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We provide an expanded description of the tadpole of Amnirana albolabris (Ranidae) that includes external linear morphometrics and colouration across a developmental series ranging from Gosner stages 26–42. This description is based on material collected in Batéké Plateau National Park in south-eastern Gabon. The diurnal tadpoles are strikingly bright orange in life, a colouration that provides effective crypsis for the tannic waters in which they live. We also provide a comparative table for all of the described Amnirana tadpoles. The tadpole of A. albolabris can be identified in life by its unique colouration or in preservative by the seven prominent skin glands, assumed to contain defensive toxins. [ABSTRACT FROM AUTHOR]

GLP test facility management refers to the proper management and organization of a facility that conducts studies according to GLP regulations. Compliance with GLP regulations is necessary for data generated in such facilities to be accepted by regulatory authorities. According to GLP Principles, Test facility management (TFM) is responsible for a wide range of tasks and responsibilities to ensure the smooth and efficient operation of the facility. The framework in which the TFM operates within the Test Facility is certainly much more complex than in the early days of the GLP, and moreover it is unlikely that anything will change from a scientific and technological point of view in the years to come. Several aspects have changed from a scientific and technological point of view, and we know that innovation is very rapid. From the above considerations emerges the need for a major change in the performance of the TFM's role. • Test Facility Management (TFM) is responsible for GLP compliance of the test facility. • There is the need for a TFM more open to scientific and technological innovation. • TFM should be more open to the collaboration with other quality systems. [ABSTRACT FROM AUTHOR]

The fungal pathogen Batrachochytrium dendrobatidis (Bd) is implicated in global declines of amphibian populations and has been documented in African specimens originally collected as far back as the 1930s. Numerous recent surveys focusing on regional pathogen prevalence have greatly increased the number of known occurrences of Bd in African species, but few studies have focused on continental distribution patterns. We analyzed all known positive occurrences of Bd in African amphibians to date, including newly reported data from Cameroon, the Democratic Republic of the Congo, Gabon, Namibia, and the Republic of the Congo. Records from both Namibia and the Republic of the Congo reported herein represent first positive occurrences for these countries. With this most comprehensive sampling of the African continent to date we identified patterns of Bd-positive occurrences associated with (1) location (i.e., biogeographic region, country), (2) taxonomy, (3) life history, and (4) threat of extinction. We used fine-grained (30 arc seconds) environmental niche models (ENMs) to predict the continental distribution of Bd and identify hotspots for the pathogen, including areas not previously modeled to have high suitability for the fungus, and areas of high amphibian biodiversity from which Bd has not yet been documented. Our ENMs predicted that the environmentally suitable range of Bd encompasses vast areas of high amphibian biodiversity, including the Congo Basin and the Albertine Rift. Although our ENMs indicated that West Africa is environmentally suitable for Bd, the fungus has not been reported west of the Dahomey Gap. Likewise, the ENMs also identified regions across the Congo Basin and coastal Angola that are environmentally suitable for the pathogen but from which Bd has not yet been reported, underscoring a need for Bd surveys in these regions. Although amphibian declines in Africa have not been directly attributed to chytridiomycosis, Bd has been detected in over one fifth of the most-threatened African amphibians. Given the presence of the hypervirulent Bd global panzootic lineage (BdGPL) in Africa, we believe that the threat of Bd as a novel pathogen may be underestimated and that focused research is urgently needed to identify which species are susceptible to Bd-driven declines. [ABSTRACT FROM AUTHOR]

The Mascarene ridged frog, Ptychadena mascareniensis , is a species complex that includes numerous lineages occurring mostly in humid savannas and open forests of mainland Africa, Madagascar, the Seychelles, and the Mascarene Islands. Sampling across this broad distribution presents an opportunity to examine the genetic differentiation within this complex and to investigate how the evolution of bioclimatic niches may have shaped current biogeographic patterns. Using model-based phylogenetic methods and molecular-clock dating, we constructed a time-calibrated molecular phylogenetic hypothesis for the group based on mitochondrial 16S rRNA and cytochrome b ( cytb ) genes and the nuclear RAG1 gene from 173 individuals. Haplotype networks were reconstructed and species boundaries were investigated using three species-delimitation approaches: Bayesian generalized mixed Yule-coalescent model (bGMYC), the Poisson Tree Process model (PTP) and a cluster algorithm (SpeciesIdentifier). Estimates of similarity in bioclimatic niche were calculated from species-distribution models ( maxent ) and multivariate statistics (Principal Component Analysis, Discriminant Function Analysis). Ancestral-area reconstructions were performed on the phylogeny using probabilistic approaches implemented in BioGeoBEARS. We detected high levels of genetic differentiation yielding ten distinct lineages or operational taxonomic units, and Central Africa was found to be a diversity hotspot for these frogs. Most speciation events took place throughout the Miocene, including “out-of-Africa” overseas dispersal events to Madagascar in the East and to São Tomé in the West. Bioclimatic niche was remarkably well conserved, with most species tolerating similar temperature and rainfall conditions common to the Central African region. The P. mascareniensis complex provides insights into how bioclimatic niche shaped the current biogeographic patterns with niche conservatism being exhibited by the Central African radiation and niche divergence shaping populations in West Africa and Madagascar. Central Africa, including the Albertine Rift region, has been an important center of diversification for this species complex. [ABSTRACT FROM AUTHOR]

ABSTRACT It is widely accepted that elevated protease activity (EPA) in chronic wounds impedes healing. However, little progress has occurred in quantifying the level of protease activity that is detrimental for healing. The aim of this study was to determine the relationship between inflammatory protease activity and wound healing status, and to establish the level of EPA above which human neutrophil-derived elastase (HNE) and matrix metalloproteases (MMP) activities correlate with nonhealing wounds. Chronic wound swab samples ( n = 290) were collected from four wound centers across the USA to measure HNE and MMP activity. Healing status was determined according to percentage reduction in wound area over the previous 2-4 weeks; this was available for 211 wounds. Association between protease activity and nonhealing wounds was determined by receiver operating characteristic analysis (ROC), a statistical technique used for visualizing and analyzing the performance of diagnostic tests. ROC analysis showed that area under the curve (AUC) for HNE were 0.69 for all wounds and 0.78 for wounds with the most reliable wound trajectory information, respectively. For MMP, the corresponding AUC values were 0.70 and 0.82. Analysis suggested that chronic wounds having values of HNE >5 and/or MMP ≥13, should be considered wound healing impaired. EPA is indicative of nonhealing wounds. Use of a diagnostic test to detect EPA in clinical practice could enable clinicians to identify wounds that are nonhealing, thus enabling targeted treatment with protease modulating therapies. [ABSTRACT FROM AUTHOR]

Small-bodied freshwater fish are commonly used in regulatory testing for endocrine disrupting compounds (EDCs) but most lack a sensitive and quantifiable androgen-specific biomarker. Brook stickleback ( Culaea inconstans ) are a North American freshwater fish whose males produce an androgen-regulated glycoprotein in the kidney called spiggin. Although spiggin induction in females has been used as an androgen-specific biomarker of exposure in other stickleback species it has not been characterized in brook stickleback. Therefore, our objective was to develop a bioassay using brook stickleback to measure estrogenic and androgenic responses and establish the sensitivity of traditional and novel biomarkers of exposure. We first developed and optimized a qPCR assay to measure spiggin and vitellogenin transcript levels in kidney and liver tissue, respectively. Basal levels were differentially expressed in mature wild-caught male and female brook stickleback. To determine their sensitivity to EDCs, fish were exposed to nominal concentrations of 1, 10 and 100 ng/L of 17α-methyltestosterone (MT) or 17α-ethinylestradiol (EE2) for 21 days (sampled at 7 and 21 days) under semi-static renewal conditions. MT and EE2 exposure induced spiggin and vitellogenin transcripts in female kidneys and male livers, respectively. Exposure to EE2 also increased hepatosomatic index in both sexes and decreased gonadosomatic index in females. Histopathological alterations were observed in the kidney of EE2-exposed fish and an increase in kidney epithelium cell height occurred in MT-exposed females. Given the sensitivity of these endpoints, the brook stickleback is a promising new freshwater fish model for EDC evaluation and a potential bioindicator for EDCs in North American freshwater environments. [ABSTRACT FROM AUTHOR]

The deer remains from the renowned Palaeolithic site of Isernia la Pineta (southern Italy) are revised. Both material already published, and new specimens from the last 15 years of excavation, is taken into account and some identifications are revised. The published assemblage consists of Megaceroides solilhacus, Cervus sp. cf. C. elaphus acoronatus, Dama sp. cf. D. clactoniana and Capreolus sp. The literature dealing with these species is discussed and the problems still unresolved are outlined. The giant deer, now assigned by most authors to the genus Praemegaceros as P. solilhacus, is the largest and most common deer species at the site, represented by numerous antler fragments plus a few isolated teeth and fragmentary postcranial elements. The retrieval of new, well-preserved specimens, namely one nearly complete antler, plus a distal portion of palmation, two neural skulls and one premaxillary bone, allows a better characterization of this otherwise still poorly understood species. The sub-specific attribution of the red deer, in the lack of more complete antler specimens, is still dubious. The fallow deer remains probably belong to Dama roberti, a recently described species from the early Middle Pleistocene of Western Europe. The morphology of the lower portion of the only preserved antler fits better with this species rather than with D. clactoniana, to which it was previously tentatively assigned. At last, the specific identity of the few roe deer remains from Isernia is discussed, but the problem remains unanswered because of lack of agreement, in the literature, about the taxonomy of the Pleistocene species. Copyright © 2015 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Within chronic wounds, the relationship between the clinical diagnosis of infection and bacterial/immuno-inflammatory responses is imprecise. This study prospectively examined the interrelationship between clinical, microbiological, and proinflammatory biomarker levels between chronic venous leg ulcers ( CVLUs) and diabetic foot ulcers ( DFUs). Wound swabs and fluids were collected from CVLUs ( n = 18) and DFUs ( n = 15) and diagnosed clinically as noninfected or infected; and qualitative/quantitative microbiology was performed. CVLU and DFU fluids were also analyzed for cytokine, growth factor, receptor, proteinase/proteinase inhibitor; and oxidative stress biomarker (protein carbonyl, malondialdehyde, and antioxidant capacity) levels. While no correlations existed between clinical diagnosis, microbiology, or biomarker profiles, increasing bacterial bioburden (≥107 colony-forming unit/mL) was associated with significant alterations in cytokine, growth factor, and receptor levels. These responses contrasted between ulcer type, with elevated and decreased cytokine, growth factor, and receptor levels in CVLUs and DFUs with increasing bioburden, respectively. Despite proteinase biomarkers exhibiting few differences between CVLUs and DFUs, significant elevations in antioxidant capacities correlated with increased bioburden in CVLU fluids, but not in DFUs. Furthermore, oxidative stress biomarker levels were significantly elevated in all DFU fluids compared with CVLUs. This study provides further insight into the contrasting disease-specific host responses to bacterial challenge within infected CVLUs and DFUs. [ABSTRACT FROM AUTHOR]

The continental highlands of the Cameroon Volcanic Line ( CVL) represent biological 'sky islands' with high levels of species richness and endemism, providing the ideal opportunity to understand how orogenesis and historical climate change influenced species diversity and distribution in these isolated African highlands. Relationships of puddle frogs ( Phrynobatrachus) endemic to the CVL are reconstructed to examine the patterns and timing of puddle frog diversification. Historical distributions were reconstructed using both elevation and geography data. Puddle frogs diversified in the CVL via several dispersal and vicariance events, with most of the locally endemic species distributed across the northern part of the montane forest area in the Bamenda- Banso Highlands ( Bamboutos Mts., Mt. Lefo, Mt. Mbam, Mt. Oku and medium elevation areas connecting these mountains). Two new species, P. jimzimkusi sp. n. and P. njiomock sp. n., are also described based on molecular analyses and morphological examination. We find that these new species are most closely related to one another and P. steindachneri with the ranges of all three species overlapping at Mt. Oku. Phrynobatrachus jimzimkusi sp. n. is distributed in the southern portion of the continental CVL, P. njiomock sp. n. is endemic to Mt. Oku, and P. steindachneri is present in the northeastern part of the montane forest area. Both new species can be distinguished from all other puddle frogs by a combination of morphological characters, including their large size, ventral coloration and secondary sexual characteristics present in males. These results highlight the Bamenda- Banso Highlands, and specifically emphasize Mt. Oku, as a centre of diversification for puddle frogs, supporting the conservation importance of this region. Our results also provide new insights into the evolutionary processes shaping the CVL 'sky islands', demonstrating that lineage diversification in these montane amphibians is significantly older than expected with most species diverging from their closest relative in the Miocene. Whereas climatic changes during the Pliocene and Pleistocene shaped intraspecific diversification, most speciation events were significantly older and cannot be linked to Africa's aridification in response to Pleistocene climate fluctuations. [ABSTRACT FROM AUTHOR]

The article focuses on amphibians of five sites within the Batéké Plateau National Park, Gabon along with the information on results of chytrid pathogen tests. It also includes four new country records including Phrynobatrachus ruthbeateae, Ptychadena uzungwensis and Xenopus pygmaeus and states that the presence of the fungus Batrachochytrium dendrobatidis (Bd) that that causes the amphibian disease chytridiomycosis was tested by using Taqman polymerase chain reaction (PCR).

Terrestrialization, the evolution of non-aquatic oviposition, and miniaturization, the evolution of tiny adult body size, are recurring trends in amphibian evolution, but the relationships among the traits that characterize these phenomena are not well understood. Furthermore, these traits have been identified as possible "key innovations" that are predicted to increase rates of speciation in those lineages in which they evolve. We examine terrestrialization and miniaturization in sub-Saharan puddle frogs (Phrynobatrachidae) in a phylogenetic context to investigate the relationship between adaptation and diversification through time. We use relative dating techniques to ascertain if character trait shifts are associated with increased diversification rates, and we evaluate the likelihood that a single temporal event can explain the evolution of those traits. Results indicate alternate reproductive modes evolved independently in Phrynobatrachus at least seven times, including terrestrial deposition of eggs and terrestrial, non-feeding larvae. These shifts towards alternate reproductive modes are not linked to a common temporal event. Contrary to the "key innovations" hypothesis, clades that exhibit alternate reproductive modes have lower diversification rates than those that deposit eggs aquatically. Adult habitat, pedal webbing and body size have no effect on diversification rates. Though these traits putatively identified as key innovations for Phrynobatrachus do not seem to be associated with increased speciation rates, they may still provide opportunities to extend into new niches, thus increasing overall diversity. [ABSTRACT FROM AUTHOR]

Abstract: Rhinoceroses (Stephanorhinus) and large bovids (Bison, Bos) from the early Middle Pleistocene of Britain are analysed with regard to their taxonomy, biometric variation, and possible biochronological significance. The localities considered are West Runton (type Cromerian), Pakefield, Westbury-sub-Mendip, and Boxgrove. The samples include important, previously undescribed material. Among the rhinos, in addition to the common Stephanorhinus hundsheimensis, upper dentitions from Pakefield and West Runton provide hints of undescribed taxa with affinity to, but distinct from, S. etruscus and S. hundsheimensis. At Boxgrove, a further rhino cf. S. megarhinus occurs, corroborating the chronological extension of this ‘Pliocene’ species into the Middle Pleistocene. A small bison referable to B. schoetensacki occurs at all sites, but in the Westbury Yellow Breccia (upper interglacial level) it is accompanied by a larger bison which may be B. priscus. Dental material from Pakefield provides evidence of additional, smaller bovid species, with features recalling Leptobos and Bubalus, but their identity is unclear; there is also larger material probably representing Bos, which if confirmed would be the oldest record of aurochs in the British Isles. [ABSTRACT FROM AUTHOR]

Abstract: Puddle frogs (Anura: Phrynobatrachidae) are one of the most species-rich sub-Saharan amphibian groups, occupying an extraordinarily diverse range of habitats. We construct the first phylogeny of puddle frogs, utilizing mitochondrial (12S rRNA, valine-tRNA, and 16S rRNA) and nuclear (RAG-1) DNA. Phylogenetic analyses are conducted using separate and combined partitions under maximum parsimony, maximum likelihood, and Bayesian criterion. Monophyly of the Phrynobatrachidae is well supported, and three major clades of Phrynobatrachus are identified. We reconstructed a biogeographic history using habitat preference, elevation, and geographic distribution. Habitat niches appear to be conserved between sister species, with the majority of species favoring forest over savanna habitats and the most recent common ancestor of the Phrynobatrachidae reconstructed as a forest species. Analyses of elevational data identify three independent colonizations of highland regions, one in each of the three major clades. Ancestral reconstructions support an East African origination of puddle frogs. Most species are restricted to one of five sub-Saharan regions and are distributed within the Eastern, Central, and Western zones with far fewer species in Southern Africa. These results elucidate the complex patterns of spatial niche partitioning that have contributed to the diversification of this widely distributed, sub-Saharan genus. [Copyright &y& Elsevier]

The article discusses a morphological study on the systematics of Phrynobatrachus scheffleri and P. kakamikro sp. n. which are frog species both found in East Africa. It says that the study used the specimens from museum collections and that morphological characters include snoutvent length (SVL), dorsal skin texture, and interorbital space (IO). It tells that DNA Sequence alignment was conducted and that frequency information was acquired via Fast Fourier Transformation. It explores the physical characteristics, the molecular genetics, and the distribution and life history of P. scheffleri and P. kakamikro sp. n.

Patterns of species divergence amongst 13 species of Phrynobatrachus from Cameroon were analysed using phylogenetic analyses of mitochondrial DNA sequence data from 12S rRNA, valine-tRNA, and 16S rRNA. A clade endemic to the mountains of western Cameroon and eastern Nigeria, part of the geologic rift zone termed the Cameroon Volcanic Line, supports the view that montane regions have acted as centres of speciation. Bioko Island (Equatorial Guinea), located 32 km off the coast of Cameroon, is populated by three different lowland Phrynobatrachus species from the mainland. Two of these species, Phrynobatrachus auritus and Phrynobatrachus cornutus reach submontane elevations on Bioko Island (up to 1200–1300 m) but are present only at lowland elevations on mainland Cameroon. A new miniature species of puddle frog of the genus Phrynobatrachus restricted to Mt Oku in the Republic of Cameroon is diagnosed on the basis of morphological characters and molecular data. Unlike all other miniature Phrynobatrachus (snout–vent length < 20 mm), males of this species have unique ventral coloration characterized by a black throat, dark brown to black pectoral and abdominal regions, and a light or white area on the proximal hind limbs. Minute spines cover the venter in males, often appearing as white asperities. The description of this new species supports the significance of this montane ecoregion as a biodiversity hotspot for anurans. [ABSTRACT FROM AUTHOR]

Abstract: A highly sensitive inductively coupled plasma mass spectrometry (ICP-MS) method with microwave-assisted sample digestion for the determination of total platinum in rat whole and ultrafiltrate plasma was developed and validated. A first step of this study concerned the optimization of the mineralization procedure, in order to obtain good extraction recovery (higher than 90%) and repeatability (less than 6%) and the absence of matrix effect. ICP-MS analysis was then performed using the “hot plasma/protective ion extraction” mode, achieving high sensitivity and very high signal/noise ratio. Iridium was added as internal standard. The method was then submitted to validation, performed according to the FDA Bioanalytical Validation Methods guidelines and to the Eurachem guide. Validation was carried out in terms of limit of detection (LOD), limit of quantitation (LOQ), linearity, precision, accuracy and stability. An instrumental LOQ of 1.9ngL−1, corresponding to a concentration of 955ngL−1 in matrix under the adopted conditions, was obtained, allowing the quantitative analysis of Pt ultratraces. Instrumental linearity was verified in the range 1.9–14,000ngL−1, corresponding to a concentration range from 955ngL−1 to 6825μgL−1 in matrix. Accuracy was evaluated by analyzing control samples for both matrices at different concentration levels; a good agreement (<15%) was obtained. Sample stability was tested by analyzing control samples maintained for 4h at room temperature or submitted to three freezing–thawing cycles. Finally, the developed method was applied to the analysis of plasma and ultrafiltrate plasma of rats treated with oxaliplatin-base drug, thus demonstrating its reliability in pharmacokinetic studies. [Copyright &y& Elsevier]

In Helicobacter pylori-induced gastritis, oxidants are generated through the interactions of bacteria in the lumen, activated granulocytes, and cells of the gastric mucosa. In this study we explored the ability of one such class of oxidants, represented by monochloramine (NH2Cl), to serve as agonists of Ca2+ accumulation within the parietal cell of the gastric gland. Individual gastric glands isolated from rabbit mucosa were loaded with fluorescent reporters for Ca2+ in the cytoplasm (fura-2 AM) or intracellular stores (mag-fura-2 AM). Conditions were adjusted to screen out contributions from metal cations such as Zn2+, for which these reporters have affinity. Exposure to NH2CI (up to 200 µM) led to dose-dependent increases in intracellular Ca2+ concentration ([Ca2+]i), in the range of 200-400 nM above baseline levels. These alterations were prevented by pretreatment with the oxidant scavenger vitamin C or a thiol-reducing agent, dithiothreitol (DTT), which shields intracellular thiol groups from oxidation by chlorinated oxidants. Introduction of vitamin C during ongoing exposure to NH2CI arrested but did not reverse accumulation of Ca2+ in the cytoplasm. In contrast, introduction of DTT or N-acetylcysteine permitted arrest and partial reversal of the effects of NH2CI. Accumulation of Ca2+ in the cytoplasm induced by NH2CI is due to release from intracellular stores, entry from the extracellular fluid, and impaired extrusion. Ca2+-handling proteins are susceptible to oxidation by chloramines, leading to sustained increases in [Ca2+]i. Under certain conditions, NH2CI may act not as an irritant but as an agent that activates intracellular signaling pathways. Anti-NH2Cl strategies should take into account different effects of oxidant scavengers and thiol-reducing agents. [ABSTRACT FROM AUTHOR]

Bioanalysis frequently involves the measurement of very low analyte concentrations in complex and potentially variable matrices. It is not possible to test in validation every possible circumstance that may be encountered when analyzing study samples; logically, therefore, some risk of obtaining erroneous results exists when validated methods are applied to study samples. An initial attempt has been made to apply a risk management tool to the bioanalytical situation, with the hope that this will stimulate further discussion on the idea of more formally addressing “risk” with regards to bioanalytical method validation. [Copyright &y& Elsevier]

An LC–MS–MS analytical method was developed for the determination of a new antidiabetic agent, JTT-501 and its main metabolite (JTP-20604) in human plasma. The compounds were isolated from plasma by protein precipitation before analysis by HPLC with atmospheric pressure positive ionisation MS–MS detection. An isotopically labelled analog of JTT-501 was used as the internal standard. Linearity was demonstrated over the calibration range of about 5–10 000 ng/ml for both compounds. The assay was validated with respect to accuracy, precision and analyte stability. This method was used for the determination of plasma concentrations for the two compounds in a clinical tolerability study. A cross-validation exercise between two different mass spectrometers, used for the determination of clinical samples, is also reported. [Copyright &y& Elsevier]

I Recommendation 1: i Urge the continued exploration of policy options that differentiate between commercial and noncommercial use of DSI, which can be practically implemented and to enable the open sharing of DSI across international borders without delay. If the ABS frameworks are extended to explicitly address DSI, they should distinguish between the commercial and noncommercial use of DSI. The debate on DSI focuses on what DSI includes, whether it is covered by the CBD or the NP and the possible implications of its inclusion or exclusion from these agreements. I Digital sequence information i (DSI), a placeholder term commonly understood to refer to information related to genetic sequences stored in a digital format, has become a foundational component to biological research and its applications, including biodiversity conservation and biotechnological innovation. [Extracted from the article]

The article focuses on a study which examined the external morphology and osteology of type of material of Phrynobatrachus nlonakoensis within the genus Arthroleptis to support a taxonomic change. External examination of the specimens showed that the species exhibits only a inner metatarsal tubercle and lacks a mid-tarsal tubercle and an outer metatarsal tubercle. The presence of rudimentary webbing on the feet of the species was previously described indicating that this species may have been assigned correctly to the genus Phyrnobatrachus.

• SPIDER, the experimental device devoted to the study of the ion source, has started operation in June 2018. • The construction of MITICA, the full-size prototype of the ITER heating neutral beam, is still in progress. • SPIDER gas injection and vacuum system is designed in order to guarantee a nominal pressure inside the Beam Source of 0.3 Pa. • SPIDER GVS is composed by several sub-systems interconnected and managed by a proper I&C architecture. • Experimental tests give evidence that the vacuum pumping system behave properly and allow the execution of long pulses. The ITER project requires at least two Heating Neutral Beam Injectors (NBIs), each accelerating up to 1 MV a 40 A beam of negative H-/D-.ions, to deliver to the plasma a total power of about 33 MW for one hour. Since these requirements have never been experimentally met, it was recognized necessary to build-up a test facility, named PRIMA including both a full-size negative ion source (SPIDER – Source for Production of Ion of Deuterium Extracted from Rf plasma) and a full prototype of the ITER injector (MITICA – Megavolt ITER Injector & Concept Advancement). This realization is made with the main contribution of the European Union, through the Joint Undertaking for ITER (F4E), the ITER Organization and Consorzio RFX (CRFX) that hosts the Test Facility in Padova, Italy. SPIDER is a Radio Frequency ion source that has the same characteristics foreseen for the ITER NBI but with beam energy limited to 100 keV. The mission of SPIDER is to increase the understanding of the source operation and to optimize the source performance in terms of extracted current density, uniformity and pulse duration. The paper describes the Gas injection and Vacuum System (GVS), from the analysis of requirements to the system commissioning. In particular, it presents the rationale behind the main design choices and specific manufacturing details of the gas injection plant feeding the RF source. Furthermore, the paper describes the interfaces with the SPIDER central interlock and safety systems. Finally, the main results of the GVS commissioning with the control and interlock systems are presented. [ABSTRACT FROM AUTHOR]

Gold welding alloys, which are used in the production of both hollow and solid gold chains, affect the optical and mechanical properties of various gold products because the corrosion resistance of the individual links depends on these properties. It is important that welding alloys with high corrosion resistance do not degrade during or after the production process. The mechanical properties of gold welding alloy wires are strongly influenced by the alloy microstructure, which has a key role in both the machinability and the quality of the wires. In the presented work, various physical and mechanical properties of gold originating from different industrial deformation processes are evaluated. Specifically, various plastic deformation grades caused by different annealing and rolling steps are analyzed. The change of the temperature, time, and velocity parameters in the annealing and lamination processes leads to the formation of different levels of residual stresses in the material, which can generate a variation in the corrosion properties of the gold wires. The change in microstructure, due to the different annealing and rolling steps, is analyzed by optical microscope (OM) and SEM observations. The residual stresses are evaluated using XRD analysis, and the variations of the mechanical properties by micro-hardness tests. The corrosion resistance is evaluated by potentiodynamic polarization tests, in which an electrolyte solution is used to simulate human sweat. Small grain size and high homogeneity of the microstructure are preferred for the final products. In this study, the samples that have been produced are shown to have lower levels of residual stresses and feature higher corrosion resistance and more favorable mechanical properties. [ABSTRACT FROM AUTHOR]

Abstract: SPIDER (Source for the Production of Ions of Deuterium Extracted from Rf plasma) is a new experimental device under development at Consorzio RFX aimed at providing a full-scale ion source prototype for MITICA (Megavolt ITer Injector and Concept Advance), the experiment devoted at supplying a full-scale prototype of the ITER Heating Neutral Beam Injector (HNB). Both experimental devices will be hosted in a new facility known as PRIMA (Padova Research on Injectors Megavolt Accelerated). The correct operation of SPIDER and MITICA will be guaranteed by process automation and plant monitoring that will be implemented using suitable controllers (cycle time greater than 10ms) in conjunction with appropriate SCADA (Supervisory Control And Data Acquisition) software. This paper presents the tests performed at Consorzio RFX to evaluate commercial and open-source SCADA packages and prepare a technical base for the selection of the SCADA system for SPIDER. Two commercial solutions and two open-source solutions (EPICS and TANGO) were investigated. The typical test-bed was represented by a SCADA system exchanging data with a PLC (Programmable Logic Controller). The case study consisted of: (a) the development of a minimal panel provided with fields for setting parameters and of a trend window; (b) the set-up of two kinds of communication, a direct connection between the SCADA and the PLC and an indirect one by means of an OPC (Object Linking and Embedding for Process Control) server. The communication performance was evaluated measuring the network traffic with a fixed number of data variables exchanged and different polling cycle times. The conclusions show that the final choice of a SCADA package for SPIDER will be between one commercial SCADA and EPICS. This choice will not depend uniquely on the results of the tests, but will be also dictated by the early schedule of the SPIDER operations. [ABSTRACT FROM AUTHOR]

Background: Leptin modulates appetite, energy expenditure and the reproductive axis by signalling via its receptor the status of body energy stores to the brain. The present study aimed to quantify the associations between 10 novel and known single nucleotide polymorphisms in genes coding for leptin and leptin receptor with performance traits in 848 Holstein-Friesian sires, estimated from performance of up to 43,117 daughter-parity records per sire. Results: All single nucleotide polymorphisms were segregating in this sample population and none deviated (P > 0.05) from Hardy-Weinberg equilibrium. Complete linkage disequilibrium existed between the novel polymorphism LEP-1609, and the previously identified polymorphisms LEP-1457 and LEP-580. LEP-2470 associated (P < 0.05) with milk protein concentration and calf perinatal mortality. It had a tendency to associate with milk yield (P < 0.1). The G allele of LEP-1238 was associated (P < 0.05) with reduced milk fat concentration, reduced milk protein concentration, longer gestation length and tended to associate (P < 0.1) with an increase in calving difficulty, calf perinatal mortality and somatic cells in the milk. LEP-963 exhibited an association (P < 0.05) with milk fat concentration, milk protein concentration, calving difficulty and gestation length. It also tended to associate with milk yield (P < 0.1). The R25C SNP associated (P < 0.05) with milk fat concentration, milk protein concentration, calving difficulty and length of gestation. The T allele of the Y7F SNP significantly associated with reduced angularity (P < 0.01) and reduced milk protein yield (P < 0.05). There was also a tendency (P < 0.1) for Y7F to associate with increased body condition score, reduced milk yield and shorter gestation (P < 0.1). A80V associated with reduced survival in the herd (P < 0.05). Conclusions: Several leptin polymorphisms (LEP-2470, LEP-1238, LEP-963, Y7F and R25C) associated with the energetically expensive process of lactogenesis. Only SNP Y7F associated with energy storage. Associations were also observed between leptin polymorphisms and calving difficulty, gestation length and calf perinatal mortality. The lack of an association between the leptin variants investigated with calving interval in this large data set would question the potential importance of these leptin variants, or indeed leptin, in selection for improved fertility in the Holstein-Friesian dairy cow. [ABSTRACT FROM AUTHOR]

Secretory compartments of neurons, endocrine cells, and exocrine glands are acidic and contain high levels of labile Zn2t Previously, we reported evidence that acidity is regulated, in part, by the content of Zn2+ in the secretory [i.e., tubulovesicle (TV)] compartment of the acid-secreting gastric parietal cell. Here we report studies focusing on the mechanisms of Zn2+ transport by the TV compartment in the mammalian (rabbit) gastric parietal cell. Uptake of Zn2+ by isolated TV structures was monitored with a novel application of the fluorescent Zn2+ reporter N-(6-methoxy-8-quinolyl)-para-toluenesulfonamide (TSQ). Uptake was suppressed by removal of external AlP or blockade of H+-K+-ATPase that mediates luminal acid secretion. Uptake was diminished with dissipation of the proton gradient across the TV membrane, suggesting Zn2+/H+ antiport as the connection between Zn2+ uptake and acidity in the TV lumen. In isolated gastric glands loaded with the reporter fluozin-3, inhibition of H+-K+-ATPase arrested the flow of Zn2+ from the cytoplasm to the TV compartment and secretory stimulation with forskolin enhanced vectorial movement of cytoplasmic Zn2+ into the tubulovesicle/lumen (TV/L) cornpartment. Our findings suggest that Zn2+ accumulation in the TV/L compartment is physiologically coupled to secretion of acid. These findings offer novel insight into mechanisms regulating Zn2+ homeostasis in the gastric parietal cell and potentially other cells in which acidic subcellular compartments serve signature functional roles. [ABSTRACT FROM AUTHOR]

[Display omitted] • Genomic phylogeography of western Central African montane puddle frogs. • Hybrids form a ladder-like pattern between parental species in phylogenetic trees. • A deep mtDNA divergence is not reflected in genome-wide data. • Hybrids are morphologically intermediate in these largely cryptic frogs. • Biogeographic history of montane forests of the Cameroon Volcanic Line. Puddle frogs of the Phrynobatrachus steindachneri species complex are a useful group for investigating speciation and phylogeography in Afromontane forests of the Cameroon Volcanic Line, western Central Africa. The species complex is represented by six morphologically relatively cryptic mitochondrial DNA lineages, only two of which are distinguished at the species level – southern P. jimzimkusi and Lake Oku endemic P. njiomock , leaving the remaining four lineages identified as ' P. steindachneri '. In this study, the six mtDNA lineages are subjected to genomic sequence capture analyses and morphological examination to delimit species and to study biogeography. The nuclear DNA data (387 loci; 571,936 aligned base pairs) distinguished all six mtDNA lineages, but the topological pattern and divergence depths supported only four main clades: P. jimzimkusi , P. njiomock , and only two divergent evolutionary lineages within the four ' P. steindachneri ' mtDNA lineages. One of the two lineages is herein described as a new species, P. amieti sp. nov. Reticulate evolution (hybridization) was detected within the species complex with morphologically intermediate hybrid individuals placed between the parental species in phylogenomic analyses, forming a ladder-like phylogenetic pattern. The presence of hybrids is undesirable in standard phylogenetic analyses but is essential and beneficial in the network multispecies coalescent. This latter approach provided insight into the reticulate evolutionary history of these endemic frogs. Introgressions likely occurred during the Middle and Late Pleistocene climatic oscillations, due to the cyclic connections (likely dominating during cold glacials) and separations (during warm interglacials) of montane forests. The genomic phylogeographic pattern supports the separation of the southern (Mt. Manengouba to Mt. Oku) and northern mountains at the onset of the Pleistocene. Further subdivisions occurred in the Early Pleistocene, separating populations from the northernmost (Tchabal Mbabo, Gotel Mts.) and middle mountains (Mt. Mbam, Mt. Oku, Mambilla Plateau), as well as the microendemic lineage restricted to Lake Oku (Mt. Oku). This unique model system is highly threatened as all the species within the complex have exhibited severe population declines in the past decade, placing them on the brink of extinction. In addition, Mount Oku is identified to be of particular conservation importance because it harbors three species of this complex. We, therefore, urge for conservation actions in the Cameroon Highlands to preserve their diversity before it is too late. [ABSTRACT FROM AUTHOR]

Abstract: Solutions of benzenesulfonic acid (BSA) in acrylonitrile in the range 1.02–6.53moldm−3 were studied by FT-Raman spectroscopy. Spectra in the region of the acid Snzenesulfonate anion SO3 stretching bands were analysed by band-fitting procedures in order to ascertain the degree of acid dissociation. This parameter changes from 0.42 (1.02M solution) to 0.185 (6.53M solution) despite the strong character of the acid. Interaction of acrylonitrile with undissociated BSA produces a new band in the ν(Cspectral region, displaced +21.4cm−1 and assigned to acrylonitrile molecules H-bonded to BSA. This displacement is in accord with the strong H-donor character of the acid. From the concentration of H-bonded acrylonitrile, the mean number of H-bonds in which each solvent molecule participates can be calculated. This number changes from ca. 0.2 in the less concentrated solution up to ca. 2.4 in the most concentrated solution. These results suggest that BSA–acrylonitrile complexes of fixed stoichiometry do not occur in the range of concentrations studied here. [Copyright &y& Elsevier]

Solutions of benzenesulfonic acid (BSA) and 4-toluenesulfonic acid monohydrate (PTSA) in dimethylsulfoxide (DMSO) were studied by FT-Raman spectroscopy in the concentration range 1.0–3.5 mol dm-3 (BSA) and 1.0–4.8 mol dm-3 (PTSA). Spectra in the region of the Raman acid complex band (C&z.sbnd;S+C&z.sbnd;C+SO3) stretches, at 1124 cm-1 were analysed by band-fitting procedures in order to ascertain the degree of acid dissociation. In BSA solutions, this parameter changes from 0.78 at 1.02 M to 0.47 at 3.5 M, despite the strong character of the acid. Interaction of DMSO with undissociated BSA produces a new band in the solvent ν(C&z.sbnd;S) Raman spectral region near 671 cm-1, displaced >15.0 cm-1, and assigned to DMSO molecules H-bonded to BSA. In PTSA solutions, hydrogen bonds are formed with the oxonium ion (H3O+) dissociated from the acid. In this case, the displacement observed is only >10.0 cm-1, indicating a weaker interaction. From the concentration of H-bonded DMSO, the solute/solvent coordination number and its inverse, the mean number of H-bonds participating in bonding with each solvent molecule can be calculated. This coordination number changes in BSA solutions in bimodal way, passing through a maximum and reaching a limit of 2 in the most concentrated solution. This number agrees with that found in the solid solvate BSA·2DMSO. In PTSA solutions, the general trend is similar, but low coordination numbers are obtained, in agreement with the low acidity of the oxonium ion. The bimodal behaviour observed in both acids is explained by the self-associated structure of the solvent. [Copyright &y& Elsevier]

Using integrative approaches, a new large-bodied species of Phrynobatrachus is described from a series of 48 specimens from the montane forests of the West Usambara and North Pare Mountains of Tanzania. The most distinguishing morphological feature separating Phrynobatrachus ambanguluensis sp. nov from similar species is the markedly overhanging and pointed upper jaw and snout. Mitochondrial 16S rRNA indicates that the new species differs from all other species with published sequence data by a minimum distance of 4.75% and is sister to P. krefftii, with which it has been confused in the past. The new species is known from two forest reserves and is of high conservation concern given these areas are highly impacted by anthropogenic change. [ABSTRACT FROM AUTHOR]

• An LC–MS/MS method for the simultaneous quantitation of enmetazobactam (also known as AAI101) and cefepime in human plasma was developed and validated. • Enmetazobactam and cefepime and their stable labelled internal standards were extracted from human plasma by protein precipitation. • The method validated over the range 0.05–50 μg/mL for enmetazobactam and 0.5–500 μg/mL for cefepime proved to be precise, accurate and selective. • This method was successfully applied to measure the concentrations of enmetazobactam and cefepime in human plasma samples following intravenous administration. A simple ultra-performance liquid chromatography-tandem mass spectrometry (UPLC–MS/MS) method was developed and validated for the simultaneous analysis enmetazobactam (also known as AAI101) and cefepime in human plasma. Sample preparation was based on protein precipitation with acetonitrile. Separation was performed on Acquity BEH HILIC column (50 mm × 2.1 mm, 1.7 μm) with a mobile phase containing ammonium formate in water and acetonitrile. The analytes were analyzed with the corresponding isotopically labeled internal standards and were detected in multiple reactions monitoring (MRM) using API 5000 triple-quadrupole mass spectrometer with electrospray (ESI) source operating in positive ion mode. The calibration curves were linear over the selected ranges (r > 0.9970 for both analytes). The intra and inter-assay precision of the Quality Control samples showed CV ≤ 15% and the accuracy was within 85 and 115% in all cases for both compounds. The lower limit of quantification was 0.05 μg/mL for enmetazobactam and 0.5 μg/mL for cefepime. [ABSTRACT FROM AUTHOR]

SPIDER, ITER's full-size beam source at the Neutral Beam Test Facility (NBTF), has been operational since 2018. SPIDER's mission is to optimize the operation of the beam source in order to reuse SPIDER's experience on MITICA, the full-size prototype of the ITER Neutral Beam Injector, and in the ITER injectors. The exploitation of SPIDER started with short, low-performance pulses lasting up to a few seconds and progressed to obtain long pulses up to 3000 seconds. Furthermore, the integration of plant and diagnostic systems has grown over time. The amount of data collected per pulse provide a measure of evolution: it has gone from a few tens of MB in the first campaign pulses to the current average value of over 130 GB, most of which produced by infrared and visible cameras. From the first operation onwards, the control systems have also evolved, including components and functions initially not foreseen or developed in a preliminary form. This includes the progressive integration of plant and diagnostic systems and of protection and safety functions. The paper initially focuses on the architecture of the SPIDER control systems, i.e. CODAS, the system delivering conventional control and data management, the central interlock system, delivering plant protection, and the central safety system delivering people and environment safety. Since we developed all systems according to the ITER guidelines for implementing control systems, the integrated SPIDER control, interlock and safety systems may provide an interesting example for developers of ITER plant systems. The paper then describes how the top-down definition and implementation of operating states and operational scenarios provides the framework for the integration of control, interlock and safety systems and the basic elements for successful operation. Finally, the paper reports the lessons learned during these years of operation with particular attention to the progressive, continuous evolution and recommissioning of systems. [ABSTRACT FROM AUTHOR]

• An LC-MS/MS method was validated to simultaneously quantify CHF6550 and its main metabolite CHF6671 in rat plasma over the range 50–50000 pg/mL. • A LC-MS/MS scientific validation was performed for the quantification of CHF6550 and CHF6671 in lung homogenate. • A protein precipitation was set up to extract CHF6550 and CHF6671 from plasma and lung homogenates. A selective and sensitive liquid chromatography-tandem mass spectrometry method was developed and validated for accurate determination of CHF6550 and its main metabolite in rat plasma and lung homogenate samples. All biological samples were prepared by simple protein precipitation method using deuterated internal standards. The analytes were separated on a HSS T3 analytical column with 3.2 min run time at flow rate of 0.5 mL/min. The detection was performed on a triple-quadrupole tandem mass spectrometer equipped with positive-ion electrospray ionization by selected-reaction monitoring of the transitions at m / z 735.3 → 98.0 for CHF6550 and m / z 638.3 → 319.2 and 638.3 → 376.2 for CHF6671. The calibration curves for plasma samples were linear between 50 and 50000 pg/mL for both analytes. The calibration curves for lung homogenate samples were linear within 0.1–100 ng/mL for CHF6550 and 0.3–300 ng/mL for CHF6671. The method was successfully applied to a 4-week toxicity study. [ABSTRACT FROM AUTHOR]

LNA-i-miR-221, a 13-mer oligonucleotide, is a new miR-221 inhibitor that could be used as a novel drug for multiple myeloma. Herein, an ion-pair reversed phase liquid chromatography–tandem mass spectrometry (LC–MS/MS) method has been developed and validated for the quantification of LNA-i-miR-221 in rat plasma. Plasma samples were prepared with an initial phenol/chloroform/isoamyl alcohol liquid–liquid extraction followed by a solid phase extraction. Chromatographic separation was performed with a gradient system on a HALO C18 column using hexafluoro-2-propanol/triethylamine buffer and methanol as mobile phase at a flow rate of 0.4 mL/min. Under these conditions LNA-i-miR-221 and the analogue internal standard are co-eluted at 1.2 min. The detection was carried out in multiple reaction monitoring (MRM) mode using a negative electrospray ionization (ESI) interface. The assay showed a good linearity within the calibration range 10–10000 ng/mL. The precision, accuracy, and recovery values were found to be <15% (<20% at LLOQ), 100 ± 15%, and 97.6–103.7%, respectively. This method was successfully applied to measure the concentrations of LNA-i-miR-221 in plasma samples following the intravenous administration during a 4-week toxicity study in rats. [ABSTRACT FROM AUTHOR]

Development projects in west Central Africa are proceeding at an unprecedented rate, often with little concern for their effects on biodiversity. In an attempt to better understand potential impacts of a road development project on the anuran amphibian community, we conducted a biodiversity assessment employing multiple methodologies (visual encounter transects, auditory surveys, leaf litter plots and pitfall traps) to inventory species prior to construction of a new road within the buffer zone of Moukalaba-Doudou National Park, Gabon. Because of difficulties in morphological identification and taxonomic uncertainty of amphibian species observed in the area, we integrated a DNA barcoding analysis into the project to improve the overall quality and accuracy of the species inventory. Based on morphology alone, 48 species were recognized in the field and voucher specimens of each were collected. We used tissue samples from specimens collected at our field site, material available from amphibians collected in other parts of Gabon and the Republic of Congo to initiate a DNA barcode library for west Central African amphibians. We then compared our sequences with material in GenBank for the genera recorded at the study site to assist in identifications. The resulting COI and 16S barcode library allowed us to update the number of species documented at the study site to 28, thereby providing a more accurate assessment of diversity and distributions. We caution that because sequence data maintained in GenBank are often poorly curated by the original submitters and cannot be amended by third-parties, these data have limited utility for identification purposes. Nevertheless, the use of DNA barcoding is likely to benefit biodiversity inventories and long-term monitoring, particularly for taxa that can be difficult to identify based on morphology alone; likewise, inventory and monitoring programs can contribute invaluable data to the DNA barcode library and the taxonomy of complex groups. Our methods provide an example of how non-taxonomists and parataxonomists working in understudied parts of the world with limited geographic sampling and comparative morphological material can use DNA barcoding and publicly available sequence data (GenBank) to rapidly identify the number of species and assign tentative names to aid in urgent conservation management actions and contribute to taxonomic resolution. [ABSTRACT FROM AUTHOR]

The mating disruption technique has been widely used for the control of several lepidopteran pests. In the present study, we assessed the efficiency of two formulations of SPLAT Neo, a wax emulsion containing E-11-hexadecenol, with and without the insecticide cypermethrin, in affecting mating disruption of Neoleucinodes elegantalis (Guenée). We also determined the best phenological age or stage of the crop for the application of the pheromone formulation, based on its effectiveness in reducing injuries on tomato fruits. We performed two field trials. The first field trial had three treatments: (1) Areas treated once (30 days after transplanting seedlings) with SPLAT Neo (mating disruption, formulation without cypermethrin); (2) Areas treated once with SPLAT Cida Neo (attract and kill, formulation with cypermethrin), and (3) Control plots, i.e. areas treated with the growers' pest management procedures, based on pre-scheduled calendar applications of conventional insecticides. The use of SPLAT Neo with and without cypermethrin resulted in a significant season-long reduction of the average number of N. elegantalis eggs throughout the tomato cycle, compared to the control. Areas that received two SPLAT Neo applications had a lower number of males captured by monitoring pheromone traps, a lower number of eggs laid in the field, and significantly lower levels of fruit injury at pre, first, and second tomato harvests. The crop subjected to a single SPLAT Neo application, however, experienced reduction in fruit injury only at the second harvest. Our data suggest that two SPLAT Neo applications promote efficient control of N. elegantalis, resulting in significant reduction of fruit damage in tomato. [ABSTRACT FROM AUTHOR]

The ITER Neutral Beam (NBI) Test Facility, under construction in Padova, Italy consists in the ITER full scale ion source for the heating neutral beam injector, referred to as SPIDER, and the full size prototype injector, referred to as MITICA. The Control and Data Acquisition System (CODAS) for SPIDER has been developed and is going to be in operation in 2016. The system is composed of four main components: Supervision, Slow Control, Fast Control and Data Acquisition. These components interact with each other to carry out the system operation and, since they represent a common pattern in fusion experiments, software frameworks have been used for each (set of) component. In order to reuse as far as possible the architecture developed for SPIDER, it is important to clearly define the boundaries and the interfaces among the system components so that the implementation of any component can be replaced without affecting the overall architecture. This work reports the experience gained in the development of SPIDER components, highlighting the importance in the definition of generic interfaces among component, showing how the specific solutions have been adapted to such interfaces and suggesting possible approaches for the development of other ITER subsystems. [ABSTRACT FROM AUTHOR]

IOA-289 is a novel small molecule inhibitor of autotaxin developed as a first-in-class therapy of fibrotic pathologies including cancer. A method for quantitation of IOA-289 in human plasma was developed using a stable isotope labeled compound ([13C 4 ]IOA-289) as internal standard. The analytes were extracted from human plasma by protein precipitation and the analysis was performed by liquid chromatography coupled with tandem mass spectrometric detection (LCMS/MS). The chromatographic separation was performed with a gradient elution from a BEH C18 column and under these conditions the retention time and the run time were 1 and 2 min, respectively. The assay was fully validated over the range 3–3000 ng/mL, proved to be accurate, precise and selective and was successfully applied to quantitate IOA-289 in plasma samples from subjects in a first-in-humanclinical trial. • IOA-289 is a novel ATX inhibitor in clinical development for the treatment of fibrotic pathologies including cancer. • An LC-MS/MS method to quantify IOA-289 in human plasma was developed and validated over the range 3-3000 ng/mL. • Protein precipitation was used to extract IOA-289 and its stable labelled internal standard from human plasma samples. • This validated assay was applied to measure concentrations of IOA-289 in human plasma in a first-in-human trial. [ABSTRACT FROM AUTHOR]

For many spatial processes, there is a natural need to find out the point of origin on the basis of the available scatter of observations; think, for instance, of finding out the home base of a criminal given the actual distribution of crime scenes, or the outbreak source of an epidemics. In this article, we build on the topological weighted centroid (TWC) methodology that has been applied in previous research to the reconstruction of space syntax problems, for example, of problems where all relevant entities are of spatial nature so that the relationships between them are inherently spatial and need to be properly reconstructed. In this article, we take this methodology to a new standard by tackling the new and challenging task of analyzing space semantics problems, where entities are characterized by properties of a nonspatial nature and must therefore be properly spatialized. We apply the space semantics version of the TWC methodology to a particularly hard problem: the reconstruction of global political and economic relationships on the basis of a small-dimensional qualitative dataset. The combination of a small set of spatial and nonspatial sources of information allows us to elucidate some intriguing and counterintuitive properties of the inherent global economic order and, in particular, to highlight its long-term structural features, which interestingly point toward the idea of longue durée developed by the distinguished French historian Fernand Braudel. [ABSTRACT FROM AUTHOR]

Artificial neural networks can be currently considered as one of the most important emerging tools in multivariate analysis due to their ability to deal with non-liner complex systems. In this work, a recently proposed neural network, called K-Contractive Map (K-CM), is presented and its performance in classification is evaluated towards other well-known classification methods. K-CM exploits the non-linear variable relationships provided by the Auto-CM neural network to obtain a fuzzy profiling of the samples and then applies the k-NN classifier to evaluate the class membership of samples. The algorithm Training with Input Selection and Testing (TWIST) is applied prior to K-CM to perform training/test data splitting for model parameter optimization and validation. This novel classification strategy was evaluated on ten different datasets and the obtained results were generally satisfactory. [ABSTRACT FROM AUTHOR]

Populations of many frogs have declined alarmingly in recent years, placing nearly one third of the > 6,000 species under threat of extinction. Declines have been attributed largely to habitat loss, environmental degradation and/or infectious diseases such as chytridiomycosis. Many frogs undergo dramatic natural population fluctuations such that long-term data are required to determine population trends without undue influence of stochastic factors. We present long-term quantitative data (individuals encountered per person hour of searching) for four monotypic frog genera endemic to an Afromontane region of exceptional importance but growing conservation concern: one endemic to the Ethiopian highlands (Spinophrynoides osgoodi) and three endemic to the Bale Mountains (Altiphrynoides malcolmi, Balebreviceps hillmani, Ericabatrachus baleensis), collected during 15 field trips to the Bale Mountains between 1971 and 2009. Only a single confirmed sighting of S. osgoodi has been made since 1995. The other three species have also declined, at least locally. E. baleensis appears to have been extirpated at its type locality and at the same site B. hillmani has declined. These declines are in association with substantial habitat degradation caused by a growing human population. Chytrid fungus has been found on several frog species in Bale, although no dead or moribund frogs have been encountered. These results expose an urgent need for more amphibian surveys in the Bale Mountains. Additionally, we argue that detrimental human exploitation must be halted immediately in at least some parts of the Harenna Forest if a conservation crisis is to be averted. [ABSTRACT FROM AUTHOR]

Abstract: The ITER Heating Neutral Beam injectors will be implemented in three steps: development of the ion source prototype, development of the full injector prototype, and, finally, construction of up to three ITER injectors. The first two steps will be carried out in the ITER neutral beam test facility under construction in Italy. The ion source prototype, referred to as SPIDER, which is currently in the development phase, is a complex experiment involving more than 20 plant units and operating with beam-on pulses lasting up to 1h. As for control and data acquisition it requires fast and slow control (cycle time around 0.1ms and 10ms, respectively), synchronization (10ns resolution), and data acquisition for about 1000 channels (analogue and images) with sampling frequencies up to tens of MS/s, data throughput up to 200MB/s, and data storage volume of up to tens of TB/year. The paper describes the architecture of the SPIDER control and data acquisition system, discussing the SPIDER requirements and the ITER CODAC interfaces and specifications for plant system instrumentation and control. [Copyright &y& Elsevier]

The cost of monitoring greenhouse gas emissions from landfill sites is of major concern for regulatory authorities. The current monitoring procedure is recognised as labour intensive, requiring agency inspectors to physically travel to perimeter borehole wells in rough terrain and manually measure gas concentration levels with expensive hand-held instrumentation. In this article we present a cost-effective and efficient system for remotely monitoring landfill subsurface migration of methane and carbon dioxide concentration levels. Based purely on an autonomous sensing architecture, the proposed sensing platform was capable of performing complex analytical measurements in situ and successfully communicating the data remotely to a cloud database. A web tool was developed to present the sensed data to relevant stakeholders. We report our experiences in deploying such an approach in the field over a period of approximately 16 months. [ABSTRACT FROM AUTHOR]

Abstract: The taxonomy and biostratigraphic significance of horses (Equus), deer (Capreolus, Dama, Cervus, Cervalces, Praemegaceros, Megaloceros) and pigs (Sus) from key British early Middle Pleistocene sites are investigated using a biometric approach. The sites compared are West Runton (type Cromerian), Pakefield, Little Oakley, Westbury-sub-Mendip, and Boxgrove. The samples include a significant amount of previously undescribed material. Stenonid horses dominate at Pakefield and West Runton, caballines at Westbury and Boxgrove, corresponding to the Mimomys/Arvicola division. The deer of Boxgrove include relatively large roe and small red deer, the latter distinguishing it from the Westbury Pink Breccia. The poorly-known giant deer Praemegaceros dawkinsi spans both the Mimomys (Little Oakley, Pakefield) and Arvicola (Boxgrove) zones of the Cromerian Complex. There is a marked shift in cervid abundance from predominant megacerines (Mimomys zone) to predominant red deer (Arvicola zone). [ABSTRACT FROM AUTHOR]

Abstract: Chemokines are known to regulate the chemotaxis of leukocytes and play an important role in immunological processes. Chemokine receptors are widely distributed in hematopoietic cells and are often co-localized with the hematopoietic-specific G16 and its close relative, G14. Yet, many chemokine receptors utilize pertussis toxin-sensitive Gi proteins for signaling. Given that both G16 and G14 are capable of linking Gi-coupled receptors to the stimulation of phospholipase Cβ, we examined the capacity of six CC chemokine receptors (CCR1, CCR2a, CCR2b, CCR3, CCR5 and CCR7) to interact with G14 and G16 in a heterologous expression system. Among the CC chemokine receptors tested, CCR1, CCR2b, and CCR3 were capable of mediating chemokine-induced stimulation of phospholipase Cβ via either G14 or G16. The G14/G16-mediated responses exhibited CC chemokine dose-dependency and were resistant to pertussis toxin (PTX) treatment. In contrast, CCR2a, CCR5 and CCR7 were unable to interact with G14 and G16. Under identical experimental conditions, all six CC chemokine receptors were fully capable of inhibiting adenylyl cyclase via Gi as well as stimulating phospholipase Cβ via 16z44, a G16/z chimera that possesses increased promiscuity toward Gi-coupled receptors. Moreover, CCR1-mediated ERK1/2 phosphorylation was largely PTX-insensitive in THP-1 monocytic cells that endogenously express Gα16. In addition, CCR1 agonist was less efficacious in mediating chemotaxis of THP-1 cells following the knockdown of Gα16 by overexpressing siRNA, indicating the participation of Gα16 in CCR1-induced cell migration. These results show that different CC chemokine receptors can discriminate against G14 and G16 for signal transduction. [Copyright &y& Elsevier]

Abstract: Operation of the new RFX machine has started in fall 2004, using a completely renewed version of its MDSplus data acquisition system. The new system runs under Linux and is highly distributed, employing approximately 20 machines which perform local data acquisition and communicate with a central server. The overall experience after several months of operation has been quite successful. In particular, the following aspects represent the major changes, besides the migration from VMS to Linux: [-] exclusive usage of the MDSplus scripting language TDI to write the device-specific application code; [-] exclusive usage of Java, and in particular of jScope, for data display in the control room and in the offices; [-] exclusive usage of Java for the coordination tools. [Copyright &y& Elsevier]

During acute exacerbations of inflammatory bowel diseases, oxidants are generated through the interactions of bacteria in the lumen, activated granulocytes, and cells of the colon mucosa. In this study we explored the ability of one such class of oxidants, represented by monochloramine (NH2CI), to serve as agonists of Ca2+ and Zn2+ accumulation within the colonocyte. Individual colon crypts prepared from Sprague-Dawley rats were mounted in perfusion chambers after loading with fluorescent reporters fura 2-AM and fluozin 3-AM. These reporters were characterized, in situ, for responsiveness to Ca2+ and Zn2+ in the cytoplasm. Responses to different concentrations of NH2Cl (50, 100, and 200 µM) were monitored. Subsequent studies were designed to identify the sources and mechanisms of NH2Cl-induced increases in Ca2+ and Zn2+ in the cytoplasm. Exposure to NH2CI led to dose-dependent increases in intracellular Ca2+ concentration ([Ca2+]i) in the range of 200-400 nM above baseline levels. Further studies indicated that NH2CI-induced accumulation of Ca2+ in the cytoplasm is the result of release from intracellular stores and basolateral entry of extracellular Ca2+ through store-operated channels. In addition, exposure to NH2CI resulted in dose-dependent and sustained increases in intracellular Zn2+ concentration ([Zn2+]i) in the nanomolar range. These alterations were neutralized by dithiothreitol, which shields intracellular thiol groups from oxidation. We conclude that Ca2+- and Zn2+-handling proteins are susceptible to oxidation by chloramines, leading to sustained, but not necessarily toxic, increases in [Ca2+]i and [Zn2+]i. Under certain conditions, NH2CI may act not as a toxin but as an agent that activates intracellular signaling pathways. [ABSTRACT FROM AUTHOR]

Summary: Objective:: This paper aims to present a specific optimized experimental protocol (EP) for classification and/or prediction problems. The neuro-evolutionary algorithms on which it is based and its application with two selected real cases are described in detail. The first application addresses the problem of classifying the functional (FD) or organic (OD) forms of dyspepsia; the second relates to the problem of predicting the 6-month follow-up outcome of dyspeptic patients treated by helicobacter pylori (HP) eradication therapy. Methods and material:: The database built by the multicentre observational study, performed in Italy by the NUD-look Study Group, provided the material studied: a collection of data from 861 patients with previously uninvestigated dyspepsia, being referred for upper gastrointestinal endoscopy to 42 Italian Endoscopic Services. The proposed EP makes use of techniques based on advanced neuro-evolutionary systems (NESs) and is structured in phases and steps. The use of specific input selection (IS) and training and testing (T&T) techniques together with genetic doping (GenD) algorithm is described in detail, as well as the steps taken in the two benchmark and optimization protocol phases. Results:: In terms of accuracy results, a value of 79.64% was achieved during optimization, with mean benchmark values of 64.90% for the linear discriminant analysis (LDA) and 68.15% for the multi layer perceptron (MLP), for the classification task. A value of 88.61% was achieved during optimization for the prediction task, with mean benchmark values of 49.32% for the LDA and 70.05% for the MLP. Conclusions:: The proposed EP has led to the construction of inductors that are viable and usable on medical data which is representative but highly not linear. In particular, for the classification problem, these new inductors may be effectively used on the basal examination data to support doctors in deciding whether to avoid endoscopic examinations; whereas, in the prediction problem, they may support doctors’ decisions about the advisability of eradication therapy. In both cases the variables selected indicate the possibility of reducing the data collection effort and also of providing information that can be used for general investigations on symptom relevance. [Copyright &y& Elsevier]

Polymeric drug conjugates are a new and experimental class of drug delivery systems with pharmacokinetic promises. The antineoplastic drug camptothecin was linked to a water-soluble polymeric backbone (MAG-CPT) and administrated as a 30 min infusion over 3 consecutive days every 4 weeks to patients with malignant solid tumours. The objectives of our study were to determine the maximal tolerated dose, the dose-limiting toxicities, and the plasma and urine pharmacokinetics of MAG-CPT, and to document anti-tumour activity. The starting dose was 17 mg m[sup -2] day[sup -1]. Sixteen patients received 39 courses at seven dose levels. Maximal tolerated dose was at 68 mg m[sup -2] day[sup -1] and dose-limiting toxicities consisted of cumulative bladder toxicity. MAG-CPT and free camptothecin were accumulated during days 1-3 and considerable amounts of MAG-CPT could still be retrieved in plasma and urine after 4-5 weeks. The half-lives of bound and free camptothecin were equal indicating that the kinetics of free camptothecin were release rate dependent. In summary, the pharmacokinetics of camptothecin were dramatically changed, showing controlled prolonged exposure of camptothecin. Haematological toxicity was relatively mild, but serious bladder toxicity was encountered which is typical for camptothecin and was found dose limiting. [ABSTRACT FROM AUTHOR]