bluuebunny/crossref_metadata_2025 huggingface dataset:
ENTREPRENEURIAL SELF-EFFICACY AND FIRM PERFORMANCE IN CHALLENGING ENVIRONMENTS: EVIDENCE FROM THE FRANCHISE CONTEXT
Authors: CUMBERLAND DENISE M. , MEEK WILLIAM R. , GERMAIN RICHARD
Published: April 2015

The purpose of the current study is to investigate the impact of the five ESE dimensions on firm performance. More specifically, we examine whether any of the five ESE dimensions are important to firm performance when the external environment is either competitively intense or technologically turbulent. This study investigated these relationships using a sample of franchisees, an important audience understudied in entrepreneurial literature. We find that the three-way interaction of competitive intensity, technological turbulence and each of ESE innovation, ESE management, and ESE financial control predicts franchisee performance. This confirms the wisdom of studying ESE as consisting of specific dimensions (as opposed to holistically) because not all ESE dimensions interact with franchisee environment in predicting performance.
Advanced Intelligence Tuning Using Hybrid of Clonal Selection and Genetic Algorithm, GM and PM
Authors: Kim Dong Hwa , Cho Jae Hoon
Published: April 2015

This paper deals with intelligent tuning by hybrid system composed of genetic algorithm and clonal selection (CS). This paper uses gain margin (GM) and phase margin (PM) to define the tuning margin of control system for optimal tuning. Up to this time, many intelligent algorithms have been tried in order to improve the intelligent controller performance for industrial areas such as power plant, motor control, chemical control, and so on. However, in the actual plant, they are many limitations in tuning approaching because of computing speed. Therefore, it is difficult to apply for getting optimum value in tuning. In this paper, novel computing scheme has been done by hybrid CS algorithm and genetic algorithm, GM, and PM to obtain an advanced value and effective approach for optimal parameters.
Interplay between magnetism and Na concentration in NaxCoO2
Authors: Assadi M. H. N. , Katayama-Yoshida H.
Published: April 2015

Through comprehensive density functional calculations, the crystallographic, magnetic and electronic properties of Na x CoO 2 (x = 1, 0.875, 0.75, 0.625 and 0.50) were investigated. We found that all Na ions in NaCoO 2 and Na 0.875 CoO 2 share the basal coordinates with O ions. However, as x decreases, some of Na ions move within the basal plane in order to reduce the in-plane Na - Na electrostatic repulsion. Magnetically, there was strong tendency for type A antiferromagnetism in the Na 0.75 CoO 2 system, while all other Na deficient systems had a weaker ferromagnetic (FM) tendency. The results on magnetism were in excellent agreement with the experiments.
Abnormal capacitance–voltage and switchable photovoltaic effect of epitaxial Mn-doped BiFeO3 thin film capacitor
Authors: Peng Zeng-Wei , Liu Bao-Ting
Published: April 2015

Epitaxial BiFe 0.95 Mn 0.05 O 3 (BFMO) film was deposited on (001)-oriented SrRuO 3 (SRO) coated SrTiO 3 (STO) substrate by radio-frequency (rf) magnetron sputtering. Indium tin oxide (ITO) was grown on BFMO/STO heterojunction to fabricate ITO/BFMO/SRO capacitor for investigating the ferroelectric and photovoltaic properties. The ITO/BFMO/SRO capacitor exhibits large remanent polarizations of 92.2 μC/cm2, 101 μC/cm2 and 109 μC/cm2 measured at 20 V, 25 V and 30 V, respectively. An observed abnormal capacitance–voltage (C–V) curve can be explained based on the ITO/BFMO interface. The calculated capacitance and junction width of ITO/BFMO interface are 105 pF and 32 nm, respectively. Additionally, it is found that photovoltaic effect of the ITO/BFMO/SRO capacitor is mainly attributed to ferroelectric polarization and internal electric field induced by defects. The photocurrent densities coming from ferroelectric polarization and internal field are 36 μA/cm2 and 23 μA/cm2, respectively. The photovoltaic output from the ferroelectric polarization is obviously larger than that from the internal electric field.
The valuation of stochastic insurance liabilities using a structural model approach
Authors: Kanno Masayasu
Published: April 2015

Liability drives insurers' businesses. This paper examines the structural model approach of credit risk for the valuation of insurance liabilities and insurers' equity, and considers a stochastic process for liability. Grosen and Jørgensen's (2002) study presents the current approach taken by insurers; however, the model's structure is very simple, and its liability structure in particular has a deterministic time function. In contrast, we analyze a model that analytically evaluates an insurer's liability with the stochastic process. Furthermore, we analyze the model's default option originally presented by Myers and Read (2001).
Petrography and characterization of microbial carbonates and associated facies from modern Great Salt Lake and Uinta Basin's Eocene Green River Formation in Utah, USA
Authors: Chidsey Thomas C. , Vanden Berg Michael D. , Eby David E.
Published: April 2015

Utah contains unique analogues of microbial hydrocarbon reservoirs in the modern Great Salt Lake and the lacustrine Eocene Green River Formation within the Uinta Basin. Characteristics of both lake environments include shallow-water, ramp margins that are susceptible to rapid widespread shoreline changes, as well as comparable water chemistry and temperature that were ideal for microbial growth and formation/deposition of associated carbonate grains. Thus, microbialites in Great Salt Lake and cores from the Green River Formation exhibit similarities in terms of microbial textures and fabrics. A detailed petrographic analysis provides unique insights into these modern and ancient deposits that can be used to determine reservoir characteristics in other microbial carbonate petroleum plays.

Great Salt Lake is a hypersaline lake and carbonate ‘factory’, containing actively forming microbial mats, stromatolites, thrombolites and associated carbonate grains. Open constructional pores are common within a spectrum of microbial structures. Green River Formation cores display excellent examples of stromatolites and thrombolites that contain primary megascopic pore and microporosity, as well as carbonate grainstones composed of ooids, peloids and skeletal material with abundant interparticle and intraparticle porosity. West Willow Creek oil field produces from a Green River microbial buildup/mound, a feature not currently recognized in Great Salt Lake.
Logic-based schedulability analysis for compositional hard real-time embedded systems
Authors: de Matos Pedro André , Pereira David , Pinho Luís Miguel , Pinto Jorge Sousa
Published: April 2015

Over the past decades several approaches for schedulability analysis have been proposed for both uni-processor and multi-processor real-time systems. Although different techniques are employed, very little has been put forward in using formal specifications, with the consequent possibility for misinterpretations or ambiguities in the problem statement. Using a logic based approach to schedulability analysis in the design of hard real-time systems eases the synthesis of correct-by-construction procedures for both static and dynamic verification processes. In this paper we propose a novel approach to schedulability analysis based on a timed temporal logic with time durations. Our approach subsumes classical methods for uni-processor scheduling analysis over compositional resource models by providing the developer with counter-examples, and by ruling out schedules that cause unsafe violations on the system. We also provide an example showing the effectiveness of our proposal.
Activation state of the hyperpolarization-activated current modulates temperature-sensitivity of firing in locus coeruleus neurons from bullfrogs
Authors: Santin Joseph M. , Hartzler Lynn K.
Published: April 2015

Locus coeruleus neurons of anuran amphibians contribute to breathing control and have spontaneous firing frequencies that, paradoxically, increase with cooling. We previously showed that cooling inhibits a depolarizing membrane current, the hyperpolarization-activated current ( Ih) in locus coeruleus neurons from bullfrogs, Lithobates catesbeianus (Santin JM, Watters KC, Putnam RW, Hartzler LK. Am J Physiol Regul Integr Comp Physiol 305: R1451–R1464, 2013). This suggests an unlikely role for Ih in generating cold activation, but led us to hypothesize that inhibition of Ih by cooling functions as a physiological brake to limit the cold-activated response. Using whole cell electrophysiology in brain slices, we employed 2 mM Cs+ (an Ih antagonist) to isolate the role of Ih in spontaneous firing and cold activation in neurons recorded with either control or Ih agonist (cyclic AMP)-containing artificial intracellular fluid. Ih did not contribute to the membrane potential ( Vm) and spontaneous firing at 20°C. Although voltage-clamp analysis confirmed that cooling inhibits Ih, its lack of involvement in setting baseline firing and Vm precluded its ability to regulate cold activation as hypothesized. In contrast, neurons dialyzed with cAMP exhibited greater baseline firing frequencies at 20°C due to Ih activation. Our hypothesis was supported when the starting level of Ih was enhanced by elevating cAMP because cold activation was converted to more ordinary cold inhibition. These findings indicate that situations leading to enhancement of Ih facilitate firing at 20°C, yet the hyperpolarization associated with inhibiting a depolarizing cation current by cooling blunts the net Vm response to cooling to oppose normal cold-depolarizing factors. This suggests that the influence of Ih activation state on neuronal firing varies in the poikilothermic neuronal environment.
Activation of nuclear factor of activated T cells 5 in the peritoneal membrane of uremic patients
Authors: Kitterer Daniel , Latus Joerg , Ulmer Christoph , Fritz Peter , Biegger Dagmar , Ott German , Alscher M. Dominik , Witowski Janusz , Kawka Edyta , Jörres Achim , Seeger Harald , Segerer Stephan , Braun Niko
Published: April 2015

Peritoneal inflammation and fibrosis are responses to the uremic milieu and exposure to hyperosmolar dialysis fluids in patients on peritoneal dialysis. Cells respond to high osmolarity via the transcription factor nuclear factor of activated T cells (NFAT5). In the present study, the response of human peritoneal fibroblasts to glucose was analyzed in vitro. Expression levels of NFAT5 and chemokine (C-C motif) ligand (CCL2) mRNA were quantified in peritoneal biopsies of five nonuremic control patients, five uremic patients before PD (pPD), and eight patients on PD (oPD) using real-time PCR. Biopsies from 5 control patients, 25 pPD patients, and 25 oPD patients were investigated using immunohistochemistry to detect the expression of NFAT5, CCL2, NF-κB p50, NF-κB p65, and CD68. High glucose concentrations led to an early, dose-dependent induction of NFAT5 mRNA in human peritoneal fibroblasts. CCL2 mRNA expression was upregulated by high concentrations of glucose after 6 h, but, most notably, a concentration-dependent induction of CCL2 was present after 96 h. In human peritoneal biopsies, NFAT5 mRNA levels were increased in uremic patients compared with nonuremic control patients. No significant difference was found between the pPD group and oPD group. CCL2 mRNA expression was higher in the oPD group. Immunohistochemistry analysis was consistent with the results of mRNA analysis. CD68-positive cells were significantly increased in the oPD group. In conclusion, uremia results in NFAT5 induction, which might promote early changes of the peritoneum. Upregulation of NFAT5 in PD patients is associated with NFκB induction, potentially resulting in the recruitment of macrophages.
Memories that last in hypertension
Authors: Itani Hana A. , Harrison David G.
Published: April 2015

In recent years, it has become clear that the immune system contributes to the genesis of hypertension. Hypertensive stimuli, such as angiotensin II, DOCA-salt, and norepinephrine, cause T cells and monocytes/macrophages to accumulate in the kidney and vasculature. These cells release inflammatory cytokines, such as IL-6, interferon-γ, and IL-17, that promote renal and vascular dysfunction. These cytokines also promote angiotensinogen production in the proximal tubule and Na+ retention in the distal nephron and contribute to renal fibrosis and glomerular damage. For several years, we have observed accumulation of memory T cells in the kidney and vasculature. Given the propensity for memory cells to produce cytokines such as interferon-γ and IL-17, interventions to prevent the formation or renal accumulation of specific memory T cell subsets could prevent end-organ damage and blood pressure elevation in response to hypertensive stimuli.
KCNJ10 (Kir4.1) is expressed in the basolateral membrane of the cortical thick ascending limb
Authors: Zhang Chengbiao , Wang Lijun , Su Xiao-Tong , Lin Dao-Hong , Wang Wen-Hui
Published: April 2015

The aim of the present study is to examine the role of Kcnj10 (Kir.4.1) in contributing to the basolateral K conductance in the cortical thick ascending limb (cTAL) using Kcnj10+/+ wild-type (WT) and Kcnj10−/− knockout (KO) mice. The patch-clamp experiments detected a 40- and an 80-pS K channel in the basolateral membrane of the cTAL. Moreover, the probability of finding the 40-pS K was significantly higher in the late part of the cTAL close to the distal convoluted tubule than those in the initial part. Immunostaining showed that Kcnj10 staining was detected in the basolateral membrane of the cTAL but the expression was not uniformly distributed. The disruption of Kcnj10 completely eliminated the 40-pS K channel but not the 80-pS K channel, suggesting the role of Kcnj10 in forming the 40-pS K channel of the cTAL. Also, the disruption of Kcnj10 increased the probability of finding the 80-pS K channel in the cTAL, especially in the late part of the cTAL. Because the channel open probability of the 80-pS K channel in KO was similar to those of WT mice, the increase in the 80-pS K channel may be achieved by increasing K channel number. The whole cell recording further showed that K reversal potential measured with 5 mM K in the bath and 140 mM K in the pipette was the same in the WT and KO mice. Moreover, Western blot and immunostaining showed that the disruption of Kcnj10 did not affect the expression of Na-K-Cl cotransporter 2 (NKCC2). We conclude that Kir.4.1 is expressed in the basolateral membrane of cTAL and that the disruption of Kir.4.1 has no significant effect on the membrane potential of the cTAL and NKCC2 expression.
Voltage gating by molecular subunits of Na+ and K+ ion channels: higher-dimensional cubic kinetics, rate constants, and temperature
Authors: Fohlmeister Jürgen F.
Published: April 2015

The structural similarity between the primary molecules of voltage-gated Na and K channels (alpha subunits) and activation gating in the Hodgkin-Huxley model is brought into full agreement by increasing the model's sodium kinetics to fourth order (m3 → m4). Both structures then virtually imply activation gating by four independent subprocesses acting in parallel. The kinetics coalesce in four-dimensional (4D) cubic diagrams (16 states, 32 reversible transitions) that show the structure to be highly failure resistant against significant partial loss of gating function. Rate constants, as fitted in phase plot data of retinal ganglion cell excitation, reflect the molecular nature of the gating transitions. Additional dimensions (6D cubic diagrams) accommodate kinetically coupled sodium inactivation and gating processes associated with beta subunits. The gating transitions of coupled sodium inactivation appear to be thermodynamically irreversible; response to dielectric surface charges (capacitive displacement) provides a potential energy source for those transitions and yields highly energy-efficient excitation. A comparison of temperature responses of the squid giant axon (apparently Arrhenius) and mammalian channel gating yields kinetic Q10 = 2.2 for alpha unit gating, whose transitions are rate-limiting at mammalian temperatures; beta unit kinetic Q10 = 14 reproduces the observed non-Arrhenius deviation of mammalian gating at low temperatures; the Q10 of sodium inactivation gating matches the rate-limiting component of activation gating at all temperatures. The model kinetics reproduce the physiologically large frequency range for repetitive firing in ganglion cells and the physiologically observed strong temperature dependence of recovery from inactivation.
In SilicoSearch of Energy Metabolism Inhibitors for Alternative Leishmaniasis Treatments
Authors: Silva Lourival A. , Vinaud Marina C. , Castro Ana Maria , Cravo Pedro Vítor L. , Bezerra José Clecildo B.
Published: April 2015

Leishmaniasis is a complex disease that affects mammals and is caused by approximately 20 distinct protozoa from the genusLeishmania. Leishmaniasis is an endemic disease that exerts a large socioeconomic impact on poor and developing countries. The current treatment for leishmaniasis is complex, expensive, and poorly efficacious. Thus, there is an urgent need to develop more selective, less expensive new drugs. The energy metabolism pathways ofLeishmaniainclude several interesting targets for specific inhibitors. In the present study, we sought to establish which energy metabolism enzymes inLeishmaniacould be targets for inhibitors that have already been approved for the treatment of other diseases. We were able to identify 94 genes and 93Leishmaniaenergy metabolism targets. Using each gene’s designation as a search criterion in the TriTrypDB database, we located the predicted peptide sequences, which in turn were used to interrogate the DrugBank, Therapeutic Target Database (TTD), and PubChem databases. We identified 44 putative targets of which 11 are predicted to be amenable to inhibition by drugs which have already been approved for use in humans for 11 of these targets. We propose that these drugs should be experimentally tested and potentially used in the treatment of leishmaniasis.
Small Molecule MYC Inhibitor Conjugated to Integrin-Targeted Nanoparticles Extends Survival in a Mouse Model of Disseminated Multiple Myeloma
Authors: Soodgupta Deepti , Pan Dipanjan , Cui Grace , Senpan Angana , Yang Xiaoxia , Lu Lan , Weilbaecher Katherine N. , Prochownik Edward V. , Lanza Gregory M. , Tomasson Michael H.
Published: April 2015

Multiple myeloma pathogenesis is driven by the MYC oncoprotein, its dimerization with MAX, and the binding of this heterodimer to E-Boxes in the vicinity of target genes. The systemic utility of potent small molecule inhibitors of MYC-MAX dimerization was limited by poor bioavailability, rapid metabolism, and inadequate target site penetration. We hypothesized that new lipid-based MYC-MAX dimerization inhibitor prodrugs delivered via integrin-targeted nanoparticles (NP) would overcome prior shortcomings of MYC inhibitor approaches and prolong survival in a mouse model of cancer. An Sn 2 lipase-labile prodrug inhibitor of MYC-MAX dimerization (MI1-PD) was developed which decreased cell proliferation and induced apoptosis in cultured multiple myeloma cell lines alone (P < 0.05) and when incorporated into integrin-targeted lipid-encapsulated NPs (P < 0.05). Binding and efficacy of NPs closely correlated with integrin expression of the target multiple myeloma cells. Using a KaLwRij metastatic multiple myeloma mouse model, VLA-4–targeted NPs (20 nm and 200 nm) incorporating MI1-PD (D) NPs conferred significant survival benefits compared with respective NP controls, targeted (T) no-drug (ND), and untargeted (NT) control NPs (T/D 200: 46 days vs. NT/ND: 28 days, P < 0.05 and T/D 20: 52 days vs. NT/ND: 29 days, P = 0.001). The smaller particles performed better of the two sizes. Neither MI1 nor MI1-PD provided survival benefit when administered systemically as free compounds. These results demonstrate for the first time that a small molecule inhibitor of the MYC transcription factor can be an effective anticancer agent when delivered using a targeted nanotherapy approach. Mol Cancer Ther; 14(6); 1286–94. ©2015 AACR.
PTEN Expression as a Predictor of Response to Focal Adhesion Kinase Inhibition in Uterine Cancer
Authors: Thanapprapasr Duangmani , Previs Rebecca A. , Hu Wei , Ivan Cristina , Armaiz-Pena Guillermo N. , Dorniak Piotr L. , Hansen Jean M. , Rupaimoole Rajesha , Huang Jie , Dalton Heather J. , Ali-Fehmi Rouba , Coleman Robert L. , Sood Anil K.
Published: April 2015

PTEN is known to be frequently mutated in uterine cancer and also dephosphorylates FAK. Here, we examined the impact of PTEN alterations on the response to treatment with a FAK inhibitor (GSK2256098). In vitro and in vivo therapeutic experiments were carried out using PTEN-mutated and PTEN-wild-type models of uterine cancer alone and in combination with chemotherapy. Treatment with GSK2256098 resulted in greater inhibition of pFAKY397 in PTEN-mutated (Ishikawa) than in PTEN-wild-type (Hec1A) cells. Ishikawa cells were more sensitive to GSK2256098 than the treated Hec1A cells. Ishikawa cells were transfected with a wild-type PTEN construct and pFAKY397 expression was unchanged after treatment with GSK2256098. Decreased cell viability and enhanced sensitivity to chemotherapy (paclitaxel and topotecan) in combination with GSK2256098 was observed in Ishikawa cells as compared with Hec1a cells. In the Ishikawa orthoptopic murine model, treatment with GSK2256098 resulted in lower tumor weights and fewer metastases than mice inoculated with Hec1A cells. Tumors treated with GSK2256098 had lower microvessel density (CD31), less cellular proliferation (Ki67), and higher apoptosis (TUNEL) rates in the Ishikawa model when compared with the Hec1a model. From a large cohort of evaluable patients, increased FAK and pFAKY397 expression levels were significantly related to poor overall survival. Moreover, PTEN levels were inversely related to pFAKY397 expression. These preclinical data demonstrate that PTEN-mutated uterine cancer responds better to FAK inhibition than does PTEN wild-type cancer. Therefore, PTEN could be a biomarker for predicting response to FAK-targeted therapy during clinical development. Mol Cancer Ther; 14(6); 1466–75. ©2015 AACR.
Mutational Profile and New IASLC/ATS/ERS Classification Provide Additional Prognostic Information about Lung Adenocarcinoma: A Study of 125 Patients from Brazil
Authors: de Melo Andreia Cristina , Karen de Sá Vanessa , Sternberg Cinthya , Olivieri Eloisa Ribeiro , Werneck da Cunha Isabela , Fabro Alexandre Todorovic , Carraro Dirce Maria , de Barros e Silva Milton José , Pimenta Inada Haynna Kimie , de Mello Evandro Sobrosa , Soares Fernando Augusto , Takagaki Tereza , Ferreira Carlos Gil , Capelozzi Vera Luiza
Published: April 2015

Aim: To show additional prognostic information about the mutational profile and new International Association for the Study of Lung Cancer/American Thoracic Society/European Respiratory Society (IASLC/ATS/ERS) classification of adenocarcinoma (ADC) in patients without epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor treatments. Methods: In human lung ADC patients (n = 125), including 24 lepidic, 67 acinar, 23 papillary, and 11 solid predominant subtypes, EGFR and KRAS were sequenced, and anaplastic lymphoma kinase (ALK) rearrangements were screened using fluorescence in situ hybridization (FISH). Results:EGFR was mutated in 21.6% of patients with 19.57% showing a mean expression. The most frequent EGFR mutation was a deletion in exon 19, followed by an L858R amino acid substitution in exon 21. KRAS was mutated in 26.4% of patients with 50% displaying mean expression. ALK rearrangement was detected in 6 patients (4.8%). Predominant acinar ADC was strongly associated with EGFR and KRAS mutation. Clinical stage, lymph node metastases, and EGFR mutation in exon 18 showed a significant difference in disease-free and overall survival, but only a trend significance for EGFR and KRAS mutations. Multivariate analysis revealed that men aged >71 years, with a history of smoking (<72 packs/year), clinical stage I/II, and acinar histologic subtype presented better survival than women aged ≤71 years, with a history of smoking (>72 packs/year), and having a predominant solid ADC and EGFR mutation in exon 18. Conclusions: These results indicate that the mutational profile and new IASLC/ATS/ERS classification provide additional prognostic information about lung ADC.
Is Cancer a Risk Factor for Cognitive Decline in Late Life?
Authors: Small Brent J. , Scott Stacey B. , Jim Heather S.L. , Jacobsen Paul B.
Published: April 2015

With advances in screening and early detection, coupled with improved treatment and care, the number of cancer survivors has risen exponentially over the past several decades. Moreover, because age is the most significant risk factor for cancer, the majority of cancer survivors are over 65 years of age. Finally, cancer survivors often experience significant health issues for many years after the treatment has subsided. In the current article, we describe select research that has focused on changes to cognitive performance associated with cancer and its treatment, i.e., alterations that have been colloquially referred to as chemobrain. Although understanding changes in cognitive performance following cancer treatment is an active area of inquiry, the experience of older adult cancer survivors has been somewhat neglected. For example, evidence is mixed as to whether changes in cognitive performance associated with normal aging are exacerbated by cancer survivorship status. It is also unclear whether a history of cancer makes it more or less likely that a person will be diagnosed with dementia or Alzheimer's disease in the future. Finally, we identify a number of areas where existing cognitive aging research can inform studies on cognitive performance following cancer treatment. Future efforts should be directed towards designing studies that focus on the experience of older adult cancer survivors and are informed by the clinical oncology and cognitive aging literature.
Nephrosclerosis: A Term in Quest of a Disease
Authors: Meyrier Alain
Published: April 2015

For a century, nephrosclerosis was ascribed to nonmalignant hypertension and aging. However, it was intuitively perceived that hypertension may follow rather than explain this nephrovasculopathy. Hypertensive nephrosclerosis was long considered a major cause of end-stage renal failure (ESRD). This is especially true in blacks of African descent but not in other ethnic populations. The term ‘nephrosclerosis' is still an easy way out to classify a patient with renal insufficiency. This leads to neglect the possibility of an overlooked nephropathy complicated by hypertension and to believe that drastic blood pressure control may retard the progression to ESRD. Several clinical and experimental lines of evidence lead to the understanding that nephrosclerosis, especially in blacks, is a genetic renovasculopathy that precedes the rise in blood pressure. The identification of coding region variants in APOL1 encoding apolipoprotein L-1 in black but also white and Asians opens new lines of research on the genetics of nephroangiosclerosis and of FSGS. Metabolic derangements, such as obesity, oxidative stress, dyslipidemia and atherosclerosis may be considered confounding factors with regard to nephrosclerosis. Histomorphometric studies led to sorting out the lesions due to aging from those stemming from hypertension. They shed new light not only on glomerular lesions that comprise ischemic obsolescence but also on glomerulomegaly and focal-segmental sclerosis, the latter due to a loss of renal autoregulation. It appears that the control of hypertension is not credited with the expected benefit for slowing the decline of renal function. ‘Nephrosclerosis' can be considered an umbrella term of poor significance that should be replaced by its pathologic description, that is, arterionephrosclerosis and incite to elucidate the various genetic and metabolic factors that lead to a lesion in quest of a specific disease.
Reversal of anticoagulants: an overview of current developments
Authors: Thiele Thomas , Selleng Kathleen , Greinacher Andreas
Published: April 2015

Several new anticoagulants have entered the clinical arena or are under clinical development. These drugs include indirect (fondaparinux) and direct oral factor Xa inhibitors (rivaroxaban, apixaban, edoxaban, betrixaban), and the direct thrombin inhibitor dabigatran. Especially the oral direct FXa and FIIa inhibitors overcome many of the shortcomings of heparins and vitamin K antagonists (VKAs). They are administered orally at a fixed dose; regular monitoring is not necessary; interaction with other drugs or nutrition occur less than with VKAs and they are at least as effective as VKAs for most indications tested. They are associated with about 50 % less intracranial bleeding than VKAs. Nevertheless, they are still associated with bleeding complications. Bleeding can occur spontaneously or as a result of trauma or urgent surgery. In such situations rapid reversal of the anticoagulant effect is highly desirable. For unfractionated heparin protamine, and for VKAs prothrombin complex concentrates are available as specific antidotes. Under clinical development are: for the direct and indirect FXa inhibitors a modified recombinant FXa (andexanet alpha), which lacks enzymatic activity; and for dabigatran a Fab fragment of a monoclonal antibody (idarucizumab). In addition a small molecule (aripazine) has entered phase I clinical trials, which seems to inhibit nearly all anticoagulants but VKAs and argatroban. This review summarises the current options and strategies in development to antagonise anticoagulants with a focus on the status of the development of antidotes for the oral direct FXa and FIIa inhibitors.
Moderate oral supplementation with docosahexaenoic acid improves platelet function and oxidative stress in type 2 diabetic patients
Authors: Colas Romain , Calzada Catherine , Lê Quang Huy , Feugier Nathalie , Cugnet Christine , Vidal Hubert , Laville Martine , Moulin Philippe , Lagarde Michel , Véricel Evelyne
Published: April 2015

Platelets from patients with type 2 diabetes are characterised by hyperactivation and high level of oxidative stress. Docosahexaenoic acid (DHA) may have beneficial effects on platelet reactivity and redox status. We investigated whether moderate DHA supplementation, given as a triglyceride form, may correct platelet dysfunction and redox imbalance in patients with type 2 diabetes. We conducted a randomised, double-blind, placebo-controlled, two-period crossover trial (n=11 post-menopausal women with type 2 diabetes) to test the effects of 400 mg/day of DHA intake for two weeks on platelet aggregation, markers of arachidonic acid metabolism, lipid peroxidation status, and lipid composition. Each two week-period was separated from the other by a six-week washout. Daily moderate dose DHA supplementation resulted in reduced platelet aggregation induced by collagen (-46.5 %, p< 0.001), and decreased platelet thromboxane B2 (-35 %, p< 0.001), urinary 11-dehydro-thromboxane B2 (-13.2 %, p< 0.001) and F2-isoprostane levels (-19.6 %, p< 0.001) associated with a significant increase of plasma and platelet vitamin E concentrations (+20 % and +11.8 %, respectively, p< 0.001). The proportions of DHA increased both in plasma lipids and in platelet phospholipids. After placebo treatment, there was no effect on any parameters tested. Our findings support a significant beneficial effect of low intake of DHA on platelet function and a favourable role in reducing oxidative stress associated with diabetes.
Care in the Last Year of Life for Community Patients With Heart Failure
Authors: Dunlay Shannon M. , Redfield Margaret M. , Jiang Ruoxiang , Weston Susan A. , Roger Véronique L.
Published: April 2015

Background—

Healthcare utilization peaks at the end of life (EOL) in patients with heart failure. However, it is unclear what factors affect end of life utilization in patients with heart failure and if utilization has changed over time.

Methods and Results—

Southeastern Minnesota residents with heart failure were prospectively enrolled into a longitudinal cohort study from 2003 to 2011. Patients who died before December 31, 2012, were included in the analysis. Information on hospitalizations and outpatient visits in the last year of life was obtained using administrative sources. Negative binomial regression was used to assess the association between patient characteristics and utilization. The 698 decedents (47.3% men; 53.4% preserved ejection fraction) experienced 1528 hospitalizations (median 2 per person; range, 0–12; 37.6% because of cardiovascular causes) and 12 927 outpatient visits (median 14 per person; range, 0–119) in their last year of life. Most patients (81.5%) were hospitalized at least once and 28.4% died in the hospital. Patients who were older and those with dementia had lower utilization. Patients who were married, resided in a skilled nursing facility, and had more comorbidities had higher utilization. Patients with preserved ejection fraction had higher rates of noncardiovascular hospitalizations although other utilization was similar. Over time, rates of hospitalizations and outpatient visits decreased, whereas palliative care consults and enrollment in hospice increased.

Conclusions—

Although patient factors remain associated with differential healthcare utilization at the end of life, utilization declined over time and use of palliative care services increased. These results are encouraging given the high resource use in patients with heart failure.
Augmentation of Limb Perfusion and Reversal of Tissue Ischemia Produced by Ultrasound-Mediated Microbubble Cavitation
Authors: Belcik J. Todd , Mott Brian H. , Xie Aris , Zhao Yan , Kim Sajeevani , Lindner Nathan J. , Ammi Azzdine , Linden Joel M. , Lindner Jonathan R.
Published: April 2015

Background—

Ultrasound can increase tissue blood flow, in part, through the intravascular shear produced by oscillatory pressure fluctuations. We hypothesized that ultrasound-mediated increases in perfusion can be augmented by microbubble contrast agents that undergo ultrasound-mediated cavitation and sought to characterize the biological mediators.

Methods and Results—

Contrast ultrasound perfusion imaging of hindlimb skeletal muscle and femoral artery diameter measurement were performed in nonischemic mice after unilateral 10-minute exposure to intermittent ultrasound alone (mechanical index, 0.6 or 1.3) or ultrasound with lipid microbubbles (2×10
8
IV). Studies were also performed after inhibiting shear- or pressure-dependent vasodilator pathways, and in mice with hindlimb ischemia. Ultrasound alone produced a 2-fold increase (
P
<0.05) in muscle perfusion regardless of ultrasound power. Ultrasound-mediated augmentation in flow was greater with microbubbles (3- and 10-fold higher than control for mechanical index 0.6 and 1.3, respectively;
P
<0.05), as was femoral artery dilation. Inhibition of endothelial nitric oxide synthase attenuated flow augmentation produced by ultrasound and microbubbles by 70% (
P
<0.01), whereas inhibition of adenosine-A
2a
receptors and epoxyeicosatrienoic acids had minimal effect. Limb nitric oxide production and muscle phospho-endothelial nitric oxide synthase increased in a stepwise fashion by ultrasound and ultrasound with microbubbles. In mice with unilateral hindlimb ischemia (40%–50% reduction in flow), ultrasound (mechanical index, 1.3) with microbubbles increased perfusion by 2-fold to a degree that was greater than the control nonischemic limb.

Conclusions—

Increases in muscle blood flow during high-power ultrasound are markedly amplified by the intravascular presence of microbubbles and can reverse tissue ischemia. These effects are most likely mediated by cavitation-related increases in shear and activation of endothelial nitric oxide synthase.
Characterisation of a topotype and other populations of Hemicriconemoides strictathecatus Esser, 1960 (Nematoda: Criconematidae) from Florida with description of H. phoenicis sp. n. from the USA
Authors: Van den Berg Esther , Tiedt Louwrens R. , Inserra Renato N. , Stanley Jason D. , Vovlas Nicola , Palomares-Rius Juan E. , Castillo Pablo , Subbotin Sergei A.
Published: April 2015

The results of morphological and molecular analyses of a Florida topotype and other populations of Hemicriconemoides strictathecatus showed that this sheathoid nematode consists of two morphotypes, both with an average stylet length of more than 70 μm, but having different tail termini, bluntly pointed or rounded. These findings confirmed the morphological similarity of H. strictathecatus with H. mangiferae, which was considered a junior synonym of this species as previously proposed by Decraemer & Geraert (1992, 1996). Populations of a sheathoid nematode with a stylet length ranging from 62.5 to 72.0 μm from Taiwan, China, South Africa and Venezuela and identified in previous studies as H. strictathecatus were found to be morphologically and molecularly different from this species and are now considered as representatives of H. litchi. Another sheathoid nematode population from Florida, considered to be H. mangiferae by McSorley et al. (1980), was also found to be morphologically and molecularly congruous with H. litchi. During nematological surveys in Florida, a new sheathoid nematode was detected on date palms imported from California into Florida and is described herein as H. phoenicis sp. n. This new species is related morphologically to the H. strictathecatus morphotype with pointed tail terminus. Both have a stylet longer than 70 μm. The new species is phylogenetically related to H. strictathecatus and H. litchi. It differs morphologically from other Hemicriconemoides species by the cuticular ornamentation of the annuli, which are marked by coarse longitudinal ridges, grooves and thick margins. Morphological and molecular characterisations of H. cocophillus from Mozambique and Florida, USA are also elucidated in this study. New phylogenies of the genus Hemicriconemoides as inferred from the analyses of the ITS rRNA, D2-D3 of 28S rRNA and partial coxI gene sequences are provided.
Ultrastructure of sperm development in the genus Ditylenchus (Nematoda: Anguinidae)
Authors: Slos Dieter , Ensafi Pooria , Claeys Myriam , Yushin Vladimir V. , Decraemer Wilfrida , Bert Wim
Published: April 2015

Spermatogenesis in Ditylenchus arachis and D. dipsaci was studied using transmission electron microscopy. Spermatogenesis includes the formation of complexes of fibrous bodies (FB) and membranous organelles (MO) in the spermatocytes, which dissociate in separated MO and FB in the spermatids. Immature spermatozoa are unpolarised cells with separate FB and MO. Mature spermatozoa are arranged in chains. Ditylenchus dipsaci is unique in having MO that have already fused with the outer membrane in immature spermatozoa and have mature spermatozoa in the male testis, proving that not only insemination plays a role in spermiogenesis. Contrary to what has been described before, spermatogenesis in Ditylenchus, and other early diverging Tylenchomorpha, follow the typical ‘rhabditid’ pattern, while the absence of MO within Tylenchomorpha appears to be an apomorphic trait for the molecular defined clade of tylenchids that exclusively parasitise higher plants. This confirms the value of traits related to spermatogenesis in nematode phylogeny.
Soil and litter nematode diversity of Mount Hamiguitan, the Philippines, with description of Bicirronema hamiguitanense n. sp. (Rhabditida: Bicirronematidae)
Authors: Qing Xue , Bert Wim , Steel Hanne , Quisado Joeseph , Tandingan De Ley Irma
Published: April 2015

The nematode diversity in soil and litter was investigated on Mount Hamiguitan, the Philippines, along four eco-habitats from elevations of 75-1600 m a.s.l. A total of 155 and 467 nematodes were identified to 39 and 62 genera from litter and soil, respectively. The nematode assemblages and diversity did not show any relation to eco-habitat or elevation. Bacterivorous nematodes were the most common group (37.5%). Acrobeloides was most abundant from the soil and Aphelenchoides from the litter. Bicirronema hamiguitanense n. sp. is herein described based on morphology, morphometrics and molecular data. The new species has the following diagnostic features: a wide lateral field one-fifth of its body diam. with four incisures forming two ornamented ridges; gubernaculum with proximal thickening; spicules (35-38 μm) and gubernaculum (18-20 μm) longer than B. caledoniense; and with 37 molecular autapomorphies supporting its new species status. The phylogenetic position of the new species within Cephalobomorpha is discussed.
Resistance genes against plant-parasitic nematodes: a durable control strategy?
Authors: Davies Laura J. , Elling Axel A.
Published: April 2015

Plant-parasitic nematodes are a major pest of all agricultural systems, causing extensive economic losses. Natural resistance (R) genes offer an alternative to chemical control and have been shown effectively to limit nematode damage to crops in the field. Whilst a number of resistant cultivars have conferred resistance against root-knot and cyst nematodes for many decades, an increasing number of reports of resistance-breaking nematode pathotypes are beginning to emerge. The forces affecting the emergence of virulent nematodes are complex, multifactorial and involve both the host and parasite of the plant-nematode interaction. This review provides an overview of the root-knot and cyst nematodeRgenes characterised to date, in addition to examining the evolutionary forces influencing nematode populations and the emergence of virulence. Finally, potential strategies to improveRgene durability in the field are outlined, and areas that would benefit from further research efforts are highlighted.
Seeing the Relationship between the uncrc and the Asylum System through the Eyes of Unaccompanied Asylum Seeking Children and Young People
Authors: Connolly Helen
Published: April 2015

The rights and experiences of unaccompanied asylum seeking children living in industrialised nations are rarely seen from the perspectives of children themselves. This paper takes a narrative based approach to report on the lives 29 unaccompanied asylum seeking young people in the uk. The research from which this paper emerges explored the ways in which they thought the rights of the United Nations Convention on the Rights of the Child (1989) were or were not being realised on their behalf. It highlights the significance of making the promises that are held within the uncrc into viable strategies of protection for unaccompanied asylum seeking children as they search for a new place to belong to and a new place that belongs in them.
Non-Governmental Organisations and the un Convention on the Rights of the Child
Authors: Polonko Karen A. , Lombardo Lucien X.
Published: April 2015

This study seeks to contribute to knowledge of the implementation of the U.N Convention on the Rights of the Child (crc). Focus was restricted to one of eight General Measures of Implementation – involvement of civil society, in particular, non-government organisations (ngos), in the implementation and monitoring of the crc. The study had three aims: (1) to develop initial indicators of ngo involvement; (2) to explore level of ngo activity; and (3) to explore which aspects of ngo involvement might have an effect on extending human rights to children in the most fundamental area of protection from violence.

Results indicate that most State Parties (sps) have at least one ngo member and 50 per cent had a National Coalition member in the Child Rights Information Network (crin). Regarding activity, at least one alternative ngo report was submitted to the crc Committee for most sps. Analyses of Concluding Observations indicate that the Committee on the Rights of the Child expressed concerns about most sp’s involvement with ngos and found very few governments encouraging ngos to take a child-rights focus. Overall, few indicators of ngo involvement were related to lower rates of child physical abuse – what appeared most important was having a government that encourages ngos to have a child-rights focus. Reasons for these findings and directions for future research are discussed.
On History and Policy: Time in the Age of Neoliberalism
Authors: Boldizzoni Francesco
Published: April 2015

It is often said that history matters, but these words are usually little more than a hollow statement. In the aftermath of the Great Recession, the view that the economy is a mechanical toy that can be fixed using a few simple tools has continued to be held by economists and policy makers and echoed by the media. The essay addresses the origins of this unfortunate belief, inherent to neoliberalism, and what can be done to bring time back into public discourse.
Francesco Boldizzoni: A Critical Comment
Authors: Klamer Arjo
Published: April 2015

In this comment on Boldizzoni (2013), I outline that his argumentation is problematic and his historical point unclear. He claims that a historical perspective exposes the ‘pseudo’-dimension in science and history. From the case of Chili, he concludes that Chicago-economics is a pseudo-science. This accusation backfires when his own argument is problematic from a scientific and historical perspective. However, I can broadly agree with what is written about the history of economics as a discipline.

I am sympathetic towards Boldizzoni’s observation about the relevance of history. I agree that we should go beyond the assumption of rational decision making, and propose a value-based approach to economics, where behaviour is seen as the realization of values, of which some values have a history. Hence, our understanding of history play a large role in understanding everyday behaviour. I argue that people need history as a source for meaningful life and action.
Revision of Navicula striolata (Grunow) Lange-Bertalot and N. rumaniensis Hustedt with the description of N. friedelhinziae sp. nov.
Authors: Wojtal Agata Zofia , Ognjanova-Rumenova Nadja , Buczko Krisztina , Siwek Janusz , Van de Vijver Bart
Published: April 2015

Navicula striolata was originally described as N. digitoradiata var. striolata from modern material collected in Sweden. After examination of a sample collected from Belgium, the variety was transferred to N. reinhardtii as N. reinhardti var. gracilior. From this time a large mix up of these and related taxa was observed in the literature. A similar species, Navicula rumaniensis had also been established in 1934 from Neogene Romanian materials but there has been much confusion regarding the status of these taxa, leading to a poor understanding of their distribution. In this study, type material of Navicula digitoradiata var. striolata, N. reinhardtii var. gracilior and N. rumaniensis are revised using light and scanning electron microscopy in order to clarify their identity and to investigate possible conspecificity. The results indicate that these species are not synonyms. Conspecificity of the modern N. digitoradiata var. striolata and N. reinhardti var. gracilior was confirmed and lectotypes of both varieties have been designated whereas N. rumaniensis proved to be a separate species. In addition, the study of Neogene material from Bulgaria revealed the presence of a new Navicula taxon—N. friedelhinziae. The morphology of these and similar taxa is discussed.
The first record of Pyxidium tardigradum Van der Land, 1964 (Ciliophora) in Romania
Authors: CIOBANU DANIEL ADRIAN , ROSZKOWSKA MILENA , MOGLAN IOAN , KACZMAREK ŁUKASZ
Published: April 2015

In three lichen samples collected from eastern part of Romania, three populations of Ramazzottius cf. oberhaeuseri (Doyère, 1840) infested by Pyxidium tardigradum Van der Land 1964 were found. In this short correspondence we present a first record of P. tardigradum in Romania and infestation rates in studied populations according to the different life stages.