In present days, the indoor spaces need more and more attention on the design of acoustic proprieties of enclosed environments such as conference rooms, classrooms and offices. In order to obtain low internal noise levels and correct speech intelligibility, indoor sound field should be studied properly.In this work, a comparison of the reverberation time measured and calculated in two rooms using different model has been made. Results clearly show that calculated results are not in agreement and differ from measured values.


In the new LITA strategic plan, members have suggested an objective for open access (OA) in scholarly communications. Some people describe OA as articles the author has to pay someone to publish. That can be true, but that's not how I think of it. OA is definitely not vanity publishing. Most OA journals are peer-reviewed. I like the definition provided by EnablingOpenScholarship: Open Access is the immediate (upon or before publication), online, free availability of research outputs without any of the restrictions on use commonly imposed by publisher copyright agreements. (1) My focus on OA journals increased precipitously when the licensing for a popular American weekly medical journal changed. We could only access online articles from one on-campus computer unless we increased our annual subscription payment by 500 percent. We didn't have the funds, and now the students suffer the consequences. I think it was an unfortunate decision the journal's publishers made. I know from experience that if a student can't access the first article they want, they will find another one that is available. Interlibrary loan is simpler than ever, but I think only the patient and curious students will make the effort to contact us and request an article they cannot obtain. In 2006 scientist Gary Ward wrote that faculty at many institutions experience problems accessing current research. When faculty teach "what is available to them rather than what their students most need to know, the education of these students and the future of science in the U.S. will suffer." He explains it is a false assumption that those who need access to scientific literature already have it. Interlibrary loans or pay-per-view are often offered by publishers as the solution to the access problem, but this misses an essential fact of how we use the scientific literature: We browse. It is often impossible to tell from looking at an abstract whether a paper contains needed methodological detail or the perfect illustration to make a point to one's students. Apart from considerations of cost, time, and quality, interlibrary loans and pay-per-views simply do not meet the needs of those of us who often do not know what we're looking for until we find it. (2) I want our medical students and tomorrow's doctors to have access to all of the most current medical research. We offer the service of providing JAMA articles to students, but I'm guessing that we hear from a small percentage of the students who can't access the full text online. Are people reading OA articles? …


Düzce province is located where the land has the most movability; this is seen on the belt in the World. It is located in a seismic zone between the European and Asian continents bordered by the Black Sea and the Mediterranean. The most important fault affecting the study area is the North Anatolian Fault Zone (NAFZ). NAFZ is a fault zone which has high activity. The earthquake of the 17 th of August 1999, located in İzmit and the earthquake of the 12 th of November in Düzce, has occurred on this fault zone, with devastating damages, loss of life and property under the light of looking at the historical and instrumental records, it is understood from the historical remains and underground debris that devastating earthquakes have occurred. The earthquakes have been investigated and traced to the ancient city of Prusias in Düzce Province, where the destruction of historic magnitude and archaeological ruins have been discovered. In addition, the samples which belong to the historical ruins created by the earthquakes could have now been seen on the ancient structures in the historic city around the Konuralp campus. In this research, the characteristics of some historical ruins belonging to the Roman period in historical ancient city was determined and damages caused by earthquakes were investigated. At the end of the research, it is was concluded that the ancient period of buildings affected by the ground movements which occurred in Konuralp Campus were completely destroyed as the result of these earthquakes.


Several two-equation turbulence models are compared to data from direct numerical simulations (DNS) of the homogeneous elliptic streamline flow, which combines rotation and strain. The models considered include standard two-equation models and models with corrections for rotational effects. Most of the rotational corrections modify the dissipation rate equation to account for the reduced dissipation rate in rotating turbulent flows, however, the DNS data shows that the production term in the turbulent kinetic energy equation is not modeled correctly by these models. Nonlinear relations for the Reynolds stresses are considered as a means of modifying the production term. Implications for the modeling of turbulent vortices will be discussed.


The migration mechanism and the minimum energy path of vacancies, interstitials, and an interstitial–vacancy pair in zinc oxide have been studied by the dimer method. The in-plane and out-of-plane migrations of zinc and oxygen vacancies are anisotropic. The kick-out mechanism is energetically preferred to zinc and oxygen interstitials that can easily migrate through the ZnO crystal lattice. In addition, the migration process of an interstitial–vacancy pair as a complex of an octahedral oxygen interstitial and a zinc vacancy is dominated by an oxygen interstitial/zinc vacancy successive migration. The energy barriers indicate that the existence of oxygen interstitial in the defect pair can promote the mobility of zinc vacancy, whereas the migration of oxygen interstitial is slowed down due to the presence of zinc vacancy. In the end, we show a possible migration path of the interstitial–vacancy pair that can be dissociated through a set of displacement movements.


Cellular senescence has been proposed as a pathophysiologic driver in the development of pelvic organ prolapse (POP), especially during aging. In this study, we aimed to determine if markers of cell senescence can be quantified from vaginal secretions collected from pre‐ and postmenopausal women with and without POP.


The General Motor's (GM) model is perhaps the most well known and established car-following model. This paper attempts to clear up the contradictions that exist on its calibration. Several unpromising aspects revealed from the literatures might have contributed for the discrepancies seen in their outcomes. The GM model parameters were calibrated using the car-following data collected by RTK GPS receivers during test track experiments. A broader calibration scheme was implemented accommodating different alternatives for model approaches, driving conditions and calibration methods in a consistent manner. The model parameters were identified, tested and characterized with improved reliability.


In this study, we have a analysis of the ARM core unit design of a remote video monitoring system. An important aspect of a remote video monitoring system is that the image information stored in the monitoring system is transmitted to a remote PC through the GSM/GPRS network. There into the application of the ARM core unit is one part of the design of the entire remote video monitoring system. An ARM core unit is designed based on ARM architecture and ARM chips. It includes hardware and software design. Practice shows high stability and reliability of the design.


Based on monthly analyses of EOS/MODIS data(local time 10:30) of Shanghai City,China from 2003 to 2005,land surface temperature(LST) is retrieved with split window algorithm and it is used indirectly to get the quarterly intensity and higher temperature area of urban heat island.Results show that: ① the mean highest LST is 13.9 ℃ in winter and 32.5 ℃,45.7 ℃ and 29.0 ℃ in spring,summer,and autumn,respectively;② the relatively higher LST area distribution has obvious seasonal variation and it moves southeast in winter,northwest in spring and summer,and draws back southeast again in autumn;③ weak urban cold island exists in urban areas during winter mornings;urban heat island exists in spring,summer and autumn;the summer's heat island is the most notable;④ LST of urban cold island centre in winter morning is 2.6 ℃ lower than that of countryside and the mean urban heat island intensity is 5.7 ℃,10.4 ℃ and 4.2 ℃ in spring,summer and autumn,respectively.


NMR based metabolomics of biofluids in cancer Guro F. Giskeødegård1, Torfinn S. Madssen1, Leslie R. Euceda1, May-Britt Tessem1, Siver A. Moestue2,3, Tone F. Bathen1. 1: Dept. of Circulation and Medical Imaging, Norwegian University of Science and TechnologyNTNU, Trondheim, Norway; 2: Dept. of Clinical and Molecular Medicine, Norwegian University of Science and Technology-NTNU, Trondheim, Norway; 3: Dept. of Health Science, Nord University, Bodø, Norway.


For sensing the information of self-propelled antiaircraft artillery's shooting quickly, this paper designs and realizes an auto-monitor and auto-detect system. Sensor was used to sample the information of shooting of self-propelled antiaircraft artillery in the system. By analyzing the information, we can hold the operation and technology status of the artillery. And the information is the direct support for the indemnification decision-making and the evaluation of capability to battle.


BACKGROUND Gall bladder functions are modulated by neurones intrinsic to the organ. Data are available on the neurochemical composition of intrinsic and extrinsic nerves innervating the gall bladder but are lacking on specific functional classes of gall bladder neurones. AIMS To characterise the intrinsic motor neurones of the gall bladder and identify their roles using pharmacological techniques. METHODS Retrograde tracing from the possum gall bladder muscle in vitro allowed identification of intrinsic motor neurones. Subsequently, their content of choline acetyltransferase and nitric oxide synthase, markers of acetylcholine and nitric oxide containing neurones, was established using immunohistochemical techniques. Organ bath pharmacology was used to evaluate neurotransmission by acetylcholine and nitric oxide in gall bladder muscle strips. RESULTS Innervation of the gall bladder musculature by neurones of both the muscular and serosal plexuses was demonstrated. A large proportion (62%) of these motor neurones were immunoreactive for nitric oxide synthase. All gall bladder neurones showed immunoreactivity for choline acetyltransferase. Organ bath pharmacology confirmed the neuroanatomical data, showing acetylcholine and nitric oxide mediating neurotransmission to the gall bladder musculature. CONCLUSIONS Neurones containing acetylcholine and nitric oxide, located within the muscular and serosal plexuses, provide excitatory and inhibitory motor innervation of the gall bladder, respectively. The large inhibitory innervation suggests active relaxation of the gall bladder during filling, mediated by intrinsic nerves.


Details are presented of a procedure for analyzing inelastic beam and beam column problems of arbitrary thin-walled open cross section, under the assumption of no strain reversal. The finite element formulation associated with such a procedure and the expressions for programming the necessary computation of section properties and element matrices are given. The technique has been illustrated by solving some simple problems for which alternative results are available.


Based on describing the environmental pollution by mining and the concept of mine clean mining technology, we further explained the technological principle and process with paste backfilling, and described the constitutes of filling material and its characteristic, the constitutes of paste backfilling system and its process in detail. What is more, this paper summarized the technological characteristic and the scope of application of paste backfilling. Finally, cooperating with a practical engineering in Daizhuang Mine, it analyzed the concrete implement process and proved the applied effect of the paste backfilling. The results show that paste backfilling mining is an effective approach to settle damage caused by coal mining to water resources, land resources, building resources. Compared with other approaches, it has some advantages, such as high security, high recovery ratio, and environment friendly, and moreover, the surface subsidence can be controlled effectively, but also solid waste, such as coal gangue, can be used as a resource with paste backfilling. This method is worth to be applied and popularized as a mine clean mining technology.


Web Services is a new component technology,and XML is the base of it.This paper mainly introduces the key technology and main protocols that could realize Web Services,such as XML,SOAP,WSDL and UDDI.This paper also discusses how to use.NET to realize Web Services in web application.


ABSTRACT The main objective of this research work was to analyze the economic analysis of maize marketing in Surulere Local Government Area of Oyo-State. The data were collected with the aid of a well structured questionnaire and were later analyzed. About half of the maize marketers (49.9%) had their age between 31-40 years in the study area, most of the maize marketers (80%) are female, while more than half of the maize marketers (60.8%) are married, and 63.3% of the respondents had no schooling experience. Again, high proportion of the marketers had experience less than 10years. For the maize marketers selling price, the significant variables include, age, educational level, major occupation, cost of shop, sellers association and they all have positive relationship with selling price. Barrier to entry and cost of loading. The age, educational level, major occupation, cost of shop and cost of loading are significant at 1% level of significance, while sellers association and barrier to entry are significant at 5% level. An adjusted R 2 value of 0.549 which implies that the regression equation accounted for 54.9% of the independent variable like age, educational level, major occupation, cost of shop and cost of loading while the remaining 45.1 percent is an accounted for which might be due to error embedded in the data itself. From the result of the study, the value of Fcal>Ftab. It is therefore concluded that there is a significant relationship between the socio-economic characteristics of the maize marketers and selling price and there is a significant relationship between cost and selling price.   Keywords: Economic analysis, Marketing, Cost, Model, Maize


AbstractIn this study, 3D coherent flow structures during incipient particle entrainment under unidirectional flow conditions were experimentally investigated. Time-resolved tomographic particle tr...


This research investigating the careers of Practice Teaching Award holders in London and the South East region drew on questionnaires to 438 PTA holders (50% response) and interviews with agency learning and development managers. A key theme to emerge was that the Award was seen as providing an opportunity to develop supervisory skills which might assist a move to management or to become a senior practitioner with staff supervisory responsibilities, and that there were many factors in their careers and organizations affecting Practice Teachers' abilities or willingness to continue supervising student social workers on placements.


This article traces the historical origins of a localized gender division of labor found in two villages on the edge of the city of Bobo-Dioulasso, Burkina Faso. Through social-historical analysis, this article demonstrates that gender divisions of labor are not simply constructed in particular places; they are constructs located near or far from other places, and thus influenced by multidimensional interactions between those places. Specifically, this article shows how the villages' location on the periphery of an important regional city has shaped their experience of European colonialism, religious change and market expansion in ways that have given particular meanings to certain kinds of work in commercial gardening. More generally, this article shows how a focus on the historical meanings of work can provide insights into local variations in gender divisions of labor.


This systematic review evaluates the efficacy and safety of duodenal-jejunal bypass liner for the treatment for patients with obesity (class I and higher) with/without type 2 diabetes mellitus.
The duodenal-jejunal bypass liner is a minimal-invasive method to reduce body weight and to control type 2 diabetes mellitus. The technology consists of a 60 cm sleeve, which is endoscopically delivered into the duodenum and a small part of the jejunum.


The objectives for this study were to explore health promotion behaviors as well as factors that promote health behaviors. This study focused on public health personnel in the southern and of the northern region. A total of 511 persons participated in this study. Statistical analysis tools used in this study included frequency analysis, percentile analysis, mean, standard deviation, and chi-square. The results of the study show that in health behavioral aspect 62.4% of participants exercised sometime, and 18.8% exercised regularly. Results also showed that 8.0% of the participants smoked regularly and 8.6% drunk alcohol regularly. 43.6% of the participants indicated a normal stress level, 38.2% a mid level of stress, and 8.8% a high level of stress. When participants were asked about factors that contributed to their stress levels, 75.7% indicated stress from work, 53.4% from school, 34.1% from their current economic situation, and 17.8% from a relationship. 72.0% of the participants released their stress by saw movies, 35.2% by played sport, and 28.0% by consulted their family members. 40.3% of participants were exposed to the health promotion behavior in the classroom. A low number of these (24.5%) were master degree students who took the offered health promotion course. 18.6% of participants were exposed to train in the health promotion behavior. 79.8% of participants had joined the health club and health network in the health promotion program. 71.6% of participants had participated and contributed community to construct the health club and health network in the health promotion program. 19.4% of participants had conducted the research on the health promotion topics. Most participants indicated that they would like to continue their schooling in the health promotion field. Diseases found in the participants include: 1) 32.5 % with peptic ulcers, 23.8% with allergies, 16.8% with migraines, and 10.4% with high levels of cholesterol. The factors that are associated with health promotion behaviors found that gender is significantly associated with exercise, non-smoking behavior, not drinking alcohol behavior, as well as Body Mass Index. (p


Objective: Children's adoption affects individuals in various ways, but regardless of its enormous relevance, socio-economic literature has devoted little attention to this phenomenon in Italy, the first-ranked country in the world for inter-country adoptions relative to its population in recent years. This paper describes the Italian adoption system by highlighting the role of accredited bodies and reporting data from the very first survey on Italian inter-country adoptions. Method: The demand for adoptive children is empirically investigated as the relation between parental satisfaction and the characteristics of both the procedure itself and those of the adoptive children. Results: Findings confirm adoptive parents' satisfaction to be inversely correlated with child age, the duration of the adoption procedure and the size of the accredited body. Conclusion: In order to improve the (successful) adoption system the Italian Government should reduce the self-selection of families, and the opacity of costs.


This field research aims to determine three things: the background of the changing fatwa  MUI on Vasectomy from 'haram' to 'halal on condition'; responses from the Moslem scholars; and the impact of fatwa on increasing the number of Vasectomy participants in Central Java. The data collection was done by using documentation and interviews while data analysis was done by using descriptive qualitative method. The results of this research are: 1) The reason for the changing fatwa on Vasectomy from 'haram' to 'halal on condition' is due to a new ' illat , namely the success of recanalization. 2) Against the new fatwa, Ulama Muhammadiyah approved it by tightening and adding certain requirements. While Ulama NU disagree on the fatwa as evidence of the success of recanalization is considered not convincing (muhaqqaqah) . 3) The new fatwa has not been an impact on increasing the number of Vasectomy participants in Central Java.


Internationalization of colleges and universities has become a general tendency in the development of higher education of the world. There is deep historical background for the development of internationalization of colleges and universities in China. To meet the requirements for internationalization development of colleges and universities,it is necessary to cultivate excellent world-oriented talents,choose and support a series of key disciplines,strengthen infrastructure construction and international cooperation and exchange,unite patriotism and internationalism,etc. so as to accelerate the course of internationalization of colleges and universities in China.


Based on analyzing the necessity of setting up periodical Maintenance window for high-speed railways, by using "slope analysis method", this paper provides the calculation method of evening-departure morning-arrival trains operation number on up and down line when setting up 2 h inspection window and the window sectional number was divided into 2, 3 and 4. The paper also summaries the influence principle of window sectional number on "feasible section" of evening-departure morning-arrival trains. In the end, taking Beijing-Guangzhou high-speed railway as example, the calculation result shows when applying 4 rectangular Maintenance window sections of "Beijing West-Shijiazhuang-Changsha South-Guangzhou South", the number of evening-departure morning-arrival trains on up and down line could reach to a maximum.


Treatment of chronic critical limb ischemia still remains one of the most serious problems of vascular surgery. Most often, chronic critical limb ischemia is caused by multi-segmental disease of arterial tree, involving both the aorto-femoral and infrainguinal vessels. In the majority of these cases, proper correction of aorto-iliac arteries is sufficient to restore the circulation in lower limbs. However, in 10-15% it is necessary to perform multi-segmental reconstructions. In these cases it is extremely important to choose the optimal inflow procedure. The aim of this retrospective study was to compare perioperative and long-term results of multisegmental reconstructions, using aorto-bifemoral, unilateral ilio-fetYIoral, and extra-anatomical bypass as inflow procedures. During the 1 0-year period (1 984-1 994), 4074 aorto-femoral reconstructions were performed for treatment of O C C ~ U S ~ V ~ arterial disease. In 449 cases (1 1 %), multi-segmental aorto-femoro-poplteaVtibial reconstructions were undertaken. Aortobifemoral bypasses was performed in 131, unilateral ilio-fet?Ioral bypasses in 288, and extraanatomical bypasses in 30 cases. In 221 cases, the operations were performed in one stage. and in 228 cases a two-stage procedure took place. Postoperative mortality was 3.8% in the aorto-bifemoral bypass group, 1 -3% in the unilateral ilio-femoral group, and 3,3% in the extraanatomical group. Primary inflow graft patency rate after 12 months was 94.7% in the aortobifemoral bypass group. 94.1% in the unilateral ilio-femoral group. and 80% in the extraanatomical group. Secondary inflow graft patency rate Was 97.8% in the aorto-bifemoral bypass group. 96.2% in unilateral ilio-femoral group, and 96.796 in extra-anatomical group. The 5-year primary and secondary graft patency rates were 90.9% and 94.7% in the aortobifemoral bypass group, 88.5% and 93.4% in the unilateral ilio-femoral group, and 66.7% and 77.3% in the extra-anatomical group, respectively. Conclusion: Unilateral ilio-femoral bypass as an inflow procedure for treatment of multilevel occlusive arterial disease is as effective as aorto-bifemoral bypass, with lower perioperative mortality and morbidity rates. Extra-anatomical bypasses are, however. less effective. O 1998 The International Society for Cardiovascular Surgery. Published by Elsevier Science Ltd. All rights reserved


Extensive experience with animals has shown that it is possible to irradiate the iris with a ruby laser without damage to the cornea, lens, or retina (Hallman, Perkins, Watts, and Wheeler, I 968, I969). The possible use of a laser to make an iridotomy for therapeutic purposes was appreciated by Flocks and Zweng (i964), and Zweng, Flocks, Kampany, Silbertrust, and Peppers (I964) reported two attempts to perform this in human eyes. In neither case was a complete iridotomy produced, but holes were produced in two pigmented irides by Zweng, Paris, Vassiliadis, Rose, and Hayes (I970). Some success in treating a small series of cases of closed-angle glaucoma and secondary glaucoma due to iris bombe has been reported (Perkins, I970, I971), and this paper is an attempt to evaluate the clinical application of laser iridotomy from the results of treating more than forty eyes.


The aim of this study is to evaluate the effect of Azotobacter vinelandii, Paenibacillus polymyxa and Pseudomonas fluorescens isolated from rhizosphere of field-grown sugarcane in Barak Valley, Assam, as nitrogen biofertilizer on sugarcane plant growth under pot experiment condition. Four types of treatment i.e control with no inoculums (T0), Azotobacter vinelandii (T1), Paenibacillus polymyxa (T2), Pseudomonas fluorescens (T3) were used as biofertilizer. The difference in the growth among different treatment is found to be statistically significant at 5% significance level.


The porphyrin-heme pathway is controlled in the liver at the level of the mitochondrial enzyme 8-aminolevulinate synthase (EC 188.8.131.52), a protein inducible in cultured avian hepatocytes by a variety of chemicals including certain 5,3-metabolites of steroid hormones. The great sensitivity of the induction process to inhibition by agents known to block transcriptional activity of genetic material suggests that some control mechanism may be operating at this level to regulate the formation of the enzyme. We report here enhancement of nuclear RNA synthesis and of Mn2+-(NH4)2SO4-stimulated DNA-dependent RNA polymerase (EC 220.127.116.11) activities by the 5,8-steroid metabolite, 3a-hydroxy-5,3-androstan-17one (etiocholanolone), in cultured avian hepatocytes during induction of the enzyme. These changes were demonstrated in the G1 phase of the hepatocyte cell cycle at a time when DNA synthesis is constant. Our findings support the view that one of the early steps in the process of induction of 5-aminolevulinate synthase by steroid metabolites requires new RNA synthesis, very probably messenger RNA, suggesting a 5,8-steroid transcriptional control mechanism for induction ofthis protein. The rate-controlling step in porphyrin-heme biosynthesis is localized at the level of the mitochondrial enzyme &.aminolevulinate synthase (ALA-synthase) [EC 22.214.171.124; succinylCoA: glycine C-succinyltransferase (decarboxylating) ] (1-4). This protein is inducible by many chemicals in vivo in chick embryo (4, 5) and in avian hepatocytes grown in primary cultures (3, 6). These chemicals include 5,8-steroid metabolites, such as 3a-hydroxy-5g3-androstan-17-one (etiocholanolone), derived from the biotransformation of sex hormones in man (3, 7), a class of hormone derivatives previously thought to be inert. The great sensitivity of the induction process to various inhibitors, particularly those preventing RNA synthesis (1, 8), implies that some control mechanism is operating at the transcriptional level to regulate the formation of the enzyme. The importance of new mRNA formation prior to induction of this specific protein in the liver has also been suggested by our previous demonstration that a-amanitin, a potent inhibitor of the nucleoplasmic DNA-dependent RNA polymerase, blocks induction of ALA-synthase in vivo by the barbiturate analogue, 2-allyl-2-isopropylacetamide (ALA), and the steroid etiocholanolone (1). Abbreviations: ALA-synthase, 5-aminolevulinate synthase; AIA, 2-allyl-2-isopropylacetamide; etiocholanolone, 3a-hydroxy-50-


The use of several techniques for non-destructive testing is a common strategy for detecting and classifying flaws in aluminium material. Techniques like multiresolution data analysis and data classifiers are valuable for obtaining as much information as possible from the flaws. The combination of both techniques allows the clear definition of several characteristics like localization, size and form. In this study, localization using Time-Frequency Distribution feature extraction and an ART2 neural network as a classifier is the main goal.


550 • J Clin Pharmacol 2007;47:550-552 T more than ever, big pharmaceutical companies are venturing into the biotechnology arena with the hope that novel therapeutic biologics will fundamentally reshape the pharmaceutical landscape. Several companies are even projecting optimistically that, within the decade, therapeutic biologics will comprise a majority of their commercial portfolios. Therapeutic biologics derived from proteins are generally thought to be less prone to untoward effects than small molecular entities derived from chemical synthesis. Although this may often hold true for certain targeted biologics, this may not be the case for all biologics. The recent unexpected outcome of the first-in-human (FIH) study of TGN1412 clearly indicates the need for extra precaution whenever an investigational product is first evaluated in humans— but perhaps even more so during initial clinical investigation of monoclonal antibodies (mAbs) designed as agonists. In the TGN1412 FIH study, for example, this superagonist anti-CD28 mAb was rapidly administered intravenously (ie, the infusion lasted 3 to 6 minutes) to 6 healthy volunteers in short sequence (ie, 10 minutes apart). Even though the selected FIH dose was only 1/500th of the reported safe animal dose, all 6 volunteers experienced an acute, immunemediated cytokine storm that unfortunately led to multiorgan failure. The Medicines and Healthcare Products Regulatory Agency (MHRA), in conjunction with the German Regulatory Authorities, subsequently conducted a series of inquiries and inspections. Their final report recently concluded that the tragic events were not the result of any errors in TGN1412 manufacturing, formulation, dilution, or administration. An independent Expert Scientific Group (ESG) appointed by the Secretary of State for Health in the United Kingdom, however, determined that— although the animal safety and toxicology studies of TGN1412 adequately fulfilled the requisite regulatory requirements—the overall preclinical program did not adequately predict a safe FIH dose. The ESG then listed 22 specific recommendations for ensuring the safety of future FIH study participants. These recommendations particularly addressed methods of determining safe starting doses in humans as well as selecting appropriate observation time periods between sequential dose administrations in early phase I studies. The serious adverse events that occurred during the TGN1412 FIH study were, in hindsight, not altogether surprising considering the inherent properties of therapeutic biologics. That is, because therapeutic mAbs are purposefully engineered to show high affinities for specific human protein targets, these mAbs may show little or no binding to the homologous animal counterparts. By contrast, classic small-molecule drugs are often more likely to show similar potencies in animals and humans. Consequently, Hansen and Leslie recommended that future preclinical studies of antibodybased biologics "should also include comparative measurements of the binding affinities for both human antigen and primate antigen, to control for unforeseen variations in protein structure." The TGN1412 incident will likely have an industrywide effect on future development strategies of novel biologic therapies. The more cautious stepwise approach that is commonly used to develop small molecular drugs, for example, might actually be safer and just as useful in the development of large molecular biologics. At the very least, stricter scrutiny of the transition from preclinical to FIH studies of therapeutic biologics is expected from institutional review boards, patient advocacy groups, and worldwide regulatory authorities alike. Biologics in the Pipeline: Large Molecules With High Hopes or Bigger Risks?


This study assessed the impact of several variables central to self-presentation theories on self-reported shyness. Data were collected from 286 Canadian college students who completed measures of shyness, expectations of rejection, interpersonal competence, and perfectionism. The sample was randomly divided in half to allow for cross-validation. Consistent with hypotheses, shyness was predicted by expectations of rejection and interpersonal competence for the initial sample. However, contrary to self-presentation theories, shyness was not predicted by high self-standards nor by perceptions that others held high expectations of the self. These findings were replicated in the cross-validation sample. Results partially support self-presentation theories of shyness and suggest that while interpersonal competence and fear of rejection are central to shyness, the shy do not necessarily hold unrealistically high standards for themselves or view others as expecting perfection from them.


Bammel, Gene, and Lei Lane Burrus-Bammel (1992). Leisure and Human Behavior, Second Edition. Dubuque, IA: Wm. C. Brown Publishers. ISBN 697-12200-X $33.50 (cloth). 433 pp. Edginton, Christopher R., Debra J. Jordan, Donald G. DeGraaf and Susan R Edginton (1995). Leisure and Life Satisfaction. Dubuque, IA: Brown and Benchmark Publishers. ISBN 0-697-13232-3. $32.25 (cloth). 443 pp. Introductory texts in parks and recreation tend to be one of two types: books that describe the leisure service delivery system or books that focus on leisure and leisure behaviors. Leisure and Human Behavior falls in the latter category while Leisure and Life Satisfaction is written in the classic "introduction to recreation and leisure services" mode. Both textbooks are intended for students beginning the quest for information about leisure and its facets. In revising their text which first appeared in 1982, Bammel and BurrusBammel stated that the book is "an interdisciplinary approach whose central focus is the role of leisure and recreation in modern life." In reality, the focus is more on a sociological and psychological analysis than a multiinterdisciplinary one since little attention is given to the economic and political science aspects of leisure. For those unfamiliar with the initial publication, Bammel and BurrusBammel do a creditable job in their discussion of leisure, work, play, and the meaning of games. They present the dominant theories related to these concepts and behaviors. To guide the reader's attention they offer two sets of questions for each chapter; opening questions serve as a guide for chapter exploration and closing questions suffice as a review. Bammel and Burrus-Bammel struggle with contradictions as is often the case when dealing with the complex issues of leisure definitions and their relationship to recreation and play behavior. Many of the contradictions are acknowledged. For example, in their discussion of leisure as an attitude leading to behaviors which are ends in themselves, thereby providing fulfillment and satisfaction, they suggest that listening to music is done just for the delight of the experience. In such an illustration they also suggested that satisfaction is the end sought. They acknowledge leisure is the result of an experience and the feelings that accompany it. Since experiences are multifaceted, however, it is difficult to ascertain which result (e.g., feeling good, performing, being with friends) created the leisure view. This problem is encountered when leisure is viewed as both an attitude and an activity. They define recreation as connoting activities that are a means to an end such as those performed for fitness, amusement, and restoration for work. In context, however, listening to music for the satisfaction resulting from the experience could also be recreational. Play activities are portrayed in much the same way as are leisure experiences; they are characterized as free, spontaneous, and pursued for their own sake. These ambiguities are typical and appear in nearly every introductory text, especially when time as a leisure dimension is discussed. To this point, Bammel and Burrus-Bammel offer an entire chapter describing in some detail different definitions and views of time. They conclude that time can be scheduled to improve one's leisure by creating larger blocks of discretionary time. By doing so, individuals are perceived to have greater opportunities for choice and these choices are often expressed in recreational pursuits. The focus becomes recreation rather than leisure with activities to reduce stress and maintain health. Recreation is one use of "leisure time." The issue of stress is intensively investigated as are traditional patterns of work, work scheduling, and the potential of new work forms such as the four-day week and job sharing. The second half of Leisure and Human Behavior is devoted to a discussion of leisure and recreation behavior regarding social groups, life stages, and the factors which condition choice. …


Technology innovation plays a key role in strengthening the competitiveness of the enterprises. It is a good method for the company to win the market within background of global economy and fierce competition. Based on the literature review of the enterprise innovation and technology development status, choosing the construction enterprise listed in top 500 companies of 2015 as an example, this paper firstly analyzed the enterprises' basic ranking status and overall competitiveness. From the perspective of technology innovation management, then explored the differences among the construction enterprises from five aspects of technology innovation: (1) R and D human resources, (2) capital investment, (3) organization management, (4) incentives mechanism, and (5) innovation cooperative mechanism. The comparison between Chinese construction companies and international construction companies are presented as well with the root cause analysis of the difference on innovation management. Research found that Chinese construction enterprises are dominated the global leading position, but the technology innovation management mode and internationality is not strong. Finally, the paper put forward corresponding countermeasures and suggestions on how to improve the innovation performance for Chinese construction enterprises. It pointed out that the Chinese construction enterprises should strengthen technological innovation management, establish a professional technological innovation system and incentives mechanism to maintain international competitiveness and achieve sustainable development goals.


Massive MIMO un-sourced random access (URA) is a promising massive random access technique for massive machine-type communications. The conventional receiver of uplink URA consists of inner covariance-based multiuser detection (CB-MUD) and outer tree-based decoding, and its performance is highly dependent on the threshold used to determine the activity state of transmit codeword in CB-MUD. In general, this threshold is involved with multiple system parameters, and difficult to optimize. In this paper, an iterative receiver consisting of CB-MUD and outer decoding is proposed. In this iterative receiver, the successive interference cancellation (SIC) strategy is employed, where the covariance information associated with codewords decided in the former iteration is peeled off and the residual covariance is used for CB-MUD in the latter iteration. Noting that the sparsity increases with iterative number, in general, the performance of CB-MUD can be improved which is demonstrated by simulations. On the other hand, multiple iterations can relax the requirement of threshold selection. Concretely, an empirical formula for the threshold setting which decreases with iteration number is presented, and its robustness to system parameters is also verified by simulations.


We report the fabrication of sub-0.1-μm-diam silicon nanopillars with a polycrystalline silicon and silicon nitride multilayer structure. The polycrystalline silicon layers, which are 20 nm thick and are separated by 2–3 nm-thick silicon nitride tunnel barriers, make potentially useful structures for the observation of single-electron charging effects. Measurements of electron transport at 4.2 K between contacts at the top and bottom of the pillars show a zero current region and current steps attributed to Coulomb blockade.


The present invention relates to an abnormality detection method of a switchgear with a self-diagnostic function, the abnormality detection method according to the present invention is an arc signal through an ultraviolet sensor for detecting ultraviolet rays generated in the switchgear and a current sensor for measuring the tracking current of the live wire And detecting a tracking signal, performing anti-aliasing sampling, performing digital filtering on the sampled signals using a digital finite impulse response lowpass filter, and performing fast Fourier transform on the digitally filtered signals to obtain peak amplitude and Calculate the peak frequency and calculate the inherent detection element for the arc signal and the tracking signal using the calculated peak magnitude and peak frequency, and check whether the calculated detection element is out of a set range and whether arc and tracking occur. Diagnose the pulse of the ultraviolet sensor The sensor performance is periodically measured by measuring the voltage of the beamer voltage and the signal input to the current sensor, and the diagnostic result and the self-diagnosis result are transmitted to a remote monitoring device using a predetermined communication method. .


From the complex motions of robots to the oxygen binding of hemoglobin, the function of many mechanical systems depends on large, coordinated movements of their components. Such movements arise from a network of physical interactions in the form of links that transmit forces between constituent elements. However, the principled design of specific movements is made difficult by the number and nonlinearity of interactions. Here, we model mechanical systems as linkages of rigid bonds (edges) connected by joints (nodes), and formulate a simple but powerful framework for designing full nonlinear coordinated motions using concepts from dynamical systems theory. We begin with principles for designing finite and infinitesimal motions in small modules, and show that each module is a one-dimensional map between distances across pairs of nodes. Next, we represent the act of combining modules as an iteration of this map, and design networks whose geometries reflect the map's fixed points, limit cycles, and chaos. We use this representation to design different folding sequences from a deployable network and a soliton, to a branched network acting as a mechanical AND gate. Finally, we design large changes in curvature of the entire network, and construct physical networks from laser-cut acrylic, origami, and 3D printed material to demonstrate the framework's potential and versatility for designing the full conformational trajectory of morphing metamaterials and structures.


This paper means to show that throughout its history the issue of ethnicity has gradually risen as a key way to obtain political legitimisation among the population of northern Afghanistan, despite not having been on the original agenda. The aim is to show that warlord polities are not static entities, but can be capable of transforming and adapting under pressure and can raise the banner of ethnic or political causes.


Water scarcity in the hill tract districts of Bangladesh becomes acute in the dry season as most of the streams, the primary source of water, dry up. However, groundwater, where available, can supply water throughout the year. In this study, a total of 37 water samples were collected and analyzed from shallow (34) and deep (3) wells in Khagrachhari Sadar to assess their geochemical type and suitability for drinking using a multiparameter groundwater quality index (GWQI), as well as their suitability for irrigation uses using the sodium adsorption ratio (SAR), residual sodium carbonate (RSC), sodium percentage (SP), and the Riverside and Wilcox classifications. The physicochemical parameters of the groundwater were characterized by relatively low EC, low pH, positive redox potentials (Eh) in millivolts, and mostly soft water. Shallow wells were dominated by Ca–HCO3- and Ca–Na–HCO3-type water, and deep wells by Na–HCO3-type water. Among major and trace ions, there were higher concentrations, exceeding safe water standards, of HCO3− in deep wells and NO3−, Fe2+, and Mn2+ in shallow wells. Irrigation water quality assessments and GWQI results reveal that most shallow wells can be considered good and safe options for both drinking and irrigation, while groundwater from deep wells requires additional caution prior to use for agricultural purposes.


Objectives Suboptimal health status (SHS) is considered to be an intermediate status between disease and health, and is characterised by a decline in vitality, in physiological function and in the capacity for adaptation. Although the incidence of SHS is high, the underlying causes remain unclear. Lifestyle is one of the most important factors affecting health status; however, the relationship between SHS and lifestyle has not been elucidated. Design Cross-sectional survey. Setting A questionnaire, based on 'Health Promoting Lifestyle Profile-II (HPLP-II)' and 'Sub-Health Measurement Scale V1.0 (SHMS V1.0)', was sent to four colleges in four districts (Guangzhou, Foshan, Zhanjiang and Shaoguan) of China between May and July 2013. Participants A total of 12 429 questionnaires were distributed during the study period, and 11 144 completed responses were received. Results The prevalence rates for the 'healthy', 'SHS' and 'disease' groups of respondents (students) were 22.81% (2542), 55.9% (6234) and 21.25% (2368), respectively. Most of the students reported a 'moderate' or 'good' lifestyle. There were significant differences in lifestyle and health status between the two genders. It was notable that health status was significantly positively correlated with lifestyle (r=0.563). For every dimension of the HPLP-II model, the mean values were lower for those participants who reported as 'SHS' or 'disease' than for those who reported that they were 'healthy'. The individual dimensions of the HPLP-II model, including 'spiritual growth', 'health responsibility', 'physical activity', 'interpersonal relations' and 'stress management' were all related to SHS. Conclusions Health status is significantly positively correlated with lifestyle. Poor lifestyle is a risk factor for SHS. Conversely, adopting a healthier lifestyle can improve SHS. Trial registration number ChiCTR-OCH-12002317.


Objective To introduce the METRx microendoscopes diskectomy system in the treatment of far lateral lumbar disc herniation.Methods Fourteen cases of far lateral lumbar disc herniation were operated with METRx from February 1999 to December 2002.Among them,the average age was 49 years old(range 41-55 years old),male in 10 cases,female in 4 cases.All cases were single disc herniation;L_(4,5) herniation in 6 discs,L_5-S_1 herniation in 8 discs;foraminal disc herniation in 6 cases,extra-foraminal disc herniation in 8 cases.Results All the cases were followed up from 12 to 46 months(average 26.5 months) with the results of excellence in 10 cases,good in 3 cases,fair in 1 case and no failure case.There were no disc infection,dura laceration,nerve root injury and herniation recurrence.Conclusions METRx is suitable for far lateral lumbar disc herniation with the advantages of minimal invasive,complete decompression of nerve root and rapid recovery.The correct approach and precise surgical technique are the key points for this operation.


The invention relates to a printing head assembly (1) comprising a printing head with a front side having one or more nozzles, said printing head comprising fluid ejection means to eject fluid from said nozzles. The printing head assembly (1) further comprises a moveable closure member (10) facing said front side and arranged to expose said nozzles in an active state of said printing head assembly (1) and to hermetically seal said nozzles in an inactive state of said printing head assembly (1). The closure member (10) avoids drying of ink in the inactive state and clogging up of the nozzles. The invention further relates to a system comprising such a printing head assembly (1).


In welding for sealing purpose, blowhole are frequently formed by a small rise of the pressure within a space sealed by welding. The critical pressure for blowhole formation was studied in relation to the clearance in weld joint.The clearance is simulated by the narrow hole provided in a block specimen. The inner space was filled with a gas and the outside of the hole was melted. The results are summarized as follows:(1) The critical pressure for blowhole formation is determined by the apparent surface tension of the molten metal and the clearance in a weld joint.(2) The relation between the critical pressure (Pcr) for blowhole formation and the diameter (D) of the gas hole was given by the equations, Pcr-54.4=534/D (for air)Pcr+192 =592/D (for argon)(3) In welding for sealing purpose, it is effective for prevention of blowhole formation to decrease the pressure in a sealing space and to minimize the clearance in a weld joint.


This research was motivated by low ability in English subject, reading comprehension in particular among students in Mechanical Engineering study program. Politeknik Harapan Bersama. Based on some related studies, SQ3R technique is as one of learning techniques that proved to enhance reading skills. This research was conducted with the assumption that the technique was able to improve reading comprehension. Therefore, the purpose of the current study was to determine the effect of SQ3R technique on students' reading comprehension. The research presented 2 variables namely SQ3R technique (X) and reading comprehension (Y). Pre-Experimental method of One Group Pretest-Posttest Design was implemented with one class of Mechanical Engineering consisting 26 male and 1 female student involved during the study. Data were gained through cloze test and observation sheet. All data were then processed and analyzed quantitatively to determine the effect of the SQ3R technique on the students' ability to comprehend the passage. The results showed that tcount (5.001) was greater than ttable (2.080). Thus, this can be concluded that SQ3R technique has positive effect (54.4%) on the students' reading comprehension.


In this paper, the static stress of the flange-coupling is analyzed by the finite-element software ANSYS 7.0. Through computing and analyzing the stress and the displacement are got and it gives the base theory to improve the force condition and the structure of the flange-coupling. What is more the paper illustrates the method of apply finite-element analysis to the calculation of internal force in design.


The field of air traffic management (ATM) has a strong interdisciplinary nature, combining of technological, management, economic and regulatory aspects. The fully understanding of the structure and dynamics underlying the system continues to be significant challenges in the field. Here we present a novel framework for the study of the structure and dynamics of the air transport system building upon recent advancement of network science and big data science, as well as taking into account of the unique operation practicals, thus bridging the gaps between academic field and operational world. We show that the structure of air transport system can be captured by four interdependent networks including airlines network, airport network, air route network, and ATM network. In particular, we present initial results on spatial-related dynamics of the system using one-year flight data records. We find by analyzing flight delay data that (i) airports with similar geographical locations exhibit similar dynamics; (ii) unlike other spatial-embedded complex systems, the propagation of flight delays or failure in the system decays slowly, and the correlations of the failure nodes reaching to 0 when the distance between them approaching to ∼ 1, 000km. Our findings may have the implications for the efficient management of air transport system.


1. If f is a real-valued function possessing a Taylor series convergent in (a — R, a + R), then it satisfies the following operational identity 1.1 in which D 2 = d 2/du 2. Furthermore, when g is a solution of y″ + λ 2 y = 0 in (a – R, a + R), then g is such a function and (1.1) specializes to 1.2 In this note we generalize these results to the real Euclidean space EN , our conclusions being Theorems 1 and 2 below. Clearly, (1.2) is a special case of (1.1) but in higher-dimensional space it is of interest to allow g, now a solution of 1.3 to possess singularities at isolated points away from the origin. It is then necessary to consider not only a neighbourhood of the origin but annular regions also.


When Liang Chaoran was collating "the Biography of Li Yuan in the Biography of Talent People in Tang Dynasties, for the mistakenly citing the recording of the "Yuanhe County Tu Zhi", thinking Yuyang was Dangtu, he made the conclusion that Li Yuan once held a post in Dangtu, so did Tao Min. In fact, there are many questions about the conclusion. Based on "the Yuanhe County Tu Zhi", "Taiping Huanyu Recording" and other books, combined with the using of the Yunyang in the poetry of Tang dynasties, it can be inferred that Yunyang in the Xu Hun's poetry is an old name, that is, it is the Danyang county, not the Dangtu.


Investigators of DTNSRDC in USA advocate that PAR-WIG has nearly twice range capability, in comparison with conventional airplanes, due to higher L/D and lower empty weight fraction. Especially PAR-WIG with a wing of low aspect ratio may have the empty weight which is about two-thirds of the conventional airplane's. In this paper empty weight is analysed, based on the data available to the present author, and compared between various kinds. Synthetic effect of the wing aspect ratio on the operational efficiency is also examined. The opinions of DTNSRDC seem to be somewhat too optimistic, and so valid only with some reduction.


This work deals with the synthesis of nano‐sepiolite (NSP) and its evaluations as potential drilling fluids (DF) additive for improvement of DF rheological properties and filtration loss. Results show that addition of NSP to the base drilling fluids stabilized its rheological properties (plastic viscosity and yield point) and improved its gel strength at normal and increased temperature and pressure. The effect of NSP on fluid loss was also investigated, and results show that NSP stabilized and improved fluid loss for both normal and high pressure and temperature conditions. Copyright © 2016 John Wiley & Sons, Ltd.


ABSTRACT There is a belief among investors that real estate is an excellent way to protect capital from depreciation due to inflation. Research does not provide a clear answer as to whether this investors' belief is correct, but some approaches indicate that simple econometric methods are not able, especially in the short term, to clearly indicate the existence of a relationship between inflation and property prices (Fogler, 1984). The purpose of the study –was to find the relationship between residential real estate prices and inflation in the Polish economic conditions. Methodology of the study - the study used cointegration analysis with the Engle - Granger test. The research was carried out in the period from the first quarter of 2009 to the fourth quarter of 2021. The real estate hedonic indices calculated by NBP (National Bank of Poland) and the actual and forecasted inflation rates published by the GUS (Central Statistical Office) and the NBP (National Bank of Poland) were used in the research. The result - the analysis led to a negative verification of the research hypothesis, as it could not be proved that real estate prices were related to the level of inflation during the researched period. Originality/value - the study fills a gap in the Polish market regarding the analysis of the possibility of using real estate as a hedge against inflation. The research concerned only the Polish market, but this issue has not been taken up for years, also in mature economies.


We describe the dynamics of a simple adaptive network. The network architecture evolves to a number of disconnected components on which the dynamics is characterized by the possibility of differently synchronized nodes within the same network (polysynchronous states). These systems may have implications for the evolutionary emergence of polysynchrony and hierarchical networks in physical or biological systems modeled by adaptive networks.


The potential role of E-cigarettes in smoking cessation is debatable, and whether they are harmful remains controversial worldwide. However, several cases of E-cigarette or vaping-associated lung injury (EVALI) have been reported in the United States. In this review, we discuss and summarize EVALI cases.


With depressing nature of economy in many countries such as Nigeria where per capita income is low, there is need for utmost consideration for cost containment measures.
Objective: The objective of this study is to conduct pharmacoeconomic evaluation of two antichlamydial indicated non-gonococcal urethritis therapeutic options and to make
recommendations for inclusion of economic evaluation of drug therapies in health policy formulations and decision making. Methods: Cost effectiveness analysis was carried out retrospectively for prescribed/dispensed antibacterials to out-patients with chlamydial implicated non-gonococcal urethritis among other infectious diseases, by examining out-patient case notes between 2005 and 2007 in Ahmadu Bello University Teaching Hospital, Zaria Nigeria. Results : The result shows that doxycycline costs N1.33/unit of effectiveness while tetracycline costs N2.77/unit of effectiveness in the treatment of chlamydial implicated non-gonococcal urethritis. Doxycycline is therefore more cost effective than tetracycline capsules. Subjecting the costs and effectiveness to sensitivity analysis did not change this conclusion. There is statistically significant difference in the effectiveness (outcome) of doxycycline (78.8%) and tetracycline (58.7%) ( x2 =9.4; p African Journal of Clinical and Experimental Microbiology Vol. 10 (1) 2009: pp. 35-46


The technical actuality of MEMS (micro-electro-mechanical system) sensors and its applications in IESI (integrated electronic standby instrument) were analyzed. The specialty of IESI and MEMS sensor in configuration and performance were investigated. The analysis shows that development of precision MEMS sensor is a critical to the IESI technology and has broad applications in flight safety.


A summary of the type of knowledge obtainable from ..pi..-nucleus inclusive studies is given. The intranuclear cascade models are illustrated by the p + /sup 58/Ni reactions at 100 MeV and then by extending the analysis to pion reactions. Analysis of gamma and proton spectra is discussed. (SDF)


Abstract This paper examines whether satellite images can be used to see a green wave in the small but geographically diverse territory of Slovenia. We used the phenological products of the MODIS satellite system to analyze and calculate the correlations between the onset, decrease, and duration of greenness on one hand, and the elevation and distance from the sea on the other. A statistically reliable significant correlation was primarily determined between onset of greenness increase (onset of the vegetation period) and elevation. The other correlations did not attain such a high significance. The results of the analysis using remote data sensing were confirmed by analysis of phenological data from the Slovenian Environment Agency, which collects data on leafing out and yellowing of beeches (Fagus sylvatica), which are the most widespread species in Slovenia.


This paper exploits the directionality in the wireless sensor network WSN by using single-beam and multibeam directional antennas. We mount a multibeam smart antenna MBSA with a main sink cluster head CH, whereas other child sink CHs and end devices use single-beam sector antennas. The unique reception and transmission property of these antennas requires a sufficient modification to suit omni mode MAC protocols. We choose IEEE 802.15.4 as the platform for the proposed MAC design and analyse the effects of these antennas on the current superframe structure. We simulate the modified MAC protocol by using the OPNET modeller under varying traffic loads and an increasing number of nodes. We find an increase in network performance in terms of delays and energy consumption and a simultaneous decrease in the level of urgency.


In rotor dynamics, the rotor nonsynchronous natural frequency vibration, or rotor instability, has been mainly ascribed to two mechanisms, i.e., internal friction effects and fluid actions. It is shown, however, in this paper that the radial clearance in ball bearing supports can also induce rotor instability through an internal-impacts mechanism. The behavior of the rotor with radial clearance in its ball bearing supports is simulated numerically. The computer simulations show that there is a speed range in which the rotor will vibrate at both the synchronous frequency and the natural frequency. Below or above this speed range, the rotor has only the synchronous response and its harmonics. An experimental investigation was conducted to verify this analysis. The experimental results agree well with the theoretical predictions.Copyright © 1993 by ASME


ABSTRACT The central question this paper explores is the significance of the dress of three Caribbean icons, Toussaint L'Ouverture, Marcus Garvey, and Fidel Castro whose contribution toward the invention and maintenance of a path of freedom out of slavery in Caribbean history is indelible. Its core argument is that their uniforms functioned as mirrors that mediated a process of interaction to construct a collective sense of identity, imagination, and liberty that transcend them.


In an attempt to identify factors associated with stillbirths and those occuring in the 1st week of life, perinatal deaths in infants born in health facilities in Marondera Districts occurred during a 7 months period 1986 were recorded and analyzed. 66 such deaths out of a total of 1900 births, giving a perinatal mortality rate of 35/1000 total births. The largest groups with identifiable cause were intrapartum asphyxia (14 deaths) and severe prematurity (birthweight 1500 gm) (8 deaths). The other associated causes of perinatal deaths were antepartum hemorrhage, code prolapse, toxemia of pregnancy, ruptured uterus, severe congenital abnormalities and intrauterine infections.


Volume 6, issue 3, doi: [10.1128/mBio.00536-15][1]. [Figure 1][2] incorrectly displayed the location of the TR34/L98H mutation in gene cyp51a . The revised [Fig. 1][2] (below) shows the correct location.

![FIG 1 ][3]

FIG 1
Circos (72) image of normalized whole-genome depth of coverage


This is a collection of the papers presented at a meeting held in Strasbourg on Sept 23, 1963, dealing with radiologic problems related to the spinal cord. Most of the papers are in French and some are in English. The editors have divided the papers into six sections: (1) problems of technique in myelography; (2) cervico-occipital region; (3) lumbar region; (4) sacral region; (5) new techniques and anesthesia; (6) incidence of complications in myelography. There are 33 papers in all, plus an introduction by Professors M. David and H. Fischgold. This represents a valuable collection of papers dealing with diseases affecting the spinal canal; the illustrations are of excellent quality.


Short periods of chilling in the presence of light (up to 6 h: 1°C; 270 W/m2) decreased the subsequent apparent photosynthesis and chlorophyll fluorescence of leaf discs of Cucumis sativus L. cv. Kleine Groene Scherpe. The extent of the injury depended on the duration of the chilling pretreatment. After 6 h the subsequent apparent photosynthesis even reached a negative value, and it increased only slightly during the next 2 1/2 h. The decrease of apparent photosynthesis was not a consequence of increased dark respiration but was of photooxidative origin since the presence of both light and oxygen was required. Preincubation in the light for 2 h at 20°C sensitized leaf discs to subsequent photooxidation during chilling. Prompt and delayed chlorophyll fluorescence decreased simultaneously after chilling and light treatment. The corresponding decrease of photosynthesis and chlorophyll fluorescence is discussed in relation to primary photooxidative damage to the photosystems in the chloroplast membrane.


The aim of this report is to present an overview of the work done by Inigo Urcelay Oca during his internship at the Institut fur Faserverbundleichtbau und Adaptronik, Strukturmechanik, DLR, in Braunschweig. The report indicates as well what the following steps should be in order to continue the work presented.
The report starts with a brief description of the manufacturing process, Fused Deposition Modelling (FDM), and the characteristics of the material, semi-crystalline thermoplastic PLA. It is followed by a brief overview of the state of the art regarding the simulation of FDM for different types of materials.
Then the work done regarding the modelling on Abaqus is explained in detailed, so that in conjunction with the comments on the scripts, the procedure that was followed and the decisions that were made can be clearly understood.
Other possible tools were also researched. An evaluation of AlphaStar software, as well as a description of its characteristics, can be found next in the report. The results obtained from the scripts written by the author are then presented, describing the convergence issues and the strategies followed to try to solve them. The results from the experimental tests are also shown.
The report ends with the author presenting the conclusions resulting from the work done, as well as the next steps to be followed in order to continue it.


Abstract With the globalization of the English language as a communication tool and the increased use of technology, the characteristics of learners and teachers are changing. In order to meet the demands of the learners, teachers must keep up-to-date and improve their teaching practices and beliefs, which necessitates professional development (PD) and in-service training for English as foreign Language (EFL) teachers. The purpose of this systematic review was to review the research studies that had been conducted in the area of EFL Teachers' Professional Development (PD) in Turkey. This meta-analysis reviewed the literature on professional development and in-service training of EFL teachers in journal articles, thesis and dissertations published between 2000 and 2012. A systematic review of literature was performed to examine the current status of EFL Teachers' professional development. Through the systematic review the methods and results of different research studies were analyzed through a collection of systematic techniques. The results of the study indicate that two broad terminologies has been used in the research literature, many of the studies were evaluative in nature and almost all of them were conducted at English Preparatory Schools at universities. Although the studies had provided many recommendations for professional development, there have been only a handful of studies that examined the impact of PD programs. Through the systematic review, the authors provided recommendations for future researchers and policy-makers.


Open quantum systems as modeled by quantum channels and quantum Markov semigroups usually decay to subspaces that are invariant under environmental interactions. It is known that finite-dimensional semigroups with detailed balance decay exponentially under modified logarithmic-Sobolev inequalities (MLSIs). Here we analyze discrete and continuous processes that include unitary components, breaking the detailed balance assumption. We find counter-examples to analogs of MLSIs for these systems. The generalized quantum Zeno effect appears for many Lindbladians that combine a decay process with unitary drift. As incompatible long-time and Zeno limits compete, strong noise often protects subsystems and subspaces from its own spread. We observe this interplay between decay and Zeno-like effects experimentally on superconducting qubits using IBM Q devices. Nonetheless, by combining MLSIs for effective self-adjoint decay processes across different times, we obtain eventual exponential decay. We similarly obtain decay rate lower bounds for discrete compositions of quantum channels.


This policy outlook analyses Russia's strategic priorities, national interests and threat perceptions by examining its latest national security strategy document. Russian foreign policy elites believe that the world is undergoing significant transformations through which the global balance of power is shifting, new power centres are emerging, and existing international institutions and rules are losing ground. As a result of these changes, the risk of conflicts and instability in the world is increasing. Against this backdrop, Moscow seeks to adapt the country to the emerging world order. The strategy document reveals that Moscow continues to distance itself from the West while deepening cooperation with Asian countries, most notably China and India. Additionally, Moscow considers dealing with domestic issues such as demographic trends, economic inequality, education and corruption as a key to the achievement of its wider national security objectives.


In this paper we describe Summit, a method and supporting software application used to help identify and analyze technology investments in healthcare. Summit is a user and use-centric approach to justifying technology investments. Its focus is on measuring the utility (defined as a function of benefits, costs, and risks) that results from technology support for specified healthcare scenarios, tasks, and technology interactions. Summit currently exists and has been used as a stand-alone application prototype and is currently being developed as a web-based, software-as-a-service (SaaS) that can be accessed and used by anyone. Though this paper will focus on modeling scenarios in the sub-domains of community Para medicine and mobile integrated healthcare, Summit can be used to analyze and justify technology investments across the healthcare spectrum.


Serum levels of fibrin degradation products (FDP) were determined using an FDP slide test (a latex agglutination reaction method) in 20 normal control women and 67 preoperative patients with ovarian tumors. In the control women the FDP levels were 2.5 μg/ml or lower. In the 14 patients with ovarian retention cysts including endometrial cysts the FDP levels were normal (2.5 μg/ml or lower). In the 40 patients with benign ovarian neoplasmas, 37 (93%) showed normal FDP levels. On the contrary, in the 12 patients with malignant ovarian tumors, abnormally high levels of FDP were observed in 9 cases (75%). These observations revealed that the preoperative measurements of serum FDP contributed to the preoperative diagnosis of malignant ovarian tumors.


The performance of the TLM measurement instrument plays important roles in the measurement results and uncertainties. To characterize a TLM measurement instrument, some indices and relevant measurement procedures can be learned from current CIE publications for photometers measuring time-averaged luminous quantities. However, as the fast and time resolved photometric data is captured, other more characteristics of TLM measurement instrument need to be addressed. In this paper, the characterization linearity, frequency response and noise properties and their of the TLM measurement instrument was studied. Considering the actual application, quality indices were proposed based on traditional appraising metrics, and the measurement procedures were developed correspondingly. Furthermore, several TLM measurement instruments were measured, and the results showed fine applicability of these quality indices.


Attackers can leverage several techniques to compromise computer networks, ranging from sophisticated malware to DDoS (Distributed Denial of Service) attacks that target the application layer. Application layer DDoS attacks, such as Slow Read, are implemented with just enough traffic to tie up CPU or memory resources causing web and application servers to go offline. Such attacks can mimic legitimate network requests making them difficult to detect. They also utilize less volume than traditional DDoS attacks. These low volume attack methods can often go undetected by network security solutions until it is too late. In this paper, we explore the use of machine learners for detecting Slow Read DDoS attacks on web servers at the application layer. Our approach uses a generated dataset based upon Netflow data collected at the application layer on a live network environment. Our Netflow data uses the IP Flow Information Export (IPFIX) standard providing significant flexibility and features. These Netflow features can process and handle a growing amount of traffic and have worked well in our previous DDoS work detecting evasion techniques. Our generated dataset consists of real-world network data collected from a production network. We use eight different classifiers to build Slow Read attack detection models. Our wide selection of learners provides us with a more comprehensive analysis of Slow Read detection models. Experimental results show that the machine learners were quite successful in identifying the Slow Read attacks with a high detection and low false alarm rate. The experiment demonstrates that our chosen Netflow features are discriminative enough to detect such attacks accurately


Tendon-driven flexible surgical robots are normally suffering from the inaccurate modeling and imprecise motion control problems due to the nonlinearities of tendon transmission. Learning-based approaches are experimental data-driven with uncertainties modeled empirically, which can be adopted to improve the inevitable issues. This work proposes a LSTM-based kinematic modeling approach with task-based data for a flexible tendon-driven surgical robot to improve the control accuracy. Real experiments demonstrated the effectiveness and superiority of the proposed learned model when completing path following tasks, especially compared to the traditional modeling.


Along with the development of the human mindset, humans begandevelop systems that can help humans in overcoming problems that arise can be solved easily. Decision tree or better known as the decision tree is an implementation of the system that humans develop in finding and making decisions for these problems by comparing various kinds of problems related to these problems and related to education. Education is a conscious and planned effort to realize learning and the learning process so that students can increase the potential needed by themselves. The function of education is very important as one of the factors driving the development of human resources with the aim of increasing the ability of the community to develop science. Thus, the teaching and learning process is one of the determining factors for the success of education in schools, the low quality of education is the result of the low quality of the learning process carried out in schools. On this occasion, the researcher made preparations for the grades of class XII students at SMK Negeri 1 Selong for 2018/2019 school year using RapidMiner as a tool and applying the Decision Tree method to assess student achievement levels as seen from the report card grades. This research is one of the school action research conducted by researchers who conducted this research in order to improve the achievement of students of SMK Negeri 1 Selong. DOI : 10.29408/jit.v3i1.1825


This paper gives an overview of ICRF plasma production in TEXTOR-94 using the present two double loop antennas, one with and one without Faraday screen, for start-up of OH discharges and conditioning / coating of the vessel. The results show that He-plasma with density up to ne0≈3×1012 cm−3 is reliably produced at the standard ICRH frequency (f=32.5 MHz) in a wide range of toroidal magnetic field BT=0.20–2.25 T (2ωci⩽ω⩽20ωci), gas pressure pHe=1×10−5−1×10−3 mbar and total RF power at generators up to PRF=2×600 kW in the best cases. In addition, H-, D-plasmas and multi-ion species plasmas (mixture of He and SiD4 up to 70%) were produced. The screenless antenna gives the largest RF power contribution, the coupling increases with pressure and by lowering BT. This novel RF technique recently allowed reliable and reproducible ICRF assisted low voltage start-up and efficient ICRF wall conditioning in between normal OH discharges in TEXTOR-94.


This paper examines various psychoanalytic conceptions of trauma, including ideas associated with classical psychoanalytic theory (Freud), object-relations theory (Khan), self-psychology (Kohut and Tolpin) and continuous construction theory (Zeanah et al.). Clinical issues germane to the psychotherapy of children are discussed, and a reciprocal storytelling technique used by the author in his work with certain traumatized children is introduced. A clinical vignette is then presented. The vignette focuses upon the psychotherapy of a 10-year-old boy who had been a victim of multiple traumata, with particular attention given to the narrative discourse that evolved in the course of this boy's therapy. The evolution of this child's narrative is illustrated through the use of transcribed material derived from different phases of the boy's treatment.


Abstract Upper Triassic strata of the nonmarine Chinle Group, the marine/nonmarine Star Peak and Auld Lang Syne Groups (western United States) and the nonmarine Germanic Keuper and marine/nonmarine Alpine Triassic comprise third order sequences that can be divided into systems tracts. Nonmarine sequences of these strata begin with fluvial conglomerate and sandsheets that represent infilling of incised topography, overlain by fluvio-lacustrine clastics (TST), with HSTs of pedoturbated/paludal siltstone and/or sheet sands that display offlap geometry. Marine sequences of these regions contain more heterogeneous facies that define either unconformity bounded, upward deepening cycles, or more discrete transgressive-regressive cycles. The nonmarine and marine sequences of these regions can be correlated by tetrapod and ammonoid biochronologies. These correlations suggest that during the Late Triassic third order global eustatic cycles significantly influenced sedimentation in nonmarine basins far inland from strandline areas.


Compliance with venous access best practices at Johns Hopkins Hospital hinged on nursing and physician management, and quality improvement programs.


Despite the growing international influence of the TOEFL (Test of English as a Foreign Language), no articles have been published on how the test is actually developed by the Educational Testing Service (ETS). In this article, the author, who worked in the Test Development department at ETS from 1984 to 1987, seeks to demystify the TOEFL reading test at both a descriptive and theoretical level. First, the author draws on data from a case study of a reading test she developed in 1986 to illustrate the technical rigor with which the test is developed, and to raise questions about its theoretical adequacy. Second, the author draws on the theory of genre proposed by Kress (1989, 1991) to (a) illustrate how the unequal relationship between test makers and test takers predisposes TOEFL candidates to a particular reading of TOEFL texts; and (b) locate the TOEFL reading test within the larger social context of the TOEFL internationally, where competence in English means access to power. The author concludes that the TOEFL–2000 test development team at ETS, who are currently reviewing the test, needs to address the washback effect of the test in consultation with both ESOL teachers and TOEFL candidates internationally.


Design of the in-situ observational sites depends on topography and hydrodynamic characteristics in the observational region, which is significantly important in marine environmental monitoring and evaluation. The tidal motion in Jiaozhou Bay and Aoshan Bay is simulated in this study using the unstructured grid, finite-volume coastal ocean model (FVCOM). With an accurate geometric representation of irregular coastlines and islands and sufficiently high horizontal resolution in narrow channels, FVCOM provides an accurate simulation of the tidal current in the bays and also resolves the strong tidal flushing processes in the narrow channels. There exist many small-scale eddies due to the interaction of tidal flushing and complex coastlines. Small-scale eddies formation will cause inhomogeneous distribution of the marine environmental element, then affects design of the in-situ observational sites. We proposed that design of the in-situ observational sites should consider nearshore eddies in order to conform to reality and enhance environmental protection.


Two fractal parameters, probability of failure (P) and fractal dimension (D), were used to evaluate the influence of cropping and wetting treatments, and aggregate size on fragmentation of soil aggregates during wet sieving. Five different sizes of aggregates (4–10, 2–4, 1–2, 0.5–1 and 0.25–0.5 mm) from five cropping treatments [conventionally cultivated continuous corn (CCC), CCC underseeded to red clover (CCR), minimally tilled continuous corn underseeded to red clover (CCRM), alfalfa (AL), and bromegrass (BR)] were subjected to two wetting treatments (rapid and slow) before being wet sieved. P increased nonlinearly with increasing aggregate size. The P of the slowly wetted agggregates was always less than that of the rapidly wetted aggregates. The P of larger aggregates, 2–4 and 4–10 mm, increased in the following order of cropping: BR = AL < CCRM < CCR = CCC. The D for the size distribution of 4- to 10-mm aggregates increased in the same order of cropping as that given previously. The D for the rapidl...


The studies were carried out, comparative, both in the plum collections of the Fruit Growing Institute Plovdiv - Bulgaria and Research Institute for Fruit Growing Pitesti - Romania, with 4 plum cultivars of different origin: 'Tuleu timpuriu' (Romania), 'Cacanska Lepotica' and 'Cacanska Najbolja' (Serbia) and 'Stanley' - control (USA). In the period 2002 - 2008 were carried out observations and determinations of: blooming and ripening times, production capacity, quality of fruit and response of plum cultivars to Plum pox virus. Varieties in both areas were noted by large fruit and superior comparative with quality control variety Stanley. In terms of yield capacity none of the 3 varieties did not exceed the control ('Stanley' cv.), in any of the two areas of culture. In Plovdiv - Bulgaria, period of blooming and ripening, of the studied varieties was earlier than in Pitesti - Romania. It should be noted that 'Tuleu timpuriu' Romanian variety gave better results in Plovdiv than in Pitesti.


The pediatric population poses diagnostic and treatment challenges in orthopaedics, and the complication of a pathologic process affecting the bone adds to those challenges. This paper focuses specifically on pathologic fractures related to tumors, although weakness in the bone can be attributable to multiple etiologies. To treat these fractures appropriately, a comprehensive approach must be used. Pathologic fractures can result from both benign and malignant conditions. For most benign lesions, standard fracture care and conservative management may be applied. Malignant lesions may present or be associated with a pathologic fracture, and although in the past the presence of a pathologic fracture may have precluded limb salvage, currently substantial evidence exists to the contrary. The most common benign and malignant lesions associated with pathologic fractures are further discussed.


We consider channel identification techniques for a transmission scheme which consists of a sequence of frames with each frame consisting of pilots and data. We consider two systems, the first one having pilots in the time multiplexed fashion, and the second one being a multi-carrier system with frequency multiplexed pilots. We consider scenarios in which the channel is both frequency and time selective. For the time multiplexed pilots system, channel estimation performance of the pilot-only technique is limited by pilot spacing. The standard optimal decision-directed techniques are computationally expensive. In response, we propose a novel two-stage estimation technique whose performance is close to that of the optimal es-timators but whose complexity is significantly less. The first stage finds smoothed estimates of the channel during previous frames, while the second stage uses these smoothed estimates for channel prediction within the current frame. The frequency multiplexed pilots system suffers from the inter-carrier interference (ICI) in doubly-selective channels. We present channel estimation techniques which take the ICI effects into account. We also present a novel pilot tone selection criterion and the theoretical MSE calculations show its efficacy for a wide range of Doppler frequencies. The performance limitation due to ICI can be reduced by employing decision-directed estimators. We develop a low-complexity estimation technique and simulation results show good performance of the proposed techniques. ii The frequency multiplexed pilots system suffers from the inter-carrier interference (ICI) in doubly-selective channels. We present channel estimation techniques which take the ICI effects into account. We also present a novel pilot tone selection criterion and the theoretical MSE calculations show its efficacy for a wide range of Doppler frequencies. The performance limitation due to ICI can be reduced by employing decision-directed estimators. We develop a low-complexity estimation technique and simulation results show good performance of the proposed techniques. 2 dedicated to my family ... iii ACKNOWLEDGMENTS First of all, I would like to thank my advisor, Prof. Phil Schniter, for his valuable advice, guidance and help throughout this work. I thank Prof. Hesham El-Gamal for agreeing to be in the thesis committee. Learning Comm theory was a great experience with his insightful comments. I thank Prof. Serrani for his excellent teaching of Estimation theory, which helped me a lot with my research. I thank my parents and sister, for their love and support. I also thank my uncles, aunts and cousins; they gave me the motivation and inspiration …


The essence of education at the school is a learning process. There is no quality of education in schools without the equal of learning quality. Various efforts to improve the quality of education in schools can be perceived as less useful if it is not touched the improvement of the learning process. Among all components of learning, the teacher is the crucial one. There is no quality of learning without the equal quality of the teachers. One of the programs held in order to empower teachers is an academic supervision. It is a series of activities to help teachers in developing their ability to manage the learning process for the achievement of academic goals. Thus, the essence of academic supervision is to help teachers in developing skills professionalism. In achieving that lofty goal, the academic supervision should be implemented in all scope of the school. Moreover, the implementation of it is done by the principal as a leader, and as well as a supervisor who can foster the good morale for teachers. Based on the mentioned background, the researcher conducts the research on the implementation of the principal academic supervision in improving teachers' professionalism in MTs Zainul Hasan Genggong Pajarakan Probolinggo. The purpose of the study is to describe the planning of the principal academic supervision in improving teachers' professionalism, to describe the implementation of the principal academic supervision in improving the teachers' professionalism, and to describe the evaluation of the principal academic supervision in improving the professionalism of teachers. This study uses qualitative research methods, and the explanation of the research results are not numerical but scientific one. The effort to obtain the valid data, the selected samples taken in this study by using purposive sampling techniques to select those that are considered most competent to understand the examined object. The data collection method uses observation, interviews, and documentaries. The observation methods are done by observing and recording, the interviews are conducted by interviewing the informants, and documentation methods are made to the objects documented. The data obtained are analyzed by using descriptive qualitative data analysis techniques, and then the validity of the data is applied by using triangulation techniques. Based on the results of the study, the implementation of principal academic supervision in improving the teachers' professionalism in MTs Zainul Hasan Genggong Pajarakan Probolinggo is concluded as follow: First, the planning of academic supervision program is organized at the beginning of the school year before starting the overall teaching and learning activities, and included in the work program or the School Budget by involving all components of the school in determining  the planning objectives, basic tools, and methods used in the academic supervision . Second, in implementing the academic supervision, the supervisor uses the individuals and groups techniques as well as the direct and indirect approaches. Third, in the results of the evaluation of academic supervision, it is found several obstacles, such as: (1) from the teachers point; the coaching process done by the principal are less as teachers often do not attend in the regular meetings as well as the meeting to implement the supervision models. (2) from the principal point; occasionally, the principal does not attend in the teachers coaching process that has been scheduled. (3) from the funds point; the lack of funds in in-service training activities caused by unbudgeted program arranged by the agency so that the teacher got less information due to the implementation done regularly.


Patients who are at risk of, or have a history of, periodontal disease requesting orthodontic treatment require careful multidisciplinary management in order to achieve optimal orthodontic and periodontal outcomes. An understanding of the periodontal tissues and the disease processes that can affect the periodontium is required by the orthodontist to ensure that patients are managed appropriately. CPD/Clinical Relevance: This paper discusses the multidisciplinary management of periodontal patients who require orthodontic treatment and methods for ensuring optimal outcomes.


Sukoharjo is one of the developing cities currently in Central Java Province. It is
demanding to increase infrastructure development in the city, where there are many
potential potencies such as education. Muhammadiyah University of Surakarta, as one of
the education centers in the city, it is required to improve facilities and infrastructure to
support the world of education. This Final Project aims to produce a 4-storey lecture
building with a regular moment frame system (SPRMB) in Sukoharjo area. The planning
of this lecture building refers to the latest Indonesian National Standard (SNI)
regulations, namely SNI 1726.2012, SNI 2847.2013, and SNI1727.20013. The planning
of this 4 floor lecture building includes columns, beams, plates, stairs, sloof, foundation.
Location of building located in Pabelan, with classification of medium land site (SD)
with response modification factor (R) = 3, building security factor (Ic) = 1.5. Using
concrete quality (f'c) = 25 MPa, longitudinal reinforcement quality (fy) = 350 MPa and
shear reinforcement (fyt) = 240 MPa. Planning results obtained 100 mm thick roof plate,
120 mm floor plate, 300/500 mm main beam, 250/350 mm child beam, and 500/500 mm
sized column. The bottom structure uses a pile of 18,000 mm in diameter using a
300/300 mm dimension, with a dimensionless pooer (750x1750x650) mm. The tools
used in this plan are SAP2000, AutoCad, Microsoft Office.
Keywords: planning, regular moment bearer frame system, building structure


A wire tensioner tip for use with a wire fixation bolt. First and second wires may be anchored to and tensioned across an external fixator frame with first and second wire tensioners. The first and second wires may be anchored at first anchor locations with first and second wire fixation bolts. First and second wire tensioner tips may engage with third and fourth wire fixation bolts, thereby preventing the third and fourth wire fixation bolts from rotating. The first and second wires may be tensioned to a desired tension with the first and second wire tensioners at the same time to prevent over-tensioning or under-tensioning. The first and second wires may be anchored at second anchor locations with third and fourth wire fixation bolts. By engaging the wire fixator bolts with the wire tensioning tips, fewer tools are required and one medical professional can tension two wires at once.


Transformation of Ca²⁺-heat shocked Escherichia
coli cells with plasmid DNA has become an indispensable
technique in the study of plasmids and in
genetic engineering. The process of induction of competence
by Ca²⁺-heat shock is still poorly understood, but it has been argued that only a small
proportion of the shocked cells is effectively rendered
competent in the process. This has been deduced
from the fact that in transformation with two different
plasmids as donor DNA, the observed frequency
of double transformants is higher than would be
expected from the observed transformation frequencies
of each of the plasmids separately.


Chronic myeloid leukemia (CML) is characterized by the BCR–ABL fusion protein produced as a result of the reciprocal translocation between a portion of the ABL tyrosine kinase gene on chromosome 9 and a region within the BCR gene on chromosome 22. The BCR–ABL oncoprotein displays constitutively elevated tyrosine kinase activity that drives the pathogenesis of CML by activating multiple signaling pathways including the RAS/MAPK, PI3K/AKT and JAK2/STAT5 pathways. The development of tyrosine kinase inhibitors (TKIs) aimed at BCR–ABL revolutionized the treatment of CML. Imatinib was the first of the TKIs to become available after it was approved by the US FDA in 2002 based upon data from the IRIS. Indeed, imatinib was associated with unprecedented rates of hematologic, cytogenetic and molecular responses in comparison with IFN-a with complete hematologic response (CHR) rates of 97%, complete cytogenetic response (CCyR) rates of 82% and major molecular response (MMR) rates on the international scale (IS) of 86% [1]. Treatment with imatinib also resulted in significantly improved rates of freedom from progression in comparison with IFN-a with an 8-year freedom from progression to accelerated or blast phase of 92% and afforded patients who were able to remain on treatment an 8-year overall survival (OS) of 85% [1]. However, imatinib use has been complicated by the development of resistance. Resistance led to 24% of patients in IRIS failing to achieve a CCyR at 18 months, which represented treatment failure [2]. Resistance also led 17% of patients on imatinib in IRIS to develop relapsed disease and 7% to develop progressive disease [2]. These numbers are, in fact, likely to be underestimates given the number of patients in the IRIS study who came off the trial and were not ultimately included in analysis. Treatment failure and disease progression due to resistance is also seen in patients treated with the subsequently approved second-generation TKIs, dasatinib, nilotinib and bosutinib. The etiology of resistance to TKIs is multifactorial and involves BCR–ABL independent and dependent mechanisms. Insufficient plasma levels of imatinib due to noncompliance, drug–drug interactions or binding to acute-phase inflammatory proteins can all result in resistance. It is known that trough plasma levels of imatinib are important for good clinical outcomes, and it has been demonstrated that patients with high imatinib exposure have better rates of CCyR, MMR and event-free survival [3]. Imatinib and all three of the second-generation TKIs are substrates for, and are extensively metabolized by, the cytochrome P450 enzymes including CYP3A4. As there are multiple drugs, food products and supplements that either induce or inhibit CYP3A4 activity, the potential for drug interactions is high. Alpha 1 acid glycoprotein has been identified as an acutephase inflammatory product that binds directly to imatinib and is frequently "As the number of drugs available for the treatment of chronic myeloid leukemia has expanded, so have the strategies for overcoming or avoiding resistance."