6-Mercaptopurine ribonucleoside 59-triphosphate was found to be an inhibitor of DNA-dependent RNA polymerases from Escherichia coli and chicken myeloblastosis cells. The inhibitor appears to compete with GTP for its binding to RNA polymerase, resulting in a reduction of RNA chain initiations. Neither 6-mercaptopurine ribonucleoside nor its monophosphate derivative caused the inhibition. These studies suggest that the antineoplastic action of 6-mercaptopurine may in part be owing to the inhibition of the activity of DNA-dependent RNA polymerase, resulting in an inhibition of cellular RNA synthesis.


There are two fundamental elements in building the strength of a country, the economy and defense. Both of these variables influence each other. A country with good economy will be able to provide sufficient defense budget. Meanwhile, good defense can provide indirect effect on the economy. The indirect impact of defense budget to economic growth is through investment. The study was conducted to examine whether the defense budget effected on the economy, particularly investment. Single equation set up to capture the effect of the defense budget on investment individually. The empirical results indicate that, the effect of the increase in the defense budget and the change in non-defense, led to the crowding out effect on investment.


In this study, I use a revised approach of the Frankfurt School in order to critically assess a recent massively multiplayer online video game, Guild Wars 2. Starting with a brief historical overview of the Frankfurt School, I proceed by applying a revision of the school's main contributions to analyzing Guild Wars 2. This includes an integration of processes of production and distribution, various levels of textual analysis, and audience reception. My main method of investigation is long-term participant observation, and throughout the article, I will argue for the use of such qualitative methods in the critical study of video games. Doing this, I have found that Guild Wars 2 offers a complex experience with enormous appeal and creative potential, while at other times being surprisingly restrictive, culminating in what Walter Benjamin would call a dialectical fairy scene.


A quantitative and qualitative study of indoor air in two hospitals in Ekpoma, Edo State was carried out. Samples were collected using the settle plate method for the enumeration of bacterial and fungal isolates. This study is aimed at checking the microbial concentration of indoor air as it relates to hospital type, ward and sampling time. The total heterotrophic microbial population varied in the wards sampled from hospital to hospital. The bacterial population ranged from 18cfu/m 3 to 288cfu/m 3 in Faithdome hospital and 8cfu/m to 494cfu/m 3 in Eromosele hospital. The fungal population ranged from 9cfu/m 3 to 26cfu/m 3 in Faithdome hospital and 3cfu/m 3 to 45cfu/m 3 in Eromosele hospital. The microbial floral isolated included six bacterial and six fungal genera among which are Staphylococcus aureus , Klebsiella spp , Streptococcus spp , Bacillus spp , Pseudomonas spp , Escherichia coli, Aspergillus spp , Penicillium spp , Candida spp , Trichophyton spp , Microsporium spp and Rhizopus spp. The degree of microbial distribution was highest in the waiting room and lowest in the theatre.


A simulation model of a converter with soft switching of transistors has been created. New calculation methods and means of measuring the equivalent frequency characteristics of converting devices with negative feedback to the problems of stability analysis have been applied. A comparative analysis of the calculated frequency characteristics of the converter in the normal operation mode with the characteristics of its linear model is presented. The features of calculating the equivalent frequency characteristics of the loop amplification of key devices are considered. It is noted that it is the equivalent frequency characteristics of the loop amplification that describe the relationship of frequency properties with the dynamics of voltage converters with pulse-width modulation and make it possible to reliably determine the real stability margins, predict the generation modes and open up the possibility of obtaining maximum negative feedback in a given frequency band of key devices. The non-minimal phase properties of the converter significantly complicate the achievement of high-quality stabilization of the output current (stabilization coefficient) of pulse stabilizers using only the deflection control principle. A successful solution to the problem is provided by the use of the principle of combined control. Compensation of the disturbance effect (changes in the supply voltage) gives a much better result than countering it through the feedback loop. It is quite realistic to exclude the influence of the input voltage u ( t ) on the output current i 2 in a static mode ( u =const) and in the absence of a negative feedback loop, which provides  for u =const in a steady state, and to provide better dynamic properties of the converter. The influence of the nonlinear properties of pulse width modulation on stability is manifested in the considered characteristics in the form of an additional phase shift and resonant bursts in the vicinity of the clock frequency subharmonics. Additional feedbacks introduced into the control loop make it possible to solve synthesis problems using the most simple technical means


T E C H N I C A L A S S I S TA N C E Introduction Malnutrition has significant negative consequences for many developing countries, particularly in terms of poor human health, lost human capital, and decreased economic productivity. Investment in nutrition was identified in 2012 by the Copenhagen Consensus (Copenhagen Consensus 2012) as a best investment for developing countries; for every US$1 spent on nutrition, there is a US$16 return in health and economic benefits (International Food Policy Research Institute 2015). Despite this, funding and support for nutrition programming is often lacking.


Abstract. Due to the increasing number of low-cost sensors, widely accessible on the market, and because of the supposed granted correctness of the semi-automatic workflow for 3D reconstruction, highly implemented in the recent commercial software, more and more users operate nowadays without following the rigorousness of classical photogrammetric methods. This behaviour often naively leads to 3D products that lacks metric quality assessment. This paper proposes and analyses an approach that gives the users the possibility to preserve the trustworthiness of the metric information inherent in the 3D model, without sacrificing the automation offered by modern photogrammetry software. At the beginning, the importance of Data Quality Assessment is outlined, together with some recall of photogrammetry best practices. With the purpose of guiding the user through a correct pipeline for a certified 3D model reconstruction, an operative workflow is proposed, focusing on the first part of the object reconstruction steps (tie-points extraction, camera calibration, and relative orientation). A new GUI (Graphical User Interface) developed for the open source MicMac suite is then presented, and a sample dataset is used for the evaluation of the photogrammetric block orientation using statistically obtained quality descriptors. The results and the future directions are then presented and discussed.


In this thesis we deal with different topics in financial mathematics, that are all related to market imperfections and to the fundamental technique of utility maximization. The work consists of three parts. In the first one, which is based on two papers, we consider the problem of optimal investment on a financial market with proportional transaction costs. We initially study the investment problem in the case where the utility function is multivariate (which is particularly suitable on currency markets) and the agent is endowed with a random claim, which can be interpreted as an option or another derivative contract. After analyzing the properties of the primal and dual problems, we apply those results to investigate, in this context, some aspects of a popular pricing technique in incomplete markets, i.e. utility indifference evaluation. In the second contribution to the transaction costs literature, we investigate the existence problem for a set of prices (called shadow prices) that would provide the same maximal utility to the agent if the market did not have frictions. These results shed some light on the link between the classical theory of frictionless markets and the quickly growing literature on transaction costs. In the second part of this thesis we consider the utility indifference pricing problem in incomplete markets, where the source of incompleteness comes from the fact that some assets in the market cannot be actively traded, which is the case for example in the framework of structural models for electricity prices. We provide a BSDE characterization for the price under mild assumptions, and then focus on the case of European claims by establishing in particular the existence of an optimal hedging strategy even when the claim presents discontinuities and is possibly unbounded. In the last contribution we analyze a simple principal-agent problem in finite time horizon, where the principal is mainly interpreted as a regulator and the agent as a firm producing some kind of polluting emissions. We separately treat both the agent's and the principal's problems and use the BSDE theory for providing necessary and sufficient conditions for optimality. We also perform some sensitivity analyses and give numerical results in order to provide a better understanding of the agents' behavior.


Computer games as an emerging phenomenon have encompassed extensive aspects of children's life that social skills are considered as one of the most important aspects. This study was conducted aiming at evaluation of the relationship between the duration of playing computer games (DPCG) and social skills. The study was a descriptive correlation type. The statistical population of research included all the students in fifth grade of primary schools in Karaj in the academic year of 2013-2014 with a sample size of 363 subjects (n=363), which were selected using the clustering – multi-stage sampling method. The study showed a significant relationship between social skills and DPCG (P<0.01). Also among the subscales of social skills, there were significant correlations between the subscales of cooperation and self-restraint and the DPCG (P<0.01), while self-assertiveness and empathy subscales had no significant correlation with the DPCG. This study illustrates that with increased DPCG, the children's social skills would decrease.


Chromium-doped carbon (Cr:C) films were fabricated by using unbalanced magnetron sputtering with chromium (Cr) and graphite (C) targets. We investigated the structural, tribological, and electrical properties of the Cr:C films fabricated with various target power densities. The surface of all the Cr:C films was smooth and uniform, and the cross section showed a more compact and clear columnar structure as the target power density increased. The root mean square surface roughness increased and the contact angle on the film surface increased with the increase in target power density. Furthermore, the hardness and elastic modulus of the Cr:C films showed improvements, while the resistivity decreased with the increase in target power density. These results are associated with the ion bombardment and resputtering owing to the effects of the applied target power density.


The task force of the international league against epilepsy (ILAE) proposed the "Diagnostic scheme for people with epileptic seizures and epilepsy" in 2001. The 2001 diagnostic scheme was updated in 2006. The ILAE Core Group recommended the new classification to replace the previous one (ILAE, 1981, 1989). However, the new classification is too complex to use for clinicians except expert epileptologists. About 10 new antiepileptic drugs are launched recently. Among them, gabapentine, topiramate, and lamotrigine have been approved in Japan as adjunctive therapy for medically intractable seizures. The advantage of the new antiepileptic drugs includes newer mechanism of action, broad spectrum of anti-seizure effects, fewer side effects, and lesser drug interactions. The rational polytherapy is necessary for refractory epilepsy. The majority of elderly patients with new onset epilepsy become seizure free on antiepileptic monotherapy, often with modest dose. We are now in the new era of epilepsy treatment.


This article shows that first language (L1) transfer may not be effectively maintained in the interlanguage due to confounding factors in the second language (L2). When two factors, A and B , are correlated in the L2, second language learners may only acquire B , even if A is present in the L1. Transfer may not be effective because B , being more robust in the input, conceals A . Native speakers, on the other hand, generalize A in spite of B . The variables in question are weight-sensitivity ( A ) and positional bias ( B ) in English, both of which can predict the location of stress in the language. I show that two seemingly target-like groups of second language learners of English (speakers of Mandarin and speakers Portuguese) fail to accurately generalize weight-sensitivity in the language, and instead display response patterns which are predictable given the existing positional bias in English stress.


This book presents the art of advanced MOSFET modeling for integrated circuit simulation and design. It provides the essential mathematical and physical analyses of all the electrical, mechanical and thermal effects in MOS transistors relevant to the operation of integrated circuits. Particular emphasis is placed on how the BSIM model evolved into the first ever industry standard SPICE MOSFET model for circuit simulation and CMOS technology development. The discussion covers the theory and methodology of how a MOSFET model, or semiconductor device models in general, can be implemented to be robust and efficient, turning device physics theory into a production-worthy SPICE simulation model. Special attention is paid to MOSFET characterization and model parameter extraction methodologies, making the book particularly useful for those interested or already engaged in work in the areas of semiconductor devices, compact modeling for SPICE simulation, and integrated circuit design.


OBJECTIVE: To determine the relative risk of hip fracture associated with postmenopausal hormone replacement therapy including the effect of duration and recency of treatment, the addition of progestins, route of administration, and dose. DESIGN: Population based case-control study. Setting: Six counties in Sweden. SUBJECTS: 1327 women aged 50-81 years with hip fracture and 3262 randomly selected controls. MAIN OUTCOME MEASURE: Use of hormone replacement therapy. RESULTS: Compared with women who had never used hormone replacement therapy, current users had an odds ratio of 0.35 (95 % confidence interval 0.24 to 0.53) for hip fracture and former users had an odds ratio of 0.76 (0.57 to 1.01). For every year of therapy, the overall risk decreased by 6% (3% to 9%): 4% (1% to 8%) for regimens without progestin and 11% (6% to 16%) for those with progestin. Last use between one and five years previously, with a duration of use more than five years, was associated with an odds ratio of 0.27 (0.08 to 0.94). After five years without hormone replacement therapy the protective effect was substantially diminished (-7% to 48%). With current use, an initiation of therapy nine or more years after the menopause gave equally strong reduction in risk for hip fracture as an earlier start. Oestrogen treatment with skin patches gave similar risk estimates as oral regimens. CONCLUSIONS: Recent use of hormone replacement therapy is required for optimum fracture protection, but therapy can be started several years after the menopause. The protective effect increases with duration of use, and an oestrogen-sparing effect is achieved when progestins are included in the regimen.


The inner part of the CMS phase II upgrade outer tracker will be built from PS modules consisting of two closely spaces silicon sensors and associated electronics and mechanics. The sensors must be assembled with a translational (x-y) alignment of approximately 40 um and a rotational alignment of 800 urad. An automated module assembly system is proposed as a method to build these modules on a large production scale. The automated system is based on the integration of a high-precision motion stage with vacuum handling and vision systems. A dedicated software application obtains images, performs pattern recognition to deduce component positions, and controls the motion and vacuum handling systems to precisely position components.


Background Different ages for diagnosis of diabetes have diverse effects on risks of cardiovascular disease, dementia, and mortality, but there is little evidence of cancer. This study investigated the relationship between diabetes at different diagnostic ages and risks of cancer incidence and mortality in people aged 37–73 years. Methods Participants with diabetes in the UK Biobank prospective cohort were divided into four groups: ≤40, 41–50, 51–60, and >60 years according to age at diagnosis. A total of 26,318 diabetics and 105,272 controls (1:4 randomly selected for each diabetic matched by the same baseline age) were included. We calculated the incidence density, standardized incidence, and mortality rates of cancer. Cox proportional hazard model was used to examine the associations of diabetes at different diagnostic ages with cancer incidence and mortality, followed by subgroup analyses. Results Compared to corresponding controls, standardized incidence and mortality rates of overall and digestive system cancers were higher in diabetes diagnosed at age 41–50, 51–60, and >60 years, especially at 51–60 years. Individuals diagnosed with diabetes at different ages were at higher risk to develop site-specific cancers, with a prominently increased risk of liver cancer since the diagnosis age of >40 years. Significantly, participants with diabetes diagnosed at 51–60 years were correlated with various site-specific cancer risks [hazard ratio (HR) for incidence: 1.088–2.416, HR for mortality: 1.276–3.269]. Moreover, for mortality of digestive system cancers, we observed an interaction effect between smoking and diabetes diagnosed at 51–60 years. Conclusion Our findings highlighted that the age at diagnosis of diabetes, especially 51–60 years, was critical risks of cancer incidence and mortality and may represent a potential preventative window for cancer.


Norwegian kveik are a recently described family of domesticated Saccharomyces cerevisiae brewing yeasts used by farmhouse brewers in western Norway for generations to produce traditional Norwegian farmhouse ale. Kveik ale yeasts have been domesticated by farmhouse brewers through serial repitching of the yeast in warm wort (>30°C) punctuated by long periods of dry storage. Kveik yeasts are alcohol tolerant, flocculant, capable of utilizing maltose/maltotriose, phenolic off flavour negative, and exhibit elevated thermotolerance when compared to other modern brewer's yeasts belonging to the 'Beer 1' clade. However, the optimal fermentation and growth temperatures (Topt) for kveik ale yeasts and the influence of fermentation temperature of the production of flavour-active metabolites like fusel alcohols and sulfur compounds (H2S, SO2) are not known. Here we show that kveik ale yeasts have an elevated optimal fermentation temperature (Topt) when compared to commercial American Ale yeast (SafAle™ US-05) and that they produce fewer off-flavours at high temperatures (>30°C) when compared to commercial American Ale yeasts. The tested kveik yeasts show significantly higher maximum fermentation rates than American Ale yeast not only at elevated temperatures (>30°C), but also at 'typical' ale fermentation temperatures (20°C-25°C). Finally, we demonstrate that kveik ale yeasts are heterogeneous in their Topt and that they attenuate standard wort robustly above their Topt unlike our control American Ale yeast which showed very poor apparent attenuation in our standard wort at temperatures ≫ Topt. Our results provide further support that kveik yeasts may possess favourable fermentation kinetics and sensory properties compared to American Ale yeasts. The observations here provide a roadmap for brewers to fine tune their commercial fermentations using kveik ale yeasts for optimal performance and/or flavour impact.


From the second half of the 1990s, an increased regard has been given to the fungal spoilage of foods as follows: 1) post-harvest diseases and losses of fruits and vegetables, 2) deterioration of low water activity foods by xerophilic fungi, 3) contamination of psychrotolerant or psychrophilic fungi on foodstuffs and processed foods during storage and distribution at low temperature, and 4) spoilage of heat processed foods and soft drinks by heat-resistant fungi. In accordance with an international concern about food safety, mycotoxin contamination of foods has gained much global attention in recent times owing to its potential health hazards. The evaluation of mycotoxin hazards is principally based on the determination of a no-observed effect level (NOEL) in long-term toxicological studies, and the application of a safety factor (usually 100). In addition to hazard assessment, data on the natural occurrence of mycotoxins in various commodities and food intake data are needed to enable exposure assessment. Thus risk assessment of mycotoxins is, in fact, the product of hazard assessment and exposure assessment. In 1997, the FAO/WHO Joint Expert Committee on Food Additives (JECFA) considered estimates of the carcinogenic potency of aflatoxins and the potential risks associated with their intake. Recently the Codex Alimentarius Commission (Codex) has established standards for aflatoxin M1 in milk and for patulin in apple juice. The Codex is an international organization, supported by FAO/WHO, aiming at facilitating world trade and protecting the health of the consumer by developing international standards for food and feeds. Apart from aflatoxins, the JECFA has measured a provisional tolerable daily intake (TDI) for ochratoxin A, patulin, deoxynivalenol, T-2/HT-2 toxins, zearalenone and fumonisins. In 2001, the mycotoxins evaluated or re-evaluated at the JECFA meeting included ochratoxin A, deoxynivalenol, T-2/HT-2 toxins, fumonisins, and aflatoxin M1. In Japan, specific regulations now exist for deoxynivalenol (1.1 ppm) in wheat grains and for patulin (50 ppb) in apple juice and its products.


Background: Text message interventions hold promise for adolescents and young adults (AYAs) with chronic health conditions, including childhood cancer survivors; however, engagement is often suboptimal. Limited research has studied mobile health intervention outcomes beyond efficacy. Understanding responsivity to different types of text messages (ie, when a participant texts back) can provide practical, actionable information to optimize engagement in future projects. Objective Within a 2-way text messaging study in AYAs who recently completed treatment for cancer, we sought to evaluate text message responsivity across different types of text messages. Methods AYAs who recently completed treatment for cancer (n=26; mean age=16 years; 62% female, 16/26 participants) received 2-way text messages about survivorship health topics over a 16-week period. Using participants' text message log data, we coded responsivity to text messages and evaluated trends in responsivity to unprompted text messages and prompted text messages of varying content (eg, medication reminders, appointment reminders, and texts about personal experiences as a cancer survivor). Results Across prompted and unprompted text messages, responsivity rapidly decreased (P ≤.001 and =.01, respectively) and plateaued by the third week of the intervention. However, participants were more responsive to prompted text messages (mean responsivity=46% by week 16) than unprompted messages (mean responsivity=10% by week 16). They also demonstrated stable responsivity to certain prompted content: medication reminders, appointment reminders, goal motivation, goal progress, and patient experience texts. Conclusions Our methodology of evaluating text message responsivity revealed important patterns of engagement in a 2-way text message intervention for AYA cancer survivors.


Detecting an exoplanetary life signal is extremely challenging with current technology because it requires a sensitive telescope and instrument that can measure the planet's reflected optical and infrared light, while distinguishing this from the star's scattered light and the terrestrial thermal noise background. This requires highly accurate adaptive optics, a coronagraph system, and a specially designed and aligned giant telescope. We present here new strategies for building such a telescope with large circular segments using adaptive optics correction independently for each of these segments prior to cophasing the segments. The foreseen cophasing technique uses focal plane images that allow piston measurements and correction between all the segments. In this context we propose to derive the segment phase error using the inverse approach knowing the segment positions and the single aperture Airy function.


The gut-liver axis is a clinical topic as a potential therapeutic target of liver diseases. The interaction between microbial products and immune responses in the liver is still unknown. In the current study, we have demonstrated IL-10-producing CD11b+ F4/80+ macrophages contribute to immune tolerance in the inflamed liver under diminished intestinal barrier function in murine tandem model of dextran sulfate sodium (DSS)-colitis and Concanavalin A (ConA)-hepatitis. DSS-ConA mice with increased intestinal permeability developed less liver injury compared with DW-ConA mice. Of note, the severity of colitis was inversely correlated with subsequently induced liver injury. In DSS-ConA livers, increased CD11b+ macrophages showed regulatory characteristics with IL-10 production in vitro. Pretreatment with α-IL-10 antibody partially exacerbated the suppressed liver injury by DSS-ConA in vivo. Furthermore, pretreatment with CD11b+ macrophages derived from DSS-ConA livers protected mice from the subsequent liver injury. Mechanistically, we observed the contribution of gut microbiota, as the immunological tolerance induced by DSS-ConA is partially ablated by gut sterilization. Pretreatment with the portal serum derived from DSS-ConA mice partially protected mice from the subsequent liver injury. These results suggest that altered gut microbiota and the metabolites that pass through the portal vein with disrupted intestinal barrier directly gave rise to immunological permissiveness against the excessive stimulation in the liver. This study clarified the contribution of the gut-liver axis in the maintenance of immune balance in the liver and highlighted the microbiota as a potential therapeutic target for liver diseases.


BACKGROUND
Barefoot running is slowly gaining a dedicated following. Proponents of barefoot running claim many benefits, such as improved performance and reduced injuries, whereas detractors warn of the imminent risks involved.

METHODS
Multiple publications were reviewed using key words.

RESULTS
A review of the literature uncovered many studies that have looked at the barefoot condition and found notable differences in gait and other parameters. These findings, along with much anecdotal information, can lead one to extrapolate that barefoot runners should have fewer injuries, better performance, or both. Several athletic shoe companies have designed running shoes that attempt to mimic the barefoot condition and, thus, garner the purported benefits of barefoot running.

CONCLUSIONS
Although there is no evidence that either confirms or refutes improved performance and reduced injuries in barefoot runners, many of the claimed disadvantages to barefoot running are not supported by the literature. Nonetheless, it seems that barefoot running may be an acceptable training method for athletes and coaches who understand and can minimize the risks.


The manuscript by Baruch Brody and Reider Lie presents a distorted image of cost comparisons and social accounts. They presuppose a static view of health systems. While there is methodological uncertainty in international comparisons, such uncertainty should not be used to justify a failure to act.


Recent advances in NLP demonstrate the effectiveness of training large-scale language models and transferring them to downstream tasks. Can fine-tuning these models on tasks other than language modeling further improve performance? In this paper, we conduct an extensive study of the transferability between 33 NLP tasks across three broad classes of problems (text classification, question answering, and sequence labeling). Our results show that transfer learning is more beneficial than previously thought, especially when target task data is scarce, and can improve performance even when the source task is small or differs substantially from the target task (e.g., part-of-speech tagging transfers well to the DROP QA dataset). We also develop task embeddings that can be used to predict the most transferable source tasks for a given target task, and we validate their effectiveness in experiments controlled for source and target data size. Overall, our experiments reveal that factors such as source data size, task and domain similarity, and task complexity all play a role in determining transferability.


Previous epidemiologic research has associated potential epichlorohydrin exposure with lung cancer and, in conjunction with allyl chloride exposure, to heart disease mortality. The study was designed to test both hypotheses by examining the mortality experience of 1,064 male employees (12,574 person-years) who had a minimum of 1 month work experience between 1957-1986 in the production or use of epichlorohydrin and allyl chloride and 1 year total employment duration at Dow Chemical's Texas Operations. Vital status follow-up occurred through 1989 of which there were 66 total deaths (standardized mortality ratio [SMR] = 80, 95% confidence interval [CI] 62-101). There were no significantly elevated SMRs for all malignant neoplasms, lung cancer, circulatory system disease, or arteriosclerotic heart disease when compared to external (U.S.) or internal (Texas Operations) populations. There were no apparent mortality trends with cumulative exposure analyses of potential epichlorohydrin exposure with and without accompanying allyl chloride exposure. A high prevalence of circulatory system death certificates were certified by nonphysicians in the local county and more than one third were described in nonspecific terms. The study results are not consistent with the prior hypothesized associations. However, the study results are limited by the cohort's size, duration of follow-up, relatively few number of observed and expected deaths, and the level of potential epichlorohydrin exposure experience.


A 200-kW fuel cell produced by International Fuel Cells (IFC), a United Technologies Company, began operation at the National Transportation Research Center (NTRC) in early June 2003. The NTRC is a joint Oak Ridge National laboratory (ORNL) and University of Tennessee research facility located in Knoxville, Tennessee. This research activity investigated the protective relaying functions of this fully commercialized fuel cell power plant, which uses ''synthesized'' protective relays. The project's goal is to characterize the compatibility between the fuel cell's interconnection protection system and the local distribution system or electric power system (EPS). ORNL, with assistance from the Electric Power Research Institute-Power Electronics Applications Center (EPRI-PEAC) in Knoxville, Tennessee, monitored and characterized the system compatibility over a period of 6 months. Distribution utility engineers are distrustful of or simply uncomfortable with the protective relaying and hardware provided as part of distributed generation (DG) plants. Part of this mistrust is due to the fact that utilities generally rely on hardware from certain manufacturers whose reliability is well established based on performance over many years or even decades. Another source of concern is the fact that fuel cells and other types of DG do not use conventional relays but, instead, the protective functions of conventional relays are simulated by digital circuits in the distributed generator's grid interface control unit. Furthermore, the testing and validation of internal protection circuits of DG are difficult to accomplish and can be changed by the vendor at any time. This study investigated and documented the safety and protective relaying present in the IFC fuel cell, collected data on the operation of the fuel cell, recorded event data during EPS disturbances, and assessed the compatibility of the synthesized protective circuits and the local distribution system. The project also addressed other important and timely issues. For instance, the study includes an evaluation of the effectiveness of the fuel cell's synthesized relay protection scheme relative to the recently issued IEEE 1547 interconnection standard. Together, these activities should serve to reduce the number of unknowns pertaining to unconventional protective circuits, to the benefit of DG manufacturers, vendors, prospective and current users of DG, and electricity suppliers/distributors. Although more grid-connect fuel cell interruptions were encountered in this study than originally anticipated, and the investigation and findings became quite complex, every effort was made to clearly summarize the interconnection causes and issues throughout the report and especially in the summary found in Sect. 4. ORNL's funding of this study is sponsored equally by (1) the Department of Energy's (DOE's) Office of Distributed Energy Resources and (2) the Distributed Generation Technologies program of the Tennessee Valley Authority (TVA).


Transnational cybercrimes (TNCCs) are cybercrimes occurring across several jurisdictions. The advancement of technology has brought about an increase in the sophistication, severity and comprehensiveness of incidents of cybercrimes such that cybercrimes can now be effortlessly transnational. In the main, however, the various legal responses to TNCCs have shown States consistently applying traditional territorially based rules to online activities by enacting laws that do not adequately address the borderless nature of the Internet. This paper examines the jurisdictional challenges of transnational cybercrimes as well as the inadequacies of present legal responses to transnational cybercrime. With the aid of the doctrinal research methodology (legal analysis), it finds that purely domestic legal responses to cybercrimes, no matter how advanced, are inadequate as a fragmented approach cannot effectively eradicate the problem created by the presence of safe havens. It concludes that a holistic approach is needed and recommends the adoption of a global instrument with international recognition of universal jurisdiction for serious categories of TNCCs capable of compromising international Peace and security, such as cyber terrorism, hacking and the creation and dissemination of malicious codes targeting critical infrastructures or leading to the denial of essential services.


The mechanistic target of rapamycin complex 1 (mTORC1) regulates cell growth and catabolism in response to nutrients through phosphorylation of key substrates. The tumor suppressor folliculin (FLCN) is a RagC/D guanosine triphosphatase (GTPase)–activating protein (GAP) that regulates mTORC1 phosphorylation of MiT-TFE transcription factors, controlling lysosome biogenesis and autophagy. We determined the cryo–electron microscopy structure of the active FLCN complex (AFC) containing FLCN, FNIP2, the N-terminal tail of SLC38A9, the RagAGDP:RagCGDP.BeFx- GTPase dimer, and the Ragulator scaffold. Relative to the inactive lysosomal FLCN complex structure, FLCN reorients by 90°, breaks contact with RagA, and makes previously unseen contacts with RagC that position its Arg164 finger for catalysis. Disruption of the AFC-specific interfaces of FLCN and FNIP2 with RagC eliminated GAP activity and led to nuclear retention of TFE3, with no effect on mTORC1 substrates S6K or 4E-BP1. The structure provides a basis for regulation of an mTORC1 substrate-specific pathway and a roadmap to discover MiT-TFE family selective mTORC1 antagonists.


Introduction.—On the 7th of May, 1885, I delivered an expository lecture before the Edinburgh Geological Society, and repeated the same on the 14th before this society, on "The Parallel Roads of Glen Roy: the Problem, its Conditions, and Solutions."* One result of these papers was that a joint excursion of members of both societies was arranged for Lochaber, to examine the problem on the spot, under the leadership of the lecturer. The excursion took place during the last week of July, from Monday, July 27th, to Saturday the 31st. The party numbered seventeen in all, of whom six were connected with the Edinburgh Society and nine with the Glasgow Society, another being a gentleman from Dorset, and the last Mr. Colin Livingstone, head master of the Public School of Fort-William, whose knowledge of the district and of the special subject is unrivalled, and whose services were of the greatest value to the party, as duly and heartily acknowledged. The whole cost of the excursion to each man was, on an average, about £5. The weather was superb, without a single shower; the sky cloudless and the air uncommonly clear, exhibiting the glorious scenery and the various phenomena to the best advantage; the party delightfully varied, bright and genial; and the whole experiences unusually pleasant, instructive, and memorable. The time at disposal did not and could not allow of detailed investigation of the numerous and difficult points involved, scattered, as these are, over a broad mountainous district, and necessitating, as they This 250-word extract was created in the absence of an abstract


Research on organisational learning, knowledge and capabilities has indeed become one of the most fruitful and interesting areas in the field of management, and has not only improved our understanding of organisations, but also helped them to face the new challenges of our turbulent age. Are our organizations learning to face a new age? What kinds of learning and knowledge are necessary to understand our age? What new lights can help us to understand organisational learning and knowledge? Are there shades? Shedding New Lights dispels uncertainties and provides a better observation and understanding of this particular phenomenon. This book includes an overview of the major topics on organisational learning, knowledge and capabilities. There are three parts: the first focuses on organisational learning, and particularly on practice and communities of practice. The second part deals with knowledge creation and transfer, two main knowledge management processes that are extremely relevant for firm performance. Finally, the third part examines the phenomenon of ambidexterity (explorative and exploitative learning) and the absorptive capacity of the firm.


Data mining and Artificial Intelligence (AI) methodologies are underdeveloped in the oil and gas industry, despite the need to improve drilling performance and remain globally competitive in all capital-intensive projects.
 Drilling companies allocate significant resources to improve well planning, drilling schedules and rig management. Well planning comprises of two main elements; drilling performance and the reduction of drill stem vibrations. Therefore, modeling methodologies such as drill string statics, dynamic tools and rate of penetration modeling are applied to determine the optimum bottom hole assembly (BHA) components and drill bit design. However, more attention is required on drill stem fatigue, non-productive time (NPT) and their impacts on drilling operations.
 In this paper, Data Analytics (DA) is applied to drilling logs taken from three wells that recorded vibration readings from different geological stratification. In turn, the work in this paper establishes a relationship between drill stem vibrations and various measurement and logging data while drilling. Statistical regression and multivariate analysis were used to examine correlations of drilling parameters, including BHA assembly, to vibration data. Therefore, the results include a composite vibration model that describes the drilling stem vibration behavior as a function of drilling parameters, and geological formations.
 Results of the vibration models built in this study indicate that the drill stem lateral vibration behaves parabolically as a function of the drill pipe length, length of drill collar, gamma ray (GR) response, and weight on bit (WOB). The analysis of drill stem vibration effect on the mechanical specific energy (MSE) was inconclusive for depths below 1350 meters. However, for depths above 1350 meters a strong correlation was observed to ROP.


The fat mass and obesity-associated protein (FTO) is an RNA N6-methyladenosine (m6A) demethylase highly expressed in diverse cancers including acute myeloid leukemia (AML). To improve antileukemia drug-like properties, we have designed 44/ZLD115, a flexible alkaline side-chain-substituted benzoic acid FTO inhibitor derived from FB23. A combination of structure-activity relationship analysis and lipophilic efficiency-guided optimization demonstrates that 44/ZLD115 exhibits better drug-likeness than the previously reported FTO inhibitors, FB23 and 13a/Dac85. Then, 44/ZLD115 shows significant antiproliferative activity in leukemic NB4 and MOLM13 cell lines. Moreover, 44/ZLD115 treatment noticeably increases m6A abundance on the AML cell RNA, upregulates RARA gene expression, and downregulates MYC gene expression in MOLM13 cells, which are consistent with FTO gene knockdown. Lastly, 44/ZLD115 exhibits antileukemic activity in xenograft mice without substantial side effects. This FTO inhibitor demonstrates promising properties that can be further developed for antileukemia applications.


National Socialism never achieved its vision of 'law'. The 1958 debate between Fuller and Hart, and subsequent literature in the Anglo-American legal philosophical tradition has thus never addressed the question of what concept of law is compatible with Nazism's ultimate goals and what we might learn from such a concept about the relationship between law and evil. This essay first shows how law reform was far from complete by the time the war ended. It then demonstrates how the mystic, 'volkish' movement informed the Nazi vision for law. It will then be seen that this concept simply does not fit with some very basic shared assumptions from which the Fuller and Hart debate proceeds. This reveals the degree to which concepts of law within the Anglo-American jurisprudential tradition must accept that law has a specific moral content. Such concepts of law are incompatible with a bullying form of oppression that was at the core of Nazism's moral bankruptcy.


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OBJECTIVE We report the case of a seemingly rare variation of a branch of the trigeminal nerve. This unusual finding is of practical importance to the neurosurgeon because ablation of this nerve(s) in such a case would require modification of technique. The existence of a bifurcated infraorbital nerve is also relevant for application of local anesthesia to portions of the face innervated by the maxillary nerve. CLINICAL PRESENTATION During cadaveric dissection of the face of a male specimen, 2 branches of the infraorbital nerve were identified emanating onto the face. The 2 branches entered separate osseous canals within the orbit to emerge via 2 infraorbital foramina. INTERVENTION The unusual variation of the trigeminal nerve branch in the reported case necessitates a change in the way in which the nerve is blocked clinically. A common practice involves blocking the infraorbital nerve as it emerges from the infraorbital foramen. The needle is aimed superiorly, posteriorly, and slightly laterally; however, to provide adequate anesthesia to both branches of the infraorbital nerve, as reported here, a needle can be inserted between the zygomatic arch and the notch of the mandible in the pterygopalatine fossa. After the needle contacts the lateral pterygoid plate, it is withdrawn slightly and angled both superiorly and anteriorly to pass into the pterygopalatine fossa. CONCLUSION Although apparently uncommon, such derangement of the infraorbital nerve should be kept in mind by surgeons during surgical procedures in the region for treatment of various disorders including trigeminal neuralgia.


A new technique based on vector quantization (VQ) is proposed for interfacing the link-level and the system level analysis of frequency hopping (FH) mobile systems. The method represents an original solution to overcome the problem that the time scales adopted within the two analysis levels are usually different, thus discouraging a direct link between them. The VQ technique is applied, as a test case, to the study of a typical FH-GSM mobile environment. The corresponding results show excellent correlation with those achievable by means of a much more time consuming, as well as often infeasible, direct approach.


We propose a position estimation technique for nonstop outdoor navigation of an autonomous mobile robot. The proposed position estimation technique is based on maximum likelihood estimation. To cope with the parallel processing of internal and external sensor information and time delay in the sensor data process, we introduce the retroactive positioning data fusion technique. The proposed technique is implemented on our small size autonomous mobile robot. An experimental result is shown, in which our robot could navigate itself without stopping even when it takes several seconds of processing time to detect landmark from external sensor data.


The advection-diffusion equation is studied via a global Lagrangian coordinate transformation. The metric tensor of the Lagrangian coordinates couples the dynamical system theory rigorously into the solution of this class of partial differential equations. If the flow has chaotic streamlines, the diffusion will dominate the solution at a critical time, which scales logarithmically with the diffusivity. The subsequent rapid diffusive relaxation is completed on the order of a few Lyapunov times, and it becomes more anisotropic the smaller the diffusivity. The local Lyapunov time of the flow is the inverse of the finite time Lyapunov exponent. A finite time Lyapunov exponent can be expressed in terms of two convergence functions which are responsible for the spatio-temporal complexity of both the advective and diffusive transports. This complexity gives a new class of diffusion barrier in the chaotic region and a fractal-like behavior in both space and time. In an integrable flow with shear, there also exist fast and slow diffusion. But unlike that in a chaotic flow, a large gradient of the scalar field across the KAM surfaces can be maintained since the fast diffusion in an integrable flow is strictly confined within the KAM surfaces.


Organic dairy farming is characterized by grazing cows in contrast to Danish conventional farms where the majority of cows are kept indoors. Cattle trampling reduces the finer macroporosity in the top 5-10 cm of the soil. This causes a low infiltration capacity at the soil surface, giving a higher probability of macropore flow from the surface. Rapid water movement through macropores bypasses the soil matrix, reducing nitrate leaching. We investigated how three years of cattle trampling in organic grass-clover fields could influence the risk of nitrate leaching in the autumn. The experimental part of this study was situated in Denmark on a loamy sand within a long-term organic dairy crop rotation trial. Experimental plots were irrigated with a concentrated solution of potassium bromide (18.5 mm for an hour). The amount of bromide in the soil water was determined at five depths (0.1, 0.3, 0.4, 0.75 and 1.0 m) 24 h after irrigation. Macropores larger than 1 mm were recorded on horizontal surfaces (0.70 m2) at the same depths. Earthworm density and biomass were registered. Bromide concentration in soil was significantly larger with the grazing regime than with the cutting regime below 0.3 m depth to at least 1 m. We observed equivalent macropore densities between the two treatments, both at 0.1 and at 0.3 m depth. The dry bulk density measured at 10 cm depth was significantly larger in the plots with the grazing regime than with the cutting regime, indicating a reduction of the porosity at this depth for the plots subjected to cattle trampling. No epigeic species were present. Cattle trampling affected mainly endogeic earthworms. Deep-burrowing species (anecic) were the least sensitive to cattle trampling. The deeper infiltration of water in soil when subjected to cattle trampling indicated that preferential flow through large macropores occurred, and that rain water may bypass the soil matrix under similar or more extreme conditions than this experiment. We expect such hydraulic functioning to reduce the risk of leaching of soil water nitrate.


Background Blocking signaling by epidermal growth factor receptor (EGFR), can effectively inhibit the proliferation and differentiation of non-small-cell lung cancer (NSCLC). Additionally, an increasing number of NSCLC patients have treatment limitations caused by EGFR overexpression or mutations. Therefore, we constructed a nanotherapy platform consisting of cetuximab (CTX) to target EGFR-sensitive NSCLC with an iron tetroxide core loading the sound-sensitive agent IR780 for dual-mode imaging diagnosis by combining targeting and sonodynamic therapy (SDT) to reshape the tumor microenvironment (TME), enhance the SDT antitumor effects and improve the therapeutic effects of EGFR sensitivity. Methods IR780@INPs were prepared by reverse rotary evaporation, CTX was adsorbed/coupled to obtain IR780@INPs-CTX, and the morphology and structure were characterized. Intracellular ROS levels and cell apoptosis first verified its killing effects against tumor cells. Then, a nude mouse lung cancer subcutaneous xenograft model was established with HCC827 cells. A real-time fluorescence IVIS imaging system determined the targeting and live distribution of IR780@INPs-CTX in the transplanted tumors and the imaging effects of the T2 sequence of the INPs by magnetic resonance imaging (MRI) 0 h, 2 h, 4 h and 6 h after administration to confirm drug efficacy. Results In vitro, US+IR780@INPs-CTX produced a large amount of ROS after SDT to induce cell apoptosis, and significant cell death after live/dead staining was observed. In vivo fluorescence imaging showed the IR780@INPs-CTX was mainly concentrated in the tumor with a small amount in the liver. MRI displayed rapid enrichment of the IR780@INPs into tumor tissue 0h after injection and the T2 signal intensity gradually decreases with time without obvious drug enrichment in the surrounding tissues. In vivo, at the end of treatment, the US+IR780@INPs-CTX group showed disappearance or a continued decrease in tumor volume, indicating strong SDT killing effects. Conclusion The combination of CTX and SDT is expected to become a novel treatment for EGFR-sensitive NSCLC.


There is no increased risk of breast cancer recurrence in women with a personal history of breast cancer who are prescribed vaginal estrogen for genitourinary syndrome of menopause. OBJECTIVE: To assess the risk of recurrence of breast cancer associated with vaginal estrogen therapy in women diagnosed with genitourinary syndrome of menopause with a history of breast cancer using a large U.S. claims database. METHODS: A U.S. health research network (TriNetX Diamond Network) was queried from January 2009 to June 2022. Our cohort consisted of women diagnosed with breast cancer within 5 years before the initial genitourinary syndrome of menopause diagnosis. Patients with active disease, defined as those undergoing mastectomy, radiation treatment, or chemotherapy within 3 months before diagnosis of genitourinary syndrome of menopause, were excluded. Recurrence was defined as mastectomy, radiation, chemotherapy, or secondary malignancy within 3 months to 5 years after the initiation of vaginal estrogen therapy for genitourinary syndrome of menopause. The study cohort included those with three or more vaginal estrogen prescriptions. The control cohort included women with breast cancer without any vaginal estrogen prescriptions after genitourinary syndrome of menopause diagnosis. Propensity matching was performed. A subanalysis by positive estrogen receptor status, when available, was performed. RESULTS: We identified 42,113 women with a diagnosis of genitourinary syndrome of menopause after breast cancer diagnosis with any estrogen receptor status, 5.0% of whom received vaginal estrogen. Of the initial cohort, 10,584 patients had a history of positive estrogen receptor breast cancer, and 3.9% of this group received vaginal estrogen. Risk of breast cancer recurrence was comparable between those who received vaginal estrogen and those who did not in both the any estrogen receptor (risk ratio 1.03, 95% CI 0.91–1.18) and positive estrogen receptor (risk ratio 0.94, 95% CI 0.77–1.15) status analyses. CONCLUSION: In a large, claims-based analysis, we did not find an increased risk of breast cancer recurrence within 5 years in women with a personal history of breast cancer who were using vaginal estrogen for genitourinary syndrome of menopause.


The uThukela Water's operations are dispersed over a vast area (18 000 km2), with over 30 service centres. The operations department is responsible for the safe, affordable operation and maintenance of water and wastewater infrastructure, guaranteeing the sustainable and optimised provision of potable water and collection and treatment of wastewater.


This article presents an open and functional architecture based on a next-generation network solution in order to seize its converged nature to guarantee interoperability among different platforms and terminals. The defined architecture is an integrated solution for end-to-end communication of various IP multimedia subsystem platforms marketed by different vendors, belonging to several operators located in different countries across Europe and supporting multiple terminals and technologies in order to experiment with a new broadband telephony service for the residential environment. This work addresses, in particular, the interoperability problems of name resolution and implementation of the session initiation protocol interface at the terminal as a key use in such a scenario. Also, several advanced services are developed and tested within the proposed architecture as a proof of concept of the IMS capability for quick service creation and deployment. The architecture proposed contributes to the reduction of obstacles and barriers among the European countries in order to adopt NGN architectures, allowing a new type of communication that is more complete and flexible.


CI-986 (5-[3,5-bis(1,1-dimethylethyl)-4-hydroxyphenyl]-1,3,4-thiadiazole-2(3H)- thione-2-hydroxy-N,N,N-trimethylethanaminium salt) is a novel anti-inflammatory compound classified as a dual inhibitor of cyclooxygenase and 5-lipoxygenase. Studies were undertaken to characterize the preclinical toxicology of the compound. CI-986 was administered to rats for 2 weeks (0, 50, 250, 750, and 1500 mg/kg) or 13 weeks (0, 20, 250, 500, and 1000 mg/kg), dogs for 2 weeks (0, 50, 150, and 500 mg/kg) or 13 weeks (0, 20, 100, and 200 mg/kg), and to monkeys for 2 weeks (0, 50, 250, and 1000 mg/kg). No drug-related deaths resulted. Mild clinical signs of toxicity were noted in rats given doses of 250 mg/kg and above. Drug-related emesis and diarrhea were absent at the low dose in the dog and monkey but increased in incidence and severity at higher doses. Severe clinical signs in monkeys (emesis and diarrhea) necessitated the lowering of the top dose to 500 mg/kg/day (administered b.i.d.) during the second week of the monkey study. Slight decreases (< 23%) in serum protein and/or albumin were noted in all studies at the higher doses. A dose-related increase in alkaline phosphatase was noted in both dog studies, with no other drug-related effect on clinical pathology parameters. A gastric ulcer occurred in one rat administered 500 mg/kg CI-986 for 13 weeks. Gastrointestinal ulcers were not noted at any other dose in rats or at any dose in dogs or monkeys. A dose-related eosinophilia of glandular stomach submucosa was noted in rats after 2 and 13 weeks of drug administration but not in dogs or monkeys. In the 2-week rat study, mean combined sex plasma drug concentrations monitored 2 hr after dose on Day 14 were 0.59, 1.10, 2.64, and 3.43 micrograms/ml for the 50, 250, 750, and 1,500 mg/kg dose groups, respectively. In the 2-week dog studies, maximum plasma drug concentrations on Day 10 or Day 11 were achieved within 2 hr of dose with mean combined sex Cmax values of 0.73, 2.05, and 2.62 micrograms/ml for the 50, 250, and 750 mg/kg groups, respectively. Hepatic microsomal induction characterized by increased microsomal protein, increased microsomal cytochrome P450 content, and increased p-nitroanisole O-demethylation activity was noted in dogs and monkeys but not rats. CI-986 was well tolerated in rats and dogs at the doses employed and in monkeys at doses up to 500 mg/kg (b.i.d.).(ABSTRACT TRUNCATED AT 250 WORDS)


The first half of this two-part article provides an overview of primary causes that led a crowd of people to coalesce with the revolutionary movement of 1910.The second half displays the disappointment produced by that very movement to those whosaw themselves immersed in "the bunch", those who won and, of course, those who ended up incorporating themselves to the revolutionary state. Beyond the historiography of the armed movement, the second part of this article points towards the Mexican revolutionary literature such as novels, stories, memoirs, etcetera. to explain the intimate, everyday reasons that launched these revolutionary actors to grab their guns and enter into action.


Gibson, G. J. and Davis, P. (1974).Thorax, 29, 726-731. Respiratory complications of relapsing polychondritis. The respiratory function of a patient with relapsing polychondritis is described. He had severe airflow obstruction due to disease of both the extra and intrathoracic large airways. Evidence of small airways disease was lacking. The airflow obstruction was probably due to a combination of structural narrowing and an enhanced dynamic effect. Despite the severity of his disease the patient's exercise capacity was only slightly reduced but he developed carbon dioxide retention on exercise. Involvement of the airways is a common feature of this rare disease and demands full physiological and radiographic assessment if tracheostomy or other surgical procedure is contemplated.


It will be argued that the "problem of demarcation" and the defining of "expertise" share common structural features that can lead to either a type of strong relativism (everyone is an expert) or ultra-scepticism (expertise does not exist). Appropriating notions from Thomas Kuhn's (1996). The Structure of Scientific Revolutions it will be argued that an "expert" in a field that has a dominant paradigm is different to an "expert" in a field that has multiple competing paradigms. To illustrate my argument I will look at the field of economics and the competing claims of experts over the likelihood of a global recession circa 2005. To this I will apply Goldman's (2001) criteria for expertise assessment and by-way of a hypothetical non-expert show that this criteria becomes deficient in expertise assessment if we only hold to what I have called a "methodological" definition of expertise. I will also introduce the notion of the "anti-expert" who is an equivalent expert, but their whole field is dependent upon the dominant paradigm for its meaning. That is, its existence is parasitic upon the success of the paradigm, rather than as a "revolutionary science" which looks to overthrown or change the paradigm.


BACKGROUND
We compared the distribution of breast cancer reproductive and hormonal risk factors by level of acculturation and country of residence in women of Mexican descent.

METHODS
To compare the distribution of breast cancer reproductive and hormonal risk factors by level of acculturation and country of residence in women of Mexican descent, taking into account level of education, we analyzed data on 581 Mexican and 620 Mexican American (MA) women with a history of invasive breast cancer from the Ella Binational Breast Cancer Study. An eight-item language-based acculturation measure was used to classify MA women. Multivariate logistic regression was used to test associations between language acculturation, country of residence, and reproductive and hormonal risk factors.

RESULTS
After adjustment for age and education, compared to women residing in Mexico, English-dominant MAs were significantly more likely to have an earlier age at menarche (<12 years; odds ratio [OR]=2.08; 95% confidence interval [CI], 1.30-3.34), less likely to have a late age at first birth (≥30 years; OR=0.49; 95% CI, 0.25-0.97), and less likely to ever breastfeed (OR=0.13; 95% CI, 0.08-0.21).

CONCLUSIONS
Differences in reproductive and hormonal risk profile according to language acculturation and country of residence are evident; some of these were explained by education. Results support continued efforts to educate Mexican and MA women on screening and early detection of breast cancer along with promotion of modifiable factors, such as breastfeeding.


University's everyday life is today transformed in an encompassing domain where diferente types of actors are connected and interrelated. Nevertheless, academic science often feels threatened by the new emerging paradigm characterized by knowledge transfer and the economic exploitation of public research results. This paradigm relates to what can be defined as the 'academic enterprise', the creation of spin-offs, applied research contracts and licensing of industrial property rights of the university. This article explores university-firm relations and tensions, discussing the increased relevance of knowledge transfer. The ideas of Ludwik Fleck, intellectual precursor of Social Studies of Science and Technology, contribute to the understanding of the difficulties of communication between different collectives, their styles of thought and the relevance of 'marginal individuals' in connecting diferente institutional spheres. Based on a qualitative approach to the case study of the University of Algarve (Portugal) and its attempts to create bridges with the business world, the texto illustrates differences between collectives of thought in the 'academic science' and the firm, the recent institutionalization of commercialization of research, and findings for policymaking and management of knowledge transfer activities.


During the crack propagation process, the crack-branching behavior makes fracture more unpredictable. However, compared with the crack-branching behavior that occurs in brittle materials or ductile materials under dynamic loading, the branching behavior has been rarely reported in welded joints under quasi-static loading. Understanding the branching criterion or the mechanism governing the bifurcation of a crack in welded joints is still a challenge. In this work, three kinds of crack-branching models that reflect simplified welded joints were designed, and the aim of the present paper is to find and capture the crack-branching behavior in welded joints and to shed light on its branching mechanism. The results show that as long as there is another large enough propagation trend that is different from the original crack propagation direction, then crack-branching behavior occurs. A high strength mismatch that is induced by both the mechanical properties and dimensions of different regions is the key of crack branching in welded joints. Each crack branching is accompanied by three local high stress concentrations at the crack tip. Three pulling forces that are created by the three local high stress concentrations pull the crack, which propagates along with the directions of stress concentrations. Under the combined action of the three pulling forces, crack branching occurs, and two new cracks initiate from the middle of the pulling forces.


In view of the serious problem of tool wear during micro-cutting process with high speed, implanting groove micro texture into the tool surface to enhance cutting properties consisting of reducing friction, exhausting heat, anti-sticking and anti-wearing based on non-smooth surface technology. Utilizing laser processing technology to machine micro groove texture in the tool surface. Performing micro-machined Al6061 alloy experiment with the high speed micro-turning experimental device which designed by own, and to evaluate cutting properties from three aspects are the chip form, the tool wear condition and the roughness of machined surface in respectively. The experimental results show that the groove micro texture have a good influence on improving wear resistance of the tool, the quality of machined surface and the chip form as well.


The synthesis and structures of the perovskites Ln1/3TaO3 are described. As the size of the Ln cation is reduced, the compounds display a sequence of structure: P4/mmm/La → Cmmm/Ce−Gd → Pmma/Tb, Dy → Pmc21/Ho, Er. Although apparently tetragonal in P4/mmm, electron diffraction patterns of Tm1/3TaO3 reveal this has a complex incommensurate structure. Likewise Gd1/3TaO3 appears metrically tetragonal, but electron diffraction and synchrotron X-ray powder diffraction demonstrate this is actually orthorhombic. The suppression of the spontaneous orthorhombic strain in Gd1/3TaO3 is thought to be due to the proximity to the first-order Cmmm−Pmma transition. Variable temperature studies show both Tb1/3TaO3 and Dy1/3TaO3 undergo a first-order Cmmm−Pmma transition upon heating.


Tyrosinase is a metalloprotein involved in the production of melanin, but overexpression of this pigment is problematic in dermatological disorders. (S)-(+)-Decursin and its analogues have been shown to exhibit inhibitory activities against melanin production in B16 murine melanoma cells and specifically inhibit tyrosinase. In order to elucidate their binding modes with mouse tyrosinase, we used computational methods to predict the structures of the complexes on the atomic level. In addition, the structure of human tyrosinase, which has high amino acid sequence identity with mouse tyrosinase, was studied to identify the possible binding mode and activity of (S)-(+)-decursin and its analogues for human treatment. The results showed that (S)-(+)-decursin and its analogues contain ester derivatives that interact with hydrophobic and aromatic residues, particularly Ile256 and Val265 in the binding site. Although human tyrosinase displayed similar interactions with the compounds, there was a key structural difference in residue 222, which caused some compounds to bind with lower binding affinities. Our results provide a foundation for the identification of new tyrosinase inhibitors for treating dermatological disorders.


OBJECTIVE
To evaluate the expression of thymidylate synthase (TS) in myoepithelial cells (MECs) of salivary adenoid tissues and explore its clinical significance.

METHODS
Immunohistochemical staining EnVision method was used to detect the expression of TS, P63, Calponin, CK5/6 and S-100 in 32 salivary gland specimens, including 10 non-neoplastic and salivary inflammation specimens, 11 mixed tumor specimens, 5 basal cell carcinoma specimens and 6 adenoid cyst carcinoma specimens. The specificity and sensitivity of TS as a specific molecular marker of salivary muscle epithelial cells were evaluated in comparison with P63, Calponin, CK5/6 and S-100.

RESULTS
The expression pattern of TS in all the salivary gland tissue specimens was identical with that of p63. TS and P63 both showed strong immunohistochemical expressions in MECs of salivary adenoid tissue specimens. Calponin, CK5/6, and S-100 showed cytoplasmic/membranous expressions in the MECs. In addition, TS exhibited weak or moderate cytoplasmic expression in a few salivary gland epithelial cells, cancer cells and scattered stromal cells, with negative expression in the cell nuclei. The expression of TS in the MECs of all the salivary adenoid specimens was highly consistent with those of P63, Calponin, CK5/6 and S-100 (P>0.05) Except for CK5/6 expression in Salivary inflammation and Salivary gland specimens. Kappa>0.75. The specificity and sensitivity of TS as a molecular marker of MECs were both 100%.

CONCLUSIONS
TS is a new specific marker of MECs for differential diagnosis of salivary gland tumors.


This paper is the first of a two-part series designed to assess and summarize extant knowledge regarding hydraulic fracturing water and wastewater management practices using a comparative, multidisciplinary approach. To provide context for both papers, the water and wastewater practices are summarized for the four focus plays: Montney, Duvernay, Barnett, and Marcellus. In Alberta and British Columbia, which host the less-studied Duvernay and Montney plays, play-scale unconventional water and wastewater data are extracted and combined from three databases: FracFocus.ca, geoSCOUT, and AccuMap. A reasonable picture of hydraulic fracturing water use and practices in western Canada emerges from the over 4,000 wells studied. From late 2011 to early 2014, the average number of fracturing stages reported increased from 7 to over 14, while reported cumulative water use approached approximately 15 million m3 in 2013, the first year for which full data in all three databases was available. The majority of wells consuming 10,000 to 50,000 m3 of water are slickwater type, located largely in the two target plays; however, several wells using >50,000 m3 of water appear in the Horn River Formation in BC. While it is possible to identify in the databases wastewater treatment facilities and deep wastewater injection wells, it is at present difficult to constrain wastewater disposal practices and chemistry in Alberta and British Columbia. The analysis points to the need for further coordination between academics, industry, and governmental agencies to develop publicly available, searchable databases that carefully document water sourcing, wastewater recycling/reuse/disposal, and chemistry, in order to properly form hydraulic fracturing water management strategies.


Wireline logs were used to document the stratigraphic framework of Upper Devonian–Mississippian strata in the Arkoma Basin, and maps of high-gamma ray (HGR) log response were used to analyze the spatial distribution of potential source rocks in the Woodford–Chattanooga and Fayetteville–Caney shale-gas systems. The Woodford–Chattanooga shale is a transgressive deposit that accumulated on an arid continental margin influenced by marine upwelling and minimal sediment influx. A broad HGR depocenter along the southwestern margin of the basin includes two areas of higher accommodation containing the thickest HGR concentrations. Basin-wide patterns of HGR likely reflect broad tectonic influence on accommodation. The proportion of chert in the formation increases eastward and southward, likely reflecting latitudinal and bathymetric influence on the accumulation of siliceous ooze. The Lower Mississippian Burlington sequence, which lies between the two shale-gas systems, comprises carbonate ramp and distal shale deposits. Proximal ramp facies form an apron around the southern flank of the Ozark uplift and grade radially basinward into distal facies. An Upper Mississippian succession in the east includes lowstand deposits of the Batesville delta, which onlap the relict Burlington ramp. Basinwide, the succession includes the transgressive Fayetteville–Caney shale overlain by regressive deposits of the proximal Pitkin Limestone and distal upper Fayetteville (Arkansas) and "false" Caney (Oklahoma) shale. The HGR shale is concentrated in an area of intermediate accommodation on the western margin of the Mississippi Embayment and just basinward of the Pitkin Limestone pinchout in Arkansas, and in an area of relatively high accommodation in Oklahoma.


ABSTRACTUniversity The University of Manchester Name Mark LongDegree Degree of PhD in the Faculty of Engineering and Physical Sciences Title Application of Radioisotopes to Polymer Chemistry: Investigation ofRadiolabelled Atom Transfer PolymerizationYear 2015The use of the radioisotope 14C in polymer chemistry has been reviewed, showing how it has been used to investigate the mechanistic aspects of free radical polymerizations, and the use of polymers in other scientific disciplines such as environmental, physical, chemical and medical sciences.An overview of the application of fluorescent spectroscopy to polymer chemistry is also reported. It covers the fundamentals of fluorescence chemistry, its application and the potential problems of the use of fluorescent labels in polymer chemistry.The application of radioisotopes to atom transfer radical polymerisation (ATRP) to investigate the fate of initiators used in the ATRP of 2-hydroxypropyl methacrylate (2- HPMA) is also reported. By using 14C radiolabelled initiators, radio thin layer chromatography (Radio TLC) and the liquid scintillation counting of fractions, collected from gel permeation chromatography (GPC), the fate of the initiating species where monitored during the polymerization of samples of 14C poly(2-HPMA), with degrees of polymerization of 10, 25 and 50 was assessed. GPC and Radio TLC, data showed that there was an under-utilisation of the initiator, 16% clearly observable at high monomer conversion (>97%), which could result in the initiation of new chains at monomer conversions of >90% and as late as 300 minutes after the polymerisation had started. These results contradict ATRP theory which states all initiator is consumed immediately at the commencement of the polymerization. 14C poly(2-HPMA) was also used to determine the efficiencies of the polymer purification methods, flash chromatography and precipitation. Although repeated precipitation increased fractionation, it was shown to be superior to flash chromatography in removing residual unreacted or terminated initiator. Finally, the possible effects of fluorescent labels on adsorption of low molecular weight 14C poly(DEAEMA) onto real surfaces (filter paper, photo graphic paper and hair) from aqueous solutions at pH=2 were investigated.Three low molecular weight samples of 14C poly(DEAEMA) were prepared by ATRP using 14C labelled initiators synthesized from alcohols of increasing hydrophobicity i.e. methyl, benzyl and 9-hydroxyfluorene (fluorescent label). The levels of adsorption were determined using phosphor imaging, oxidation of organic samples and liquid scintillation counting.Results indicated that differences in the chemistry of the polymer end groups can affect adsorption of the 14C poly(DEAEMA) and polymer assembly at the air/water interface. There was greater adsorption of polymers with a fluorescent end group. The increasing deposition was attributed to the increasing hydrophobicity of the polymer end group. Moreover, the controlled placement of one fluorescent label per polymer chain can influence the polymer?s properties, prompting the question, is the use of fluorescent groups to assess polymer behaviour and properties viable?


OBJECTIVES
Although there is no consensus on the management of bronchogenic cyst, most surgeons advocate early removal, even in asymptomatic patients. To evaluate the feasibility and safety of video-assisted thoracic surgery (VATS) in the management of bronchogenic cysts and long-term follow-up, a retrospective analysis was performed.

METHODS
From January 1995 to April 2013, we retrospectively reviewed the charts of 113 patients who underwent VATS resection of bronchogenic cysts in our institution. Resection of the bronchogenic cysts by VATS was initially performed in patients who had a cyst in the thoracic cavity and no evidence of severely dense adhesion to other organs or tissues on a CT scan. Also, patients with a history of previous thoracic surgeries, in addition to those with concomitant diseases requiring surgical treatment, were enrolled in our series. Operations were carried out using the conventional three-port technique and histological examinations confirmed the diagnosis of benign bronchogenic cyst containing a ciliated columnar epithelial lining.

RESULTS
The median size of the cysts was 3.7 cm in their greatest diameter (range, 1-10 cm). One hundred and nine patients with bronchogenic cyst were resected completely by VATS. In 4 cases, VATS was converted to open thoracotomy or median sternotomy: major adhesion to the bronchus in 2, left innominate venous injury in 1 and repair of bronchial tear by surgery in 1. We identified 5 intraoperative complications of tracheobronchial tear, vascular injury and oesophageal laceration. The median operation time was 96.8 min (range, 15-320 min). There were no operative mortalities or major postoperative complications. Patients with VATS excision were discharged after a median of 3.7 days postoperatively. The long-term follow-up ranged from 1 to 11 years, with a median follow-up of 4.2 years. There were no late complications or recurrences.

CONCLUSIONS
Considering the low conversion and complication rate, VATS was safe and effective in the resection of the bronchogenic cysts. The size and the location of cysts were not important considerations in selecting the surgical method. VATS excision should be considered the primary therapeutic option in the management of patients with bronchogenic cysts.


Summary Policy change is a core goal of community social workers. This study aims to identify the motivational and facilitating factors associated with community social workers' engagement in policy practice, defined as policy involvement undertaken in the workplace context. The sample comprised of 106 community social workers employed by local government in Israel and the data were collected between June 2015 and February 2017. Findings The findings showed that community social workers are more likely to engage in policy when they enjoy higher professional status, possess more policy practice resources, have higher psychological involvement in politics, are more involved in political and professional networks, and sense that they enjoy greater organizational support for policy practice. Applications In seeking to enhance the engagement of community social workers in the policy process, social work education should provide future community social workers with policy practice skills and a sense of psychological engagement in politics. It should also encourage their participation in political networks and offer training that affords them opportunities to develop the organizational skills needed to further macro goals in a social service agency setting. In their workplace, community social workers seeking to engage in policy practice need to nurture an organizational culture that supports social workers' policy involvement. Given that this study is on a single Israeli sample, future research on community social workers in additional work settings and in other countries is required in order to advance knowledge on this crucial, yet understudied, form of professional activity.


Glass is one of the most difficult materials to be machined due to its brittle nature and unique structure such that the fracture is often occurred during machining and the surface finish produced is often poor. CNC milling machine is possible to be used with several parameters making the machining process on the glass special compared to other machining process. However, the application of grinding process on the CNC milling machine would be an ideal solution in generating special products with good surface roughness. This paper studies how to optimize the different machining parameters in glass grinding operation on CNC machine seeking for best surface roughness. These parameters include the spindle speed, feed rate, depth of cut, lubrication mode, tool type, tool diameter and tool wear. To optimize these machining parameters in which the most significant parameters affecting the surface roughness can be identified, Taguchi optimization method is used with the orthogonal array of L8(26). However, to obtain the most optimum parameters for best surface roughness, the signal to noise (S/N) response analysis and Pareto analysis of variance (ANOVA) methods are implemented. Finally, the confirmation test is carried out to investigate the improvement of the optimization. The results showed an improvement of 8.91 % in the measured surface roughness.


The objective of this study is to determine the optimum electrolyte composition for molten carbonate fuel cells. To accomplish this, the contractor will provide: (1) Comprehensive reports of on-going efforts to optimize carbonate composition. (2) A list of characteristics affected by electrolyte composition variations (e.g. ionic conductivity, vapor pressure, melting range, gas solubility, exchange current densities on NiO, corrosion and cathode dissolution effects). (3) Assessment of the overall effects that these characteristics have on state-of-the-art cell voltage and lifetime.


This paper documents an application of model checking to formally verify an interrupt‐driven Slats and Flaps Control Unit software programmed in C, one component of a certain type of Chinese aircraft. Our objective was to identify errors rather than to prove correctness. We focused on the correctness of the algorithms used in the buffer operations, which are very common and important in aircraft software. In the verification, a total of four flawed code fragments was identified, including a minor efficiency issue. According to the programming team, this is regarded as a very successful result, and this project is the first successful attempt to apply model checking to the practice of verifying onboard aircraft software in China. Thanks to its completeness and reality, this case study can also serve as a complete and valuable real‐world example for teaching and learning model checking. Copyright © 2013 John Wiley & Sons, Ltd.


Abstract The order Asaphida has been characterized by the possession of a globular protaspis and a ventral median suture. The superfamily Dikelocephaloidea was included in the Asaphida, although there has been no reliable ontogenetic information for this superfamily, and thus whether dikelocephaloids had a protaspis of globular shape has remained unclear. The ontogenetic study of the dikelocephaloid trilobite, Asioptychaspis subglobosa, from Korea reveals that the protaspis of A. subglobosa is not of globular morphology but of general benthic adult-like morphology, heralding that the Dikelocephaloidea may not be closely related to other trilobite groups within the Order Asaphida. This protaspid morphology is clearly distinguished from the highly globular protaspis of the Remopleuridioidea, which has been considered the sister group to the Dikelocephaloidea. In addition, the ontogenetic development of the free cheeks shows that A. subglobosa possessed anteriorly yoked free cheeks during the early phase of development but formed a ventral median suture by splitting the yoked cheeks in the later phase of ontogeny. This contrasts with the previously suggested mode of ventral median suture formation of the Order Asaphida. This alternative mode of ventral median suture formation of A. subglobosa, along with non-asaphoid protaspid morphology, warrants removal of the Dikelocephaloidea from the current Order Asaphida. This study further demonstrates that the ventral median suture did not evolve only once in the evolutionary history of trilobites. With the addition of the mode here documented for Asioptychaspis, the ventral median suture is now known to have developed independently and in a different fashion at least three times in the history of Cambrian trilobites.


A clear-cut difference between chromatin melting curves of cells from the patient with Down's disease and his mother and ones from healthy individuals and the proband's father was shown by fluorescence microscopy and acridine orange staining on human fibroblasts incubated in autologous serum. These data suggest the presence of an obvious genetic correlation between phenotypically healthy mother and her sick child. The identity of the chromatin structure of the patients detected both on lymphocytes and other type of cells, human fibroblasts, allows a suggestion that the phenomenon of the altered chromatin structure is typical generally of the given individual's tissues. Certain changes in the cell chromatin structure are mediated by the effect of autologous serum.


Objective: Study the effect of Omani coffee on the glycemic responses and glycemic index (GI) of commonly consumed snack foods in Oman. Methods: We evaluated 9 Omani snack foods including doughnut, croissant, cheese, chicken and fried egg sandwiches, sambosa (vegetables), fried and boiled vermicelli, white bread with red beans for their proximate composition and GI. The proximate composition was determined according to AOAC,[1] whereas GI was measured in 12 healthy human volunteers as described by Wolever et al.[2] Results: The proximate composition of snack foods differed significantly (P < 0.05). The moisture, crude protein and fat contents in foods ranged from 21.9 to 67.5%, 4.3 to 17% and 2.7 to 23.4 %, respectively. Almost similar blood glucose responses were observed when snack foods were given with either water or Omani coffee. Significant (P < 0.05) differences were observed in the GI of these foods, which ranged between medium and high GI category. The GI of these foods (with water) ranged between 60 and 75, whereas with Omani coffee the GI values ranged between 64 and 78. Higher GI values were observed for doughnut and cheese sandwich, whereas sambosa (vegetables) showed the lowest value. Overall, no significant (P < 005) differences were observed in the GI of snack foods when served either with water or with Omani coffee. Conclusion: The GI of Omani snack foods differed significantly. However, Omani coffee did not affect the GI of these snack foods.


Since 1999, use of electronic calls has been legal for hunting lesser snow geese (Chen caerulescens caerulescens; hereafter snow geese) during special seasons or times of day when other waterfowl species could not be hunted in prairie Canada. Prior to expanding the use of electronic calls for hunting snow geese during fall hunting seasons, effects of these calls on nontarget goose species must be examined. Accordingly, we examined the vulnerability of Canada (Branta canadensis) and white-fronted geese (Anser albifrons) (dark geese) to electronic snow goose calls and 3 goose decoy sets (dark, mixed, and white) during the 1999 fall hunting seasons in Manitoba and Saskatchewan. Canada geese were 2.3 times more likely to fly within gun range (P<0.001) and the mean number killed/hour/hunter was 2.5 times greater (P=0.043) during control periods when hunters were silent or used traditional calling methods (i.e., hand-held and voice calls) than when hunters used electronic snow goose calls. Flock response and kill rate for Canada geese declined as proportions of white decoys increased in decoy sets (P<0.001). White-fronted geese were 1.8 times more likely to fly within gun range (P=0.050) and the mean number killed/hour/hunter was 5.0 times greater (P=0.022) during control periods than during periods when electronic snow goose calls were used. Flock response for white-fronted geese also declined as the proportion of white decoys increased in decoy sets (P<0.001). The legalization of electronic snow goose calls during fall hunting seasons in prairie Canada should not result in increased harvest of nontarget dark geese.


The recent growth in snack food types has led to increasing demand for attractive snack food packaging. To attract consumers' attention successfully, it is essential to influence their decisions by meeting their packaging needs. This study examines the interrelationship between different packaging design characteristics and their influence on consumers' purchase decisions. Twenty-five design professionals and 121 students participated in the study. A survey developed for applying the Decision-Making Trial and Evaluation Laboratory (DEMATEL) method was used to evaluate the importance of design characteristics. The results showed that color, shape, image, line, and typography were the five most essential design characteristics influencing consumer purchase behavior, and that image is the most significant impact factor on consumer purchase decisions. Surprisingly, materials and technology have little influence on consumers' decisions. Therefore, enhancing these packaging design characteristics can improve the interaction between snack food packaging and consumers and increase food sales.


The self-consistent model, developed previously to describe phonon coupling (PC) effects in magnetic moments of odd magic and semi-magic nuclei, is extended to quadrupole moments. It is based on the theory of finite Fermi systems with the use of the perturbation theory in $g_L^2$, where $g_L$ is the vertex creating the $L$-phonon. Accounting for the phonon tadpole diagrams is an important ingredient of this model. The calculation scheme is based on the Fayans energy density functional DF3-a and does not contain any adjusted parameters. The odd In and Sb isotopes are considered, which are the proton-odd neighbors of even tin nuclei. The $2^+_1$ phonon is taken into account which quadrupole moment is one ingredient of the calculation scheme. The corresponding values were found by us previously. Two main PC corrections, due to the phonon $Z$-factor and due to the phonon-induced interaction, have opposite signs and cancel strongly each other, leaving room for other `small' corrections, so that the resulting PC correction is much lower than the absolute values of each of two main ones. However, it remains noticeable, making the overall agreement with the data significantly better.


Leukemia is a complex disease pathologically manifested at the DNA, mRNA and protein level. Understanding leukemia pathogenesis is prevalently focused on mutations at the DNA (or mRNA) level, however the functional consequences of these changes on cellular machineries are not fully clarified. Since proteome analysis provides link between gene sequence and cellular physiology, proteomics can contribute to elucidate mechanism of disease and response to treatment. Moreover some alterations are manifested only at the protein level including subcellular localisation, post-translational modification (e.g. phosphorylation), protein cleavage or protein-protein interactions.

Performing large-scale protein analysis of primary leukemia samples requires the development of more effective proteomic approaches as well as new analytical strategies. Here, we present novel microsphere-based antibody array format with automatical analysis tool that can follow changes in expression and post-translational modification of leukemia associated proteins with regards to intracellular localisation and protein cleavage in primary childhood acute leukemia (AL).

Size Exclusion Chromatography-Microsphere-based Affinity Proteomics (SEC-MAP) is a set of 1728 populations of fluorescently-labeled microbeads, each carrying an antibody against respective human protein. Native cellular proteins (and their complexes) are isolated using detergents, labeled with biotin and subjected to size exclusion chromatography to obtain 24 molecular weight fractions. The fractions are incubated with SEC-MAP microbeads and the antibody-protein binding is detected using fluorescently-labeled streptavidin by flow cytometry. Flow cytometer resolves color-code of each microbead population and reads the amount of bound protein. The signals from 24 size fractions are combined and protein binding is detected as protein reactivity peaks similar to bands on western blot. The analysis is performed using automatic software created in R. It allows for automatic processing of fcs files as well as advanced follow-up analysis including quality control, normalisation, protein peaks recognition and clustering of results

We have examined the expression of cytoplasmic (n=980) and membrane (n=769) proteins in 69 primary samples of AL obtained at diagnosis according to the Institutional Ethics Committee Giudelines. For the normalisation of protein expression we have used Loess normalisation commonly used in mRNA profiling studies.

Due to ability of SEC-MAP to separate proteins according their molecular weight we have identified not only the expression of proteins but also the size that corresponds to its monomeric or multimeric presence and furthermore could serve as a control of proteolysis. We have revealed the sensitivity to proteolysis of 4 standard house-keeping proteins (Akt, Abl, β-actin and β2-microglobulin). Abl and Akt proved to be better controls of proteolysis. Detected with SEC-MAP or western blot, β-actin and β2-microglobulin, unlike Abl and Akt, have not been found in their cleaved forms in the proteolytically digested samples. Thus we have identified proteolysis in 12 samples which have been subsequently excluded from the analysis. So far we have identified 44 proteins (including CD markers distinguishing lineage specificity e.g. CD22, CD3, CD33) which have been differentially expressed in different subtypes of AL (B-cell precursor acute lymphoblastic leukemia, BCP-ALL, n=35), T-cell acute lymphoblastic leukemia (T-ALL, n=9) and acute myeloid leukemia (AML, n=13) (Multiple Testing Procedures - Bioconductor Package multtest, p<0.05). We have verified the expression using flow cytometry or western blot. From non-CD markers, we have found e.g. BLNK, DBN1, PAX5, PTK2 overexpressed in BCP-ALL, EIF5A, LAT, SH2D1A, SSEA4 overexpressed in T-ALL and CEBPA, CTBP2, GLUD1, LCP(pY145) and PTPN6 overexpressed in AML.

In summary, SEC-MAP proved to be strong proteomic tool capable of identifying leukemia phenotype as well as providing novel insights into the protein expression and post-translational modification of primary childhood AL. Moreover it can bring complementary information about proteolysis not captured by planar arrays (western blot) which can significantly affect proteomic results.

Supported by GAUK 596912, IGA NT13462, IGA NT12397, P302/12/G101, UNCE 204012, 00064203.

Disclosures: No relevant conflicts of interest to declare.


Background: We studied the effects of vitamin D3 supplementation on serum levels of 25-hydroxyvitamin D and typical clinical symptoms in children with autism spectrum disorder (ASD). Methods: We enrolled 5 male and 1femaleJapanesechildren with ASD aged 3years. Serum25-hydroxy vitamin D was measured prior to after 9months of supplementation with oral vitamin D3 oil (2μg /day of vitamin D3, corresponding to twice the daily requirement). The Childhood Autism Rating Scale (CARS), Short Sensory Profile (SSP), Vineland-II were used to assess the severity of autism-related traits. Data were analyzed using a Wilcoxon test. Results: The 25-hydroxy vitamin D level were=20 ng/mL and Conclusion: These findings show that vitamin D supplementation might ameliorate typical clinical symptoms in children with autism spectrum disorder.


Introduction Increases in plant species diversity may increase the community diversity effect and produce community over-yielding. Epichloë endophytes, as symbiotic microorganisms, are also capable of regulating plant communities, but their effects on community diversity effects are often overlooked. Methods In this experiment, we investigated the effects of endophytes on the diversity effects of host plant community biomass by constructing artificial communities with 1-species monocultures and 2- and 4-species mixtures of endophyte-infected (E+) and endophyte-free (E-) Achnatherum sibiricum and three common plants in its native habitat, which were potted in live and sterilized soil. Results and discussion The results showed that endophyte infection significantly increased the belowground biomass and abundance of Cleistogenes squarrosa, marginally significantly increased the abundance of Stipa grandis and significantly increased the community diversity (evenness) of the 4-species mixtures. Endophyte infection also significantly increased the over-yielding effects on belowground biomass of the 4-species mixtures in the live soil, and the increase in diversity effects on belowground biomass was mainly due to the endophyte significantly increasing the complementary effects on belowground biomass. The effects of soil microorganisms on the diversity effects on belowground biomass of the 4-species mixtures were mainly derived from their influences on the complementary effects. The effects of endophytes and soil microorganisms on the diversity effects on belowground biomass of the 4-species communities were independent, and both contributed similarly to the complementary effects on belowground biomass. The finding that endophyte infection promotes belowground over-yielding in live soil at higher levels of species diversity suggests that endophytes may be one of the factors contributing to the positive relationship between species diversity and productivity and explains the stable co-existence of endophyte-infected Achnatherum sibiricum with a variety of plants in the Inner Mongolian grasslands.