost layers.


In the last decades the demand for animal source food (ASF) has increased. In response to a rising demand for ASF, animal numbers and animal productivity increased, due to science and technological developments. Currently we see that the demand for ASF is stagnating or decreasing due to socio-economic factors like environmental concerns, human health concerns and changing socio-cultural values (animal welfare). Given current high consumption levels of ASF in Europe, two main strategies can be followed to come to healthy and sustainable diets: reducing the impact of livestock production per kg of output by sustainable intensification, or improve human health and the environment by changing dietary patterns.


In 1998, the American anthropologist Will Roscoe referred to pre-colonial North America as "the queerest continent on the planet" (Roscoe 1998, 4), expressing a more universally accepted idea that before settlers arrived in North America, Indigenous peoples embraced and celebrated queer and trans people. Building on this anachronistic assumption, this article investigates the historical and anthropological constructions of the 'Sacred Queer Native' trope and argues that its attendant discourses perpetuate an idea of the 'Sacred Queer Native' figure as a mythological Noble Savage doomed to perish. The anthropological accounts therefore serve as settler colonial tools of elimination, relegating (queer) Indigenous peoples to the past, while emulating their 'queerness' in order to legitimize modern Lesbian and gay identities. At the same time, Indigenous poets celebrate(d) the same figuration as a strategy for empowerment, reclaiming historical positions of power and sovereignty through celebratory and often erotic poetries that directly and indirectly critique settler colonial heteropatriarchy. The article concludes that the contentions over the figure of the Sacred Queer Native and its anti-colonial, Indigenouscounter-construction, Two-Spirit, illustrates both the constructedness of gender and sexualities and the need for continued critique in the field.


This paper examines the design philosophy of classical Suzhou gardens in China, with regards to their natural and architectural elements on the moral education of the inhabitants. Through studying the metaphorical connotations of garden elements, the author reflects on their propositions for contemporary environmental ethics, aesthetic appreciation, and moral education. As such, the article is structured around three themes: classical Chinese gardens cultivating environmental ethics, classical Chinese gardens cultivating an appreciation of aesthetics, and classical Chinese gardens cultivating moral characters. The essay finally suggests that classical Chinese gardens are landscapes for self-cultivation.


Ocimum basilicum belongs to the family Lamiaceae which is known to have anticancer and many other bioactivities. Phoma eupyrena, Emericella nidulans lata and Chaetomium olivaccium were isolated from the different organs of the Basil plant. Root, stem and leaf's endophytes extracts of this plant, were tested for phytochemical constituents, antioxidant and anti- α-amylase activities. Phytochemical screening of fungal endophyte extracts revealed the presence of alkaloids, steroids, terpenoids and saponins.  Quantitative determination of total phenolics, total flavonoids and various in vitro antioxidant  activities (DPPH, H2O2, α-Amylase,  reducing power and antioxidant capacity) of methanolic extract was carried out using colorimetric methods.  The results of this study displayed that antioxidant activities differ significantly in the endophyte's extract of the plant. The flavonoid content appeared in phoma extract only. The  IC50 values  for  DPPH  radical scavenging was in the order of  PHE > EME >  CHE, the values  were  63.3% >  56.2% > 26.8%  at 100µg/ml, respectively.  The scavenging activity for hydrogen peroxide of various extracts  was in the order of PHE  > CHE > EME respectively. The highest inhibitory activity of α-amylase was in PHE followed by EME then CHE. Finally, we concluded that Ocimum basilium has strong scavenging activity and phytochemical contents, and confirm this plant may be good as antitumor and also is very useful for the management of other diseases.


A fundamental problem in estuarine microbiology studies is the accurate determination of the density in the water column of both free-living bacteria and those attached to suspended particulate matter. When a water sample is filtered and the filter is viewed by epifluorescence microscopy, counts can be made of the numbers of bacteria which are seen on the filter background (free-living) and those which appear to lie on sediment particles (both free-living and attached). With only the additional knowledge of the proportion of the filter area covered by particles (a quantity that is straightforwardly determined by stereological point counting), results from geometric probability were used to determine the expected number of bacteria which are hidden by particles and hence to provide an estimation scheme for the true densities of free-living and attached bacteria. Variance equations based on a Taylor series are given, and a partial check of the method is attempted with controlled mixtures of bacteria and sediment. An alternative procedure is also proposed, in which the natural attached/free-living ratio is altered by an intervention experiment, allowing an estimation which is less model dependent but more labor intensive. Both methods are applied to a series of samples from the Tamar estuary, United Kingdom, taken in April 1985. A notable conclusion is that there are always more free-living than attached bacteria in the water column throughout the estuary.


In humans and other animals, behavioral responses to threatening stimuli are an important component of temperament. Among children, extreme behavioral inhibition elicited by novel situations or strangers predicts the subsequent development of anxiety disorders and depression. Genetic differences among children are known to affect risk of developing behavioral inhibition and anxiety, but a more detailed understanding of genetic influences on susceptibility is needed. Nonhuman primates provide valuable models for studying the mechanisms underlying human behavior. Individual differences in threat‐induced behavioral inhibition (freezing behavior) in young rhesus monkeys are stable over time and reflect individual levels of anxiety. This study used the well‐established human intruder paradigm to elicit threat‐induced freezing behavior and other behavioral responses in 285 young pedigreed rhesus monkeys. We examined the overall influence of quantitative genetic variation and tested the specific effect of the serotonin transporter promoter repeat polymorphism. Quantitative genetic analyses indicated that the residual heritability of freezing duration (behavioral inhibition) is h2 = 0.384 (P = 0.012) and of 'orienting to the intruder' (vigilance) is h2 = 0.908 (P = 0.00001). Duration of locomotion and hostility and frequency of cooing were not significantly heritable. The serotonin transporter polymorphism showed no significant effect on either freezing or orienting to the intruder. Our results suggest that this species could be used for detailed studies of genetic mechanisms influencing extreme behavioral inhibition, including the identification of specific genes that are involved in predisposing individuals to such behavior.


Background: Diurnal fluctuations in clotting factors, occurrence of thrombosis, and stroke have been reported. We sought to evaluate the distribution of stroke occurrence and differences in stroke characteristics and outcomes in a biracial population. Methods: Patients presenting to our center with acute ischemic stroke of known symptom onset were identified by retrospective chart review. Patients were grouped into one of four onset periods: 00:01-06:00, 06:01-12:00, 12:01-18:00, and 18:01-00:00. We compared demographics, baseline stroke severity, blood pressure and glucose levels, IV tPA treatment rates, stroke etiology, complications, and early clinical outcomes. Results: The 244 patients with a known time of onset were included in analyses; the distribution of stroke onset and comparison of other collected variables are demonstrated in the figure and table, respectively. Stroke onset 00:01-06:00 was less frequent, but associated with significantly higher median NIHSS score (p=0.005). Patients with stroke onset 00:01-06:00 were more often African-American, had atherothrombotic mechanisms (large artery or small artery infarctions), received IV tPA, and had reduced frequency of good mRS, though statistical significance was not achieved. Time interval of stroke onset was not an independent predictor of death, good outcome (mRS 0-2), or favorable discharge disposition (home or inpatient rehabilitation). Discussion: The most severe ischemic strokes occurred in early AM hours, but were less common than stroke onset during other time intervals. A larger sample is required to determine why ischemic stroke is more severe with early AM onset, if blacks are more susceptible to early AM stroke, and if early AM stroke is less responsive to tPA.


A phospholipid requirement of 2-acetamidofluorene N- and ring-hydroxylation was investigated with partially delipidated microsomal fraction from livers of 3-methylcholanthrene-pretreated hamsters. Butan-1-ol extraction of microsomal fraction removed 90% of the total lipid content without any appreciable effect on microsomal proteins. Such extracted microsomal fractions had much lower capacity to N- and ring-hydroxylate 2-acetamidofluorene: 25 and 44% of control respectively. Addition of butan-1-ol-extracted total lipid restored both oxidations to some extent, whereas addition of phosphatidylcholine fraction restored both oxidations almost completely. Addition of synthetic phospholipid, dilauroyl phosphatidylcholine, restored both oxidations to a large extent, whereas synthetic dipalmitoyl or distearoyl phosphatidylcholine was ineffective in restoring these oxidations.


Low- and full-fat cheeses were fermented by Lactobacillus acidophilus and adjunct cultures Streptococcus thermophilus. After ripening for 90d at 4°C, the main flavor substances were determined by gas chromatograph. The results showed that more than 28 main flavor components were founded in full-fat cheese, and at least 19 were founded in low-fat cheese. In low-fat cheese, there was a higher content of 9-(Z)- octadecenoic acid and 10-hydroxy-octanoic acid methyl ester, which their relative mass fraction were 19.20% and 18.79% respectively. In full-fat cheese, there was a higher content of hexadecanoic acid methyl ester and 9-Octadecenoic acid(Z)-methyl ester, which their relative mass fraction were 24.27%and 23.37% respectively.


Abstract Hydropower development clearly has a significant role to play in the closer integration of different parts of the Himalayas and in facilitating downstream benefits throughout South Asia. However, the neo-liberal approach to infrastructure-led growth frequently overlooks the significant social, economic and political issues associated with this model of development in the region. Furthermore, the ongoing securitisation of water constrains the terms of debate under the guise of a unified national interest and enables large-scale dams to be constructed without due process. To desecuritise water in the Himalayas is to open up this dialogue and in so doing create the conditions for just and sustainable development.


The paper presents the results of the comparison of the achromatic simultaneous contrast effect on two different printing substrates. The presented samples contain 10 different variations of background lightness and have a value range from 10 to 100% RTV in increments of 10% RTV (external square) that surrounds the primary stimulus (internal square) of the constant lightness of 50% RTV on a specifically constructed design. In the psychophysical visual experiment conducted on ten subjects for each sample, the intensity and direction of the variation of the occurrence of lightness in the CIEΔE00 system has been determined. The verified technique of simultaneous binocular harmonization was used. The results of the statistical analysis give the direction and intensity of the effect on a coated and uncoated substrate. The conducted Student's t-test of the comparison of arithmetic means of lightness variations clearly shows that the effect of simultaneous contrast is more strongly manifested on an uncoated substrate on samples with 10%, 20%, 40%, 50%, 90% and 100% of the RTV of the background (p<0.05). On samples with 30%, 60%, 70% and 80% of the RTV of the background, there are no statistically significant differences between the samples (p<0.05).


Background/Aims: Balloon-assisted endoscopy allows us to diagnose gastrointestinal (GI) stromal tumors (GISTs) in the small bowel including endoscopic ultrasonography and taking biopsy. The aim of this study was to retrospectively clarify clinical and endoscopic characteristics of small bowel GISTs using double-balloon endoscopy (DBE). Methods: We reviewed 25 patients who underwent DBE and were diagnosed with GISTs. The risk of GISTs was stratified using the National Institute of Health (NIH) consensus criteria. We evaluated the available DBE route, the diagnostic yield of biopsy examination, and the relationship between endoscopic characteristics and recurrence-free survival (RFS). Results: Of all 25 patients, 23 had any endoscopic findings related to GIST. They were detected using the antegrade approach in 91.3%. GISTs were classified into high risk (n = 7), intermediate risk (n = 4), low risk (n = 10), and very low risk (n = 4) based on surgical specimens. The diagnostic result of biopsy was 46.7% (7/15), but it was difficult to predict the NIH risk group. Endoscopic characteristics were not associated with RFS. The NIH risk group was significantly associated with RFS. Conclusions: Antegrade DBE was preferable for exploring small bowel GIST, but the diagnostic ability of biopsy examination was limited.


Background: Dengue virus (DENV) causes up to 390 million infections yearly, of which 96 million are clinically manifested. Approximately 500,000 people with severe dengue require hospitalization each year and there are at least 25,000 deaths among children from Asian and Latin American countries. DENV is endemic in more than 100 countries. Chemical and biological controls have been implemented in targeting Aedes aegypti and Aedes albopictus mosquitoes, but these control practices failed to stem the dengue transmission. As a result, dengue vaccine has become a potential option recommended by WHO to be implemented in dengue endemic regions. Currently, several vaccine candidates are being evaluated in clinical studies. Amongst the vaccine candidates, live attenuated vaccines (LAV) are the furthest along the development pipeline. The most advanced vaccine, CYD-TDV (Dengvaxia) has been licensed in 19 countries. Several other live attenuated vaccines, as well as DNA, subunit, inactivated virus, viral-vectored and subunit-based vaccines, are under development and evaluation in preclinical or clinical studies. Each of the live-attenuated vaccine candidates targets on molecular determinants of virulence in DENV, with the emphasis on attenuating the DENV and inducing a balanced tetravalent immune response against all the four dengue serotypes.
Aims: This review presents several different vaccine approaches and their construction strategies, providing an insight into the development of future dengue vaccines such as live attenuated vaccines, DNA vaccines, sub-unit protein vaccines and viral vectored vaccines.
Methods: Recent development status of dengue vaccine candidates was reviewed based on the published data and an online registry for clinical trials (ClinicalTrials.gov) which is run by the U.S. National Library of Medicine, National Institutes of Health.
Results: Increasing burden of dengue necessitates the development of a safe and efficacious tetravalent dengue vaccine. Various vaccine strategies are being developed for disease prevention, each has its own strengths and limitations. Dengvaxia is a licensed dengue vaccine in 19 countries but it has been suspended in the Philippines in December 2017 due to its potential risks in children <9 years of age and seronegative vaccinees. TDV was able to elicit neutralizing antibodies as well as cross protective T cell responses against all four dengue serotypes and protected mice and nonhuman primates against challenge with wild type DENV. Seroconversion was achieved in both seronegative and seropositive adults and children <1.5 years of age with a single dose. TV003/TV005 was able to elicit multifunctional T cell response in addition to the humoral response. Seroconversion in 90 per cent of seronegative adults was observed with a single dose of TV005. However, eliciting a balanced immune response against all the four dengue serotypes remained the major impediment.
Conclusion : Dengvaxia has been launched in 11 countries but it has been withdrawn in the Philippines due to adverse effects in young children. Experimental vaccines such as TDV and TV003/TV005 are live attenuated vaccines which are currently in phase III clinical trials. Continued field trials will further our understanding of immune correlates of protection or risk.


This work represents an attempt to understand the nature of micron and attrition milled nano-sized titanium powders on two different aspects, i.e., pressure-induced phase change and thermal expansion. Contraction in the volume of unit cell in terms of decrease in interplaner spacing ( d ) has been observed in both powders and tends to restore upon annealing. At a given pressure, nano titanium shows a smaller decrease in d relative to micron titanium. The stress analysis of the compacts indicates higher value of residual stresses and deformations in micron powder than in nano powder. The dilatometric study reveals, first, the release of internal stresses and entrapped gases causes huge expansion in nanopowder compacts during heating. Secondly, there is no significant difference in the expansion coefficients of sintered micro- and nanocrystalline titanium samples.


A model of structural transformations of amorphous into quasi‐amorphous BaTiO3 is suggested. The model is based on previously published data and on X‐ray photoelectron spectroscopy data presented in the current report. Both amorphous and quasi‐amorphous phases of BaTiO3 are made up of a network of slightly distorted TiO6 octahedra connected in three different ways: by apices (akin to perovskite), edges, and faces. Ba ions in these phases are located in the voids between the octahedra, which is a nonperovskite environment. These data also suggest that Ba ions compensate electrical‐charge imbalance incurred by randomly connected octahedra and, thereby, stabilize the TiO6 network. Upon heating, the edge‐to‐edge and face‐to‐face connections between TiO6 octahedra are severed and then reconnected via apices. Severing the connections between TiO6 octahedra requires a volume increase, suppression of which keeps some of the edge‐to‐edge and face‐to‐face connections intact. Transformation of the amorphous thin films into the quasi‐amorphous phase occurs during pulling through a steep temperature gradient. During this process, the volume increase is inhomogeneous and causes both highly anisotropic strain and a strain gradient. The strain gradient favors breaking those connections, which aligns the distorted TiO6 octahedra along the direction of the gradient. As a result, the structure becomes not only anisotropic and non‐centrosymmetric, but also acquires macroscopic polarization. Other compounds may also form a quasi‐amorphous phase, providing that they satisfy the set of conditions derived from the suggested model.


c PhD student in International Relations, Kharazmi University, Iran C H R O N I C L E A B S T R A C T This paper investigates the role of exports in the regional markets on the performance of supply chain. The study first determines critical variables affecting exports for entering into the regional markets and then measures the effects of these variables on the effectiveness of supply chain performance. The study uses two questionnaires, one for measuring the effects of various factors on export development and the other for measuring supply chain performance in Likert scale. Cronbach alpha for the mentioned questionnaires were calculated as 0.84 and 0.78, respectively. The population of the survey includes all small and medium enterprises active in city of Tehran, Iran and the study selects a sample of 250 people as a sample size. Using factor analysis, the study has determined seven factors including product development, government support, strategic orientation, customer satisfaction, competitive pressures, organizational capability and distribution strategies for entry into regional markets. In addition, the implementation of structural equation modeling has disclosed that product development and distribution strategies maintained the highest impact on export activities.


This study aims to explore the pharmacodynamics of chelidonine, the active ingredient in greater celandine (Chelidonium majus L.), on in vitro rat bladder and trachea tissue, and evaluate its cell protective effects on primary lung and kidney cell lines. The study was carried out via repeated applications of acetylcholine, atropine, verapamil and oxybutynin, alongside Ca++ in a calcium-free environment, on urinary bladder tissue, and repeated applications of acetylcholine, atropine, carbachol and mecamylamine on trachea tissue. At the same time, cell viability and catalase and superoxide dismutase activity was measured on primary cell lines obtained from lung and kidney tissue samples. The study has shown that chelidonine has a relaxant effect on bladder and trachea tissues, and it may be mentioned that this effect is produced via muscarinic receptors. In addition, chelidonin caused a statistically insignificant increase in cell viability in primary lung and kidney cell lines at increasing doses (1 and 4 μg/ mL), but this increase remained at the control group level. In contrast, chelidonin caused a significant decrease in cell viability at the same cell lines at doses of 8 and 16 μg/mL. In conclusion, it is suggested that greater celandine, which is used in folk medicine, and its active ingredient chelidonine might have beneficial effects on asthma, urinary incontinence and other urinary tract and respiratory diseases among others.


Global Climate Models (GCM) can provide reliable climate information on global, continental and large regional scales covering what could be a vastly differing landscape (from very mountainous to flat coastal plains for example) with greatly varying potential for floods, droughts or other extreme events. Horizontal resolution limits the possibility to address smaller scale ranging from regional to local. Regional Climate Models (RCM) applied with higher spatial resolution over a limited area and driven by GCMs can provide more appropriate information on such smaller scales supporting more detailed impact and adaptation assessment and planning. Therefore Regional Climate Models (RCMs) have an important role to play by providing projections with much greater detail and more accurate representation of localized extreme events.


A stochastic background of gravitational waves with astrophysical origins may have resulted from the superposition of a large number of unresolved sources since the beginning of stellar activity.Its detection would put very strong constraints on the physical properties of compact objects,the initial mass function and star formation history.On the other hand,it could be a 'noise' that would mask the stochastic background of its cosmological origin.We review the main astrophysical processes which are able to produce a stochastic background and discuss how they may differ from the primordial contribution in terms of statistical properties.Current detection methods are also presented.


This review provides an overview of the current status of the published data on diffusion magnetic resonance (MR) imaging of chest tumors. Diffusion MR imaging is a non-invasive imaging technique that measures the differences in water mobility in different tissue microstructures and quantifies them based on the apparent diffusion coefficient. Diffusion MR imaging has been used for the characterization, grading and staging of lung cancer as well as for differentiating central tumors from post-obstructive consolidation. In addition, this technique helps in differentiating malignant from benign pulmonary and mediastinal tumors as well as in the characterization of pleural mesothelioma and effusion. Diffusion MR imaging can be incorporated into routine morphological MR imaging to improve radiologist confidence in image interpretation and to provide functional assessments of chest tumors during the same examination. Diffusion MR imaging could be used in the future as a functional imaging technique for tumors of the chest.


The density, population size-structure, and fecundity of the exotic snail Potamopyrgus antipodarum are described, for a period of two years, on two shores subject to different levels of disturbance in Lake Purrumbete. The population dynamics of Potamopyrgus antipodarum showed the same seasonal pattern in the numbers of embryos carried per individual female in both years, but seasonal patterns in density and potential reproductive output of the population differed between shores. Densities of Potamopyrgus antipodarum were high, with a trend for highest densities to occur in spring and summer. The population consisted almost entirely of females, which is indicative of a parthenogenic mode of reproduction. Fecundity was high, with the number of embryos carried per female peaking in spring. In summer, the population was dominated by small individuals, but some small snails were present at all times of the year. Potamopyrgus antipodarum was found to be a very successful invader of Lake Purrumbete, with high densities, high fecundity, parthenogenesis and the presence of embryos throughout the year contributing to this success.


Vasculitis is characterized by inflammation of the blood vessel wall, which can lead to vascular occlusion, ischaemia, and end-organ injury. The exact causes of most of the primary systemic vasculitides (PSV) are not fully understood; a monogenic cause is strongly suspected in a minority of cases, particularly when similar features occur in first-degree relatives; and/or disease onset is very early in life. The central hypothesis to this thesis is that there are novel monogenic causes of vasculitis affecting the young that may be revealed using next generation sequencing (NGS). The aim of this study was therefore to: 1. use NGS to identify novel candidate genes that could cause vasculitis in children; and 2. to study the potential pathogenic role of any candidate genes identified. Seven probands from 6 families (Sielicka et al.) with different phenotypes of vasculitis were recruited. Whole exome sequencing (WES) was performed in all probands. Homozygous or compound heterozygous loss-of-function mutations in CECR1 (cat eye syndrome chromosome region, candidate 1), which encodes adenosine deaminase type 2, were identified in 4 probands of family A, B and C causing deficiency of adenosine deaminase type 2 (DADA2). Clinical features of DADA2 resemble polyarteritis nodosa. Further investigation in relatives of the probands, and a cohort of childhood PAN revealed an additional 17 affected individuals, 8 of whom were asymptomatic at the time of study. The main clinical features of DADA2 were: cutaneous involvement (66.7%), neurological involvement (52.4%) and immunological involvement (33.3%). Disease was well controlled in 11 patients using anti-TNF-α therapy. Functional studies revealed that ADA2 enzyme activity and CECR1 mRNA expression were decreased in DADA2 in all subjects with homozygous or compound heterozygous mutations (irrespective of whether they were symptomatic or not); and revealed important age-dependent physiological changes in ADA2 activity of healthy controls. DADA2 affects the function and polarisation of macrophages, and may represent a novel vasoprotective pathway. A novel homozygous missense mutation in Protein Kinase C Delta gene (PRKCD) c.1294G>T;p.Gly432Trp was identified in the proband of family D and her sister, who presented with early onset juvenile systemic lupus erythematosus. PRKCD encodes protein kinase C delta, which plays a role in apoptosis and proliferation of multiple cells, including B lymphocytes. The proband of family E presented with early onset cutaneous leukocytoclastic vasculitis, and recurrent bacterial infections. Immunological studies revealed abnormal functional complement assay. A novel homozygous mutation in the complement factor I gene (CFI) was identified. Complement factor I is a C3b/C4b inactivator. The phenotype described herein is therefore novel, since cutaneous leukocytoclastic vasculitis is not typical of CFI deficiency, although recurrent bacterial infections are recognized. The proband of family F presented with digital vasculitis, recurrent infections, and absence of serum C1q. C1q is a protein in the classical complement pathway and mainly produced by macrophages. No mutation in C1q genes was identified using standard Sanger sequencing, or from WES. RNA sequencing also revealed no mutation in any C1q gene; and mRNA expression of all 3 C1q genes was normal. C1q staining of macrophages (using confocal microscopy and intracellular flow cytometric analysis) revealed intracellular accumulation of C1q, suggesting a new syndrome of impaired C1q release, and functional C1q deficiency. These studies confirm my central hypothesis that monogenic vasculitides are an important clinical concern in some children; and yet again demonstrate the diagnostic utility of NGS. Future studies leading directly from the work described in this thesis are also considered.


Edited by Patti J Thureen and William W Hay. Published by Cambridge University Press, New York, 2006, £165.00 (US$300.00), pp 692. Hardback. ISBN 0-5218-2455-9.

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In an age when babies are surviving at earlier gestations, it is vital that we have an accurate and up-to-date understanding of their extrauterine metabolic and nutritional requirements. We now know that optimum fetal and neonatal nutrition is reflected in long-term health, therefore all the information and advice that we gather can only be beneficial. This book has it all.

Reference books are becoming less fashionable as the internet has come to the forefront. However, I think this is a book which should be part of …

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Energy consumed by computation and cooling represents the greatest percentage of the average energy consumed in a data centre. As these two aspects are not always coordinated, energy consumption is not optimised. Data centres lack an integrated system that jointly optimises and controls all the operations in order to reduce energy consumption and increase the usage of renewable sources. GENiC is addressing this through a novel scalable, integrate energy management and control platform for data centre wide optimisation. We have implemented a prototype of the platform together with workload and thermal management algorithms. We evaluate the algorithms in a simulation based model of a real data centre. Results show significant energy savings potential, in some cases up to 40%, by integrating workload and thermal management.