PURPOSE
Administration of voriconazole, an antifungal triazole, causes transient visual disturbances in patients and attenuates the b-wave of the ERG. We sought to identify the retinal target of voriconazole underlying the effect on the ERG b-wave.

METHODS
Electroretinograms were recorded from mice before and after intraperitoneal injection of voriconazole. The effect of voriconazole on ON-bipolar cells was tested by patch-clamp recordings of ON-bipolar cells in mouse retinal slices. Effects of voriconazole on mGluR6 and TRPM3 were assessed by patch-clamp recordings of Chinese hamster ovary (CHO) and HEK293 cells transfected with either TRPM3 or mGluR6 plus Kir3.1/Kir3.4.

RESULTS
Voriconazole attenuated the ERG b-wave in mice, and inhibited ON-bipolar cell responses evoked by application of CPPG, an mGluR6 antagonist, onto the ON-bipolar cell dendrites, indicating that voriconazole blocks a step in the mGluR6-TRPM1 signal transduction pathway. Voriconazole almost completely blocked capsaicin-activated currents in ON-bipolar cells, which have been attributed to direct activation of the TRPM1 cation channel. Furthermore, application of voriconazole to CHO cells expressing TRPM3, a closely related channel to TRPM1, showed that voriconazole reversibly blocked pregnenolone sulfate-stimulated TRPM3 currents in transfected cells. In contrast, voriconazole only slightly inhibited mGluR6-mediated activation of G-protein activated inward rectifier potassium (GIRK) currents in cotransfected cells, suggesting that mGluR6 is not the primary target of voriconazole in ON-bipolar cells.

CONCLUSIONS
The visual disturbances associated with voriconazole are likely due to block of TRPM1 channels in retinal ON-bipolar cells. Other neurological effects of voriconazole may be due to block of TRPM3 channels expressed in the brain.


Purpose

Using the Theory of Planned Behaviour (TPB) framework, this study explored whether the standard TPB constructs explained variance in Gen Y individuals' intentions to join their ideal organisation.

Design/methodology/approach

A mixed methods approach was used featuring qualitative and quantitative methods.

Findings

The overall TPB model accounted for a significant 51.6% of the variance in intention to join one's ideal organisation in the next six months with the significant predictors in the model being subjective norm and perceived behaviour control but not attitude.

Research limitations/implications

Using graduating students from a single Australian university sample may mean that the current findings may not extend to all Gen Y individuals. The current study has demonstrated the explanatory utility of the TPB in relation to graduate Gen Y's intention to join their ideal organisation, providing further evidence of the robustness of the TPB framework in an organisational setting.

Practical implications

These findings have implications for enhancing understanding of the most effective recruitment processes for Gen Y students entering the workforce. The findings could inform recruitment policies and strategies to attract Gen Y applicants.

Originality/value

To our knowledge this study is the first application of the TPB to this topic. The current research extends the recruitment literature with a theoretically-based investigation. Identification of factors which inform organisational recruitment strategies, allow organisations to stand out from their competitors and potentially achieve a larger application pool from which to select the best human capital and sustain competitive advantage.


In the last twenty years, the question has been raised of what audience there is for parascience in our societies: in what measure does the public say it believes in the reality of a number of phenomena such as explanation of personality by astrological signs, thought transference and bewitchment? This article is based on comparative analysis of the results of five opinion surveys conducted between 1982 and 2000 on belief in 11 parascientific phenomena. The data indicate that, contrary to a commonly held view, such belief does not seem to have grown perceptibly over the period. With regard to socio-demographic and ideological determinants, there are certain regularities: woman, young people, and people who believe in an afterlife are more inclined to say they believe in parascience.


This research explores the decision making processes of individuals and groups engaged in
child protection practice within social services departments in the UK. The emphasis of the
research was to consider how the application of psychological theories and concepts might
allow a descriptive and interpretative evaluation of decision processes in child protection
practice. The research sought to elaborate upon much of previous social work literature in that
it focused upon the processes of decision making rather than the outcomes for participants.
Similarly it sought to elaborate upon literature in decision theory in that it focused upon real
world, ongoing and naturalistic decision situations. The theoretical framework used in the
research was an integrated model of decision making under conditions of risk proposed by
Whyte (1989,1991). This model outlines circumstances under which individuals and groups
may take decisions in the directions of risk or caution.

The methodological approach was grounded in the principles of qualitative research. Drawing
upon Forster (1994) and Yin (1989) documentary analysis was applied to case studies. The
research considered documents in relation to two categories of child protection cases. Initially
those where children who were already known to child protection practitioners had died,
namely, child death inquiry reports. Ongoing cases within a local authority child protection
department, where the outcomes and decision making were considered to be positive, were
then analysed. The interpretation from the first stage of the research suggested that all the
concepts outlined in Whyte's model could have explanatory value and that the deaths of
children could be a consequence of the ways in which decisions are framed and which leave
children in situations of risk. The second stage involved the analysis of documents in relation
to eight ongoing cases within a local authority. The number of group meetings held in the eight
cases was 38 and in 71% of these the operation of the certainty effect in the direction of risk
was evident. In the remaining 39% there was evidence that the certainty effect operated in the
direction of caution. Within the documents there was some evidence of group polarisation and
groupthink. Resources were committed and escalated consistently in order to ensure the
effectiveness of initial plans of action despite evidence that these were unsuccessful in terms of
the overall well being of the children.

The decisions were shown to be bounded by the 'objective' principles of the Children Act 1989
and Working Together (1991). However themes that emerged from the analysis of the cases
suggest that there is a 'subjective' influence on decision processes. Evident within the analysis
was a shared fundamental belief in keeping children with their mothers. Both these objective
and subjective influences suggest that almost inevitably decision making in child protection
practice will be driven in directions that result in courses of action that involve potential and
actual risks for children. The findings emphasise how an explicit recognition of the
multifaceted nature of decision making can assist in more reflective practice. The ways in
which national and local policy impacts upon decision processes, at the level of the individual
and groups, need to be monitored in order that the needs of children in situations that involve
risk remain paramount.


During analyses of ditch cuttings samples from wells 34/10-53A and 35/9-F-1H drilled by Statoil ASA in the North Viking Graben, North Sea, 16 specimens pertaining to Aratrocypris were found. One specimen was found at 1260 m (depth below KB) in 35/9- F-1H within an interval of Lower Paleocene claystones, and based on its white chalky preservation characteristics is considered reworked from Maastrichtian chalk. The remaining 15 specimens were found among ostracod-rich microfossil assemblages of Early Cretaceous age in a sample at 4190 m of 34/10-53A, and at 2166 m of 35/9-F-1H. Although these samples contain numerous ostracods, the occurrence at such a low stratigraphical level was unexpected since Aratrocypris , hitherto, has not been found older than Coniacian/Santonian. Their preservation condition as orange-stained opaque carapaces is the same as that of the remainder of the assemblage found at that level in the Lower Cretaceous. For this reason the possibility of it being caved from higher levels of the well is ruled out. The find, therefore, represents the earliest record of the genus, and is important also when considering its early zoogeographical distribution.

Ostracods occur in well 35/9-F-1H at two levels: Lower Paleocene and Lower Barremian–Lower Hauterivian. Each assemblage has a very different style of preservation which allows them to be easily separated. Ostracod assemblages of the younger level are white, translucent carapaces, a preservational style consistent with the abundant foraminifera …


All geological changes result from the transfer of matter and energy, the study of which is the goal of thermodynamics. Investigating natural processes thus necessarily involves thermodynamic considerations. This has long been practiced implicitly, as shown by the smart reflections made by "natural philosophers" from antiquity to the 18th century about topics ranging from atmospheric phenomena to the early history of the Earth. Since the early 19th century, investigations explicitly take advantage of a rigorous framework that deals with chemical and thermal aspects of the Earth's activity. Far from being abstruse, these principles can in fact be summarized in a simple and concise way.


More than 2800 published fluid inclusion data (primary inclusions) from eighteen typical Mississippi Valley-type (MVT) Zn-Pb deposits and districts were examined to study possible relationships between MVT fluid properties and metal tonnages and ore grades. The mean Th and salinity values for fifteen MVT deposits and districts are 122°C ± 21°C and 20.7 ± 2.6 wt% CaCl 2 equivalent, respectively. In general, temperatures increase from pre-ore to ore stages, and salinities decrease from ore to post-ore stages. From post-ore to late calcite stages, salinity and temperature decrease with various trends within specific districts. Several conclusions are drawn: first, results show that Hanor's (1996) salinity threshold for metal-rich basinal fluids applies to typical MVT ore fluids (~16 wt% CaCl 2 equivalent). Second, the lower limit of mean Th values of measured MVT deposits and districts (n = 15) of ~75°C is similar to Hanor's (1996) observed temperature threshold for metal-rich basinal brines of ~60°C (n = 224). Third, there is no statistically significant relationship between fluid inclusion homogenization temperatures (Th) and metal tonnages or ore grades. Fourth, there seems to be a tendency for large tonnage districts/deposits to be associated with mean fluid salinities that are relatively low (~16 to 21 wt% CaCl 2 equivalent) within the overall range of salinity means (~16 to 26 wt% CaCl 2 equivalent). There is also a correlation between higher ore grades and higher salinities. Finally, comparison with other sedimentary rock-hosted Zn-Pb deposit types shows a trend of salinity decrease and temperature increase from MVT, sandstone-hosted and diapir-related Pb-Zn deposits, to vein-type and Irish-type Pb-Zn deposits, and then to sedex deposits. However, more data are needed for sedex deposits. The salinity threshold for significant Zn-Pb transport decreases to ≥~10 wt% CaCl 2 equivalent at ~250°C. This study suggests that fluid inclusion analysis during exploration may be useful in assessing ore-forming potential (threshold salinity) and possible ore grades (salinity).


The poor performance often attributed to many public employment services may be explained in part by a delegation problem between the central office and local job centers. In markets characterized by frictions, job centers function as match-makers, linking job seekers with relevant vacancies. Because their search intensity in contacting employers and collecting data is not verifiable by the central authority, a typical moral hazard problem can arise. To overcome the delegation problem and provide high-powered incentives for high levels of search effort on the part of job centers, we propose output-related schemes that assign greater staff capacity to agencies achieving high strike rates.


Much attention has focused on biological regulation through control of gene transcription. But control mechanisms don't stop there, and new evidence is accumulating that suggests that extensive interactions between proteins and mRNAs provide posttranscriptional mechanisms for controlling translation of RNAs to protein. Gerber et al. conducted a genome-wide search for mRNAs that associated with PUMILIO (Pum), an RNA binding protein from Drosophila. Pum and related proteins in yeast were already known to function in a broad range of biological processes, particularly in development. These range from anterior-posterior patterning in the fly embryo--which results in part through control of the abundance of a key transcription factor--to germ cell development and neuronal development and function. However, only a handful of target mRNAs have been identified. That is no longer a problem, as the authors' screen, in which RNAs that associated with an affinity-tagged fragment of Pum were identified after conversion to fluorescently tagged cDNA probes and hybridization to a DNA microarray, yielded on the order of 1000 mRNAs from adult tissue that showed specific association with Pum. These included the interactors known from traditional forward genetic studies. Similar analysis of material from embryos yielded a couple hundred different interactors. Even allowing for the usual caveats regarding false-positive and false-negative results of such methods, the screen appears to substantially expand the reach of the biological effects of Pum. Exploration of the gene ontology annotations for functions of the sequences identified showed enrichment for mRNAs involved in nucleotide metabolism and transcriptional regulation and transcripts localized to organelle membranes. In the embryo samples, Pum appeared to associate preferentially with regulators of axis formation. The authors suggest that the results with Pum argue for "a highly organized and multifaceted posttranscriptional regulatory system in multicellular organisms." A. P. Gerber, S. Luschnig, M. A. Krasnow, P. O. Brown, D. Herschlag, Genome-wide identification of mRNAs associated with the translational regulator PUMILIO in Drosophila melanogaster. Proc. Natl. Acad. Sci. U.S.A. 103, 4487-4492 (2006). [Abstract] [Full Text]


Background and Objectives The low number of umbilical cord blood cells is an important barrier to successful bone marrow transplantation. Therefore, the growth of these cells while maintaining their functional characteristics is of great importance. Culturing cells on 3D scaffolds like DBM has greatly contributed to the simulation of the mechanical and chemical micro-environment of the bone marrow tissue. There are also specific compounds for proliferation without differentiation of cells one of which is nicotinamide. Materials and Methods In this experimental study, hematopoietic stem cells (HSCs) were cultured 7 days in DBM under the following conditions of (1) negative control, (2) cytokine, (3) nicotinamide, (4) nicotinamide and cytokine. After 7 days, cell count, purity using flow cytometry, colony forming unit assay and apoptosis were evaluated and performed. The data were analyzed using Anova. Results Our results indicated that in all cases, the combination of nicotinamide and cytokine was accompanied with more proliferation, more CD34 + cells, less apoptosis, and higher colonyforming ability than other groups. Conclusions Nicotinamide is a very suitable compound for the development of umbilical cord blood cells given the role of the former in preventing epigenetic changes that are the outcome of laboratorial cell culture and the simulation of bone marrow niche by DMB.


Tuning tools attempt to configure a database to achieve optimal performance for a given workload. Selecting an optimal set of physical structures is computationally hard since it involves searching a vast space of possible configurations. Commercial DBMSs offer tools that can address this problem. The usefulness of such tools, however, is limited by their dependence on greedy heuristics, the need for a-priori (offline) knowledge of the workload, and lack of an optimal materialization schedule to get the best out of suggested design features. Moreover, the open source DBMSs do not provide any automated tuning tools. This demonstration introduces a comprehensive physical designer for the PostgreSQL open source DBMS. The tool suggests design features for both offline and online workloads. It provides close to optimal suggestions for indexes for a given workload by modeling the problem as a combinatorial optimization problem and solving it by sophisticated and mature solvers. It also determines the interaction between indexes to suggest an effective materialization strategy for the selected indexes. The tool is interactive as it allows the database administrator (DBA) to suggest a set of candidate features and shows their benefits and interactions visually. For the demonstration we use large real-world scientific datasets and query workloads.


Accelerator mass spectrometry 14C ages on monospecific marine microfauna from raised mud record initial deglaciation of the eastern coast of Scotland before 21.0 cal ka bp. Two subsequent ice-margin readvances occurred prior to the Loch Lomond Advance and are identified from ice-contact deposits overlying marine mud. The Lunan Bay Readvance dates to <20.2 cal ka bp, and possibly <18.2 cal ka bp. The younger Perth Readvance occurred between c. 17.5 cal ka bp and 14.5 10Be ka. Within dating uncertainties, these readvances are similar in age to ice-margin fluctuations documented from the Irish Sea Basin and northwestern Ireland and record three near-synchronous fluctuations of much of the British–Irish Ice Sheet margin during the last deglaciation, suggesting a common response to regional climate forcing.


This paper intends to argue that there are two inherent challenges and dilemmas that may incapacitate rising calls to develop a distinguished cohort of researchers at universities, including CUT. Firstly, it seems the episteme knowledge-base in research of the current cohort of staff members does invite a look in askance as to its depth and breadth. Do we sufficiently exude competence to develop budding researchers of note? Secondly, and deducing from my informal interviews and discussions with B.Ed Honours students since 2006; we somewhat fall short as lecturers to model the quintessential research expertise necessary to develop the students' phronetic research experiences - the success of which would reconcile with their practical reality in their diverse teaching and learning situations and circumstances.
How then do we build a research capacity that catapults us from this somewhat research doldrums in the School of Teacher Education at CUT to become a School of Teacher Education recognised nationally and internationally as a School of Teacher Education which is enveloped in the validity and reliability of generating quality research?
This paper explores various "givens' and "intellectual needs." And, quite academically, may rumble about conceptual and perceptual impediments and hurdles which under-gird the laborious exercise of undertaking research; though fulfilling to academic autarkical pride when done excellently.


This book provides the most comprehensive survey of contemporary Palestinian art to date. The development of contemporary practice, theory and criticism is understood as integral to the concomitant construction of Palestinian national identities. In particular the book explores the intricate relationship between art and nationalism in which the idea of origin plays an important and problematic role. The book deconstructs the existing narratives of the history of Palestinian art, which search for its origins in the 19th century, and argues that Palestinian contemporary art demonstrates pluralistic, politically and philosophically complex attitudes towards identity and nation that confound familiar narratives of origin and belonging. The book builds upon theories of art, nationalism and post-colonialism particularly in relation to the themes of fragmentation and dispersal. It takes the Arabic word for Diaspora Shatat (literally broken apart) as a central concern in contemporary understanding of Palestinian culture and develops it, along with Edward Said's paradoxical formula of a 'coherence of dispersal' as the organising concept of the book. This aspect of contemporary Palestinian art is peculiarly suited to the conditions produced by the globalisation of art and we show how Palestinian artists, despite not having a state, have developed an international profile.


The Mechanistic Empirical Pavement Design Guide (M-E PDG) provides a number of new approaches for characterizing materials to be used in 21st Century pavement design. The M-E PDG software uses numerical models to analyze traffic, climate, subgrade and laboratory measurements of material properties to predict the performance of various pavement designs over their entire service life. A key element of the mechanistic design approach is the prediction of the response of the pavement materials, and thus of the pavement itself. The M-E PDG provides three hierarchical input levels: Level 1 is site/project specific with actual tests resulting in higher accuracy, Level 2 from less than optimal testing or by correlations and Level 3 from the agency database or user selected default values. Since obtaining Level 1 material inputs require considerable testing effort and cost, Level 1 data for M-E PDG analysis may not be possible all the times. In such situations, Level 2 or 3 inputs can still be used to perform M-E PDG analysis and predict design life of pavement. The objective of this study is to compare M-E PDG predicted distresses of different input level data from a recently constructed Continuously Reinforced Concrete Pavement (CRCP) project at I-64 Battlefield blvd, Chesapeake, Virginia. The original design of this pavement was done using the 93 AAHSTO design method several years before the construction. This paper also documents the efforts associated with the laboratory and field procedures used for level 1 input characterization. The FHWA Mobile Concrete Laboratory (MCL) had performed all the concrete materials characterization for level 1 input on this project. M-E PDG software (version 1.1) is used to obtain the predicted distresses for the pavement structure using the same thickness obtained by AASHTO method. This paper also discusses the difference in predicted distresses when level 1 and level 3 traffic data was used. Results shows that there were significant differences in predicted distresses between Level 1 and Level 3 concrete properties inputs for M-E PDG analysis depending upon the type of Level 3 input used.


Computing Science is a science of constructive methods. The solution of a problem has to be described formally by constructive techniques, if it is to be evaluated on a computer. The Marktoberdorf Advanced Study Institute 1988 presented a comprehensive survey of the recent research in constructive methods in Computing Science. Some approaches to a methodological framework and to supporting tools for specification, development and verification of software systems were discussed in detail. Other lectures dealt with the relevance of the foundations of logic for questions of program construction and with new programming paradigms and formalisms which have proven to be useful for a constructive approach to software development. The construction, specification, design and verification especially of distributed and communicating systems was discussed in a number of complementary lectures. Examples for those approaches were given on several levels such as semaphores, nondeterministic state transition systems with fairness assumptions, decomposition of specifications for concurrent systems in liveness and safety properties and functional specifications of distributed systems. Construction methods in programming that were presented range from type theory, the theory of evidence, theorem provers for proving properties of functional programs to category theory as an abstract and general concept for the description of programming paradigms.


Assimilating soil moisture from satellite remote sensing into land surface models (LSMs) has potential for improving model predictions by providing real-time information at large scales. However, the majority of the research demonstrating this potential has been limited to datasets based on either airborne data or synthetic observations. The limited availability of satellite-retrieved soil moisture and the observed qualitative difference between satellite-retrieved and modeled soil moisture has posed challenges in demonstrating the potential over large regions in actual applications. Comparing modeled and satellite-retrieved soil moisture fields shows systematic differences between their mean values and between their dynamic ranges, and these systematic differences vary with satellite sensors, retrieval algorithms, and LSMs. This investigation focuses on generating observation operators for assimilating soil moisture into LSMs using a number of satellite–model combinations. The remotely sensed soil moisture products come from the Tropical Rainfall Measuring Mission (TRMM) Microwave Imager (TMI) and the NASA/Earth Observing System (EOS) Advanced Microwave Scanning Radiometer (AMSR-E). The soil moisture model predictions are from the Variable Infiltration Capacity (VIC) hydrological model; the 40-yr European Centre for Medium-Range Weather Forecasts (ECMWF) Re-Analysis (ERA-40); and the NCEP North American Regional Reanalysis (NARR). For this analysis, the satellite and model data are over the southern Great Plains region from 1998 to 2003 (1998–2002 for ERA-40). Previous work on observation operators used the matching of cumulative distributions to transform satellite-retrieved soil moisture into modeled soil moisture, which implied perfect correlations between the ranked values. In this paper, a bivariate statistical approach, based on copula distributions, is employed for representing the joint distribution between retrieved and modeled soil moisture, allowing for a quantitative estimation of the uncertainty in modeled soil moisture when merged with a satellite retrieval. The conditional probability distribution of model-based soil moisture conditioned on a satellite retrieval forms the basis for the soil moisture observation operator. The variance of these conditional distributions for different retrieval algorithms, LSMs, and locations provides an indication of the information content of satellite retrievals in assimilation. Results show that the operators vary by season and by land surface model, with the satellite retrievals providing more information in summer [July–August (JJA)] and fall [September–November (SON)] than winter [December–February (DJF)] or spring [March–May (MAM)] seasons. Also, the results indicate that the value of satellite-retrieved soil moisture is most useful to VIC, followed by ERA-40 and then NARR.


Abstract. Increased concentrations of aerosol can enhance the albedo of warm low-level cloud. Accurately quantifying this relationship from space is challenging due in part to contamination of aerosol statistics near clouds. Aerosol retrievals near clouds can be influenced by stray cloud particles in areas assumed to be cloud-free, particle swelling by humidification, shadows and enhanced scattering into the aerosol field from (3-D radiative transfer) clouds. To screen for this contamination we have developed a new cloud–aerosol pairing algorithm (CAPA) to link cloud observations to the nearest aerosol retrieval within the satellite image. The distance between each aerosol retrieval and nearest cloud is also computed in CAPA. Results from two independent satellite imagers, the Advanced Along-Track Scanning Radiometer (AATSR) and Moderate Resolution Imaging Spectroradiometer (MODIS), show a marked reduction in the strength of the intrinsic aerosol indirect radiative forcing when selecting aerosol pairs that are located farther away from the clouds (−0.28±0.26 W m−2) compared to those including pairs that are within 15 km of the nearest cloud (−0.49±0.18 W m−2). The larger aerosol optical depths in closer proximity to cloud artificially enhance the relationship between aerosol-loading, cloud albedo, and cloud fraction. These results suggest that previous satellite-based radiative forcing estimates represented in key climate reports may be exaggerated due to the inclusion of retrieval artefacts in the aerosol located near clouds.


Study. Practice. Review. Approach the new 2009 CompTIA A+ exam with confidence The CompTIA A+ certification is the industry standard in terms of measuring a technician's hardware and software knowledge. As the most popular entry-level certification, it is particularly popular among individuals switching from another career to computers. This kit features a trio of essential titles for anyone planning to take the 2009 CompTIA A+ certification exam CompTIA A+ Complete Study Guide, 2E: Provides clear and concise information on crucial hardware and operating system maintenance, as well as real-world examples CompTIA A+ Complete Review Guide: An ideal companion learning tool that is broken into two parts; the first corresponds to A+ Essentials (220-701) while the second part corresponds to the IT technician's experience PC Technician Street Smarts, 2E: Focuses on the most common and challenging tasks PC technicians must face-and best practices for handling these tasks With this complete certification kit, you'll be completely ready to take the new CompTIA A+ exams!


The frequency and level of cellular and humoral responses to seven synthetic peptides from asexual blood stages of Plusinodium falciparirnt were measured in two cohorts of children living in areas highly endemic for malaria in Gabon and Cameroon. A prospective longitudinal study was conducted for one year in these sites to examine the relationship between specific in vitro immune responses and susceptibility to clinical malaria. Clinical protection was related to high proliferative responses (merozoite surface antigen-1 (MSA-11 and MSA-2 peptides) as well as to elevated antibody levels (schizont extract, MSA-2, and rhoptry-associated protein-1 (RAP-11 peptides) in the village of Dienga, Gabon. Higher response rates of interferon-y but lower response rates of tumor necrosis factor- a to four and six peptides, respectively, were observed in Dienga than in Pouma that were independent of the older age of the Gabonese children. Age accounted only for the higher prevalence rate in Dienga of the antibody responders to the peptide from Pfl55king-infected erythrocyte surface antigen (RESA). Our results support the inclusion of epitopes from MSA-1, MSA-2, RAP-1, and Pfl55/RESA antigens in a subunit vaccine against malaria, but show that a longitudinal clinical, parasitologic, and immunologic study conducted according to identical criteria in two separate areas may lead to contrasting observations, demonstrating the geographic limitation of the interpretation of such results.


The proliferation of small arms and light weapons has been a concern for many during the last decade. Nongovernmental organizations and governments have been working hand-in-hand to deal with the issue. Governments are responsible for the safety and security of their citizens and thus change and enforce policy to adapt to our ever-evolving world. Non-governmental organizations assess impact and responses; as representatives of civil society they monitor the state and suggest policy changes to facilitate a safer environment. Should the situation arise where the general public perceives the state as being unable to carry out its duty to protect them, the populace may try to protect itself. One of the main occurrences shaping a community's perception of insecurity is needless violence during crime.


We propose and demonstrate a new type of degree-of-polarization (DOP)-based differential-group-delay (DGD) monitor using an optical filter such that the DGD monitoring range and DOP dynamic range are dramatically increased. We apply this technique to varying pulsewidth return-to-zero (RZ), carrier-suppressed RZ (CSRZ), and alternate-chirped RZ (ACRZ) signals and show that by optimally setting the position, bandwidth, and shape of a filter, we can double the DGD monitoring range compared to traditional DOP-based DGD monitors. Using our technique, the DGD monitoring ranges for 10, 20, and 40 Gb/s /spl sim/12.5-ps pulsewidth RZ signals are increased by 32, 33, and 12 ps, respectively. We also show that a narrow-band optical filter, offset from the center of the optical spectrum by the bit-rate frequency, can double the dynamic range of DOP-based DGD monitors for non-RZ (NRZ) signals.


Although scholars have long studied why presidents "go public" on a host of topics, no research has specifically investigated presidential statements about Supreme Court cases. To examine this significant issue, we have cataloged the number of times presidents have commented publicly on Supreme Court cases from the Eisenhower to Obama administrations. We posit that presidents discuss judicial decisions primarily to assist in their pursuit of policy and reelection goals, and to enhance their historical legacy. Our empirical findings lend support to our expectations, revealing that reelection years, media attention to the Court's decisions, and partisanship shape the volume of monthly presidential remarks on Supreme Court cases. Taken as a whole, this research contributes to our understanding of presidential speechmaking, executive-judicial branch interactions, and the methods presidents use to implement Supreme Court decisions.


This article examines the efforts of the Amazigh (Berber) identity movement during the last 7 years to redefine the content of North African states' collective national identities, and the responses of state and other societal actors during a period of renewed political contestation. In highlighting the increasingly charged and contested political environment in North Africa, it argues that (a) the Berber-Amazigh identity movement has registered important symbolic achievements, (b) translating these symbolic achievements into concrete ones remains enormously difficult, and (c) the discourse and praxis of the Amazigh current has become increasingly militant, and even ethnonational.


Combining the shaded relief topography model and the slope map from the Digital Terrain Model (DTM) images, topographical map, field occurrences and petrography, the volcanic sequences of the Huangtsuishan Volcano Subgroup (HVS) can be constructed. Two types of volcanic centers can be identified in this area. One is the Tachienhou volcanic dome, which may be located in the center of an older caldera. The other is the Huangtsui composite volcano, which is composed of interbedding lava flows and pyroclastic deposits with a volcanic crater named the Huangtsui pond at the summit. Eight lava plateaus radiated from Mts. Huangtsui and Tachienhou to the north and the east can be distinguished based on the DTM images. The volcanic deposits are comprised of four lithofacies, the lava flows, pyroclastic breccias, tuffs and lahars on the base of field occurrences. At least thirteen layers of lava flow, named the H1 to H13 can be recognized in the HVS and can be reconstructed and categorized into four stages. An old and large volcano erupted lava flows to form the products of stages one and two, then collapsed to form a caldera with a dome for the third stage. The latest stage of lava flow was poured out from the Huangtsui volcano, which formed a crater at the summit.


This article presents an overview of the changes that took place in the syntactic use of the quantifiers ea and oait "ever" between 1250 and 1800 on the basis of the Frisian Language Corpus. Occurrences of Frisian ea and oait "ever" were classified and counted depending on the type of syntactic construction in which they were found. The constructions which were distinguished tend to correlate with the interpretation which the quantifier receives. This classification was performed for three main periods of the language: 1250–1550; 1550–1700; 1700–1800. It turns out that these periods saw some significant changes in the use of these quantifiers. Special attention is given to the peculiar behaviour of ea "ever" in relative clauses. It turns out that it displays properties both of free choice items and of negative polarity items. Furthermore, Frisian turns out to have been affected by language contact with Dutch at quite an early date, around 1700, when it borrowed oait to replace native ea . This change is analyzed as a case of reinforcement in the sense of Hopper & Traugott (2006). Our overall analysis supports a construction-specific analysis of changes in the use of quantifiers.


There are numerous techniques that can be used for the decoration of polymeric substrates,
dye sublimation, self-colouring, paint spraying, granular injection paint technology, pad
printing, in-mould decoration and hot foil stamping. Dye sublimation was selected for this
research as it was found to be both the most relevant technology area for IDT Systems
Limited and the least understood. It is a customisable digital process which uses specialist
Cyan, Magenta, Yellow and Black (CMYK) inkjet-able dyes that are transferred into a
substrate via a carrier. During the process heat is applied which transforms the dyes from a
solid into a gas phase. Analysis of literature identified a number of knowledge gaps, which
are addressed during this research and detailed in this report.
Initial experimentation concluded that the sublimation dyes can penetrate a range of
commercially available amorphous polymers, comparably to semi-crystalline types. These
findings dispute previously published work, but these also lacked rigorously recorded
methodologies to confirm comparable data. All of the materials, equipment and
methodologies used throughout this research were therefore developed in this report.
Further detailed experimentation was completed, using amorphous polycarbonate, (PC) and
semi-crystalline polybutylene terephthalate, (PBT) focusing on the process time and
temperature to understand their influence on the level of dye penetration. The results
revealed that increasing the process temperature and time improves the level of dye
penetration and that comparable penetration levels were noted at 140-180 oC. Further
research identified the importance of free volume in the polymer, this increases in size and
connectivity as temperature increases above the glass transition points. Additional
experimentation confirms that the free volume enables the dyes to penetrate into the
polymer.
Characterisation of the CMYK sublimation dyes was completed using Differential Scanning
Calorimetry enabling the thermal transitions to be identified. Visual experimentation
confirmed that the dyes start and finish sublimation between 145-210 oC.
As no software tool existed to visualise the dye penetration, one was developed using
MatLab. The tool imports and then interpolates the data and graphically outputs it for the
user. This allows a quicker set up time of the process and reduces the number of samples to
be destroyed.
As a direct result of the innovations described in this report, the industrial sponsor has
benefited with an increase in commercial exploitation. Aspects of this research have been
published, presented and a patent has been published, details are provided within.


For interested readers who have other vocational plans, its authors-experienced researchers themselves-provide an intimate view of the way professional scholars go about their specialized and challenging tasks. This extensively revised Fourth Edition takes full account of recent developments that have virtually revolutionized certain important areas of the discipline. The computer, as newly written pages demonstrate, not only has eliminated much of the drudgery formerly associated with the gathering, storage, and retrieval of raw data but has made possible many analytical and lexical operations that had been beyond human capacity, yet without diminishing the amount of sheer brain work still required to produce a genuine contribution to knowledge. The book also suggests that "traditional" literary studies, freshly evaluated, are compatible with the current emphasis on critical theory, not inimical to it. The ongoing revision of the literary canon under the impact of women's studies, African-American studies, and other movements, as well as the intensified scholarly and critical interest in present-day writers, is reflected in the book's hundreds of illustrative examples, extensive lists of several related books and articles, and hands-on exercises. The exercises range from the simple, short answer type that offer practice in the use of secondary materials such as can be found in any college library, to projects that may occupy a number of weeks of research in primary sources and are geared to the extensive holdings of large university libraries. The basic rationale and structure of the book, having proved themselves in previous editions, remain unchanged. The first half outlines the principles underlying the critical examination of evidence and describes in detail the chief branches of literary inquiry. Further chapters offer practical advice on bibliographical procedure and note-taking, particularly as these are made more efficient by electronic aids, and on the writing of scholarly papers (in one of the best discussions of the craft of expository prose t be found in any textbook); guide the student through the great American and British libraries whose stocks of books and manuscripts are indispensable to original literary research; and reviews the rewards, obligations, and ethics of the profession.


: Control methods based on regressor matrix and vector of uncertain variables, are the common approaches in control of nonlinear systems that are successfully extended to mobile robot control applications. To establish the controller in regressor based approaches, rewriting the process model in the parameterized form of regressor with uncertainties is essential. Evidently, this main drawback became a motivation for development of the regressor free control strategies. Controller design principle of the regressor free approaches are based on good estimation of the unknown dynamics by function approximation techniques (FAT). In this study, the systematic trajectory-tracking dynamic control design of nonholonomic mobile robot using (FAT) approach is illustrated. The robot dynamics is estimated using Fourier series approximation using variety of orthogonal basis functions such as Bessel, Laguerre, Chebyshev, and Legendre orthogonal basis functions. The function approximated dynamic of the system compliance with stability requirements is directly used in trajectory tracking control design of nonholonomic mobile robot. The results of the proposed method is compared with the inverse dynamic control method, two main regressor based adaptive inverse dynamics, and passivity based adaptive control approaches. The impressive quality of the performance of FAT based control algorithm is presented .


Late disclosure of the large scale of sterilization practices in the Nordic countries created an outburst of scandal: did these policies rely on coercion? To what extent? Who in the end was responsible? Sterilization practices targeted underpriviledged people first. The mentally retarded and women were their first victims. Operations were very frequently determined by other people's manipulative or coercive influences. Should the blame be put on the Social-Democrats in power throughout the period (except in Finland and Estonia)? Apart from Denmark, perhaps, local physicians and local services, more than governments, seemed to have strongly supported sterilization practices. Teetotalers and feminists shared responsibilities. How can one explain that eugenics finally declined? Based on a sound application of the Hardy-Weinberg law, the science of the eugenicists was correct. Was it politics? But uncovering of the Nazi crimes had only a very small impact on eugenics. Some authors underline the fact that the Nordic scientific institutions were particularly suited to liberal values. Others point to the devastating effect on eugenics once hereditarist psychiatry fell from favour in the middle of the sixties.


Employing tools drawn from economics and urban studies - particularly agglomeration economics, public choice, and the wisdom of Woody Allen's classic film Annie Hall - this essay provides a theoretical explanation for the prevalence of big city political corruption. The essay argues that the reason we see more government corruption in big cities than in other jurisdictions is that they are largely immune to the traditional cures for corruption, exit and voice. The location decisions of big city residents are, under dominant theories of urban economic theory, sticky in the face of bad governance, reducing the effect of inter-jurisdictional competition on the behavior of officeholders. Further, big cities rarely if ever see real partisan competition, leaving under-informed voters without the tools to punish all but the worst forms of unresponsive or corrupt governance. Traditional remedies - ranging from encouraging exit to non-partisan elections - either do not solve the problem or create substantial costs of their own. The essay concludes by arguing that election laws in cities should be reformed in order to encourage the development of political parties that are differentiated on local issues. Alternatively, cities should provide voters with locally specific party-like heuristics by allowing prominent elected officials like Mayors to endorse other local officials on the ballot. This would improve local democracy, and thereby address the root causes of urban political corruption.


T cell immunoglobulin and mucin-4 (TIM-4), mainly expressed on antigen presenting cells, plays a versatile role in immunoregulation. CD1d-restricted invariant natural killer T (iNKT) cells are potent cells involved in the diverse immune responses. It was recently reported that recombinant TIM-4 (rTIM-4) alone enhanced cytokine production in NKT hybridoma, DN32.D3 cells. Hence, we hypothesized that TIM-4 might regulate iNKT cell biology, especially their function of cytokine secretion. For the first time, we identified that TIM-4 was expressed in thymus iNKT cells, and its expression increased upon iNKT cell migration to the secondary lymphoid organs, especially in lymph nodes. Using TIM-4-deficient mice, we found that lack of TIM-4 did not disturb iNKT cell development, maturation, peripheral homeostasis and cytokine secretion. Moreover, TIM-4 deficiency did not alter the polarization of iNKT sublineages, including NKT1, NKT2 and NKT17. Finally, the mixed bone marrow transfer experiments further confirmed normal iNKT cell development and function from TIM-4-deficient bone marrow. In conclusion, our data suggest that TIM-4 is expressed on iNKT cells but dispensable for their development and function.


Of the numerous structurally-controlled, sediment-hosted Cu deposits throughout the
Proterozoic Western Fold Belt of the Mt lsa lnlier, the two most significant are the giant Mt
Isa Cu deposit (255 Mt @ 3.3% Cu) and the Mammoth deposit (16.8 Mt @ 3.4% Cu). The
deposits are hosted in deformed Proterozoic sediments that range in age from 1740 to 1652
Ma. Copper mineralisation is hosted in breccias and veins, which appear to be fault
controlled and is interpreted as occurring approx. 150 Ma after deposition of the host rocks
during regional deformation (1590 to 1500 Ma; Isar) Orogeny). The Mammoth deposit is
located approximately 115 km to the north of Mt lsa, and copper mineralisation is hosted
within the Palaeoproterozoic Whitworth Quartzite of the Myally Subgroup. Understanding
the local geological and geochemical controls at Mammoth will assist in the development of
a genetic model and exploration targeting of similar deposits in ancient, structurally
deformed, sedimentary basins in Australia and elsewhere in the world.
Structural studies using orientation and kinematic data from mineralised veins and bounding
faults have provided a new understanding of the mechanisms that localised Cu
mineralisation at the Mammoth deposit. The Mammoth deposit formed during E-W
transpression localised at the intersection of the Mammoth and Portal Faults during periods
of high fluid pressure (Pf), subsequent to slip episodes, when the principle stresses were
sub-equal (0.3 :+.- cs2 al ). Dilation was achieved when fluid pressure (PO exceeded the tensile
strength (T) of the host rock as indicated: 1) by the irregular development of syndeformational
quartz-Cu sulfide extensional veins; and 2) by the regular development of syndeformational
quartz-Cu sulfide extensional veins along bedding planes when a i a3 . The Mammoth deposit has 6 major ore lenses that extend over 1,100 metres vertically and
have a strike extent of 100 to 300 m and widths from 10 to 75m. Within these lenses, Cu
mineralisation is hosted in veins and breccias adjacent to the intersection of the Mammoth
and Portal Faults. A new textural classification scheme, consisting of five categories was
used to describe the variations of brecciation and fracturing of the Whitworth Quartzite during
hypogene mineralisation. The grade of Cu mineralisation in these units is variable, but is
high around zones of intense brittle deformation in the breccia units reflecting zones of
enhanced permeability. Wall rock alteration, replacement and cementation of the breccia
units by the hypogene mineral assemblage took place after and/or during the fragmentation.
Hypogene Cu mineralisation consists of chalcopyrite, bornite and chalcocite. Supergene
chalcocite (± covellite) has variably overprinted and enriched the hypogene assemblage.
Hypogene and supergene chalcocite within the deposit are texturally and paragenetically
distinct. A four stage paragenetic sequence has been defined across the Mammoth ore zones: Stage I) hypogene pyrite and quartz; Stage II) hypogene chalcopyrite, bornite,
chalcocite and carrollite (trace) + chlorite, illite and quartz; Stage III) supergene hematite,
chalcocite, covellite and wittichenite, and Stage IV) supergene kaolinite, chalcocite, covellite
and wittichenite. Hypogene Cu sulfides are broadly zoned within the Mammoth ore zones
from hangingwall to footwall and up dip. This zonation is: 1) Stage ll hypogene chalcocite ±
bornite; 2) Stage II bornite ± hypogene chalcocite and 3) Stage II chalcopyrite ± bornite.
Microanalytical trace element geochemistry of sulfide minerals from the Mammoth deposit
confirmed paragenetic interpretations. These investigations involved the development of a
new analytical technique to obtain high quality, sub-ppm, quantitative data from the in situ
microanalysis of sulfide minerals using laser ablation (LA) ICP-MS analysis. Pyrite,
chalcopyrite, bornite and both supergene and hypogene chalcocite were analysed. Stage III
supergene chalcocite is enriched in Bi and depleted in both Ag, Co, Sb, and As compared to
Stage ll hypogene chalcocite. No differences were detected in trace element composition
between disseminated and veined styles of Stage I pyrite. Stage I pyrite has elevated
contents of As, Co, Ni, Sb, and Pb compared to chalcopyrite, bornite and chalcocite. Bornite
is anomalously enriched in Bi compared to the other sulfides minerals The processes of meteoric and supergene alteration have led to complex geochemical
dispersion patterns overprinting geochemical patterns developed during hypogene
mineralisation. Whole-rock geochemistry analysis across the deposit revealed a distinct
metal zonation. Elevated Co, Ni, CaO and P205 contents form a narrow halo (4_ 2 to 5m) -
around the hypogene ore zones at Mammoth. Along the ore equivalent structural horizon
Zn, Co, and Ni are enriched distal (100 to 200m) to the ore zones. In contrast, Cu, Bi, As
and Fe, initially at or below detection, all increase with proximity to the ore zones.
Mineralised structures that have undergone supergene modification also have a similar suite
of trace elements (Cu, Pb, Zn, Ni, Bi, Sb, and As). Their level of enrichment is significantly
lower than their un-oxidised equivalent but more enriched than the enclosing host rocks.
These suites of trace elements form potential vectors to differentiate mineralised and unmineralised
structures and can be used to identify Mammoth style mineralisation in surface
or near surface leached structures.
Sulfur, 0 - D and Pb isotopic investigations allow characterisation of the ore fluids and
identification of potential metal source reservoirs. Lead isotopic ratios from Mammoth ore
samples lie along an isochron that originates from the Eastern Creek Volcanics at 1540 Ma,
indicating that the Eastern Creek Volcanics were the source of Pb, and by inference Cu,
contained in the Mammoth deposit. The 6 34S values of Stage I pyrite (- 15 to - 7 %o; mean =
— 12 %o) and Stage II Cu and Cu-Fe sulfides (— 19 to — 1 %o; mean = - 8 °/00) supports the
conclusion that the Eastern Creek Volcanics were the source of metals and sulfur as they
represent the only probable source of light sulfur in the Western Fold Belt. The calculated
8180 and 6D fluid composition in equilibrium with Stage I quartz and Stage ll chlorite yielded
a range of — 10 to -2 Too 6 180 and —2 to + 11 Too 8 180 and —41 to —56 %o 8D respectively.
These values suggest the fluid had two end members: 1) dominantly meteoric fluid and 2)
fluid originating from metamorphic processes.
Geological, isotopic, paragenetic, geochemical and structural data suggest the Mammoth Cu
deposit formed synchronous with regional deformation when channelised flow of hot salineoxidised
Cu-enriched fluid generated by metamorphic devolatilisation, leached Cu and S
from the Eastern Creek Volcanics, and was focussed along the Esperanza, Mammoth and
Mammoth Extended Faults. Upon reaching the Whitworth Quartzite, a build up of fluid
pressure combined with the existing regional stress field, created the appropriate conditions
for brittle failure in the quartzite forming dilational sites for sulfide precipitation. The hot
metal and sulfur-bearing fluid mixed with a deep circulating methane-bearing hydrothermal
fluid originally of meteoric origin. Changes in the physicochemical conditions upon this
mixing destabilise the metal chlorine complexes resulting in sulfide precipitation. All of these
attributes cumulatively broaden the classification of the metamorphogenic style of Cu
deposit. Most notable of which is that the Mammoth deposit provides evidence that
metamorphogenic Cu deposits can be hosted in host rocks other than meta-carbonates.
This new model for the genesis of the Mammoth deposit has developed new criteria for the
exploration of similar resources in the Western Fold Belt; including the world class Mt Ise Cu
deposit. The exploration strategy currently in use throughout the Western Fold Belt of the Mt
Ise Idler has traditionally focused on sites where structural geometries potentially gave rise
to dilatational fault jogs during deformation. This research provides evidence that structural
geometries that had the potential to create zones of E-W compression and/or N-S extension
should now be included in exploration targeting.


In this study, the reaction between Co(III)-EDTA and hypophosphite ion, catalyzed by Pd(II), was chosen as the indicator reaction. The inhibition kinetics of this catalytic reaction were investigated in the presence of iodide ion and the possibility of its analytical application was evaluated. Catalyzers other than PdCl2 (Pt, Au and Ni salts) were assayed for the indicator reaction and it was observed that these catalysts have no effect on the reaction. The important variables that affected the reaction rate were investigated and the optimum conditions giving maximum sensitivity were established. The calibration graph, prepared following the inhibition kinetic method, gave a curve exhibiting a linear relationship (r = -0.9878) between the initial rate and iodide concentrations up to 35 ng.mL-1 I-. Iodide was quantitatively be determined in the range 2-35 ng.mL-1I- with a detection limit of 1.2 ng.mL-1 I- (3Sb/m criterion). The RSDs of the method (n = 5) for 7 and 14 ng.mL-1 are 1.19 and 0.81%, depending on the iodide concentration, respectively. The reaction was monitored spectrophotometrically by measuring the change in absorbance over time at 540 nm. Iodide in trace amounts had a strong inhibitory effect under optimum conditions. The possibility of the estimation of trace amounts of iodide based on its inhibitory effect was investigated. The method was applied to the determination of iodide in water, urine, table salt and some drug samples, and was compared with the modified Sandell-Kolthoff method. The determination of the iodide content of biological fluids is important both in malnutrition conditions and in metabolic and epidemiological studies of thyroid diseases. The main advantage of this proposed method for the determination of iodide in urine samples is that it does not necessitate an additional pretreatment step. The quantitative method developed, based on inhibition kinetics, is practical, fast and economical. For this reason, it is a technique open to research for the development of application fields (chemistry, biochemistry, environmental, pharmaceutical chemistry etc.).


Like any citizen, a victim of domestic violence (DV) may call the police for help when she needs it. And yet, when a victim calls the police, she not only seeks law enforcement assistance but also invokes her constitutional right to seek one of the most fundamental services the government can provide-protection from harm. That right, recently described by the Supreme Court as "essential to freedom," is the right "to petition the Government for a redress of grievances" guaranteed by the First Amendment.This Article argues that a combination of law and policy initiatives produces negative collateral consequences for DV victims that flow directly from calling the police, thereby creating an impediment to the right of victims to petition. The vast majority of DV victims do not report the violence to the police. Feminist legal scholars and policymakers widely acknowledge that this underreporting is a major roadblock to the justice system's ability to effectively address DV.The underreporting problem is most severe with battered mothers. In many jurisdictions across the country, police report battered mothers to Child Protective Services (CPS) as a matter of course, without any investigation of actual risk to the child. The practice serves a wellintentioned goal: by referring all DV cases to CPS, the police bring to the attention of the state at-risk children who might otherwise fall under the radar. However, given the notorious treatment of DV victims and their children by CPS, a significant number of victims choose not to call the police at all, for fear of having their children taken away.In addition to the chilling effect on victims' calls for help, a sweeping practice of reporting all DV calls to CPS inundates the agency with reports it must, by law, investigate. In the last decade, 60 percent of the reports made each year were unsubstantiated. While an across-the-board, "reportall" policy may be motivated by a praiseworthy goal, a reporting practice that produces fewer, but more accurate, referrals to CPS would provide greater protection to children. The Petition Clause requires as much.This Article lays out the claim that these systemic barriers to reporting DV create such a significant impediment to calling the police that they violate the right to petition. It first defines the right to petition, reviews its history and purpose, and demonstrates that it has been overshadowed by, and confused with, the right to speech. Building on the growing body of scholarly literature suggesting that this should not be so, the Article shows that, while the rights of speech and petition overlap, they are not coextensive. Judicial analysis of the right to petition should not be identical to that of speech. Rather, in evaluating petition claims by DV victims, the courts should apply strict scrutiny analysis: only by proving a compelling state interest and the use of the least restrictive means for achieving that interest should government policies that infringe upon a victim's right to call the police survive. Furthermore, even under a less-than-strict level of scrutiny, the report-all practice should be unconstitutional. The Article concludes by identifying other government practices that deter victims' reports that might implicate the Petition Clause. It then discusses the broader, political implications of viewing a call to the police as an invocation of a constitutional right to petition and makes the case that the right to petition has as of yet untapped potential for feminist legal scholars and policymakers addressing DV.


In this 21 st century of unprecedented global, national and regional threats and innovative technologies, this study underscores the unique authentic transformational leadership challenges posed in emergency management systems. These open complex systems adapt to a range of critical emergency events, including mass emergencies, disasters and catastrophes. This qualitative research study based on grounded theory examines the phenomenology of emergency management systems by deploying triangulation to isolate the particular theoretical underpinnings of authentic transformational leadership models relevant to this domain. Using a key informant approach and a semistructured confidential questionnaire, the perspectives of 103 emergency, health care and technological leaders of diverse professional backgrounds on the challenges of emergency management systems are presented. The response rate was 83.5 percent from 81 organizations across Canada. This study underscores the need for authentic transformational leadership and identifies seven critical and specific leadership imperatives for this domain. The implications for hospital and health care administrators are also presented. This qualitative study of diverse emergency system leaders is original in that it has not hitherto been done across Canada nor internationally. This study underscores the relevance of leadership theory and principles in the extant literature, but extends this to highlight those that are critical and unique to leaders of emergency management systems. In so doing, calls on the need for authentic transformation leadership of an order and caliber yet to be fully potentiated to manage future emergency events in Canada.


This thesis explores the theory that International Humanitarian Non-governmental Organisations (IHNGOs) have increasingly become part of the world-ordering security agenda of developed western states since the end of the Cold War. It argues that the adoption of humanitarian aid and development activities by intervening military forces in Afghanistan, criticised by IHNGOs for blurring the boundaries between humanitarian and military actors, is a symptom of, rather than the central reason for, reduced humanitarian space in Afghanistan. This study contends that the central issue is the wider integration of political, military and humanitarian action into the process of state-building as a way to pacify areas of conflict and instability that otherwise present potential security threats to the developed world. This has become even more pronounced with the aims of the Global War on Terror (GWOT) since 2001.

The merging of humanitarian aid and development with security in the pursuit of stable states has occurred as an international response to the humanitarian crises and intra-state wars since the end of the Cold War. Military involvement of this kind is typified in Afghanistan by Provincial Reconstruction Teams (PRTs) that combine security and development action. During the 1990s humanitarianism also underwent a metamorphosis as concern about the role aid could have in fuelling conflict and a desire to ameliorate the underlying causes of poverty and conflict led many aid agencies to adopt a new vision of humanitarianism that had political and social goals beyond those of just meeting the immediate needs of populations in crisis. Another feature of humanitarian interventions of the 1990s was the ambitious expectations placed upon IHNGOs and intervening military forces from the international community to manage or resolve these crises without a corresponding level of long-term political, economic and military commitment. These issues are also present in post-2001 Afghanistan where IHNGOs initially supported an international intervention and a new government which has since been faced with a growing insurgency. Consequently, involvement with state-building, governance, rights and development have placed IHNGOs at odds with the insurgents.

A case study approach is used to examine five major IHNGOs and how they fit into the context of the international state-building project in post-2001 Afghanistan. The central finding of this study is that the integration of humanitarian aid and development into state-building as a means to enhance international security has seriously compromised the claims to the principles of neutrality, impartiality and independence central to the concept of humanitarian space and consequently the security of the IHNGOs in the ongoing Afghanistan conflict.

To overcome these problems this study suggests that IHNGOs should place their humanitarian aid activity under a separate umbrella organisation that operates under the neutral, impartial and independent principles adhered to by the International…


Recent work on quantum annealing has emphasized the role of collective behavior in solving optimization problems. By enabling transitions of large clusters of variables, such solvers are able to navigate their state space and locate solutions efficiently despite having only local connections between elements. However, collective behavior is not exclusive to quantum annealers, and classical solvers that display collective dynamics should also possess an advantage in navigating a non-convex landscape. Here, we propose a simple model that demonstrates this effect, based on the recently suggested digital memcomputing machines (DMMs), which utilize a collection of dynamical components with memory connected to represent the structure of the underlying optimization problem. This model, when applied to finding the ground state of the Ising spin glass, undergoes a transient phase of avalanches which can span the entire lattice. We then show that a full implementation of a DMM exhibits superior scaling compared to other methods when tested on the same problem class. These results establish the advantages of computational approaches based on collective dynamics.


Posterior sampling for reinforcement learning (PSRL) is a useful framework for making decisions in an unknown environment. PSRL maintains a posterior distribution of the environment and then makes planning on the environment sampled from the posterior distribution. Though PSRL works well on single-agent reinforcement learning problems, how to apply PSRL to multi-agent reinforcement learning problems is relatively unexplored. In this work, we extend PSRL to two-player zero-sum extensive-games with imperfect information (TZIEG), which is a class of multi-agent systems. More specifically, we combine PSRL with counterfactual regret minimization (CFR), which is the leading algorithm for TZIEG with a known environment. Our main contribution is a novel design of interaction strategies. With our interaction strategies, our algorithm provably converges to the Nash Equilibrium at a rate of $O(\sqrt{\log T/T})$. Empirical results show that our algorithm works well.


Summary and Conclusions
Certain antibiotics derived from various types of Streptomyces possess definite antimalarial properties. Against Plasmodium cathemerium in the canary, aureomycin and terramycin have marked prophylactic effect and even afford complete protection in some instances when administered for 10 days or longer. Aureomycin has a suppressive effect equal to that of quinine, and terramycin a relatively poor suppressive effect against the blood parasites. Chloramphenicol has a meager prophylactic and suppressive effect only in maximum tolerated doses. None of these drugs proved to be curative, either alone or in combination with quinine. Dihydrostreptomycin, neomycin, rimocidin, thiolutin, and two Brucella-active lyophilized broths were totally ineffective.
The same three antibiotics, aureomycin, terramycin, and chloramphenicol, show a suppressive effect in P. berghei infections in the white mouse. Aureomycin is again nearly equivalent to quinine, while terramycin and chloramphenicol both have rather low quinine equivalents of 0.16 and 0.17 respectively. Neomycin had no suppressive effect on P. berghei infections.
The marked prophylactic effect of certain of these antibiotics, confirming previous reports of such activity by others indicates further search for more effective preparations in this group. To our knowledge, causal prophylaxis is demonstrated by only two other compounds against P. cathemerium infections—metachloridine (Wiselogle, 1946) and Endochin (unpublished observations). As this type of antimalarial activity may be interpreted as bearing chiefly on the exo-erythrocytic forms of the parasite, there is a possibility that among the antibiotics or a combination of one of them with another antimalarial will be found a less toxic curative agent for vivax malaria.


A number of states have adopted a preference for voluntary hospitalization over involuntary civil commitment for adults with severe mental illness who require inpatient treatment. Frequently, however, the very disabilities that call for inpatient treatment also disrupt an individual patient's capacity to participate fully in the decision-making process by which hospital admission is elected. When impaired patients have a court-appointed guardian, difficult questions can arise as to the power of the guardian to consent to the ward's admission for inpatient psychiatric treatment. In some states, the guardian may not consent to the ward's admission. In others, the guardian's authority to arrange for voluntary inpatient care may depend on his or her obtaining specific court authorization. Additional requirements apply in other states, often created by the interplay between the laws regulating mental hospital admission and those governing the powers and responsibilities of guardians. Involuntary commitment statutes in virtually every state require that the individual must be dangerous to himself or herself or others. Voluntary hospitalization, by contrast, generally is based on the patient's need for and amenability to treatment. If a guardian is not permitted to consent to voluntary admission, the more restrictive involuntary commitment standard, with its dangerousness criterion in particular, may make it difficult or impossible to arrange for inpatient care for some patients with severe mental disabilities who do not present an imminent risk of harm, but who would benefit from such treatment. Patients who are assisted by guardians should be able to gain access to inpatient psychiatric treatment without running the gauntlet of involuntary civil commitment, if the substantive standards and procedural requirements put in place by state law can be made adequate to insure that third-party decision-makers are acting with respect for the values held by these patients and, to the extent possible, are seeking to serve their best interests. This Article provides a brief history of the law in this area, explores the role that informed consent plays in voluntary hospitalizations, provides an analysis of the interests in tension, and offers a framework for an effective statutory approach to the area.


Characterization of Light Weight Composite Proppants. (December 2008) Mandar Chaitanya Kulkarni, B.E., Sardar Patel University, India Chair of Advisory committee: Dr. Ozden Ochoa The research objectives are to develop experimental and computational techniques to characterize and to study the influence of polymer coating on the mechanical response of walnut shell particles to be used as proppants. E3-ESEM and Zeiss Axiophot LM are used to study the cellular microstructure and feasibility of polymer infiltration and uniform coating. Three main testing procedures; single particle compression, heating tests on coated and uncoated walnut shell particles and 3-point flexure tests are undertaken. In in-situ ESEM observations on both the coated and uncoated particles showed signs of charring at about 175 – 200 oC. Single particle compression test are conducted with random geometry particles and subsequently with four distinct shape categories to minimize the statistical scatter; flat top, round top, cone top, and high aspect ratio. Single particle tests on uniformly cut cuboid particles from walnut shell flakes are used to capture the nonlinear material response. Furthermore cyclic compression loads are imposed on flat top particles which reveal that significant permanent deformation set in even at low load levels. Computational models include Hertzian representation, 2D and 3D finite element models to simulate single coated and uncoated particles under compression. The elastic material with geometric nonlinear representation is not able to simulate the compression response observed during testing. The inelastic material representation is able to significantly improve the compression response and address the influence of geometric shape on particle response. A single uniform layer of polymer coat is introduced on the 3D models with nonlinear material definition. Coating provides a marginal improvement in load vs displacement response of the particles while increasing the ability of the particle to withstand higher loads.


Abstract Knowledge of climate variability is relevant and challenging to farmers, decision makers and the population in general. Ninety percent of Burkina Faso working population is engaged in agriculture which accounts for 39% of gross domestic product. Located in central Burkina, the basin has four dams, of which the most important Loumbila is managed for the capital's water supply. A change of climate may affect the water resources most likely and is expected to limit the access to sufficient quality water. In order to characterize climate variability and changes, long-term records of temperature and precipitation (1961 to 2012) were analyzed. By applying R-climdex and R, indices were calculated based on an approach recommended by the World Meteorological Organization Expert Team on Climate Change Detection and Indices. Four indices related to precipitation and other related to temperature were selected. Results show that signs of changing climate in Massili have already emerged including a slight decrease of total precipitation amount and also a delayed rainfall onset along with an earlier cessation resulting to a shorter rainfall period. Although the total precipitation decreased in the basin, occurrence of extremely wet days has slightly increased. The cold spell has decreased while warm spell has increased.


Partial flow rate operation of hydroturbines with constant pitch blades causes complex unstable cavitating flow in the diffuser cone. A particle image velocimetry (PIV) system allows investigating the flow velocity field in the case of a developing cavitation vortex, the so-called vortex rope, at the outlet of a Francis turbine runner. The synchronization of the PIV flow survey with the rope precession allows applying the ensemble averaging by phase technique to extract both the periodic velocity components and the rope shape. The influence of the turbine setting evel on the volume of the cavity rope and its centerline is investigated, providing a physical knowledge about the hydrodynamic complex phenomena involved in the development of the cavitation rope in Francis turbine operating regimes.

https://infoscience.epfl.ch/record/139263/files/Analysis of the Cavitating Draft Tube Vortex in a Francis Turbine Using Particle Image Velocimetry Measurements in Two-Phase Flow.pdf


This essay examines how securitization served as a new coupling rod joining cycles in real estate and banking markets and created a new pathway for financial contagion in the "subprime" financial crisis. Legal changes promoted the growth of securitization and improved this crisis transmission line. The essay examines the history of legislative and regulatory changes that facilitated bank participation in the markets for mortgage-backed securities. The essay then explains how securitization failed to mitigate the credit, liquidity, and interest rate risk associated with real estate when losses in residential markets became correlated nationwide. It then discusses how regulation contributed to this, as the spread of securitization and financial industry consolidation created a nationwide market for mortgages. The essay telescopes out from securitization to discuss an often overlooked danger of bank investments in real estate: the cyclicality of real estate losses. The essay analyzes the evidence that real estate prices exhibit positive serial correlation. It also summarizes historical evidence of the correlation between banking and real estate crises. The essay then looks at feedback mechanisms between banking and real estate markets, including research on bank leverage cycles.The essay next provides a very high level outline of various approaches to decoupling bank and real estate crises and the advantages and drawbacks of various approaches. These approaches include curbing bank investments in real estate and mortgage-backed securities, using bank regulations as a more surgical tool to fix problems with securitization, and developing countercyclical approaches to regulations of mortgage markets and bank investments in them. The essay then concludes by discussing the political dynamics that will shape and constrain any of these policy approaches.


File systems are fundamental for computers and devices with data storage units. They allow operating systems to understand and organize streams of bytes and obtain readable files from them. There are numerous file systems available in the industry, all with their own unique features. Understanding how these file systems work is essential for computer science students, but their complex nature can be difficult and challenging to grasp, especially for students at the beginning of their career. The Zion File System Simulator was designed with this in mind. Zion is a teaching and experimenting tool, in the form of a small application, built to help students understand how the I/O manager of an operating system interacts with the drive through the file system. Users can see and analyze the structure of a simple, flat file system provided with Zion, or simulate the most common structures such as FAT or NTFS. Students can also create their own implementations and run them through the simulator to analyze the different behaviors. Zion runs on Windows, and the application is provided with dynamic-link libraries that include the interfaces of a file system and a volume manager. These interfaces allow programmers to build their own file system or volume manager in Visual Studio using any .NET language (3.0 or above). Zion gives the users the power to adjust simulated architectural parameters such as volume and block size, or performance factors such as seek and transfer time. Zion runs workloads of I/O operations such as "create," "delete," "read," and "write," and analyzes the resulting metrics including I/O operations, read/write time, and disk fragmentation. Zion is a learning tool. It is not designed for measuring accurate performance of file systems and volume managers. The robustness of the application, together with its expandability, makes Zion a potential laboratory tool for computer science classes, helping students learn how file systems work and interact with an operating system.


The aim of study was to examine the effectiveness of PATHS program on children's and teachers' behaviors by evaluating perceptions of children and teachers in regard to their relationships with each other. The sample included 129 children (5-6 aged) and 28 teachers in the intervention group and 114 children (5-6 aged) and 30 teachers in the comparison group. The Classroom Atmosphere Rating Scale, the Teaching Style Rating Scale, Teacher Self Report Assessment, Head Start Competence Scale, Student–Teacher Relationship Scale-STRS, and Semi-Structured Play Interview were used to gather data. According to the results, teachers in PATHS classrooms were observed to be more competent in terms of quality of the classroom climate though there were no differences between social-emotional behaviors of children. While teachers' perceptions did not yield any differences in regard to their relationships with children, children in intervention classes described relationships with teachers significantly more positively than the others.


In this paper we report a novel application-basedmodel as a suitable alternative for the classification and identification ofattacks on a computer network, and thus guarantee its safety from HTTP protocol-based malicious commands. The proposed model is built on a self-recurrentneural network based on wavelets architecture with multidimensional radialwavelons, and is therefore suited to work online by analyzing non-linearpatterns in real time to self-adjust to changes in its input environment. Sixdifferent neural network based systems have been modeled and simulated forcomparison purposes in terms of overall performance, namely, a feed forwardneural network, an Elman network, a fully connected recurrent neural network, arecurrent neural network based on wavelets, a self-recurrent wavelet networkand the proposed self-recurrent wavelet network with multidimensional radialwavelons. Within the models studied, this paper presents two recurrentarchitectures which use wavelet functions in their functionality in verydistinct ways. The results confirm that recurrent architectures using waveletsobtain superior performance than their peers, in terms not only of theidentification and classification of attacks, but also the speed ofconvergence. DOI: http://dx.doi.org/10.5755/j01.itc.43.4.4626


Abstract Background/objectives: Extremes of birthweight (BW) have been associated with increased rates of metabolic risks. The objective was to study the prevalence of metabolic risks markers among obese and overweight (OW) subjects according to BW. Subjects/methods: A cross-sectional study was performed in a cohort of 1002 patients (2–18 years, 40.6% male) evaluated for OW or obese subjects in two private clinics. Anthropometrics, fasting lipids, glycemia, and insulin were obtained. Results: Of the subjects, 76.1% were born appropriate for gestational age (AGA), 10.9% small for gestational age (SGA), and 13% large for gestational age (LGA). Children born LGA presented a more severe degree of obesity compared with those born AGA and SGA (p<0.0001). No differences in glycemia, insulin, and lipid levels were detected among the groups. Abnormal glucose was found in 37 subjects: one with type 2 diabetes mellitus (from the previously glucose-intolerant subjects), 10 with glucose intolerance, and 27 with impaired fasting glucose. According to Boney criteria, 6.6% of the patients (6–18 years old) exhibited metabolic syndrome (MS) (69.4% AGA, 12.9% SGA, and 17.7% LGA). Conclusions: Being born LGA represents a higher risk of severe obesity. At this age, the most frequent component of MS was an abnormal lipid profile with low high-density lipoprotein and high triglycerides. Finally, the most frequent finding associated with abnormalities of glucose tolerance was a family history of diabetes. Thus, BW, lipid profile, and family history are mandatory when these patients are evaluated.


This paper presents analysis of power flow management in wind power and wave power. This paper proposed an integrated wind and wave power generation system fed to an ac power grid or connected with an isolated load using a dc microgrid using FUZZY controller. The proposed dc microgrid connects with a wind power generator through a voltage -source converter (VSC), a wave power generator through a VSC, an energy storage battery through a bidirectional dc/dc converter, a resistive dc load through a load dc/dc converter, and an ac power grid through a bidirectional grid - tied inverter. The studied integrated wind and wave system joined with the dc microgrid is modeled and simulated using MATLAB/Simulink model design reveals that the proposed integrated control system can maintain stable operation to supply power under different operating conditions using the proposed dc microgrid by varying duty ratios of individual converter and pitch angle of wind system is shown.


In European External Action Service, Mauro Gatti provides a legal analysis of the EU's 'foreign ministry' and assesses its capability to promote coherence in EU external relations.


Water availability is the most limiting factor to global plant productivity, yet photosynthetic responses to seasonal drought cycles are poorly understood, with conflicting reports on which limiting process is the most important during drought. We address the problem using a model‐data synthesis approach to look at canopy level fluxes, integrating twenty years of half hour data gathered by the FLUXNET network across six Mediterranean sites. The measured canopy level, water and carbon fluxes were used, together with an inverse canopy ecophysiological model, to estimate the bulk canopy conductance, bulk mesophyll conductance, and the canopy scale carbon pools in both the intercellular spaces and at the site of carboxylation in the chloroplasts. Thus the roles of stomatal and mesophyll conductance in the regulation of internal carbon pools and photosynthesis could be separated. A quantitative limitation analysis allowed for the relative seasonal responses of stomatal, mesophyll, and biochemical limitations to be gauged. The concentration of carbon in the chloroplast was shown to be a potentially more reliable estimator of assimilation rates than the intercellular carbon concentration. Both stomatal conductance limitations and mesophyll conductance limitations were observed to regulate the response of photosynthesis to water stress in each of the six species studied. The results suggest that mesophyll conductance could bridge the gap between conflicting reports on plant responses to soil water stress, and that the inclusion of mesophyll conductance in biosphere–atmosphere transfer models may improve their performance, in particular their ability to accurately capture the response of terrestrial vegetation productivity to drought.


Over the past few decades, several factors have contributed to what numerous revenue agencies and academic authors have characterized as a significant increase in tax avoidance activity. This paper considers both the causes of increased tax avoidance activity over the past several years as well as governmental responses to this phenomenon in key common law jurisdictions, notably Australia, Canada, New Zealand, the United Kingdom and the United States. Part 2 examines the concept of tax avoidance, distinguishing unacceptable or abusive tax avoidance both from illegal tax evasion on the one hand and acceptable tax planning or tax minimization on the other. Part 3 considers the causes of recent tax avoidance activity and its adverse effects for domestic tax systems. Part 4 reviews government responses to tax avoidance, examining both legislative reforms and administrative innovations. Part 5 considers whether these legislative and administrative measures are sufficient to the address the problem of tax avoidance in the 21st century, concluding that, although they can be expected to discourage some abusive tax avoidance, there is also much that remains to be done.


The widespread infusion of pro-market and business management principles into the public sector has impeded the behaviour of civil servants who are motivated by intrinsic motives, not external ones. Besides, the infusion of such principles caused great threats to basic values of the civil service, like equity, fairness, justice, accountability, impartiality, political neutrality, public welfare and other values related to the public sector. From here, public service motivation (PSM) emanates as a reaction against these principles/techniques in the civil service. PSM has been studied in different developed countries; however, it was almost ignored in developing countries, especially Arab states. This study focuses on two significant under theorized areas: the conceptualization of PSM in the Lebanese civil service, and the identification of an external dimension (political factors) and its role in facilitating or obstructing the development of this construct.


A new paradigm for automatic nonphotorealistic rendering (NPR) is introduced in this paper. Existing NPR approaches can be categorized in two groups depending on the type of input they use: image based and object based. Using multiple images as input to the NPR scheme, we propose a novel hybrid model that simultaneously uses information from the image and object domains. The benefit not only comes from combining the features of each approach, but most important, it minimizes the need for manual or user assisted tasks in extracting scene features and geometry, as employed in virtually all state-of-the-art NPR approaches. We describe a particular implementation of such an hybrid system and present a number of automatically generated pen-and-ink style drawings. This work then shows how to use and extend well developed techniques in computer vision to address fundamental problems in image representation and rendering.


The loss mechanisms and the behavior of secondary flows downstream of a large scale, linear turbine cascade have been investigated experimentally. A five-blade replica of the cascade used by Langston et al. at United Technologies Research Center was used for the present tests. Detailed flow measurements, using five-hole and three-hole probes, were made at four different planes, one just upstream of the trailing edge and the rest downstream. The secondary flow field at each measurement plane was found to be dominated by a single large passage vortex, which decayed in strength because of the mixing occurring in the flow. More than one-third of the losses were found to occur downstream of the trailing edge. This rise in total pressure loss in the present tests was almost entirely explained by a corresponding dissipation of the secondary kinetic energy of the flow. A mixing analysis of the flow was done to predict the additional losses due to ''mixing'' until the flow became completely uniform.


Randomized classification trees are among the most popular machine learning tools and found successful applications in many areas. Although this classifier was originally designed as offline learning algorithm, there has been an increased interest in the last years to provide an online variant. In this paper, we propose an online learning algorithm for classification trees that adheres to Bayesian principles. In contrast to state-of-the-art approaches that produce large forests with complex trees, we aim at constructing small ensembles consisting of shallow trees with high generalization capabilities. Experiments on benchmark machine learning and body part recognition datasets show superior performance over state-of-the-art approaches.


The contribution of nano-scale particles observed using Atom Probe Tomography in an increase of yield strength of conventional and advanced HSLA steels was studied. The advanced HSLA steel showed higher yield strength than conventional HSLA steel. There were two types of carbides, which primarily contribute to an increase in yield strength of conventional HSLA steel: (i) coarse TiC with average size of 25±5nm and (ii) fine TiC with average radius of 3±1.2nm. The presence of two types of carbides was found in the microstructure of advanced HSLA steel: (i) nano-scale Ti0.98Mo0.02C0.6 carbides with average radius of 2.2±0.5nm, and (ii) C19Cr7Mo24 particles with an average radius of 1.5±0.3nm. The contribution of precipitation hardening in the yield strength of advanced HSLA steel due to the nano-scale particles was 174MPa, while this value in the conventional HSLA steel was 128MPa.


College student-athletes and first-year students are two undergraduate populations at risk for heavy-episodic drinking and alcohol-related negative consequences. In this study, 63 (56% female, 62% Caucasian) first-year student-athletes completed a preliminary questionnaire assessing demographic characteristics, athlete-specific drinking motives, alcohol-related negative consequences, and season status. Scores of five or more on the ,4 UDIT-C defined the at-risk subsample. Participants who met the criteria for hazardous drinking (n = 19) reported higher levels of alcohol-related negative consequences and drinking motives. A logistic regression, with these variables, successfully distinguished between the two groups. Sport-related coping2, and positive reinforcement drinking motives, emerged as the most robust predictors of hazardous drinking. Implications for screening, prevention, and brief intervention strategies for first-year student-athletes are discussed.


BACKGROUND: Tumor cell proliferation, invasion and metastasis are known to be mediated, at least in part, through degradation of basement membrane by neutral metalloproteinases (MMP) produced by tumor and stromal cells. MMP-9 is known to play a significant role in breast tumor cell invasion and metastasis via degradation of ECM components and activation of cytokines and chemokines. MMP-9 is known to cleave type IV collagen, one of the most abundant collagens of the extracellular matrix. Our lab has found that the fully processed (68 kDa) form of MMP-9 generated in tumor and stromal cells is also capable of cleaving type I collagen molecule with similar characteristics of MMP‐1. This observation raises questions regarding the significance of each MMP in tumor cell invasion and metastases. Thus, in combating tumor growth and invasion, understanding the mechanism of substrate specificity and design of a novel therapeutic compound that is capable of specifically down regulating MMP-9 expression are of interest. METHOD: DNAzymes are catalytic oligonucleotides that bind to and cleave specific mRNA, resulting in a decreased protein expression. The safety and efficacy of anti-MMP-9 DNAzyme (AM9D) in vivo was determined by injecting 35S‐labeled AM9D (35S-AM9D) into the tail vein of healthy and MMTV-PyMT transgenic mice and the amount of 35S-AM9D accumulated in different tissues was measured as a function of time. The effect of AM9D treatment on breast tumor progression was tested by four once‐weekly intratumoral injections of two concentrations of AM9D into mammary tumors of MMTVPyMT transgenic mice at early stages of tumor development. The tumor sizes were measured at the end of the experiments. The effect of AM9D treatment on early stage experimental metastasis and survival was evaluated by injecting FVB female mice with 1x106 luciferase labeled mammary tumor epithelial cells (luc‐MTEC) isolated from MMTV‐PyMT mice and treating the animals with AM9D, control DNAzyme, or PBS for 3 weeks or up to 10 weeks, respectively. The mechanism of substrate specificity of 68 kDa MMP‐9 was determined by generating a series of truncated and site directed mutant forms of MMP‐9. Specific amino acid residue in sequence 444PRPEPEPRPPTTT456 in the hinge region responsible for substrate selectivity of the enzyme was then identified by alanine‐scanning site directed mutagenesis. The charged amino acid residues (Arg445, Glu447, Glu449, and Arg451) were individually replaced by Ala and the proteolytic activity of the mutant enzymes toward Mca‐PLGL(Dpa)AR‐NH2 , gelatin, and type I collagen was determined. RESULTS: Treatment of MDA‐MB‐231 breast cancer cell line with AM9D in vitro resulted in decreased invasion potential of the cells and intratumoral treatment of MMTV‐PyMT mice in vivo resulted in delayed rate of tumor growth and retarded final tumor volume by up to 51%. This decrease in tumor growth was correlated with decreased MMP-9 protein production within the treated tumor tissues. Tumors treated with AM9D were also less vascular compared to control and untreated tumors. Furthermore, DNAzyme administered IV is distributed to major organs including lung, without showing any organ toxicity. Intravenous administration of AM9D and control DNAzyme in animals bearing luc‐MTECs were able to decrease the number of gross lung macro metastasis. In addition, AM9D treatment increased progression‐free survival but did not have an effect on overall survival of animals inoculated with luc‐MTECs compared to control DNAzyme and PBS treatment. These data indicate that AM9D can be used individually or as an adjuvant to current chemotherapy for breast cancer. To further illuminate the role of MMP-9 in tumor growth and metastases the mechanism of substrate specificity of the enzyme was studied. Site directed and deletion mutagenesis revealed that interaction of Glu415 in the active site with Glu447 and/or Arg451 in the hinge region makes the active site rigid, preventing full length MMP-9 from cleaving type I collagen. Disruption of this interaction, on the other hand, provides the flexibility necessary for the enzyme's active site to change conformation and be able to bind and cleave type I collagen substrate. CONCLUSION: Given that MMP-9 is capable of cleaving type I collagen and its down regulation hinders the development of breast cancer in an animal model, AM9D could prove useful as an adjuvant therapy against breast carcinoma cell invasion. Document Type Dissertation Degree Name Doctor of Philosophy (PhD) Program Biomedical Sciences Research Advisor Tayebeh Pourmotabbed, Ph.D.