Introduction. Brain stroke is considered to be the third main cause of death in developed
countries, the first two being cardiovascular diseases and cancer, and the second one
regarding worldwide population.
Objective. The aim of the research was to compare the quality of life of the patients who
were treated in hospitals having a longer period of rehabilitation in spa conditions with
the quality of life of the patients who did not have any rehabilitation treatment in hospitals.
Methods. The method that was used is a prospective cohort study. It included 196 patients at
the age of 30 to 79, all of them being the citizens of Nis district. Te cohort consisted of the
patients who had had an acute brain stroke for the first time in their lives (ABS) during 2011,
2012, and 2013. The beginning of the study was defined by the date of the first ABS. The
study lasted from the 1st of April 2011. until the 15th of August 2013. The control group
consisted of 60 patients who did not have any rehabilitation treatment in hospital after the
first ABS. The functional recovery of patients was followed by use of Barthel index (BI) and
of the Modified Rankin scale (RS).The questionnaires which were used:The general
questionnaire used for estimating the quality of life was the Short form SF 36 (SF-36), the
specific questionnaire for examining the functional status of neurological patients who
survived brain stroke were the Stroke Impact Scale (SIS), "Mini-mental state examination"
(MMSE), the level of neurological damage was measured by NHSS, EQ VAS and EQ5D.
The questionnaires were used four times: at the admission, 1, 3, and 6 months after the stroke.
Multivariant linear regression analysis was applied.
Results. ABS leads to a significant destruction and decrease of HRQOL in all of its domains.
Since physical functions of patients were the weakest immediately after the acute brain
stroke, and their disability was greatest at the admission , they evaluated their own health
condition and their quality of life as being lowest at the admission and within the first month.
At the end of the research the quality of life was significantly higher with the patients who
had rehabilitation treatment in hospitals.
Conclusion. The quality of life of patients after ABS is significantly damaged and lower both
in the early phase of recovery and 6 months after the stroke. Six months later the patients
from the experimental group had a significantly higher quality of life in comparison with
those from the control one.


PIK3CA, the gene encoding the p110α catalytic subunit of PI3K (phosphoinositide 3-kinase), is mutated in approximately 20% of sporadic CRCs (colorectal cancers), but the role of these mutations in the pathogenesis of CRC remains unclear. In the present study we used a novel mouse model to investigate the role of the Pik3caH1047R mutation, the most common PIK3CA mutation in CRC, during the development and progression of intestinal cancer. Our results demonstrate that Pik3caH1047R, when expressed at physiological levels, is insufficient to initiate intestinal tumorigenesis; however, in the context of Apc (adenomatous polyposis coli) loss, which is observed in 80% of CRCs and by itself results in benign intestinal adenomas, the Pik3caH1047R mutation promotes the development of highly aggressive and invasive adenocarcinomas in both the small and large intestines. The results of the present study show that an activating Pik3ca mutation can act in tandem with Apc loss to drive the progression of gastrointestinal cancer and thus this disease may be susceptible to therapeutic targeting using PI3K pathway inhibitors.


Part of this work has been submitted to the Transactions on Circuits and Systems for Video Technology (TCSVT). Abstract We investigate the problem of collaborative video streaming in overlay networks. We exploit path and source diversity, as well as basic processing capabilities of network nodes in order to increase the overall throughput and improve the video quality at the clients. We consider an architecture where several streaming servers simultaneously deliver video information to a set of clients. The servers apply Raptor coding on the video packets for error resiliency, and the forwarding peer nodes selectively combine the Raptor coded video packets in order to increase the packet diversity. We analyze the performance of selective network coding and we describe its application in video streaming systems. We further define the source and channel rate allocation in such a collaborative streaming system by estimating the expected symbol diversity at clients. The optimization is defined as minmax and it is solved by a low-cost bisection based method. The experimental evaluation demonstrates that our system typically outperforms Raptor video streaming systems that do not use network coding, or systems that perform decoding and encoding in the network nodes. Finally, our solution presents a low complexity and only requires small buffers in the network coding nodes, which are certainly important advantages for deployment in practical streaming systems.


The failure to consider the collective bargaining relationship already established between labor and management constitutes a major deficiency in the research on collaboration, especially since labor unions are likely to play a significant role in organizational reform. The purpose of this research is to analyze the successful labor-management reform initiative in the city of Indianapolis using a model of collaboration developed by the authors.


In "Revolution or Renaissance", D. Paul Schafer subjects two of the most powerful forces in the world - economics and culture - to a detailed and historically sensitive analysis. He argues that the economic age has produced a great deal of wealth and unleashed tremendous productive power; however, it is not capable of coming to grips with the problems threatening human and non-human life on this planet. After tracing the evolution of the economic age from the publication of Adam Smith's "The Wealth of Nations" in 1776 to the present, he turns his attention to culture, examining it both as a concept and as a reality. What emerges is a portrait of the world system of the future where culture is the central focus of development. According to Schafer, making the transition from an economic age to a cultural age is imperative if global harmony, environmental sustainability, economic viability, and human well-being are to be achieved.


The genus Agaronia includes dominant predators in the eulittoral zone of dissipative sandy beaches of the tropical Eastern Pacific, which show specific adaptations to this environment such as swashsurfing locomotion. We studied A. propatula in its natural habitat in El Salvador and Costa Rica, and performed field experiments to obtain insights into its ecology, behaviour and sensory physiology. Agaronia propatula is not attracted by carrion and preys mostly on the ubiquitous beach snail Olivella semistriata. This, however, reflects community composition rather than prey specialization; A. propatula is an investigative hunter and will, quite literally, attack everything that moves (with the notable exception of echinoids). Prey is identified at short range by tactile and, to a lesser degree, by chemosensation located in the propodium. We found no evidence for long-distance sensory capabilities; A. propatula rather seems to rely on the regular physical structure of its wave-dominated environment when it moves between its shallow subtidal resting zone and its upper intertidal hunting grounds where potential prey predictably congregates. On the other hand, behavioural patterns such as the rapid yet haphazard cruising of foraging individuals, or the complex prey capture sequence in which the prey is transferred to a metapodial pouch, are similar in A. propatula and Oliva. Thus, our results lead us to speculate that the development of behavioural features that proved adaptive in the intertidal environment was essential in the evolution of Agaronia from Oliva-like ancestors.


Abstract The book attempts to shed light on the preconditions for Finnish economic growth in the next 10–15 years. Based on economic research, we discuss the central determinants of economic growth and assess how these determinants fare in Finland. The time span is longer than one business and electoral cycle, but it is still relatively short, so that most of technologies on which growth relies are already present. The book contains 12 chapters and each chapter has its own authors. On one hand, the central message of the book is encouraging. Finnish economic and political institutions and the knowhow of people are in good shape. Finland has all preconditions to utilize well new technology in order to increase the well-being and do so after taking into account the constraints imposed by the environment. On the other hand, it is evident that good outcomes will not be reached without determined and patient policies. The most important policy challenges concern strengthening of education and research, transformation of the economy toward carbon neutrality, prevention of exclusion, increase of work-based immigration and the ability of labor markets to adjust to different kinds of shocks.


Transcription Activator-Like Effectors (TALEs) Hybrid Nucleases for Genome Engineering Application Gene targeting is a powerful genome engineering tool that can be used for a variety of biotechnological applications. Genomic double-strand DNA breaks generated by engineered site-specific nucleases can stimulate gene targeting. Hybrid nucleases are composed of DNA binding module and DNA cleavage module. Zinc Finger Nucleases were used to generate double-strand DNA breaks but it suffers from failures and lack of reproducibility. The transcription activator–like effectors (TALEs) from plant pathogenic Xanthomonas contain a unique type of DNA-binding domain that bind specific DNA targets. The purpose of this study is to generate novel sequence specific nucleases by fusing a de novo engineered Hax3 TALE-based DNA binding domain to a FokI cleavage domain. Our data show that the de novo engineered TALE nuclease can bind to its target sequence and create double-strand DNA breaks in vitro. We also show that the de novo engineered TALE nuclease is capable of generating doublestrand DNA breaks in its target sequence in vivo, when transiently expressed in Nicotiana benthamiana leaves. In conclusion, our data demonstrate that TALEbased hybrid nucleases can be tailored to bind a user-selected DNA sequence and generate site-specific genomic double-strand DNA breaks. TALE-based hybrid nucleases hold much promise as powerful molecular tools for gene targeting applications.


Background: Zika virus is a flare-up mosquito-borne virus that manifests itself in sporadic human infections with Zika fever. It has a serious affect in pregnant women. Mother transmits Zika virus infection to her infant during the time of delivery which results in the birth of newborn with microcephaly and some neurological malformations. Molecular studies revealed that the 3'UTR of Zika virus genome plays a vital role in viral replication and pathogenicity. So, the 3'UTR can be a suitable target for the prevention of viral multiplications and degree of pathogenicity. The activity of the 3' UTR of Zika virus genome can be controlled by blocking or down regulating its expression through RNAi technology. RNAi works by silencing or turning off target gene expression using siRNA. Hence there arises an urgent need to design potential siRNA against the target sequence of Zika virus genome to control its replication and pathogenicity. This study is aimed to predict potential siRNA based therapeutics that might be used for the treatment of Zika virus infection. Methods: Designing siRNA against the target region of different strains of Zika virus is difficult due to its genetic diversity. Therefore, the work is done on the basis of rational siRNA designing method by targeting the 3'UTR of Zika virus strains. The prediction of potential siRNA was done by using various computational tools as searching target sequences, multiple sequences alignment, secondary structure prediction, siRNA-Target sequence interaction prediction and finally the evaluation of effectiveness of predicted and depicted siRNA. Results: Out of sixty siRNA only four potential siRNA were predicted and depicted rationally for silencing 3'UTR of 37 different Zika virus genome used in the study through RNAi technology. Conclusion: The outcomes of this study are four potential siRNA molecules which might be used as a potential antiviral RNA based therapeutics to suppress the Zika virus mediated infection. Key words: Antiviral RNA, RNAi technology, siRNA, Zika virus, 3' UTR region.


Luminescent Solar Concentrators (LSCs) use fluorescent materials and light guides to convert direct and diffuse sunlight into concentrated wavelength-shifted light that produces electrical power in small photovoltaic (PV) cells with the goal of significantly reducing the cost of solar energy utilization. In this paper we present an optimization analysis based on the implementation of a genetic algorithm (GA) subroutine to a numerical ray-tracing Monte Carlo model of an LSC, SIMSOLAR-P. The initial use of the GA implementation in SIMSOLAR-P is to find the optimal parameters of a hypothetical "perfect luminescent material" that obeys the Kennard Stepanov (K-S) thermodynamic relationship between emission and absorption. The optimization balances the efficiency losses in the wavelength shift and PV conversion with the efficiency losses due to re-scattering of light out of the collector. The theoretical limits of efficiency are provided for one, two and three layer configurations; the results show that a single layer configuration is far from optimal and adding a second layer in the LSC with wavelength shifted material in the near infrared region significantly increases the power output, while the gain in power by adding a third layer is relatively small. The results of this study provide a theoretical upper limit to the performance of an LSC and give guidance for the properties required for luminescent materials, such as quantum nanocrystals, to operate efficiently in planar LSC configurations.


Most extant studies of corporate social and environmental reporting (CSER) tend to examine the volume of CSER by companies. In contrast, the significance of this thesis lies in its focus on key stakeholders who are users of CSER and their needs. The perspectives of multiple key stakeholders, including investing, procuring and campaigning stakeholders, are investigated with respect to what they perceive to be valuable social and environmental reporting in supporting decision making. This thesis also goes beyond CSER and examines social and environmental reporting from other sources, including but not limited to reporting arising from private meetings between companies and stakeholders and information about companies' social and environmental impact or performance from information intermediaries. Stakeholder perceptions on the value and the qualitative characteristics of social and environmental reporting have been sought through semi-structured questionnaire with individuals drawn from the key stakeholder groups. Consistent with stakeholder theory, it is expected that stakeholder needs may vary. The findings in this thesis support a hypothesised relationship between the value of social and environmental reporting and information qualitative characteristics. Other key findings show that the availability of social and environmental reporting affects stakeholders' extent of use of social and environmental reporting and that the drivers for the value of information and the extent of use of information are different. The findings present important implications for both company managers and policy-makers. Company managers are better informed concerning stakeholder information needs. Thus they are better equipped to make decisions about the extent, scope and form of CSER. Furthermore, this thesis enables policy-makers to assess whether CSER requirements under current regulatory mechanisms reflect stakeholder needs. Finally this thesis has contributed towards enriching literature in the CSER area.


Using a matched employer-employee dataset on Italy we look at the spatial distribution of wages among provinces. We find evidence of both urbanization and market potential externalities, with the second one being more relevant. However, spatial sorting of skills is at work and explains a great deal of spatial wage variability. We further show that this sorting is only partially due to migrations and it dampens estimates of spatial externalities. The evidence concerning the sorting of firms is instead quite weak. In the paper, we also find support of self-selection of migrants based on skills and a moderate evidence of the wage growth hypothesis. Finally, we show that the well-established correlation between the employer size and workers' skills is not simply the outcome of a co-location phenomenon.


This paper describes a CAAD teaching strategy in which some Artificial
Intelligence techniques are integrated with 3D modelling exploration. The
main objective is to lead the students towards "repertoire" acquisition and
creative exploration of design alternatives. This strategy is based on
dialogue emulation, graphic precedent libraries, and 3D modelling as a
medium of design study.

The course syllabus is developed in two parts: a first stage in which the
students interact with an intelligent interface that emulates a dialogue.
This interface produces advice composed of either precedents or possible
new solutions. Textual descriptions of precedents are coupled with
graphical illustrations and textual descriptions of possible new solutions
are coupled with sets of 3D components. The second and final stage of
the course is based on 3D modelling, not simply as a means of
presentation, but as a design study medium. The students are then
encouraged to get the system's output from the first stage of the course
and explore it graphically. This is done through an environment in which
modelling in 3D is straightforward allowing the focus to be placed on
design exploration rather than simply on design presentation. The
students go back to the first stage for further advice depending on the
results achieved in the second stage. This cycle is repeated until the
design solution receives a satisfactory assessment.


This paper describes a team's efforts to transform the educational experience for electrical and computer engineering (ECE) students by demonstrating the importance of mathematics and the power of mathematical thinking. Math is a mainstay in ECE education. A holistic understanding of ECE concepts is highly dependent on students' grasp of key topics in mathematics, yet students are often intimidated by the mathematics required for the major and struggle to see why math matters. The dismal consequence is that students lack motivation and confidence, and eventually abandon the major. In 2015, the ECE department received a five-year RED (Revolutionizing Engineering Departments) grant from the National Science Foundation to revamp the current engineering educational system. Performing research that leads to scalable and sustainable change in engineering education, the department is, in effect, throwing away courses to help students learn more meaningfully and effectively. The new pedagogical and organizational model treats the undergraduate degree as a complex system, giving consideration to the interconnectivity and integration of fundamental concepts across the program. This holistic approach emphasizes knowledge integration and weaves key threads (creativity, foundations, and professionalism) throughout the curriculum, stitching together and reinforcing relevant themes from the freshman to senior years. With the goal of showing students why math is critical to becoming a successful engineer, this paper focuses on the foundations thread of the RED project. Even though the foundations thread encompasses topics in both math and science, this paper shines a light on mathematics and the role it plays in retention. The paper highlights the importance of the foundations "thread champion," a newly assigned role held by a faculty member who teaches subjects in the technical core of the ECE junior year and holds a joint faculty appointment in the Department of Mathematics. Working in concert with a Graduate Teaching Fellow, the thread champion and fellow faculty are garnering interest and building motivation by showing students that almost every calculation they perform is critical to solving real-world engineering problems. Whether putting a problem into the context of an engineering application such as the smart phone, or highlighting the fascinating history of mathematics, this paper explains the process the team is using to demonstrate why math matters – now and in the future. The team will know they are successful when students begin to view courses such as calculus as a building block for deeper learning instead of a subject to endure and disregard.


Introduction Rotational atherectomy (RA) during primary PCI (PPCI) for STEMI is relatively contraindicated because of the perceived increased risk of no-reflow. However, RA PPCI may sometimes be required to restore flow in heavily calcified coronary arteries. Previously only very limited observational data has described the use of RA in PPCI. Aim We report the clinical and procedural characteristics, and in hospital outcomes, of 21 patients who underwent RA PPCI at our centre between 2006 and 2016, Methods A retrospective review of the PCI database and medical records. Results 21 patients (age 78(10) years (mean (SD)), 12 men) underwent RA during PPCI (0.4% of all PPCI). 3 patients had cardiogenic shock at presentation and 2 had out of hospital cardiac arrest. Hypertension (n=19), smoking history (n=18), hypercholesterolemia (n=16), diabetes (n=6) and chronic kidney disease (n=6 with eGFR<60) were frequently present. Aspirin was given to 20/21 patients and clopidogrel, ticagrelor and prasugrel to 10, 9 and 3 patients respectively. Heparin was used in all patients, glycoprotein (GP) IIBIIIA inhibitor in 10 and bivalirudin in 2. Radial access was used in 14 and femoral in 7. Initial TIMI flow grade was 0, 1, 2 and 3 in 11, 2, 1 and 7 patients respectively. The target vessel was the RCA in 14, Cx in 4, LMS in 2 and LAD in 1. All were severely calcified with visible thrombus in 13/21. The lesion length was 36(19) mm (range 12–72 mm). The vessel diameter was 2.5–2.99 mm in 5, 3–3.49 mm in 10 and 3.5–4.0 mm in 6. RA was used because of anticipated difficulty with conventional PCI in 7/21 and uncrossable/unexpandable lesions in 14/21. The number of burrs used was 1.33 (0.48) and the final burr was 1.25, 1.5, 1.75 and 2 mm in 4, 11, 4 and 1 patient respectively. The burr-to-artery ratio was <0.4 in 5 and 0.4–0.6 in 16. The final procedure was DES in 17, BMS in 3 and POBA followed by CABG in 1. A temporary pacemaker was used in 3 cases and intra-aortic balloon pump in 3 cases. There were no perforations, no tamponade and no vascular complications. The median(range) pain-to-PCI time was 180 min (114–544); door-to-PCI time 49 min (21–186, 14 patients <60 min) and procedure time was 119 min (66-175). Procedural difficulty caused door-to-PCI>60 min in 5/7 patients while medical/logistic reasons contributed in the other 2. 1 patient underwent CT scanning prior to PCI; 1 underwent an urgent MDT discussion before PCI. Final flow was TIMI 3 in 19/21 and TIMI 2 in 2/21 cases. The procedure was complicated by 1 event of distal embolization. There was 1 event of peri-procedural cerebral infarction. 20/21 patients survived to hospital discharge. Conclusions Our study suggests that RA PPCI can be performed safely in a small group of predominantly elderly, complex patients in whom conventional techniques are inadequate or unsuccessful. It is associated with a relatively long procedure time but we did not experience a marked increase in no-reflow.


Evaluation of adverse drug reactions (ADRs) is important to the assessment of risk factors in an aim to ensure maximum benefits of drug therapy. This study was done to assess the types of ADRs presenting to the Accident and Emergency department (A&E) of the University Hospital of the West Indies. Admissions to the A&E associated with drugs were followed on a weekly basis for 19 weeks from October 2007 to February 2008 using the patient logbook. Medical records of patients with suspected ADRs were collected and evaluated by an Emergency Medicine Consultant of A & E to confirm the occurrence of ADRs and the suspected drug. Of the 8170 admissions to A&E, 48 (0.6%) were related to ADRs, with most occurring in females and the mean age (+/- standard error) was 58.9 (+/- 3.4) years. Drug induced hypoglycaemia accounted for 28 (56.3%) cases of ADRs and included mainly patients on insulin, with or without a sulphonylurea therapy. Most of these diabetic patients also had co-morbidities and were on multi-drug therapy (18). Allergic reactions accounted for 10 (21%) of the ADR outcomes. Other drugs accounting for ADRs included cardiovascular drugs (10.4%), analgesic/anti-inflammatory medications (8.3%), drugs acting on the central nervous system (8.3%) and anti-infectives (8.3%). It is concluded that drug-induced hypoglycaemia is the major ADR presenting to the A&E of the University Hospital of the West Indies; it is a preventable ADR and therefore further investigation should evaluate possible factors attributed to the occurrences.


How do political parties guarantee enforcement of a clientelistic exchange? This research note empirically supports a catalog of clientelism compliance enforcement tactics. It also suggests that by focusing on the personalization of tactics and the constraints they place on individual voters, we can evaluate how intrusive these tactics are and further help to bridge existing instrumentalist and reciprocity theories of client compliance. The supporting evidence comes from interviews carried out with 73 elected Argentine local and provincial officials. How persuasive or coercive the tactics need to be to make clients comply with their part of the bargain has implications for our understanding of the legitimacy of the clientelistic bondage and our assessment of the roles of patrons and brokers in such exchanges.


This collection of original essays documents technology's centrality to the history of early America. Unlike much previous scholarship, this volume emphasizes the quotidian rather than the exceptional: the farm household seeking to preserve food or acquire tools, the surveyor balancing economic and technical considerations while laying out a turnpike, the woman of child-bearing age employing herbal contraceptives, and the neighbors of a polluted urban stream debating issues of property, odor, and health. These cases and others drawn from brewing, mining, farming, and woodworking enable the authors to address recent historiographic concerns, including the environmental aspects of technological change and the gendered nature of technical knowledge. Brooke Hindle's classic 1966 essay on early American technology is also reprinted, and his view of the field is reassessed. A bibliographical essay and summary of Hindle's bibliographic findings conclude the volume. The contributors are Judith A. McGaw, Robert C. Post, Susan E. Klepp, Michal McMahon, Patrick W. O'Bannon, Sarah F. McMahon, Donald C. Jackson, Robert B. Gordon, Carolyn C. Cooper, and Nina E. Lerman.


Multi view imaging has attracted increasing attention recently and has become one of the potential avenues in future video systems. We aim to make more reliable and robust automatic feature extraction and natural 3D feature construction from 2D features detected on a pair of frontal and profile view face images. We propose several heuristic algorithms to minimize possible errors introduced by prevalent non-perfect orthogonal condition and non-coherent luminance. In our approach, we first extract the 2D features that are visible to both cameras in both views. Then, we estimate the coordinates of the features in the hidden profile view based on the visible features extracted in the two orthogonal views. After that, based on the coordinates of the extracted features, we deform a 3D generic model to perform the desired deformation based modeling. Finally, the face model is texture-mapped by projecting the input 2D images onto the vertices of the face model. As the reconstructed 3D face model is MPEG4 compliant, it can be readily animated by standard MPEG4 facial animation parameters (FAPs). Present study proves the scope of resulted facial models for practical applications like face recognition and performance driven facial animation.


Foundations are sometimes placed very close to each other because of space limitations or to limit the footing loads or to accommodate certain structural details. When footings are placed at close spacing, they interact with each other and the behaviour of each individual footing is altered compared to that of a single isolated footing. Also, foundations are often subjected to cyclic live loads in addition to self-weight of the structure causing change in soil performance below it. The design of foundations placed close to each other and subjected to cyclic loading is very complex as both of the phenomena (i.e., footing interference and cyclic load) affects the behaviour of foundation soil. The presence of clayey soil deposits in the construction site adds further uncertainty to this problem because there is no consensus among the researchers regarding interfering footing behaviour on clay. To uncover the actual behaviour of two closely spaced surface strip footings on clay deposits under cyclic loading, small-scale experimental studies with footings placed at two different spacings were carried out in the Civil Engineering laboratory at the University of New South Wales (UNSW@ADFA). The study shows that the application of low-frequency cyclic load improves the bearing capacity and stiffness of foundation soil (clay), irrespective of the interfering footing spacing. Also, the permanent deformation of interfering footings placed at closer spacing is found to be smaller compared to that of footings placed at wider spacing.


During the late 1990s public pension funds across the United States accrued large actuarial surpluses. The seemingly flush conditions of the pension funds led legislators in most states to substantially improve retirement benefits for public workers, including teachers. In this study we examine the benefit enhancements to the teacher pension system in Missouri. The enhancements resulted in large windfall gains for teachers who were close to retirement when the legislation was enacted. By contrast, novice teachers, and teachers who had not yet entered the labor force, were made worse off. The reason is that front-end contribution rates have been raised for current teachers to offset past liabilities accrued from the enhancements. Total teacher retirement compensation, net of contribution costs, is lower for young teachers today as a result of the enhancement legislation. Given sharp increases in pension costs in other states, this finding may generalize to young teachers in many other plans.


A computer analysis of 2328 protein sequences comprising about 60% of the Escherichia coli gene products was performed using methods for database screening with individual sequences and alignment blocks. A high fraction of E. coli proteins--86%--shows significant sequence similarity to other proteins in current databases; about 70% show conservation at least at the level of distantly related bacteria, and about 40% contain ancient conserved regions (ACRs) shared with eukaryotic or Archaeal proteins. For > 90% of the E. coli proteins, either functional information or sequence similarity, or both, are available. Forty-six percent of the E. coli proteins belong to 299 clusters of paralogs (intraspecies homologs) defined on the basis of pairwise similarity. Another 10% could be included in 70 superclusters using motif detection methods. The majority of the clusters contain only two to four members. In contrast, nearly 25% of all E. coli proteins belong to the four largest superclusters--namely, permeases, ATPases and GTPases with the conserved "Walker-type" motif, helix-turn-helix regulatory proteins, and NAD(FAD)-binding proteins. We conclude that bacterial protein sequences generally are highly conserved in evolution, with about 50% of all ACR-containing protein families represented among the E. coli gene products. With the current sequence databases and methods of their screening, computer analysis yields useful information on the functions and evolutionary relationships of the vast majority of genes in a bacterial genome. Sequence similarity with E. coli proteins allows the prediction of functions for a number of important eukaryotic genes, including several whose products are implicated in human diseases.


This report has assessed programmes available to UK commissioners, rather than considering programmes from around the world. This is the first time that EIF have used their own robust methods for rating the evidence and costs of early intervention programmes. The programmes included in this assessment were identified through systematic methods as part of the Best Start at Home review published in 2015. This included a range of programmes that supported the non-physical development of children between conception and age five through direct engagement with the parent. In Foundations for Life the evidence for the programmes was reviewed and rated by EIF and external experts, as well as being scrutinised by the EIF Evidence Panel of leading academics in the field of early intervention.

Parent child interactions in the early years matter. Parents and care givers lay the foundations for children's life skills including the ability to build productive relationships, emotional regulation, communication, and problem solving. Some parents, however, struggle to provide their child with a sufficiently nurturing environment or need some help along the way and so benefit from high quality support that is matched to their situation.

The report shows that there are a number of early signals of risk to children's development such as child behaviour problems, insecure attachment, delayed development of speech and language and lack of maternal sensitivity, which can be effectively responded to by available, well-evidenced programmes or for which new programmes are under development.

Key findings:
• The report found that although the overall evidence base for programmes available in the UK is not yet mature, there is a range of well evidenced and promising interventions that, if carefully commissioned to ensure they fit with local need and context, are likely to be effective in tackling problems identified in the early years.
• The evidence is strongest for programmes that target based on early signals of risk, such as child behaviour problems, insecure attachment, delayed development of speech and lack of maternal sensitivity, although other types of programmes have also been found effective.
• It found 17 programmes are well-evidenced, and a further 18 have preliminary evidence of impact. Many others at an earlier stage of development are committed to developing their evidence, and must be supported to do so.
• Five programmes were rated by the EIF review as having had "no effect" in a rigorous study which failed to show consistent benefits for children. This doesn't necessarily mean that these programmes will never work, some may adapt and be found to be effective in the future.
• If commissioned, targeted and implemented carefully, many of these 75 programmes have the potential to enhance development and tackle problems identified in the early years and, for example, improve children's behaviour and achievement at school or prevent mental health problems when they are older


In this paper, it is argued that money supply in a narrow sense and repo interest rate are two independent monetary policy instruments when the effect of interest rate policy cannot be efficiently transmitted to the economy through the monetary and financial markets. In this case, the control of money supply is necessary to reduce the discrepancy between the repo interest rate and the interest rates at which private agents lend and borrow. Using a simple macro-economic model, this study shows how a twopillar monetary policy strategy as practiced by the European central bank (ECB) can be conceived to guarantee macroeconomic stability and the credibility of monetary policy. This strategy can be interpreted as a combination of inflation targeting and monetary targeting. Well conceived monetary targeting with a commitment to a long-run money growth rate corresponding to inflation target could reinforce the credibility of central bank announcements and the role of inflation target as strong and credible nominal anchor for private inflation expectations. However, an inflation-targeting regime associated with Friedman's money supply rule can generate dynamic instability in output, inflation and money demand. Three feedback monetary targeting rules, of which the design depends on economic structure and central bank preferences, are discussed relative to their capability of warranting macroeconomic stability.


Uncertainty over the trajectory of seawater oxygenation in the coming decades is of particular concern in the light of geological episodes of abrupt global warming that were frequently accompanied by lowered seawater oxygen concentrations. Here we present an assessment of global seawater oxygenation from an interval of one of these warming episodes, the Paleocene-Eocene Thermal Maximum (PETM, 55.9 m.y. ago). Our results, obtained from Integrated Ocean Drilling Program Expedition 302 Site M0004 in the Arctic Ocean, are based on molybdenum isotope determinations and molybdenum, rhenium, and uranium abundances. These data indicate a small global expansion of low-oxygen marine environments in the upper part of the PETM interval compared with the present day. More extensive seawater deoxygenation may have occurred for as long as ∼100 k.y., associated with a high rate of global warming and carbon oxidation at the start of the PETM. Our data also reveal molybdenum isotope compositions in Arctic Ocean deposits that are outside the range currently documented in marine environments. These exceptional compositions could reflect either the influence of hydrothermal inputs or equilibrium isotope fractionations associated with molybdenum sulfide speciation.


In this paper we present Semanta – a fully-implemented system supporting Semantic Email Processes, integrated into the existing technical  landscape and using existing email transport technology. By applying Speech Act Theory, knowledge about these processes can be made explicit, enabling machines to support email users with correctly interpreting, handling and keeping track of email messages, visualizing email threads and workflows, and extracting tasks and appointments from email messages. Whereas complex theoretical models and semantics are hidden beneath a simplistic user interface, the enabled functionalities are clear for the users to see and take  advantage of. The system's evaluation proved that our experiment with Semanta has indeed been successful and that semantic technology can be applied as an extra layer to existing technology, thus bringing its benefits into everyday computer usage.


In this paper, we seek to produce forecasts of commodity price movements that can systematically improve on naïve statistical benchmarks. We revisit how well changes in commodity currencies perform as potential efficient predictors of commodity prices, a view emphasized in the recent literature. In addition, we consider different types of factor-augmented models that use information from a large data set containing a variety of indicators of supply and demand conditions across major developed and developing countries. These factor-augmented models use either standard principal components or the more novel partial least squares (PLS) regression to extract dynamic factors from the data set. Our forecasting analysis considers ten alternative indices and sub-indices of spot prices for three d ifferent commodity classes across different periods. We find that, of all the approaches, the exchange-rate-based model and the PLS factor-augmented model are more likely to outperform the naïve statistical benchmarks, although PLS factor-augmented models usually have a slight edge over the exchange-rate-based approach. However, across our range of commodity price indices we are not able to generate out-of-sample forecasts that, on average, are systematically more accurate than predictions based on a random walk or autoregressive specifications.


In the literature, there are at least two equivalent two-factor Gaussian models for the instantaneous short rate. These are the original two-factor Hull White model (see [3]) and the G2++ one by Brigo and Mercurio (see [1]). Both these models first specify a time homogeneous two-factor short rate dynamics and then by adding a deterministic shift function '(·) fit exactly the initial term structure of interest rates. However, the obtained results are rather clumsy and not intuitive which means that a special care has to be taken for their correct numerical implementation.


The Nrf2 has been identified as a key molecular player in orchestrating adaptive cellular interactions following a wide spectrum of cellular conditions that could be either extracellular or intracellular. The encoded transcription factor regulates genes, which contain antioxidant response elements (ARE) in their promoters; many of these genes encode proteins involved in response to environmental stress, detoxifying enzymes, metabolic enzymes, injury, and inflammation, which includes the production of free radicals. The association between oxidative stress and inflammation with progression of diabetic nephropathy and cardiomyopathy has been described. The prevention of diabetic nephropathy and cardiomyopathy has become a global concern for those who are working in diabetic care management. Therefore, activation of Nrf2 has the potential to protect against macromolecular damage. Studies have demonstrated the beneficial role of Nrf2 induction in the prevention of DN. Upon exposure of cells to oxidative stress or electrophilic compounds, Nrf2 dissociates from Keap1 and translocates into the nucleus to bind to antioxidant-responsive elements in the genes encoding antioxidant enzymes. Upregulation of these Nrf2-dependent antioxidants promotes detoxification and antiinflammatory function. Thus, the Nrf2 activators have been suggested for preventing diabetic nephropathy.


The purpose of this chapter is to present an online system for a 3D representation of programming students' profiles on software metrics that quantify effort and quality of programming from the analysis of source codes. In this representation, each student profile is a three-dimensional vector represented by a set of programming solutions developed by a student and mapped on 348 metrics of software during a programming course. Applying this profile representation, we developed a system with the following functionalities: generation of student's timelines to verify the evolution of metrics in a sequence of programming solutions over a course, different visualizations of these variables, automatic selection of representative codes for composition of rubrics with less effort of evaluation and selection of metrics that more influence in scores attributed by teachers. The advantages of this system are to enable the analysis of where the learning difficulties begin, the monitoring of how a class evolves along a course and the dynamic composition of rubric representations to inform assessment criteria. The system proposed therefore presents itself as a relevant tool to assist teachers about decisions of an evaluative process, allowing in fact to assist students from the beginning to the end of a course.


Background: Missing data constitutes a common phenomenon, especially, in questionnaire-based, population surveys or epidemiological studies, with the statistical power, the efficiency and the validity of the conducted analyses being significantly affected by the missing information. The aim of the present work was to investigate the socio-demographic, lifestyle and clinical determinants of low response rate in a self- rating multi-item scale, estimating the individuals' hostility and direction of hostility. Methods: 3042 apparently healthy volunteers residing in the Athens metropolitan area participated in the ATTICA epidemiological study [1514 (49.8%) were men [46 years old (SD= 13 years)] and 1528 (50.2%) were women [45 years old (SD= 14 years)]]. Hostility and Direction of Hostility was assessed with the Hostility and Direction of Hostility (HDHQ) scale. Binary logistic regression with backward model selection was used in order to identify the key demographic, clinical and lifestyle determinants of higher non-response rate in the HDHQ scale. Results: The vast majority of the participants (87.0%) had missing information in the HDHQ scale. Older age, lower educational level, poorer health status and unhealthy dietary habits, were found to be significant determinants of high nonresponse rate, while female participants were found to be more likely to have missing data in the items of the HDHQ scale. Conclusions: The present work augments prior evidence that higher non-response to health surveys is significantly affected by responders' background characteristics, while it gives rise to research towards unrevealed paths behind this claim.


We propose minimum mean square error (MMSE)-based beamforming techniques for a multiantenna relay network, where a base station (BS) equipped with multiple antennas communicates with a number of single-antenna users through a multiantenna relay. We specifically solve three optimization problems, namely, 1) the sum-power minimization problem, 2) the mean-square-error (MSE) balancing problem, and 3) the mixed quality-of-service (QoS) problem. Unfortunately, these problems are not jointly convex in terms of beamforming vectors at the BS and the relay amplification matrix. To circumvent this nonconvexity issue, the original problems are divided into two subproblems, where the beamforming vectors and the relay amplification matrix are alternately optimized, whereas the other is fixed. Three iterative algorithms are developed based on convex optimization techniques and general MSE duality. Simulation results are provided to validate the convergence of the proposed algorithms.


Property is closely associated with freedom. Following the demise of the feudal property system, property ownership in Anglo-American law came to imply an individual's freedom to act as she pleases on her land. For their part, modern property theories—whether right-based, utilitarian, or relational—employ the normative value of freedom to justify ownership. Courts and scholars have always acknowledged the fact that this freedom of the owner cannot be absolute: an owner's freedom to do as she pleases on her land is often limited to protect other owners. However, the consensual assumption remains that an owner is not subject to affirmative duties. She is free, according to conventional wisdom, to choose to do nothing with her property. This Article argues that this assumption is simply wrong. Owners are not free to ignore their land. Property law has always subjected them to an obligation to maintain their land up to a specific standard. This obligation, dubbed here "the duty to maintain," is enforced through an array of legal rules and practices. This Article chronicles these rules and practices for the first time, classifying them in accordance with the enforcement mechanism they employ. It then justifies these diverse rules and practices—and the general duty to maintain—in light of the different theories of property. In this fashion, this Article illustrates that ownership, both as a legal institution and as a normative concept, inherently and inevitably incorporates a duty to maintain.


There has been diversification of Indian diets away from foodgrains to high value products like milk, meat products, vegetables and fruits. Food-processing industry has been registering good growth since the past few decades and particularly after nineties. The conditions are now ideal for the growth of this industry. The central government has taken some steps to deregulate and encourage the sector after 1991. However, the role of states is vital. The government of Andhra Pradesh released a policy in November 2003. There are no major initiatives in the policy and still can be called a good beginning. As against the robust growth at the All-India level, the growth rate in net value - added in the nineties was almost the same as that in the eighties in the state. Against this background, the study is taken up in the state of Andhra Pradesh with the following objectives 1. To study the opportunities and challenges in processing of rice, fruits and vegetables, oilseeds and livestock products 2. To study the working of contracts between processors and farmers 3. To identify the future areas 4. To recommend suitable policy options The contracts are working, on the whole, well in both oil palm in West Godavari and gherkin in Chittoor district of the state. The firms try to attract with favourable conditions initially, but later tighten them as a part of agribusiness normalization. Therefore caution is needed before a final conclusion can be drawn on the usefulness of contract farming in the state for the farming community. The contracts in oil palm 3 are widespread, covering many farmers and stabilized. The total extent under gherkin is very low. The contracts work through facilitator in gherkin. There are some signs of some mistrust between the facilitator-company and local farmers. The contracts are also evolving gradually to accommodate both parties. The participation of small farmers in oil palm cultivation is almost negligible. On the other hand, in gherkin, participation of small farmers was considerable. The contracts are oral and price is not assured in oil palm. In oil palm gardens, the depletion of ground water level is faster compared to other crops. In the case of gherkin, the processing industry is totally dependent on exports for sustenance, which may not be ideal. The establishment of an independent ministry of food processing and department, enacting of contract farming laws and providing for an efficient arbitration in cases of contract violation, encouraging NGOs participation in food processing sector, formation of product-wise farmers' associations, changing the animal slaughter laws and formation of some more agri-export zones for livestock products are some of the recommendations under institutional aspects. In the case of taxes and subsidies, the recommendations are - exemption from sales tax and market cess and relaxation of duties and taxes on packing material industry. Under research and training, large scale publicity to promote processed foods, undertaking demand driven research by developing processable varieties and required equipment, establishing food processing training centers, developing technology for the tiny food processing units, evolving marketing plan covering the recently emerging super markets, DWCRA bazaars, international markets etc., are some of the suggestions. In case of infrastructure, encouraging some large aseptic packaging units, establishment of a radiation technology plant, encouraging private sector in cold storages, precooling units, pack houses etc., establishment of training courses for service and repair of food processing machinery, formation of expert consultant committee and provision of one incubator are the major suggestions. Other major recommendations are provision of insurance facilities to all horticultural crops and livestock products, taking steps to ensure participation of small farmers in the contract farming, launching of a common brand of mango juice and enactment to regulate the feed industry and nurseries in the state.


Variational Autoencoders (VAEs) are expressive latent variable models that can be used to learn complex probability distributions from training data. However, the quality of the resulting model crucially relies on the expressiveness of the inference model. We introduce Adversarial Variational Bayes (AVB), a technique for training Variational Autoencoders with arbitrarily expressive inference models. We achieve this by introducing an auxiliary discriminative network that allows to rephrase the maximum-likelihood-problem as a two-player game, hence establishing a principled connection between VAEs and Generative Adversarial Networks (GANs). We show that in the nonparametric limit our method yields an exact maximum-likelihood assignment for the parameters of the generative model, as well as the exact posterior distribution over the latent variables given an observation. Contrary to competing approaches which combine VAEs with GANs, our approach has a clear theoretical justification, retains most advantages of standard Variational Autoencoders and is easy to implement.


The coculture of cord blood mononuclear cells (CB MNCs) and alginate beads containing rabbit bone marrow (BM) mesenchymal stem cells (MSCs) was investigated in three kinds of culture mediums under the static condition for 7 days. The total nucleated cell density was measured every 24 hours. Flow cytometric assay for CD34+ cells and methylcellulose colony assays were carried out at 0,72 and 168 h. The results show that the total nucleated cell number is multipled by (15±2.85) times,CD34+ cells (5.33±0.32) times and colony-forming units in culture (CFU-Cs) (5.6±1.21) times respectively at the end of the 7th day's coculture in the serum-free medium supplemented with conventional dose of cytokines. Microcapsules may be the appropriate coculture protocol and the encapsulated rabbit BM MSCs illustrate remarkable effects on CB hematopoietic stem/progenitor cells expansion when serum or proper cytokines are added under the static condition.


The emergence of king crabs from a hermit crab-like ancestor is one of the most curious events in decapod evolution. King crabs comprise two taxa, Lithodidae and Hapalogastridae, and while lithodids have formed the focus of various anatomical studies, the internal anatomy of hapalogastrids has never been studied although this group might represent a more ancestral morphological condition within king crabs than lithodids do. To better understand the evolutionary transformation of pagurid-like hermit crabs into king crabs, we studied the hemolymph vascular system and associated organs of representatives of Hapalogaster and present here the first micro-computer tomography data pertaining to the internal anatomy of hapalogastrids. Our results for Hapalogastridae are compared with existing and new data on Paguridae and Lithodidae and are discussed in the light of the process of carcinization or evolutionary transformation into a crab-like habitus. Hapalogaster resembles both pagurids on the one hand and lithodids on the other, not only with regard to external morphological characters but also in terms of certain internal anatomical features. In this and other respects, Hapalogaster represents an evolutionary intermediate form that connects pagurids and lithodids.


Scholars often regard the Qing-Korean relationship as the most representative instance of the so-called tributary system, the Sino-centric hierarchical world order in early modern East Asia. It was also the most stable one, established in 1637 and ending as late as 1895 after the Qing's total defeat in the first Sino-Japanese War. Precisely because this bilateral relationship was so typical and so stable, it was also unique in many ways. Although the Manchu regime largely inherited Ming China's institutions in dealing with Korea (and, later, with other foreign states), this legacy revealed new meanings in the context of the Manchu conquest of China. As the Qing's first and last subordinate state in the region, Chosŏn Korea served as both an ideological and a practical model in shaping the Qing's geopolitical construction.
 Beginning and ending with military clashes, the Qing-Chosŏn hierarchical relationship from the early 17th to the late 19th centuries was nourished and solidified by more peaceful interactions. Generally conducted under the Confucian zongfan (宗藩) principles, these interactions included rituals, diplomatic missions, trade, negotiations, cross-border jurisdiction, and cultural exchanges. Far from being imposed unilaterally by the Qing, the bilateral relationship was mutually constructed in a long process in which the Korean government and literati played a proactive role. During this time, the Korean attitude toward the Qing underwent a gradual change, from hostility to nuanced acceptance. In the late 19th century the two countries tried but failed to adjust their relationship in order to survive the geopolitical threat from industrialized, colonial powers. The collapse of the Qing-Chosŏn hierarchy eventually led to the rise of new national identities in both China and the Korean Peninsula in the 20th century.


Hotels constitute one of the main, and still expanding, pillars of the tourism sector and are highly unique among other commercial buildings. Resource intensive and frequently inefficient systems and operational routines applied in the sector, result in considerable environmental impact and indicate an urgent need for more environmentally sound practices and products in the hotel industry. A certain level of activity in the area of reducing resource use has been observed for quite some time but the motivation for this was related to cost-benefit issues rather than the environment. Furthermore, most of the initiatives are still considered to be best practice case studies and not daily routines. The constantly increasing prices of basic commodities, such as energy resources and water, encourage the implementation of energy and water efficiency and conservation measures in hotel facilities. To this end, numerous guidelines and initiatives have been produced by hotel-related organisations. The study of attitudes among 610 European hoteliers indicated that, at the moment, the level of environmental awareness among hotel managers is not high enough to introduce significant changes, although attitudes differ depending on the country of origin and the corporate policy. The prospects of significant cost savings, as well as customer demand were identified as the most likely parameters to enhance environmental responsibility among hoteliers. The popularity of CSR reporting and sustainability indices, especially among the larger companies, leads the author to believe that the industry is preparing to change. Many of the companies running hotels are also reporting their environmental management goals and indicators of environmental performance, while benchmarking and all types of comparison league tables are gaining popularity. There is, however, no system or methodology of data collection and monitoring that is universally accepted or applicable throughout the hotel sector. Furthermore, the accuracy and validity of the published performance indicators and benchmarks is widely debated due to large variations in the figures reported. The analyses performed on data from over 180 upscale and mid-market European chain hotels (Hilton International and Scandic) indicated that even among relatively uniform (service-wise) hotels the amenities offered did influence consumption, further complicating the concept and applicability of uniform benchmarking and resource consumption modelling. It was thus concluded that, creating a uniform model for all hotels is almost impossible, or would require a significant amount of very detailed input data, and that the results could still be highly inaccurate. Instead, it was suggested that it might actually be more accurate to develop models for individual hotels. Such an approach would allow for the modelling of the behaviour of all types of hotels with no size, type of services or standard limitations. Multi-variate step-wise regression analyses performed on individual Scandic hotels in Sweden indicated that energy consumption was dependent on the outdoor air temperature/actual heating degree days, while water consumption was mainly influenced by the number of guest-nights sold. Experience gained by the author during the process of the Hilton Environmental Reporting system upgrade allowed for the formulation of a set of rules of thumb that ought to be followed in the design of similar schemes. The experience of various regions and numerous companies also suggests that well designed and implemented environmental and resource management programs bring significant benefits at an individual as well as a corporate level. This study provides an indication of the strategies that can be used by various stakeholders in the process of development and implementation of such programs. This research further suggests that future developments in environmental performance indicators and benchmarking may best be served by disaggregating hotels into modules (such as guest-rooms, catering outlets, conference centres) and developing consumption models and best practice indicators for these particular components. The individual efficiencies/performance indicators should then be combined and weighted to provide a just overall evaluation of a facility that could then be compared to a benchmark (developed in the same manner). In a similar manner, sustainability assessment schemes and indicators for destinations and communities could be developed. However, more accurate and differentiated knowledge of the individual performance of sub-systems is necessary to proceed with such an alternative. In addition, the methodologies for data collection and reporting procedures, at all levels of the company and sector, need to be standardized and detailed


[Abstract]Research within clinical, organisational and community contexts, generally equates an individual's sense of well-being with the absence of adverse psychological states.
More recently, proponents of 'positive psychology' have drawn attention to positive affective states, like happiness and joy. The focus on affective states relates to a Subjective Well-Being (SWB) approach to well-being. In contrast, a Psychological Well-Being (PWB) approach considers the role of mastery and efficacy beliefs, a
sense of autonomy and positive relatedness with others, as separate dimensions that are related to SWB. Two studies tested the hypothesis that two affect dimensions of
SWB, Positive (PA) and Negative (NA) Affect, were independently related to PWB.
In both studies, factor analysis differentiated between items from two SWB and PWB measures, whilst correlations between the well-being factors were moderate. A
preliminary study reported PWB to be a significant predictor of SWB after controlling for Demographics and Negative Life Events. A lack of association between Negative Life Events and PA suggests independent effects for two broad SWB dimensions. Using an Organisational Health Research Framework (OHRF), a study of high-school teachers further controlled for a five-factor model of personality and both Positive and Negative Organisational Climate. PWB was still identified as a significant predictor of SWB after controlling for demographic, organisational climate and personality variables. Independent effects on positive and negative SWB
dimensions were also identified. Assessing change of both dependent and independent variables with two waves of data supported the independence of SWB outcomes and the strong effect of PWB on SWB across time. Higher levels of PWB
were mostly related to better SWB outcomes (lower negative and higher positive SWB states). Although the OHRF proposes reciprocal effects of employee wellbeing
and personality on perceptions of climate, the strongest effects were those reported whereby organisational climate and individual characteristics, being mostly independent of each other, strongly predicted employee SWB within and across waves. Implications for future employee well-being research are that organisational interventions need to address reducing negative and improving positive facets of the organisation. Individual interventions which promote PWB components would appear to be a most important avenue by which to improve employee SWB, by reducing NA and improving PA states.


Antibiotic drugs have revolutionized the field of medicine for almost 90 years. However, continued use has led to the rise of antibiotic resistant bacteria, motivating the need for alternative treatments. Several strategies to combat this phenomenon have been investigated, with biomimetic strategies gaining significant appeal due to inherent compatibility with physiologically relevant environments. In this review, we will discuss current antimicrobial strategies and then present an overview on biomimetic antimicrobial material-based strategies for combating antibiotic resistant bacteria.


The paper sought to examine the impact of instability in primary commodity export earnings and the level of commodity dependence on economic growth in Sub Saharan Africa (SSA).  Fixed effects panel data estimator was used in the empirical estimation. The findings of the study suggest that there is a negative relationship between instability in export earnings and economic growth. The results also indicate that the level of commodity dependence matter in determining economic growth in the region. The results of the paper have economic development policy implications for SSA economies and these are not farfetched. First, it appears the difficult growth experience of SSA is not solely due to instability in export receipts. The question of continued dependence on a narrow range of primary commodities is also matter of great importance.


We show that the disposition to focus on favorable or unfavorable outcomes of risky situations affects willingness to take risk as measured by the general risk question. We demonstrate that this disposition, which we call risk conception, is strongly associated with optimism, a stable facet of personality, and that it predicts real-life risk taking. The general risk question captures this disposition alongside pure risk preference. This likely contributes to the predictive power of the general risk question across domains. Our results also rationalize why risk taking is related to optimism.


An early assemblage of obsidian artifacts Levallois technology is the name for the stone knapping technique used to create tools thousands of years ago. The technique appeared in the archeological record across Eurasia 200 to 300 thousand years ago (ka) and appeared earlier in Africa. Adler et al. challenge the hypothesis that the technique's appearance in Eurasia was the result of the expansion of hominins from Africa. Levallois obsidian artifacts in the southern Caucasus, dated at 335 to 325 ka, are the oldest in Eurasia. This suggests that Levallois technology may have evolved independently in different hominin populations. Stone technology cannot thus be used as a reliable indicator of Paleolithic human population change and expansion. Science, this issue p. 1609 An assemblage of obsidian artifacts suggests independent origins of stone knapping in different hominin populations. The Lower to Middle Paleolithic transition (~400,000 to 200,000 years ago) is marked by technical, behavioral, and anatomical changes among hominin populations throughout Africa and Eurasia. The replacement of bifacial stone tools, such as handaxes, by tools made on flakes detached from Levallois cores documents the most important conceptual shift in stone tool production strategies since the advent of bifacial technology more than one million years earlier and has been argued to result from the expansion of archaic Homo sapiens out of Africa. Our data from Nor Geghi 1, Armenia, record the earliest synchronic use of bifacial and Levallois technology outside Africa and are consistent with the hypothesis that this transition occurred independently within geographically dispersed, technologically precocious hominin populations with a shared technological ancestry.


We present the first spectro-interferometric observations of the circumstellar envelope (CSE) of a B[e] supergiant (CPD -57' 2874), performed with the Very Large Telescope Interferometer (VLTI) using the beam-combiner instruments AMBER (near-IR interferometry with three 8.3 m Unit Telescopes or UTs) and MIDI (mid-IR interferometry with two UTs). Our observations of the CSE are well fitted by an elliptical Gaussian model with FWHM diameters varying linearly with wavelength. Typical diameters measured are ^ 1 .8 x 3 .4 mas or ^ 4. 5 x 8 . 5 AU (adopting a distance of 2 . 5 kpc) at 2. 2 µm, and ^ 12 x 15 mas or ^ 30 x 38 AU at 12 µm. We show that a spherical dust model reproduces the SED but it underestimates the MIDI visibilities, suggesting that a dense equatorial disk is required to account for the compact dust-emitting region observed. Moreover, the derived major-axis position angle in the mid-IR ( ^ 144° ) agrees well with previous polarimetric data, hinting that the hot-dust emission originates in a disk-like structure. Our results support the non-spherical CSE paradigm for B [e] supergiants.


According to the Energy Information Administration two fifths of the energy used by US wood products manufacturers comes from electricity and natural gas, the costs of which have pointedly increased over the last decade. Empirical indications exist that higher energy prices affect the industry's profitability. Together with other developments such as, for example, unfavorable trends in hardwood stumpage prices, higher transportation costs, increasing government regulations, a challenging economic situation, or the ongoing globalization of markets, the US hardwood industry has to cope with some serious challenges threatening its profit potential. To understand the impact of energy prices on wood products manufacturers' profitability and to gain insights regarding actions the industry is taking to respond to energy-related challenges, a survey was conducted among Eastern US primary hardwood products manufacturers in late 2010. Results show that, overall, the share of energy expenses on total production costs of respondents was 7.9%. A majority of respondents (61.8%) agreed that their energy expenses have increased by an average of 18.7% during the last five years. Half of the respondents reported a 5% or higher negative impact of higher energy prices on their profits over the same period. Actions undertaken by the industry to alleviate the negative impact of rising energy prices are presented in a second paper in this two-part series.


Based on the estimation of standardized precipitation–evapotranspiration index (SPEI) and standardized runoff index (SRI), this study investigated the variability and correlation of hydrological drought and meteorological drought in a humid climate region–the Poyang Lake catchment in China. Results indicate that the occurrences of hydrological droughts in the catchment are different from those of meteorological drought on both a seasonal and annual basis. However, annual variability of both indices showed the same periodic variation characteristics during the study period. With comparison of the performance of SPEI and SRI time series at different timescales, our observation reveals that the two drought indices show a higher degree of similarity and correlation as timescales increased. In addition, SRI is found to be less variable than SPEI at shorter timescales and it shows an obvious hydrologic delay of about one to two months in response to SPEI at timescales >12 months. Due to hydrologic detention of subsurface soil moisture, shallow groundwater and perhaps reservoir storage, a two-month timescale of SPEI is found to be more appropriate for river discharge monitoring, especially for those rivers with similar drainage area, climate and geographical conditions as in this study region.


Because of the frequency of multiple sites of involvement, a thorough evaluation of the entire spinal canal is essential for detection and treatment of spinal compression in cancer patients. For the examination of the entire spinal canal in cancer patients, a modified approach is described using water-soluble contrast medium (metrizamide), oil-based material (Pantopaque), and a "squeezing" technique for a complete myelographic block. Of 240 patients who underwent myelography for possible spinal compression, the squeezing technique was applied through a lumbar puncture to demonstrate a complete block in 39 patients; six of these had more than one block. Of the other 201 patients, the quality of the myelograms was satisfactory or excellent in 189 (94%).


Section 6602(a) of Chapter 66 of Title 29 of 64 Delaware Laws permits the
Delaware Division of Libraries to contract with "any public library, including privately
incorporated public libraries or public library systems." The purpose of these contracts is to "encourage the maintenance and development of proper standards, including personnel standards, hours of operation, library materials, collection standards, and interlibrary resources sharing. "In addition, this section provides for the "development of a statewide public library service."


Myoepithelioma, a benign tumor, occurs with a frequency of 1.5% among all salivary gland tumors, and it most commonly affects the parotid gland. Nearly the entire epithelium is composed of neoplastic myoepithelial cells exhibiting spindle, plasmacytic, epithelial-like, and clear cells. Case Report : A 52-year-old woman with myoepithelioma of the palate. The patient was referred to our hospital with a chief complaint of swelling on the right side of the palate. Following clinical and intraoral examinations, the tumor was removed under general anesthesia. Viewed microscopically, the tumor was seen to be surrounded by a fbrous membrane, primarily composed of a solid growth of neoplastic myoepithelial cells, virtually surrounding a hyaline-like eosinophilic substance. Immunohistochemical examination revealed strongly-positive reactions by the tumor cells for widespectrum cytokeratin (CK wide), vimentin, and S-100 proteins. CK 7, smooth muscle actin (SMA), p63, and glial fibrillary acidic protein (GFAP) gave weakly-positive reactions. Conclusion: Based on the fndings, a pathological diagnosis of myoepithelioma was reached.


The European Landscape Convention (ELC) emphasises that the public should be extensively involved in the processes of landscape protection, planning and management. In spite of the emerging interest in the relationship between animals and landscapes in the study of animal geography, little is known about the influence of the landscape-animal component on public aspirations and the values attributed to landscape. We conducted a survey in the form of an image-based questionnaire in order to evaluate the influence of certain animal species, in this case livestock, on landscape preferences. The results show that all grazing animals have a positive impact on landscape preferences, although some species seem more popular than others. The preference for scenes with animals decreases, however, when compared with scenes with other landscape features (vegetation, traditional buildings or water). Significant differences in preferences for scenes with animals were observed according to certain sociodemographic variables such as gender, familiarity with the landscape and direct involvement in livestock farming. Of the groups surveyed, livestock farmers showed the strongest preferences for the scenes with animals. The findings of this study can be applied within the citizen participation policies encouraged by the ELC, as well as in the protection, management and planning of rural landscapes in which livestock is an appreciable feature.


Abstract : Modern society depends on software systems of ever-increasing scope and complexity in virtually every sphere of human activity, including business, finance, energy, transportation, education, communication, government, and defense. Because the consequences of failure can be severe, dependable functionality and security are essential. As a result, software assurance is emerging as an important discipline for the development, acquisition, and operation of software systems and services that provide requisite levels of dependability and security. This report is the first volume in the Software Assurance Curriculum Project sponsored by the U.S. Department of Homeland Security. This report presents a body of knowledge from which to create a Master of Software Assurance degree program, as both a stand-alone offering and as a track within existing software engineering and computer science master?s degree programs. The report details the process used to create the curriculum and presents the body of knowledge, curriculum architecture, student prerequisites, and expected student outcomes. It also outlines an implementation plan for faculty and other professionals who are responsible for designing, developing, and maintaining graduate software engineering programs that have a focus on software assurance knowledge and practices. The second volume, Undergraduate Course Outlines (CMU/SEI-2010-TR-019), presents seven course outlines that could be used in an undergraduate curriculum specialization for software assurance.


A green-eyed mouse called Noah and a blue-eyed mouse called Raffaella see each other's eyes through a small hole in a wall. Both mice let their imagination run wild thinking what strange creature the eye belongs to. Beautifully illustrated, humorously written and brilliantly designed with a real hole in each of its pages to create a peep-show effect, this charming book is a visual treat for children and their parents.


The plutonic rocks of the Samail ophiolite in the southeastern Oman Mountains formed in a spreading-ridge magma chamber that was repeatedly replenished by primitive magma. An average composition of the parent magma for the Samail ocean crust is calculated by mass balance of the igneous stratigraphy. The average parent magma was in equilibrium with most early-formed cumulus minerals from the ophiolite and is very similar to primitive mid-ocean ridge basalt. The magma is basaltic—in contrast to the picritic melts proposed as parents for some ophiolites. Although the average parent magma composition is basaltic, field evidence suggests that individual batches of magma that fed the magma chamber varied in composition because of mantle processes. The primary mantle melts were probably picritic, but owing to reaction during ascent through the upper mantle and mixing or density entrapment within an open-system crustal-level magma chamber, these picritic melts were probably not erupted on the seafloor.


Abstract The paper focuses on the reservoir heterogeneity of a sandstone formation in which the main issue is the evaluation of diagenetic features. Integrated data from field observations as well as petrographic and geochemical analyses from surface and core sections from different structural settings were applied. In the shallow marine Pétervására Sandstone, eogenetic minerals are comprised of calcite, pyrite and siderite; mesogenetic minerals are albite, ankerite, calcite, quartz, mixed layer clays and kaolinite. Dissolution occurred during mesogenetic and telogenetic phases. Ankerite is only present in the core setting, where the sandstone is at ca. 900 m depth and diagenetic calcite predates quartz cementation. Based on stable isotopic values (δ13 CV-PDB −18.3 to −11.4 ‰ and δ18 OV-PDB −9.5 to −7.2 ‰), diagenetic calcite is of mesogenetic origin and was precipitated from fluids migrated along fault zones from the underlying, organic matter-rich formation. In outcrop setting, on the other hand, calcite is present in a larger quantity and postdates quartz cementation. Carbon isotope data (δ13 CV-PDB = −9.9 to −5.1 ‰) indicate less contribution of light isotope, whereas more negative oxygen isotopic values (OV-PDB = −13.1 to −9.9 ‰) likely imply higher temperature of mesogenetic fluids.However, carbon–oxygen isotope covariation can indicate precipitation from meteoric fluid. In this case, further analyses are required to delineate the final model.


Purpose: The purpose of this presentation is to share the findings from a research study funded by the National Institute for Health Research Services and Delivery Research Programme. Support workers make up the majority of the workforce in health and social care services for older people. There is evidence to suggest that support workers are not deployed as effectively as possible, are often undervalued, and there are gaps in understanding support worker roles across different care settings. The review was designed to answer the question: how can workforce development interventions improve the skills and the care standards of support workers within older people's health and social care services? Design: The review was conducted in four iterative stages over 18 months:(1) development of a theoretical framework and initial programme theory; (2) retrieval, review and synthesise evidence relating to interventions designed to develop the support workforce guided by the programme theories; (3) 'testing out' the synthesis findings to refine the programme theories, and establish their practical relevance/potential for implementation, and (4) forming recommendations about how to improve current workforce development interventions to ensure high standards in the care of older people. Findings: Eight CMO configurations emerged from the review process, which provide a programme theory about 'what works' in developing the older person's support workforce. The findings indicate that the design and delivery of workforce development should consider and include a number of starting points, specifically; personal factors about the support worker; the specific requirements of workforce development, and the fit with broader organisational strategy and goals. Conclusions: The review has resulted in an explanatory account of how the design and delivery of workforce development interventions work to improve the skills and care standards of support workers within older people's health and social care services. Contribution: Whilst the theory is specific to our synthesis context of workforce development, we believe the context-mechanism and outcome explanations are sufficiently abstract to be transferable across workforce development in the public services in general.


The proportion of alleles identical by descent (IBD) determines the genetic covariance between relatives, and thus is crucial in estimating genetic variances of quantitative trait loci (QTL). However, IBD proportions at QTL are unobservable and must be inferred from marker information. The conventional method of QTL variance analysis maximizes the likelihood function by replacing the missing IBDs by their conditional expectations (the expectation method), while in fact the full likelihood function should take into account the conditional distribution of IBDs (the distribution method). The distribution method for families of more than two sibs has not been obvious because there are n(n - 1)/2 IBD variables in a family of size n, forming an n x n symmetrical matrix. In this paper, I use four binary variables, where each indicates the event that an allele from one of the four grandparents has passed to the individual. The IBD proportion between any two sibs is then expressed as a function of the indicators. Subsequently, the joint distribution of the IBD matrix is derived from the distribution of the indicator variables. Given the joint distribution of the unknown IBDs, a method to compute the full likelihood function is developed for families of arbitrary sizes.


Blast-induced neurotrauma (BINT) is a major societal concern due to the complex expression of neuropathological disorders after exposure to blast. Disruptions in neuronal function, proximal in time to the blast exposure, may eventually contribute to the late emergence of the clinical deficits. Besides complications with differential clinical diagnosis, the biomolecular mechanism underlying BINT that gives rise to cognitive deficits is poorly understood. Some pre-clinical studies have demonstrated cognitive deficits at an acute stage following blast overpressure (BOP) exposure. However, the behavioral deficit type (e.g., working memory) and the mechanism underlying injury prognosis that onsets the cognitive deficits remains to be further investigated. An established rodent model of blast neurotrauma was used in order to study impaired behavioral and neuropathological outcomes following blast. Anesthetized rats were exposed to a calibrated BOP using a blast simulator while control animals were not exposed to BOP. Behavioral changes in working memory and anxiety were assessed with standard behavioral techniques (novel objected recognition paradigm and light and dark box test) at acute and chronic stages (range: 3 hours – 3 months). In addition, brains were assayed for neurochemical changes using proton magnetic resonance spectroscopy (MRS) and neuropathology with immunohistochemistry in cognitive regions of brain (hippocampus, amygdala, frontal cortex and nucleus accumbens) Early metabolic changes and oxidative stress were observed along with a compromise in energy metabolism associated with sub-acute (7 days following BOP exposure) active neurodegeneration and glial scarring. Data suggested GABA shunting pathway was activated and phospholipase A2 regulated arachadonic acid pathway may be involved in cellular death cascades. In addition, increased myo-inositol levels in medial pre-frontal cortex (PFC) further supported the glial scarring and were associated with impaired working memory at a sub-acute stage (7 days) following BOP exposure. Chronic working memory issues and anxiety associated behavior could be related to chronic activation of microglia in hippocampus and astrocytes in amygdala respectively. Furthermore, these results from MRS could be directly translated into clinical studies to provide a valuable insight into diagnosis of BINT, and it is speculated that gliosis associated markers (myo-inositol) may be a potential biomarker for blast-induced memory impairment.


1. The rocky habitat communities of Lake Malawi contain a high diversity of ecologically similar, predominantly herbivorous, cichlid fish species. How so many species can coexist is still unknown.

2. Adult males of the majority of these species hold permanent territories which form dense multispecies mosaics across the shores.

3. The study examined six coexisting species of cichlids from the rocky habitat where males are known to control access to the algal food resources within their territorial space. These included four sibling species of the Pseudotropheus (Tropheops) species complex, which are specialized epilithic algal herbivores, and two sibling species of the trophically more generalist P. (Maylandia) species complex which feed upon both epilithic algae and plankton.

4. The hypotheses that both intraspecific and interspecific territoriality occur in these communities and that interspecific aggression initiated by territorial males is preferentially directed at species with the most similar diets to their own were tested.

5. It was found that males preferred to exclude conspecific intruders, while they tolerated intruders with different diets to their own. Also, male P. (Tropheops) preferentially excluded similar heterospecific dietary specialists, while male P. (Maylandia) tolerated similar heterospecific dietary generalists.

6. Based on this study, it is proposed that interspecific territoriality may be reducing competition between species with different diets and promoting their coexistence, while it may be enhancing competition between species with the same diet. Furthermore, it suggests that ecological generalism may be reducing the intensity of interspecific competition, while specializations for the same resources may be increasing competition.


Recent reforms have given regulators broad powers to "bail-in" bank creditors during financial crises. We analyze efficient bail-ins and their implementation. To preserve liquidity, regulators must avoid signaling negative private information to creditors. Therefore, optimal bail-ins in bad times only depend on public information. As a result, the optimal policy cannot be implemented if regulators have wide discretion, due to an informational time-inconsistency problem. Rules mandating tough bail-ins after bad public signals, or contingent convertible (co-co) bonds, improve welfare. We further show that bail-in and bailout policies are complementary: if bailouts are possible, then discretionary bail-ins are more effective.


This study examines the linguistic and historical aspects of possession in the correspondence of John Paston II, a fifteenth-century Norfolk gentleman. The aim is to complement previous studies that analyze possessive constructions at a more general level by focusing on specific and everyday usage. A major problem with the analysis of possessive constructions is the wide range of semantic relations they encode. This problem is considered through the notion of identity to show how the possessive relation can be conceptually described in terms of material, social and body space. Linguistically, the possessive relation can be divided into an assertive, informative type in which ownership is central and an inherently relational type in which kinship and body relations are central.


The principle of Minimum Differentiation arises as the equilibrium outcome in spatial models when price is fixed (Hotelling 1929). Conversely, when firms set prices independently, models suggests that firms will differentiate in order to reduce the intensity of price competition (d'Aspremont et al. 1979). Yet in many competitive industries where firms compete on price, firms are observed to collocate. This puzzle has been referred to as the Hotelling paradox. We propose an explanation for this puzzle based on two simple observations. The first is that markets are imperfectly informed of the alternatives that are available within a category. That is, despite the marketing investments of competing firms, there is a significant fraction of the market that is uninformed about a firm's offer. The second observation is that the awareness of local products tends to be marginally higher than the awareness of non-local products. The magnitude of this effect is a function of the category but this effect permeates all markets where consumer heterogeneity is location (or geographically) based. With these two simple observations, we propose a model that recovers both minimal and maximal differentiation as a function of the degree to which consumers are aware of products. Specifically, maximum differentiation will occur when consumers are well informed about the products in the market, but minimum differentiation will occur when consumers have low awareness of the products. Moreover, the model explains why competing products possess similar characteristics in the introductory stage of the Product Life Cycle but firms naturally move to differentiated offerings as a category matures. In an extension, we make the level of informedness a choice variable for the firms. The extension confirms the intuition of the base model but also demonstrates how media intensity can be used to create endogenous differentiation between firms. The need to differentiate through location is attenuated when firms differentiate through the choice of media intensity, and firms may not choose maximum informedness even if advertising is free.


Half-Heusler thermoelectric materials have attracted extensive research interest over the last two decades owing to their thermal stability, mechanical strength, and moderate efficiency. This article presents an ab initio theoretical evaluation of the electrical and thermal transport properties of three bismuth-based most promising thermoelectric alloys, selected out of 54 stable half-Heusler compounds. These are brand new compounds which are recently proposed to be stable (Nature Chem.7, 308 (2015)) and may have interesting properties. The calculated band structures of the three compounds, namely HfRhBi, ZrIrBi and ZrRhBi, served as a hint for their promising thermoelectric properties. HfRhBi and ZrIrBi turn out to be narrow band gap semiconductors while ZrRhBi is a moderate band gap semiconductor. A detailed study of the carrier concentration and temperature dependence of the Seebeck coefficient, power factor, lattice and electronic thermal conductivity and hence the figure of merit (ZT) is carried out. In contrast to most promising known thermoelectric materials, we found a high power factor for these materials (highest ∼17.36 mW m−1 K−2 for p-type ZrIrBi). All three systems (especially p-type) show high ZT values, as high as 0.45 for the ideal crystals. The maximum ZT and the corresponding optimal n- and p-type doping concentrations are calculated, which shall certainly provide guidance for future experimental work.


Understanding the root cause of a defect is critical to isolating and repairing buggy behavior. We present Causal Testing, a new method of root-cause analysis that relies on the theory of counterfactual causality to identify a set of executions that likely hold key causal information necessary to understand and repair buggy behavior. Using the Defects4J benchmark, we find that Causal Testing could be applied to 71% of real-world defects, and for 77% of those, it can help developers identify the root cause of the defect. A controlled experiment with 37 developers shows that Causal Testing improves participants' ability to identify the cause of the defect from 80% of the time with standard testing tools to 86% of the time with Causal Testing. The participants report that Causal Testing provides useful information they cannot get using tools such as JUnit. Holmes, our prototype, open-source Eclipse plugin implementation of Causal Testing, is available at http://holmes.cs.umass.edu/.


Objectives: The aim of the treatment of tibial plateau fractures is to obtain a pain-free and fully functional knee with closed reduction, percutaneous cannulated screw fixation and hexapodal external fixator reconstruction for high energy compound upper tibial fractures. Methods: Patients with comminuted tibial plateau fractures underwent closed reduction, percutaneous fixation with cannulated screws, and reconstruction with hexapodal external fixator. The follow-up period was 24 months. Results: The clinical and radiological results were good or excellent. The average knee flexion was 125°. Conclusion: Our results are successful in the initial stage, however, it should be pointed out that during the long term follow-up osteoarthritis may develop leading to worsening of the condition. Level of Evidence IV, Case Series.


Although ecotourism is fast growing industry information on travels to different ecotourism destinations are often not easily accessible. This paper reports reviews of literature on eco-tourists behaviour regarding choice of destination for ecotourism and factors influencing the choice. The importance of information in marketing of ecotourism and eco-tourists' satisfaction are discussed. The eco-tourists who are visiting a destination for the first time go through all stages in the decision-making process and extensive information search before choosing the destination to visit. Eco-tourists who have visited the destination in the past go through only some of the stages and limited information search. Eco-tourists' choice of an ecotourism destination are influenced by factors such as, the family, friends, societal values, preferences, safety and promotions related to the destination. Decision regarding re-visiting an ecotourism destination depends on the level of satisfaction that the eco-tourist experienced during his or her first time visit to the destination. Eco-tourists who are satisfied with the ecotourism destination during their first time visit are likely to re-visit the destination but those who are not satisfied are not likely to re-visit. For ecotourism managers to sustain the inflow of eco-tourists to different ecotourism destinations and revenue in the ecotourism industry it is important for the managers to strive towards meeting expectations of eco-tourists and make information regarding the destinations more accessible.


Background: The inhibition of both hydrolysis products of acetylcholine (ACh), Acetylcholinesterase (AChE) and Butyrylcholinesterase (BChE), is essential for successful treatment of Alzhemier patients. Objectives: This study was investigated inhibition potentials of recently synthesized disubstituted tacrines derivatives on going our research against AChE, BChE and carbonic anhydrase cyctosolic (hCA I and II) enzymes to explore the Structure activity relationship (SAR). Methods: Inhibitory activities of tested compounds against AChE and BChE were measured by spectrophotometric method, developed by Ellman et al. Furthermore, the disubstituted tacrines were determined as inhibitors of two physiologically relevant CA isoforms, the cytosolic hCA I and II by an esterase assay method. Results: The silyl, thiomethyl and cyano substituted seven membered hydrocycle tacrines (9, 11 and 14) significantly inhibited AChE, compared with starting compound 3 (6,8-dibromo-2,3,4,5-teytrahydro-1H-cyclohepta[1,2-b] quinoline) and reference compounds, galantamine and tacrine, while methoxy substituted seven membered hydrocycle tacrine derivative 10 showed selective inhibition against BChE (IC50= 563 nM). Interestingly, disubstituted tacrines displayed higher or parallel inhibition to galantamine. Additionally, all these tacrine analogues were recorded to be powerful inhibitor compounds of the cytosolic isoenzyme hCA I with Ki in the range of 43.81–471.67 nM, as well as a moderate selectivity toward hCA II isoenzyme with Ki in the range from 87.14 to 614.68 nM compared with AZA, as standard. Conclusion: The disubstituted seven membered hydrocycle tacrine analogues 9-12 and 14 may have promising anti Alzhemier drug candidate and dibromo six membered hydrocycle 2 and dibromo seven membered hydrocycle 3 derivatives may be novel hCA I and II enzyme inhibitors.