We present a supersymmetric model with two dark matter (DM) components explaining the galactic positron excess observed by PAMELA/HEAT and ATIC/PPB-BETS: One is the conventional (bino-like) lightest supersymmetric particle (LSP) χ, and the other is a TeV scale meta-stable neutral singlet ND, which is a Dirac fermion (N,Nc). In this model, ND decays dominantly into χe+e− through an R parity preserving dimension 6 operator with the life time τN ∼ 1026 sec. We introduce a pair of vector-like superheavy SU(2) lepton doublets (L,Lc) and lepton singlets (E,Ec). The dimension 6 operator leading to the ND decay is generated from the leptophilic Yukawa interactions by W ⊃ NecE+LhdEc+m3/2l1Lc with the dimensionless couplings of order unity, and the gauge interaction by ℒ ⊃ (2)1/2g′ẽc*ecχ+h.c. The superheavy masses of the vector-like leptons (ML,ME ∼ 1016 GeV) are responsible for the longevity of ND. The low energy field spectrum in this model is just the MSSM fields and ND. Even for the case that the portion of ND is much smaller than that of χ in the total DM density [𝒪(10−10) ≲ nND/nχ], the observed positron excess can be explained by adopting relatively lighter masses of the vector-like leptons (1013 GeV ≲ ML,E ≲ 1016 GeV). The smallness of the electron mass is also explained. This model is easily embedded in the flipped SU(5) grand unification, which is a leptophilic unified theory.


Proximity-based services (PBS) are a subclass of location-based services that aim to detect the closest point of interest by comparing relative position of a mobile user with a set of entities to be detected. Traditionally, the performances of PBS are measured on the basis of the norm of the estimation error. Although this performance criterion is suitable for location-based services that aim tracking applications, it does not give enough information about the performance of PBS. This paper provides a novel framework quantifying the system performance of PBS by making use of spatially quantized decision regions that are determined according to service properties. The detection problem in PBS is modeled by an M-ary hypothesis test, and analytical expressions for correct detection, false alarm, and missed detection rates are derived. A relation between location estimation accuracy requirements that are mandated by regulatory organizations and the performance metrics of PBS is given. Additionally, a flexible cost expression that can be used to design high-performance PBS is provided. A system deployment scenario is considered to demonstrate the results. By using this framework, PBS designers can improve their command on the services' behavior and estimate service performance before deployment. Copyright © 2011 John Wiley & Sons, Ltd.


The discovery of the AMP-activated protein kinase (AMPK) more than a decade ago has shed much light on the cellular response to stresses characterized by a fall in the concentration of ATP and an increase in the AMP/ATP ratio. All conditions known to increase this ratio activate AMPK, whose major role is to act as an emergency signal to conserve ATP. It does so by inhibiting anabolic processes and by activating pathways producing ATP. In recent years, our laboratory has discovered new targets of AMPK. The purpose of this short review is to summarize our contribution to this field.


We cast the classic problem of achieving k-anonymity for a given database as a problem in algebraic topology. Using techniques from this field of mathematics, we propose a framework for k-anonymity that brings new insights and algorithms to anonymize a database. We focus on the simpler case when the data lies in a metric space which is instrumental in introducing the main ideas and notation. Specifically, by mapping a database to the Euclidean space and by considering the distance between datapoints, we introduce a simplicial representation of the data and show how concepts from algebraic topology, such as the nerve complex and persistent homology, can be applied to efficiently obtain the entire spectrum of k-anonymity of the database for various values of k and levels of generalization. For this representation, we provide an analytic characterization of conditions under which a given representation of the dataset is k-anonymous. We introduce a weighted barcode diagram which, in this context, becomes a computational tool to tradeoff data anonymity with data loss expressed as level of generalization. Some simulations results are used to illustrate the main idea of the paper.


Thyroid incidentaloma is defined as a new identified thyroid lesion occasionally detected during imaging studies. Incidence of thyroid incidentalomas is relatively rare in patients with lymphoma. Because of high rate of malignancy, these lesions with high intensity focal 18FDG uptake detected on positron emission tomography with computed tomography (PET/CT) should undergo to biopsy regardless of size.


Heterokaryons between fibroblasts from patients with classical Xeroderma pigmentosum (X.P.) and fibroblasts from normal or heterozygous subjects have indicated that normal cells contain at least three- to fourfold the amount of 'X.P.-enzyme' necessary for maximal unscheduled DNA synthesis and that the reduced enzyme levels in heterozygotes can be detected using heterokaryons with a high ratio of X.P. to heterozygous nuclei. Furthermore, a kinetic study of complementation in heterokaryons suggests that the 'X.P.-enzyme' is, probably, not a monomer and that its function may be dependent upon binding to an acceptor and formation of a stable complex which turns over slowly. Patients with the same clinical form of X.P. (classical type) may carry defective enzymes which do or do not bind to the acceptor. Our findings and the evidence in favour of a close correlation in the kinetics of the different aspects of the excision repair of DNA prompt us to suggest that the enzymes of this repair system may assemble to form a 'repair organelle'.


Based on phenotypic tests, 49 out of 168 isolates of Pseudomonas syringae obtained from various organs of diseased tissue originating from various regions in Poland, were identified as P. syringae pv. morsprunorum race 1 (Psm1), 10 as race 2 of this pathovar (Psm2), 53 as pathovar syringae (Pss) and 56 as an atypical taxon. The pathogenicity test on immature sweet cherry fruits divided the tested strains into two groups: one with isolates causing black brown necrosis and the second containing isolates inducing water soaked superficial lesions. Phenotypic and genetic studies on toxins production by bacteria showed that all Pss produced syringomycin. However, only some Psm1 isolates have the gene for coronatine production. All strains belonging to Psm2 possessed genes encoding yersiniabactin. Results of genetic analyses (rep-PCRs, PCR MP) confirmed the homogeneity of isolates within pathovar morsprunorum and the atypical taxon and revealed diversity within pathovar syringae. A detailed polyphasic approach including phenotypic and genetic characterization applied for eight strains from the atypical taxon showed that the strains represent a novel species of the genus Pseudomonas for which Pseudomonas cerasi sp. nov. (non Griffin, 1911) is proposed.


Objective. Anastomotic fistulas in digestive surgery is a serious complication that can lead to patient's death. The identification of paraclinical laboratory samples to allow early diagnosis of fistulas would allow an optimal patient's management. Materials and method. We conducted a prospective study on 41 cancer patients operated for gastric tumors between 2016 and 2017 in the First Clinic of General Surgery and Oncology of the "Prof. Dr. Alexandru Trestioreanu" Institute of Oncology, Bucharest. All patients were subjected to gastric resections or gastrojejunal anastomoses. Therefore, digestive sutures were performed. Postoperative follow-up included the determination of C-reactive protein (CRP), monitoring of leukocyte counts in the peritoneal cavity (from a biological product harvested from the chest tube), associated with the number of leukocytes in the blood. Depending on the values of these biological samples and the clinical evolution, other paraclinical investigations were used to confirm the diagnosis in selected cases. Results. The data obtained showed that patients with digestive fistulas had a rapid increase and maintained high values of CRP and leukocytes in the peritoneal cavity, which was associated with an increase in leukocytes' blood count. Changes occur approximately two days prior to clinical signs and their confirmation by imaging (ultrasound, CT scan). Conclusion. Regular and standardized monitoring of CRP, leukocytes in the peritoneal cavity and leukocytosis on days 1, 3 and 5 allows the early identification of patients at risk for fistula and the rapid selection of patients requiring additional explorations and/or surgery.


In recent years, a remarkably simple physical picture of the Lyman-alpha forest has emerged, which allows detailed predictions to be made and turns the forest into a powerful probe of cosmology. We point out ways in which such a picture can be tested observationally, and explore three areas in which the Lyman-alpha forest can yield valuable constraints: the reionization history, the primordial mass power spectrum and the cosmological constant or its variants. The possibility of combining with other high redshift observations , such as the Lyman-break galaxy surveys, to provide consistency checks and complementary information is also discussed.


We provide a proof-of-concept demonstration using a novel method for estimating depth-integrated distributions of chlorophyll from archives of data from ships, buoys or gliders combined with remotely sensed data of sea surface temperature (SST) and surface chlorophyll a (chl a) from satellites. Our area of application has contrasting hydrographic regimes, which include the dynamic southern Benguela upwelling system and the stratified waters of the Agulhas Bank, South Africa. The method involves using self-organising maps (SOMs), a type of artificial neural network, to identify 'typical' chl a profiles regardless of their statistical form, provided several of a similar shape have been found in the training set. These are arranged in a linear array, ranging from uniform profiles low in chl a to profiles with high surface or subsurface peaks. We then use generalised modelling to relate these characteristic profiles to remotely sensed surface features, viz. surface chl a and SST, as well as area, season, and water depth (a proxy for distance offshore). The model accounts for 87% of the variability in chl a profile and is used to predict the type of profile likely for each pixel in monthly remote sensing composites of SST and surface chl a and then to estimate integrated chl a and primary production with the aid of a light model. Primary production peaks in mid-summer, reaching 5 mgC m(-2) d(-1) locally, with an average over the whole area and all seasons of 1.4 mg C m(-2) d(-1). Seasonal variation is greatest in the southern part of the west coast, and lowest in the stratified southeast. Annual primary production for the southern Benguela region including the Agulhas Bank is ca. 156 million tC yr(-1). This is the most robust estimate of primary production in the Benguela system to date because it combines the spatial and temporal coverage provided by remote sensing with realistic vertical chl a profiles.


The aim of this single-arm, phase II study was to estimate the tumor response rate and safety profile of erlotinib HCl (erlotinib, Tarceva™, OSI-774) monotherapy in patients with refractory, recurrent, HER1/EGFR-positive epithelial ovarian tumors, who had failed prior taxane and/or platinum-based chemotherapy. Thirty-four patients received 150 mg erlotinib orally once daily for up to 48 weeks or until disease progression or dose-limiting toxicity. Two patients had partial responses, lasting 8+ and 17 weeks, giving an objective response rate of 6% (95% confidence interval [CI], 0.7–19.7%). Fifteen patients (44%) had stable disease, and 17 patients (50%) had progressive disease. Median overall survival was 8 months (95% CI, 5.7–12.7 months), with a 1-year survival rate of 35.3% (95% CI, 19.8–53.5%). Patients with rash survived significantly longer than those without (P = 0.009), correlating with rash grade. Erlotinib was generally well tolerated. The most frequent erlotinib-related adverse events were rash (68%) and diarrhea (38%). Erlotinib had marginal activity but was generally well tolerated. The safety profile appears more favorable than typically experienced with standard chemotherapeutic agents, which is encouraging in these heavily pretreated patients. Combination of erlotinib with chemotherapy or other targeted agents should be considered.


What determines the direction of technological change within an industry? In this presentation it is argued that technological exemplars play a key role. An exemplar is a design model or pattern to be built upon and imitated. Koen Frenken's model of technological paradigm formation suggests that the selective construction of a design over time produces an exemplar with 'locked-in' core elements. These core elements channel future change along a particular technological trajectory. Here a new model is presented that suggests that, where competitive forces are sufficient, 'two-tier' selection (both selective construction of designs and selection of firms at the industry level) results in a dominant exemplar and associated trajectory at the industry level. Variety reducing forces interact with variety generating forces such that the balance determines whether or not a trajectory will emerge. Friday 28th February, 15:30 INET Oxford Seminar Room, Eagle House, Walton Well Road, OX2 6ED


American employers and workers underinvest in employer training. Underinvestment occurs because training generates externalities, because turnover is excessive, because the tax system discourages training investment, and because workers lack access to loans that would allow them finance heavy investments in training (Bishop 1991). During the election campaign, President Clinton proposed stimulating training by requiring employers to spend some minimum percentage of their wage bill on training or else be subject to a special tax. France has had such a mandate since 1972, so the design of an American training mandate is likely to benefit from a careful examination of the French program. The French have demonstrated that a training mandate is administratively and politically feasible, but their mandate is not optimally designed for U.S. implementation. The paper concludes with some recommendations about how a U.S. mandate to spend on training should be structured.


In many ways, new electronic communication technologies have brought about unprecedented changes to the newspaper industry. Increasingly web based content and newspaper sites are turning to a subscription based business model. This dissertation will examine the factors that influenced The Irish Times newspaper to turn to a subscription based business model for their website Ireland.com and potential consumers' opinions about such paid services.

The author has written an Ireland.com case study to examine how Ireland.com has evolved from The Irish Times website to Ireland.com vertical portal. The case study examined the business model of Ireland.com and traced the steps involved in moving from a registration model to a subscription model, with a detailed examination of the effects of changes on Ireland.com.

An online survey which was conducted on Ireland.com targeting existing subscribers to Ireland.com. The objective was to establish how subscribers perceive the existing 'premium content' subscription package, in terms of quality and value, to establish why they are willing to pay for content online.

The results of this survey (which had a 15% response rate - demonstrating loyalty from their subscribers) has led the author to the conclusion that Ireland.com subscribers are willing to pay for news content online, as they perceive the content as being of the highest quality and delivered in an unbiased fashion leading to overall perception of value, in the minds of their subscribers. Ireland.com subscribers are well educated, in the ABCi bracket and are working or self employed, are loyal to Ireland.com brand which represents quality, unbiased news with valuable added services i.e. premium email, breaking news, Irish Times newspaper and their 10 yr archive service.

As borne out by the case study and the level of response to the online survey, together with the level of subscriptions and subscription-based, added value services, it is clear that the subscription model employed at Ireland.com is indeed a success. Subscriptions account for 31% of revenue for Ireland.com.

Ireland.com is one of the first Irish portal sites to successful implement the subscription ipqdel. Ireland.com have a loyal customer base so adding extra value to their products and services are a number one priority with Ireland.com. However, Ireland.com has had their up and downs, with the streamlining of the organisation in 2002, due to financial pressures. Heavy investment is still required on the part of The Irish Times (parent company) if Ireland.com are to maintain their position in the marketplace, as one of the leading web portals for news content online, in Ireland.

Todays under 25 year olds are also the first generation to have grown up with the internet and attracting them to static media like newspapers can be difficult. In the online world of infinite content, only time will tell if young readers adopt newspapers and their websites as their main source for content or if their competitors publish a more alluring product tailored to the desires of youth.


Objective To assess the impact of modifications to radical neck dissection on postoperative quality of life. Design Cross-sectional study using a self-administered neck dissection questionnaire and an arm abduction test. Setting Department of Otolaryngology–Head and Neck Surgery, Kobe University Hospital. Patients Seventy-four patients who had undergone neck dissection for the treatment of head and neck cancer. Main Outcome Measures Arm abduction test results and responses to questions on quality of life related to neck dissection. Results Forty-one patients underwent bilateral neck dissections, and 33 patients underwent unilateral neck dissection. Level V nodes were dissected in 74 necks. Among them, the spinal accessory nerve (SAN) was resected in 29 necks. Patients who had neck dissections that spared the SAN had better shoulder function. When the SAN was preserved, patients without dissection of level IV and V nodes had better scores on measures of pain and constriction of the neck. Sacrifice of the sternocleidomastoid muscle and/or the SAN had a significant effect on daily activities, work, and leisure. The arm abduction test scores and answers to questions regarding shoulder function were significantly correlated. Conclusions Modifications to radical neck dissection contribute to improvements in the postoperative quality of life after neck dissection. A multicenter study using the arm abduction test and questionnaire used in this study is currently in progress to further evaluate the impact of modifications to radical neck dissection on quality of life after surgery.


Abstract Cooperation among individuals has been key to sustaining societies. However, natural selection favors defection over cooperation. Cooperation can be favored when the mobility of individuals allows cooperators to form a cluster (or group). Mobility patterns of animals sometimes follow a Lévy flight. A Lévy flight is a kind of random walk but it is composed of many small movements with a few big movements. The role of Lévy flights for cooperation has been studied by Antonioni and Tomassini, who showed that Lévy flights promoted cooperation combined with conditional movements triggered by neighboring defectors. However, the optimal condition for neighboring defectors and how the condition changes with the intensity of Lévy flights are still unclear. Here, we developed an agent-based model in a square lattice where agents perform Lévy flights depending on the fraction of neighboring defectors. We systematically studied the relationships among three factors for cooperation: sensitivity to defectors, the intensity of Lévy flights, and population density. Results of evolutionary simulations showed that moderate sensitivity most promoted cooperation. Then, we found that the shortest movements were best for cooperation when the sensitivity to defectors was high. In contrast, when the sensitivity was low, longer movements were best for cooperation. Thus, Lévy flights, the balance between short and long jumps, promoted cooperation in any sensitivity, which was confirmed by evolutionary simulations. Finally, as the population density became larger, higher sensitivity was more beneficial for cooperation to evolve. Our study highlights that Lévy flights are an optimal searching strategy not only for foraging but also for constructing cooperative relationships with others.


In this article I ask what recent moral psychology and neuroscience can and can't claim to have discovered about morality. I argue that the object of study of much recent work is not morality but a particular kind of individual moral judgment. But this is a small and peculiar sample of morality. There are many things that are moral yet not moral judgments. There are also many things that are moral judgments yet not of that particular kind. If moral things are various and diverse, then empirical research about one kind of individual moral judgment doesn't warrant theoretical conclusions about morality in general. If that kind of individual moral judgment is a peculiar and rare thing, then it is not obvious what it tells us about other moral things. What is more, it is not obvious what its theoretical importance is to begin with—that is, why we should care about it at all. In light of these arguments, I call for a pluralism of methods and objects of inquiry in the scientific investigation of morality, so that it transcends its problematic overemphasis on a particular kind of individual moral judgment.


Summary The environment within the metabolically active polymorphonuclear leucocyte during phagocytosis is conducive to the germination of phagocytically ingested spores of Clostridium botulinum type A. Specific metabolic inhibitors of leucocyte function—glyceraldehyde, hydrocortisone, colchicine, methimazole and azide—were used to study metabolic pathways during phagocytosis that may be responsible for inducing spore germination within the leucocyte. Leakage of 45Ca from labelled Cl. botulinum spores was taken as evidence of spore germination. Release of free 45Ca from phagocytosed spores in sporeleucocyte mixtures in in-vitro systems was normal in the presence of hydrocortisone, methimazole, azide and methimazole+azide. These findings indicate that H2O2 production, iodination and myeloperoxidase activities during phagocytosis are not required for germination. In the presence of glyceraldehyde or colchicine, release of 45Ca from spore-leucocyte mixtures was profoundly inhibited and this indicates that glycolysis and lysosome degranulation are essential for intraleucocytic spore germination. In leucocytes from patients with a genetic abnormality of phagocytosis, i.e., chronic granulomatous disease of childhood (CGD), germination of spores was significantly depressed. Since normal mechanisms of H2O2 production and possibly of lysosomal degranulation are blocked in CGD leucocytes, the results suggest that H2O2 and lysosomal enzymes are involved in triggering spore germination in this model. Nevertheless, a limited release of 45Ca was observed and this seems to indicate that small amounts of lysosomal enzymes are available for reaction with engulfed spores in CGD leucocytes. The results of these studies with metabolic inhibitors and genetic blocks lead to the view that germination of spores of Cl. botulinum within leucocytes is triggered by the combined action of lowered pH resulting from glycolysis together with lytic enzymes resulting from degranulation of lysosomes.


Neuroscience
Alzheimer's disease is a progressive brain disease that leads to dementia and eventual death. Soluble aggregates of amyloid-β peptides (oligomers) accumulate in Alzheimer's brains and strongly impair cognitive function. Most of our knowledge about the disease comes from studying rodents, which are imperfect models. In an attempt to develop a better disease model, Forny-Germano et al. injected amyloid-β oligomers into the brain ventricles of macaques. The authors detected the proteins in nerve cells in several memory-related regions of the brain. There they triggered typical Alzheimer's pathologies such as synapse loss and activation of microglia cells and astrocytes. Given the similarities between human and macaque brains, this model may be an important step toward understanding Alzheimer's pathogenesis and developing effective therapies.

J. Neurosci. 34 , 13629 (2014).

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Alumina surface with La and Pd

CREDIT: E.J. PETERSON ET AL., NATURE COMMUNICATIONS 5 , 4885 © 2014 MACMILLAN PUBLISHERS LIMITED

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The China Health Authority alerted the World Health Organization (WHO) on December 31 2019, to several cases of pneumonia of unknown aetiology in Wuhan City in Hubei Province in central China. Since December 8, 2019, these cases had been reported, worked at or lived around the local Huanan Seafood Market.

Radiology finding may vary with patients age, disease progression, immunity status, comorbidity, and initial medical intervention. In a study describing 41 of the initial cases of 2019-nCoV infection, all 41 patients had pneumonia with abnormal findings on chest computed tomography (CT-scan). Abnormalities on chest CT-scan were also seen in another study of 6 cases, in which all of them showed multifocal patchy ground-glass opacities notably nearby the peripheral sections of the lungs.

Complete autopsy studies were almost nonexistent in the initial phases of the outbreak; reasonably so, due to concerns related to infectivity, transmission rates, and biosafety. The few reports initially published were limited to postmortem biopsies in COVID-19–positive patients or from lobectomy specimens initially resected for lung adenocarcinoma, but patients were later found to be COVID-19–positive (7). Pathologic features of exudative and proliferative phases of diffuse alveolar damage (DAD) were noted in these initial reports and overlapping features with SARS were also noted. Later complete autopsies performed in United States further supported the presence of DAD.

The predominant pattern of lung lesions in COVID-19 patients is DAD, as described for the other two coronavirus that infect humans, SARS-CoV and MERSCoV. Hyaline membrane formation and pneumocyte atypical hyperplasia are frequently found. The main relevant finding is the presence of platelet-fibrin thrombi in small arterial vessels; this important observation fits into the clinical context of coagulopathy which dominates in these patients and which is one of the main targets of therapy.

The macroscopic features of COVID-19 are likely to be in the chest and may include pleurisy, pericarditis, lung consolidation and pulmonary oedema. Lung weight may be increased above normal. It should be noted a secondary infection may be superimposed on the viral infection that can lead to purulent inflammation more typical of bacterial infection.

The pulmonary histologic characteristics of COVID-19 resembled those observed in diseases caused by other Betacoronavirus infections such as severe acute respiratory syndrome4 and Middle East respiratory syndrome.

Histopathology of the lungs showed diffuse alveolar damage, consistent with early acute respiratory distress syndrome in 8 cases. Predominant findings were hyaline membranes, activated pneumocytes, microvascular thromboemboli, capillary congestion, and proteinenriched interstitial edema. As described by Wang and colleagues, a moderate degree of inflammatory infiltrates concurred with clinically described leukopenia in patients with COVID-19 and predominant infiltration of lymphocytes fit the picture of a viral pathogenesis.


The proton exchange membrane direct methanol fuel cells (PEMDMFC) shows considerably lower performance than the hydrogen fuel cell because of inefficient methanol oxidation and the crossover of the methanol through the membrane that separates the anode from the cathode. This paper describes an electrochemical method to measure the crossovered methanol for Nafion® 117 membrane in function of the time. The permeation rate is calculated both by electroanalytical and gas chromatography methods at 25°C. The results are discussed.Copyright © 2004 by ASME


Gel-phase (19)F NMR spectroscopy is a useful monitoring technique for solid-phase organic chemistry due to the high information content it delivers and swift acquisition times, using standard NMR spectrometers. This paper describes the synthesis of the novel linker 2-(2-fluoro-4-hydroxymethyl-5-methoxy-phenoxy)acetic acid in 29% yield over seven steps, using nucleophilic aromatic substitutions on 2,4,5-trifluorobenzonitrile as key steps. Following standard solid-phase synthesis a peptide could be cleaved from the linker using 20% TFA in CH(2)Cl(2) in 30 minutes, in contrast to a previously described monoalkoxy linker that requires 90% TFA in water at elevated temperature. A resin-bound peptide could be successfully glycosylated using only two equivalents of a thioglycoside donor, activated with N-iodosuccinimide and trifluoromethanesulfonic acid, and subsequent cleavage and deprotection gave the target glycopeptide. Direct glycosylation of the linker itself followed by mild acidic cleavage gave a fully protected hemiacetal for further chemical manipulation.


This article describes the fabrication of hollow manganese/cobalt oxide nanoparticles (MCO NPs) with a tunable size through a redox reaction and the Kirkendall effect for cancer imaging and drug delivery. MCO-70 NPs (with an average size of 70 nm) can act as glutathione (GSH)-responsive contrast agents for dual T1/T2-weighted magnetic resonance imaging (MRI). The degradation of MCO NPs by GSH led to the enhancement of their T1 and T2 signals by 2.24- and 3.43-fold compared with those of MCO NPs before degradation, respectively. Antitumor agents such as doxorubicin (Dox) could be encapsulated inside the cavity of the hollow MCO NPs (MCO-70-Dox) and be released in the presence of GSH. The MCO-70-Dox NPs showed good tumor growth inhibition effects in vitro and in vivo, and can be promising drug delivery vehicles and MRI contrast agents for tumor diagnosis and reporting drug release.


The recent resurgence of plant remedies results from several factors like effectiveness of plant medicines and lesser side effects compared to modern medicines. In the present scenario, the need for basic scientific investigations on medicinal plants used in the indigenous systems becomes imminent. This is evident by the increase in number of reports by various investigators supporting the claims of medicinal plants and a dramatic increase in the share of plant products in pharmaceutical market. The present review aims to give data highlighting the present trends in research of medicinal plants accredited with antiurolithiatic activity. This may help investigators to identify and develop appropriate lead compounds or plant products beneficial in the management of urolithiasis.


In premitotic tobacco BY-2 cells, the nucleus moves from the periphery to the central region of the cell and settles there. This premitotic migration of the nucleus occurs in the presence of aphidicolin, an inhibitor of DNA polymerase α, which suppresses the formation of the preprophase band of microtubules (PPB). Thus, the formation of the PPB is not a prerequisite for this premitotic nuclear migration. Tethered by transvacuolar cytoplasmic strands, which contain both microtubules and actin filaments, the nucleus migrates to the site of future division. This migration is not prevented by disruption of actin filaments caused by treatment with cytochalasin, suggesting that microtubules play an important role in the premitotic migration of the nucleus. In the preprophase cell, microtubules were present in the PPB and in cytoplasmic strands, which extended from the nucleus to the periphery of the cell near the PPB and near the poles, and which were associated with actin filaments. At the end of prophase, microtubules in the cytoplasmic strands and the PPB disappeared, leaving actin filaments in the transvacuolar cytoplasmic strands. Thereafter, the position of the mitotic apparatus (or that of the cytokinetic phragmoplast) was maintained by cytoplasmic strands that contained only actin filaments. The disruption of microtubules by treatment with propyzamide prevented the formation of the PPBlike band of actin filaments, as well as that of the PPB itself. From these results, we propose the following hypothesis. In premitotic tobacco BY-2 cells, microtubules change their arrangement irrespective of the presence of actin filaments. The resultant premitotic network of microtubules serves as a scaffold for building up the mitotic network of actin filaments, which plays an important role in maintaining the position of the mitotic apparatus and in controlling the direction of expansion of the phragmoplast.


Selective conversion of biomass-derived substrates in heterogeneous catalysis can be achieved through the functionalization of nanoparticles with surface modifiers (ligands). However, full understanding of reaction mechanisms at the atomic level of detail is still limited. Herein we rely on computational approaches to address this challenge. We employ Density Functional Theory to understand the role of phosphine-decorated palladium nanoparticles in the decarbonylation of fatty acids to produce linear α-olefins. While self-assembled monolayers of monodentate ligands completely passivate the metal surface, the flexibility of bidentate counterparts allows the creation of transient cavities that: (i) enhance selectivity and (ii) prevent catalyst deactivation. Such detailed insight provided by theory can pave the way for a rational design of metal–ligand interfaces in biomass upgrading.


The Fridtjovbreen glacier surged for 12 yr (1991–2002). The maximum extent with a run-out distance of ∼4 km was reached after 7 yr. On the basis of ice-front behavior, the active phase of the surge can be divided into four stages: increased ice flow but stable ice-front position (30 months), advancing ice front (54 months with an average advance rate of 2.5 m day −1 ), maximum extent (12 months), and retreating ice front with persistent ice flow (∼36 months). The most prominent landforms developed during this surge are a network of composite thrust moraines on the deglaciated seafloor, with a sediment architecture indicating that ice flux persisted during the glacial retreat. Drawdown of land-based ice contributed to the protracted deceleration phase, and the intense thrusting was a result of ice flow along an undulating seafloor and the buttressing effect of a seasonally frozen fjord.


Hemophagocytic lymphohistiocytosis (HLH) is a rare life-threatening condition. Uncontrolled proliferation of activated lymphocytes secreting high amounts of inflammatory cytokines seems to be the main pathogenesis. The diagnosis of HLH can often be difficult. It may presents in many forms such as fever of unknown origin, hepatitis, acute liver failure, and sepsis-like illness. Here we present a newborn galactosemia case presented with HLH. Close monitoring of the diagnostic criteria of HLH during the course of galactosemia-associated hemophagocytosis, both before and after dietary treatment, should be performed in order to fully determine if the triggering mechanism is infection or accumulation of metabolites. Conflict of interest:None declared.


PT. PLN Distribusi Jawa Barat company supplying electricity to reach over 42,196 km which includes the province of West Java. Number of consumers which reaches more than 9 million costumers, or 22% of the costumers number PLN nationally, make PLN DJB is a largest unit electricity company PLN was in Indonesia. The distribution of electrical energy transmission up to subscribers was the principal activity conducted by PLN DJB. The distribution of electricity to produce value for customers PLN DJB company. Enterprise architecture is one of the methods that can be used to harmonize business strategy and strategies ti designed as required by business. TOGAF ADM is one of a framework that can be used as reference in establishing the enterprise architecture. Output of research is blueprint architecture business, data, application of technology and roadmap development TI in PLN DJB. Expected , with the design enterprise architecture on the distribution in PLN DJB can be reference develop the distribution of both in terms of business and information technology. Keywords: Enterprise Architecture, TOGAF ADM, Energy Company


Abstract Background The aim of the Million Person Study of Low-Dose Health Effects (MPS) is to examine the level of radiation risk for chronic exposures received gradually over time and not acutely as was the case for the Japanese atomic bomb survivors. Nuclear power plant (NPP) workers comprise nearly 15 percent of the MPS. Leukemia, selected cancers, Parkinson's disease, ischemic heart disease (IHD) and other causes of death are evaluated. Methods and material The U.S. Nuclear Regulatory Commission's Radiation Exposure Information and Reporting System (REIRS) and the Landauer, Inc. dosimetry databases identified 135,193 NPP workers first monitored 1957–1984. Annual personal dose equivalents [Hp(10)] were available for each worker. Radiation records from all places of employment were sought. Vital status was determined through 2011. Mean absorbed doses to red bone marrow (RBM), esophagus, lung, colon, brain and heart were estimated by adjusting the recorded Hp(10) for each worker by scaling factors, accounting for exposure geometry and energy of the incident gamma radiation. Standardized mortality ratios (SMR) were calculated. Radiation risks were estimated using Cox proportional hazards models. Results Nearly 50% of workers were employed for more than 20 years. The mean duration of follow-up was 30.2 y. Overall, 29,124 total deaths occurred, 296 from leukemia other than chronic lymphocytic leukemia (CLL), 3382 from lung cancer, 140 from Parkinson's disease and 5410 from IHD. The mean dose to RBM was 37.9 mGy (maximum 1.0 Gy; percent >100 mGy was 9.2%), 43.2 mGy to lung, 43.7 mGy to colon, 33.2 mGy to brain, and 43.9 mGy to heart. The SMRs (95% CI) were 1.06 (0.94; 1.19) for leukemia other than CLL, 1.10 (1.07; 1.14) for lung cancer, 0.90 (0.76; 1.06) for Parkinson's disease, and 0.80 (0.78; 0.82) for IHD. The excess relative risk (ERR) per 100 mGy for leukemia other than CLL was 0.15 (90% CI −0.001; 0.31). For all solid cancers the ERR per 100 mGy (95% CI) was 0.01 (–0.03; 0.05), for lung cancer −0.04 (–0.11; 0.02), for Parkinson's disease 0.24 (–0.02; 0.50), and for IHD −0.01 (–0.06; 0.04). Conclusion Prolonged exposure to radiation increased the risk of leukemia other than CLL among NPP workers. There was little evidence for a radiation association for all solid cancers, lung cancer or ischemic heart disease. Increased precision will be forthcoming as the different cohorts within the MPS are combined, such as industrial radiographers and medical radiation workers who were assembled and evaluated in like manner.


The metabolism of endogenous nutrients was examined in pancreatic islets of control and Goto-Kakizaki (GK) rats. At the ultrastructural level, no glycogen was found in the islet cells of GK rats, a situation similar to that prevailing in normal islets. Likewise, by measuring the output of L-lactate from islets first incubated at 16.7 mM D-glucose and then at 2.8 mM D-glucose, no evidence of glycogenolysis was found in the islets of GK rats. The production of NH4+ and that of 14CO2 from islets prelabelled with either L-[U-14C]glutamine or [U-14C]palmitate were higher, however, in GK than in control rats. The changes in NH4+ and 14CO2 production evoked by D-glucose, by a non-metabolized analogue of L-leucine (2-amino-bicyclo[2,2,1]heptane-2-carboxylic acid; BCH) and by 3-phenylpyruvate were qualitatively comparable in control and GK rats. The secretory response to these three secretagogues was severely decreased in the islets of GK rats. This coincided with an impaired enhancing action of D-glucose on the conversion of [2-3H]glycerol into 3HOH. It is concluded that the catabolism of endogenous amino and fatty acids in islets is greater in GK than in control rats, especially at low D-glucose concentration. This may account, in part at least, for the altered secretory response to BCH and 3-phenylpyruvate. For glucose-induced insulin release, however, an impaired acceleration of the glycerol phosphate shuttle apparently also participates in the secretory defect.


The simultaneous intracellular delivery of multiple types of payloads, such as hydrophobic drugs and nucleic acids, typically requires complex carrier systems. Herein, we demonstrate a self-deliverable form of nucleic acid-drug nanostructure that is composed almost entirely of payload molecules. Upon light activation, the nanostructure sheds the nucleic acid shell, while the core, which consists of prodrug molecules, disintegrates via an irreversible self-immolative process, releasing free drug molecules and small molecule fragments. We demonstrate that the nanostructures exhibit enhanced stability against DNase I compared with free DNA, and that the model drug (camptothecin) released exhibits similar efficacy as free, unmodified drugs toward cancer cells.


s 25th Nordic Congress on Military Medicine S41 POSTER PRESENTATIONS In alphabetical order by first author Contamination Control Area (CCA): A New Concept for CCA Design and Nuclear, Biological and Chemical (NBC) Procedures for Ground Personnel


Abstract This study aims to characterize human stratum corneum (SC), focusing on those lipid transitions that occur at or below physiologically relevant temperatures. In the past, a lipid transition near 35 °C had been thought to be variable and a consequence of superficial sebaceous lipid contamination. However, analysis here indicates that it is widely present, and cannot be attributed to sebum production. We demonstrate that this transition represents a solid-to-fluid phase change for a discrete subset of SC lipids. The reversibility of this transition upon reheating, and its absence in extracted lipid samples imply that these lipids are not uniformly present throughout the SC, but would appear to be differentially distributed in response to terminal differentiation. Further, such an arrangement could involve a close association with other nonlipid (e.g., protein) components. Evidence for a new transition at ~55 °C is presented that suggests the loss of crystalline orthorhombic lattice structure. The existence of orthorhombic structure at physiologic temperature is reasoned to involve ceramides and/or free fatty acids. Localization of these lipids at the level of the corneocyte envelope supports a comprehensive picture of water transport across the SC, whereby diffusion occurs primarily via the intercellular lipids. This view, coupled with the hydration-induced changes in lipid disorder observed here provides additional insight into the mechanism by which skin occlusion increases permeability. Summarily, these results i) emphasize the inherent danger of over-interpreting experiments with isolated SC lipids, ii) emphasize the potential advantage(s) of employing several biophysical techniques to study SC structure, and iii) indicate that a full characterization of lipid phase behavior is requisite to our eventual understanding of SC structure and permeability function, particularly those phase transitions that occur near or at normal skin temperature.


Two series of piperazinyl-pyrrolo[1,2-a]quinoxaline derivatives were prepared via a Buchwald–Hartwig cross-coupling reaction and then evaluated for their ability to inhibit the drug efflux activity of CaCdr1p and CaMdr1p transporters of Candida albicans overexpressed in a Saccharomyces cerevisiae strain. In the initial screening of twenty-nine piperazinyl-pyrrolo[1,2-a]quinoxaline derivatives, twenty-three compounds behaved as dual inhibitors of CaCdr1p and CaMdr1p. Only four compounds showed exclusive inhibition of CaCdr1p or CaMdr1p. Further biological investigations were developed and for example, their antifungal potential was evaluated by measuring the growth of control yeast cells (AD1-8u−) and efflux pump-overexpressing cells (AD-CDR1 and AD-MDR1) after exposition to variable concentrations of the tested compounds. The MIC80 values of nineteen compounds ranging from 100 to 901 μM for AD-CDR1 demonstrated that relative resistance index (RI) values were between 8 and 274. In comparison, only seven compounds had RI values superior to 4 in cells overexpressing Mdr1p. These results indicated substrate behavior for nineteen compounds for CaCdr1p and seven compounds for CaMdr1p, as these compounds were transported via MDR transporter overexpressing cells and not by the AD1-8u− cells. Finally, in a combination assay with fluconazole, two compounds (1d and 1f) have shown a synergistic effect (fractional inhibitory concentration index (FICI) values ≤ 0.5) at micromolar concentrations in the AD-MDR1 yeast strain overexpressing CaMdr1p-protein, indicating an excellent potency toward chemosensitization.


Stimuli associated with taking drugs are notorious instigators of relapse. There is, however, considerable variation in the motivational properties of such stimuli, both as a function of the individual and the nature of the stimulus. The behavior of some individuals (sign trackers, STs) is especially influenced by cues paired with reward delivery, perhaps because they are prone to process information via dopamine-dependent, cue-driven, incentive salience systems. Other individuals (goal trackers, GTs) are better able to incorporate higher-order contextual information, perhaps because of better executive/attentional control over behavior, which requires frontal cortical cholinergic activity. We hypothesized, therefore, that a cue that "sets the occasion" for drug taking (a discriminative stimulus, DS) would reinstate cocaine seeking more readily in GTs than STs and that this would require intact cholinergic neurotransmission. To test this, male STs and GTs were trained to self-administer cocaine using an intermittent access schedule with periods of cocaine availability and unavailability signaled by a DS+ and a DS−, respectively. Thereafter, half of the rats received an immunotoxic lesion that destroyed 40–50% of basal forebrain cholinergic neurons and later, after extinction training, were tested for the ability of noncontingent presentations of the DS+ to reinstate cocaine seeking behavior. The DS+ was much more effective in reinstating cocaine seeking in GTs than STs and this effect was abolished by cholinergic losses despite the fact that all rats continued to orient to the DS+. We conclude that vulnerability to relapse involves interactions between individual cognitive–motivational biases and the form of the drug cue encountered. SIGNIFICANCE STATEMENT The most predictable outcome of a diagnosis of addiction is a high chance for relapse. When addicts encounter cues previously associated with drug, their attention may be unduly attracted to such cues and these cues can evoke motivational states that instigate and maintain drug-seeking behavior. Although sign-tracking rats were previously demonstrated to exhibit greater relapse vulnerability to Pavlovian drug cues paired with drug delivery, here, we demonstrate that their counterparts, the goal trackers, are more vulnerable if the drug cue acts to signal drug availability and that the forebrain cholinergic system mediates such vulnerability. Given the importance of contextual cues for triggering relapse and the human cognitive–cholinergic capacity for the processing of such cues, goal trackers model essential aspects of relapse vulnerability.


Transgenic potatoes (Solanum tuberosum L.) overexpressing Arabidopsis thaliana (L.) Heynh. phytochrome B (phyB) have been reported to exhibit a substantially modified plant architecture, increased photosynthetic performance, reduced photoinhibition, delayed leaf senescence, and increased tuber yield. A greenhouse and a growth chamber experiment were conducted at Braunschweig, Germany, to elucidate the crop physiological basis for the yield differences between moderately phyB-overexpressing transgenic (Dara-5) and wild-type potato plants. In the greenhouse experiment, Dara-5 leaves showed a 23% greater leaf carbon exchange rate (CER) at light saturation, 32% greater leaf conductance, and 21% longer green leaf area duration (GLAD) than the wild-type plants. The transgenic plants partitioned a considerably greater portion of their biomass to stems and roots, but tuber and total biomass yield did not significantly differ among genotypes. The leaves and stems of the transgenic plants had lower starch and soluble sugar concentrations but consistently higher N concentration than those of the nontransgenic plants. Light response curves showed increasing CER superiority of Dara-5 leaves with increasing photosynthetic photon flux (PPF), suggesting higher productivity of the transgenic plants in high-radiation environments. Therefore, the two genotypes were compared in growth chambers at low, medium, and high light levels of300, 600, and 900 μmol m -2 s -1 PPF. Leaf CER of the transgenic plants reached 123, 115, and 120% of the wild-type plants at low, medium, and high PPF, but only at low PPF did the transgenic plants produce significantly greater (+8%) tuber yield than the nontransgenic plants. It is supposed that enhanced C loss from respiration is responsible for the lack of consistent transgenic yield superiority.


Green-emitting Y3Al5O12: Tb phosphor materials have been widely studied because of their high luminescence efficiency and stability under the conditions of high irradiance with an electron beam. In this paper, Green-emitting phosphor of yttrium aluminum garnet (Y3Al5O12 or YAG) doped with Tb3+, Ce3+ and Gd3+ was synthesized by sol-gel method. By means of TG/DSC, XRD, and photoluminescence (PL) performance, the sintering condition and its influence on the powder's emitting performance were studied. The experimental results showed that, Y2.8Tb0.12 Ce0.08-x GdxAl5O12 synthesized by sol-gel method was a kind of phosphor of good performance. When the value of x was set at 0.04, the best emitting performance was obtained. The Y3Al5O12: Tb, Ce, Gd particles had fine size, spherical shape, filled morphology, high crystallinity, and good brightness.


Deep learning methods have been actively researched for cross-modal retrieval, with the softmax cross-entropy loss commonly applied for supervised learning. However, the softmax cross-entropy loss is known to result in large intra-class variances, which is not not very suited for cross-modal matching. In this paper, a deep architecture called Deep Semantic Embedding (DSE) is proposed, which is trained in an end-to-end manner for image-text cross-modal retrieval. With images and texts mapped to a feature embedding space, class labels are used to guide the embedding learning, so that the embedding space has a semantic meaning common for both images and texts. This way, the difference between different modalities is eliminated. Under this framework, the center loss is introduced beyond the commonly used softmax cross-entropy loss to achieve both inter-class separation and intraclass compactness. Besides, a distance based softmax cross-entropy loss is proposed to jointly consider the softmax cross-entropy and center losses in fully gradient based learning. Experiments have been done on three popular image-text cross-modal retrieval databases, showing that the proposed algorithms have achieved the best overall performances.


In this paper a signal modeling technique based upon finite mixture autoregressive probabilistic functions of Markov chains is developed and applied to the problem of speech recognition, particularly speaker-independent recognition of isolated digits. Two types of mixture probability densities are investigated: finite mixtures of Gaussian autoregressive densities (GAM) and nearest-neighbor partitioned finite mixtures of Gaussian autoregressive densities (PGAM). In the former (GAM), the observation density in each Markov state is simply a (stochastically constrained) weighted sum of Gaussian autoregressive densities, while in the latter (PGAM) it involves nearest-neighbor decoding which in effect, defines a set of partitions on the observation space. In this paper we discuss the signal modeling methodology and give experimental results on speaker independent recognition of isolated digits. We also discuss the potential use of the modeling technique for other applications.


This essay draws upon the work of Erving Goffman and Michael Silverstein to read Shakespeare's first poem as a guide to mastering the burgeoning early modern art of conversation. The epyllion follows the conversation manuals of its day in embracing the aphorism as a charismatic form of talk, but it departs from its precedents in attributing to the aphorism an overtly erotic force. By according to the aphorism the power to turn conversation into an erotic encounter, Venus and Adonis elaborates its period's most seductive fantasy of talk.


The paper describes a new class of stochastic processes, which generalizes the concept of self-similarity. This class of processes is suitable for traffic modeling since it permits to take into account the presence of several traffic components with different statistical properties and defines proper conditions for the convergence of the aggregated traffic to suitable limit processes. The main result of the paper is that under adequate normalization conditions the aggregation of heterogeneous flows converges to the sum of two independent processes (α-Stable Levy Motion and Fractional Brownian Motion), able to take into account the self-similar nature of broadband traffic as well is its bursty (i.e., non Gaussian) marginal distribution.


To determine the effects of care and monitoring provided at home to children in whom Enterobius vermicularis is detected and their mothers on the presence of observing the parasite and the knowledge and practices of the children and their mothers on the issue. This study used a pre‐test‐post‐test quasi‐experimental design. In the study, 20 students and their mothers were determined as the experimental group, while 18 students and their mothers were determined as the control group. Home visits were made to the families of the children in the experimental group for 6 months. At these home visits, health education on the parasite was provided to the mothers and the children. There were highly significant differences between the experiment and control groups in terms of E. vermicularis presence, knowledge and hygiene practice scores (p < .001).


The biosynthetic precursors of the mammalian tachykinins, alpha-, beta-and gamma-preprotachykinins, contain a common N-terminal region of 74 amino acids. A polyclonal antiserum was raised against a synthetic peptide representing N-tyrosylated beta-preprotachykinin-(48-56)-peptide as predicted from the nucleotide sequence of cloned DNA complementary to human beta-preprotachykinin mRNA. By using this antiserum in radioimmunoassay, a single immunoreactive peptide was identified in an extract of a human pheochromocytoma that produced substance P and neurokinin A. Partial microsequencing and determination of the amino acid composition of the peptide indicated identity with preprotachykinin-(20-56)-peptide. Thus the data demonstrate that the Ala19-Glu20 bond in preprotachykinin is the site of cleavage of the signal peptide.


The relationship between environmental change and hominin evolution remains obscure. For the most part, this stems from the difficulty of reconstructing ancient hominin habitats. Bovids are among the most frequently utilized paleoenvironmental indicators, but little is known about the habitat preferences of extinct taxa. It is generally assumed that fossil bovids both ate the same things and occupied the same habitats as their closest extant relatives. We test the first part of this assumption by reconstructing the diets of seven bovids from Makapansgat Limeworks, South Africa. Since diet and habitat are linked, these reconstructions have implications for our understanding of fossil bovid habitat tolerances. Ecomorphological and stable carbon isotope analyses are employed, allowing us to take advantage of the strengths and overcome the weaknesses of both. In most cases, fossil bovids did have similar diets to their extant relatives, and probably occupied similar habitats. Gazella vanhoepeni and Aepyceros sp., however, were almost exclusive browsers, and not mixed feeders like their living counterparts.


Cancer is a major cause of human morbidity and mortality, and the risk of developing cancer is about one in three life times. Neuroblastoma is the most common extra-cranial solid tumor among children and arises from early sympathetic nervous system (SNS) cells arrested in their development. Generally, a low tumor cell differentiation correlates to poor prognosis. Solid tumors, like neuroblastoma, frequently contain regions of oxygen deficiency ? hypoxia ? caused by a high rate of cellular proliferation and abnormal intratumoral blood supply. In this hypoxic microenvironment cancer cells undergo genetic and molecular changes, allowing continued survival and proliferation. Tumor hypoxia is also associated with increased aggressiveness, resistance to therapy and poor outcome. Cancer cells become less differentiated in response to hypoxia, which we previously demonstrated in neuroblastoma as well as breast cancer cells, indicating an evolvement of a more aggressive phenotype. In the present studies we find evidence of potential mechanisms behind the hypoxia-mediated de-differentiation of neuroblastoma cells. Hypoxia (1% O2) induced the expression of the negative transcription factor ID2 (Paper I), involved in blocking the function of tissue-specific basic helix-loop-helix (bHLH) proteins, such as the SNS-specifying transcription factors HASH-1 and dHAND. Hypoxic up-regulation of ID2 was dependent on direct in vivo DNA-binding and activity of hypoxia-inducible factors (HIF), the master transcriptional regulators of oxygen homeostasis. Induction of ID2 expression occurs as an early HIF-mediated hypoxic event, potentially leading to a more immature state. HIF-1alpha and HIF-2alpha, however differently, are both essential for normal development and are highly implicated in tumor progression. In Paper II we show that HIF-1alpha and HIF-2alpha share several target genes, but mediate regulation of these under different temporal and oxygen-dependent conditions. Interestingly, HIF-2alpha, but not HIF-1alpha, was present in neuroblastoma tumor cells near blood vessels, and thus in apparently better oxygenized tumor regions. In vitro, HIF-1alpha protein was transiently stabilized at hypoxia and primarily governed acute hypoxic responses, whereas HIF-2alpha became more important at prolonged hypoxia. In addition, high HIF-2alpha activity, including induction of classic hypoxic targets such as VEGF, was detected in cultured neuroblastoma cells already at 5% O2, a physiologically relevant oxygen level, similar to the findings in vivo. In a large clinical neuroblastoma material, significant correlations between high HIF-2alpha levels and high VEGF content, advanced tumor stage and poor outcome were found. These observations clearly suggest an oncogenic role of HIF-2alpha, and implicate HIF-2alpha as an independent prognostic marker in neuroblastoma. The MXI1 (MAX-interactor 1) gene, a reported MYC antagonist, has been detected by us and others as a commonly hypoxia-induced gene. In Paper III we further demonstrate that HIF proteins, via direct binding to hypoxia-response elements (HRE), up-regulate MXI1 mRNA and protein in both hypoxic neuroblastoma and breast cancer cells. Interestingly, reducing MXI1 levels had no overall effects on MYC/MYCN activity in hypoxic neuroblastoma cells. Instead, MXI1 appeared to be important in augmenting the hypoxic response, potentially by enhancing specific HIF-1 target gene induction. HIF proteins are primarily stabilized and activated in response to lowered oxygen concentrations. However, growth factor-induced signaling can promote HIF-1alpha protein synthesis as well as transactivation, even under normoxic conditions. In Paper IV we characterize a novel such a pathway, where stem cell factor (SCF)-evoked c-Kit-signaling leads to increased HIF-1alpha protein, HRE-activation and induction of several HIF-1alpha targets, such as VEGF and GLUT1, already at normoxia. In addition we find a reciprocal positive feedback loop between c-Kit and HIF-1alpha, where induced HIF-1alpha mediates reinforcement of c-Kit expression. Overall, this thesis shows the impact of HIF proteins on tumor cell behavior, principally as central hypoxic transcriptional regulators governing the expression of genes with potential importance in several biological processes, such as growth and differentiation, determining cancer cell aggressiveness as well as adaptation to low oxygen conditions. (Less)


Geostatistical tools have been used to study the impact of additional small scale catch data (star survey design) on the spatial analysis of fish, regarding different biological groups of dab, Limanda limanda and whiting, Merlangius merlangus . A standard survey carried out in January (2001-2003) in a meso-scale area in the German Bight was modified by additional small-scale sampling in 2002 and 2003. Adopting the star survey reduced the small-scale variability for medium-sized and male dab, as indicated by lower values of the nugget effect and an increased resolution of the spatial dependency. For whiting no reduction in the small scale variability could be detected; a significant difference in the spatial structuring was only found for two different size groups of whiting. Uncertainty of mean catches of dab and whiting was reduced in 2002, while in 2003 the effect of the star survey was less pronounced due to the high local density of the nearby stations. We conclude that the star survey design can be an inexpensive and effective procedure — depending on the species studied and/or the positioning of the nearby stations — when a minimised small-scale variability and a reduction of uncertainty in mean biomass of fish are the focus of interest.


Theory: This paper provides a comparative study of legislative institutions in the United States and Japan. It explains the rise of committee-based legislative organizations as an institutional choice made by rational legislators deciding how best to regularize their career advancement subject to electoral and constitutional constraints. Hypotheses: We argue that the rise of careerism within a legislature leads to a regularized system of career advancement, or a seniority system. Furthermore, the details of this system depend on the heterogeneity of intra-party preferences and each country's electoral and constitutional system. To the extent that parties can offer members electoral security and influence over policy, they will retain control over the policy-making process. Otherwise, control will devolve to smaller organizational units, such as committees. Methods: We develop a new measure of seniority within committees. We present statistical evidence linking a rise in average tenure within both legislatures to a regularization of careers, and detailing the nature of committee-based seniority in each country. Results: In the United States, single-member electoral districts, alternating party control, and a separation of powers system gave legislators an incentive to create committee-based policy jurisdictions. In Japan, multi-member districts, singleparty control, and a parliamentary system led to a unique two-tiered seniority system in which members rise first through committees and then through cabinet posts.


The spatiotemporal evolutions of microstructure and motion in the transient relaxation toward the steady supercooled liquid state after quenching a dusty plasma Wigner liquid, formed by charged dust particles suspended in a low pressure discharge, are experimentally investigated through direct optical microscopy. It is found that the quenched liquid slowly evolves to a colder state with more heterogeneities in structure and motion. Hopping particles and defects appear in the form of clusters with multiscale cluster size distributions. Via the structure rearrangement induced by the reduced thermal agitation from the cold thermal bath after quenching, the temporarily stored strain energy can be cascaded through the network to different newly distorted regions and dissipated after transferring to nonlinearly coupled motions with different scales. It leads to the observed self-similar multiscale slowing down relaxation with power law increases of structural order and structural relaxation time, the similar power law decreases of particle motions at different time scales, and the stronger and slower fluctuations with increasing waiting time toward the new steady state.


Abstract Large debris flows in steep-sloped ravines debouching to the Rimac River, in metropolitan Lima (Peruvian capital), have resulted in considerable loss of life and property adversely impacting communities in the region. Temporal, spatial and volumetric features of debris flows are difficult to predict, and it is of utmost importance that achievable management solutions are found to reduce the impact of these catastrophic events. The emotional and economic toll of these debris flows on this increasingly densely populated capital city in South America is devastating where communities must live in such inadequate and dangerous conditions. To address this problem, the application of advanced Japanese technology, Sustainable Actions Basin Orientation (SABO), has been investigated using a geomorphological modelling to develop an implementation plan. Rayos de Sol stream basin in Chosica, was selected as a pilot to develop the proposal, as it is considered high risk due to the presence of ancient debris flows and recent flows in 2012, 2015 and 2017. The recurrence of debris flows in this location has resulted in numerous deaths and catastrophic property losses. This study combines geologic and geomorphic mapping and hydraulic and landform evolution numerical modelling. The implementation of a SABO Master Plan based on the multidisciplinary assessment hazard scenarios, will allow the implementation of feasible mitigation actions. The SABO technology has been applied successfully in Japan and other countries in areas with steep short slopes, similar to the conditions surrounding the Peruvian capital. Results from this study will be presented to the Peruvian Government as part of an action plan to manage debris-flow impact. KEY POINTS High-risk mass slope failure is linked to poor urban planning in urban developing regions of Lima the capital of Peru. A multidisciplinary study including geotechnical and hydrological analysis, engineering design, and socio-economic research is required to implement a SABO Master Plan, and this basin is pilot study basin. At the present time, a maintenance programme for existing hydraulic structures should be implemented, and a flood risk management plan developed may propose the relocation of some communities and infrastructure.


Many types of pricing models incorporating different forms of demand functions have emerged in the past years. In an earlier work, a piecewise-defined Complementarity-Constrained Demand Function (CCDF) was discussed to correct certain weaknesses in commonly used demand functions. The authors introduced a Complementarity-Constrained (CC) pricing model incorporating the CCDF in that same work. However, there was a lack of numerical implementations therein. Hence in a separate work, we developed an algorithm using MATLAB to compare a generic pricing model and a CC pricing model. Experiments were performed to compare the revenues from the two models for certain ranges of parameters defining the demand function. In this work, we conduct further numerical testing by simulating the bidding behaviours of different types of customers and using simulated demand data to compare the models. We find that the use of the CC model leads to higher revenues for certain simulated scenarios.


The effects of an n-3 PUFA-enriched diet on cardiac cell membrane phospholipid fraction compositions and associated protein kinase-C (PKC) translocation modification have never been studied in higher mammals. This is of importance since membrane fatty acid composition has been shown to influence PKC signalling pathways. In the present study, we have tested whether the incorporation of n-3 PUFA in cardiac membrane phospholipids correlated with changes in the fatty acid composition of diacylglycerols (DAG) and led to a differential translocation of PKC isoforms. Two groups of five dogs were fed the standard diet supplemented with palm oil or fish oil for 8 weeks. Dogs fed a fish oil-enriched diet showed a preferential incorporation of EPA and, to a lesser extent, of DHA, at the expense of arachidonic acid, in the circulating TAG, plasma phospholipids, erythrocyte phospholipids and cardiomyocyte phospholipid fractions. Analysis of 1,2-DAG fatty acid composition also indicated a preferential enrichment of EPA compared with DHA. Associated with these results, a reduction in the expression of PKC-δ and PKC-ε isoforms in the particulate fractions was observed whereas no effect was seen for PKC-α and PKC-ζ. We conclude that a fish oil-enriched diet induces a modification in fatty acid composition of cardiac membrane phospholipids, associated with a differential translocation of PKC isoforms. These results can be explained by the production of structurally different DAG that may participate in some of the protective effects of n-3 PUFA against various chronic diseases.


A cyanine based spirocyclic metal ion probe has been reported, which can be tuned easily for targeting various metal ions. The mechanism of selective sensing was verified by designing two novel compounds IR-NCS and IR-PYR, which can selectively sense Hg2+ and Zn2+/Cd2+ ions respectively in a mixed aqueous medium and physiological pH. The spectral changes in both the cases are in the near infrared (NIR) region. Both chemodosimetric and coordination based approaches were used for sensing the cations. The complete mechanism of the sensing events was studied using UV-Vis and fluorescence spectroscopy. Additional insight about the experimental findings was corroborated by theoretical studies using DFT calculations. The confocal microscopic study revealed that the probe IR-NCS can be effectively used for detecting intracellular levels of Hg2+ ions without showing any toxic effect to the model human cells.


Viruses build nucleotide Z, identified in meteorites, replacing adenine in DNA genomes Genomic DNA is composed of four standard nucleotides, each with a different nucleobase: adenine (A), thymine (T), cytosine (C), and guanine (G). These nucleobases form the genetic alphabet, ATCG, which is conserved across all domains of life. However, in 1977, the DNA virus cyanophage S-2L was discovered with all instances of A substituted with 2-aminoadenine (Z) throughout its genome (1, 2), forming the genetic alphabet ZTCG. Studies revealed interesting properties of Z-substituted DNA (dZ-DNA) (3–6), but little of Z synthesis was understood. On pages 516 and 512 of this issue, Sleiman et al. (7) and Zhou et al. (8), respectively, characterize viral Z biosynthesis. On page 520, Pezo et al. (9) identify a Z-specific DNA polymerase that is responsible for assembling dZ-DNA from nucleotides. All three studies identify additional "Z-genomes" in diverse bacteriophages (viruses that infect bacteria), which may have offered evolutionary advantages alongside standard ATCG DNA since life began.


Purpose
The ramp-up in humanitarian logistics operations is a stage when the demand surges, often at the start of an emergency. In response, agility is a key strategy used by the humanitarian organizations (HOs). However, the HOs are constrained by their existing resources and have to respond in the ramp-up process under their resource dependency. The purpose of this paper is to develop a framework on agility-building strategies used by HOs for the ramp-up.

Design/methodology/approach
This study applies both the dynamic capabilities perspective and resource dependence theory to humanitarian relief operations, and develops four testable propositions to explore the agility-building strategies of the HOs for the ramp-up process. A multiple-case study is conducted on six international HOs operating in Indonesia to verify them, in addition to an extensive literature search.

Findings
The case study shows that the human resource management, pre-positioning, standardization and supplier management of the HOs are all related to their resources and environment in the ramp-up process. The authors highlight the practical differences between the few super large, resource rich and centralized HOs with the second-tier HOs.

Research limitations/implications
Given the small sample size and single country as the site of study, some findings may not be applicable to the other HOs or in other regions.

Practical implications
The propositions could be applicable to other HOs operating under similar environments, and potentially to the commercial enterprises operating in a highly volatile environment with severe resource scarcity.

Originality/value
This study provides new insights into ramp-up operations and into how HOs build their agility and reduce their resource dependencies. Theoretically, the paper applies two established theories in the strategic management literature to a new field.


In Service-Oriented Architecture, each application is often designed as a set of abstract services, which defines its functions. A concrete service(s) is selected at runtime for each abstract service to fulfill its function. Since different concrete services may operate at different quality of service (QoS) measures, application developers are required to select an appropriate set of concrete services that satisfies a given Service-Level Agreement (SLA) when a number of concrete services are available for each abstract service. This problem, the QoS-aware service composition problem, is known NP-hard, which takes a significant amount of time and costs to find optimal solutions (optimal combinations of concrete services) from a huge number of possible solutions. This paper proposes an optimization framework, called E3, to address the issue. By leveraging a multiobjective genetic algorithm, E3 heuristically solves the QoS-aware service composition problem in a reasonably short time. The algorithm E3 proposes can consider multiple SLAs simultaneously and produce a set of Pareto solutions, which have the equivalent quality to satisfy multiple SLAs.


Despite the 28% decline in under-five mortality (U5M) between 1990 and 2017 in sub-Saharan Africa, U5M remain considerably high in Nigeria as a result of poor progress in child survival practices. This persistence high rate of U5M has necessitated this study by examining the interaction influence of maternal sociodemographic factors and ANC utilisation on under-five mortality in Nigeria. Data on a weighted nationally representative sample of 127,202 birth history from the 2018 Nigeria Demographic and Health Survey were analysed to estimate the risks of U5M using Cox proportional regression. The study established that the risks of U5M were significantly lower for children whose mothers had 4 or more ANC visits (HR: 0.65, CI: 0.50-0.85), but increased for children whose mothers delivered in a private health facility (HR: 1.44, CI: 1.01-1.88). With respect to socio-demographic factors, the risks of U5M significantly reduced for children of mothers with secondary or tertiary education (HR: 0.68, CI: 0.55-0.86) and children of mothers found in the highest wealth quintile households (HR: 0.64, CI: 0.51-0.81) relative to those in the reference categories. Though not significant, the risks of U5M varied across place and region of residence. The study established that the risks of U5M are associated with poor maternal socio-demographic factors and incomplete or inadequate ANC utilisation during pregnancy in Nigeria. Hence, the need to re-strategise women empowerment plans and further re-training of private healthcare providers/workers on the importance of complete and adequate ANC  utilisation towards achieving SDG 3 target of reducing maternal and child mortality in Nigeria.
Keywords: Maternal socio-demographic factors, ANC utilisation, under-five mortality, Nigeria


Folk perceptions of language diversity often differ from the criteria laid out by linguists and have particular implications for applied/sociolinguists since the collective identification of language diversity largely determines the ways in which individuals regard the categorisation of their own (and others) linguistic uses as belonging to a specific social and/or regional variety. Folk perceptions can thus help define speech communities as well as explain sociolinguistic other phenomena. This paper provides a critical analysis of the existing folk linguistic research into language variation in a number of different contexts: the UK, the USA, France and Japan. It is hoped that the information gained will help build up a more detailed sociolinguistic picture of the complex and often contradictory nature of lay individuals' attitudes towards linguistic variation. In the final sections of the paper the authors argue for a greater deal of recognition within modern linguistics of the value of examining folk perceptions of language diversity.


Temporary rainpools near Khartoum, Sudan, are inhabited by the notostracan crustacean Triops which completes its life cycle within 4 weeks. The annual rains fall in late summer, and throughout the winter and early summer the eggs of Triops remain in the dried mud or dust where they may be exposed to temperatures up to 80�C. Laboratory experiments show that they can withstand temperatures up to within 1�C of boiling, but are killed in partial vacuum by 70�C, at atmospheric pressure by 100�C, or under pressure by 105�C. Exposure to high temperature seems to be necessary to break the egg diapause.


On December 14 and 27, 1763, rioters in western Pennsylvania attacked and killed nearly two dozen Conestoga Indians living near Lancaster, Pennsylvania. Five weeks later, two hundred and fifty men, calling themselves the Paxton Boys, marched on Pennsylvania to kill Indians housed there for their protection. These events sparked outrage, as pro- and anti-Paxtonite authors debated the attacks. Defenders of the massacre claimed that they had not only the right but the duty as good British subjects to kill "alien" Indians within the colony's borders. This article argues that these efforts to articulate the civic rights and duties in the aftermath of the massacre represented a subtle attempt to redefine imperial authority on the frontier. The Paxton rioters, in their actions and their post-hoc justifications, seized sovereign power of life and death and the ability to delimit the meanings of allegiance, casting themselves as sovereign subjects on the frontier.


This paper presents a new selection-based question answering dataset, SelQA. The dataset consists of questions generated through crowdsourcing and sentence length answers that are drawn from the ten most prevalent topics in the English Wikipedia. We introduce a corpus annotation scheme that enhances the generation of large, diverse, and challenging datasets by explicitly aiming to reduce word co-occurrences between the question and answers. Our annotation scheme is composed of a series of crowdsourcing tasks with a view to more effectively utilize crowdsourcing in the creation of question answering datasets in various domains. Several systems are compared on the tasks of answer sentence selection and answer triggering, providing strong baseline results for future work to improve upon.


Results from electrical and optical measurements of boron in compensated p-type 4H–SiC layers doped with Al, N, and B are reported. The layers were produced by sublimation epitaxy and characterized by secondary ion mass spectrometry, capacitance–voltage, and cathodoluminescence techniques. The boron-related contribution to the net acceptor concentration in the layers as well as the boron-related emission at ∼505 nm are detected for various growth conditions. The effect of the concentrations of the attendant impurities Al and N, concentration ratio of Al to N atoms, and growth rate on the site-occupying behavior of boron in the layers is discussed.


The purpose of this study is to deepen understandings of the experience of
married women who place their husbands into a nursing home. Interpretive
research investigates our lived experience and addresses questions of being. A
phenomenological study allows the particular and the unique meanings to be
disclosed. Meaning and significance of placing one's husband into a nursing
home remains hidden in much of the literature as a consequence of theoretical
constructs entrenched within the positivist paradigm. The purpose of this study
for nurses is found in bringing to the nursing discourse another perspective on this
phenomenon. The insights gained from this study may radicalise thought and
inform nursing practice.
Conversation was chosen in anticipation of narrowing the gap between the
researcher and the researched. These women's stories were descriptively written
using their words. The philosophical thought of Heidegger helped guide the
methodology and generate the understandings of the study. Through reflection on
the conversations, understandings emerged. Three themes: connectedness; living
out the tensions and re-discovery of self formed the thematic statement which
describes the everyday experience of these three women.
The lived experience of married women who place their husbands into a nursing
home is expressed through a constant working towards maintaining a meaningful
connection with their husband, whilst finding a new way of being as they live out
the tensions associated with that placement.


3814 Synthetic food dyes are present at high levels in many foods. The average American consumes over 10 grams of these food additives each day. There is considerable public interest in potential adverse health effects of synthetic food dyes. Extensive research has been conducted to ensure that the currently approved food dyes do not cause cancer. However, the possibility that these agents might inhibit cancer has not yet been addressed. Based on their chemical structures, we hypothesized that certain synthetic food dyes may form complexes with planar chemical carcinogens and inhibit carcinogen uptake in a manner similar to that of the successful cancer chemopreventive agent chlorophyllin (CHL). Five food dyes were compared in vitro for their ability to modulate dibenzo[a,l]pyrene (DBP) and aflatoxin B1 (AFB1)-induced mutagenicity. FDA approved (FD&C) Blue No. 2 (Blue 2) and Red No. 40 (Red 40) each inhibited mutagenicity of DBP and AFB1 in bacterial reverse mutation assays. The concentration of Blue 2 producing 50% inhibition of mutagenicity (IC50) towards DBP was 12 nmol/plate. The IC50s for AFB1-induced mutagenicity were 49 and 58 nmol/plate for Red 40 and Blue 2, respectively. Blue 2 and Red 40 were then tested towards AFB1-induced carcinogenicity. Rainbow trout fry were fed diets containing 40 ppb AFB1 alone or in combination with one of the food dyes (at 2000 or 4000 ppm) for one month. Nine months later trout were sampled and livers examined for the presence of tumors. AFB1-induced tumor incidence was significantly inhibited by co-treatment with either Red 40 (2000 ppm) or Blue 2 (2000 or 4000 ppm). Protection provided by the food dyes was comparable to that provided by 2000 ppm CHL. These results suggest that the synthetic food dyes Blue 2 and Red 40 may be effective cancer preventive agents.


In this paper, we seek to determine what factors drive the adoption of green purchasing among municipalities in Mexico and the success of their implementation. Given the lack of research and theory in the area, this study is exploratory in nature. We applied the green purchasing survey developed by Arizona State University to all municipalities in Mexico with a population of 25,000 or more inhabitants. Using the least absolute shrinkage and selector operator method (LASSO), we reduced the set of measures, which we then employed in a logistic regression to predict whether the municipality would adopt a green purchasing policy. We found that complementary environmental practices, department rules, and city-wide contracts to reduce purchasing costs have a positive and significant effect on the propensity to adopt green purchasing policies, but the time for routine low-cost purchases has a negative effect on green purchasing policy adoption. Then, using two-stage least squares, we developed a model of the factors leading to successful implementation of green purchasing. We found that complementary environmental policies, environmental practices, environmental program knowledge, and city-wide contracts to reduce purchasing costs are positively and significantly related to successful implementation. However, department resources and the time for routine low-cost purchase are significant, but negatively related.


: 1. alpha-Human atrial natriuretic peptide (7.5 pmol min-1 kg-1) was infused intravenously into eight healthy men after pretreatment with lithium carbonate (750 mg) or placebo. 2. Baseline sodium excretion was significantly increased after lithium, but the natriuresis during infusion of alpha-human atrial natriuretic peptide was attenuated. 3. Similar decreases in plasma renin activity with infusion of alpha-human atrial natriuretic peptide occurred on both days. 4. Administration of lithium may be associated with pharmacological effects and further work is required to validate the use of lithium clearance as a marker of proximal renal tubular sodium handling.


Members of the B cell lymphoma-2 (Bcl-2) family are pivotal arbiters of mitochondrially mediated apoptosis, a process of fundamental importance during tissue development, homeostasis, and disease. At the structural and mechanistic level, the mammalian members of the Bcl-2 family are increasingly well understood, with their interplay ultimately deciding the fate of a cell. Dysregulation of Bcl-2-mediated apoptosis underlies a plethora of diseases, and numerous viruses have acquired homologs of Bcl-2 to subvert host cell apoptosis and autophagy to prevent premature death of an infected cell. Here we review the structural biology, interactions, and mechanisms of action of virus-encoded Bcl-2 proteins, and how they impact on host-virus interactions to ultimately enable successful establishment and propagation of viral infections.


Software developers' performance has a direct impact on software development productivity. An understanding of the factors that affect this performance could help determine where to concentrate management efforts (and related financial resources) form a practical standpoint, and where to focus research efforts form an academic perspective. To gain further insight into these factors, this study extends prior research by integrating elements from expectancy theory, goal-setting theory, and organizational behavior specific to the software development process. The research results provide new insights regarding the relative importance of how expectancy theory, goal-setting theory, and individual characteristics affect the perceived performance of software development professionals. These preliminary findings indicate that goal-setting theory may have complex implications for software development performance. Goal difficulty has a negative relationship to performance but a positive relationship to effort. Because of this off-setting effect, the degree of goal difficulty has a relatively small overall effect on performance. Goal clarity also has a relatively small effect on performance. Individual ability has the strongest direct effect on perceived performance, more than twice as strong as the effects o work effort, personality dimensions, and perceived characteristics of the task. High achievement needs were directly related to both effort and perceived performance, whereas self-esteem and locus of control have a direct relationship to perceived performance.


Introduction: Some previous studies have shown the effect of K2EDTA, heparin, citrate, kalioxalate on lipid test results [1,2,3], but no studies on sodium fluoride - potassium oxalate. Furthermore, it is also important to ensure sample stability during testing. We performed this study to evaluate the effect of NaF-KOx on lipid results and lipid stability when storing.

Methods: A cross-sectional study was conducted on the residual of 150 pairs of serum and NaF-KOx plasma samples from the patients at the University Medical Center 2. These patients participated voluntarily after signing the consent form. We divided the samples into groups: serum (group 1), unpreserved plasma (group 2); stored plasma for 24 hours at 2-8°C (group 3), and stored plasma for 48 hours at 2-8°C (group 4). All samples were analyzed on an AU480 system – Beckman Coulter. The data would be processed using Stata 10.0.

Results: The results difference between these groups: 2,3,4 compared to group 1 was statistically significant (p < 0.001). Total cholesterol, triglycerides, HDL-C, and LDL-C concentrations in group 2 decreased, respectively: 5.83%; 6.77%; 5.12%; 5.96%. We found the lipid test results of group 3 and group 4 also reduced compared to group 1: cholesterol decreased by 5.25%, 5.77%; triglycerides by 6.7%, 6.49%; HDL-C by 5.8, 7.22%; and LDL-C by 4.79%; 5.05%. After 48 hours, cholesterol, HDL-C, and LDL-C concentration continued to reduce, while the difference in triglycerides concentration was not statistically significant.

Conclusions: NaF-KOx anticoagulant reduces lipid test results. We should not use NaF-KOx plasma to measure lipid tests.


BACKGROUND. Little research has examined indebtedness and the choice of continued subspecialty training. Concerns about a decline in the proportion of primary care physicians obliges medical educators to understand factors that influence the choice of subspecialty training. METHOD. Survey data on 437 pediatricians who graduated between the years 1981 and 1987 were collected in 1991. Logistic regression was used to examine the influences of sex, race, graduation year, type of medical school, and educational debt (adjusted for inflation) on whether a pediatrician had trained in a subspecialty. RESULTS. Three variables were associated with subspecialty training. Men and whites were significantly more likely to have trained in subspecialties, as were earlier graduates. Type of medical school and debt did not enter the equation. CONCLUSION. Other variables were found to be more influential than indebtedness in the career decisions of primary care and subspecialty pediatricians. Distinguishing between subspecialties that have noticeably higher incomes and those that serve to enhance primary care pediatrics may be illuminating. That men and whites were more likely to train in subspecialty pediatrics suggests that financial considerations, if present, may be masked under other cultural and societal factors.


The Connemara Dalradian terrane was emplaced over the Delaney Dome Formation from the NNW by near orthogonal movement on the Mannin Thrust, a linkage that has survived later movement. Rb-Sr isotopic analyses of micas and whole rocks from the Delaney Dome mylonites constrain the age of movement on the thrust to 447 ±4Ma. This time of thrusting correlates with much other tectonic activity in the Caledonides and may represent a time of 'docking' of the Midland Valley block with the more northerly terranes.


Mandatory breaks for truck drivers are nowadays scheduled after the route has been decided. However, in some cases it is beneficial to plan these breaks during waiting time caused by truck driving bans. Optimally planning a single break considering driving bans can be done using Dijkstra's algorithm with multiple labels. This has large effects on predicted travel times: 17% of the analysed routes having a night rest obtain an earlier arrival time by 5 hours on average. However, the computation times of this algorithm are long. A novel heuristic version of time-dependent contraction hierarchies leads to significant reductions in computation times from several seconds to several milliseconds per route. Experiments show that the solutions are still optimal for a representative test set consisting of 10,000 route queries.


Primary hemostasis exploration involves many tests, but most of them are highly specialized. Meanwhile, a few simple and reliable assays can make possible a first orientation of the diagnosis in a routine laboratory. This review is organized in four parts. It highlights the importance of pre-analytical steps when exploring hemostasis, especially a carefully conducted clinical history and blood collecting conditions. It first presents the tests involved in the global exploration: the platelet count, the bleeding time, the occlusion time and the prothrombin consumption test. Then, this review presents the tests essential for the diagnosis of thrombocytopenia, von Willebrand disease and platelet disorders. Finally, we discussed about the limits and the future of diagnosis in primary hemostasis, and more particularly about endothelial cells and the adhesion proteins that are implicated.


This article presents a simple method for identifying distributional dynamic properties of economies using the ideas of concordance and discordance. It can be employed to examine the strength and validity of the results of other methods. The method has the advantage of comparing distributions at two points without relying on intermediary data between the two time points. We present results that suggest there is more 'strong-divergence' than 'strong-convergence' in GDP between countries over the time period 1960 to 2000 although the distribution exhibits both convergent and divergent characteristics.


Purpose An assessment of the effectiveness of progenitor mesenchymal stem cell as injections and as part of a polymer hydrogel for the wounds treatment. Materials and Methods Fixed-size wounds (average area of 135.8 mm2) were modeled on the back of white Wistar rats, aged 9 months. Mesenchymal stem cells (MSC) isolated from a human umbilical cord were injected into the wounds once on the modeling day (SC group). In other animals, MSC were periodically applied externally as one of the components in the polymer hydrogel (Polymer_sc group). The systemic effect of the cells was assessed via the analysis of intact contralateral wounds located on the opposite side of the same animal's back (groups Control_sc and Control_Psc, respectively). The reference intact wounds belonged to the Control_0 group. The wound area was studied in dynamics. Descriptive microscopy was supplemented by an assessment of the collagen fibers' maturity, the epidermal layers, and the number of fibroblasts and leukocytes in different parts of the wounds. Results Both the local and systemic application of MSC led to an improvement in wound regeneration. During the acute inflammatory phase (up to 3 days), the method and place of application did not affect the dynamics of wound healing. The use of Polymer_sc ultimately demonstrated the best effectiveness. The anti-inflammatory effect of MSC was confirmed by a decrease in leukocyte infiltration in the wound centers (Polymer_sc and SC groups) and edges (all groups, with the greatest extent in the Polymer_sc group). The proliferative phase that expresses itself via accelerated growth in fibroblast number and collagen production was affected in the Control_Psc group and mostly in the Polymer_sc group. Conclusion The applications of MSC in various ways improve and accelerate wound healing even in old animals. The best performance was achieved in the Polymer_sc group.