bluuebunny/crossref_metadata_2025 huggingface dataset:
Modifying theLibyan fiscal regime to optimise its oil reserves and attract more foreign capital part 1:LEPSA Iproposal
Authors: Balhasan Saad A. , Towler Brian F. , Miskimins Jennifer L.
Published: June 2013

The currentExploration andProductionSharingAgreementIV(EPSA IV) has deficiencies that militate against increased capital investment inLibya's petroleum industry. This paper proposes an improved technique for determining the equity split called the ‘share equation’. The proposed share equation would simplify the Libyan fiscal regime and will provide an incentive for foreign oil companies to invest more during the contract period by raising their percentage share of production when they increase their capital expenditure. More capital expenditure will lead to increasing the recoverable reserves and will subsequently improve the oil recovery for individual fields and for the entire country. The share equation will change the percentage share of production automatically with any change in the oil price. It will increase the percentage share of production of theLibyanNationalOilCorporation when the price goes up, and increase the percentage share of production of the foreign oil companies when the oil price goes down. Furthermore, the share equation takes into consideration the probability of success in each of theLibyan basins. The foreign oil companies will get an increased reward when deciding to take more risks by exploration in unknown basins such as theKufra basin andCyrenaica platform. But, the share equation will eliminate the restrictive parameters likeAandBfactors, base factor andRratio in the currentEPSA IVmodel. This proposal for modifying theLibyan fiscal oil regime aims to increaseLibyan oil reserves and attract more foreign capital. By giving more flexibility to the foreign oil companies, theLibyan oil sector will get more contributions of foreign capital and technology. This will improveLibyan oil production and increase the remaining oil reserves. We call this new agreement theLibyanExploration andProductionSharingAgreementI.
Ectopic expression of cytosolic superoxide dismutase and ascorbate peroxidase leads to salt stress tolerance in transgenic plums
Authors: Diaz‐Vivancos Pedro , Faize Mohamed , Barba‐Espin Gregorio , Faize Lydia , Petri Cesar , Hernández José Antonio , Burgos Lorenzo
Published: June 2013

To fortify the antioxidant capacity of plum plants, genes encoding cytosolic antioxidants ascorbate peroxidase (cytapx) and Cu/Zn‐superoxide dismutase (cytsod) were genetically engineered in these plants. Transgenic plum plants expressing the cytsod and/or cytapx genes in cytosol have been generated under the control of the CaMV35S promoter. High levels of cytsod and cytapx gene transcripts suggested that the transgenes were constitutively and functionally expressed. We examined the potential functions of cytSOD and cytAPX in in vitro plum plants against salt stress (100 mm NaCl). Several transgenic plantlets expressing cytsod and/or cytapx showed an enhanced tolerance to salt stress, mainly lines C5‐5 and J8‐1 (expressing several copies of sod and apx, respectively). Transformation as well as NaCl treatments influenced the antioxidative metabolism of plum plantlets, including enzymatic and nonenzymatic antioxidants. Transgenic plantlets exhibited higher contents of nonenzymatic antioxidants glutathione and ascorbate than nontransformed control, which correlated with lower accumulation of hydrogen peroxide. Overall, our results suggest that transformation of plum plants with genes encoding antioxidant enzymes enhances the tolerance to salinity.
Identification of anaplastic lymphoma kinase break points and oncogenic mutation profiles in acral/mucosal melanomas
Authors: Niu Hai‐Tao , Zhou Qi‐Ming , Wang Fang , Shao Qiong , Guan Yuan‐Xiang , Wen Xi‐Zhi , Chen Li‐Zhen , Feng Qi‐Sheng , Li Wei , Zeng Yi‐Xin , Zhang Xiao‐Shi
Published: June 2013

Acral and mucosal melanomas, the two most common subtypes of melanoma in China, exhibit different genetic alterations and biologic behavior compared with other subtypes of melanomas. The purpose of this study was to identify the genetic alterations in patients with acral or mucosal melanomas in southern China. Fluorescence in situ hybridization (FISH), immunohistochemistry (IHC) analysis, polymerase chain reaction (PCR), and quantitative real‐time reverse transcriptase PCR (qRT‐PCR) were used to assess the anaplastic lymphoma kinase (ALK) break points. Furthermore, a mass spectrometry–based genotyping platform was used to analyze 30 acral melanomas and 28 mucosal melanomas to profile 238 known somatic mutations in 19 oncogenes. ALK break points were identified in four acral cases (6.9%). Eight (13.8%) cases harbored BRAF mutations, six (10.3%) had NRAS mutations, four (6.9%) had KIT mutations, two (3.5%) had EGFR mutations, two (3.5%) had KRAS mutations, two (3.5%) had MET mutations, one (1.7%) had an HRAS mutation, and one (1.7%) had a PIK3CA mutation. Two cases exhibited co‐occurring mutations, and one case with a BRAF mutation had a translocation in ALK. This study represents a comprehensive and concurrent analysis of the major recurrent oncogenic mutations involved in melanoma cases from southern China. These data have implications for both clinical trial designs and therapeutic strategies.
Evaluation of PAX3 genetic variants and nevus number
Authors: Ogbah Zighereda , Badenas Celia , Harland Mark , Puig‐Butille Joan A. , Elliot Fay , Bonifaci Nuria , Guino Elisabet , Randerson‐Moor Julie , Chan May , Iles Mark M. , Glass Daniel , Brown Andrew A. , Carrera Cristina , Kolm Isabel , Bataille Veronique , Spector Timothy D. , Malvehy Josep , Newton‐Bishop Julia , Pujana Miquel A. , Bishop Tim , Puig Susana
Published: June 2013

The presence of a high nevus number is the strongest phenotypic predictor of melanoma risk. Here, we describe the results of a three‐stage study directed at identifying risk variants for the high nevus phenotype. At the first stage, 263 melanoma cases from Barcelona were genotyped for 223 single‐nucleotide polymorphisms (SNPs) in 39 candidate genes. Seven SNPs in the PAX3 gene were found to be significantly associated with nevus number under the additive model. Next, the associations for seven PAX3 variants were evaluated in 1217 melanoma cases and 475 controls from Leeds; and in 3054 healthy twins from TwinsUK. Associations with high nevus number were detected for rs6754024 (P values < 0.01) in the Barcelona and Leeds datasets and for rs2855268 (P values < 0.01) in the Barcelona and the TwinsUK sets. Associations (P values < 0.001) in the opposite direction were detected for rs7600206 and rs12995399 in the Barcelona and TwinsUK sets. This study suggests that SNPs in PAX3 are associated with nevus number, providing support for PAX3 as a candidate nevus gene. Further studies are needed to examine the role of PAX3 in melanoma susceptibility.
Cilostazol improves cognitive function in patients with mild cognitive impairment: a retrospective analysis
Authors: Taguchi Akihiko , Takata Yu , Ihara Masafumi , Kasahara Yukiko , Tsuji Masahiro , Nishino Madoka , Stern David , Okada Masahiro
Published: June 2013

Background and purpose

Cerebral ischemia and accumulation of amyloid β (Aβ) are major risk factors for the development of dementia, including vascular dementia and Alzheimer's disease. Cilostazol, an antiplatelet drug, has been shown to improve cerebral circulation and reduce accumulation of Aβ. In this study, the long‐term effect of cilostazol on cognitive function was investigated retrospectively.

Methods

Medical records at Sumotoitsuki Hospital were surveyed to find all patients treated with cilostazol and evaluated by the Mini‐Mental State Examination (MMSE) during at least two visits separated by an interval of more than 6 months. Patients receiving anti‐dementia drugs were excluded. Temporal changes in MMSE scores were compared between patients treated with cilostazol (n = 70) and those who ceased administration of this drug (n = 22). The mean follow‐up period was 691 days.

Results

Decrease in MMSE score was significantly ameliorated by administration of cilostazol. Subgroup analysis revealed that cilostazol significantly improved MMSE score in patients with mild cognitive impairment, though no significant effect was observed in patients with normal cognitive function or dementia.

Conclusions

Although there are limitations to such a retrospective study, these results significantly encourage undertaking a prospective cohort study to determine the effect of cilostazol on mild cognitive impairment where no treatments currently exist.
Consumption of Bovine Spongiform Encephalopathy (BSE) Contaminated Beef and the Risk of Variant Creutzfeldt‐Jakob Disease
Authors: Chen Chu‐Chih , Wang Yin‐Han , Wu Kuen‐Yuh
Published: June 2013

To date, the variant Creutzfeldt‐Jakob disease (vCJD) risk assessments that have been performed have primarily focused on predicting future vCJD cases in the United Kingdom, which underwent a bovine spongiform encephalopathy (BSE) epidemic between 1980 and 1996. Surveillance of potential BSE cases was also used to assess vCJD risk, especially in other BSE‐prevalent EU countries. However, little is known about the vCJD risk for uninfected individuals who accidentally consume BSE‐contaminated meat products in or imported from a country with prevalent BSE. In this article, taking into account the biological mechanism of abnormal prion PrPres aggregation in the brain, the probability of exposure, and the expected amount of ingested infectivity, we establish a stochastic mean exponential growth model of lifetime exposure through dietary intake. Given the findings that BSE agents behave similarly in humans and macaques, we obtained parameter estimates from experimental macaque data. We then estimated the accumulation of abnormal prions to assess lifetime risk of developing clinical signs of vCJD. Based on the observed number of vCJD cases and the estimated number of exposed individuals during the BSE epidemic period from 1980 to 1996 in the United Kingdom, an exposure threshold hypothesis is proposed. Given the age‐specific risk of infection, the hypothesis explains the observations very well from an extreme‐value distribution fitting of the estimated BSE infectivity exposure. The current BSE statistics in the United Kingdom are provided as an example.
Beyond Value‐at‐Risk: GlueVaR Distortion Risk Measures
Authors: Belles‐Sampera Jaume , Guillén Montserrat , Santolino Miguel
Published: June 2013

We propose a new family of risk measures, called GlueVaR, within the class of distortion risk measures. Analytical closed‐form expressions are shown for the most frequently used distribution functions in financial and insurance applications. The relationship between GlueVaR, value‐at‐risk, and tail value‐at‐risk is explained. Tail subadditivity is investigated and it is shown that some GlueVaR risk measures satisfy this property. An interpretation in terms of risk attitudes is provided and a discussion is given on the applicability in nonfinancial problems such as health, safety, environmental, or catastrophic risk management.
Bringing Data to Life into an Introductory Statistics Course with Gapminder
Authors: Le Dai‐Trang
Published: June 2013

Gapminder is a free and easy to use software for visualising real‐world data in multiple dimensions. The simple format of the Cartesian coordinate system is used in a dynamic and interactive way to convey a great deal of information. This tool can be readily used to arouse students' natural curiosity regarding world events and to increase the motivation to understand statistics.
The Adaptive Nature of Eye Movements in Linguistic Tasks: How Payoff and Architecture Shape Speed‐Accuracy Trade‐Offs
Authors: Lewis Richard L. , Shvartsman Michael , Singh Satinder
Published: June 2013

We explore the idea that eye‐movement strategies in reading are precisely adapted to the joint constraints of task structure, task payoff, and processing architecture. We present a model of saccadic control that separates a parametric control policy space from a parametric machine architecture, the latter based on a small set of assumptions derived from research on eye movements in reading (Engbert, Nuthmann, Richter, & Kliegl, 2005; Reichle, Warren, & McConnell, 2009). The eye‐control model is embedded in a decision architecture (a machine and policy space) that is capable of performing a simple linguistic task integrating information across saccades. Model predictions are derived by jointly optimizing the control of eye movements and task decisions under payoffs that quantitatively express different desired speed‐accuracy trade‐offs. The model yields distinct eye‐movement predictions for the same task under different payoffs, including single‐fixation durations, frequency effects, accuracy effects, and list position effects, and their modulation by task payoff. The predictions are compared to—and found to accord with—eye‐movement data obtained from human participants performing the same task under the same payoffs, but they are found not to accord as well when the assumptions concerning payoff optimization and processing architecture are varied. These results extend work on rational analysis of oculomotor control and adaptation of reading strategy (Bicknell & Levy, ; McConkie, Rayner, & Wilson, 1973; Norris, 2009; Wotschack, 2009) by providing evidence for adaptation at low levels of saccadic control that is shaped by quantitatively varying task demands and the dynamics of processing architecture.
Canine ocular neoplasia: a review
Authors: Labelle Amber L. , Labelle Philippe
Published: June 2013

Ocular neoplasia is relatively rare in dogs but can have significant impact on vision, comfort, and longevity. Prognosis for life and for the globe varies with tumor type. In this review, the clinicopathologic features of the most common canine ocular neoplasms are detailed, with emphasis on histologic and immunohistochemical characteristics.
A comparative study of corneal sensitivity in birds of prey
Authors: Lacerda Rodrigo P. , Obón Elena , Peña Maria T. , Costa Daniel , Ríos Jose , Leiva Marta
Published: June 2013

Objective

To determine and compare the corneal sensitivity in healthy wild diurnal and nocturnal birds of prey (BP) indigenous to Catalonia (Spain), and to establish if age is a determining factor in corneal sensitivity in those species.

Methods

Ophthalmic examination was performed in 105 BP. Only birds with no ocular abnormalities were included in the study (n = 81): 21 diurnal BP (Falco tinnunculus: 16 fledglings, 5 adults) and 60 nocturnal BP (20 Athene noctua [9 fledglings, 11 adults], 20 Strix aluco [15 fledglings, 5 adults], and 20 Otus scops [6 fledglings and 14 adults]). Corneal touch threshold (CTT) was determined for each eye in five different corneal regions. Five attempts to cause a blink reflex were made in each region, and when three or more reflexes were positive, the pressure was deemed the CTT. Statistical analysis was performed using a Student's t‐test for independent data or an anova model. The results between species and age groups were compared using the Generalized Estimated Equations model.

Results

There were no significant differences between any of the corneal regions (P = 0.25), or between the right (CTT = 4.9 ± 1.7 cm) and left (CTT = 4.8 ± 1.7 cm) eye in any of the species (P = 0.692). No difference was found between diurnal and nocturnal species (P = 0.913). Considering all the species, a significant difference was found between the mean CTT of fledglings (5.4 ± 1.2 cm) and adults (4.1 ± 2 cm), P < 0.001. A significant difference was found between fledglings and adults of A. noctua (P < 0.001) and S. aluco (P = 0.002).

Conclusions

There is no significant difference in CTT between the different corneal regions in all the species studied. Corneal sensitivity is similar between diurnal and nocturnal birds of prey. Age is a determining factor in the CTT of A. noctua and S. aluco, with fledglings having a significantly higher CTT.
A systematic review of the psychometric properties of self‐reported scales assessing burn contractures reveals the need for a new tool to measure contracture outcomes
Authors: Ehanire Tosan , Vissoci Joao Ricardo Nickenig , Slaughter Keimun , Coêlho Rafael , Bond Jennifer , Rodrigues Clarissa , Pietrobon Ricardo , Levinson Howard
Published: June 2013

Approximately 40% of burn patients develop scar contractures. It is unknown which scar contracture therapy best optimizes activities of daily living (ADL).The appropriateness of self‐reported outcome tools in measuring anti‐scar contracture therapies has not been assessed. We conducted a systematic review to determine the quality of existing self‐reported scales in measuring ADL among burn patients by analyzing and comparing psychometric properties—factor analysis, validity, reliability, and responsiveness. EMBASE, LILACS, American Psychological Association PsycNET databases were searched for relevant articles. Forty‐one articles discussing 10 burn and non‐burn–specific scales met eligibility criteria of ADL assessment, and available psychometric analyses. A common strength in most scales was good overall reliability. Common weaknesses were insufficient data on factor analyses, content validity specific to ADL assessment, and responsiveness. The psychometric analyses studies on these scales had poor sample variability. There is insufficient data on the dimensionality and responsiveness of existing scales to support their use for measuring ADL in burn patients. Existing scales do not comprehensively measure ADLs as an isolated parameter. A psychometrically valid, comprehensive self‐reported burn contracture scale that measures ADLs among a diverse group of burn patients needs to be developed to optimize burn contracture treatments and develop new therapies.
Direct contact of fibroblasts with neuronal processes promotes differentiation to myofibroblasts and induces contraction of collagen matrix in vitro
Authors: Fujiwara Toshihiro , Kubo Tateki , Kanazawa Shigeyuki , Shingaki Kenta , Taniguchi Manabu , Matsuzaki Shinsuke , Gurtner Geoffrey C. , Tohyama Masaya , Hosokawa Ko
Published: June 2013

Wound healing is often delayed in the patients whose sensory and autonomic innervation is impaired. We hypothesized that existence of neurites in the skin may promote wound healing by inducing differentiation of fibroblasts into myofibroblasts with consequent wound contraction. In the current study, we examined the effect of neurons on differentiation of fibroblasts and contraction of collagen matrix in vitro using a new co‐culture model. Neuronal cell line, PC12 cells, of which the neurite outgrowth can be controlled by adding nerve growth factor, was used. Rat dermal fibroblasts were co‐cultured with PC12 cells extending neurites or with PC12 cells lacking neurites. Then, differentiation of fibroblasts into myofibroblasts and contraction of the collagen matrix was evaluated. Finally, we examined whether direct or indirect contact with neurites of PC12 cells promoted the differentiation of fibroblasts. Our results showed that fibroblasts co‐cultured with PC12 extending neurites differentiated into myofibroblasts more effectively and contracted the collagen matrix stronger than those with PC12 lacking neurites. Direct contact of fibroblasts with neurites promoted more differentiation than indirect contact. In conclusion, direct contact of fibroblasts with neuronal processes is important for differentiation into myofibroblasts and induction of collagen gel contraction, leading to promotion of wound healing.
Toll‐like receptor 4 signaling regulates the acute local inflammatory response to injury and the fibrosis/neovascularization of sterile wounds
Authors: Brancato Samielle K. , Thomay Alan A. , Daley Jean M. , Crane Meredith J. , Reichner Jonathan S. , Sabo Edmond , Albina Jorge E.
Published: June 2013

The role of Toll‐like receptor 4 (TLR4) in the regulation of inflammation and fibrosis in sterile wounds was investigated in TLR4 signal‐deficient (C3H/HeJ or TLR4−/−) and control mice using the subcutaneously implanted polyvinyl alcohol sponge wound model. Total and differential wound cell counts 1, 3, and 7 days after injury did not differ between C3H/HeJ and C3H/HeOuJ animals. Blood monocytes from both strains expressed CCR2 equally. Day one wounds in C3H/HeJ mice contained fewer Gr‐1high wound macrophages, CCL3, and CCL5, and more CCL17 than those in controls. The accumulation of CCL2, CX3CL1, tumor necrosis factor‐α, interleukin (IL)‐6, IL‐10, IL‐12, and interferon‐γ in wound fluids was not TLR4 dependent. Wound macrophages from C3H/HeJ and C3H/HeOuJ mice expressed CCR4 and CCR5, but not CCR1 or CCR3. Wound macrophage recruitment was not altered in CCR5−/− mice or in C3H/HeOuJ animals injected with neutralizing anti‐CCL3 and anti‐CCL5 antibodies. Neutralization of the CCR4 ligand CCL17 in C3H/HeJ mice did not alter wound macrophage populations. There was a twofold increase in collagen content and number of neovessels in 21‐day‐old wounds in C3H/HeJ vs. C3H/HeOuJ mice. There were no differences between strains in the number of myofibroblasts in the wounds 7 or 21 days postwounding. The increased fibrosis and angiogenesis in wounds from /HeJ mice correlated with higher concentrations of transforming growth factor‐β and fibroblast growth factor 2 in wound fluids from these animals. Wound fluids did not contain detectable lipopolysaccharide and did not induce IκBα degradation in J774.A1 macrophages. Results support a role for endogenous ligands of TLR4 in the regulation of inflammation and repair in sterile wounds.
Detection of lymphangiogenesis by near‐infrared fluorescence imaging and responses to VEGF‐C during healing in a mouse full‐dermis thickness wound model
Authors: Hall Mary A. , Robinson Holly , Chan Wenyaw , Sevick‐Muraca Eva M.
Published: June 2013

Noninvasive, longitudinal near‐infrared fluorescence (NIRF) imaging was used to detect and quantify lymphangiogenesis following a full‐dermis thickness incision in the presence and absence of locally administered vascular endothelial growth factor‐C (VEGF‐C), a well‐known regulator of lymphangiogenesis. Peripheral cytokines/chemokines were also measured in treated and sham‐injected animals. Lymphangiogenesis was detected via NIRF imaging by day 7–8 and confirmed by intravital microscopy, while angiogenesis was observed by day 2–3 postincision (PI). All lymph vessel parameters quantified were significantly greater on wounded vs. nonwounded sides of mice. Lymph vessel parameters appeared larger on wounded sides of VEGF‐C– relative to NaCl‐treated mice, although differences were not significant. Interleukin‐1α and interleukin‐22 were significantly elevated at day 7 PI relative to respective preincision levels in VEGF‐C‐treated mice, and decreased by day 21 PI to levels nearing those measured preincision. For the majority of cytokines/chemokines measured, mean responses were significantly greater in VEGF‐C– vs. NaCl‐treated animals. Local VEGF‐C administration may stimulate lymphangiogenesis during tissue repair and regeneration via mediating systemic cytokine/chemokine levels. NIRF imaging can be utilized to detect lymphangiogenesis during wound healing, and offers a promising platform to complement current methods for monitoring wound status and studying the effects of growth factors on healing.
Role of salivary vascular endothelial growth factor (VEGF) in palatal mucosal wound healing
Authors: Keswani Sundeep G. , Balaji Swathi , Le Louis D. , Leung Alice , Parvadia Jignesh K. , Frischer Jason , Yamano Seiichi , Taichman Norton , Crombleholme Timothy M.
Published: June 2013

The mucosa of alimentary tract heals more rapidly than cutaneous wounds. The underlying mechanisms of this enhanced healing have not been completely elucidated. Constant exposure to salivary growth factors has been shown to play a critical role in mucosal homeostasis and tissue repair. Angiogenesis also has an essential role in successful wound repair. One of the main angiogenic growth factors, vascular endothelial growth factor (VEGF), has a pleiotropic role in tissue repair via neovascularization, reepithelialization, and regulation of extracellular matrix. We have previously reported a critical role for salivary VEGF in bowel adaptation after small bowel resection. We hypothesize that salivary VEGF is an essential stimulus for oral mucosal tissue repair, and use the murine palatal wound model to test our hypothesis. In a loss‐of‐function experiment, we removed the primary source of VEGF production through selective submandibular gland (SMG) sialoadenectomy in a murine model and observed the effects on wound closure and neovascularization. We then performed a selective loss‐of‐function experiment using the protein VEGF‐Trap to inhibit salivary VEGF. In a gain‐of‐function experiment, we supplemented oral VEGF following SMG sialoadenectomy. After SMG sialoadenectomy, there was significant reduction in salivary VEGF level, wound closure, and vessel density. Lower levels of salivary VEGF were correlated with impaired neovascularization and reepithelialization. The selective blockade of VEGF using VEGF‐Trap resulted in a similar impairment in wound healing and neovascularization. The sole supplementation of oral VEGF after SMG sialoadenectomy rescued the impaired wound healing phenotype and restored neovascularization to normal levels. These data show a novel role for salivary‐VEGF in mucosal wound healing, and provide a basis for the development of novel therapeutics aimed at augmenting wound repair of the oral mucosa, as well as wounds at other sites in the alimentary tract.
Adenylyl cyclase 6 mediates the action of cyclic AMP‐dependent secretagogues in mouse pancreatic exocrine cells via protein kinase A pathway activation
Authors: Sabbatini Maria E. , D’Alecy Louis , Lentz Stephen I. , Tang Tong , Williams John A.
Published: June 2013

Key points

Cyclic AMP (cAMP), produced from ATP and the enzyme adenylyl cyclase (AC), plays an important role in the regulation of pancreatic exocrine cells.

We identified five AC isoforms in pancreatic exocrine cells. AC3, AC4, AC6 and AC9 are expressed in both pancreatic acini and duct fragments, whereas AC7 is expressed only in duct fragments.

In mice deficient in AC6, cAMP formation and protein kinase A activation were impaired. As a consequence, a reduction in amylase secretion and pancreatic fluid production was observed.

These results indicate that AC6 plays a regulatory role in pancreatic exocrine cells.

Abstract  Both secretin and vasoactive intestinal polypeptide (VIP) receptors are responsible for the activation of adenylyl cyclases (ACs), which increase intracellular cyclic AMP (cAMP) levels in the exocrine pancreas. There are nine membrane‐associated isoforms, each with its own pattern of expression and regulation. In this study we sought to establish which AC isoforms play a regulatory role in pancreatic exocrine cells. Using RT‐PCR, AC3, AC4, AC6, AC7 and AC9 were found to be expressed in the pancreas. AC3, AC4, AC6 and AC9 were expressed in both pancreatic acini and ducts, whereas AC7 was expressed only in pancreatic ducts. Based on known regulation by intracellular signals, selective inhibitors and stimulators were used to suggest which isoforms play an important role in the induction of cAMP formation. AC6 appeared to be an important isoform because protein kinase A (PKA), PKC and calcium all inhibited VIP‐induced cAMP formation, whereas calcineurin or calmodulin did not modify the response to VIP. Mice with genetically deleted AC6 were studied and showed reduced cAMP formation and PKA activation in both isolated pancreatic acini and duct fragments. The absence of AC6 reduced cAMP‐dependent secretagogue‐stimulated amylase secretion, and abolished fluid secretion in both in vivo and isolated duct fragments. In conclusion, several AC isoforms are expressed in pancreatic acini and ducts. AC6 mediates a significant part of pancreatic amylase and fluid secretion in response to secretin, VIP and forskolin through cAMP/PKA pathway activation.
Classification of frequency response areas in the inferior colliculus reveals continua not discrete classes
Authors: Palmer Alan R. , Shackleton Trevor M. , Sumner Christian J. , Zobay Oliver , Rees Adrian
Published: June 2013

Key points

Neurons in the auditory midbrain, the inferior colliculus, are selectively sensitive to combinations of sound frequency and level as illustrated by their frequency/level receptive fields. Different receptive field shapes have been described, but we do not know if these represent discrete classes reflecting afferent inputs from individual sources, or a more complex pattern of integration.

In this study we used objective methods to analyse the receptive fields of over 2000 neurons in the guinea pig inferior colliculus.

Subjectively we identified seven different receptive field classes, but objectively these classes formed continua with many neurons having receptive field shapes intermediate to these extremes.

These findings are consistent with neurons receiving inhibitory inputs of different strength and frequency disposition but not consistent with neurons reflecting inputs only from individual brainstem nuclei.

These results are important for understanding the functional organisation of the inferior colliculus and its role in auditory processing.

Abstract  A differential response to sound frequency is a fundamental property of auditory neurons. Frequency analysis in the cochlea gives rise to V‐shaped tuning functions in auditory nerve fibres, but by the level of the inferior colliculus (IC), the midbrain nucleus of the auditory pathway, neuronal receptive fields display diverse shapes that reflect the interplay of excitation and inhibition. The origin and nature of these frequency receptive field types is still open to question. One proposed hypothesis is that the frequency response class of any given neuron in the IC is predominantly inherited from one of three major afferent pathways projecting to the IC, giving rise to three distinct receptive field classes. Here, we applied subjective classification, principal component analysis, cluster analysis, and other objective statistical measures, to a large population (2826) of frequency response areas from single neurons recorded in the IC of the anaesthetised guinea pig. Subjectively, we recognised seven frequency response classes (V‐shaped, non‐monotonic Vs, narrow, closed, tilt down, tilt up and double‐peaked), that were represented at all frequencies. We could identify similar classes using our objective classification tools. Importantly, however, many neurons exhibited properties intermediate between these classes, and none of the objective methods used here showed evidence of discrete response classes. Thus receptive field shapes in the IC form continua rather than discrete classes, a finding consistent with the integration of afferent inputs in the generation of frequency response areas. The frequency disposition of inhibition in the response areas of some neurons suggests that across‐frequency inputs originating at or below the level of the IC are involved in their generation.
Gas System Leakage Pressure Decay©
Authors: Doyle David F.
Published: June 2013

An inactive gas piping system with minor leaks may require repressurizing if the system pressure cannot be allowed to fall to atmospheric pressure, for example, to maintain cleanliness. In this study, a simple hand calculation is developed to predict static (leakage only) pressure decay, and thus the repressurizing frequency, of such a gas piping system. This method can also be used to estimate the maximum leakage flowrate in the event that automatic repressurizing is required. This prediction method was tested and validated.
Effects of Prior Stress Relaxation on the Prediction of Creep Life Using Time and Strain Based Methods
Authors: Payten Warwick M. , Snowden Ken U. , Dean David W.
Published: June 2013

A critical requirement for both next generation conventional and nuclear plants is the development of simplified inelastic design and fitness for purposes procedures that give a reasonably accurate prediction of the complex multiaxial time dependent stress strain behavior. The accumulation of this inelastic strain in the form of coupled creep-fatigue damage over time is one of the principal damage mechanisms which will eventually lead to crack initiation in critical, high temperature equipment. Two main procedures that address creep-fatigue loading are generally used, either a time fraction or a ductility exhaustion approach. It is generally accepted that these methods enable conservative predictions within a factor of 2 to 3 and hence are reliable methods for code based design and fitness for purpose type assessments. However, for complex cycles, this may not be the case; for example, prior relaxation cycles are found to accelerate the creep rupture of the material with the result that a significant reduction in creep life can be observed. An investigation was undertaken into the influence of prior relaxation on resultant failure using a typical low alloy ferritic power station steel. Both time-based and strain based methods were used to predict the damage caused by the stress relaxation cycles followed by operation at steady state. The predictions found that while ductility exhaustion methodologies based on mean properties were adequate in predicting the failure life, time fraction methods were found to be extremely nonconservative for mean properties and only lower bound solutions provided an estimate of remaining creep life. The ASME time fraction approach, using isochronous curves was found to be extremely conservative for K = 0.67, but was able to predict similar damages to ductility exhaustion when K = 1 was used. The Monkman-Grant approach resulted in predictions that erred on the conservative side. The results have implications for both current and future conventional and nuclear power stations as it may be difficult for time based approaches to account accurately for complex cycling, shakedown conditions or stress relaxation at welds.
Damage Caused by Dynamic/Cyclic Loading of a Detonation Chamber
Authors: Takashima Yasuhito , Ohata Mitsuru , Tagawa Tetsuya , Minami Fumiyoshi , Simoens Bart , Lefebvre Michel H. , Nickell Robert E. , Koide Kenji , Kitamura Ryusuke , Hayashi Koichi , Asahina Joseph K.
Published: June 2013

The plastic damage caused by multiple dynamic loading and its influence on the ductility and toughness of 3.5% Ni steel (SA203E) and C steel (SA516M) were examined for the discussion of integrity design of detonation chambers. V-notched specimens and hourglass specimens were welded on the 1/7-scale model of a 1-ton explosive class detonation chamber and subjected to 30 detonation shots. It has been indicated that 30 detonation shots caused prestrain in the specimens. The ductility was reduced by the prestrain. The Charpy impact toughness was affected as well in a lower temperature. It has been noted that the damage is developed with fatigue crack growth at the notch root of the V-notched specimen.
Experimental Investigation of Failure Estimation Method for Stainless Steel Pipes With a Circumferential Crack Subjected to Combined Tensile and Torsion Loads
Authors: Li Yinsheng , Hasegawa Kunio , Miura Naoki , Hoshino Katsuaki
Published: June 2013

When a crack is detected in a stainless steel pipe during in-service inspections, the failure estimation method given in codes such as the ASME Boiler and Pressure Vessel Code Section XI or JSME Rules on Fitness-for-Service for Nuclear Power Plants can be applied to evaluate the structural integrity of the cracked pipe. In the current codes, the failure estimation method includes the bending moment and tensile force due to pressure. The torsion moment is assumed to be relatively small and is not considered. Recently, analytical investigations considering multiaxial loads including torsion were conducted in several previous studies by examining the limit load for pipes with a circumferential crack. A failure estimation method for the combined bending moment, torsion moment, and internal pressure was proposed. In this study, the failure behavior of pipes with a circumferential crack subjected to multiaxial loads including the torsion is investigated to provide experimental support for the failure estimation method. Experiments were carried out on small size stainless steel cylinders containing a circumferential surface or through-wall crack, subjected to the combined tensile load and torsion moment. Based on the experimental results, the proposed failure estimation method was confirmed to be applicable to cracked pipes subjected to combined tensile and torsion loads.
Critical Section Selection Methodology for the U.S. EPRTM Standard Nuclear Power Plant
Authors: Jung Se-Kwon , Goodman Adam , Harrold Joseph , Alchaar Nawar
Published: June 2013

A three-tier critical section selection methodology that is used to identify critical sections for the U.S. EPRTM standard nuclear power plant (NPP) is presented. The critical section selection methodology includes three complementary approaches: qualitative, quantitative, and supplementary. These three approaches are applied to Seismic Category I structures in a complementary fashion to identify the most critical portions of the building whose structural integrity needs to be maintained for postulated design basis events and conditions. Once the design of critical sections for a particular Seismic Category I structure is complete, the design for that structure is essentially complete for safety evaluation purposes. Critical sections, taken as a whole, are analytically representative of an “essentially complete” U.S. EPRTM design; their structural design adequacy provides reasonable assurance of overall U.S. EPRTM structural design adequacy.
Flexible Carbon Nanotube Composite Sensors for Medical Device Application
Authors: Eichhorn Wade R. , Sezen A. Serdar
Published: June 2013

Flexible carbon nanotube composite sensors for medical device applications have been developed using small loadings of multi-walled carbon nanotubes dispersed into medical grade liquid silicone rubber for the purpose of measuring stress, strain and load placed on or by a medical device. The sensors may be attached to a medical device or molded within a medical device, such as an expandable balloon.
CdZnS quantum dots formed by the Langmuir–Blodgett technique
Authors: Milekhin Alexander G. , Yeryukov Nikolay A. , Sveshnikova Larisa L. , Duda Tatyana A. , Protasov Dmitry Yu. , Gutakovskii Anton K. , Batsanov Stepan A. , Surovtsev Nikolay V. , Adichtchev Sergey V. , Himcinschi Cameliu , Dzhagan Volodymir , Haidu Francisc , Zahn Dietrich R. T.
Published: June 2013

CdZnS quantum dots (QDs) with systematically varied Zn content (from 0 to 100%) are formed in an organic matrix using the Langmuir–Blodgett technique. Annealing of the QD structures leads to a removal of the organic matrix and an increase in the Zn content for free-standing CdZnS QDs. After annealing, the size of QDs as determined from UV–vis absorption experiments is in good agreement with electron microscopy measurements. Analysis of UV–vis absorption and Raman scattering data demonstrates strong changes in the content of the CdZnS QDs upon annealing. A model of the process of QD formation is developed using the precipitation model and is found to adequately describe the experimental results.
Maintaining tumor targeting accuracy in real‐time motion compensation systems for respiration‐induced tumor motion
Authors: Malinowski Kathleen , McAvoy Thomas J. , George Rohini , Dieterich Sonja , D'Souza Warren D.
Published: June 2013

Purpose:

To determine how best to time respiratory surrogate‐based tumor motion model updates by comparing a novel technique based on external measurements alone to three direct measurement methods.

Methods:

Concurrently measured tumor and respiratory surrogate positions from 166 treatment fractions for lung or pancreas lesions were analyzed. Partial‐least‐squares regression models of tumor position from marker motion were created from the first six measurements in each dataset. Successive tumor localizations were obtained at a rate of once per minute on average. Model updates were timed according to four methods:never, respiratory surrogate‐based (when metrics based on respiratory surrogate measurements exceeded confidence limits), error‐based (when localization error ≥3 mm), and always (approximately once per minute).

Results:

Radial tumor displacement prediction errors (mean ± standard deviation) for the four schema described above were 2.4 ± 1.2, 1.9 ± 0.9, 1.9 ± 0.8, and 1.7 ± 0.8 mm, respectively. Thenever‐update error was significantly larger than errors of the other methods. Mean update counts over 20 min were 0, 4, 9, and 24, respectively.

Conclusions:

The same improvement in tumor localization accuracy could be achieved through any of the three update methods, but significantly fewer updates were required when therespiratory surrogate method was utilized. This study establishes the feasibility of timing image acquisitions for updating respiratory surrogate models without direct tumor localization.
Mechanosensitive ATP Release Maintains Proper Mucus Hydration of Airways
Authors: Button Brian , Okada Seiko F. , Frederick Charles Brandon , Thelin William R. , Boucher Richard C.
Published: June 2013

Airway epithelial cells use purinergic signaling to optimize fluid secretion and mucus clearance.
A Plant Homolog of Animal Glutamate Receptors Is an Ion Channel Gated by Multiple Hydrophobic Amino Acids
Authors: Tapken Daniel , Anschütz Uta , Liu Lai-Hua , Huelsken Thomas , Seebohm Guiscard , Becker Dirk , Hollmann Michael
Published: June 2013

Hydrophobic amino acids, rather than glutamate, activate the
Arabidopsis
glutamate receptor homolog AtGLR1.4.
Science Signaling
Podcast: 11 June 2013
Authors: Button Brian , VanHook Annalisa M.
Published: June 2013

A feedback mechanism that involves purinergic signaling ensures proper hydration of airway mucus.
Thank Your Mother
Authors: Vignieri Sacha
Published: June 2013

Mothers’ stress levels in free-ranging red squirrels increase baby growth in anticipation of overcrowding.
Synergistic Activity of Colistin plus Rifampin against Colistin-Resistant KPC-Producing Klebsiella pneumoniae
Authors: Tascini Carlo , Tagliaferri Enrico , Giani Tommaso , Leonildi Alessandro , Flammini Sarah , Casini Beatrice , Lewis Russell , Ferranti Simone , Rossolini Gian Maria , Menichetti Francesco
Published: June 2013

Infections caused by carbapenem-resistant KPC-producing
Klebsiella pneumoniae
are responsible for high rates of mortality and represent a major therapeutic challenge, especially when the isolates are also resistant to colistin. We used the checkerboard method to evaluate the synergistic activity of 10 antibiotic combinations against 13 colistin-resistant KPC-producing
K. pneumoniae
isolates (colistin MIC range of 8 to 128 mg/liter). Colistin plus rifampin was the only combination that demonstrated consistent synergistic bacteriostatic activity against 13/13 strains tested, reducing the colistin MIC below the susceptibility breakpoint (MIC ≤ 2 mg/liter) in 7/13 strains at rifampin concentrations ranging from 4 to 16 mg/liter. Bactericidal synergistic activity was also documented for 8/13 tested strains. Other antimicrobial combinations with carbapenems, gentamicin, and tigecycline showed variously synergistic results. Colistin plus rifampin also exhibited bacteriostatic synergistic activity against 4/4 colistin-susceptible KPC-producing
K. pneumoniae
isolates (colistin MIC range of 0.5 to 2 mg/liter) and 4/4 ertapenem-resistant extended-spectrum beta-lactamase (ESBL)-producing
K. pneumoniae
isolates (ertapenem MIC range of 16 to 32 mg/liter). Collectively, our data suggest that colistin plus rifampin is the most consistently synergistic combination against KPC-producing
K. pneumoniae
isolates, including colistin-resistant strains. Colistin-rifampin combinations may have a role in the treatment of multidrug-resistant
K. pneumoniae
and may possibly slow the selection of heteroresistant subpopulations during colistin therapy.
A Modified Zinc Acetate Gel, a Potential Nonantiretroviral Microbicide, Is Safe and Effective against Simian-Human Immunodeficiency Virus and Herpes Simplex Virus 2 Infection
In Vivo
Authors: Kenney Jessica , Rodríguez Aixa , Kizima Larisa , Seidor Samantha , Menon Radhika , Jean-Pierre Ninochka , Pugach Pavel , Levendosky Keith , Derby Nina , Gettie Agegnehu , Blanchard James , Piatak Michael , Lifson Jeffrey D. , Paglini Gabriela , Zydowsky Thomas M. , Robbiani Melissa , Fernández Romero José A.
Published: June 2013

We previously showed that a prototype gel comprising zinc acetate (ZA) in carrageenan (CG) protected mice against vaginal and rectal herpes simplex virus 2 (HSV-2) challenge as well as macaques against vaginal simian-human immunodeficiency virus reverse transcriptase (SHIV-RT) challenge. In this work, we modified buffers and cosolvents to obtain a stable, nearly iso-osmolal formulation and evaluated its safety and efficacy against SHIV-RT and HSV-2.
In vitro
toxicity to lactobacilli and
Candida albicans
was determined. Macaques were given daily doses of ZA and CG (ZA/CG) or CG alone vaginally for 14 days and challenged with SHIV-RT 24 h later. Mice were challenged vaginally or rectally with HSV-2 immediately after a single gel treatment to measure efficacy or vaginally 12 h after daily gel treatment for 7 days to evaluate the gel's impact on susceptibility to HSV-2 infection. The modified ZA/CG neither affected the viability of lactobacilli or
C. albicans
nor enhanced vaginal HSV-2 infection after daily ZA/CG treatment. Vaginal SHIV-RT infection of macaques was reduced by 66% (
P
= 0.006) when macaques were challenged 24 h after the last dose of gel. We observed 60% to 80% uninfected mice after vaginal (
P
< 0.0001) and rectal (
P
= 0.008) high-dose HSV-2 challenge. The modified ZA/CG gel is safe and effective in animal models and represents a potential candidate to limit the transmission of HIV and HSV-2.
First Description of KPC-2-Producing Klebsiella oxytoca in Brazil
Authors: Almeida Anna C. S. , Cavalcanti Felipe L. S. , Martins Willames M. B. , Vilela Marinalda A. , Gales Ana C. , Morais Junior Marcos A. , Morais Márcia M. C.
Published: June 2013

The present work reports the detection of the first case of nosocomial
Klebsiella oxytoca
producing class A carbapenemase KPC-2 in Brazil. The isolate KPN106 carried a 65-kb IncW-type plasmid that harbors the
bla
KPC
gene and Tn
4401
b. Moreover, we detected the presence of a class 1 integron containing a new allele,
arr-8
, followed by a 5′-truncated
dhfrIIIc
gene. In view of the recent results, we emphasize the high variability of the bacterial and genetic hosts of this resistance determinant.