The t(10;11)(p13;q14) is a recurring translocation resulting in the fusion of the CALM and AF10 genes. The leukemogenic CALM/AF10 fusion genes codes for a 1595 amino acids protein. This translocation was first identified in a patient with hystiocytic lymphoma and was subsequently found in patients with AML, T-ALL and malignant lymphoma. This translocation is found in younger patients and is associated with a poor prognosis.
The CALM/AF10-associated leukemias can exhibit myeloid, lymphoid or mixed lymphoid-meyloid features, indicating a stem cell or an early commited progenitor as the target cell of leukemic transformation. At the present time the target cells in CALM/AF10-associated leukemogenesis are unknown. It is also not known which target genes are up or downregulated by the presence of the CALM/AF10 fusion protein.
To answer these questions, the following experiments were performed:
1) Five transgenic mouse lines, two expressing CALM/AF10 under the control of the immunoglobulin heavy chain enhancer promoter and three under the control of the murine proximal Lck promoter were generated. Although the CALM/AF10 expression was confirmed to be present and specific to the cells targeted by the promoters used (B- and T-cell progenitors for IgH and Lck promoters, respectively), the transgenic animals did not show a phenotype that could be detected after meticulous clinical, haematological, immunological, flow cytometrical and immunohistopatological analysis .
2) We performed molecular characterization of several CALM/AF10 patient samples: A group of 13 patients with different types of leukemia: case 1 (AML M2), case 2 (Acute Biphetnotypic leukemia), case 3 (Pre T-ALL), case 4 (Acute Undifferentiated Leukemia), case 5 (PreT-ALL), cases 6 and 7 (ProT-ALL), case 8 (T-ALL), case 9 (AML), case 14 (T-ALL), case 15, 16 and 17 (AML) with a t(10;11) translocation detected by cytogenetic analysis suggesting a CALM/AF10-rearrangement. The samples were analyzed for the presence of the CALM/AF10 and AF10/CALM fusion transcripts by RT-PCR and sequence analysis. All these patients were found to be positive for the CALM/AF10 fusion. In addition, we analyzed a series of twenty-nine patients with T-ALL with T-cell receptor ≥¥ rearrangement. Among these patients, four (case 10 to 13) were positive for the CALM/AF10 fusion transcript, indicating a high incidence of CALM/AF10 fusions in this group of leukemia.
Three different breakpoints in CALM at nucleotide 1926, 2091 and a new exon, with 106 bases inserted after nt 2064 of CALM in patient 4 were found. In AF10 four breakpoints were identified: at nucleotide position 424, 589, 883 and 979. In patient 16 we found an extra exon before nt 424 of AF10. In seven patients it was also possible to amplify the reciprocal AF10/CALM fusion transcript (case 1, 3, 4, 8, 9, 10 and 14). There was no correlation between disease phenotype and breakpoint location. Ten CALM/AF10 positive patients were analyzed using oligonucleotide microarrays representing 33,000 different genes (U133 set, Affymetrix). Analysis of microarray gene expression signatures of these patients revealed high expression levels of the polycomb group gene BMI1, the homeobox gene MEIS1 and the HOXA cluster genes HOXA1, HOXA4, HOXA5, HOXA7, HOXA9, and HOXA10. The overexpression of HOX genes seen in these CALM/AF10 positive leukemias is reminiscent to the pattern seen in leukemias with rearrangements of the MLL gene, normal karyotypes and complex aberrant karyotypes suggesting a common effector pathway (i.e. HOX gene deregulation) for these diverse leukemias. In addition, the general pattern of gene expression of CALM/AF10 patients when compared to other leukemia subtypes and to normal bone marrow was dominated by a global downregulation of genes some of them with function identified as related to important molecular mechanisms, such as membrane trafficking, cell growth regulation, proliferation, differentiation and tumor suppression.
3) We cloned CALM/AF10 fusion gene into a vector that allowed us to induce the expression of CALM/AF10 using doxycycline in transiently and stably-transfected NIH3T3 and HEK293 cells. This system will be an important tool to identify direct CALM/AF10 target genes and to answer the question whether continued CALM/AF10 expression is necessary to maintain the CALM/AF10-associated expression pattern.


Many keyhole interventions rely on bi-manual handling of surgical instruments, forcing the main surgeon to rely on a second surgeon to act as a camera assistant. In addition to the burden of excessively involving surgical staff, this may lead to reduced image stability, increased task completion time and sometimes errors due to the monotony of the task. Robotic endoscope holders, controlled by a set of basic instructions, have been proposed as an alternative, but their unnatural handling may increase the cognitive load of the (solo) surgeon, which hinders their clinical acceptance. More seamless integration in the surgical workflow would be achieved if robotic endoscope holders collaborated with the operating surgeon via semantically rich instructions that closely resemble instructions that would otherwise be issued to a human camera assistant, such as "focus on my right-hand instrument." As a proof of concept, this paper presents a novel system that paves the way towards a synergistic interaction between surgeons and robotic endoscope holders. The proposed platform allows the surgeon to perform a bimanual coordination and navigation task, while a robotic arm autonomously performs the endoscope positioning tasks. Within our system, we propose a novel tooltip localization method based on surgical tool segmentation and a novel visual servoing approach that ensures smooth and appropriate motion of the endoscope camera. We validate our vision pipeline and run a user study of this system. The clinical relevance of the study is ensured through the use of a laparoscopic exercise validated by the European Academy of Gynaecological Surgery which involves bi-manual coordination and navigation. Successful application of our proposed system provides a promising starting point towards broader clinical adoption of robotic endoscope holders.


Interactive GIS maps created by overlapping facility data including roads and infrastructure with population and service delivery data permitted strategic deployment of mobile voluntary medical male circumcision (VMMC) services to underserved rural communities. The percentage of VMMCs performed in rural areas jumped from 48% in 2011 to 93% in 2014. Interactive GIS maps created by overlapping facility data including roads and infrastructure with population and service delivery data permitted strategic deployment of mobile voluntary medical male circumcision (VMMC) services to underserved rural communities. The percentage of VMMCs performed in rural areas jumped from 48% in 2011 to 93% in 2014. Background: Based on the established protective effect of voluntary medical male circumcision (VMMC) in reducing female-to-male HIV transmission, Tanzania's Ministry of Health and Social Welfare (MOHSW) embarked on the scale-up of VMMC services in 2009. The Maternal and Child Health Integrated Project (MCHIP) supported the MOHSW to roll out VMMC services in Iringa and Njombe, 2 regions of Tanzania with among the highest HIV and lowest circumcision prevalence. With ambitious targets of reaching 264,990 males aged 10–34 years with VMMC in 5 years, efficient and innovative program approaches were necessary. Program Description: Outreach campaigns, in which mobile teams set up temporary services in facilities or non-facility settings, are used to reach lesser-served areas with VMMC. In 2012, MCHIP began using geographic information systems (GIS) to strategically plan the location of outreach campaigns. MCHIP gathered geocoded data on variables such as roads, road conditions, catchment population, staffing, and infrastructure for every health facility in Iringa and Njombe. These data were uploaded to a central database and overlaid with various demographic and service delivery data in order to identify the VMMC needs of the 2 regions. Findings: MCHIP used the interactive digital maps as decision-making tools to extend mobile VMMC outreach to "the last kilometer." As of September 2014, the MOHSW with MCHIP support provided VMMC to 267,917 men, 259,144 of whom were men were aged 10–34 years, an achievement of 98% of the target of eligible males in Iringa and Njombe. The project reached substantially more men through rural dispensaries and non-health care facilities each successive year after GIS was introduced in 2012, jumping from 48% of VMMCs performed in rural areas in fiscal year 2011 to 88% in fiscal year 2012 and to 93% by the end of the project in 2014. Conclusion: GIS was an effective tool for making strategic decisions about where to prioritize VMMC service delivery, particularly for mobile and outreach services. Donors may want to consider funding mapping initiatives that support numerous interventions across implementing partners to spread initial start-up costs.


"Handbook of Pentecostal Christianity" is an easy-to-read guide designed for those interested in learning about one of the fastest-growing religious traditions in the world. Adam Stewart's unique collection presents concise, yet comprehensive explanations of some of the most important terms and concepts needed to understand the origins and development, as well as the beliefs and practices, of Pentecostalism worldwide. Twenty-four scholars from five continents provide entries, which are written from disciplinary perspectives as diverse as anthropology, biblical studies, black church studies, history, religious studies, sociology, and theology. The fifty entries shed light on such topics as the Azusa Street Mission and Revival, Baptism of the Holy Spirit, exorcism, Godly Love, prophecy, snake handling, and the Word of Faith movement. Each entry also includes a brief list of references and suggestions for further reading. These brief, engaging explanations of aspects of Pentecostalism can be read on their own or alphabetically from start to finish. In its entirety, Stewart's text provides the reader with an introduction to the history, theology, practices, and contemporary forms of Pentecostalism as it stands at the outset of the twenty-first century. Stewart's handbook is an appealing introduction to Pentecostalism suitable for both students of religion and the curious general reader.


Over the past 25 years, industrial and organizational (I-O) psychologists have made great strides forward in the area of teams research. They have developed and tested meso-level theories that explain and predict the behavior of individuals in teams and teams operating within and across organizations. The continued contributions of I-O psychologists to theory and research on teams require us to address the challenges—several of which were well described in the focal article (Guzzo, Fink, King, Tonidandel, & Landis, 2015)—and embrace the opportunities that are being ushered in by big and broad data streams (Hendler, 2013). We suggest that a principal unique value add of the I-O psychologist to the basic scientific endeavor of understanding small teams comes in the form of theory—theories that explain why, when, how, and to what end individuals form relationships needed for teams to function in unison toward the accomplishment of collective goals. Some have argued that the big data revolution means "the end of theory," suggesting petabyte data render theoretical models obsolete (Anderson, 2008). On the contrary, we submit that big-data enabled social science holds the promise of rapid progress in social science theory, particularly in the area of teams.


Abstract Entropy is a contemporary buzzword in landscape architecture used to describe a vast range of material, environmental and social processes. Most uses of the word are loose appropriations of a very specific thermodynamic principle. This paper first explores some of the more common applications of entropy to describe post-industrial case study projects explored by Robert Smithson, Matthew Gandy, Gilles Clément and John Beardsley. It then suggests that entropy is a lens for understanding particular challenges associated with designing in landscapes that bear the traces of past industrial occupation. It concludes by offering a design technique using physical models of salt crystallisation, sand dispersal, sedimentation and water flow, for engaging with these themes as part of the design process. The paper suggests that viewing post-industrial sites through the lens of entropy raises productive design questions and that the indeterminacies of entropic processes are analogous to productive indeterminacies in the design process.


Can computer-based models, using publicly available information, be used as off-site early warning systems (EWS) to identify banks that will become inadequately capitalized in the near future? The EWS models analyzed in this article are able to detect the early onset of financial distress one year in advance with a reasonable degree of accuracy. Although simple EWS models do as well as or better than more sophisticated ones, more sophisticated models could provide detailed information about individual bank strengths and weaknesses.


In this article, Professor Wasserman introduces, defines, and explores a new form of expression, labeled symbolic counter-speech. Symbolic counter-speech is an outgrowth of two free expression concepts: the right and opportunity to communicate through symbols and the Brandeisian imperative of counter-speech as the acceptable answer to objectionable speech. Symbolic counter-speech responds to a symbol on its own terms, countering the message presented by a particular symbol while using that symbol as the vehicle or medium for the contrary message. Symbolic counter-speech includes a range of expressive actions, from silent non-participation with a symbol or symbolic ceremony to confrontation of the symbol with a different, contrary symbol to attacks on the original symbol by destroying it or altering it to create a new message. Professor Wasserman considers symbolic counter-speech in the post-September 11 environment, when the United States has fallen back into to what Vincent Blasi labeled a pathological period, a period in which commitment to free speech wanes and in which government is especially likely to engage in systemic suppression. Although there have not been widespread governmental restrictions on expression, the primary feature of previous pathologies, there has been a dramatic increase in government and private patriotic symbolism and expression and of intolerance for objections to that patriotism. This has been particularly true with regard to the American flag and its complementary symbols, such as the Pledge of Allegiance, the national anthem and God Bless America. The focus of this paper is the increase in patriotic symbolism, along with incidents of counter-speech to that symbolism, at professional and collegiate sporting events, the primary forum in American society in which crowds of adults regularly engage in patriotic expression. Finally, the concept of symbolic counter-speech and these examples of flag-related symbolic counter-speech illustrate the inconsistency between principles and traditions of freedom of speech and the movement for flag preservation, which logically would eliminate all symbolic counter-speech directed against the flag and its complements.


Hematopoietic stem cell homing and engraftment are crucial to transplantation efficiency, and clinical engraftment is severely compromised when donor-cell numbers are limiting. The peptidase CD26 (DPPIV/dipeptidylpeptidase IV) removes dipeptides from the amino terminus of proteins. We present evidence that endogenous CD26 expression on donor cells negatively regulates homing and engraftment. By inhibition or deletion of CD26, it was possible to increase greatly the efficiency of transplantation. These results suggest that hematopoietic stem cell engraftment is not absolute, as previously suggested, and indicate that improvement of bone marrow transplant efficiency may be possible in the clinic.


Abstract : The Battle of Britain is thought to be the greatest air battle in history. This battle began on 10 July 1940 and ended on 31 October 1940. It followed the German Blitzkrieg of the Low Countries and France and the ignoble British retreat through Dunkirk. During the previous months the German Luftwaffe had triumphed over the air forces of Poland, Norway, Holland, Belgium and France and had destroyed all but 66 of the 260 British Hurricanes sent to support the British Army in France. The German victories gave rise to beliefs of invincibility which were replaced by feelings of frustration and failure as the Battle of Britain progressed. Arguably the lack of a coherent plan for the German invasion of Britain, Operation Sealion, and the heroics of the British pilots and ground crews influenced the outcome of the Battle of Britain. However, it is the contention of this study that the Command and Control systems of the British coupled with the technology that made those systems possible were responsible for the British victory. The individual systems, radar, radio, Identification Friend or Foe (IFF), direction finding and intelligence, and how they were integrated into the command and control structures are discussed.


Definitions of 'knowledge' and its relationships with 'data' and 'information' are varied, inconsistent and often contradictory. In particular the traditional hierarchy of data-information-knowledge and its various revisions do not stand up to close scrutiny. We suggest that the problem lies in a flawed analysis that sees data, information and knowledge as separable concepts that are transformed into one another through processing. We propose instead that we can describe collectively all of the materials of computation as 'noetica', and that the terms data, information and knowledge can be reconceptualised as late-binding, purpose-determined aspects of the same body of material. Changes in complexity of noetica occur due to value-adding through the imposition of three different principles: increase in aggregation (granularity), increase in set relatedness (shape), and increase in contextualisation through the formation of networks (scope). We present a new model in which granularity, shape and scope are seen as the three vertices of a triangular prism, and show that all value-adding through computation can be seen as movement within the prism space. We show how the conceptual framework of the noetic prism provides a new and comprehensive analysis of the foundations of computing and information systems, and how it can provide a fresh analysis of many of the common problems in the management of intellectual resources.


Establishment of marine protected areas, including fully protected marine reserves, is one of the few management tools available for local communities to combat the deleterious effect of large scale environmental impacts, including global climate change, on ocean ecosystems. Despite the common hope that reserves play this role, empirical evidence of the effectiveness of local protection against global problems is lacking. Here we show that marine reserves increase the resilience of marine populations to a mass mortality event possibly caused by climate-driven hypoxia. Despite high and widespread adult mortality of benthic invertebrates in Baja California, Mexico, that affected populations both within and outside marine reserves, juvenile replenishment of the species that supports local economies, the pink abalone Haliotis corrugata, remained stable within reserves because of large body size and high egg production of the protected adults. Thus, local protection provided resilience through greater resistance and faster recovery of protected populations. Moreover, this benefit extended to adjacent unprotected areas through larval spillover across the edges of the reserves. While climate change mitigation is being debated, coastal communities have few tools to slow down negative impacts of global environmental shifts. These results show that marine protected areas can provide such protection.


An electromagnetic (EM) inverse scattering problem that involves the reconstruction of microwave images for three-dimensional (3-D) objects is considered in this paper. This ill-posed and nonlinear problem is treated as a global optimization problem, and is solved :by the application of micro-genetic algorithm (m-GA). The reconstructed results obtained by m-GA have shown that it is an effective technique for microwave image reconstruction.


Abstract Background: Using the Resource Based View (RBV) and the Integrated Sustainability Framework (ISF) as theoretical foundation, this study proposes and empirically examines hypotheses on how different types of IS-enabled sustainability initiatives are used to enable environmental and social sustainability in the four quadrants of the ISF. Method: The study uses a mixed-method approach, combining multiple-case study and non-parametric statistical analysis (Friedman test). IS-enabled sustainability initiatives were collected from Global Reporting Initiative (GRI) reports of six leading global sustainability companies across three industries with different levels of IS/IT use intensity during 2009-2015 period. Results: The study finds empirical quantitative and qualitative support for the proposed hypotheses. In different quadrants of the ISF, companies were found to use different types of IS-enabled sustainability initiatives in different patterns to enable sustainability strategy. Conclusions: The study opens the IS box to provide further theoretical and empirical insights on how companies combine IS and business resources to develop different types of IS-enabled sustainability initiatives to help them address sustainability (both environmental and social) across the ISF. The study is among early IS research that adopts GRI reports as data source and presents a method for extracting GRI data for IS and sustainability research. Researchers and practitioners can both find the study's findings instructive.


Mice received an injection of sheep erythrocytes (SRBC) into the footpad "prepared" or "not prepared" with a 7‐day‐prior injection of a protein‐bound polysaccharide from Coriolus versicolor (PSK; KrestinR), and the ultrastructure of in situ macrophages was studied at various intervals after the injection. A single SRBC injection into the footpad induced linear cell arrangements of several macrophages. The macrophages showed no prominent morphological alterations after SRBC digestion. When PSK‐stimulated subcutaneous macrophages were challenged by SRBC, they rapidly sent out numerous long cytoplasmic projections which radiated in all directions. Such projections of neighboring macrophages tended to contact one another. At the following stage, a pronounced sequential alteration was noted, characterized by the interlocking of elongated projections. This provided massive aggregations of "activated" macrophages. These observations suggest the possibility that intercellular communication among "activated" macrophages was elicited, particularly in the subcutaneous region, and maintained through an intensive interaction of cytoplasmic projections. Further, the present results histologically support our previous report which shows that the "PSK‐prepared" footpad site but not the "prepared" one supports development of a splenic humoral immune response following injection of superimposed SRBC.


Income taxation may not only affect investment behavior by distorting payoffs, it may also have a more subtle, psychological effect, by biasing investors' perceptions of the financial consequences. In a laboratory experiment that allows us to vary the taxation method, while keeping the financial outcomes constant, we find clear evidence that aggregated income taxation (comparable to profit taxation) with complete loss deduction induces a sustained bias towards more risk-taking, while disaggregated income taxation (comparable to a transaction taxation with loss offset) does not. We suggest that this bias may be exploited to increase the volume of private investments by choosing aggregated income taxation, if investors are (too) risk-averse, and to decrease the volume and the risk by choosing disaggregated income taxation, if investors are (too) risk-seeking


In carbon dioxide utilization by cyclometalated five-membered ring products, the following compounds are used in four types of applications: 1. 2-Phenylpyrazole iridium compounds, pincer phosphine iridium compounds and 2-phenylimidazoline iridium compounds are used as catalysts for both formic acid production from CO2 and H2, and hydrogen production from the formic acid. This formic acid can be a useful agent for H2 production and storage for fuel cell electric vehicles. 2. Other chemicals, e.g., dimethyl carbonate, methane, methanol and CO, are produced with dimethylaminomethylphenyltin compounds, pincer phosphine iridium compounds, pincer phosphine nickel compound and ruthenium carbene compound or 2-phenylpyridine iridium compounds, and phenylbenzothiazole iridium compounds as the catalysts for the reactions with CO2. 3. The five-membered ring intermediates of cyclometalation reactions with the conventional substrates react with carbon dioxide to afford their many types of carboxylic acid derivatives. 4. Carbon dioxide is easily immobilized at room temperature with immobilizing agents such as pincer phosphine nickel compounds, pincer phosphine palladium compounds, pincer N,N-dimethylaminomethyltin compounds and tris(2-pyridylthio)methane zinc compounds.


Abstract. We show that methylglyoxal forms light-absorbing secondary organic material in aqueous ammonium sulfate and ammonium nitrate solutions mimicking tropospheric aerosol particles. The kinetics were characterized using UV-Vis spectrophotometry. The results suggest that the bimolecular reaction of methylglyoxal with an ammonium or hydronium ion is the rate-limiting step for the formation of light-absorbing species, with kNH4+II=5×10−6 M−1 min−1 and kH3O+II≤10−3 M−1 min−1. Evidence of aldol condensation products and oligomeric species up to 759 amu was found using chemical ionization mass spectrometry with a volatilization flow tube inlet (Aerosol-CIMS). Tentative identifications of carbon-nitrogen species and a sulfur-containing compound were also made using Aerosol-CIMS. Aqueous solutions of methylglyoxal, with and without inorganic salts, exhibit significant surface tension depression. These observations add to the growing body of evidence that dicarbonyl compounds may form secondary organic material in the aerosol aqueous phase, and that secondary organic aerosol formation via heterogeneous processes may affect seed aerosol properties.


Abstract. As urban land expands rapidly across the globe, much concern has been raised that urbanization may alter the terrestrial carbon cycle. Urbanization involves complex changes in land structure and multiple environmental factors. Little is known about the relative contribution of these individual factors and their interactions to the terrestrial carbon dynamics, however, which is essential for assessing the effectiveness of carbon sequestration policies focusing on urban development. This study developed a comprehensive analysis framework for quantifying relative contribution of individual factors (and their interactions) to terrestrial carbon dynamics in urbanized areas. We identified 15 factors belonging to five categories, and we applied a newly developed factorial analysis scheme to the southern United States (SUS), a rapidly urbanizing region. In all, 24 numeric experiments were designed to systematically isolate and quantify the relative contribution of individual factors. We found that the impact of land conversion was far larger than other factors. Urban managements and the overall interactive effects among major factors, however, created a carbon sink that compensated for 42% of the carbon loss in land conversion. Our findings provide valuable information for regional carbon management in the SUS: (1) it is preferable to preserve pre-urban carbon pools than to rely on the carbon sinks in urban ecosystems to compensate for the carbon loss in land conversion. (2) In forested areas, it is recommendable to improve landscape design (e.g., by arranging green spaces close to the city center) to maximize the urbanization-induced environmental change effect on carbon sequestration. Urbanization-induced environmental change will be less effective in shrubland regions. (3) Urban carbon sequestration can be significantly improved through changes in management practices, such as increased irrigation and fertilizer and targeted use of vehicles and machinery with least-associated carbon emissions.


Using computational modeling, we examine how varying the arrangement of binary mixtures of polymer grafted nanoparticles (PGNs) in a network affects the mechanical properties of the composite. The free ends of the grafted chains on the PGNs contain reactive groups that can form labile bonds with reactive ends on nearby PGNs, and thereby form extensive networks. This bond formation is reversible, with the bonds breaking and reforming at a specified rate. The two types of particles in the network differ in the strength of the labile bonds that they form with their neighbors, forming both relatively strong and weak interconnections. We examine the response of this dynamic network to tensile deformation when the binary PGNs are arranged in an alternating, layered structure or a random mixture. We determine the ultimate tensile properties (strength, toughness), the strain recovery and behavior under cyclic loading for samples with the layered and random architectures. We demonstrate that the layered structures display self-healing behavior and exhibit enhanced mechanical properties relative to the random system. Using our model, we can tune both the spatial and temporal characteristics of the hybrid material. Thus, the approach provides a useful tool for determining how to tailor these parameters to achieve superior mechanical behavior in PGN networks.


Established theories in international business come to different conclusions when specifically applied to the analysis of the international activities of start-up companies in high-technology industries. Using a new dataset of 495 British and German start-ups operating in high-technology industries, we analyse the differences between those companies that have built up international activities and those which only compete in their home country. Our findings suggest that the key discriminatory variables are: age, the extent to which the product requires customisation, regularity of R&D activities, and the international professional experience of the founders. These findings suggest that internationalisation of New Technology Based Firms is best explained by adopting elements from a number of different theoretical frameworks.


OF DISSERTATION HUMAN CARDIOVASCULAR RESPONSES TO SIMULATED PARTIAL GRAVITY AND A SHORT HYPERGRAVITY EXPOSURE Orthostatic intolerance (OI), i.e., the inability to maintain stable arterial pressure during upright posture, is a major problem for astronauts after spaceflight. Therefore, one important goal of spaceflight-related research is the development of countermeasures to prevent post flight OI. Given the rarity and expense of spaceflight, countermeasure development requires ground-based simulations of partial gravity to induce appropriate orthostatic effects on the human body, and to test the efficacy of potential countermeasures. To test the efficacy of upright lower body positive pressure (LBPP) as a model for simulating cardiovascular responses to lunar and Martian gravities on Earth, cardiovascular responses to upright LBPP were compared with those of head-up tilt (HUT), a well-accepted simulation of partial gravity, in both ambulatory and cardiovascularly deconditioned subjects. Results indicate that upright LBPP and HUT induced similar changes in cardiovascular regulation, supporting the use of upright LBPP as a potential model for simulating cardiovascular responses to standing and moving in lunar and Martian gravities. To test the efficacy of a short exposure to artificial gravity (AG) as a countermeasure to spaceflight-induced OI, orthostatic tolerance limits (OTL) and cardiovascular responses to orthostatic stress were tested in cardiovascularly deconditioned subjects, using combined 70o head-up tilt and progressively increased lower body negative pressure, once following 90 minutes AG exposure and once following 90 minutes of -6o headdown bed rest (HDBR). Results indicate that a short AG exposure increased OTL of cardiovascularly deconditioned subjects, with increased baroreflex and sympathetic responsiveness, compared to those measured after HDBR exposure. To gain more insight into mechanisms of causal connectivity in cardiovascular and cardiorespiratory oscillations during orthostatic challenge in both ambulatory and cardiovascularly deconditioned subjects, couplings among R-R intervals (RRI), systolic blood pressure (SBP) and respiratory oscillations in response to graded HUT and dehydration were studied using a phase synchronization approach. Results indicate that increasing orthostatic stress disassociated interactions among RRI, SBP and respiration, and that dehydration exacerbated the disconnection. The loss of causality from SBP to RRI following dehydration suggests that dehydration also reduced involvement of baroreflex regulation, which may contribute to the increased occurrence of OI.


This paper amounts to a discussion about justice: it is about whether just outcomes for the individual vis-a-vis 'lines of jurisprudence' and case law should matter within the democratic framework of Canada's governing institutions. In the case of Alberta Union of Public Employees v. Lethbridge Community College, [2004] 1 S.C.R. 727, 2004 SCC 28 the Supreme Court of Canada overturned the highest Court in Alberta in the latter's ruling that an employee deprived of both her employment and right to tenure without cause must receive the justice of reinstatement. Even at the close of the original appeal before a split arbitration board, one arbitrator of three, like the Alberta Court of Appeal later ruled, decided that reinstatement was the only option the employer had under the law. In this paper I will argue that the Supreme Court erred in its decision in this instance because it chose to support its own dictum of preserving "industrial peace" over and against what the Alberta Court of Appeal, labour arbitrator Bartee, and I see as the most important issue: the upholding of an employee's rights as spelled out in the collective agreement. This was not a case where industrial peace should have been the underlying concern primarily because a Canadian employee was robbed by her employer of contractual and statutory rights under the collective agreement and the law respectively. The Court, more concerned with what this decision might mean in future for "industrial peace," felt they could justify their decision by employing the tactic of a long discussion on the jurisprudence relating to the broad remedial powers given to arbitration boards to settle disputes arising from their own dicta but yet in conflict with the collective agreement and statute law. Notwithstanding how one wishes to order the nexus of factors which need to be considered in a case such as this, for instance the rights of the employee/employer, power of the board, right to an appeal, etc., I argue the court erred by not choosing the breach of a Canadian citizen's legal and contractual rights as the single most important factor in this case. Cases involving dismissal really turn on whether the employee was fired for cause or without cause, and if the latter, then, as the Alberta Court of Appeal saw clearly, reinstatement is the only option. The Supreme Court, though, had something else at the front of their minds and front and centre in their decision: their own mantra of "industrial peace" pre-empted by a long, philosophically dislocated, discussion about the broad remedial powers of arbitration boards. I will argue that this decision needs overturning because it extinguishes a fundamental principle of justice in Canada: citizens cannot be deprived of their tenure of employment without just cause under a collective agreement.


Patients with type 2 diabetes (T2D) could improve its glucose control with a multidisciplinary cultural management. Coaching en Diabetes (CoeD) is a multicomponent program for steel workers and their direct families with T2D when their A1C is >9% as an effort to increase attachment to medical treatment. The program focusses on the empowerment and glucose treatment sensibilization through a group medical visit, improvement of self-management and medical treatment. CoeD is performed by a multidisciplinary team (internist, nutritionist, diabetes educator, social worker, etc.). The aim of this study is to evaluate the effect of this program in glycemic control through 2 years of follow-up. This is a retrospective and longitudinal study of patients with uncontrolled T2D at Clinica Nova from Monterrey, Mexico. This study was conducted from May 2017 to 2019. We used descriptive statistics and ANOVA of repeated measures when it was appropriate. We included a total of 153 [115 (75.2%) males], with a mean (SD) age of 62.9 (11.2) years. The duration of T2D was 9.7 (6.6) years. During the follow-up 26 patients (17%) left the program, 2 of them died in relation to cardiovascular disease. All patients maintained a controlled blood pressure. We found a reduction of A1C of 1.5% [Mean (SD) 9.8% (1.5) to 8.3% (1.6), p=0.032) and fasting glucose of 41.8 mg/dl [Mean (SD) 180mg/dl (67) to 138.2mg/dl (55), p=0.021). These reductions were maintained through the 24 months of follow-up. The CoeD program was successful in reducing and sustaining A1C and pre-prandial glucose reduction in this group of patients. Disclosure M. Romero-Ibarguengoitia: None. O.M. Cantu Santos: None. D. Gutierrez Gonzalez: None. R. Gonzalez Facio: None. A. Gonzalez-Cantu: None.


Background To assess the prevalence and characteristics associated with macular atrophy (MA) in eyes with neovascular age-related macular degeneration (nAMD) treated with vascular endothelial growth factor (VEGF) inhibitors. Methods This was a retrospective, cross-sectional study of nAMD eyes that commenced anti-VEGF between January 2006 and August 2016. MA (absent/extrafoveal/subfoveal) was graded by treating practitioners based on multimodal imaging from April 2016. The prevalence of MA over time and risk factors of MA were assessed. Results The prevalence of MA in a cohort of 1689 eyes was 9.9% (22/222) in eyes within 1 year of starting treatment, 41.5% (71/171) after 5 years and 48.4% (30/62) after 9 years of treatment. Risk factors for subfoveal MA included the proportion of visits at which the lesion was graded as inactive ((adjusted OR (AOR) 3.72 for the highest vs lowest the quartile of frequency of inactive gradings (95% CI 2.33 to 6.07)), age (AOR 1.05 per year (95% CI 1.02 to 1.07)), baseline visual acuity (AOR 3.9 for ≤35 letters vs ≥70 letters (95% CI 2.4 to 6.4)) and the number of injections received (AOR 1.20 every 10 injections (95% CI 1.08 to 1.33)). Similar associations were observed with extrafoveal MA. Conclusions The risk of MA appeared to drop in eyes that had not developed it within 5 years. Low choroidal neovascularisation activity was by far the strongest predictor. We could not determine whether the increased prevalence of MA with time was due to anti-VEGF treatment or the natural history of the condition.


We investigate the survivable traffic-grooming problem for optical mesh networks employing wavelength-division multiplexing (WDM) and dedicated protection. We consider the dynamic-provisioning environment in which a connection arrives at random, holds for a random amount of time, and then departs. A typical connection request may require bandwidth less than that of a wavelength, and it may also require protection from network failures, typically fiber cuts. On the basis of generic grooming-node architecture, we propose two approaches--protection-at-lightpath (PAL) level and protection-at-connection (PAC) level--for grooming a connection request. Here we investigate dedicated protection. In a companion paper [IEEE J. Sel. Areas Commun. 21, 1367 (2003)], we investigate shared protection, which leads to a substantially different treatment. For dedicated protection, we prove that the problem of provisioning a connection under PAC is NP-complete, propose effective heuristics for both schemes, and define comprehensive performance metrics to compare PAL with PAC with respect to wavelength or grooming-port efficiency. Our findings are as follows. Under today's typical connection-bandwidth distribution in which lower-bandwidth connections outnumber higher-bandwidth connections, PAC outperforms PAL (in terms of bandwidth-blocking ratio, lightpath use, and wavelength use) if the number of grooming ports is large; however, PAL outperforms PAC (in terms of bandwidth-blocking ratio and grooming-port use) when the number of grooming ports is moderate or small.


An experimental investigation of oil retention and pressure drop characteristics for R1234yf, R134a and R410A with POE 100 is presented, for horizontal and vertical suction lines of 10.2 mm internal diameter. Conditions of operation include a saturation temperature of 13 °C and a superheat of 15 °C, with the superficial vapor velocity and the Oil in Circulation Ratio (OCR) both varied in the range of 1-6 m/s and 1-5 % respectively. The effect of lubricant viscosity on oil retention and pressure drop is also presented by comparing results with those of POE 32, under the same conditions of operation.


[Introduction] Digitisation is by no means a completely new phenomenon. By the time of the dotcom boom of the late 1990s at the latest, it was clear that the economy was facing a massive upheaval. A good decade and a half later, internet corporations are already established players in the corporate world. If the topic of digitisation is still omnipresent in 2015, making headlines in the business press under the catchphrase »Industry 4.0« day after day, there are good reasons for this. Previous experience with the digital revolution - as seen in the music industry and the media landscape, for instance - provides a foretaste of what many other industries might be about to undergo. Big data, connectivity and artificial intelligence are the buzzwords that stand for the next round of the digital revolution and underpin the concept of the digital economy. Today, it is not just the multitude of innovations that astounds but also the speed with which business and society are being turned inside out. The fast pace of change can largely be explained by the fact that markets are being created in the digital economy that operate in line with the »winner takes it all« principle. This means that speed is a key success factor for enterpreneuers and enterprises, as the prospect of global market domination is dangled. That such potential success is triggering something of a gold-rush mood comes as no great surprise. At the same time, though, both established companies and workers who fear for their jobs are becoming increasingly nervous. With this study, we hope to contribute to a better understanding of this digital upheaval and provide an insight into the prospective changes that can be expected in business and society. In section 2, we describe the underlying concepts and special features of the digital economy. We then focus on four selected topics with a view to pinpointing the economic consequences of digitisation. First, we outline the German business model (section 3) and consider whether the current structure of the German economy forms a good foundation for mastering the challenges of the digital revolution. In section 4, we use the example of 3D printing to examine the potential of digital technologies to disrupt economies. We then go on in section 5 to use the automotive sector to explore the possible consequences for one of Germany's key industries. In section 6, we highlight the consequences of digitisation for the financial sector. Finally, in section 7 we draw up implications for economic policy and examine whether the market economy is in any position to channel the peculiarities of the digital economy in such a way that the newly created prosperity benefits all social groups and not just a digital elite.


The system of electronic prescription has been recently developed and used in the developed countries especially due to improvements of and with the help of information technologies.
When considering the level of information technology, it is surprising that electronic prescription has still been being prepared in the paper environment. Electronic prescription is a fundamental component of the electronic patient record, which seems to be the final target of health area. It has so important benefits such as; determining the most suitable drug and dosage for the patient, eliminating illegible hand-writing, shortening time for accessing the drug knowledge, enable to access the knowledge of drug and prescription at any time by mobile tools, enabling doctor and pharmacist to gain time, self updating the drug knowledge including fees, seeing and comparing the drug information, seeing the indications and contraindications of drugs while prescribing and thus informing the patient, decreasing side effects and drug allergies by this way, composing macros for favorite prescriptions, enable doctors to customize their drug lists, giving the retrospective and prospective statistical and epidemiological research facilities, contribution to medicine education by giving decision support for medical students, decreasing the interim approval mechanisms, contribution to both patient and medical workers' satisfaction, easing the medico-legal inspections. Besides of its advantage, it brings some difficulties such as; data and communication security, interoperability, the need for legal arrangements, the needs for hardware, software and other sources, scalability, difficulty in adaptation of medical staff to new system. The system of electronic prescription will be an inevitable part of our life in near future. Besides of benefits, it brings some difficulties. To overcome these difficulties, cooperation of universities, public and private institutions is needed.


People with Noonan syndrome have distinctive facial features such as a deep groove in the area between the nose and mouth (philtrum), widely spaced eyes that are usually pale blue or blue-green in color, and low-set ears that are rotated backward. Affected individuals may have a high arch in the roof of the mouth (high-arched palate), poor teeth alignment, and a small lower jaw (micrognathia). Many children with Noonan syndrome have a short neck, and both children and adults may have excess neck skin (also called webbing) and a low hairline at the back of the neck.


In this article, we report on recent ad- vances in a spectral nodal method for the numerical solution of multislab atmospheric radiation prob- lems. Here, we derive a set of periodic relations for the coefficients of the bidirectional functions of our method, and we use these periodic relations to im- prove a recently developed computational scheme for solving a set of multislab atmospheric radiation problems with an arbitrary number and type of op- tically stationary layers. We present numerical re- sults for a set of prototype problems that show the effect of stratospheric ozone depletion on the amount of ultraviolet-B radiation that reaches the Earth's surface.


This paper reviews a new framework for analyzing the interrelationship between inequality, unemployment, labor market frictions, and foreign trade. This framework emphasizes firm heterogeneity and search and matching frictions in labor markets. It implies that the opening of trade may raise inequality and unemployment, but always raises welfare. Unilateral reductions in labor market frictions increase a country's welfare, can raise or reduce its unemployment rate, yet always hurt the country's trade partner. Unemployment benefits can alleviate the distortions in a country's labor market in some cases but not in others, but they can never implement the constrained Pareto optimal allocation. We characterize the set of optimal policies, which require interventions in product and labor markets.


The discovery of a growing number of exoplanets and even extrasolar systems supports the scientific consensus that it is possible to find other signs of life in the universe. The present work proposes for the first time, an explicit mechanism inspired by the dynamics of biological dispersion, widely used in ecology and epidemiology, to study the dispersion of biogenic units, interpreted as complex organic molecules, between rocky or water exoplanets (habitats) located inside star clusters. The results of the dynamic simulation suggest that for clusters with populations lower than 4 M/ly it is not possible to obtain biogenic worlds after 5 Gyr. Above this population size, biogenic dispersion seems to follow a power law, the larger the density of worlds lesser will be the impact rate (β . ) value to obtain at least one viable biogenic Carrier habitat after 5 Gyr. Finally, when we investigate scenarios by varying β, a well-defined set of density intervals can be defined in accordance to its characteristic β value, suggesting that biogenic dispersion has a behavior of "minimal infective dose" of "minimal biogenic effective" events by interval i.e. once this dose has been achieved, doesn't matter if additional biogenic impact events occur on the habitat.


Here we first time report, the investigation of stable surface (2 mm) oxidized graphite electrode prepared via the anodic oxidation of graphite in different electrolyte medium such as KOH, H2SO4 and KH2PO4. In the electrochemical surface oxidation route, high quality graphene oxide was produced on surface of the graphite rod. The formation of oxidized graphite (Graphene oxide) was proved by X-ray Diffraction (XRD) and Raman spectroscopy analysis. The synthesis product was also characterized by Scanning Electron Microscopy (SEM), etc. The surface oxidized graphite electrode was used for the simultaneous determination of 692 mV catechol and 1.31 V methylparaben. Unbuffered 0.1 M Na2SO4 was used as Supporting Electrolyte (SE), as hydro-alcoholic solution (in 1/4 ethanol/water volume ratio, i.e., 20% volume of ethanol in the final working solution from the cell). The fast and sensitive electrochemical responses for the detection of catechol and methylparaben at a potential between 0 to 1.5 V were obtained. The cyclic voltammetric measurements yielded calibration plots with very superior linearity and high sensitivity Results demonstrated that the electrochemically surface modified graphite electrode displayed a good performance along with high sensitivity and long-term stability.


Background and Purpose: Lymphotoxin α (LTA), one of the tumor necrosis factor family proteins, is an important proinflammatory cytokine and appears to play a putative role in the inflammatory process of atherosclerosis. Recent genetic studies have suggested that variations in the gene encoding LTA, which affect its expression and biological function, may contribute to the development of vascular diseases. We conducted a case-control study to clarify the association of LTA gene polymorphisms with ischemic stroke in a large Japanese population. Methods: Genotyping for LTA A252G and C804A polymorphisms was achieved by a rapid-cycle polymerase chain reaction and melting curve analysis using fluorescent probes in 1,044 incident cases of ischemic stroke recruited from the Fukuoka Stroke Registry and 1,044 age- and sex-matched control subjects recruited from the Hisayama Study. Results: The overall distribution of allele and genotype for each polymorphism was similar between stroke patients and control subjects. The allele frequencies of 252G and 804A were slightly lower in stroke patients than in control subjects; however, conditional logistic regression analysis adjusted for potential risk factors found no association between the risk of ischemic stroke and either polymorphism. In terms of stroke subtype, we also found no association of these polymorphisms with any subtypes of ischemic stroke. Conclusions: Neither the A252G nor C804A polymorphism of the LTA gene was associated with stroke overall and any subtypes of ischemic stroke in the Japanese population.


A technique for recovering the phase from single fringe-pattern images is presented. It is based on the estimation of the local frequency of the pattern by successive decoupled estimation of the local orientation, direction, and magnitude of the frequency field. Once this field is known, the local phase is recovered from the complex output of an adaptive quadrature filter. It is shown that by the use of Gauss–Markov measure field models all these estimation steps may be implemented by solving linear systems of equations (i.e., minimizing quadratic functions), which makes the procedure robust and computationally efficient. Examples are presented of the application of this technique to the recovery of phase from single electronic speckle-pattern interferograms.


Singing Games in Early Modern Italy: The Music Books of Orazio Vecchi. By Paul Schleuse. (Music and the Early Modern Imagination.) Bloomington: Indiana University Press, 2015. [x, 372 p. ISBN 9780253015013 (hardcover), $50; ISBN 9780253015044 (ebook), $49.99.] Music examples, tables, illustrations, appendix, works cited, index. In the past few decades, scholars of the early modern period have devoted increasing and well-deserved attention to the crucial role that games and recreational activities played in the culture of the time, showing how these reflected their practitioners' aesthetic and moral values. Notable examples of this trend include the influential work of Alessandro Arcangeli (Recreation in the Renaissance: Attitudes Towards Leisure and Pastimes in European Culture, c. 1425-1675 [New York: Palgrave MacMillan, 2003]) and, in the field of music history, the works of Laurie Stras (" 'Al gioco si conosce il galantuomo': Artifice, Humour and Play in the 'Enigmi musicali' of Don Lodovico Agostini." Early Music History 24 [2005]: 213-86) and Katelijne Schiltz (Music and Riddle Culture in the Renaissance [Cambridge: Cambridge University Press, 2015]). Paul Schleuse's monograph is a welcome and valuable contribution to scholarship on this subject, as it seeks to shed light on "singing as social play and music written and published to function this way in late sixteenth-century Italy" (p. 1). To accomplish this task, Schleuse focuses on the secular music books of the Modenese composer Orazio Vecchi (1550-1605), on whom he is a widely acknowledged expert. Vecchi's music, Schleuse argues, constitutes an ideal case study for an understanding of music making as a recreational activity. Working for most of his career in rather peripheral centers of northern Italy, Vecchi appears to have composed many of his secular works not for ratified courtly environments, such as that of Ferrara (where professional musicians would perform before high nobility), but rather for less formal social gatherings (often in "bourgeois" households) where amateurs would sing for their own enjoyment, not necessarily before an audience. Embedding a wide range of stylistic registers and rich references to contemporaneous cultural and social codes, Vecchi's music-and the literary texts thereof, many of which Vecchi wrote himself-afforded these amateur musicians an opportunity not only to engage in playful conversation, but also and most importantly to reflect on their own identities and values. Throughout his monograph, Schleuse provides insightful readings of Vecchi's secular music, shedding light on his imaginative use of styles, forms, and genres, and on his ability to construct social and cultural meaning through music and poetry. Schleuse divides his monograph into six chapters. He devotes the first four chapters to a particular music book, or sets of books. by Vecclii, and arranges them chronologically, from the publication of Vecchi's first two books of four-voice canzonettas in 1578/79 and 1580 respectively, to the appearance of L'Amfiparnaso in 1597. The last two chapters center on themes that cut across the works of Vecchi as well as those of other late sixteenth-century composers who engaged with similar genres. Chapters 5 and 6 focus on competition as a form of social conversation, as seen in pieces that depict games, and the musical and literary representation of identities, with a focus on gender and sexuality. Chapter 1 explores Vecchi's development of a new musical genre, that of the four-voice canzonetta. Schleuse portrays works of this kind as recreational polyphony meant to bridge the gap between the rustic villanella tradition and the more elevated madrigal. The hybrid quality of this genre is in many respects reflective of the social status of its intended performers and audience, who typically did not have access to prestigious courts and regarded ratified courtly culture with a mix of fascination and wariness. …


We describe the underlying challenges on the adoption of ehealth (or e-health) in Tanzania which encompasses the use of Information and Communication Technology (ICT) in healthcare services. The study aimed at bridging the knowledge gap of ehealth adoption for improved healthcare services in Tanzania. The survey was conducted in regions namely Iringa and Morogoro, Tanzania using a structured questionnaire to health service recipients and providers. The findings show that the challenges include inadequate ICT skills, high cost of ICT in relation to economic status of community members, less developed infrastructure including lack of imaging equipment, small proportion of Internet users and lack of information about suitable ICT solutions. The findings have an important implication in various sectors including policy formulations aimed at increasing the adoption of ehealth for improved services.


An active learning (AL) algorithm seeks to construct an effective classifier with a minimal number of labeled examples in a bootstrapping manner. While standard AL heuristics, such as selecting those points for annotation for which a classification model yields least confident predictions, there has been no empirical investigation to see if these heuristics lead to models that are more interpretable to humans. In the era of data-driven learning, this is an important research direction to pursue. This paper describes our work-in-progress towards developing an AL selection function that in addition to model effectiveness also seeks to improve on the interpretability of a model during the bootstrapping steps. Concretely speaking, our proposed selection function trains an `explainer' model in addition to the classifier model, and favours those instances where a different part of the data is used, on an average, to explain the predicted class. Initial experiments exhibited encouraging trends in showing that such a heuristic can lead to developing more effective and more explainable end-to-end data-driven classifiers.


This edited collection of articles from Computer Music Journal provides a timely and convenient source of tutorials on OOP languages and software design techniques and surveys a wide range of existing applications of this technology to music and digital signal processing. Object-oriented programming (OOP) is perhaps the most important new software engineering technology of the past decade and promises to be a key factor in much of the software of the 1990s. This edited collection of articles from Computer Music Journal provides a timely and convenient source of tutorials on OOP languages and software design techniques and surveys a wide range of existing applications of this technology to music and digital signal processing. Included are the popular OOP languages LISP, Smalltalk-80, and Objective-C, and applications such as music description and composition, real-time performance, and digital signal processing.Contents. Introduction. Tutorials and Technology. Machine Tongues VIII: The Design of a Smalltalk Music System, Glenn E. Krasner. Machine Tongues IX: Object-Oriented Programming, Henry Lieberman. Machine Tongues XI: Object-Oriented Software Design, Stephen Pope. Music Representation and Processing Tools. Flavors Band: A Language for Specifying Musical Style, Christopher Fry. FORMES: Composition and Scheduling of Processes, Xavier Roder and Pierre Cointe. An Introduction to the MODE System - A Musical Object Development Environment, Stephen Pope. An Overview of the Sound and Music Kits for the NeXT Computer, David Jaffe and Lee Boynton. Composition Systems. The Kyma/Platypus Computer Music Workstation, Carla Scaletti. An Introduction to the Creation Station, Henry Flurry. TTrees: A Tool for the Compositional Environment, Glendon Diener. Signal Processing Systems. Javelina: An Environment for Digital Signal Processor Software Development, Kurt Hebel. Virtual Digital Signal Processing in an ObjectOriented System, David Mellinger, Guy Garnett, and Bernard Mont-Reynaud.


The introduction of firearms and metal arrowheads has been connected to momentous changes in North American Aboriginal subsistence activities and military relations, based on an alleged superiority of European technology over indigenous distance weapons, such as the bow and arrow. This dissertation compares Aboriginal cultures on the Northwestern Great Plains (Blackfoot) and in the Central Subarctic (Swampy Cree) and their reasons for retaining indigenous technology, adopting European technology or combining the two, and the impact of these actions on their cultures and history from the early fur trade to the treaty and reservation period. In spite of their many shortcomings, muzzle-loading smoothbore firearms were of importance in altering military relations between Aboriginal peoples in both regions. However, this effect was not based simply on superiority of these weapons, but rather on the ways Aboriginal people adapted them to their own needs and employed them in combat. Due to limitations in available materials for the manufacture of bows and arrows, climate constraints and an increasing emphasis on trapping, the Swampy Cree and other Subarctic peoples were more predisposed to adopt firearms. In contrast, on the Plains the increasing importance of mounted bison hunting favoured the retention of archery. Plains peoples used firearms mainly in combat, in combination with indigenous weapons. In the Subarctic firearms gradually replaced archery for big game hunting and combat, but the bow and arrow survived well into the twentieth century as a weapon to hunt small game and birds. On the Plains, in contrast, after the destruction of the bison herds both hunting and archery lost their former importance by the late 1800s.


In this project two approaches have been used to gain insights into the identity and molecular regulation of interneurons in the brain. First, a general molecular characterization of GABAergic neuron subtypes has been performed and second, novel fate determinants specifically for olfactory bulb interneurons have been identified and investigated in detail. GABAergic neurons, the largest population of inhibitory neurons in the brain, play crucial roles in information processing. While most of these neurons are interneurons, some, for example in the striatum, represent projection neurons. So far, biochemical, morphological, and electrophysiological properties served as exclusive criteria for the classification of GABAergic neurons. Although these parameters allow for a partial description of subpopulations, a systematic dichotomy is not available. Therefore, the general molecular characteristics of GABAergic neurons were analyzed and differences among distinct brain regions were defined. Transgenic GAD67-GFP mice in concert with flow cytometric cell sorting were used to isolate GABAergic neurons from defined regions of the postnatal mouse brain, namely olfactory bulb, cortex, striatum and cerebellum. Subsequently, gene expression profiling as well as cell surface proteome analysis were carried out and identified genes were validated by in situ hybridization and qPCR. Potential new marker genes for GABAergic neurons and candidate factors necessary for their differentiation and general functionality were determined. Clustering of gene expression data revealed major differences between hind- and forebrain GABAergic neurons indicating a correlation between their development and localization. For example, while GABAergic neurons of the forebrain are characterized mainly by three groups of transcription factors, namely the Distal-less-family, the POU-family and the ETS/FOX-family; specific members of the ZIC- and LHX-family define hindbrain inhibitory neurons. Olfactory bulb interneurons are generated throughout live by adult neuronal stem cells localized in the subventricular zone. While considerable information is available concerning the generation and migration of these cells, the molecular mechanisms regulating their terminal differentiation are barely understood. Therefore, mature interneurons from the periglomerular layer and their specific precursors were isolated by microdissection and magnetic cell sorting. Gene expression analysis was performed by microarray analysis. Several candidate factors to be involved in the differentiation of olfactory bulb interneurons were identified. The bHLH transcription factors NeuroD1 and NeuroD2 were analyzed for their functional relevance in vivo. Using in vivo electroporation, overexpression of these transcription factors was induced in postnatal forebrain stem cell populations as well as their progeny, namely neuronal precursors and mature neurons of the olfactory system. It was shown that high expression of NeuroD2 delayed the differentiation of Type A neuronal precursor cells into granule- and periglomerular neurons. In contrast, overexpression of NeuroD1 induced the premature and ectopic differentiation of precursor cells. Furthermore, NeuroD1 induced specifically a dopaminergic phenotype, indicating that it represents a novel key fate determinant for the specification of periglomerular interneurons, possibly with a GABA/dopamine bifunctional neurotransmitter phenotype. In conclusion, this study represents a comprehensive molecular basis for the understanding of spatially as well as temporally defined GABAergic neuron subpopulations and led to the identification of novel fate determinants for the differentiation of inhibitory interneuron subpopulations.


The bulb mite (Rhizoglyphus robini) causes damage to a number of crop and ornamental plant species, including saffron (Crocus sativus). A split-plot experiment based on a randomised complete-block design was conducted between 2011 and 2015 to investigate the effects of solarisation using transparent plastic along with planting date and first irrigation on the population of bulb mite, yield of saffron, size of corms produced and extent of corm infection. Solarisation significantly decreased the mite population and increased the saffron yield (P<0.01). Increased yields were achieved by planting in June rather than in September. However, the use of irrigation immediately after planting in June increased the mite population and decreased saffron yields. A combination of solarisation in the first year and planting in June of the next year with no irrigation after planting resulted in a reduction of 94% in the population of the mites and a 3.48-fold increase in saffron yield. In Iran, saffron corms should be planted in June but not irrigated until September. If planting does occur in September then irrigation should be applied immediately after planting.


Multicomponent quantum Hall systems with internal degrees of freedom provide a fertile ground for the emergence of exotic quantum liquids. Here, we investigate the possibility of non-Abelian topological order in the half-filled fractional quantum Hall (FQH) bilayer system driven by the tunneling effect between two layers. By means of the state-of-the-art density-matrix renormalization group, we unveil ``fingerprint'' evidence of the non-Abelian Moore-Read Pfaffian state emerging in the intermediate-tunneling regime, including the ground-state degeneracy on the torus geometry and the topological entanglement spectroscopy (entanglement spectrum and topological entanglement entropy) on the spherical geometry, respectively. Remarkably, the phase transition from the previously identified Abelian (331) Halperin state to the non-Abelian Moore-Read Pfaffian state is determined to be continuous, which is signaled by the continuous evolution of the universal part of the entanglement spectrum, and discontinuities in the excitation gap and the derivative of the ground-state energy. Our results not only provide a ``proof-of-principle'' demonstration of realizing a non-Abelian state through coupling different degrees of freedom, but also open up a possibility in FQH bilayer systems for detecting different chiral $p\text{\ensuremath{-}}\text{wave}$ pairing states.


PURPOSE
To develop a physics-based approach to improve the accuracy and robustness of the ill-conditioned problem of unfolding megavoltage bremsstrahlung spectra from transmission data.

METHODS
Spectra are specified using a rigorously-benchmarked functional form. Since ion chambers are the typical detector used in transmission measurements, the energy response of a Farmer chamber is calculated using the EGSnrc Monte Carlo code, and the effect of approximating the energy response on the accuracy of the unfolded spectra is studied. A proposal is introduced to enhance spectral sensitivity by combining transmission data measured with multiple detectors of different energy response and by combining data from multiple attenuating materials. Monte Carlo methods are developed to correct for nonideal exponential attenuation (e.g., scatter effects and secondary attenuation). The performance of the proposed methods is evaluated for a diverse set of validated clinical spectra (3.5-25 MV) using analytical transmission data with simulated experimental noise.

RESULTS
The approximations commonly used in previous studies for the ion-chamber energy response lead to significant errors in the unfolded spectra. Of the configurations studied, the one with best spectral sensitivity is to measure four full transmission curves using separate low-Z and high-Z attenuators in conjunction with two detectors of different energy response (the authors propose a Farmer-type ion chamber, once with a low-Z, and once with a high-Z buildup cap material), then to feed the data simultaneously to the unfolding algorithm. Deviations from ideal exponential attenuation are as much as 1.5% for the smallest transmission signals, and the proposed methods properly correct for those deviations. The transmission data with enhanced spectral sensitivity, combined with the accurate and flexible spectral functional form, lead to robust unfolding without requiring a priori knowledge of the spectrum. Compared with the commonly-used methods, the accuracy is improved for the unfolded spectra and for the unfolded mean incident electron kinetic energy by at least factors of three and four, respectively. With simulated experimental noise and a lowest transmission of 1%, the unfolded energy fluence spectra agree with the original spectra with a normalized root-mean-square deviation, %Δ(ψ), of 2.3%. The unfolded mean incident electron kinetic energies agree, on average, with the original values within 1.4%. A lowest transmission of only 10% still allows unfolding with %Δ(ψ) of 3.3%.

CONCLUSIONS
In the presence of realistic experimental noise, the proposed approach significantly improves the accuracy and robustness of the spectral unfolding problem for all therapy and MV imaging beams of clinical interest.


Historians have speculated over the existence of an 1841 plan by the French foreign minister François Guizot to internationalize Jerusalem as a Christian city, a plan holding major implications for the eventual emergence of a Jewish state and for European–Ottoman relations. This article aims, based on fresh archival and other sources, to provide a definitive evaluation of Guizot's plan, its scope, and its motivations. It broadens the field to encompass other great power plans mooted in 1841, including plans of a Protestant yet Zionist flavour, and it reassesses the political weight of early nineteenth-century European religious impulses with regard to Palestine.


Between 1989-1991, I studied the effects of livestock grazing on vegetation and small mammals in semiarid shrub-grassland habitats of south-central Utah. Responses were measured at 2 spatial habitat scales; patches and macrohabitats. Patch-scale data were obtained from 4 small (<1 ha) livestock exclosures and nearby grazed areas. Macrohabitat-scale data were collected at 4 actively grazed sites and 4 comparable, excellent condition sites, ungrazed for 30+ years. Ungrazed patch and macrohabitat sites had more surface litter, greater perennial grass cover, and taller perennial grass plants, but treatment response varied among sites. Small mammal responses were apparent only at the macro-habitat scale, where ungrazed sites had 50% greater species richness and 80% higher abundance. Small mammal reproductive activity and biomass were not affected by rest from grazing at either scale. Small mammal community composition varied greatly among sites and within treatments. This variability has important implications for ecological monitoring efforts involving these species.


On October the 15th 2017, the American actress Alyssa Milano tweeted the phrase #MeToo to openly declare her experience of sexual harassment by the movie mogul Harvey Weinstein. By the end of the following day, MeToo had been re-tweeted more than half a million times and on Facebook received more than 12 million posts in 24 hours. Finally, the lid was being lifted on decades of abuse and harassment in the entertainment industry. There was an immediate response from British theatre with leading directors calling for a sea-change. The Royal Conservatoire of Scotland already had strategies to ensure respect and tolerance in the training of its young artists. Alongside additional policies directly linked to the aftermath of MeToo, we also enabled a new role, that of Intimacy Choreographer.


An artificial neural network (ANN) model has been applied to the prediction of key weld geometries produced using gas metal arc welding (GMAW) with alternating shielding gases. This is a recently developed method of supplying two individual shielding gases to the weld area in which the gases are discretely supplied at a given frequency. The model can be used to predict the penetration, leg length, and effective throat thickness for a given set of weld parameters and alternating shielding gas frequency. A comparison of the experimental and predicted geometries matched closely and demonstrates the effectiveness of this software approach in predicting weld outputs. The model has shown that the application of alternating shielding gases increases the penetration and effective throat thickness of a fillet weld while the leg length is reduced. A sensitivity analysis was performed that showed travel speed is the most influential input parameter when predicting weld geometries. This is to be expected for any given welding setup due to the influence of the travel speed on the heat input. The sensitivity analysis also showed that the shielding gas configuration had the lowest influence on the output of the model. The output from the model has demonstrated that the use of alternating shielding gases during GMAW results in a step change in the weld metal geometry. This suggests that, in the case of alternating shielding gases, an increased travel speed is required to produce a similar weld geometry to that of the conventional Ar/20%CO2 technique.


Since its discovery, the CRISPR/Cas9 system has been at the focus of fundamental researchers, genome engineers, and the general public alike. Despite being in the spotlight for several years, aspects of the precise molecular mechanism of Cas9 activity remain ambiguous. We use single-molecule Foerster resonance energy transfer (smFRET) to reveal Cas9 target search mechanism with nanometer sensitivity. We have developed single-molecule assays to monitor transient interactions of Cas9 and DNA in real time. Our study shows that Cas9 interacts with the protospacer adjacent motif (PAM) sequence weakly, yet probing neighboring sequences via lateral diffusion. This dynamic mode of interactions leads to translocation of Cas9 to another PAM nearby and consequently an on-target sequence. We propose a model in which lateral diffusion competes with 3-dimensional diffusion and thus might aid PAM finding and consequently on-target binding.


Airport operations are undergoing significant change, having to meet pandemic requirements in addition to intrinsic security requirements. Although air traffic has declined massively, airports are still the critical hubs of the air transport network. The new restrictions due to the COVID-19 pandemic pose new challenges for airport operators in redesigning airport terminals and managing passenger flows. To evaluate the impact of COVID-19 restrictions, we implement a reference airport environment. In this reference Airport in the Lab environment we will demonstrate the operational consequences derived from the new operational requirements. In addition, countermeasures to mitigate any negative impacts of these changes are tested. The results highlight emerging issues that the airport will most likely face and possible solutions. Finally, we could apply the findings and lessons learned from our testing at our reference airport to a real airport.


Background and Aim: Swimming is an ideal physical activity for the elderly population because of its low impact on joints and minimal risk of injury. Previous studies have proven that swimming has beneficial effect on skeletal and cardiovascular health. But studies to assess effects of swimming on cognitive health of elderly are lacking. Methods: This study was undertaken to assess and compare the level of cognition among elderly swimmers and non swimmers. 50 elderly subjects who regularly swim and 50 elderly non swimmers were recruited. Digit symbol substitution test and Digit vigilance test were done to assess the mental speed and attention of the subjects. Results: Results were statistically analyzed using students t test to compare between the groups. Swimmers took less time to complete both Digit symbol substitution test and Digit vigilance test than non swimmers. Conclusion: Elderly swimmers had better mental speed and attention compared to non swimmers.


Hypnea bryoides collected from the Arabian Sea on the southern coast of Oman was investigated for κ-carrageenan optimal extraction conditions. The effects of different conditions of alkali treatment (4, 6, and 8% w/v NaOH), temperatures (70, 75, and 80°C), and time (2, 2.75, 3.5 hours) on carrageenan yield and chemical and thermal properties were evaluated. Yield was significantly affected by alkaline concentration and temperature, with highest value of 26.74 ± 5.01%. Molecular weights of the extracted carrageenan were significantly reduced by increased temperatures and ranged from 5.95 ± 0.49 × 105 Da to 13.90 ± 0.14 × 105. FTIR showed that samples under all extraction conditions were similar and confirmed the presence of κ-carrageenan with no traces of μ-precursor. Sulfate content was also significantly reduced by alkaline concentration (from 4% to 6%) and ranged from 7.62 ± 5.52% to 17.02 ± 0.14. Thermal properties showed more sensitivity towards temperature and alkaline strength parameter than time. In addition, melting and gelling temperatures were significantly correlated with the molecular weight, but not sulfate content. In conclusion, mild extraction conditions were found to be more efficient in introducing the intended structural modification while getting the highest yield and quality.


In 1839 fifty-eight men left Montreal for the penal colony of New South Wales. They were ordinary people who had been caught up in the political whirlwind of the 1838 rebellion. Even though they were all civilians, they had been tried by court martial. Convicted of treason, their properties forfeited to the crown, they paid a heavy price for rebellion. And as convicts in Australia, they were considered the lowest of a bad lot. During their years there, however, they earned the respect of Sydney's citizens.


Successful endovascular therapy for acute ischemic stroke (AIS) requires optimal patient selection and effective tools, and also the rapid delivery of treatment from the time of symptom onset. Time to treatment for patients with AIS remains, arguably, the most important modifiable factor in improving outcomes.

Although intravenous tissue plasminogen activator (tPA) administration has been extended to 4.5 h,1 ,2 fewer than one-third of eligible patients receive it within the target door to needle (DTN) time of 60 min.3 This failure to achieve benchmark times has led to 'Target: Stroke', a national quality improvement initiative of the American Heart Association/American Stroke Association which aims to increase the timeliness of intravenous tPA administration. Over the past 20 years, tremendous efforts in developing primary stroke centers and implementing strategies based on the development of these centers have led to a dramatic reduction in DTN times, but there is much room for improvement.

Studies in myocardial infarction (MI) have shown the critical importance of time in improving outcome for patients undergoing percutaneous coronary intervention (PCI). In a large meta-analysis of 27 MI trials,4 a strong relationship between PCI-related time delay and benefits from primary angioplasty was observed in high-risk patients (r=–0.50, β= –0.075 (95% CI –0.189 to 0.04)), with 131 min as the equipoint between PCI and medical therapies. Moreover, for every 10 min reduction in time to PCI, MI mortality was also reduced.4 In a prospective PCI trial investigating the relationship between time and outcome, patients randomized <2 h after symptom onset demonstrated a strong trend towards a lower 30-day death rate with PCI than with medical treatment (2.2% vs 5.7%, p=0.058), with no difference observed in those randomized after 2 h.5

A similar emphasis on time to treatment in AIS studies has also …


In this paper the load optimization of a combined cycle power plant under consideration of the real cost of lifetime usage is accomplished by exploiting hybrid systems, i.e., systems evolving according to continuous dynamics, discrete dynamics, and logic rules. The possibility of turning on/off the gas and steam turbines, the operating constraints (minimum up and down times) and the different types of start up of the turbines characterize the hybrid behavior of a combined cycle power plant. In order to model both the continuous/discrete dynamics and the switching between different operating conditions we use the framework of Mixed Logic Dynamical systems. Next, we recast the economic optimization problem as a Model Predictive Control (MPC) problem, that allows us to optimize the plant operations by taking into account the time variability of both prices and electricity/steam demands. Because of the presence of integer variables, the MPC scheme is formulated as a mixed integer linear program that can be solved in an efficient way by using commercial solvers.


The USEPA's ambient water quality criteria (AWQC) for cyanide were developed in 1984. Recently, however, concerns have arisen that the AWQC for cyanide have been problematic to implement and may not accurately reflect either the toxic forms or bioavailable concentrations of cyanide in water, sediments, and tissues of aquatic organisms. Also, the cyanide criteria typically have been implemented based on total cyanide concentrations rather than the free cyanide concentrations that formed the basis of the criteria calculations. New knowledge on cyanide toxicity, cyanide speciation and its measurement, and the relative toxicity of bioavailable cyanide species suggested that a re-evaluation of the aquatic toxicity data and chemistry that serve as the basis of the current national criteria is warranted.

In response to these concerns, studies sponsored by the Water Environment Research Foundation (WERF) evaluated the formation and fate of cyanide in municipal wastewater effluents. Kavanaugh et al. (2003) evaluated the reliability of several analytical methods for measurement of cyanide species at low (ppb) concentrations, along with studies to evaluate the sources, transport, and fate of cyanide species in wastewater treatment plants (WWTPs) and receiving waters. Results indicated that potentially toxic forms of cyanide can be generated in WWTPs from several chemical processes, including dissociation of thiocyanate by chlorination or UV disinfection, chlorination in the presence of residual ammonia, nitrosation, and photolysis of ferrocyanate. Models were developed for predicting the fate of these compounds in surface waters downstream of WWTP effluents to establish where organisms might be most at risk from cyanide exposure. While implementation of these results could assist in the development of site-specific water quality standards for cyanide, a more thorough update to the National AWQC was warranted to apply our more current scientific understanding of cyanide toxicology to the derivation of aquatic life criteria.

The present study was therefore undertaken to review and update knowledge of the aquatic toxicity of cyanide, and to develop recommended updates to the existing national AWQC to enhance the scientific basis of the concentrations and chemical forms of cyanide specified for protection of aquatic organisms. This update was conducted according to USEPA guidance for derivation of AWQC for protection of aquatic life, and is based both on an extensive literature review and on new toxicity studies that fill key data gaps.

This re-evaluation of cyanide criteria also includes consideration of impacts on benthic (sediment) organisms, wildlife that consume aquatic biota, and possible effects to threatened and endangered species to ensure that revised criteria are adequately protective of the entire aquatic ecosystem.

This title belongs to WERF Research Report Series

ISBN: 9781843397533 (Print)

ISBN: 9781780403755 (eBook)


We develop a dynamic general equilibrium model with many different industries, in which firms set prices strategically in product markets. Our approach extends previous literature by endogenizing the market price of risk and allowing for more general risk structures. General equilibrium in the model is shown to exist under general conditions. Strategic interaction between firms amplifies business cycles, small changes in long-term growth rates can have drastic effects on the equilibrium outcome, whereas temporary changes in productivity have marginal impact, and the overall competitiveness of the economy only depends on long-term growth. A firm's expected returns are affected by the industrial environment in which it operates, in line with what has been observed in the empirical literature. Overall, our model suggests that industry characteristics should be informative about the expected returns of individual firms over the business cycle.


Cell polarity and tight junctions (TJs) are necessary for intact epithelia. Loss of tight junction integrity is consistent with a display of mesenchymal phenotype which is characteristic of metastatic progression. Occludin, the first identified transmembrane protein identified to localize at tight junctions, has been implicated in regulating tight junction function and cellular polarity. The N-terminal region of occludin has been shown to be an important factor in tight junction maintenance but the mechanism is not yet known. Extensive studies by other researchers have been performed to examine factors that drive EMT, while little is known about their functional reversibility in MET. A model system of EMT ↔ MET was previously established using Pa4 cells, an immortalized epithelial cell line derived from rat parotid gland. Stable introduction of an oncogenic form of the kinase Raf1 into Pa4 was used to derive a mesenchymal phenotype (Pa4Raf1) that demonstrates anchorage-independent growth that coincides with a loss of functional TJs including down-regulation of occludin. The N-terminal region of occludin (66 amino acids) was cloned and used as a bait to pull down protein binding partners in Pa4 and Pa4Raf1 cell lysates. This region of occludin was coupled to a hexa-histidine sequence (His-tag). The resulting protein was expressed in E. coli, purified using magnetic nickel beads, and used as a bait to pull down potential binding partners for this region of occludin present in two cell lines: Pa4 and Pa4-Raf1. Importantly, N-terminal region of occludin has a series of serine and tyrosine residues that are predicted to be phosphorylated by a wide range of kinases. In this regard, Ser8, Ser45, Tyr12, Tyr22, Tyr29 and the poly-proline region (Pro-Leu-Ser-Pro-Pro-Pro-Tyr-Arg-Pro) of the N-terminal bait peptide were mutated in order to further elucidate the functions of these residues. Serine was mutated to aspartic acid, tyrosine to glutamic acid, and proline to alanine. The binding partners were also knocked down to identify their effects on occludin colocalization. Many of the potential binding partners that were identified are involved in apoptosis, metastasis and/or cellular oxidation. This research seeks for ways by which manipulating these identified binding partners will transform a cell from a mesenchymal phenotype to an epithelial phenotype.


An aneurysm is a permanent localized (i.e., focal) dilation of an artery that has at least a 50% increase in diameter compared with the expected normal diameter of the artery in question. For practical reasons, however, most reports document an aneurysm of the infrarenal aorta when diameter reaches 3 cm or more. The risk of an aneurysm is rupture, and therefore the treatment goal is to treat the aneurysm long before it has been ruptured. It was not until 1991 that an aneurysm was treated by means of an open repair. The advances notwithstanding, open aneurysm repair continues to cause substantial morbidity and requires a prolonged hospital admission and intensive care stay as well as a long recovery period. In addition, a significant number of patients are deemed high-risk candidates for open repair because of significant comorbidities. All of these issues provided a major incentive for the development of less invasive procedures. In 1991, Parodi et al. in Argentina and Volodos et al. in the Ukraine both reported a technique for endovascular aneurysm repair. Since then, treatment of aneurysms of the abdominal aorta shifted from open repair to the less invasive endovascular repair. In this thesis, the long-term outcome of this treatment modality is described alongside the possible complications. Also, we mentioned many anatomical aneurysm and stent-graft fixation risk factors which influence outcome after endovascular aneurysm repair. And finally we describe the use of endovascular stent-grafts to treat other arterial pathology: the para-anastomotic aneurysm after previous open repair. The long-term results were good. Most complication could be resolved by means of a second endovascular procedure. We identified many risk factors which influence the durability of this procedure. When treating patients by means of this procedure, the risk factors have to be taken into account. The treatment of paraanastomotic aneurysms was promising and should replace the open repair to treat these kind of late complications after previous open repair. Overall, the endovascular treatment of patients with an aneurysm of the abdominal aorta will increase and eventually all patients will be treated by means of an endovascular technique.


Several impacts of climate change may depend more on changes in mean daily minimum (Tmin) or maximum (Tmax) temperatures than daily averages. To evaluate uncertainties in these variables, we compared projections of Tmin and Tmax changes by 2046–2065 for 12 climate models under an A2 emission scenario. Average modeled changes in Tmin were similar to those for Tmax, with slightly greater increases in Tmin consistent with historical trends exhibiting a reduction in diurnal temperature ranges. In contrast, the inter‐model variability of Tmin and Tmax projections exhibited substantial differences. For example, inter‐model standard deviations of June–August Tmax changes were more than 50% greater than for Tmin throughout much of North America, Europe, and Asia. Model differences in cloud changes, which exert relatively greater influence on Tmax during summer and Tmin during winter, were identified as the main source of uncertainty disparities. These results highlight the importance of considering separately projections for Tmax and Tmin when assessing climate change impacts, even in cases where average projected changes are similar. In addition, impacts that are most sensitive to summertime Tmin or wintertime Tmax may be more predictable than suggested by analyses using only projections of daily average temperatures.


The contamination of recreational waters by waterborne pathogens poses a health threat to beach users. Recently, the importance of beach sand to the biological quality of beach water has been realized and verified. This study examined how urban rainfall runoff from a tributary stream affects the concentrations of fecal indicator bacteria (FIBs) in beach sand at a marine beach on the island of Oahu, Hawaii. Rainfall runoff was found to cause temporary increases in concentrations of enterococci and E. coli at Waialae-Kahala Beach, and beach foreshore sand and submerged sand were strongly influenced by beach water. High concentrations of enterococci and C. perfringens were consistently detected in beach submerged, foreshore, and backshore sands, indicating that beach sands may be important reservoirs of enterococci and C. perfringens. Additionally, the effects of rainfall runoff on FIBs in an inland freshwater stream were also investigated in the Manoa Stream watershed. Concentration spikes of FIBs always corresponded to rainfall runoff, and although the same rainfall runoff effects were observed for different land uses (i.e. forest versus urban), much higher concentrations of FIBs were detected in the urban reaches than in the forest reach of Manoa Stream. Furthermore, large numbers of FIBs were detected persistently in Manoa Stream bank soil. Urban and forest land uses, however, did not affect soil FIB concentrations. The concentrations of the traditional FIBs (i.e. enterococci and E. coli) correlated with prior cumulative rainfall and soil moisture levels, supporting the possibility of growth of enterococci and E. coli in soil. qPCR quantification of enterococci was found to correlate with mEI agar plate counts in beach water, but not in beach sand and estuarial and freshwater samples from streams, which indicates that the presence of naked DNAs, VBNC cells, and PCR inhibitory compounds can have a significant impact on qPCR outcomes.


Typhoid infections have become an alarming concern with the increase of multidrug resistant strains of Salmonella serovars. The new pathogenic Gram-negative strains are
resistant to most antibiotics such as chloramphenicol, ampicillin, trimethoprim, ciprofloxacin and even co-trimoxazole and their derivatives thereby causing numerous outbreaks in the Indian subcontinent, Southeast Asian and African countries. Conventional and modern methods of typing had been adopted to differentiate outbreak strains.
However, identifying the most indispensable proteins from the complete set of proteins of the whole genome of Salmonella sp., comprising the Salmonella pathogenicity islands (SPI) responsible for virulence, has remained an ever challenging task. We have adopted a network-based method to figure out, albeit theoretically, the most significant proteins which might be involved in the resistance to antibiotics of the Salmonella sp. An understanding of the above will provide insight into conditions that are encountered by this pathogen during the course of infection, which will further contribute in identifying new targets for antimicrobial agents.


A global format is developed for momentum and energy consistent time integration of second‐order dynamic systems with general nonlinear stiffness. The algorithm is formulated by integrating the state‐space equations of motion over the time increment. The internal force is first represented in fourth‐order form consisting of the end‐point mean value plus a term containing the stiffness matrix increment. This form gives energy conservation for systems with internal energy as a quartic function of the displacement components. This representation is then extended to general energy conservation via a discrete gradient representation. The present procedure works directly with the internal force and the stiffness matrix at the time integration interval end‐points, and in contrast to previous energy‐conserving algorithms, it does not require any special form of the energy function nor use of mean value products at the element level or explicit use of a geometric stiffness matrix. An optional monotonic algorithmic damping, increasing with response frequency, is developed in terms of a single damping parameter. In the solution procedure, the velocity is eliminated and the nonlinear iterations are based on the displacement components alone. The procedure represents an energy consistent alternative to available collocation methods, with an equally simple implementation. Copyright © 2014 John Wiley & Sons, Ltd.