Antimicrobial peptides (AMPs) are relatively short peptides endowed with broad spectrum antimicrobial, anti-inflammatory immunomodulating and wound healing enhancement activity. They are essential components of the innate immune system of higher eukaryotes providing the first line of defense against microbial invasions. AMPs are extremely heterogeneous in length, structure, aminoacid composition and, more importantly, molecular mechanism of bacterial killing. From this point of view AMPs can be divided in at least four wide classes: (i) cationic antimicrobial peptides (CAMPs); (ii) anionic antimicrobial peptides (AAMPs); (iii) histidine-rich antimicrobial peptides (HAMPs), and (iv) AMPs with intracellular targets (DNA, RNA, ribosomes, chaperons, enzymes).
The pharmacological potential of AMPs, and especially of AMP mixtures, is obvious. However the costs of pharmaceutical formulations including two or more peptides separately produced would be so high that even a very interesting pharmacological activity would not compensate for the effort needed to prepare the mixture. Accordingly, the aim of the present project is to develop a strategy to prepare mixtures of two or more AMPs with costs, production times and amount of work comparable to those necessary for the production of a single recombinant AMP.
Two alternative strategies were evaluated, one exploiting a previously optimized-carrier protein for the production of recombinant AMPs as fusion proteins, and an alternative strategy aiming to prepare a carrier-less precursor composed only by AMP modules.
The carrier developed by our group, ONC-DCless-H6, was able to effectively drive to inclusion bodies both a highly cationic sequence of about 50 residues [(P)PAP-A3(Pro26)] containing two CAMP-like sequences and a modular sequence (AT2H) of more than 100 residues including 2 anionic, 2 cationic and a histidine rich module. In both cases expression yields were high (>200 mg/L and >100 mg/L, respectively). Purification by IMAC provided a protein with good yield and purity. Purified recombinant proteins were hydrolyzed in 0.1 M acetic acid at 60°C to cleave the acid labile Asp-Pro sequences at the junction sites between consecutive AMP modules. The efficiency was very high in the case AT2H, which provided only the desired peptides, thus indicating that all the acid labile Asp-Pro sequences underwent cleavage with an efficiency higher than 95%. Only in the case of (P)PAP-A3(Pro26), the internal Asp-Pro sequence was cleaved with an efficiency of only about 85%. The comparison of the sequences adjacent to the different Asp-Pro cleavage sites in (P)PAP-A3(Pro26) and AT2H suggested that in order to obtain a very high cleavage efficiency a flexible sequence, rich in small and/or coil-preferring amino acids should be present at least on one side of the Asp-Pro site. This information will be useful for the design of further fusion proteins.
The carrier-less strategy was tested by preparing two modular precursors, AT5H (containing 5 anionic, 5 cationic and a histidine rich module) and AT4LH (containing 4 anionic, 4 cationic and a histidine rich module). AT5H and AT4LH showed relatively low expression levels (15 and 30 mg/L, respectively) and a different behavior of the inclusion bodies formed upon recombinant expression. In fact, the inclusion bodies, differently from those generated by ONC-DCless-H6, were soluble in 2 M urea thus suggesting a lower compactness/stability. A possible cause of the low expression levels could be the non-optimal codon usage of the coding sequences necessary for avoiding the presence of identical direct repeats which would have made difficult the chemical synthesis of the coding sequences. Low expression levels, in turn, could have contributed to the formation of "unstable" inclusion bodies. Indeed, it is well known that inclusion bodies formation is generally related to high expression levels. In the future, alternative approaches based on ligation of multiple copies of a smaller fragment could allow preparing coding sequences where all the repeats have an optimal codon usage.


Populations of large herbivores are generally considered to be food limited, escaping the regulatory effects of predation through their large body size, migratory behaviour and/or the occurrence of alternate prey species. In the Australian arid and semi-arid zones, the availability of forage biomass is considered to be the primary driver of fluctuations in kangaroo abundance. However, little is known about the population dynamics of the smaller sympatric macropods. We examined the demographic traits of a large colony of yellow-footed rock-wallabies (Petrogale xanthopus celeris), following a 2-year period of above average rainfall. The population was located within a conservation reserve that was subject to a predator control program around its perimeter and on neighbouring properties. The low predator abundance provided an opportunity to gauge the strength of bottom-up population processes. During the two years of the study, the population declined in size by 53%, resulting from both the virtual absence of juvenile recruitment and the loss of adult wallabies. Although reproductive output was high, low pouch young and juvenile survival rates resulted in few individuals progressing into the adult population. With minimal recruitment, the rate of population decline (r=0.77) matched the observed adult survival rate (Φ=0.76). Despite average rainfall conditions during the study, survival rates across all age-classes were equivalent to those reported for other rock-wallaby populations during periods of scarcity. The reduced survival rates were attributed to low levels of forage resources, particularly around the wallabies' refuge sites, suggesting the bottom-up regulation of the colony at high densities. The data suggest that the colony was at temporarily high abundance, following a rainfall driven pulse of recruitment. Conservation management actions for this species should focus on increasing juvenile survival rates within declining populations, through the control of feral goats (Capra hircus), rabbits (Oryctolagus cuniculus) and red foxes (Vulpes vulpes).


Walnut, Juglans regia (L.) is an economically significant plant for its immense nutritive and economic value. The breeding character of walnut has lent it a wide diversity in genetic characteristics. The principal vegetative and common traditional agronomic traits together with biochemical characterization i.e., karyotyping and isoenzyme expression have been the early research methods. However, these techniques are time-consuming and susceptible to the environmental variations. Literature is meager in the distribution, applied applications in general and the use of agriculture biotechnology in particular in case of walnut plants. The bio-techniques like molecular markers are adequate in number and there is little or no diversity in the method employed for research on walnuts. Despite basic research method, the organization of information, its retrieval and presentation structures, form elaboration experienced immense advancement via molecular markers such as RFLP, ISSR, RAPD AFLP, SSR and SNP. This appraisal in its first part provides detailed information regarding the present scenario of data on biogeographical distribution, health benefits of walnut worldwide and current applications in the agroforestry management, biochemical evaluations and applied uses of a walnut tree which is relevant for both basic and applied research. The review in its second part sheds light on the application of sophisticated agricultural biotechnology techniques such as use of molecular markers to evaluate, realize the full potential of walnut for increasing its quality, quantity and for its sustainable production which cannot be obtained through usual breeding techniques to meet the demands of a projected world population.


IntroductionEvaluations of healthcare utilisation for children and young people (CYP) with chronic conditions, are increasingly relying upon routinely collected healthcare data to estimate healthcare burden and inform national policy and practice. However, chronic conditions are not consistently or accurately recorded making it difficult to conduct valid epidemiological analyses.
Objectives and ApproachWe explored routinely collected healthcare datasets of 2,122,914 CYP in the English Clinical Practice Research Dataset (CPRD) and 1,636,252 CYP in the Welsh Secure Anonymous Information Linkage (SAIL) databank to identify patients with CP (an exemplar of a chronic neurodisability) from diagnosis coding (G80-83.3). Linked primary care, hospital admission outpatient and mortality data were searched from birth and populations of CYP aged 0-25 years between 2004 and 2014 with and without CP were identified. We detected the ascertainment sources and compared the results from CPRD and SAIL. In a sample of cases G80-83 codes were validated against clinical records.
Results
England: Some 7,500 cases of CP were identified (period prevalence: 3.5 per 1000 CYP). Of those, 36.6% were identified from hospital admissions; 20.6% from GP data, 42.0% were in both datasets with 0.8% from outpatient/ONS mortality data.
Wales: Some 5,400 cases of CP were identified (period prevalence: 3.3 per 1000 CYP). Of those, 38.6% were identified from hospital admissions, 25.3% from GP data, 36.0% were in both datasets, and 0.1% from mortality/outpatient datasets.
729/877(83.1%) cases coded as G80-83 in secondary care case notes were validated cases of CP leaving 16.9% that were incorrectly coded. Approximately 70% of G80 cases were recorded as G80.8-9 (CP other/unspecified). Roughly 30% of cases were only coded as CP on one occasion within the primary and secondary care datasets.
Conclusion/ImplicationsSimilar proportions of CP cases were identified in the two datasets giving similar period prevalences. Inconsistent and incorrect coding will affect the accuracy of these figures and precludes any analysis by disease type/severity. Improved coding of chronic conditions is needed before accurate healthcare analysis of routine data can be undertaken.


Purpose: The purpose of this study was to compare the effects of resiniferatoxin (RTX) and botulinum toxin (BTX) on the bladder detrusor function in a cyclophosphamide (CYP)-induced cystitis rat model. Materials and Methods: Sprague-Dawley rats were divided into 5 groups (1: saline treated, 2: CYP and BTX treated, 3: CYP and RTX treated, 4 and 5: CYP treated and sham operated as the counterpart of groups 2 and 3, respectively, with normal saline). 100mg/kg CYP was injected every third day for five weeks. Cystometrograms were performed after the BTX and RTX treatments. Results: 1. The normal control group and the CYP-treated only group. In the CYP-treated group, the time of micturition frequency, the maximal detrusor pressure on the cystometergram (Pvesmax at CMG), the maximal detrusor pressure on the pressure-flow study (Pvesmax at pr/flow) and the episodes of irregular contractions were increased. 2. The CYP-only group and the CYP/BTX or CYP/RTXtreated groups. In the CYP/BTX or CYP/RTX treated groups, the time of micturition frequency, the Pvesmax at CMG, the Pvesmax at pr/flow and the episode of irregular contractions were decreased. 3. The CYP/BTXtreated group and the CYP/ RTXtreated group. There was no statistically significant difference between the two groups regarding micturition frequency, the PvesMax at CMG and the PvesMax at pr/flow, the Dhfo and the episodes of involuntary contractions (p>0.05). Conclusions: Intravesical administration of BTX or RTX blocked the CYP-induced detrusor overactivity as was shown by the restoration of the micturition frequency, the intravesical pressure and the involuntary contraction episodes to a control level. There was no statistically significant difference between the two groups regarding the urodynamic parameters. (Korean J Urol 2006;47:47-54)


Lattice deformers are a popular option for modeling the behavior of elastic bodies as they avoid the need for conforming mesh generation, and their regular structure offers significant opportunities for performance optimizations. Our work expands the scope of current lattice-based elastic deformers, adding support for a number of important simulation features. We accommodate complex nonlinear, optionally anisotropic materials while using an economical one-point quadrature scheme. Our formulation fully accommodates near-incompressibility by enforcing accurate nonlinear constraints, supports implicit integration for large time steps, and is not susceptible to locking or poor conditioning of the discrete equations. Additionally, we increase the accuracy of our solver by employing a novel high-order quadrature scheme on lattice cells overlapping with the model boundary, which are treated at sub-cell precision. Finally, we detail how this accurate boundary treatment can be implemented at a minimal computational premium over the cost of a voxel-accurate discretization. We demonstrate our method in the simulation of complex musculoskeletal human models.


Abstract We deal with the buy-and-hold choice of fund portfolios by considering multiple states of nature (future market scenarios). These states are associated with goals in the sense that the investor pursues to optimize a classical financial objective function as much as possible whatever the states of nature. As this classical function is very cumbersome for handling, a satisficing proxy is used. This proxy is Stochastic Goal Programming (SGP), a recent uncertainty multiobjective model characterized as follows: (a) it relies on Von Neumann and Morgenstern's-Arrow's Eu(R) principles in a framework of bounded rationality; (b) its moderate computational burden allows easy application to large scale problems. In SGP, the variability matrices of goals are aggregated by Arrow's risk aversion coefficients. Concerning the case study, the states of nature are Eurostoxx market index scenarios defined from time series. As an opportunity set of assets, we use a large set of funds managed by an international consultancy. Potential returns on each fund are related to each scenario by using betas. As eliciting betas can be made from different samples leading to different results, we use fuzzy logic to decide among these different results in a framework of imprecision/uncertainty. Our approach is new as it combines SGP and fuzzy tools.


It has come to the authors' attention that their article entitled "The protective effects of human umbilical cord mesenchymal stem cells on damaged ovarian function: A comparative study" (BioScience Trends. 2016; 10(4):265-276) included an error in Figure 4 (F, H). The corrected Figure 4 is printed below.


The present paper presents a model of investment decisions made by corporations. The decisions in question are perceived as part of corporate strategies, defined in a behavioural way. The model attempts to integrate the classical microeconomics\' point of view with that of the new institutional economics, formalizing the resulting assumptions on the grounds of three theories of games: Selten\'s, Harsany\i's and Nash\'s. Corporate strategies are defined as a set of four games: the capital market game, the corporate governance game, the product markets game and the social responsibility game. The four games are played in parallel and in mutual interaction, each of them being a temporarily normalized sub-game of the Selten\'s extensive game with imperfect recall, and being played as a Harsanyi\'s game with imperfect information and various degrees of cooperation. In each of the four games the presence of Nash\'s dynamic equilibrium, manifested as a critical level of consistency in individual players\' strategies, is of crucial importance. In presence of Nash\'s dynamic equilibrium, corporations orient their behaviour towards development, technological progress included. In the absence of Nash\'s dynamic equilibrium corporations would orient their strategies exclusively on managing risk.


This article identifies challenges involved in teaching a mathematics class with 350 or more students. It discusses issues of preparation, organization, course administration, instruction, use of technology, and student management, while offering constructive help and useful techniques for teaching large mathematics classes. General reflections from three instructors on their large class teaching experiences are followed by a model of how large freshmen Calculus courses are conducted at Simon Fraser University in Burnaby, BC.


How NPS helped my USAF career: "I use my NPS Modeling and Simulation education every day in my present job. It allowed me to advance my technical career, contribute to the USMC training community, and enhance DoD level joint M&S initiatives. The unique NPS education environment allowed me to interface with sister services and the international community."


Little is known about the function and regulation of the Na+-K+-2Cl-cotransporter NKCC1 in vascular smooth muscle. The activity of NKCC1 was measured as the bumetanide-sensitive efflux of86Rb+from intact smooth muscle of the rat aorta. Hypertonic shrinkage (440 mosmol/kgH2O) rapidly doubled cotransporter activity, consistent with its volume-regulatory function. NKCC1 was also acutely activated by the vasoconstrictors ANG II (52%), phenylephrine (50%), endothelin (53%), and 30 mM KCl (54%). Both nitric oxide and nitroprusside inhibited basal NKCC1 activity (39 and 34%, respectively), and nitroprusside completely reversed the stimulation by phenylephrine. The phosphorylation of NKCC1 was increased by hypertonic shrinkage, phenylephrine, and KCl and was reduced by nitroprusside. The inhibition of NKCC1 significantly reduced the contraction of rat aorta induced by phenylephrine (63% at 10 nM, 26% at 30 nM) but not by KCl. We conclude that the Na+-K+-2Cl-cotransporter in vascular smooth muscle is reciprocally regulated by vasoconstrictors and nitrovasodilators and contributes to smooth muscle contraction, indicating that alterations in NKCC1 could influence vascular smooth muscle tone in vivo.


The distinction between physiological (apoptotic) and pathological (necrotic) cell deaths reflects mechanistic differences in cellular disintegration and is of functional significance with respect to the outcomes that are triggered by the cell corpses. Mechanistically, apoptotic cells die via an active and ordered pathway; necrotic deaths, conversely, are chaotic and passive. Macrophages and other phagocytic cells recognize and engulf these dead cells. This clearance is believed to reveal an innate immunity, associated with inflammation in cases of pathological but not physiological cell deaths. Using objective and quantitative measures to assess these processes, we find that macrophages bind and engulf native apoptotic and necrotic cells to similar extents and with similar kinetics. However, recognition of these two classes of dying cells occurs via distinct and noncompeting mechanisms. Phosphatidylserine, which is externalized on both apoptotic and necrotic cells, is not a specific ligand for the recognition of either one. The distinct modes of recognition for these different corpses are linked to opposing responses from engulfing macrophages. Necrotic cells, when recognized, enhance proinflammatory responses of activated macrophages, although they are not sufficient to trigger macrophage activation. In marked contrast, apoptotic cells profoundly inhibit phlogistic macrophage responses; this represents a cell-associated, dominant-acting anti-inflammatory signaling activity acquired posttranslationally during the process of physiological cell death.


To understand the current community structure on reefs in the Dry Tortugas, we conducted specieslevel surveys of macroalgae, coral diversity, herbivorous and game fishes, urchins, and substratum composition (e.g., rugosity) in shallow (3to 5-m depth) low-relief reef and hardbottom habitats in October 2007. We had particular interest in the ecological process of herbivory inside and outside of the "no-take" Research Natural Area (RNA) designated by the U.S. National Park Service in 2007, and establishing a baseline to assess future changes to trophic functioning. Diadema antillarum and herbivorous fish abundance, percent cover of macroalgae, and species richness of corals and gorgonians at the 18 randomly selected survey sites were not significantly different inside vs. outside of the RNA. Mean densities of D. antillarum ranged from 0.01 to 0.54 individuals m, with 11 of the 18 sites having densities above 0.10 individuals m. Both D. antillarum density and coral species richness were positively correlated to rugosity of the substratum. Diadema antillarum density was also positively related to percentage of the substratum composed of Acropora cervicornis rubble. Improved trophic functioning and increases in D. antillarum can improve reef condition in the Dry Tortugas, and the RNA is an important management tool to achieve increases in reef resilience to global-scale stressors.


Appropriately, "Why I Am Not a Painter"--which in fact suggests that he is--contains no visual images at all, though it describes the development of a painting. As in Pollock, what replaces image is not so much plot, though the poem does tell a story and imply an argument, as the movement of the individual line, frequently circling back on itself to create the duration as well as the depth and texture of a particular experience.


Pesticides are use in agriculture for their capacity to reduce pest and protect foods. Since their introduction in Africa by colonial masters, the use of these chemicals is constantly growing. Herbicides and insecticides are the two dominant categories. Although they are used in small quantities by farmers who own small exploitation, the frequency of their use, as well as overuses and misuses, constitutes serious factors of exposure and health risks. Farm workers are more vulner-able to occupational effects from pesticide inhalation and skin contacts. Failure to wear protective equipment and observe good agricultural practices explained health symptoms that are frequently experienced: eye and skin irritation, nausea, vomiting, and headache. Population is subject to chronic health effects due to repeated dietary intake of pesticides. Most consumed staple foods on the continent (cereals, vegetables, and fruits) have been found to be contaminated by one or multiple residues of pesticides. The level of residues is often higher than regula-tory limits. Organization of surveillance programs to monitor concentration of pesticide residues remains inexistent in most countries, same for toxicovigilance systems to documented poisoning cases. Current data underline the need to carry out pesticide health risk assessment in order to appreciate the threats they pose for public health.


The bloody confrontation between Utes and the U.S. Cavalry at the Colorado Ute Indian Agency in 1879 was a significant chapter in U.S. history. The government and Colorado citizens used this battle as a rhetorical flashpoint to justify removal of Utes from their land. This conflict presents an opportunity to revisit nineteenth-century violence over land. I suggest that a religious studies framework can deepen our understanding of the entanglement of tensions among ethnicity, morality, and land use. Ute Indians pastured hundreds of horses on land that Nathan Meeker, the white Indian agent, wished to plow. This paper argues that notions of religious and racial difference framed the land conflict between Meeker and the Utes, even as both groups viewed land as a means to gain status.


The spread of inaccurate and misleading information may alter behaviours and complicate crisis management, especially during an emergency like the COVID-19 pandemic. This paper aims to investigate information diffusion during the COVID-19 pandemic by evaluating news consumption on YouTube. First, we analyse more than 2 million users' engagement with 13,000 videos released by 68 YouTube channels, labelled with a political bias and fact-checking index. Then, we study the relationship between each user\~Os political preference and their consumption of questionable (i.e., poorly fact-checked) and reliable information. Our results, quantified using measures from information theory, provide evidence for the existence of echo chambers across two dimensions represented by political bias and the trustworthiness of information channels. We observe that the echo chamber structure cannot be reproduced after properly randomising the users' interaction patterns. Moreover, we observe a relation between the political bias of users and their tendency to consume highly questionable news.


Although arabinose isomerase (E.C. 22.214.171.124), a commercial enzyme for edible tagatose bioconversion, can be expressed in an Escherichia coli system, this expression system might leave noxious by-products in food. To develop an eligible tagatose bioconversion with food-safe system, we compared the tagatose production activity of immobilized arabinose isomerase expressed in Bacillus subtilis (a host generally recognized as safe) with that of the enzyme expressed in E. coli. A 48% increase in tagatose production (4.3 g tagatose/L at 69.4 mg/L·hr) was found using the B. subtilis-expressed immobilized enzyme system, compared to the E. coli-expressed enzyme system (2.9 g tagatose/L). The increased productivity with safety of the B. subtilis-expressed arabinose isomerase suggests that it is a more eligible candidate for commercial tagatose production.


Increased use of SBRT and hypofractionation in radiation oncology practice has posted a number of challenges to medical physicist, ranging from planning, image-guided patient setup and on-treatment monitoring, to quality assurance (QA) and dose delivery. This symposium is designed to provide current knowledge necessary for the safe and efficient implementation of SBRT in various linac platforms, including the emerging digital linacs equipped with high dose rate FFF beams. Issues related to 4D CT, PET and MRI simulations, 3D/4D CBCT guided patient setup, real-time image guidance during SBRT dose delivery using gated/un-gated VMAT/IMRT, and technical advancements in QA of SBRT (in particular, strategies dealing with high dose rate FFF beams) will be addressed. The symposium will help the attendees to gain a comprehensive understanding of the SBRT workflow and facilitate their clinical implementation of the state-of-art imaging and planning techniques.

LEARNING OBJECTIVES
1. Present background knowledge of SBRT, describe essential requirements for safe implementation of SBRT, and discuss issues specific to SBRT treatment planning and QA. 2. Update on the use of multi-dimensional and multi-modality imaging for reliable guidance of SBRT. 3. Discuss treatment planning and QA issues specific to SBRT. 4. Provide a comprehensive overview of emerging digital linacs and summarize the key geometric and dosimetric features of the new generation of linacs for substantially improved SBRT. NIH/NCI; Varian Medical Systems; F. Yin, Duke University has a research agreement with Varian Medical Systems. In addition to research grant, I had a technology license agreement with Varian Medical Systems.


In order to study the falling film flow process outside the horizontal circular tube, experiment is adopted in this paper to investigate the effects of liquid spray density and spray temperature on the liquid film flow pattern transformation and pattern distribution. Meanwhile, the temperature distribution characteristics of the horizontal tubes are analyzed. The high - speed camera was used to photograph the flow pattern of the liquid film, and the K - type thermocouples were used to measure the tubes wall temperature. The results show that (1) as the spray density increases, the liquid film is converted from a droplet flow to a columnar flow and then to a sheet flow; (2) the critical spray density of the flow pattern conversion will reduce with the spray liquid temperature increasing; (3) the critical spray density of 10% glycerol solution for flow pattern conversion is bigger than that of water; (4) the tube wall circumferential temperature increased with the increase of spray density, and the tubes wall circumferential temperature decreased with the increase of the circumferential angle in the range of the circumferential angle from 0° to 135° and rose slightly from 135° to 180°; (5) the tube wall circumferential temperature of water is higher than that of the 10% glycerol solution.


Melanin-based dorsal pattern polymorphisms are common in reptiles and generally evolve under the interaction between opposite selective pressures, notably thermal advantage in cold environments and background matching to avoid predation. When those pressures change over space and time, the relative frequencies of morphs can vary across the species range. However, no previous study has analysed the spatial patterns of variation of morphs under a phylogenetic perspective in addition to the adaptive responses to natural selection. In this study, we focused on the distributional patterns of the three dorsal morphs of Podarcis muralis at wide-range scale to assess how they associate with geography, climate, microhabitat, phylogeny and sexual dimorphism. By using open access data from iNaturalist, we assembled a dataset of 4096 georeferenced points with information on sex and morph. Data were analysed through Bayesian GLMs, and four alternative models were formulated depending on the specific factors affecting morphs' frequency. The dorsal morphs are not randomly distributed in Europe, but follow clear geographic patterns, vary with altitude and habitats, show sex-specific trends, and correlate with the phylogenetic history of the species. When comparing models, the phylogenetic model always obtained the best performance, and no overlap with other models occurred, thus best explaining the distributional patterns of dorsal morphs. The evolutionary processes, in addition to present environmental pressures, can significantly affect local-scale microevolutionary adaptations, influencing the current distribution of dorsal phenotypes across the species range. More generally, results point out the importance of considering the evolutionary processes when analysing distributional patterns of polymorphisms.


Abstract Background Circulating tumor cells (CTCs) enter peripheral blood from primary breast cancer tumors and seed liver metastasis (BCLM). The genome-wide sequencing of CTCs offers noninvasive diagnostic factor for survival in BCLM patients, which but has been impeded by low single-cell genome coverage of scarce CTCs. Methods We conducted a prospective clinical investigation to confirm the diagnostic value of genome-wide sequencing in BCLM. We have developed the genome-wide pattern differences in copy number variations (CNVs) and to improve a CNV signature as an adjunct test for the routine histopathologic classification of BCLM. We compared the consistency and efficiency of genome-wide sequencing of CTCs with other comment detection methods. Furthermore, functional prediction of candidate gene biomarkers was confirmed in BCLM patients. Results CTCs were isolated from 26 patients with BCLM, 12 of which were successfully profiled for high CTCs (> 15), including matched archival primary tumor from 17 patients. Our results characteristic cancer-metastatic variations and insertions/deletions in exomes of CTCs. Comparison with primary breast tumors in metastatic niches cell revealed similar frequencies of BCLM genomic copy number aberrations. Higher CTCs frequencies (> 35) are correlated with disease severity and metastatic progress, which suggesting effective value of CTCs for variety of staging of BCLM. The CNV pattern of CTC is similar to that of hepatic metastasis, but the mutation pattern of CTC is different from that of primary lesion. Twenty- five genes were identified as a CNV signature of BCLM. Functional pathways analysis shows all these genes might play similar and critical roles in migration and progression of BCLM that could be independent risk factors for BCLM (p  Conclusions Our approach utilized to explore reproducibility of cancer-specific CNVs involved in progression of metastatic breast cancer. Our study contributed a new potential non-invasive biomarker for CTC-based cancer diagnostics of BCLM to monitor therapeutic efficacy of targeted therapies. Editorial acknowledgement The authorswould like to express their appreciation to appreciate Southwest Medical Universityfor its financial support. We also wish to thank the oncology and pathology technicians of The Affiliated Hospital of Southwest Medical University for their assistance in the work reported here. We also thank the anonymous referee for his/her very helpful comments, which remarkably improved the quality of this research. Legal entity responsible for the study The authors. Funding Has not received any funding. Disclosure All authors have declared no conflicts of interest.


1. The aim of this study was to investigate the roles of hypertension, ?2- adrenoceptors and neurotransmission in the regulation of rat blood vessel responses. 2. Experiments were carried out using the tail artery and aorta of spontaneously hypertensive rats (SHR), and comparisons were made with vessels from the normotensive control strain, Wistar Kyoto (WKY). 3. Rings of aorta and proximal tail artery from SHR were heavier than those from WKY, despite being cut to the same length. This indicated a structural difference, so the histology of the vessels was examined using light microscopy. 4. Both the wall thickness and lumen diameter of the aorta were greater in SHR compared to WKY, but there was no difference in wall thickness to lumen ratio. The area of the medial layer was increased in SHR relative to control. 5. There was no difference in the wall thickness of the proximal part of the tail anery between SHR and WKY rats, but the lumen diameter was reduced in SHR relative to control, giving a greater wall thickness to lumen ratio. The media area was decreased in SHR compared to WKY. 6. Wall thickness was increased and lumen diameter decreased in the distal part of the tail artery from SHR compared to WKY, giving a greater wall thickness to lumen ratio. The media area was increased in SHR compared to WKY. 7. Mechanical responses to drugs were investigated in the aorta and proximal tail artery from SHR and compared to responses obtained in vessels from WKY rats, using both isometric tension and perfusion pressure recording. 8. In the aorta, isometric tension responses to the vasoconstrictor phenylephrine (PE; 10-9-3x10-5M) were lower in rings from SHR compared to responses in rings from WKY, with a lower maximum response. There was no difference in the EC50 for PE between SHR and WKY. In contrast, responses to the endothelium-dependent vasodilator carbachol (10-9-3x10-5M) were greater in rings from SHR compared to relaxations in rings from WKY, with a greater maximum response and a lower EC50. Using the endothelium-independent vasodilator sodium nitroprusside (SNP) there was no difference between hypertensive and control rats at the lower end of the concentration-response curve (3x10-11-10-8M). At the higher concentrations (3x10-8-3x10-6M) however, aortic rings from SHR were more responsive to SNP than were rings from WKY rats, with a greater maximum relaxation, although the EC50 was unchanged. There was no difference in the vasorelaxant response to the beta-adrenoceptor agonist isoprenaline (3x10-10-10-5M) between hypertensive and control rats. 9. In tail artery rings, isometric tension responses to PE (10-8-3x10-5M), noradrenaline (NA ; 10-9 - 10-5M) and UK-14,304 (3x10-10 - 3x10-5M) were greater in SHR compared to WKY with an increased maximum response, but there was no difference in the EC50. Yohimbine (50nM) produced a rightward shift in the concentration-response curve to UK-14,304 in tail artery rings from both SHR and WKY rats. 10. In perfused segments of rat tail artery the response to NA was much greater in vessels from SHR than in vessels from WKY. When expressed as a percentage of the maximum response achieved however, responses in vessels from SHR were lower than in those from WKY. 11. The relaxations produced by SNP (3x-10- 3x10-5M) and isoprenaline (10-8 - 10-4M) were lower in tail artery rings from SHR compared to those in rings from WKY. In vessels from hypertensive rats, SNP did not fully relax the PE-induced precontraction, whereas isoprenaline did not fully relax the precontraction in either hypertensive or control rats. Carbachol produced little or no response in either group of rat. 12. The biochemical response underlying NA-induced contraction in the rat tail artery was investigated by measuring accumulation of total inositol phosphates in response to NA. The basal phosphoinositide (PI) hydrolysis was higher in vessels from SHR than in those from WKY, and 10-5M NA, which had produced increased contractile responses, gave a greater stimulation of PI hydrolysis in vessels from hypertensive rats as compared to control. 13. Preliminary experiments were carried out with rats of two different age groups (12-17 weeks and 6-9 weeks). 14. When tail artery segments were cannulated at one end ("single cannulation") and perfused with Krebs solution at a constant rate, the response to NA (10-3 - 100mug) was greater in older rats than in younger rats. The response to field stimulation (Supramaximal voltage 80V, 50 pulses, 0.4ms duration, 0.5-80Hz) tended to be greater in older than in younger rats. (Abstract shortened by ProQuest.).


Background and Objectives: Though medical expulsive therapy for ureteric stones is increasingly used these days, some recent randomized controlled trials have questioned its benefit. This study evaluates the result of treatment of ureteric stones with tamsulosin.
Materials and Methods: This prospective study involved ultrasonographically confirmed cases of uncomplicated unilateral ureteric stones. All patients received tamsulocin 0.4 mg daily for 2 to 6 weeks. The primary end point was stone expulsion. The secondary endpoints were the use of analgesics and adverse events.
Results: One hundred and sixty two patients completed the study. Ninety seven patients were male and male to female ratio was 3:2. The mean age was 34.9 ± 9.8 (range: 18-71) years. The mean stone size was 6.17 ± 1.68 (range: 3.3-11.2) mm. By the end of 2, 4 and 6 weeks, cumulative stone expulsion rate was 110 (69.1%), 121 (74.7%) and 126 (77.8%) respectively. For the 49 stones of size £ 5 mm, the expulsion rate was 47 (95.9%) by the end of 6 weeks. The expulsion rates for stones of size > 5 - 7 mm, > 7 – 9 mm and ³ 9 mm were 59 (85.5%), 17 (53.1%) and 3 (25%) respectively by the end of 6 weeks. Lower ureteric stones had the highest expulsion rate of 106 (87.6%) by the end of 6 weeks, and the rate was lowest for upper ureteric stones (34.6%). Ten (6.1%) patients required additional analgesics during the course of treatment. Eleven (6.8%) patients complained of mild light-headedness and dizziness which subsided in a few days.
Conclusion: Tamsulocin appears to facilitate expulsion of ureteric stones especially the distal ones. The benefit of tamsulocin seems to be maximum for the stones of size up to 9 mm. Further large scale randomized controlled trial should better define the real benefit and more rationale use of tamsulocin in routine clinical practice.


Surface and subsurface high-frequency (>1 Hz) noise data were recorded using nearly identical instrumentation at three widely separated sites in the United States (Amarillo, Texas; Datil, New Mexico; and Pinedale, Wyoming) for extended periods of time under varying wind conditions. While the sites are geologically distinct, the near-surface noise environments have many common features that we believe may be due in large part to the presence of a surficial layer of highly attenuative unconsolidated material at each site. Noise levels seen at or near the surface (5 m or less) are much higher (up to 30 dB) and much more variable (power range up to 44 dB) than those seen at depth (the smallest range was 9 dB for 1951 m at Amarillo). The greatest gains in noise level reduction are realized within the first 100 m and probably much shallower (< ∼ 10 m). Regardless of the wind profile or local lithology, all sites show an excellent correlation between increased noise levels and higher wind speed, even at significant depths (367 m at Amarillo). Wind-generated noise is broadband (at least 15 to 60 Hz) and apparently nonlinear, increasing dramatically when a wind speed threshold is exceeded (3 to 4 m/sec within a few meters of the surface; as high as 8 m/sec at a depth of a few hundred meters). It is possible to be essentially completely shielded from the wind-generated component of seismic noise by deploying instruments at sufficient depth, but we observed this only for the two deepest deployments (1219 and 1951 m, both at Amarillo). Reducing the wind profile at the surface, however, can yield similar reductions for a much smaller cost. Cultural or "workday" noise, if present (depending on the remoteness of the site), is typically much weaker (10 dB or less) than wind noise but may propagate very effectively to great depths and therefore could be of concern for very deep deployments where wind is not a factor.


While unstable on present-day Mars, liquid water was an important geologic agent in Mars' past. This work investigates the nature and timing of aqueous processes on ancient Mars, focusing on the earliest epoch of Mars history, the Noachian (>3.7 Gyr), and strata bearing alteration minerals. This work seeks: (1) a refined understanding of what is knowable about past aqueous conditions based on remote visible/near-infrared (VNIR) analyses of altered surfaces; (2) a greater understanding of the changing habitability potential of Mars through time and, more broadly, (3) an increased understanding of aqueous environments during the first billion years of the evolution of a terrestrial planet. Orbital data from the Compact Reconnaissance Imaging Spectrometer for Mars (CRISM) VNIR imaging spectrometer were used to identify key minerals and characteristic mineral assemblages, including hydrated silicates and carbonates. Coupling mineral identifications with high resolution morphology to assess stratigraphic relationships allows constraining past environmental conditions. The findings herein point to temporally and spatially variable settings of aqueous alteration on ancient Mars, including lacustrine, near-surface leaching, and subsurface hydrothermal environments. This diversity indicates multiple potentially habitable environments early in Mars history. Terrestrial field and laboratory investigations of mineralogic determinations derived from VNIR spectroscopy versus other techniques show that (1) infrared spectroscopy correctly characterizes the mineralogy of rocks from Mars-analogue weathering and hydrothermal systems in Iceland and (2) quantitative abundances for simple mixtures of smectite clays with mafic minerals can be successfully estimated with Hapke and Shkuratov radiative transfer models in well-controlled laboratory settings. Presently employed VNIR quantitative analyses techniques are, however, challenged by multi-component mixtures with complex textures or multiple grain sizes. Qualitative remote VNIR mineralogic analyses can be used synergistically with ground-based analytical techniques such as microscopic imaging, x-ray diffraction and geochemical analyses to elucidate further details of alteration mineral formation conditions. The multiple environments of aqueous alteration revealed through VNIR study of Mars' ancient rocks represent key targets for future exploration.


The aim of this study was to develop an exposure system which enables in vitro experiments to be conducted under variously modulated radiofrequency exposures. Based on the evaluation of different possible systems, it was decided to realize a system based on rectangular waveguides. The system was optimized for the following parameters: (1) homogeneity of the cell exposure, (2) simultaneous exposure of several Petri dishes, (3) efficiency, (4) strict environmental control, (5) quick and easy access to the Petri dishes, (6) cost, and (7) simple operation by non-engineering personnel. The implemented control software enables investigation of a wide spectrum of amplitude modulation schemes between 0.1 Hz and 1 kHz, including the modulation schemes of current and future digital mobile communication systems as well as other exposure protocols. The system described has been initially utilized for a study on the differentiation and cell functions of embryonic stem cells. Detailed numerical and experimental dosimetry and environmental tests have demonstrated that it meets all target objectives. The entire system including the sham exposure system fits into a single incubator. It enables the carrying out of various experiments designed to test biological responses to RF exposures at 1.2-1.7 GHz by using various modulation schemes and long term exposure protocols as well as simultaneous data logging.


The Cavender-Felsenstein edge-length invariants for binary characters on 4-trees provide the starting point for the development of "customized" invariants for evaluating and comparing phylogenetic hypotheses. The binary character invariants may be generalized to k-valued characters without losing the quadratic nature of the invariants as functions of the theoretical frequencies f(UVXY) of observable character configurations (U at organism 1, V at 2, etc.). The key to the approach is that certain sets of these configurations constitute events which are probabilistically independent from other such sets, under the symmetric Markov change models studied. By introducing more complex sets of configurations, we find the quadratic invariants for 5-trees in the binary model and for individual edges in 6-trees or, indeed, in any size tree. The same technique allows us to formulate invariants for entire trees, but these are cubic functions for 6-trees and are higher-degree polynomials for larger trees. With k-valued characters and, especially, with large trees, the types of configuration sets (events) used in the simpler examples are too rare (i.e., their predicted frequencies are too low) to be useful, and the construction of meaningful pairs of independent events becomes an important and nontrivial task in designing invariants suited to testing specific hypotheses. In a very natural way, this approach fits in with well-known statistical methodology for contingency tables. We explore use of events such as "only transitions occur for character i (i.e., position i in a nucleic acid sequence) in subtree a" in analyzing a set of data on ribosomal RNA in the context of the controversy over the origins of archaebacteria, eubacteria, and eukaryotes.


AIMS
The effect of 'binge drinking' coupled or not with chronic nicotine administration on nucleus accumbens (NAc) glutamate, arginine, taurine and hydroxyl radical levels has been investigated in these present studies.

METHODS AND RESULTS
Ethanol, 2 or 3 g/kg, has been administered to male or female adult rats in a 'binge-type' regime for 3 weeks, +/- nicotine, and changes in glutamate, arginine and taurine content in the NAc, assayed by microdialysis after a further dose of ethanol. The basal concentration of NAc glutamate increased 8-fold in the female adult rats but did not change significantly after further doses of ethanol. In contrast, the male adult rats showed no changes in basal glutamate content but exhibited a dose-dependent increase in NAc glutamate after further doses of ethanol. NAc arginine basal levels decreased significantly in both male and female adult rats after further doses of ethanol. Co-administration of nicotine modified the toxicity of ethanol as exemplified by diminishment of both the basal NAc glutamate release as well as modifying the release of this excitatory amino acid after further ethanol doses, particularly in female rats. In addition, the marked changes in arginine release after further ethanol doses were less evident. There was no evidence for increased hydroxyl radical production in the NAc after 'binge drinking' +/- nicotine.

CONCLUSION
There appeared to be a greater vulnerability to ethanol toxicity in female adult rats after 'binge drinking'. It remains unclear whether the increased release of glutamate during the microdialysis evokes activation of inducible nitric oxide synthase (iNOS), which would utilize arginine in the formation of nitric oxide.


In general the mechanical handling of objects in space is performed by manipulators, whose number of actuators is consistent with the number of required degrees of freedom. In addition, manipulators can be equipped with redundant drives, providing the manipulator with more actuators than the mobility actually requires. Thus, an active distribution of drive torques is enabled.Accordingly, this research intends to analyze the effects of torque distribution in over-actuated manipulators relating to load-optimized and energy-efficient handling. By developing torque distribution strategies the maximum torque levels can be reduced and the required drive power thus be decreased. This results in an increased drive utilization, which improves the energy-efficiency of the handling system. On this basis, an innovative handling concept is analyzed, which represents an over-determined system given the number of actuators. Hence, it is shown that the drive utilization of manipulators can be significantly improved by means of actuation redundancy. For this purpose different mathematical optimization approaches are analyzed, which solve the over-actuated system with defined optimization targets. Here, the optimal torque distribution is found using an algorithm, which minimizes the maximum torque for each object position. The results demonstrate the efficiency of active torque distribution in terms of over-actuated manipulators. For a further approach it is planned to develop control methods including optimized torque distribution strategies in order to improve the performance and the energy efficiency of the entire manipulator.Copyright © 2014 by ASME


Our aim is to explore how wages inequalities translate into standard of living inequalities in different European countries. Wage inequalities are measured at the individual level. They can be increased or reduced by two institutions: the household and the tax-benefit system. Standards of living are therefore defined at the intersection of three institutions: the labour market, the family and the state (through social transfers). We propose a new methodology to distinguish the impact of these three institutions on standard of living inequalities. An empirical application is conducted for the employed population in different European countries with a focus on France, Spain, the United Kingdom, Germany, Sweden and Poland. Results are in line with expectations except for Germany, which does not conform to expectations for a corporatist regime.


Based on the results of the Diabetes Prevention Program Outcomes Study (DPPOS), in which metformin significantly decreased the development of diabetes in individuals with baseline fasting plasma glucose (FPG) concentrations of 110–125 vs. 100–109 mg/dL (6.1–6.9 vs. 5.6–6.0 mmol/L) and A1C levels 6.0–6.4% (42–46 mmol/mol) vs. <6.0% and in women with a history of gestational diabetes mellitus, it has been suggested that metformin should be used to treat people with prediabetes. Since the association between prediabetes and cardiovascular disease is due to the associated nonglycemic risk factors in people with prediabetes, not to the slightly increased glycemia, the only reason to treat with metformin is to delay or prevent the development of diabetes. There are three reasons not to do so. First, approximately two-thirds of people with prediabetes do not develop diabetes, even after many years. Second, approximately one-third of people with prediabetes return to normal glucose regulation. Third, people who meet the glycemic criteria for prediabetes are not at risk for the microvascular complications of diabetes and thus metformin treatment will not affect this important outcome. Why put people who are not at risk for the microvascular complications of diabetes on a drug (possibly for the rest of their lives) that has no immediate advantage except to lower subdiabetes glycemia to even lower levels? Rather, individuals at the highest risk for developing diabetes—i.e., those with FPG concentrations of 110–125 mg/dL (6.1–6.9 mmol/L) or A1C levels of 6.0–6.4% (42–46 mmol/mol) or women with a history of gestational diabetes mellitus—should be followed closely and metformin immediately introduced only when they are diagnosed with diabetes.


Simulation and experimental development of a driving system and control for an axial flux permanent magnet machine has been developed. The complete system, including the machine design and construction, has been accomplished due to the collaboration among different universities in Brazil and Sweden. Final experimental setup is aimed for testing a passive levitation system, which can be used as small flywheel energy storage. Simulations have been implemented using Simulink. The design and construction of different components of the driving system are presented, in a way so they can be reproduced. Control strategy has been implemented using Labview and Compact-Rio. Results show the functionality of the complete system at a nominal speed of 2800 rpm.


Objective: To survey in the literature the role of the nurse in the care of people with urinary incontinence (UI). Methods: Integrative literature review from the publications within the period of 2013 in the databases: BDENF, LILACS, Web of Science, PubMed and SciELO, in the Portuguese, English and Spanish languages. The sample consisted of 11 publications, most of them in English. Results: The data were categorized into three dimensions of care: educational (three articles), care (eight articles) and management (an article, which was also categorized as care). Educational: although nurses presented superficial and incomplete knowledge about incontinence, playful strategies were used for teaching. Assistance: the use of superabsorbent diapers and pads, 3% dimethicone impregnated wipes, spray for the formation of polymer film for incontinence-associated dermatitis, pelvic musculature, urethral massage, bladder training, and eating habits modification were recommended. Gerencial: the quality of nursing care for the elderly with UI was evaluated through protocols, standards and Standard Operational Procedures (SOPs). Conclusion: There is a shortage of studies on the subject and it was evidenced that the nurse assumes an assistance role in urinary incontinence, although its knowledge is incipient.


Creativity Under Duress in Education? introduces a new framework—creativity under duress in education. Leading creativity researchers and educational scholars discuss creative theory and practice from an educational lens that is provocative. Across international contexts, this book combines insights from creativity and educational research; rich illustrations from classrooms, schools, and other professional settings, and practical ideas and strategies for how anyone invested in education can support creative teaching and learning.
Readers will encounter diverse perspectives from an international cast of authors exploring cutting-edge ideas for creativity and innovation as a foremost priority for economies in the new millennium. At the same time, they consider forces of authority, control, and constraint that impact creative education and innovation within educational systems, extending to the professions. Educators and those interested in the future of education are vitally important to this conversation around research-based and practical analyses of creativity in and beyond the classroom. Addressed are these major issues: (1) creativity frameworks of theory and action in education, (2) research investigations into creativity and education, and (3) applications of creativity theory in real-world practice.
Dynamic, this book presents a bridge between draconian contexts of assessment and explosive creativity in diverse places. A key contribution of the volume is its validation and promotion of creativity and innovation for students, teachers, professors, leaders, employers, policymakers, and others seeking ways to profoundly improve learning and transform education. In tackling the seemingly irreconcilable issues of creativity and accountability in K–12 institutions, higher education, and policy circles, worldwide, this work offers a message that is both cautionary and inspiring.


The aim of the paper is to understand the causes of the growth differential created between the Mediterranean and the Nordic economies since the creation of Euro. The Minsky's financial instability hypothesis and the Kalecki's five determinants of profits are used in the paper as interpretative tool in order to disentangle the sources of this growth divergence. In light of this analysis, the economic crisis in the Eurozone endogenously spreads in the economic system, and it is not, as many believe, the consequence of an exogenous shock. The two regions represent two different growth models, and this, in turn, makes a symmetric fiscal policy unsuccessful. Trade imbalances and the subsequent flow of profits differential is what has triggered and later exacerbated this divergent path. This emphasizes the necessity of a mechanism able to automatically counterbalance the persistent flows of profits from South to North. To this respect, a mechanism similar to the Keynes's Clearing Union is proposed to offset this source of instability, i.e., an institution able to prevent the creation of imbalances as well as to restore convergence between the two blocks.


Roots of terrestrial plants are designed to take up water and nutrients. At the same time, uptake of unwanted compounds, for example toxic, and infection by soil borne pathogens must be avoided. Specific unicellular tissues, the endodermis and the exodermis, allow roots to establish and maintain this selectivity. The endodermis represents an unicellular cell layer separating the central cylinder of the root from the cortex. The exodermis represents an unicellular cell layer located at the outer surface of the root directly below the root epidermis. Both tissues are characterised by specific cell wall modifications. In early developmental stages the anticlinal radial walls exhibit Casparian bands, composed of the polymers suberin and lignin. In a subsequent developmental state a suberin lamella is deposited on the inner surface of endo- and exodermal cell walls. These apoplastic barriers, mainly composed of suberin, significantly affect radial uptake of water and dissolved nutrients and radial loss of oxygen.

Key Concepts:

Casparian bands, composed of lignin and suberin, form characteristic cell wall modifications in radial walls of endodermal and exodermal cells.

Suberin lamellae are deposited onto the inner surface of endodermal and exodermal cell walls.

Apoplastic barriers in roots are established by the deposition of suberin into and onto the cell wall.

Suberised apoplastic barriers in roots help to establish root selectivity in nutrient uptake.

The endodermis, forming an 'inner' apoplastic barrier in the root, is important in preventing nutrients actively concentrated in the xylem from passively diffusing back to the soil.

The exodermis, forming an 'outer' apoplastic barrier at the root surface, mainly establishes the root/soil interface between the root and the soil environment surrounding the root.

As an adaptation to various environmental stress factors (e.g. drought, salt, heavy metal stress, oxygen deficiency, etc.) suberisation of apoplastic barriers is significantly modified.

Fatty acid elongases and cytochrome P450 hydroxylases represent important key enzymes in suberin biosynthesis.

Keywords:

apoplastic barrier;
Casparian band;
endodermis;
exodermis;
hypodermis;
nutrient uptake;
plant root;
suberin;
transport


Adenocarcinoma of the pancreas is a devastating disease with a dismal prognosis. Recent data by the American Cancer Society showed that the 5-year survival rate of patients with pancreatic carcinoma remains at 5% which makes it the most deadly form of cancer known.1 These figures are primarily due to the fact that most tumours are diagnosed at a stage where surgical treatment is no longer possible as the tumour is already in a locally advanced or even metastasised stage. All efforts to provide a systemic therapy to patients with advanced disease have failed. The only approved treatments consist of the nucleosid anlogon gemzitabine and the tyrosine kinase inhibitor erlotinib. However, even combinations of these drugs have no major impact on the survival of patients with pancreatic carcinoma.

Why is this tumour so chemoresistant and how can we overcome this obstacle to improve treatment responses? Several biological features might contribute to the resistance towards systemic treatments. First, ductal carcinomas of the pancreas are genetically highly unstable tumours.2 Recent analysis of pancreatic cancers revealed a multitude of genetic alterations which affected a dozen different …


Background: Cucumber mosaic virus (CMV) has isometric particles with a diameter of about 28 - 29 nm. Detection and prevention are the critical steps in the control of plant viruses. Detection in a large number of samples is still done by serological methods due to their robustness and perhaps low cost. Objectives: To this end, our aim was to express the CMV CP gene in E. coli to be used as the antigen for antibody production in the future. Materials and Methods: Coat Protein (CP) gene cDNA from an isolate (B13) of Cucumber Mosaic Virus (CMV) was subcloned from pTZ57RCMVCP to pET21a expression vector and transformed to E. coli strain Rosetta. Expression of CMV CP was successful and confirmed by Sodium Dodecyl Sulfate Polyacrylamide Gel Electrophoresis (SDS-PAGE), wherein a ~30- kDa protein band was revealed. Induction by Isopropyl-Thiogalactoside (IPTG) at final concentrations of 0.5 to 2 mM appeared to produce similar results as to the amount of the expressed protein, which was judged by intensity of the band on SDS-PAGE. Results: The identity of the expressed protein was confirmed by immunoassays such as western blot, Dot-Immunobinding Assay (DIBA) and Enzyme-Linked Immunosorbent Assay (ELISA) by the use of anti-CMV antibody. Conclusions: This is the first report of expression of CMV CP gene in Iran, which is important for the preparation of anti-CMV antibody and paving the way for the use of the virus coat protein as a nanomaterial.


Abstract As a result of recent methodological developments in connection with enhanced computational capacity, theoretical methods have become increasingly valuable and reliable tools for the investigation of solutions. Simulation techniques utilizing a quantum mechanical (QM) approach for the treatment of the chemically most relevant region so-called hybrid quantum mechanical/molecular mechanical (QM/MM) simulations have reached a level of accuracy that often equals or may even surpass experimental methods. The latter is true in particular whenever ultrafast (i.e., picosecond) dynamics prevail, such as in labile hydrates or structure-breaking systems. The recent development of an improved QM/MM framework, the quantum mechanical charge field (QMCF) ansatz, enables a broad spectrum of solute systems to be elucidated. As this novel methodology does not require any solute solvent potential functions, the applicability of the QMCF method is straightforward and universal. This advantage is bought, however, at the price of a substantial increase of the QM subregion, and an attendant increase in computational periods to levels of months, and even a year, despite parallelizing high-performance computing (HPC) clusters. Molecular dynamics (MD) simulations of chemical systems showing increasing complexity have been performed, and demonstrate the superiority of the QMCF ansatz over conventional QM/MM schemes. The systems studied include Pd2+, Pt2+, and Hg22+, as well as composite anions such as PO43- and ClO4-.


Learn how to use the Groups config.txt directive to create groups of resources, define users and assign access in EZproxy. The Group directive allows you to create groups of resources, define users of these groups, and assign users access to those resource groups. For example, you can create student, faculty, and alumni groups, and assign access to different resources for each of these groups—students can access a certain set of resources, faculty a different set, and alumni, still a different set. Additionally, you can allow students and faculty to access certain resources while restricting alumni access.


As the world's second economy, China has been developing at breath taking pace over the last 30 years. City development planner are blindly seeking to be big, for example, a small city should become middle size city, a middle size city should become a big city, a big city should become a metropolitan city, and a metropolitan city should become an international mega city. City municipalities seek higher GDP year by year. City mayors will do whatever as long as they could make the most profit and build their city's profile. Today, real estate is the highest profit industry in China. In order to bring in more financial support, urban planning is done in favor of those with power and capital instead of consideration of equality and fairness. There are increasing conflicts for the different classes of people in the city because the social gaps between the classes are growing.


Our comprehensive meta-analysis combined prevalence figures of childhood sexual abuse (CSA) reported in 217 publications published between 1980 and 2008, including 331 independent samples with a total of 9,911,748 participants. The overall estimated CSA prevalence was 127/1000 in self-report studies and 4/1000 in informant studies. Self-reported CSA was more common among female (180/1000) than among male participants (76/1000). Lowest rates for both girls (113/1000) and boys (41/1000) were found in Asia, and highest rates were found for girls in Australia (215/1000) and for boys in Africa (193/1000). The results of our meta-analysis confirm that CSA is a global problem of considerable extent, but also show that methodological issues drastically influence the self-reported prevalence of CSA.


OBJECTIVE Metformin is the first pharmacological option for treating type 2 diabetes. However, the use of this drug is not recommended in individuals with impaired kidney function because of the perceived risk of lactic acidosis. We aimed to assess the efficacy and safety of metformin in patients with type 2 diabetic kidney disease (DKD). RESEARCH DESIGN AND METHODS We conducted a retrospective observational cohort study of 10,426 patients with type 2 DKD from two tertiary hospitals. The primary outcomes were all-cause mortality and end-stage renal disease (ESRD) progression. The secondary outcome was metformin-associated lactic acidosis. Taking into account the possibility that patients with less severe disease were prescribed metformin, propensity score matching (PSM) was conducted. RESULTS All-cause mortality and incident ESRD were lower in the metformin group according to the multivariate Cox analysis. Because the two groups had significantly different baseline characteristics, PSM was performed. After matching, metformin usage was still associated with lower all-cause mortality (adjusted hazard ratio [aHR] 0.65; 95% CI 0.57–0.73; P < 0.001) and ESRD progression (aHR 0.67; 95% CI 0.58–0.77; P < 0.001). Only one event of metformin-associated lactic acidosis was recorded. In both the original and PSM groups, metformin usage did not increase the risk of lactic acidosis events from all causes (aHR 0.92; 95% CI 0.668–1.276; P = 0.629). CONCLUSIONS In the present retrospective study, metformin usage in advanced chronic kidney disease (CKD) patients, especially those with CKD 3B, decreased the risk of all-cause mortality and incident ESRD. Additionally, metformin did not increase the risk of lactic acidosis. However, considering the remaining biases even after PSM, further randomized controlled trials are needed to change real-world practice.


As a new fan of the CW's paranormal series  Supernatural , I paid little attention to actor Misha Collins outside the omnipresent trenchcoat of his character, Castiel—until a kairotic question from a fellow conference panelist pointed me in the direction of Collins' Twitter feed. I was struck by Collins' 140-character shots of performative trolling, Tweets that sang to me in shades, gleeful rhetorical waves, of the sophists, particularly because of the actor's interest in, and unique definition of, social change. Building on that sophistic seed, I argue here that Collins' construction of a megalomaniacal Twitter persona known as the Overlord has afforded him a particular kind of disruptive ethos, one he's used to persuade his fans to regard both "normalcy" as a social problem and acts of art and public performance as effective means of addressing that ill. Ultimately, I suggest that listening carefully to how Collins' fan community defines, enacts, and understands "social change"-- rather than measuring their rhetoric against a fixed understanding of what such change can and should look like--may allow those of us outside of this community, and others like it, might add to our understand of the "new ways of thinking about citizenship and collaboration" at work within the many, varied, and beautiful spaces of fandom (Jenkins 257).


3D city models have been widely used in different applications such as urban planning, traffic control, disaster management etc. Effective visualisation of 3D city models in various scales is one of the pivotal techniques to implement these applications. In this thesis, a framework is proposed to visualise the 3D city models both online and offline using City Geography Makeup Language (CityGML) and Extensible 3D (X3D) to represent and present the models. Then, generalisation methods are studied and tailored to create 3D city scenes in multi-scale dynamically. Finally, the quality of generalised 3D city models is evaluated by measuring the visual similarity from the original models. In the proposed visualisation framework, 3D city models are stored in CityGML format which supports both geometric and semantic information. These CityGML files are parsed to create 3D scenes and be visualised with existing 3D standard. Because the input and output in the framework are all standardised, it is possible to integrate city models from different sources and visualise them through the different viewers. Considering the complexity of the city objects, generalisation methods are studied to simplify the city models and increase the visualisation efficiency. In this thesis, the aggregation and typification methods are improved to simplify the 3D city models. Multiple representation data structures are required to store the generalisation information for dynamic visualisation. One of these is the CityTree, a novel structure to represent building group, which is tested for building aggregation. Meanwhile, Minimum Spanning Tree (MST) is employed to detect the linear building group structures in the city models and they are typified with different strategies. According to the experiments results, by using the CityTree, the generalised 3D city model creation time is reduced by more than 50%. Different generalisation strategies lead to different outcomes. It is important to evaluate the quality of the generalised models. In this thesis a new evaluation method is proposed: visual features of the 3D city models are represented by Attributed Relation Graph (ARG) and their similarity distances are calculated with Nested Earth Mover's Distance (NEMD) algorithm. The calculation results and user survey show that the ARG and NEMD methods can reflect the visual similarity between generalised city models and the original ones.


This paper studies how an important feature of software adoption impacts a software vendor's preference between perpetual and subscription-based licensing: Customers are uncertain about their valuation of the software prior to adoption. We show that customer valuation uncertainty causes the equilibrium outcome to depart from that of standard durable-goods theories in two aspects: (1) Contrary to the conventional wisdom of durable-goods theories that subscription-based licensing is optimal, perpetual licensing can be more profitable for the vendor than subscription-based licensing under some conditions. This result offers a possible explanation for the historical prevalence of perpetual licensing in many software markets. (2) When subscription-based licensing is optimal, our theory suggests a low-then-high variable pricing path. In contrast, standard durable-goods theories suggest charging the monopoly leasing price in each period. Such a variable pricing path and the resulting adoption pattern are consistent with market observations (e.g., pricing strategy by Adobe Systems). We also examine a variation of subscription-based licensing in which the vendor offers a menu of subscription options varying in license duration and shows that customer valuation uncertainty is critical for this strategy to outperform perpetual licensing under some conditions. Moreover, we find that customer valuation uncertainty can cause the vendor to prefer a licensing strategy that is not socially optimal.


This paper describes a delta-sigma ( ) digital-to- analog converter (DAC) architecture that combines a polyphase de- composition of the interpolation filter and a time-interleaved error- feedback modulator. Noise-shaped oversampling is achieved while clocking the digital circuitry at the Nyquist rate. The de- sign of a third-order 4-bit modulator with eight times oversam- pling using the architecture is presented. Results from a prototype current-DAC driven by a VHDL simulation of the digital design at 2.66 GHz show that 56-dB linearity is achievable in 90-nm CMOS within a 1-V supply over a 155-MHz signal bandwidth making the architecture suitable for emerging ultra-wide-band and 60-GHz radio applications.


File migration is a key technology to improve the efficiency of cluster file systems. In this paper, we give a thermal model that shows the file access frequency at each node of a cluster. Based on this model, we introduce a file migration policy, which can balance the workload of clustering server nodes. It is used to decide the optimal place of a single file in the cluster environment under a heavy workload. And the results of the simulation comparison experiments show that using this policy can decrease the average file access response time of a 4, 8, or 16 node cluster at a rate of about 35.52%, 62.43% and 49.07%, respectively. Furthermore, if the nodes are a uniform number, migration on the application server end will lower the accelerated speed of the average response time, i.e., the heavier the total workload, the more efficient the policy. In general, this policy can efficiently reduce the average file access response time, give a good extendibility and enhance the performance of the cluster file system as a whole.


Post-secondary education is expected to substantially contribute to the cognitive growth and professional achievement of students studying science, technology, engineering, and mathematics (STEM). Yet, there is limited understanding of how students studying STEM develop a professional identity. We used the lens of self-authorship to develop a model for STEM student professional identity development. We applied the model to frame our assessment of the relationship between the level of STEM students' perceptions of their professional identities and their educational experiences, learning preferences, and comfort with faculty interactions. We found a misalignment between students' perception of themselves as professionals and the expectations for their actions in professional situations. We also found that students engaged in learning activities similar to the activities of STEM professionals communicated higher levels of professional identity development. We provide implications for our research and directions for ongoing investigations.


Background: Intensive speech-language therapy (SLT) can promote recovery from chronic post-stroke aphasia, a major consequence of stroke. However, effect sizes of intensive SLT are moderate, potentially reflecting a physiological limit of training-induced progress. Transcranial direct current stimulation (tDCS) is an easy-to-use, well-tolerated and low-cost approach that may enhance effectiveness of intensive SLT. In a recent phase-II randomized controlled trial, 26 individuals with chronic post-stroke aphasia received intensive SLT combined with anodal-tDCS of the left primary motor cortex (M1), resulting in improved naming and proxy-rated communication ability, with medium-to-large effect sizes. Aims: The proposed protocol seeks to establish the incremental benefit from anodal-tDCS of M1 in a phase-III randomized controlled trial with adequate power, ecologically valid outcomes, and evidence-based SLT. Methods: The planned study is a prospective randomized placebo-controlled (using sham-tDCS), parallel-group, double-blind, multi-center, phase-III superiority trial. A sample of 130 individuals with aphasia at least 6 months post-stroke will be recruited in more than 18 in- and outpatient rehabilitation centers. Outcomes: The primary outcome focuses on communication ability in chronic post-stroke aphasia, as revealed by changes on the Amsterdam-Nijmegen Everyday Language Test (A-scale; primary endpoint: 6-month follow-up; secondary endpoints: immediately after treatment, and 12-month follow-up). Secondary outcomes include measures assessing linguistic-executive skills, attention, memory, emotional well-being, quality of life, health economic costs, and adverse events (endpoints: 6-month follow-up, immediately after treatment, and 12-month follow-up). Discussion: Positive results will increase the quality of life for persons with aphasia and their families while reducing societal costs. After trial completion, a workshop with relevant stakeholders will ensure transfer into best-practice guidelines and successful integration within clinical routine. Clinical Trial Registration: www.ClinicalTrials.gov, identifier: NCT03930121.


SUMMARY: Twelve strains of Rhizobium sp. from wild and cultivated leguminous plants growing in the Belgian Congo were examined. All were bacillary or filamentous, weakly Gram-positive, and produced occasional refractile, heat-resistant spores; all grew alternatively in the form of very tiny, Gram-negative rods with polar flagella (if motile), and without spores. Botanical evidence suggests that the host plants are primitive members of the family Leguminosae, and if the characters of these strains of Rhizobium are also to be regarded as primitive, this evidence supports the view that Rhizobium is related to Azotobacter and the Bacillaceae.


The wavelet multiresolution interpolation Galerkin method in which both the unknown functions and nonlinear terms are approximated by their respective projections onto the same wavelet space is utilized to implement the spatial discretization of the highly coupled and nonlinear Von Karman equation for thin circular plates with various types of boundary conditions and external loads. Newton's method and the assumption of single harmonic response are then used for solving the static bending and free vibration problems, respectively. Highly accurate wavelet solutions for an extremely wide range of deflections are finally obtained by the proposed method. These results for moderately large deflections are in good agreement with existing solutions. Meanwhile, the other results for larger deflections are rarely achieved by using other methods. Comparative studies also demonstrate that the present wavelet method has higher accuracy and lower computational cost than many existing methods for solving geometrically nonlinear problems of thin circular plates. Moreover, the solutions for large deflection problems with concentrated load support the satisfactory capacity for handling singularity of the proposed wavelet method. In addition, a trivial initial guess, such as zero, can always lead to a convergent solution in very few iterations, even when the deflection is as large as over 46 times thickness of plate, showing an excellent convergence and stability of the present wavelet method in solving highly nonlinear problems.


China, and other developing nations, stand at a transportation planning crossroads--whether to follow the American highway/privatized motorization model or to optimize their existing mass transit/nonmotorized transportation model. This Comment charts the history of transportation development in China and indicates its destination in light of China's recent embrace of the car industry as a "pillar" of the nation's economy. It then considers motor vehicles' adverse effects, and assesses the value of mass and nonmotorized transportation as viable alternatives. In order to stall or reverse a process not supported wholeheartedly by the Chinese citizenry, this Comment determines whether China's internal city planning regime, environmental laws, and court system allow citizens to participate in and to challenge monumental decisions such as those affecting transportation development and the environment. Concluding that bottom-up strategies are currently ineffective, this Comment then considers top-down pressure through the United Nations Framework Convention on Climate Change ("UN/FCCC"). If not dissuaded, developing countries will undergo a chain reaction of mass motorization, building up a greenhouse gas emission debt many times over what may be reduced by the First World. Of the existing top-down strategies, the COP-3, slated for December 1997 in Kyoto, Japan, seems promising.


In this paper, we introduce a new load balancing user association scheme for millimeter wave (mmWave) cellular networks in which intelligent reflecting surface (IRS) is applied in the cellular network to improve the coverage region of each cell and mitigate mmWave vulnerability to non-line of sight (N-LoS) paths. The user association scheme improves network performance significantly by adjusting the interference according to the association. We study the IRS-assisted mmWave cellular network where one IRS is deployed to assist in the communication from the base station (BS) to mobile users (MUs) in each cell. We balance BS loads and maximize a network utility by optimizing the user association with a matching game. Simulation results show that the proposed scheme significantly improves the throughput compared to conventional user association techniques.


We present evidence for the factorization of the world-sheet path integrals for 2d conformal field theories on the disk into bulk and boundary contributions. This factorization is then used to reinterpret a shift in closed string backgrounds in terms of boundary deformations in background independent open string field theory. We give a proof of the factorization conjecture in the cases where the background is represented by WZW and related models.


Summary. A major issue in autologous blood stem cell transplantation (ABSCT) for leukaemia is whether peripheral blood stem cell (PBSC) harvests are less contaminated with leukaemic cells than bone marrow mononuclear cells (BMMNC). We compared leukaemic contamination in PBSC harvests and BMMNC, obtained simultaneously, by using reverse transcriptase polymerase chain reaction (RT‐PCR) of leukaemia‐specific chimaeric messenger RNA (mRNA), in three patients with Philadelphia chromosome (Ph)‐positive acute lymphoblastic leukaemia (ALL), one with Ph‐positive acute myelogenous leukaemia (AML), and two with acute promyelocytic leukaemia (APL). Our two‐step PCR method employed 'nested primers' in the second step and can detect one leukaemic blast diluted into 106 HL‐60 cells. In three of four patients with Ph‐positive ALL and AML we detected leukaemic contamination in both PBSC harvests and BMMNC. In the remaining patient with ALL, both PBSC harvests and BMMNC were PCR‐negative. Both PBSC harvests and BMMNC from one patient with APL were PCR‐positive. In contrast, PBSC harvests from another patient with APL, whose BMMNC could not be obtained because of bone marrow necrosis, were PCR‐positive after the first course of consolidation chemotherapy, but became PCR‐negative after the second course. The present study does not support the hypothesis that PBSC harvests are less contaminated by leukaemic cells than BMMNC, but suggests that PBSC harvests are contaminated when BMMNC are contaminated.


Cellular mobile systems designed to handle multimedia services are currently being developed. The primary goal for any mobile system is to provide a satisfactory quality of service, both to operators and customers. Providing good quality of service while maintaining system stability requires accurate knowledge of the system load. In particular, it is important to be able to predict how a resource management decision will affect the stability of the network. This thesis addresses the problem of characterizing and estimating the uplink load in a cellular system using CDMA (Code Division Multiple Access) in the radio interface.Uplink load can be related directly to the uplink power control problem of finding transmitter powers to support the users' quality of service requirements. This yields a rather theoretical view. Another way of looking at uplink load is to relate it to the total received power users induce in the base station antennas. Both of these views are handled and relations between them are established in this thesis.The literature survey on uplink load provided in this work concludes that practical estimates of the uplink load are generally what can be referred to as decentralized estimates; they use information gathered only in the immediate vicinity of the estimates' host node. As an alternative to these estimates, a number of centralized estimates based on information readilyavailable to the system are proposed. The usage of information from several cells makes them more sensitive to the soft capacity inherent in all CDMA cellular systems.Extensive simulations in an advanced WCDMA (Wideband Code Division Multiple Access) simulator show that the estimates statistically perform well and the performance is insensitive to non uniform traffic load.In the time domain, the load approximation can be described as oscillations superimposed on a slowly varying bias. If occasional high loads can be accepted, a non-oscillative signal representing the uplink load can be used to further increase the utilization of the resources. An algorithm is proposed to estimate the bias and a prediction of it.


A pilot-scale membrane process for the concentration of effluent from an alkaline peroxide mechanical pulping (APMP) plant was investigated. Specifically, the cross-flow velocity and volume reduction were optimized again for a higher flux and a lower system energy consumption. A mathematical model was established to obtain the optimal parameters. Estimates were obtained of the expected savings in energy and water. The obtained optimal concentration conditions were: molecular weight cut-off at 10,000 Dalton, trans-membrane pressure at 3 bar, feed temperature at 50 oC, cross-flow velocity at 2 m/s, and volume reduction at 0.9. The average permeate flux under these conditions was 43.21 l/m2.h. The total solids content was increased from 25.47 g/L in the feed to 128.36 g/L in the concentrate. The permeate had low total solids content of 11.03 g/L, Chemical Oxygen Demand of 9180 mg/l, and Biochemical Oxygen Demand of 5870 mg/L. Such qualities would allow the permeate to be reused in the APMP process after a light biochemical treatment. With this new membrane concentration process, about 1402 kWh energy can be saved and 22 m3 effluent discharge can be reduced for each ton of pulp produced.


Abstract Gonadal function is critically dependant on regulated secretion of the gonadotropin hormones from anterior pituitary gonadotroph cells. Gonadotropin biosynthesis and release is triggered by the binding of hypothalamic GnRH to GnRH receptor expressed on the gonadotroph cell surface. The repertoire of regulatory molecules involved in this process are still being defined. We used the mouse LβT2 gonadotroph cell line, which expresses both gonadotropin hormones, as a model to investigate GnRH regulation of gene expression and differential display reverse transcription-polymerase chain reaction (RT-PCR) to identify and isolate hormonally induced changes. This approach identified Fanconi anemia a (Fanca), a gene implicated in DNA damage repair, as a differentially expressed transcript. Mutations in Fanca account for the majority of cases of Fanconi anemia (FA), a recessively inherited disease identified by congenital defects, bone marrow failure, infertility, and cancer susceptibility. We confirmed expression and hormonal regulation of Fanca mRNA by quantitative RT-PCR, which showed that GnRH induced a rapid, transient increase in Fanca mRNA. Fanca protein was also acutely upregulated after GnRH treatment of LβT2 cells. In addition, Fanca gene expression was confined to mature pituitary gonadotrophs and adult mouse pituitary and was not expressed in the immature αT3-1 gonadotroph cell line. Thus, this study extends the expression profile of Fanca into a highly specialized endocrine cell and demonstrates hormonal regulation of expression of the Fanca locus. We suggest that this regulatory mechanism may have a crucial role in the GnRH-response mechanism of mature gonadotrophs and perhaps the etiology of FA.


The last decade has seen a concerted effort by the National Association of Purchasing Management (NAPM) and many influential academics and practitioners to promote the development of purchasing and materials management programs at universities and colleges across the United States. These efforts have been predicated on the assumption that if more universities sponsor purchasing and materials management programs, the number of graduates seeking employment in the field will increase, thereby enhancing the professional stature of purchasing. The NAPM Professorship program, the Doctoral Student Grant program, the Case Writing Workshop in Purchasing Management, and the Case Teaching Workshop are examples of efforts by NAPM to foster purchasing education. In 1965, more than 300 universities and colleges in the United States reported that they regularly taught purchasing courses in various formats as part of their business school curricula.|1~ More recent studies have found that there are in excess of 40 schools that have formal purchasing programs that award degrees at the baccalaureate or masters level or both.|2~ All these institutions strive to provide a quality education in purchasing to hundreds of students across the United States. Some of these programs are deemed more successful than others, and some are better known than others. Some programs attract the attention of corporate recruiters from across the country, some do not. What perceptual factors distinguish one purchasing program from another? What criteria are considered most important in creating the reputation of a program? Are there differences in perceptions held by academics and practitioners? OVERVIEW OF THE RESEARCH In January of 1992, a study was initiated at Arizona State University to answer these and other questions. An extensive questionnaire was mailed to 700 practicing purchasing managers and academics asking them to evaluate certain aspects of the current purchasing and materials management academic environment. The data bases for the survey mailing were two subsets of the large NAPM membership files. The first subset of potential respondents was taken from the NAPM membership list of "dues-free" members that were specifically linked to an academic institution. The second subset was simply a random sample of 100 practitioners categorized as class II members of NAPM--that is, middle managers. The research team received 181 responses to the survey. Of the 181 responses, 138 completed questionnaires were usable for the analyses described in this article. The 138 responses were received from both practitioners and academics, with 34 coming from practitioners and 104 from academics. Respondents resided in 34 states and the District of Columbia, as profiled in Table I. The length of employment for all 138 respondents is graphically depicted in Figure 1. FINDINGS Rating Program Performance A key question in the survey asked respondents to assess the usefulness of the following seven criteria in evaluating collegiate purchasing programs. The respondents were not asked to evaluate any particular college or university program using these criteria, but simply to indicate how important these criteria were to them in evaluating the reputation of a first-rate university or college purchasing program. 1. Reputation of the faculty 2. Research contribution of the institution to the field of purchasing 3. Quality of alumni encountered in the work place 4. Departmental reputation 5. Overall university reputation 6. Undergraduate curriculum 7. Graduate curriculum Table I DISTRIBUTION OF RESPONDENT LOCATIONS Percentage Percentage Percentage of of of State Responses State Responses State Responses AL 1.4 IL 1.4 NM 1.4 AR 1. …


HYPOTHESIS
This study was designed to evaluate prospectively oncological factors determining survival after resection of tumors of the papilla, comparing local and radical oncological resection. We hypothesized that, in malignant lesions of the ampulla, the T and N stages are major determinants of the patient's long-term outcome.

BACKGROUND DATA
The frequency of malignant lesions in adenomas of the papilla is about 26%. Villous adenoma of the ampulla is considered a premalignant lesion. Local excision has been recommended for benign adenoma and pancreatoduodenectomy for malignant lesions.

PATIENTS AND METHODS
From January 1, 1982, through June 30, 1997, 171 patients with tumors of the ampulla of Vater were surgically treated. Demographics, intraoperative factors, tumor pathological findings, and postoperative short- and long-term follow-up data were documented prospectively. Of the patients, 45 had adenoma of the papilla and 126 had malignant lesions of the ampulla.

RESULTS
Local resection was performed in 40 of the 45 patients with adenoma. In 98 of the 126 patients with malignant lesions, a radical Kausch-Whipple resection or pylorus-preserving pancreatoduodenectomy was used. Of the patients with benign adenoma, 40 had local resection and 5 had pylorus-preserving pancreatic head resection, with a hospital mortality of 0%. Thirty of 35 patients had villous adenoma, 9 (30%) of the 30 with severe dysplasia. Of the 126 patients with malignant lesions, 98 had partial pancreatoduodenectomy and 10 had ampullectomy, with an overall hospital mortality of 3.1% for patients who underwent resection. Seventy-eight of the 98 patients had an R0 resection. The 5-year survival probability for all patients who underwent resection was 84% for cancer stage I, 70% for stage II, and 27% for stage III. In 8 patients with villous adenoma and carcinoma in situ and in 10 patients with cancer in the adenoma, ampullectomy with local lymph node dissection was performed. In 4 of the patients who had villous adenoma and a carcinoma in stage pT1 N0, an R0 resection was performed, resulting in cure of cancer. On the basis of a multivariate regression analysis, the prognosis after oncological resection of cancer of the ampulla is determined by the absence of lymph node metastasis (P<.05), the absence of infiltration into the pancreatic head tissue (P<.05), and the application of an R0 resection.

CONCLUSIONS
In patients with villous adenoma of the ampulla, ampullectomy was an adequate surgical treatment. In patients with a low-risk cancer in stages pTis and pT1 N0 M0, G1 or G2, a local resection with ampullectomy including local lymph node dissection is justified. An oncological resection of cancer of the ampulla by means of a pylorus-preserving partial pancreatoduodenectomy or the Kausch-Whipple resection is the surgical procedure of choice; the 3- and 5-year survival rates were 72% and 52%, respectively, in patients with R0 resections.


Recent work suggests non-financial firms have acted like financial intermediaries particularly in emerging economies. This paper corroborates these findings but then asks "why?" The results indicate evidence for carry-trade activities, but they are focused on countries with higher levels of capital controls, particular controls on inflows. There is little evidence for such activities given other potential motives. It is posited that this phenomenon is due more to the reaction of countries in the face of low global interest rates, quantitative easing and strong capital inflows than incomplete markets or the retreat of global banks due to impaired balance sheets or tighter regulations.


ABSTRACT The effects of intradermal injection of interferon α -2 β on normal human skin were studied in 12 healthy adult volunteers using 500, 000 international units recombinant human interferon α-2β, 3 times a week for five injections (n = 6) and nine injections (n = 6). Saline injections served as control sites. Lymphocytic infiltrates and the population of epidermal Langerhans' cells in the injection areas were observed. The results showed that epidermal Langerhans' cells (both adenosine triphosphatase positive and CD-1 +) decreased significantly whereas human leukocyte antigen-DR expression in keratinocytes was enhanced. Dermal CD-3 + (Pan T cells), CD-4 + (T helper cells) and human leukocyte antigen DR + cells increased. No significant differences in the number of CD-19 + (B cells) and CD-57 + (NK cells) were observed. There were no significant differences between the five-injection and nine-injection groups.