Hox paralog group 2 (PG2) genes are evolutionarily conserved developmental regulatory genes that function to specify rhombomere (r) and pharyngeal arch (PA) identities in animal embryos. Several rounds of whole genome duplications in animals including one specific to ray-finned fishes and post-genome duplication independent gene loss have resulted in divergent Hox PG2 gene complements across evolutionarily divergent teleost fishes. Divergence in gene complements may have in part been responsible for generating divergent Hox PG2 gene expression patterns and specification of hindbrain and PA-derived structures during the evolution of osteichthyan embryogenesis. In this dissertation I describe the cDNA cloning and expression analysis of Japanese medaka (Oryzias latipes) Hox PG2 genes. I show that there are only two functional canonical genes hoxa2a and b2a and that a previously identified hoxa2b gene is a transcribed pseudogene [psi]hoxa2b. The canonical genes hoxa2a and b2a were expressed in developing rhombomeres and PAs in a manner that was generally conserved throughout the osteichthyans. By contrast [psi]hoxa2b was expressed at detectable levels only in noncanonical Hox PG2 gene expression domains including the ventral-most aspect of the neural tube the pectoral fin buds and the caudal-most region of the embryonic trunk indicative that regulatory control elements needed for spatiotemporal specification of expression have diverged from the canonical orthologs. In order to understand whether sequence divergence within cis-regulatory control elements are linked to the divergent expression patterns of the medaka hoxa2 paralogs conserved genomic sequences upstream of the medaka hoxa2a and [psi]hoxa2b genes were tested functionally using a transgenic GFP reporter system. The medaka hoxa2a r3/5 enhancer region (r3/5ER) was shown to direct reporter gene expression in r4 PA2 and the posterior PAs while the r3/5ER of [psi]hoxa2b directed reporter gene expression in r3-7 PA2 and the posterior PAs which is different from transgenic mapping studies of the orthologous regions tested in chick and mouse embryos. These analyses provide evidence for significant post-genome duplication divergence in cis-regulatory element function in the r3/5ER of osteichthyans. Further they question the ancestral nature of the r3/5ER prior to the evolutionary split of sarcopterygians (lobe-finned fishes) from the actinopterygians (ray-finned fishes).


At a time when welfare regimes in Anglophone countries are being reshaped to reflect neoliberal ideology, there is little by way of empirical, qualitative research which directly addresses the question of how jobless families live or are affected by their circumstances, particularly in regional Australia. This study combines a consideration of questions of social structure as they pertain to jobless families at the theoretical level with an ethnographic journey into their life worlds. It aims to understand the impact of long-term joblessness upon the families and to explore the interconnections between system and life world. I adopt Layder's (1997, 1998) theoretical and methodological formulations as the most appropriate means to underpin an investigation of this nature. The study is comprehensively situated within a structural context which examines discourses and events that have exerted an influence on our present social arrangements, including an analysis of relevant social policy. Semi-structured, in-depth interviews were conducted with two non-purposive samples and analysed using a modified Grounded Theory approach as advocated by Layder (1998). It was found that the current welfare regime helps to stabilise the capitalist global economy and does at least provide a precarious stability for those excluded from the labour market. Whilst families receiving long-term income support are not a homogeneous group, they are subject to hidden injuries in common. The linkages between system and life world are theorised in terms of the displacement principle, -viwhich holds that the displacement of a problem does not solve it, but merely relocates it elsewhere. It is used to explain both large-scale displacements as well as microprocesses occurring within jobless families. Long-term joblessness is found often to have destructive consequences for intimacy, though family structure may remain intact. This is partly due to a welfare regime which disrespects its beneficiaries. I argue that social policy must be informed by an alternative discourse which includes social or welfare rights as a part of human rights, based upon a recognition of mutual interdependency and an ethic of care. This is vital if future policy directions are to accord equal respect to all citizens.


We present a systematic analysis of state-of-the-art polarizable and flexible water models from a many-body perspective, with a specific focus on their ability to represent the Born-Oppenheimer potential energy surface of water from the gas to the liquid phase. Using coupled cluster data in the completed basis set limit as a reference, we examine the accuracy of the polarizable models in reproducing individual many-body contributions to interaction energies and harmonic frequencies of water clusters and compare their performance with that of MB-pol, an explicit many-body model that has been shown to correctly predict the properties of water across the entire phase diagram. Based on these comparisons, we use MB-pol as a reference to analyze the ability of the polarizable models to reproduce the energy landscape of liquid water under ambient conditions. We find that, while correctly reproducing the energetics of minimum-energy structures, the polarizable models examined in this study suffer from inadequate representations of many-body effects for distorted configurations. To investigate the role played by geometry-dependent representations of 1-body charge distributions in reproducing coupled cluster data for both interaction and many-body energies, we introduce a simplified version of MB-pol that adopts fixed atomic charges and demonstrate that the new model retains the same accuracy as the original MB-pol model. Based on the analyses presented in this study, we believe that future developments of both polarizable and explicit many-body models should continue in parallel and would benefit from synergistic efforts aimed at integrating the best aspects of the two theoretical/computational frameworks.


The process by which the somatotrope lineage emerges in the developing pituitary is regulated by the activity of specific signaling and transcription factors expressed during development. We set out to understand the contribution of FOXO1 to that process by using a mouse model in which FOXO1 is prematurely expressed in the pituitary primordium. Expression of FOXO1 in the oral ectoderm as early as embryonic day (e)9.5 resulted in pituitary gland hypoplasia and reduced expression of anterior lobe hormone transcripts at e18.5. Of note, the relative numbers of somatotropes and thyrotropes were also decreased at e18.5. LHX3 and PITX2, markers of pituitary identity, were present in a reduced number of cells during the formation of the Rathke pouch. Thus, premature expression of FOXO1 may affect adoption of pituitary identity during differentiation. Our results demonstrate that the timing of FOXO1 activation affects its role in pituitary gland organogenesis and somatotrope differentiation.


The problem of fixed satellite broadcast reception is considered. The possibility of reducing the requirements on the antenna front-end dimensions is investigated. Interference processing and mitigation techniques are employed to cope with the increased level of adjacent system interference at the satellite broadcast receiver resulting from the less directive antenna. A novel satellite reception front-end antenna based on a multiple input receiver is proposed to adapt the interference processing methods to the broadcast reception scenario. The potential performance of the devised scheme is thoroughly discussed and assessed by extensive software simulations.


Normothermic retrograde continuous cardioplegia is a revolutionary development for myocardial preservation in cardiac surgery. Despite excellent reports regarding this technique, the surgical community has expressed concern over technical problems encountered. The method of normothermic retrograde continuous cardioplegia in current use requires both large total crystalloid volumes and large potassium loads to deliver adequate cardioplegia. We have developed a technique that eliminates these problems. The heart is stopped by an initial infusion of normothermic cardioplegic solution through a coronary sinus catheter. The infusate is then converted to normothermic pump blood. Small boluses of potassium chloride are added intermittently to maintain cardiac arrest. We applied this technique to 35 patients undergoing cardiac valve surgery. The average volume of crystalloid cardioplegia required was 125 mL (range, 40 to 155 mL), and the average total potassium load was 52 mEq (range, 2 to 100 mEq). Clinically significant sequelae were noted in 4 patients (11%), and 1 (3%) died of pneumonia on the 28th postoperative day. The method we describe is a safe and effective alternative to the current technique of normothermic retrograde continuous cardioplegia and offers both physiologic and technical advantages to patients undergoing cardiac valve procedures.


Diffusion MRI is established as an essential tool for both clinicians as well as biomedical scientists. Its application plays an important role in diagnosis and management of acute stroke, tumors, trauma, and infectious disease, among myriad other applications. Furthermore, diffusion studies are crucial for understanding disease processes caused by developmental and neurodegenerative disorders. The latest developments in quantitative diffusion imaging have broadened the potential application of the technique for both clinical and research applications. However, ongoing research is critical in order to further improve the accuracy and reproducibility of quantitative diffusion MRI techniques. Correlation time diffusion (D-CT) is emerging as an alternative technique for obtaining diffusion qMRI data[1][2][3]. Using the D-CT technique, T1 relaxation data is analyzed, using a modified BPP relaxation theory, in order to calculate the correlation times of protons' stochastic processes and relate these times to solution viscosity in order to calculate proton diffusion coefficients, ADCs. vi The purpose of our study was to compare age related changes, during childhood and early adulthood, of global brain diffusion coefficients obtained by correlation time technique to global brain diffusion coefficients obtained by a conventional pulsed field gradient technique. In our study, we used the data of 27 subjects (0.5-24 years old), who were scanned with Mixed-TSE and DW-SS-SE-EPI pulse sequences. Subsequently, we processed the resulting directly acquired images to generate T1, T2, PD, ADC maps as well as volumetric data. We used the student t-test and linear regression analysis to compare and interpret our data. Our results show a strong positive correlation between the volumetric data. Good correlation between ADC values was observed, with the widest discrepancy between DCT, DPFG (about 17%) observed in the youngest subjects, and the smallest discrepancy noted in the older subjects.


A dental impression is a positive replica of the teeth, the surrounding gingiva and the border between them; the purpose of which is to create an accurate master model. Two major techniques for impressions exist today: The conventional and the digital impressions. The current article describes both techniques. In the conventional impressions, it is important to choose a proper tray, stock or custom, and to mix the material properly. The commonly used impression techniques for making a conventional impression are described with a review on the effect of the technique on its accuracy. The effect of the wash bulk on the accuracy of the stone dies and/or the restoration is discussed, as well. The digital impressions with their advantages and disadvantages are described in comparison to the conventional impressions. Although, digital impressions eliminate some of the negative characteristics of conventional impressions, proper soft-tissue management and isolation of tooth preparation margins is still mandatory.


The Mozambique tilapia Oreochromis mossambicus (Teleostei, Cichlidae) has been transplanted worldwide during the 20th century, and now belongs to the list of the most invasive species. Using a geometric morphometric approach, we describe body shape differentiation among 15 populations from native (Mozambique) and invaded (New Caledonia and Guadeloupe) ranges. A dominant phylogeographic signal is detected, despite the broad range of environmental conditions at the local scale. This result suggests that phylogeographic background rather than phenotypic plasticity responding to environmental variation constitutes the main factor correlated with shape divergence. This could result from successive founder events that occurred during the process of colonization of new geographic areas, and therefore strongly suggests heritable phenotypic differentiation. In addition, shape changes along a major axis of divergence hypothetically refer to different swimming abilities, possibly related to divergent functional requirements between the native and invaded ranges. Overall, patterns of contemporary shape diversification in O. mossambicus probably result from both phylogenetic constraints and adaptive divergence processes. We show that critically taking into account recent phylogenetic history of populations as a constraint on rapid phenotypic divergence is necessary for an improved view of contemporary evolution. © 2012 The Linnean Society of London, Biological Journal of the Linnean Society, 2012, 105, 369–381.


A new class of supersonic nonequilibrium flows is studied on the basis of solving the Boltzmann and model kinetic equations with the aim to consider new nonlinear structures in open systems and to study anomalous transfer properties in relaxation zones. The Unified Flow Solver is applied for numerical simulations. Simple gases and gases with inner degrees of freedom are considered. The experimental data related to the influence of the so-called optical lattices on the supersonic molecular beams are considered and numerical analysis of the nonequilibrium states obtained on this basis is made. The nonuniform relaxation problem with these distributions is simulated numerically and anomalous transport is confirmed. The conditions for strong changes of the temperature in the anomalous transfer zones are discussed and are realized in computations. PACS: 05.20.Dd, 47.45.Ab, 51.10.+y


We show that changes in market conditions significantly affect cross-autocorrelations and speed of adjustment in weekly stock returns. We find significant positive cross-autocorrelations between weekly returns on a portfolio of small firms and lagged large-firm portfolio returns only when the lagged aggregate market has experienced a decline in value. These positive-return cross-autocorrelations are also associated with lower abnormal portfolio trading volume and greater delays in the adjustment of individual stock prices to (negative) market-wide information, particularly for small firms. The effect of lagged market states cannot be explained by market microstructure biases such as nonsynchronous trading or thin trading.


The success of a free microvascular tissue transfer is based on a sufficient microanastomosis which meets the following requirements: a pedicle placed without kinking or twisting, good drainage, a well-defined recipient vessel, integrity of the endothelium, and duration of ischemia. The extent of skin and muscle necrosis increases significantly with increases in ischemia time. Reperfusion of ischemic tissue results in local and systemic damage associated with the release of oxygen free radicals, polymorphonuclear leucocytes, and such endothelial hormones as Endothelin-1, EDRF (endothelial-derived relaxing factor), thromboxane, complement, and cytokines. Ischemia-reperfusion disrupts the delicate balance that maintains homeostasis in the microcirculation. This review discusses the clinical and therapeutic aspects of such injury, concentrating on perioperative management in free flap transfer. It points out the possible influence of Endothelin-1 on vasospasm at the site of anastomosis, and emphasizes the importance of the endothelium as a highly dynamic network. Finally, future diagnostic and therapeutical aspects are discussed.


Ribosome-inactivating proteins (RIPs) are a family of plant toxic enzymes that permanently damage ribosomes and possibly other cellular substrates, thus causing cell death involving different and still not completely understood pathways. The high cytotoxic activity showed by many RIPs makes them ideal candidates for the production of immunotoxins (ITs), chimeric proteins designed for the selective elimination of unwanted or malignant cells. Saporin-S6, a type 1 RIP extracted from Saponaria officinalis L. seeds, has been extensively employed to construct anticancer conjugates because of its high enzymatic activity, stability and resistance to conjugation procedures, resulting in the efficient killing of target cells.
Here we investigated the anticancer properties of two saporin-based ITs, anti-CD20 RTX/S6 and anti-CD22 OM124/S6, designed for the experimental treatment of B-cell NHLs. Both ITs showed high cytotoxicity towards CD20-positive B-cells, and their antitumor efficacy was enhanced synergistically by a combined treatment with proteasome inhibitors or fludarabine. Furthermore, the two ITs showed differencies in potency and ability to activate effector caspases, and a different behavior in the presence of the ROS scavenger catalase. Taken together, these results suggest that the different carriers employed to target saporin might influence saporin intracellular routing and saporin-induced cell death mechanisms.
We also investigated the early cellular response to stenodactylin, a recently discovered highly toxic type 2 RIP representing an interesting candidate for the design and production of a new IT for the experimental treatment of cancer.


I show how to run an N-time-step Markov chain simulation in a circular fashion, so that the state at time 0 follows the state at time N-1 in the same way as states at times t follow those at times t-1 for 0<t<N. This wrap-around of the chain is achieved using a coupling procedure, and produces states that all have close to the equilibrium distribution of the Markov chain, under the assumption that coupled chains are likely to coalesce in less than N/2 iterations. This procedure therefore automatically eliminates the initial portion of the chain that would otherwise need to be discarded to get good estimates of equilibrium averages. The assumption of rapid coalescence can be tested using auxiliary chains started at times spaced between 0 and N. When multiple processors are available, such auxiliary chains can be simulated in parallel, and pieced together to give the circularly-coupled chain, in less time than a sequential simulation would have taken, provided that coalescence is indeed rapid.
The practical utility of these procedures is dependent on the development of good coupling schemes. I show how a specialized random-grid Metropolis algorithm can be used to produce the required exact coalescence. On its own, this method is not efficient in high dimensions, but it can be used to produce exact coalescence once other methods have brought the coupled chains close together. I investigate how well this combined scheme works with standard Metropolis, Langevin, and Gibbs sampling updates. Using such strategies, I show that circular coupling can work effectively in a Bayesian logistic regression problem.


In Florida, urbanization has caused habitat fragmentation coupled with a major decline in the available habitat for native species. Native scrublands are of particular concern as they are deemed priority habitat by the Florida Fish and Wildlife Conservation Commission (FWC). Florida Atlantic University's Ecological Preserve—home to a keystone species, the gopher tortoise (Gopherus polyphemus)— is a prime example of such a fragmented, degraded scrub habitat. Our research focused on how fragmentation affected habitat suitability, as determined by the distribution of tortoise burrows in the preserve. We found significant correlations between higher burrow densities and minimal (< 50 %) shrub and canopy cover. Burrow densities were also higher in areas of greater herbaceous cover and organic soil content. These correlations were in agreement with previous findings reported in the literature. However, 23% of the preserve area was covered with invasive vines that, unless controlled, could further degrade the habitat. Our data suggest how a plan could be developed and implemented for the better management of gopher tortoises in the FAU Preserve.


This study examines the cracking of GaN films grown on Si(111) substrates, with particular focus on the effect of the density of crack-initiating defects (CIDs) on the crack spacing. The relationship between the CID density and crack spacing was examined by comparing specimens of the same thickness and under the same stress but with different CID density. The CID density in the GaN layer was changed by varying the ion-implanted area using patterning prior to metal–organic chemical vapor deposition (MOCVD) growth. The crack spacing decreased with increasing CID density, but this effect could not be explained by the previous model. Therefore, a CID-density related factor, nd, was newly introduced to explain the crack spacing and film stress relationship.


Neuronal perikarya were isolated from rat cerebral cortex at different stages of postnatal development. Membranes sedimenting at 100000 g were obtained from these neurons to study several glycosyltransferases of the dolichol pathway. Enzyme activities from stages before and during synapse formation were compared (days 5 and 15 respectively). Dolichyl diphosphate (Dol-P-P) N-acetylglucosamine, dolichyl phosphate mannose and dolichyl phosphate glucose synthases and the enzymes catalysing Dol-P-P-GlcNAc2Man9Glc3 formation were higher at day 15 of postnatal development. The glycosyl transfer of the latter compound to endogenous protein(s) as well as to a dinitrophenyl-heptapeptide was also measured. The activity was higher at day 15. Furthermore, the activity of dolichyl phosphate mannose synthase was also measured during the time when the number of synapses ceased to increase (day 36) and in the adult stage. The activity of dolichyl phosphate mannose synthase was higher at day 36 than at day 15, and declined in the adult stage. From these results it may be concluded that there is an increase in the glycosylation of asparagine-type glycoproteins during synapse formation in the neurons of the cerebral cortex.


Speech recognition failures and limited vocabulary coverage pose challenges for speech interaction with characters in games. We describe an end-to-end system for automating characters from a large corpus of recorded human game logs, and demonstrate that inferring utterance meaning through a combination of plan recognition and surface text similarity compensates for recognition and understanding failures significantly better than relying on surface similarity alone.


ABSTRACT This article compares the communication strategies of party and candidate accounts on Instagram during the 2017 German federal election. Building upon previous research, we conceptualize how the digital architecture of the platform determines its communication norms and how the actual communication practices implemented by parties and candidates follow or violate these norms. Therefore, we analyze how Instagram is used to implement different campaign strategies, focusing on (1) the use of network-related Instagram features-like Hashtags-, (2) text-integrated images, (3) dominant visual themes, (4) visual personalization, and (5) the addressing of policy issues. Since Germany's voting system rewards both candidate- and party-focused campaigning, the country is an ideal case study for an appropriate comparison of party and candidate accounts. We conducted a quantitative content analysis of all 581 posts published on party and candidate accounts during the four weeks before the election. The results suggest that parties and candidates used complementary communication strategies instead of relying on a single tactic. We are able showing that parties in parts strategically violated Instagram's communication norms to convey hard-to-visualize policy messages while candidates prefered to post professional personalized posts. The presented findings provide a starting point for future studies on the perceptions and behavioral outcomes of different campaign strategies.


Electroactive soft elastomers require huge electric field for a meaningful actuation. We demonstrate, by means of numerical simulation, that this can be dramatically reduced and large deformations can be achieved with suitably designed heterogeneous actuators. The mechanism by which the enhancement is attained is illustrated with the aid of both idealized and periodic models.


Cotton (Gossypium, Malvaceae) has been spun, woven and dyed since prehistoric times. Four cotton species are economically important; these are Gossypium arboreum (tree cotton), G. barbadense (American pima cotton), G. herbaceum (levant cotton) and G. hirsutum (American upland cotton). Previous research has been conducted examining the pollen grains of the Malvaceae and there is a key that differentiates the four economically important species of Gossypium by their pollen grains. However, the cotton pollen found in boll weevils, Anthonomus grandis Boheman, and other insect pests cannot be keyed to the species using the published key. The objective of this research was to determine if the pollen grains of these four species could be differentiated and develop a key that works for cotton pollen found in insect pests. Flowers of the four taxa were collected from USDA greenhouses and fields and dried. Both unacetolysed and acetolysed pollen grains were examined with light and scanning electron microscopy. The length and width of 300 pollen grains and 100 processes (spines) of each taxon were measured. There were no size differences between the acetolysed and the unacetolysed grains. Gossypium barbadense and G. hirsutum represent the largest grains (mean =106.7 and 94.9 µm, respectively) and the longest processes (mean= 17.7 and 15.2 µm, respectively). Differentiation of these taxa can be useful in the determination of the origin of insect pests that attack cotton when different cotton species are grown within a region. However, additional research is needed on the varieties and cultivars of cotton.


This study assessed the impact of climate change on water availability and variability in two subbasins in the upper Blue Nile basin of Ethiopia. Downscaled future climate data from HadCM3 of A2 (medium-high) and B2 (medium-low) emission scenarios were compared to the observed climate data for a baseline period (1961–1990). The emission scenario representing the baseline period was used to predict future climate and as input to a hydrologic model to estimate the impact of future climate on the streamflow at three future time horizons: 2020–2045, 2045–2070 and 2070–2100. Results suggest that medium-high emission scenario best represents the local rainfall and temperature pattern. With A2 scenario, daily maximum/minimum temperature will increase throughout the future time horizons. The minimum and maximum temperature will increase by 3.6 °C and 2.4 °C, respectively, towards the end of the 21st century. Consequently, potential evapotranspiration is expected to increase by 7.8%, although trends in annual rainfall do not show statistically meaningful trends between years. A notable seasonality was found in the rainfall pattern, such that dry season rainfall amounts are likely to increase and wet season rainfall to decrease. The hydrological model indicated that the local hydrology of the study watersheds will be significantly influenced by climate change. Overall, at the end of the century, streamflow will increase in both rivers by up to 64% in dry seasons and decrease by 19% in wet seasons.


Service-oriented architecture (SOA) has been widely adopted in the development of many net-centric application systems. In SOA, services potentially from different domains are composed together to accomplish critical tasks. In these systems, security and trustworthiness are the major concerns that have not been well addressed. Many access control models have been developed to ensure proper accesses to critical resources from local as well as external domains. Also, many data provenance schemes have been proposed in recent years to support data quality assessment and enhancement, data reproduction, etc. However, none of the existing mechanisms consider both access control and data provenance in a unified model. In this paper, we propose an integrated role-based access control and data provenance model to secure the cross-domain interactions. We develop a role-based data provenance scheme which tracks the roles of the data originators and contributors and uses this information to help evaluate data trustworthiness. We also make use of the data provenance information and the derived data quality attributes to assist with role-based access control. In this integrated model, the secure usage of a data resource must also consider the quality and trustworthiness of the data. To realize this concept, we develop an extended access control model in which access permissions are specified with constraints over the provenance attributes. Also, to assure confidentiality, we record the access constraints from the data originators and contributors to help decide how the data should be further disseminated.


The purpose of this paper is to synthesize and assess existing literature on memory encoding and other cognitive processes to determine the potential benefits and drawbacks of studying with music. This paper examines and discusses the results of past studies on aspects such as context dependent memory, music's impact on mood, state dependent memory, the Yerkes-Dodson law, and the seductive detail effect. How to utilize music in a way that is the least distracting to study ability is also examined, and the idea that studying with music may offer the least hinderance to memory encoding only when it is typical, familiar, slow in tempo, low in intensity, and low in complexity is highlighted. Based on the benefits associated with studying with music and because of how potential detrimental effects can be mitigated and controlled, background music is recommended as a beneficial tool to use to enhance time spent studying.


Episodic hypoxic events in estuaries can alter the trophic dynamics of important benthic predators. During hypoxic upwelling events mobile predators may reduce their feeding activity as they migrate to relatively shallower, oxygenated water, and may reinvade deep-water habitats dur- ing relaxation of hypoxia to exploit vulnerable infaunal prey (e.g. clams and polychaete worms) that have reduced their burial depth in response to hypoxia. We used biotelemetry techniques with con- current measurements of dissolved oxygen (DO) to monitor the feeding and movement responses of free-ranging blue crabs Callinectes sapidus to episodic hypoxic upwelling and subsequent relaxation events within the Neuse River Estuary (NRE), North Carolina, USA. Although telemetered crabs fed in hypoxic water with DO concentrations as low as 1.01 mg l -1 , percent feeding occurrence declined slightly when crabs were exposed to mild (DO = 2 - 4 mg l -1 ) and severe hypoxia (DO 4 mg l -1 ). Crabs reduced the proportion of time spent feed- ing during hypoxic upwelling conditions except for the most severe events when DO dropped rapidly from normoxia to severe hypoxia. The proportion of time crabs spent feeding did not increase and crabs did not reinvade deeper water habitats during relaxation events, as was hypothesized. These results are somewhat inconsistent with previous studies and we suggest that crabs may have fed on prey other than benthic infauna, or that upwelling events may not have lasted long enough to cause infauna to migrate close enough to the sediment surface to be vulnerable to predation by blue crabs. Our study highlights the importance of examining the complex interaction between the hydrody- namics of episodic events and various behaviors (e.g. feeding and movement) when trying to under- stand the impact of these events on estuarine trophic dynamics.


To the Editor: While we welcome research into regional anesthesia in order to improve the quality of our medical provision, the study by Abdallah et al. demonstrates highly relevant problems in research in this area. First, the authors describe the interscalene block as one that poses dangers to certain populations. This may be true for a minority of patients such as those with severe respiratory impairment, but the vast majority of patients are not restricted by any ensuing respiratory compromise. Studies of healthy patients demonstrate that the phrenic nerve palsy is of no clinical relevance. Given that 2.5 yr in three hospitals were required to obtain the 136 patients in this study, there does not appear to be a large group of patients likely to benefit from a new block. It has to be realized that regional anesthesia provision remains far from universal. Although the interscalene technique has been around for many years and refined with the use of ultrasound, a recent Canadian study demonstrated that only around half of shoulder surgery patients were receiving a nerve block for ambulatory surgery. This is likely much lower in many other health systems. One of the reasons for this is likely a lack of training and confidence of anesthesia providers in performing the block; lack of resources also contributes. Refining blocks further, and in effect making them more difficult, is unlikely to benefit the population as a whole. It needs to become a more significant priority in the provision of regional anesthesia that basic blocks are able to be performed competently by more anesthesiologists rather than the ever increasing number of new blocks with small, unclear benefits.


The new complexes [Cu(PPh3)2(KTZ)2]NO3 (1), [Cu(PPh3)2(CTZ)2]NO3 (2), [Au(KTZ)2]Cl (3), [Au(CTZ)2]Cl (4) and Pt(KTZ)2Cl2 (5) were prepared by reaction of KTZ, CTZ (where CTZ: 1-[(2-chlorophenyl)-diphenylmethyl]-1H-imidazole and KTZ: cis-1-acetyl-4-[4-[[2-(2,4-dichlorophenyl)-2-(1H-imidazol-1-ylmethyl)-1,3-dioxolan-4-yl]methoxy]phenyl]piperazine) and their respective metal salts or metal complexes under mild conditions. They were characterized using NMR, UV-vis and IR spectroscopies, microanalytical analysis and mass spectrometry. Complex (5) was also investigated using computational methods (DFT) to evaluate the geometry configuration around the Pt(II) coordination sphere; the results showed that the trans complex is the most stable one. The antifungal activities of these new compounds 1–5 and some of our reported metal-based azole drug derivatives such as Pt(CTZ)2Cl2 (6), [Au(PPh3)(KTZ)]PF6 (7) and [Au(PPh3)(CTZ)]PF6 (8) were evaluated against sporotrichosis agents (Sporothrix schenckii, Sporothrix brasiliensis and Sporothrix globosa). Their selectivities towards fungal cells were also evaluated. Complexes [Cu(PPh3)2(KTZ)2]NO3 (1), [Cu(PPh3)2(CTZ)2]NO3 (2), [Au(PPh3)(KTZ)]PF6 (7) and [Au(PPh3)(CTZ)]PF6 (8) inhibited fungal growth and killed fungi at concentrations in the nanomolar range and were more active than CTZ or KTZ alone. Microscopy analysis using scanning electron microscopy showed that the complexes 1, 2, 7 and 8 interfered with the cell shape. All the metal–azole complexes tested were more selective for fungi than for mammalian cells and human red blood cells, revealing that they are promising molecules for the development of new antifungal compounds.


Theanine, a unique and abundant non-proteinogenic amino acid in tea, confers to the tea infusion its umami taste and multiple health benefits. Its content in new tea shoots is dynamic in winter and spring. However, its seasonal accumulation pattern and the underlying regulation mechanism of tea plants remain largely unknown. In this study, we measured the theanine contents in the roots and leaf buds of 13 tea cultivars at four time points from winter to spring (Dec. 12, Mar. 1, Mar. 23, and Apr. 13). We found theanine accumulated significantly in the roots to as high as ∼6% dry weight. We found theanine content in the roots was constant or slightly decreased on Mar. 1 compared with Dec.12 but increased consistently on Mar. 23 and then decreased on Apr. 13 in all 13 cultivars. In the leaf buds, theanine content kept increasing from Mar. 1 to Mar. 23 and decreasing from Apr. 13 in most of the 13 cultivars, meaning it was probably both season- and developmental stage-dependent. The expression of theanine biosynthesis and amino acid transporter genes in the roots and buds at the four time points was then examined. The correlation analyses between the gene expression and theanine content suggested the expression of theanine-biosynthesis genes was generally and negatively correlated with theanine content; however, the expression of amino acid transporter genes including CsLHT was generally and positively correlated with theanine contents. Finally, we showed that CsLHT has theanine transport activity. Taken together, this study provided insight into the seasonal regulation of theanine biosynthesis and transport in tea plants during winter and spring.


The electro-spark deposition (ESD) processing method is a kind of the electric discharge machining method. It is a method of generating not the processing on a liquid inside but the spark discharge in the atmosphere, and stiffening and coating the surface of the metallic substrate with the deposition of the electrode material. In this research, the surface modification on the extrusion die bearing by the ESD processing method is tried, and the performance is evaluated. In addition, it is investigated the correlation between the abrasion of the electrical discharge coating layer and the surface properties of hot-extruded 5056 high strength aluminum alloy. As a result, it has been understood that the ESD processing of the super-hard alloy whose WC, TiC, and Co are principal ingredients is effective in the extension at the tool life and the prevention of the tearing (crack) of the extrusion material.


This report describes a new mechanism that performs the spreading and isolation of stacked cards using an array of vacuum holes. The separation and isolation of cards including tickets and bills are key operations in the backyard of stations and banks. Operations must be performed robustly against oil or water attached on cards in a small operational area. This report introduces a simple mechanical system that can perform the spreading and isolation of stacked cards robustly.


In this paper the effect of bounded input perturbations on the stability of nonlinear globally asymptotically stable delay differential equations is analyzed. We investigate under which conditions global stability is preserved and if not, whether semiglobal stabilization is possible by controlling the size or shape of the perturbation. These results are used to study the stabilization of partially linear cascade systems with partial state feedback.


Purpose

This paper aims to present case study evidence on the changes in the relations between chief executive officers (CEOs) of large firms and shareholders in the past three decades of the twentieth century. In line with insights from agency theory, the CEOs have experienced increased scrutiny from their principals, the shareholders. This development has affected financial communication and investor relations as well as stock market prices.

Design/methodology/approach

The Dutch electronics firm Royal Philips NV in the transition period of 1971-2001 has been studied using publicly available disclosures and stock market prices. A descriptive case study approach is combined with event study methodology.

Findings

It was observed that the increased emphasis on shareholder interests has affected the interactions between Philips' respective CEOs and the shareholders' reactions to strategic decisions as measured by stock price changes. Around the beginning of the twenty-first century, clarity and openness in CEO communication was the norm and deviations were punished with volatile stock prices.

Research limitations/implications

The study relies on publicly available data.

Originality/value

The case study of Philips can be extrapolated to other exchange-listed firms in the late twentieth century, which faced changed expectations about the role of the CEO, investor relations and the CEO's accountability toward shareholders. This transition is relevant not only as a historical observation, but also as a background to studies in finance and management about top management and financial markets.


Objectives: The increasing sensitivity of forensic analysis methods allows to investigate less and less amount of biological samples. For samples of low quality or quantity, there are stochastic events that require intensive statistical analysis.
Methods: There are several models how to calculate the probability of a given set of alleles. We have described three of them and compared them to verify their accuracy.
Results: The two models proposed in [1] extend so far the most widely used model by the possibility of dropout and peak areas of individual alleles. The first one is incorrect, while the second model highly improves the possibility of DNA mixture analysis.
Conclusions: We have shown the inaccuracy of one of the recently proposed models. We have added the possibility of determining the dropout probability into the second model, otherwise this model overestimates the probabilities calculated.


Can an act learned through conditioning be adequately presented in a subsequent different situation under which it may be useful to the individuals? We approached this question, working on ants, and staying at a level basic compared to the largely developed Applied Behavior Analysis (ABA) discipline. We simply conditioned the ants of both colonies A and B to a green hollow cube (= the conditioned stimulus CS1) associated with sugar water (= the unconditioned stimulus US1), and to basilica (= the conditioned stimulus CS2) associated with meat (= the unconditioned stimulus US2). We then deprived colony A of sugar water and colony B of meat. Thereafter, when confronted to the two conditioned stimuli at the same time, the ants of colony A chose CS 1 (previously associated with sugar water), and the ants of colony B chose the CS 2 (previously associated with meat). The ants chose thus the CS corresponding to the US of which they were deprived. They applied thus a behavior learned through conditioning in a subsequent situation under which this behavior may be useful. During our test experiment, the ants strongly responded to the adequate CS due to their high motivation resulting from starvation. Conditioning techniques might also be usefully used during humans' treatment under the ABA discipline. Increasing the patients' motivation during some conditioning performed for caring them may enhance the impact of that conditioning on the treatment efficiency.


Tau is a major microtubule-associated protein which induces bundling and stabilization of axonal microtubules (MTs). To investigate the interaction of tau with MTs in living cells, we expressed GFP-tau fusion protein in cultured Xenopus embryo neurons and performed time-lapse imaging of tau-labeled MTs. Tau uniformly labeled individual MTs regardless of their assembly/disassembly status and location along the axon. Photobleaching experiments indicated that interaction of tau with MTs is very dynamic, with a half-time of fluorescence recovery of the order of 3 seconds. Treatment of cells with taxol, a drug that suppresses MT dynamics, rapidly induced detachment of tau from MTs. Although binding of tau to straight MTs was uniform, there was a heightened concentration of tau at the sites of high MT curvature. Our results suggest that dynamic interaction of tau with MTs may modify local mechanical properties of individual MTs and play a crucial role in the remodeling of the MT cytoskeleton during neuronal plasticity.


Prosecutors — the most powerful actors in the American criminal justice system — largely avoid accountability for misconduct. To promote fairer processes and results, prosecutors must be held to account for violations of defendants' due process and fair trial rights and the related ethical rules that help protect those rights. An important thread of scholarly work makes clear the need for effective methods of ensuring prosecutorial accountability. Yet, empirical evidence consistently suggests that prosecutors almost universally evade accountability for infringing upon defendants' rights. No method seems to address the problem effectually, whether it be internal or external professional discipline, criminal liability, civil liability, electoral accountability, or an even broader conception of accountability — case-specific remedies provided to criminal defendants who fell victim to prosecutorial misconduct. While many have concluded that these modes of accountability have not been up to the task, it appears that few critiques explicitly draw on a reservoir of powerful explanatory and potentially curative tools hidden in plain sight: deterrence theory.
The central theory underlying our criminal justice system's methods of punishing lawbreakers provides crucial insights into how we might also promote prosecutorial accountability. This Article draws upon the deterrence theory of criminal justice to demonstrate ways in which current approaches to prosecutorial accountability fail to fulfill the key deterrent values of certainty and swiftness (celerity). In both design and operation, current approaches overlook the central importance of ensuring potential wrongdoers are on notice about sanctions for ethical and legal breaches, and instead deal with misconduct after-the-fact in an ad hoc manner.
Evaluating existing modes of accountability from a deterrence perspective proves useful in three ways. First, it provides a theoretical account of the status quo's failure to hold prosecutors accountable. Regimes of prosecutorial accountability remain somewhat undertheorized, and their numerosity, design, and construction have resulted in both confusion and a disquieting accountability deficit. Deterrence is a useful perspective from which to understand the system's breakdown and identify paths to correct the course. Second, deterrence principles provide helpful language to describe modes of accountability and bridge the gaps between them. Someone studying the professional disciplinary regime, for example, may not be able to easily draw upon what happens in the electoral accountability regime. Deterrence can help fill the void. Third, deterrence offers a normative framework that can advance the discourse about solutions to address the system's failure.


The paper describes a quantitative structure-activity relationship (QSAR) study of IC 50 values of benzimidazole derivatives on escherichia coli methionine aminopeptidase. The activity of the 32 inhibitors has been estimated by means of multiple linear regression (MLR) and artificial neural network (ANN) techniques. The results obtained using the MLR method indicate that the activity of derivatives of benzimidazoles on Co II -loaded escherichia coli methionine aminopeptidase depend on different parameters containing topological descriptors, Burden eigen values, 3D MoRSE descriptors and 2D autocorrelation descriptors. The best artificial neural network model is a fully-connected, feed forward back propagation network with a 5-4-1 architecture. Standard error for the training set using this network was 0.193 with correlation coefficient 0.996 and for the prediction set standard error was 1.41 with correlation coefficient 0.802. Comparison of the quality of the ANN with different MLR models showed that ANN has a better predictive power. KEY WORDS : QSAR, Artificial neural network, Multiple linear regression, Molecular descriptors, Escherichia coli methionine aminopeptidase Bull. Chem. Soc. Ethiop. 2010 , 24(3), 317-325.


Patients undergoing abdominal oncologic surgical procedures require particular surgical and anesthesiologic considerations. Traditional pain management, such as opiate treatment, continuous epidural analgesia, and non-opioid drugs, may have serious side effects in this patient population. We evaluated erector spinae plane (ESP) blocks for postoperative pain management following elective oncologic abdominal surgeries. In this single-center, prospective, and randomized study, we recruited 100 patients who underwent elective oncological abdominal surgery between December 2020 and January 2022 at Soroka University Medical Center in Beer Sheva, Israel. We compared postoperative pain levels in patients who were treated with a preincisional ESP block in addition to traditional pain management with intravenous opioids, non-steroidal anti-inflammatory drugs (NSAIDs), and acetaminophen, compared to patients who were only given traditional pain management (control). Patients who were treated with a preincisional ESP block demonstrated significantly lower Visual Analog Scale scores at 60 minutes and 4, 8, and 12 hours following the surgery, compared to the control group (p < 0.001). Accordingly, patients in the ESP group required less morphine from 60 minutes to 12 hours after surgery, but they required increased non-opioid postoperative analgesia management at 4, 8, and 12 hours after surgery (p from 0.002 to <0.001) compared to the control group. In this study, we found ESP blocks to be a safe, technically simple, and effective treatment for postoperative pain management after elective oncologic abdominal procedures.


By analyzing isofemale strains extracted from a natural population of Nasonia vitripennis, we detected variation for the sex ratios produced in fresh hosts (first sex ratios) and in previously parasitized hosts (second sex ratios). Under simple assumptions of population structure, this between-strain heterogeneity of first sex ratios results in heterogeneity of fitnesses. There is approximately ten percent difference in average fitnesses between the strains. (The fitnesses of second sex ratios are analyzed in the accompanying paper.) Average first and average second sex ratios are uncorrelated. There is significant between-female heterogeneity within some strains for first sex ratios but not for second sex ratios. In addition, the average direct-developing and diapause first sex ratios (but not second sex ratios) are significantly correlated. There are significant correlations between the direct-developing and diapause sex ratios produced by the same female. The strains differ in their effects on the sex ratio and size of another female's brood in the same host. Data on these types of variation for sex ratio traits are essential for further progress in the study of sex ratio evolution.


Paleomagnetic and archeomagnetic records are used in both regional and global studies of Earth's magnetic field. We present a description and assessment of five newly compiled data sets, also used in the companion paper by Korte et al. (2009) to produce a series of time‐varying spherical harmonic models of the geomagnetic field for the last 3000 years. Data are drawn from our compilation of lake sediment records and from the online database, GEOMAGIA50v2. The five selections are available from the EarthRef Digital Archive at http://earthref.org/cgi‐bin/erda.cgi?n=944. Data are grouped according to the source of material, and we conducted separate assessments of reliability for archeomagnetic artifacts and lava flows (the ARCH3k_dat data set) and for sediments (SED3k_dat). The overall number of data is 55% greater than in previous compilations. Constrained data sets were selected using different criteria for each group. Winnowing of archeological data was based on uncertainties supplied by the original data providers. The lake sediment data assessment relied on preassigned age uncertainties and one or more of the following: comparisons with archeomagnetic data from the same region, regional consistency among several lakes, and consistency with global archeomagnetic models. We discuss relative merits of a larger unconstrained data set or a smaller (possibly) more reliable one. The constrained data sets eliminate a priori up to 35% of the available data in each case and rely on potentially subjective assessments of data quality. Given the limited data available our analyses indicate that iterative rejection of a small number (1–1.5%) of outlying data during global field modeling is a preferable approach. Specific regional comparisons among the models and data support the conclusion that Korte et al.'s outlier‐free CALS3k.3 model based on all available measurements from sediments and archeological artifacts currently provides the best global representation of the 0–3 ka field; the ARCH3k.1 model provides a better fit to the denser European archeomagnetic data and may be better in that region.


Modification of aldose reductase (AR) by the nitrosothiols S-nitroso-N-acetyl penicillamine (SNAP) and N-(beta-glucopyranosyl)-N(2)-acetyl-S-nitrosopenicillamide (glyco-SNAP) resulted in a 3-7-fold increase in its k(cat) and a 25-40-fold increase in its K(m) for glyceraldehyde. In comparison with the native protein, the modified enzyme was less sensitive to inhibition by sorbinil and was not activated by SO(2-)(4) anions. The active-site residue, Cys-298, was identified as the main site of modification, because the site-directed mutant in which Cys-298 was replaced by serine was insensitive to glyco-SNAP. The extent of modification was not affected by P(i) or O(2), indicating that it was not due to spontaneous release of nitric oxide (NO) by the nitrosothiols. Electrospray ionization MS revealed that the modification reaction proceeds via the formation of an N-hydroxysulphenamide-like adduct between glyco-SNAP and AR. In time, the adduct dissociates into either nitrosated AR (AR-NO) or a mixed disulphide between AR and glyco-N-acetylpenicillamine (AR-S-S-X). Removal of the mixed-disulphide form of the protein by lectin-column chromatography enriched the preparation in the high-K(m)-high-k(cat) form of the enzyme, suggesting that the kinetic changes are due to the formation of AR-NO, and that the AR-S-S-X form of the enzyme is catalytically inactive. Modification of AR by the non-thiol NO donor diethylamine NONOate (DEANO) increased enzyme activity and resulted in the formation of AR-NO. However, no adducts between AR and DEANO were formed. These results show that nitrosothiols cause multiple structural and functional changes in AR. Our observations also suggest the general possibility that transnitrosation reactions can generate both nitrosated and thiolated products, leading to non-unique changes in protein structure and function.


During the past few years, a lot of work has been done on behavioral models and simulation tools. But a need of modeling strategy still remains. The VHDL-AMS language supports the description of analog electronic circuits using ordinary differential algebraic equations (ODAEs), in addition to its support for describing discrete-event systems. For VHDL-AMS to be useful to the analog design community, efficient semiconductor device models must be available. In this paper potential merits of the new IEEE VHDL-AMS standard in the field of modeling of semiconductor devices are discussed. The device models for diodes and the principles, techniques and methodology used to achieve the design of an analytical third generation Spice transistor MOS model named EKV are presented. This is done by taking into account the thermoelectrical effect with VHDL-AMS, and with relevant parameters set to match a deep submicron technology developed in VHDL-AMS. The models were validated using system vision from mentor graphics.


Background AMP-activated protein kinase (AMPK) is a heterotrimeric enzyme that is evolutionarily conserved from yeast to mammals and functions to maintain cellular and whole body energy homeostasis. Studies in experimental animals demonstrate that activation of AMPK in skeletal muscle protects against insulin resistance, type 2 diabetes and obesity. The regulatory γ3 subunit of AMPK is expressed exclusively in skeletal muscle; however, its importance in controlling overall AMPK activity is unknown. While evidence is emerging that gamma subunit mutations interfere specifically with AMP activation, there remains some controversy regarding the impact of gamma subunit mutations [1]–[3]. Here we report the first gain-of-function mutation in the muscle-specific regulatory γ3 subunit in humans. Methods and Findings We sequenced the exons and splice junctions of the AMPK γ3 gene (PRKAG3) in 761 obese and 759 lean individuals, identifying 87 sequence variants including a novel R225W mutation in subjects from two unrelated families. The γ3 R225W mutation is homologous in location to the γ2R302Q mutation in patients with Wolf-Parkinson-White syndrome and to the γ3R225Q mutation originally linked to an increase in muscle glycogen content in purebred Hampshire Rendement Napole (RN-) pigs. We demonstrate in differentiated muscle satellite cells obtained from the vastus lateralis of R225W carriers that the mutation is associated with an approximate doubling of both basal and AMP-activated AMPK activities. Moreover, subjects bearing the R225W mutation exhibit a ∼90% increase of skeletal muscle glycogen content and a ∼30% decrease in intramuscular triglyceride (IMTG). Conclusions We have identified for the first time a mutation in the skeletal muscle-specific regulatory γ3 subunit of AMPK in humans. The γ3R225W mutation has significant functional effects as demonstrated by increases in basal and AMP-activated AMPK activities, increased muscle glycogen and decreased IMTG. Overall, these findings are consistent with an important regulatory role for AMPK γ3 in human muscle energy metabolism.


MutY adenine glycosylases prevent DNA mutations by excising adenine from promutagenic 8-oxo-7,8-dihydroguanine (OG):A mismatches. Here, we describe structural features of the MutY active site bound to an azaribose transition state analog which indicate a catalytic role for Tyr126 and approach of the water nucleophile on the same side as the departing adenine base. The idea that Tyr126 participates in catalysis, recently predicted by modeling calculations, is strongly supported by mutagenesis and by seeing close contact between the hydroxyl group of this residue and the azaribose moiety of the transition state analog. NMR analysis of MutY methanolysis products corroborates a mechanism for adenine removal with retention of stereochemistry. Based on these results, we propose a revised mechanism for MutY that involves two nucleophilic displacement steps akin to the mechanisms accepted for 'retaining' O-glycosidases. This new-for-MutY yet familiar mechanism may also be operative in related base excision repair glycosylases and provides a critical framework for analysis of human MutY (MUTYH) variants associated with inherited colorectal cancer.


The antonymy arouses various discussions in various studies, especially the extreme or scalable opposition, it is complete and partial, negation and opposition. On the basis of many studies it is argued and accepted that the antonyms deny each other but at the same time assert themselves. Compound antonymic words are more numerous than the merged words (agglutinations). By analyzing the syntactic relationships between the elements of these words, they emerge entirely only as deterministic compounds. From the lexical-grammatical point of view these are nouns, adjectives and few adverbs and pronouns. In this work, the antonymic pairs, nouns and adjectives, are treated, which are widely used in the Albanian economic terminology. The systemic organization of terminology is also helped by the antonymic contrasts. Contrary to synonymy and homonymy, the antonymy characterizes the terminology positively, precisely because it proves the systematic connection of terms for a developed terminology in the system.


: The association between necrotizing fasciitis and tuberculosis is extremely rare. We report two cases in which the initial clinical presentation of tuberculosis was that of necrotizing fasciitis proven by histopathology. Repeated adequate surgical debridement was performed in both. In one patient, acid-fast bacillus was cultured from a discharging sinus one year postoperatively. The other patient was diagnosed to have pulmonary tuberculosis two months postoperatively. The diagnosis of tuberculosis should be suspected in patients with necrotizing fasciitis with recurrence or unexpected slow response to surgery.


Objective. To systematically screen for behavioral and mental health problems and psychosocial stressors (PS) in newly referred patients and adult caregivers (PACs) in a pediatric weight management program. Methods. We used the Strengths and Difficulties Questionnaire (SDQ), the Center for Epidemiologic Studies Depression Scale (CES-D) for caregivers and patients ≥18 years, and assessed urgent mental health concerns and psychosocial stressors. Results. A total of 243 PACs were screened; data were unavailable for 6. Compared with US normative data for the SDQ–Parent Proxy Version, the proportion of patients in our sample with borderline/abnormal total difficulties and conduct problems scores was greater for all age groups. Among adult caregivers with complete CES-D, 18.4% were at risk for depression. Eleven percent of patients screened positive for urgent mental health problems. Overall, 43% of patients and 57.4% of caregivers had PS. Conclusions. Systematic screening identified untreated symptoms and significant PS. Addressing these complex problems likely requires collaborative approaches with community providers.


PURPOSE
To our knowledge this study represents the first analysis monitoring the efficacy of cyproterone acetate (CPA) monotherapy for achieving castrate testosterone levels prior to administering a luteinizing hormone-releasing analogue (LHRHA) for treating prostate cancer in the prostate specific antigen (PSA) era.

MATERIALS AND METHODS
Patients with untreated locally advanced or metastatic prostate cancer were recruited prospectively. Treatment involved a 28-day course of oral cyproterone acetate and LHRHA depot injection on day 14. Patients had serum PSA, luteinizing hormone and testosterone monitored at intervals during a 56-day period.

RESULTS
A total of 15 patients with a mean age of 74 years completed the study. Near castrate serum testosterone was achieved on day 7 (mean +/- 95% CI 83.38 +/- 17.87 ng/dl). There was a significant testosterone increase after LHRHA administration on day 14 compared with the level of 160.23 +/- 36.60 ng/dl on day 16 (p <0.01). Serum luteinizing hormone mirrored testosterone, increasing from a mean of 4.93 +/- 0.61 to 15.4 +/- 6.12 nmol/l after LHRHA administration (p <0.01). Mean serum PSA demonstrated a decrease from 199.25 +/- 6.12 microg/l at day 0 to 43.77 +/- 33.08 microg/l by day 56. There was no increase in serum PSA after LHRHA administration.

CONCLUSIONS
Two weeks of priming with CPA does not eliminate the surge in serum testosterone (testosterone flare) upon LHRHA administration but the testosterone increase does not exceed pretreatment levels. Furthermore, 2 weeks of CPA may not offer a benefit over 1 week in lowering serum testosterone. Finally, there is no increase in serum PSA when LHRHA is administered after priming with CPA.


Surface X-ray diffraction has been employed to quantitatively determine the geometric structure of an X-ray-induced superhydrophilic rutile-TiO2(110)(1 × 1) surface. A scatterer, assumed to be oxygen, is found at a distance of 1.90 ± 0.02 Å above the five-fold-coordinated surface Ti atom, indicating surface hydroxylation. Two more oxygen atoms, situated further from the substrate, are also included to achieve the optimal agreement between experimental and simulated diffraction data. It is concluded that these latter scatterers are from water molecules, surface-localized through hydrogen bonding. Comparing this interfacial structure with previous studies suggests that the superhydophilicity of titania is most likely to be a result of the depletion of surface carbon contamination coupled to extensive surface hydroxylation.


: This study presents the first record of the recently colonizing lugworm species Arenicola defodiens in the Iberian Peninsula, and both A. defodiens and Arenicola marina in the Ria de Aveiro lagoon (northwest Portugal). We aimed firstly to provide a distinction between these 2 species, using combined morphological and genetic approaches, and secondly to determine their spatial distribution in the lagoon. Morphological characteristics such as annulation pattern, gill morphology, and faecal cast size enabled differentiation between both species, and we provide an updated taxonomic key for the valid species of the Family Arenicolidae known in the Iberian Peninsula. To confirm the distinction between A. defodiens and A. marina , 16S rDNA and COI gene sequencing analyses were performed. The percentage of nucleotide divergence between A. defodiens and A. marina was 13.5% for COI and 5% for 16S, and phylogenetic analyses showed that these are closely related species. Recent surveys conducted in Ria de Aveiro lagoon indicate that both species are dispersing throughout the system. Lugworm faecal casts were observed for the first time at 4 sites in 2009, and then at 7 sites in 2011. In 2014, A. marina was recorded at 2 intertidal sites of the Ria de Aveiro, which were characterized by very fine and medium sand. A. defodiens displayed a wider distribution, being reported at 13 intertidal and 5 subtidal sites where sediment characteristics ranged from mud to medium sand. A. marina densities ranged from 20.5 to 26.0 ind. m 2 , higher than those recorded for A. defodiens , which did not exceed 3 ind. m 2 . The expansion and the establishment of arenicolids in the Ria de Aveiro lagoon could be a result of the 2009-2010 and 2010-2011 cold winters. Possible consequences of the spread of these bioturbators in this lagunar ecosystem are discussed.


Understanding the factors that contribute to the origin and maintenance of species, and elucidating the mechanisms that influence species' distribution across the landscape are two goals that are fundamental to evolutionary biology and ecology. I combined field and laboratory experiments, a robust phylogeny, and species distribution data from herbaria to test a series of hypotheses that address variation in the distribution of species, and, the evolution and maintenance of reproductive isolating barriers, key components for understanding speciation. I used species in the genus Collinisa to test the following main hypotheses: 1) An extension of Baker's Law: Among similar aged sister-taxa pairs, species more proficient at autonomous self-fertilization should be better colonizers and thus should have larger range sizes than their sister-taxa that are less proficient at autonomous selfing, 2) Bateson-Dobzhansky-Muller (BDM) model of reproductive isolation: Intrinsic postzygotic isolation barriers increase as divergence time increases among species, and 3) Reinforcement of reproductive isolation: early selfing can evolve in response to heterospecific pollen receipt, and may thus act as a prezygotic reproductive isolating barrier that is reinforced in sympatry. I found that species most proficient at selfing had significantly larger range sizes than their sister-taxa that were less proficient at selfing. Thus, mating system did explain differences in the ranges sizes of similar aged sister-taxa. To address the second hypothesis, I first tested for allopatric speciation in this genus, and found strong support for allopatric speciation in the California clade of Collinsia. But I did not find strong support overall, likely because of large range-shifts in the northeastern clade, which obscured the expected pattern of increasing range overlap with increasing divergence time. In support of the BDM model, I found that post-mating pre- and postzygotic isolation increased with increasing divergence time. And finally, in support of the final prediction, I found that when C. rattanii was sympatric with C. linearis it self-pollinated at a significantly earlier stage, suggesting that earlier selfing may be acting to reinforce of reproductive isolation in sympatry.


The National Highway Asset Management Project consists of rehabilitation and maintenance works on the paved road network in Argentina, and, it is not foreseen that significant environmental impacts will occur; therefore, the project has been classified as Category B in accordance with the Bank's operational directive 4.01. However, minimal environmental risks may arise, and mitigation measures shall be activated. To this end, this environmental assessment (EA) is structured in four pillars: a) environmental evaluation of subprojects; b) capacity assessment of the Environmental Unit of the Direccion Nacional de Vialidad (DNV), the National Directorate of Highways; c) revision of existing mechanisms to implement environmental activities; and, d) compliance with environmental legislation. An analysis of the Environmental Management Unit of DNV identified two activities that need improvement: 1) updating the current environmental management and evaluation manual - MEGA93 -; and, 2) developing an institutional strengthening plan for DNV's environmental and social management. Finally, contractors are required to comply with the legislation imposed by the Environmental Authority, relative to the corresponding jurisdiction. The EA contains the environmental analysis (v. 1), technical specifications (V. 2), institutional strengthening plan (V. 3), an updated manual on environmental management for construction of highways (V. 4), and, evaluation checklists of subprojects (V. 5).


Surface chemical characteristics of root cell walls extracted from two tobacco genotypes exhibiting differential tolerance to Mn toxicity were studied using potentiometric pH titration and Fourier transform infrared spectroscopy. The Mn-sensitive genotype KY 14 showed a stronger interaction of its cell wall surface with metal ions than did the Mn-tolerant genotype Tobacco Introduction (T.I.) 1112. This observation may be attributed to the relatively higher ratio of COO(-) to COOH in KY 14 cell walls than that found in the cell walls of T.I. 1112 in the pH range of 4 to 10. For both genotypes, the strength of binding between metal ions and cell wall surface was in the order of Cu > Ca > Mn > Mg > Na. However, a slightly higher preference of Ca over Mn was observed with the T.I. 1112 cell wall. This may explain the high accumulation of Mn in the leaves of Mn-tolerant genotype T.I. 1112 rather than the high accumulation of Mn in roots, as occurred in Mn-sensitive KY 14. It is concluded that surface chemical characteristics of cell walls may play an important role in plant metal ion uptake and tolerance.


Quantification of global sustainable energy security (ES) becomes urgent, but the concepts of ES are still not clear. Thus, this paper is originated from philosophical ES studies, in which the various concepts came from the differences in determining the observed multi-matters (energy, equipment, human, and ecosystem: EPME) and point of view to see the EPME. Therefore, this research is aimed at measuring the EPME variables, producing ES material quantities (Q es ). Q es is derived after a 4-stage unification and is defined in a formula. The formula is then applied to calculate the top ten populous nations in the world from 1990 to 2015. Based on the top Q es values, the rankings are Russia (Fed.), USA, Japan, Brazil, China, Indonesia, India, Nigeria, Pakistan, and Bangladesh. The results also highlighted the Q es disparities between nations. A relationship between Q es and National Power Indicator (NPI) was also explored, indicating the ES saturation in the USA and Japan; and the macro energy-policy instability phenomenon in Nigeria. In addition, a comparison of Q es ranking to those of other scholars' results was presented. Finally, the macro sustainable energy policy implication is also highlighted.


This project is a continuation of my specialization project which was focused on studying theoretical concepts related to case based reasoning method, rule based reasoning method and integration of them. The integration of rule-based and case-based reasoning methods has shown a substantial improvement with regards to performance over the individual methods. Verdande Technology As wants to try integrating the rule based reasoning method with an existing case based system. This project focuses on designing, implementing and testing of a demo system that demonstrates the development of a rule based reasoning component and integrating it with the existing case based system of Verdande Technology As.


Prostate require high levels of steroidogenic enzymes such as 5α‐reductase (5α‐r) and Aromatase (Aro) for the formation of active steroids. Dihydrotestosterone (DHT), the prostate dominant androgen, is converted from testosterone (T) by the action of 5α‐r. Aro provides an alternative pathway for estrogen, via T aromatization. Since prostatic maintenance is dependent on both reciprocal stromal–epithelial interaction and regulation by steroids, this study aimed to elucidate what the absence of 5α‐r and Aro enzymes provokes in the prostate microenvironment after their long‐term inhibition. Data obtained 1 day after the 30 consecutive days of enzymatic inhibition with Finasteride (5α‐r inhibitor) and Letrozole (Aro inhibitor) demonstrated a marked stromal remodeling, with an increased deposition of extracellular matrix (ECM) proteins besides androgen receptor (AR) overexpression in the three phases of postnatal development analyzed. The subepithelial area of acini from ventral prostate presented collagen and reticular fibers accumulation, besides various altered and active fibroblasts. The AR content immunostaining was elevated after enzymatic inhibition therapy, mainly in the nuclei of epithelial cells. Similar data were observed in the ventral prostates even 21 days after the end of treatments. Results obtained following the long‐term inhibition of 5α‐r and Aro are relevant and highlight the actions of these enzymes as crucial not only for the maintenance of tissue architecture and ECM arrangement but also for androgen and AR function. The long‐term absence of their action imposes a novel situation on the prostate from which its normal physiology could not be restored by the conclusion of the treatments. Microsc. Res. Tech., 2009. © 2009 Wiley‐Liss, Inc.


A The newspaper production process has come a long way from the old days when the paper was written, edited, typeset and ultimately printed in one building with the journalists working on the upper floors and the printing presses going on the ground floor. These days the editor, subeditors and journalists who put the paper together are likely to find themselves in a totally different building or maybe even in a different city. This is the situation which now prevails in Sydney. The daily paper is compiled at the editorial headquarters, known as the prepress centre, in the heart of the city, but printed far away in the suburbs at the printing centre. Here human beings are in the minority as much of the work is done by automated machines controlled by computers.


for Down-syndrome. We prospectively measured and compared prenasal soft tissue thickness (PT) and nasal bone length (NBL) in second trimester euploid and trisomy-21 fetuses. Methods: Using 2D abdominal ultrasound the measurement of PT and NBL was taken in mid-sagittal plane of the fetal head identifying diencephalon, tip of the nose, lips, maxilla, mandible, nasal bone in weeks 16–23 in the second trimester. The PT is the shortest distance from the bottom edge of the os frontale to the outer surface of the overlying skin. The nasal bone was measured from this view. The insonation angle was 90◦ (perpendicular) to the nasal bone. NBL/PT ratios of euploid fetuses between 16–23 weeks were analyzed and validated by Shapiro-Wilke test. We used software (SigmaStat 12 & SigmaPlot 12) to create graphs, the regression line and the percentiles curves (5th –25th –75th –95th) have been calculated from the normal values. We used the normal graphs to visualize and compare trisomy 21 cases to euploids (P < 0.0001). Results: Analyzes of 810 euploid and 19 fetuses with trisomy 21 measured between the 16–23 gestational weeks were done. In euploid fetuses the mean PT and NBL increased steadily between 16 and 33 weeks' gestation. The difference in the median PT values between the two groups was greater than would be expected by chance. There was a statistically significant difference (P = <0.001) Mann-Whitney Rank Sum Test. All of the 19 fetuses with trisomy 21 the NBL/PT values were lower than 5th percentile curve of the euploid group. Conclusions: CIn fetuses with trisomy 21 the NBL/PT ratio was significantly lower compared to euploid ones. The NBL/PT ratio was found to be very sensitive and specific marker for trisomy 2.


The primary focus of the Oklahoma Weather Modification Program is to suppress hail and augment rainfall. Initiated in the fall of 1996, the demonstration program is patterned after similar successful efforts underway in Kansas, North Dakota, Texas and Alberta, Canada. In 1997 and 1998, the statewide program incorporated an independent evaluation to measure results, although no randomized cloud seeding operations were conducted. Results of the evaluation are promising. Prompted, in part, by the need for additional resources to implement the program at the desired capacity, the State Legislature passed legistation in 1999 to create a cooperative, long-term funding mechanism between state and the Oklahoma's insurance industry. Potential interstate cooperation with weather modification efforts in Texas and Kansas bode well for the continuation and future growth of the program.


Regional shocks are an important feature of the U.S. economy. Households' ability to self-insure against these shocks depends on how they affect local interest rates. In the U.S., most borrowing occurs through the mortgage market and is influenced by the presence of government-sponsored enterprises (GSEs). We establish that despite large regional variation in predictable default risk, GSE mortgage rates for otherwise identical loans do not vary spatially. In contrast, the private market does set interest rates which vary with local risk, and we postulate that the lack of regional variation in GSE mortgage rates is likely driven by political pressure. We use a spatial model of collateralized borrowing to show that the national interest rate policy substantially affects welfare by redistributing resources across regions.


SUMMARY Foodborne outbreaks of cryptosporidiosis are uncommon. In Denmark human cases are generally infrequently diagnosed. In 2005 an outbreak of diarrhoea affected company employees near Copenhagen. In all 99 employees were reported ill; 13 were positive for Cryptosporidium hominis infection. Two analytical epidemiological studies were performed; an initial case-control study followed by a cohort study using an electronic questionnaire. Disease was associated with eating from the canteen salad bar on one, possibly two, specific weekdays [relative risk 4·1, 95% confidence interval (CI) 2·1–8·3]. Three separate salad bar ingredients were found to be likely sources: peeled whole carrots served in a bowl of water, grated carrots, and red peppers (in multivariate analysis, whole carrots: OR 2·1, 95% CI 1·1–4·0; grated carrots: OR 2·1, 95% CI 1·2–3·9; peppers: OR 3·3, 95% CI 1·7–6·6). We speculate that a person excreting the parasite may have contaminated the salad buffet.


Plans are underway to construct twelve large hydropower projects on the un-dammed lower and middle mainstream Mekong River in Laos, Thailand, and Cambodia. One of the planned projects is a 30–32 meter–high hydroelectric dam with an expected 240 MW installed generating capacity to be built on the Hou Sahong Channel, less than one kilometer north of the Laos–Cambodia border, in the Khone Falls area of Khong District, Champasak Province, southern Laos. The project's objective is to generate revenue by exporting electricity to Thailand or Cambodia. Concerns have been raised about the Don SahongDam(DSD), however. The main ones relate to potential repercussions on aquatic resources, and especially wild-capture fisheries dependent on migratory fish. This article examines the regional implications of the DSD, including possible impacts on food security, nutrition, and poverty alleviation. Fisheries losses in the Mekong Region from the DSD would negatively affect the nutrition of hundreds of thousands or even millions of people, especially in parts of Laos, Cambodia, and Thailand where nutritional standards are already low. Mekong fisheries are integral to food security in the region, and the DSD would make it difficult for governments, especially in Laos and Cambodia, to reach their health-related United Nations Millennium Development Goals and their objectives for reducing poverty.


This paper looks at where people work, in relation to an organization's central (head) office, and its effect on levels of organizational fit. It will suggest that organizational fit may be reduced according to whether employees work in the head office, regional offices or are home-anchored. The question as to the extent to which regional and/or home-anchored employees still have some degree of fit (and possible reasons for this) or regionality becomes a safe haven for misfits (and the implications of this) will also be considered.

The paper considers and questions, in the light of ASA theory, whether misfits are likely to leave or, indeed, in a regional or home-anchored situation, may become centres for organizational learning/innovation and/or resistance. It goes on to suggest a means for testing the hypotheses with a study of employees at the Open University.


Continuing the series of workshops begun in 1996 (Luck, 1997; Doran et al., 1997; d'Inverno et al., 1997; Fisher et al., 1997) and held in each of the two years since (Luck et al., 1998; Aylett et al., 1998; Binmore et al., 1998; Decker et al., 1999; Beer et al., 1999), the 1999 workshop of the UK Special Interest Group on Multi-Agent Systems (UKMAS'99) took place in Bristol in December. Chaired and organised by Chris Preist of Hewlett Packard Laboratories, with support from both HP and BT Laboratories, the workshop brought together a diverse range of participants, from the agent community in both the UK and abroad, to discuss and present work spanning all areas of agent research. Although dominated by computer scientists, also present at the meeting were electronic engineers, computational biologists, philosophers, sociologists, statisticians, game-theorists, economists and behavioural scientists, with both academia and industry well represented. Indeed, numbers attending these workshops continue to grow, reflecting the continued and rising interest in agent-based systems. The meeting truly demonstrated the wider view of what the term "agency" implied to research in other disciplines and the questions raised at the end of presentations were a pertinent reminder of the diversity of the audience.


Roentgenometric and roentgenodensitometric chronobiological characteristics of space and time remodeling of the bone tissue in tail vertebra XI and XII after osteotomy of the right femur are described. Examination of 179 white non-inbred male rats revealed circadian periodicity of vertebral bone tissue remodeling. Dynamics of asymmetry of this process also has a circadian periodicity.


Successful surgical correction of coarctation of the aorta was first accomplished in 1945. 1,2 With improving operative techniques it is now generally agreed that the uncomplicated defect is best repaired during childhood. Most fatalities, however, occur during the first year, and attention more recently has been directed to surgical intervention in infancy. The purpose of this paper is to review 53 consecutive cases from a diagnostic and operative point of view. Bonnet 3 originally classified this condition as being of either the infantile or adult type. This classification corresponds in general to the anatomical separation of preductal and postductal coarctation depending upon whether the constriction of the aorta occurs proximal or distal to the mouth of the ductus arteriosus. Others 4 have subdivided these groups further on the basis of whether or not the ductus is patent. Even at operation, however, anatomic classification is often difficult or even impossible, since


In the last years, we have seen a growing interest of the scientific community first and commercial
vendors then, in new technologies like Grid and Cloud computing. The first in particular, was born to
meet the enormous computational requests mostly coming from physic experiments, especially Large
Hadron Collider's (LHC) experiments at Conseil Europeen pour la Recherche Nucleaire (European
Laboratory for Particle Physics) (CERN) in Geneva. Other scientific disciplines that are also benefiting
from those technologies are biology, astronomy, earth sciences, life sciences, etc. Grid systems allow
the sharing of heterogeneous computational and storage resources between different geographically
distributed institutes, agencies or universities. For this purpose technologies have been developed to
allow communication, authentication, storing and processing of the required software and scientific
data. This allows different scientific communities the access to computational resources that a single
institute could not host for logistical and cost reasons. Grid systems were not the only answer to this
growing need of resources of different communities. At the same time, in the last years, we have seen
the affirmation of the so called Cloud Computing. Cloud computing is a model for enabling
convenient, on-demand network access to a shared pool of configurable computing resources (e.g.:
networks, servers, storage, applications, and services) that can be rapidly provisioned and released with
minimal management effort or service provider interaction. The use of both computational paradigms
and the utilization of storage resources, leverage on different authentication and authorization tools.
The utilization of those technologies requires systems for the accounting of the consumed resources.
Those systems are built on the top of the existing infrastructure and they collect all the needed data
related to the users, groups and resources utilized. This information is then collected in central
repositories where they can be analyzed and aggregated. Open Grid Forum (OGF) is the international
organism that works to develop standards in the Grid environment. Usage Record - Working Group
(UR-WG) is a group, born within OGF aiming at standardizing the Usage Record (UR) structure and
publication for different kinds of resources. Up to now, the emphasis has been on the accounting for
computational resources. With time it came out the need to expand those concepts to other aspects and
especially to a definition and implementation of a standard UR for storage accounting. Several
extensions to the UR definition are proposed in this thesis and the proposed developments in this field
are described. The Distributed Grid Accounting System (DGAS) has been chosen, among other tools
available, as the accounting system for the Italian Grid and is also adopted in other countries such as
Greece and Germany. Together with HLRmon, it offers a complete accounting system and it is the tool
that has been used during the writing of the thesis at INFN-CNAF.
• In Chapter 1, I will focus on the paradigm of distributed computing and the Grid infrastructure
will be introduced with particular emphasis on the gLite middleware and the EGI-InSPIRE
project.
• In Chapter 2, I will discuss some Grid accounting systems for computational resources with
particular stress for DGAS.
• In Chapter 3, the cross-check monitoring system used to check the correctness of the gathered
data at the INFN-CNAF's Tier1 is presented.
• In Chapter 4, another important aspect on accounting, accounting for storage resources, is
introduced and the definition of a standard UR for storage accounting is presented.
• In Chapter 5, an implementation of a new accounting system for the storage that uses the
definitions given in Chapter 4 is presented.
• In Chapter 6, the focus of the thesis move on the performance and reliability tests performed on
the latest development release of DGAS that implements ActiveMQ as a standard transport
mechanism.
• In Appendix A are collected the BASH scripts and SQL code that are part of the cross-check
tool described in Chapter 3.
• In Appendix B are collected the scripts used in the implementation of the accounting system
described in Chapter 5.
• In Appendix C are collected the scripts and configurations used for the tests of the ActiveMQ
implementation of DGAS described in Chapter 6.
• In Appendix D are collected the publications in which I contributed during the thesis work


This paper estimates the marginal abatement costs (MACs) for CO2 emission in the Indian coal-based thermal power sector employing a non-parametric by-production approach. The estimates so obtained are compared with those from weak and joint-disposabilitybased approaches. In contrast to the other two approaches, by-production approach computes the MAC as the reduction in electricity generation necessitated by a reduction in coal (heat) input when emission generation is reduced by one unit. Under this approach, the estimates of the reduction in heat input per-unit reduction in emission generation lie in a small range around the same computed for the true data-generating process. The MACs varied widely between 58.92 to 102.28 USD/metric-ton of CO2, with a mean value of 85 USD/metric-ton in 2015, indicating a tremendous potential for emission-trading or a Pigouvian tax as policy tools for correcting the allocative inefficiencies in this sector.


Lubricated reciprocating tests were conducted on an SRV tester to investigate effects of stroke and frequency on frictional and wear properties of flaky graphite cast iron used for marine cylinder liner by varying frequency and stroke under a given sliding velocity in boundary and mixed lubrication regime. It was clarified that changes in coefficient of friction were significantly dependent on stroke and frequency: in boundary lubrication, coefficient of friction at steady state showed a lower value at a combination of lower frequency and therefore larger stroke. In mixed lubrication, however, a combination of lower frequency and larger stroke produced a higher friction. In boundary lubrication where no run-in process was observed, higher frequency contributed to producing rougher surfaces resulting in higher friction. In mixed lubrication bordering on boundary lubrication higher frequency promoted run-in, enhancing film formation and lowering friction. Effects of frequency and stroke also reflected on wear, changes in separation voltage between a disk and a ball specimen, which were in accordance with changes in friction.


We propose a novel methodology for fault detection and diagnosis in partially-observed Boolean dynamical systems (POBDS). These are stochastic, highly nonlinear, and derivativeless systems, rendering difficult the application of classical fault detection and diagnosis methods. The methodology comprises two main approaches. The first addresses the case when the normal mode of operation is known but not the fault modes. It applies an innovations filter (IF) to detect deviations from the nominal normal mode of operation. The second approach is applicable when the set of possible fault models is finite and known, in which case we employ a multiple model adaptive estimation (MMAE) approach based on a likelihood-ratio (LR) statistic. Unknown system parameters are estimated by an adaptive expectation-maximization (EM) algorithm. Particle filtering techniques are used to reduce the computational complexity in the case of systems with large state-spaces. The efficacy of the proposed methodology is demonstrated by numerical experiments with a large gene regulatory network (GRN) with stuck-at faults observed through a single noisy time series of RNA-seq gene expression measurements.


Aerosol treatment with RU 41821, a glycoprotein extract from Klebsiella pneumoniae, was tested in mice for its effect on the kinetics of the induction of bronchoalveolar cells (i.e., alveolar macrophages, monocytes, lymphocytes, and polymorphonuclear leukocytes). RU 41821 led to an increase in the total number of bronchoalveolar cells. The largest increase was observed for polymorphonuclear leukocytes, and more moderate increases occurred in the numbers of alveolar macrophages, monocytes, and lymphocytes. The alveolar macrophages recruited in response to RU 41821 were activated, as indicated by luminol-dependent chemiluminescence in response to stimulation by opsonized zymosan. The effects of five RU 41821 aerosol treatments and those of a single treatment were further examined in vivo by aerosol infection of mice inoculated with a mouse-pathogenic influenza virus. The maximum protective effect was obtained after five once-a-day treatments and was correlated with the largest increase in the total number of bronchoalveolar cells.


BACKGROUND: Multiple myeloma (MM) is the most common hematologic malignancy in the African American population, with an incidence more than 2 times higher than Caucasian population [Landgren O et al Blood 2006]. Historically, the African American MM patients have had better outcomes compared with other races [Ailawadhi S et al Br J Haematol 2012], but no biologic explanations exist for this observation. Greenberg et al [Blood Cancer J 2015] have recently reported on differences in commonly observed baseline cytogenetic abnormalities (CA) between African American and Caucasian MM patients seen at Mayo Clinic (Rochester, MN), Cook County Hospital (Chicago, IL) and University of Maryland (Baltimore, MD). We examined the MM cohort at our referral center to validate these observations.

PATIENTS & METHODS: The Levine Cancer Institute MM database was interrogated for all patients presenting with MM between January 2012 and April 2015. Baseline clinical and pathology variables were compared between the African American and Caucasian cohorts. Continuous variables were compared using nonparametric rank tests, while incidences and proportions (e.g. CAs including t(11;14), t(4;14), monosomy13/del13q and del17p) were compared using Fisher's exact tests.

RESULTS: A total of 662 patients were identified; excluding those with MGUS classification, 368 patients were included in the analysis (African Americans n = 130, Caucasian n = 238). The median age of African American MM patients was significantly younger than Caucasian MM patients (median age 60 years vs. 65 years, p=0.010), with similar gender distribution. There was a numerically larger proportion of African American patients with anemia (40.8% vs 30.8%, p =0.166), however, there was no significant difference in degree of BM plasmacytosis amongst the two groups. The overall distribution of MM patients by IMWG risk stratification (Chng et al, Leukemia 2013) was also similar between the two groups. The African American MM patients had a numerically higher incidence of a metaphase abnormality on conventional cytogenetics (21.7% vs. 13.9%, p =0.154). They had a significantly lower incidence of t(11;14) [7.7% vs. 16%, p=0.024], a numerically higher incidence of t(4;14) [6.2% vs. 3.8%, p=0.309], and similar incidence of deletion 13/del13q [22.3% vs. 18.9%, p= NS ] and del17p [7.7% vs. 7.6%, p= NS ].

CONCLUSIONS: The present dataset is the largest single institution report on CA racial differences in MM patients. We found that unlike previous reports of lower incidence of t(4;14) or del17 p in African American MM patients by Greenberg et al, we have observed a higher incidence of t(4;14) and similar incidence of del17p in our experience compared to Caucasian MM patients. The different pattern of CA distribution compared to published literature may represent geographic heterogeneity and potentially influence survival outcomes.

Disclosures Cogdill: Celgene: Speakers Bureau; Onyx: Speakers Bureau; Millennium: Speakers Bureau; Novartis: Speakers Bureau. Usmani: Celgene: Honoraria, Speakers Bureau; Onyx: Honoraria, Research Funding, Speakers Bureau; Janssen Oncology: Honoraria, Research Funding; Sanofi: Honoraria, Research Funding; Pharmacyclics: Research Funding; Millennium: Honoraria, Speakers Bureau; Array BioPharma: Honoraria, Research Funding.