bluuebunny/crossref_metadata_2025 huggingface dataset:
Impact of Food Restriction on Ovarian Development, RFamide‐Related Peptide‐3 and the Hypothalamic–Pituitary–Ovarian Axis in Pre‐Pubertal Ewes
Authors: Li H , Song H , Huang M , Nie H , Wang Z , Wang F
Published: July 2014

Content

RFamide‐related peptide‐3 (RFRP‐3), the mammalian ortholog of gonadotropin‐inhibiting hormone, has been implicated as a mediator between reproduction and energy balance. This study aimed to investigate the physiological effects of RFRP‐3 on the process of ovarian development in food‐restricted pre‐pubertal ewes. The results showed that food restriction significantly inhibited the ovarian development and follicular growth. The data of qPCR in the hypothalamic–pituitary–ovarian (HPO) axis showed that food restriction not only upregulated RFRP‐3 mRNA expression but also downregulated the mRNA expression of gonadotropin‐releasing‐hormone receptor, follicle‐stimulating hormone receptor and luteinizing hormone receptor (LHR). Immunohistochemistry of RFRP‐3 in the ovaries suggested that RFRP‐3 may regulate the follicular development. These results suggested that the changes of RFRP‐3 in response to food restriction might influence the HPO axis and inhibit ovarian development.
Restoring the American Chestnut: Optimizing Founder Spacing to Promote Population Growth and Genetic Diversity Retention
Authors: Rogstad Steven H. , Pelikan Stephan
Published: July 2014

Efforts are underway to return the American chestnut (Castanea dentata) to eastern forests of North America following its decline due to the introduction of the chestnut blight (Cryphonectria parasitica). Approaches include developing blight‐resistant chestnut lines through breeding programs and via genetic engineering. Reestablishment of resistant chestnut to eastern forests would produce one of the most extensive ecological restoration transformations ever attempted. However, this undertaking is costly and optimization of reintroduction methods is needed. We used the computer programNEWGARDENto model whether some patterns of founder placement (regular vs. random spacing at differing densities) produce more rapidly expanding populations across a range of gene dispersal distance conditions (via both offspring and pollen). For a simulated introduction project employing 169 founders, placing founders randomly in a square of side 0.85 km produced higher rates of predicted population growth compared with larger or smaller squares under near gene dispersal conditions; this side distance was 1.0 km under far gene dispersal conditions. After 100 population bouts of mating and under near gene dispersal conditions, the trial with founder placement producing the greatest population expansion rate exhibited a 314% increase in census size compared with the founder pattern yielding the slowest expansion. Neither loss of alleles nor inbreeding or subdivision was significantly increased under the founder placement patterns yielding the most descendants. Exploring different numerical and geometrical founding scenarios usingNEWGARDENcan provide first estimates of founding patterns or stand manipulations that will return the most descendants produced per founder planted in restoration projects.
Increase in Wedge‐tailed Shearwaters and Changes in Soil Nutrients following Removal of Alien Mammalian Predators and Nitrogen‐fixing Plants at Kaena Point, Hawaii
Authors: VanderWerf Eric A. , Young Lindsay C. , Crow Susan E. , Opie Eryn , Yamazaki Hironao , Miller Christopher J. , Anderson David G. , Brown Leland S. , Smith David G. , Eijzenga Jakob
Published: July 2014

A predator‐proof fence was built at Kaena Point Natural Area Reserve, Hawaii in 2010 as part of an ecosystem restoration project. All non‐native mammalian predators were removed and are now excluded. Non‐native plants are being removed and native species are being outplanted. We monitored abundance and reproduction of Puffinus pacificus (wedge‐tailed shearwaters), collected soil samples before and after fence construction, and examined the relationship between changes in shearwater numbers and soil nutrients. Shearwater numbers increased over time, from 11 young produced in 1994 to 3,274 in 2012. The average number of shearwaters produced during the 3 years before and after fence construction increased from 614 ± 249 to 2,359 ± 802 (384% increase). The average number of shearwater pairs attempting to nest also increased during the same periods, from 3,265 ± 827 to 4,726 ± 826 (45% increase). Soil samples from 2010 to 2013 showed an overall decline in concentration of ammonium (NH4+) and no change in concentration of nitrate (NO3−) or orthophosphate (PO43−). However, there was a positive relationship between changes in shearwater numbers and changes in ammonium. Examination of spatial patterns in nutrient abundance showed that the highest nutrient concentrations occurred in areas dominated by the non‐native nitrogen‐fixing plants Leucaena leucocephala and Prosopis pallida. Removal of these plants caused local nutrient declines, but increases in shearwater numbers have countered this at some points. We anticipate that shearwaters and other seabirds will replace non‐native plants as the dominant source of nitrogen and phosphorous and facilitate recovery of a native‐dominated plant assemblage.
Soil Properties and Spatial Processes Influence Bacterial Metacommunities within a Grassland Restoration Experiment
Authors: Murphy Cheryl A. , Foster Bryan L.
Published: July 2014

Metacommunity theory proposes that a collection of local communities are linked by dispersal and the resulting compositions are a product of both niche‐based (species sorting) and spatial processes. Determining which of these factors is most important in different habitats can provide insight into the regulation of community assembly. To date, the metacommunity organization of heterotrophic soil bacteria is largely unknown. Spatial variation of soil bacterial communities could arise from (1) the resource heterogeneity produced by plant communities through root exudation and/or litter inputs; (2) the heterogeneity of soil environmental properties; and (3) pure spatial processes, including dispersal limitation and stochastic assembly. Understanding the relative importance of these factors for soil bacterial community structure and function could increase our ability to restore soil communities. We utilized an ongoing tallgrass prairie restoration experiment in northeastern Kansas to assess if restoring native plant communities produced changes in bacterial communities 6 years after restoration. We further examined the relative importance of the spatial heterogeneity of plant communities, soil properties, and pure spatial effects for bacterial community structure in the old‐field restoration site. We found that soil bacterial communities were not influenced by plant restoration, but rather, by the local heterogeneity of soil environmental properties (16.9% of bacterial community variation) and pure spatial effects (11.1%). This work also stresses the idea that restoring bacterial communities can take many years to accomplish due to the inherent changes that occur to the soil after cultivation and the time it takes for the re‐establishment of soil quality.
Survival and Growth of Planted Uniola paniculata and Dune Building Using Surrogate Wrack on Perdido Key Florida, U.S.A.
Authors: Hooton Natalie , Miller Deborah L. , Thetford Mack , Sean Claypool B.
Published: July 2014

The increasing number of stresses on coastal dune ecosystems requires the use of more effective restoration strategies to enhance dune‐building and increase vegetation reestablishment. In this study, the use of a wheat straw as a surrogate wrack was an effective method to improve growth of spring planted Uniola paniculata (sea oats). Approximately 1,000 U. paniculata plugs were planted within 21 × 4 m plots at six replicate sites. Two weeks later, plantings were divided into 11 × 4 m subplots with half of the subplots receiving five bales of wheat straw and the remaining subplots receiving no wheat straw. This surrogate wrack layer measured approximately 10 cm in depth. Mean aboveground biomass of U. paniculata 6 months after planting with surrogate wrack was 9.25 ± 1.00 g compared with 2.18 ± 0.24 g without surrogate wrack. Number of tillers, tiller height, and basal width were also greater at the end of the first growing season for plants treated with surrogate wrack (p < 0.05). Two years after planting, significantly more inflorescences occurred and aboveground biomass (g/m2) was greater with than without surrogate wrack. Sand accumulation was notably greater with surrogate wrack (11.16 cm) than without wrack (7.78 cm) 8 months after planting (p = 0.1093). However, relative sand accumulation was significantly greater with than without surrogate wrack 2 years after planting. Increased sand accumulation suggests surrogate wrack either directly or indirectly traps more sand by creating an additional obstacle or promoting the growth of dune grasses.
Respiratory disease and respiratory physiology: Putting lung function into perspective interstitial lung disease
Authors: Berend Norbert
Published: July 2014

The interstitial lung diseases pathologically involve the pulmonary interstitium but may also involve the airways, pleura and pulmonary circulation. They may be idiopathic, be part of other conditions, or be related to drug or environmental exposures. This review will focus on diagnostic and prognostic information provided by lung function tests in the idiopathic interstitial pneumonias, particularly idiopathic pulmonary fibrosis and non‐specific interstitial pneumonia. These disorders are characterized by small stiff lungs with impaired gas exchange. Lung function tests, particularly lung volumes and gas transfer, used initially on patient presentation and then repeatedly on follow up, together with high‐resolution computed tomography scans, can generate predictive formulae which are superior to single tests and can be used to provide useful information to assess the natural history of the disease or guide therapy. The concomitant presence of emphysema may mask the degree of restriction and may have adverse prognostic implications when accompanied by pulmonary hypertension.
Five Books on Sacrifice: New Approaches in Sacrifice Studies
Authors: O'Leary Joseph
Published: July 2014

These books, each of which is grounded in familiarity with historical sources and at the same time alert to philosophical and theological questions, reveal that sacrificial studies are thriving. Grand theories have been enfeebled, but a rich repertory of hermeneutical strategies is being applied all the more freely to the vast material from many cultures. Bloodshed is no longer indisputably central, even in discussion of the classical and well‐documented traditions of India, Israel, and Greece. Past attempts to rationalize sacrifice, through spiritualization for example, are confuted by the sturdy texture of ritual. Despite the opacity of archaic rituals and texts, the social function of sacrificial customs and their potential pathologies are better understood, and interconnect with sacrificial dynamics in our own culture. The sacrificial interpretation of Calvary and the Eucharist is better appreciated as a rich and powerful New Testament construct, despite attempts to whittle it away. Yet those such as René Girard who urge a change of theological paradigm now have impressive critical resources at their disposal.
A Methodology for Risk Analysis Based on Hybrid Bayesian Networks: Application to the Regasification System of Liquefied Natural Gas Onboard a Floating Storage and Regasification Unit
Authors: Martins Marcelo Ramos , Schleder Adriana Miralles , Droguett Enrique López
Published: July 2014

This article presents an iterative six‐step risk analysis methodology based on hybrid Bayesian networks (BNs). In typical risk analysis, systems are usually modeled as discrete and Boolean variables with constant failure rates via fault trees. Nevertheless, in many cases, it is not possible to perform an efficient analysis using only discrete and Boolean variables. The approach put forward by the proposed methodology makes use of BNs and incorporates recent developments that facilitate the use of continuous variables whose values may have any probability distributions. Thus, this approach makes the methodology particularly useful in cases where the available data for quantification of hazardous events probabilities are scarce or nonexistent, there is dependence among events, or when nonbinary events are involved. The methodology is applied to the risk analysis of a regasification system of liquefied natural gas (LNG) on board an FSRU (floating, storage, and regasification unit). LNG is becoming an important energy source option and the world's capacity to produce LNG is surging. Large reserves of natural gas exist worldwide, particularly in areas where the resources exceed the demand. Thus, this natural gas is liquefied for shipping and the storage and regasification process usually occurs at onshore plants. However, a new option for LNG storage and regasification has been proposed: the FSRU. As very few FSRUs have been put into operation, relevant failure data on FSRU systems are scarce. The results show the usefulness of the proposed methodology for cases where the risk analysis must be performed under considerable uncertainty.
The Impact of Mega‐Catastrophes on Insurers: An Exposure‐Based Analysis of the U.S. Homeowners’ Insurance Market
Authors: Hagendorff Bjoern , Hagendorff Jens , Keasey Kevin
Published: July 2014

Insurance is a key risk‐sharing mechanism that protects citizens and governments from the losses caused by natural catastrophes. Given the increase in the frequency and intensity of natural catastrophes over recent years, this article analyzes the performance effects of mega‐catastrophes for U.S. insurance firms using a measure of market expectations. Specifically, we analyze the share price losses of insurance firms in response to catastrophe events to ascertain whether mega‐catastrophes significantly damage the performance of insurers and whether different types of mega‐catastrophes have different impacts. The main message from our analysis is that the impact of mega‐catastrophes on insurers has not been too damaging. While the exact impact of catastrophes depends on the nature of the event and the degree of competition within the relevant insurance market (less competition allows insurers to recoup catastrophe losses through adjustments to premiums), our overall results suggest that U.S. insurance firms can adequately manage the risks and costs of mega‐catastrophes. From a public policy perspective, our results show that insurance provides a robust means of sharing catastrophe losses to help reduce the financial consequences of a catastrophe event.
A Scenario‐Based Evaluation of the Middle East Respiratory Syndrome Coronavirus and the Hajj
Authors: Gardner Lauren M. , Rey David , Heywood Anita E. , Toms Renin , Wood James , Travis Waller S. , Raina MacIntyre C.
Published: July 2014

Between April 2012 and June 2014, 820 laboratory‐confirmed cases of the Middle East respiratory syndrome coronavirus (MERS‐CoV) have been reported in the Arabian Peninsula, Europe, North Africa, Southeast Asia, the Middle East, and the United States. The observed epidemiology is different to SARS, which showed a classic epidemic curve and was over in eight months. The much longer persistence of MERS‐CoV in the population, with a lower reproductive number, some evidence of human‐to‐human transmission but an otherwise sporadic pattern, is difficult to explain. Using available epidemiological data, we implemented mathematical models to explore the transmission dynamics of MERS‐CoV in the context of mass gatherings such as the Hajj pilgrimage, and found a discrepancy between the observed and expected epidemiology. The fact that no epidemic occurred in returning Hajj pilgrims in either 2012 or 2013 contradicts the long persistence of the virus in human populations. The explanations for this discrepancy include an ongoing, repeated nonhuman/sporadic source, a large proportion of undetected or unreported human‐to‐human cases, or a combination of the two. Furthermore, MERS‐CoV is occurring in a region that is a major global transport hub and hosts significant mass gatherings, making it imperative to understand the source and means of the yet unexplained and puzzling ongoing persistence of the virus in the human population.
Modeling Adversaries in Counterterrorism Decisions Using Prospect Theory
Authors: Merrick Jason R. W. , Leclerc Philip
Published: July 2014

Counterterrorism decisions have been an intense area of research in recent years. Both decision analysis and game theory have been used to model such decisions, and more recently approaches have been developed that combine the techniques of the two disciplines. However, each of these approaches assumes that the attacker is maximizing its utility. Experimental research shows that human beings do not make decisions by maximizing expected utility without aid, but instead deviate in specific ways such as loss aversion or likelihood insensitivity. In this article, we modify existing methods for counterterrorism decisions. We keep expected utility as the defender's paradigm to seek for the rational decision, but we use prospect theory to solve for the attacker's decision to descriptively model the attacker's loss aversion and likelihood insensitivity. We study the effects of this approach in a critical decision, whether to screen containers entering the United States for radioactive materials. We find that the defender's optimal decision is sensitive to the attacker's levels of loss aversion and likelihood insensitivity, meaning that understanding such descriptive decision effects is important in making such decisions.
The Drivers of Month-of-Birth Differences in Children’s Cognitive and Non-Cognitive Skills
Authors: Crawford Claire , Dearden Lorraine , Greaves Ellen
Published: July 2014

Previous research has found that children who are born later in the academic year have lower educational attainment, on average, than children who are born earlier in the year, especially at younger ages; much less is known about the mechanisms that drive this inequality. The paper uses two complementary identification strategies to estimate an upper bound of the effect of age at test by using rich data from two UK birth cohorts. We find that differences in the age at which cognitive skills are tested accounts for the vast majority of the difference in these outcomes between children who are born at different times of the year, whereas the combined effect of the other factors (age of starting school, length of schooling and relative age) is close to zero. This suggests that applying an age adjustment to national achievement test scores may be an appropriate policy response to overcome the penalty that is associated with being born later in the academic year. Age at test does not, however, explain all of the difference in children's view of their own scholastic competence. Age adjusting national achievement test scores may help to overcome differences in ability beliefs between children who are born at different times of the year, but our results suggest that additional policy responses may be required.
The NTT transcription factor promotes replum development in Arabidopsis fruits
Authors: Marsch‐Martínez Nayelli , Zúñiga‐Mayo Víctor M. , Herrera‐Ubaldo Humberto , Ouwerkerk Pieter B. F. , Pablo‐Villa Jeanneth , Lozano‐Sotomayor Paulina , Greco Raffaella , Ballester Patricia , Balanzá Vicente , Kuijt Suzanne J. H. , Meijer Annemarie H. , Pereira Andy , Ferrándiz Cristina , de Folter Stefan
Published: July 2014

Fruits are complex plant structures that nurture seeds and facilitate their dispersal. The Arabidopsis fruit is termed silique. It develops from the gynoecium, which has a stigma, a style, an ovary containing the ovules, and a gynophore. Externally, the ovary consists of two valves, and their margins lay adjacent to the replum, which is connected to the septum that internally divides the ovary. In this work we describe the role for the zinc‐finger transcription factor NO TRANSMITTING TRACT (NTT) in replum development. NTT loss of function leads to reduced replum width and cell number, whereas increased expression promotes replum enlargement. NTT activates the homeobox gene BP, which, together with RPL, is important for replum development. In addition, the NTT protein is able to bind the BP promoter in yeast, and when this binding region is not present, NTT fails to activate BP in the replum. Furthermore, NTT interacts with itself and different proteins involved in fruit development: RPL, STM, FUL, SHP1 and SHP2 in yeast and in planta. Moreover, its genetic interactions provide further evidence about its biological relevance in replum development.
Safety of intrathecal administration of cytosine arabinoside and methotrexate in dogs and cats
Authors: Genoni S. , Palus V. , Eminaga S. , Cherubini G. B.
Published: July 2014

The objective of the study was to retrospectively evaluate the short‐term safety of intrathecal administration of cytosine arabinoside alone or in combination with methotrexate in dogs and cats. One hundred and twelve dogs and eight cats admitted between September 2008 and December 2013, diagnosed with suspected inflammatory (meningoencephalomyelitis of unknown aetiology) or neoplastic disease affecting brain or spinal cord and treated with an intrathecal administration of cytosine arabinoside alone or in combination with methotrexate were included in the study. Recorded information regarding possible adverse events during administration while recovering from anaesthesia and during hospitalization period were evaluated. The results showed that one patient developed generalized tonic‐clonic seizure activity after administration of cytosine arabinoside and methotrexate during recovery from anaesthesia, however responded to intravenous administration of diazepam. On the base of our results we can conclude that intrathecal administration of cytosine arabinoside alone or in combination with methotrexate is a safe procedure in dogs and cats.
Mechanical ventilation and management of an adult horse with presumptive botulism
Authors: Taylor Sandra D. , Toth Balazs , Townsend Wendy M. , Bentley Robin Timothy
Published: July 2014

Objective

To describe the clinical course, management, and outcome of a horse with a presumptive diagnosis of botulism treated with long‐term mechanical ventilation.

Case Summary

A 6‐year‐old Quarter Horse gelding with a history of esophageal obstruction was evaluated for progressive tetraparesis. Generalized and progressive skeletal muscle weakness characterized by recumbency, decreased tongue, tail, eyelid, and anal tone, and respiratory failure was observed. Anticholinergic signs including decreased salivation, xerophthalmia, and ileus were also noted. A presumptive diagnosis of botulism was made, although mouse inoculation and spore identification testing were negative. Pentavalent botulism antitoxin was administered on Day 3. The horse was maintained on a water mattress and was managed with mechanical ventilation for 2 weeks. Complications encountered included necrotic rhinitis, intertrigo, decubital ulceration, jugular and cephalic vein thrombophlebitis, corneal ulceration, and transient ventricular tachycardia. The horse showed marked improvement in skeletal muscle strength and parasympathetic nervous system function, allowing it to be successfully weaned from the ventilator but suffered large colon volvulus on Day 21 and was euthanized.

New or Unique Information Provided

To the authors’ knowledge, this is the first report of successful weaning from long‐term mechanical ventilation and management of recumbency using a water mattress in an adult horse with presumptive botulism.
Possible delayed respiratory depression following intrathecal injection of morphine and bupivacaine in an alpaca
Authors: LdoVet Miguel Martínez , Murison Pamela J. , Murrell Jo
Published: July 2014

Objective

To describe general anesthesia and successful treatment of an alpaca, which developed respiratory arrest 2 hours after intrathecal injection of morphine and bupivacaine.

Case Summary

A 10‐day‐old female alpaca weighing 7.3 kg was presented to our hospital with a fractured right tibia. The cria was anesthetized to repair the fracture with a dynamic compression plate. Anesthesia was induced with IV propofol and maintained with sevoflurane in 100% oxygen. Prior to the start of surgery the alpaca received an unintended intrathecal injection of 0.6 mL of a solution of 0.5 mg morphine (0.068 mg/kg) and 1.5 mg bupivacaine (0.2 mg/kg), after an attempted lumbo‐sacral epidural. The alpaca developed respiratory arrest 120 minutes after the intrathecal injection was administered. Adequate hemoglobin‐oxygen saturation was maintained despite minimal intermittent manual ventilation, but marked hypercapnia developed (PaCO2of 17.3 KPa [130 mm Hg]). Delayed respiratory depression resulting from cephalad migration of intrathecal morphine was suspected. Ventilation was supported until the end of surgery when sevoflurane was discontinued. The trachea remained intubated, 100% oxygen was supplied, and ventilation was supported at 2–4 breaths/min for the next 60 minutes, but no attempts to breathe spontaneously were detected. Intravenous naloxone (0.3 mg [0.04 mg/kg]) was administered slowly to effect until adequate spontaneous ventilation and full consciousness returned. The anesthetic recovery of the alpaca was rapid and uneventful after the opioid antagonist was given.

New Information Provided

Delayed respiratory depression is a potential complication after intrathecal administration of morphine. Careful dose‐adjustment may reduce the risk, and close monitoring will result in early detection and treatment of this complication.
Influence of cross‐match on posttransfusion packed cell volume in feline packed red blood cell transfusion
Authors: Weltman Joel G. , Fletcher Daniel J. , Rogers Catherine
Published: July 2014

Objective

To evaluate the influence of major cross‐match on transfusion efficacy based on the change in PCV following packed red blood cell (pRBC) administration in cats.

Design

Retrospective study from January 2000 to December 2010.

Setting

University Teaching Hospital.

Animals

Two hundred nine cats received 233 type‐specific pRBC transfusions as treatment for anemia. Forty‐three transfusions were cross‐match compatible and 190 were not screened with cross‐match.

Interventions

Pretransfusion major cross‐match.

Measurements and Main Results

Signalment, body weight, dosage of pRBC transfusion, pretransfusion PCV, posttransfusion PCV, IV fluid volumes administered between the measurement of the pretransfusion PCV and posttransfusion PCV, time delay between pretransfusion PCV measurement and transfusion administration, time between administration of transfusion and posttransfusion PCV measurement, and major cross‐match testing data were extracted from the medical records of cats receiving pRBC transfusions and were evaluated for their influence on posttransfusion PCV scaled to dose of pRBC administered. The mean pretransfusion PCV was significantly lower for cross‐match compatible transfusions (13.7 ± 4.2%) compared to noncross‐matched transfusions (16.1 ± 4.5%; independent samples t‐test, P < 0.0001). The PCV increase posttransfusion scaled by dose was significantly greater for cross‐match compatible transfusions (1.02 ± 0.51%/mL/kg) than for noncross‐matched transfusions (0.74 ± 0.65%/mL/kg; independent samples t‐test, P = 0.0093). Of age, dose of pRBCs, cross‐match status, reason for transfusion, pretransfusion PCV, and dose of IV fluids administered between the pretransfusion and posttransfusion PCV, only pRBC dose, cross‐match status, and pretransfusion PCV were independent predictors of change in PCV with transfusion on multiple regression analysis (coefficient = 0.507, P < 0.0001; coefficient = 1.64, P = 0.041; coefficient = –0.235, P = 0.0009, respectively).

Conclusions

In this retrospective study, administration of type‐specific, cross‐match compatible pRBC transfusions resulted in significantly greater increases in the posttransfusion PCV when compared to administration of typed, noncross‐matched pRBCs. Future prospective studies evaluating the effect of cross‐match on transfusion efficacy in cats are warranted.
Nonlinear Reduced Order Models for the Structural Dynamics of Combustor Systems With Prestress and Friction
Authors: Jung Chulwoo , Epureanu Bogdan I. , Baik Sanghum , Huffman Marcus B.
Published: July 2014

An efficient methodology to capture the nonlinear responses of combustor systems with prestress and Coulomb friction is developed. The combustor systems experience wear at the interfaces between components due to flow-induced vibrations. In particular, wear has been observed at the interface between the transition piece and the hula seal, and at the interface between the hula seal and the liner. These interfaces are prestressed, and their vibratory response has a softening nonlinearity caused by Coulomb friction combined with microslip. In addition, the contact between the hula seal and the transition piece is that between a convex surface and a concave surface. Hence, geometric nonlinearity of the contact stiffness in the normal direction is present also. These phenomena are hard to capture by full-order finite element (FE) approaches because they require time marching or harmonic balancing of very large models. To address this issue, we develop reduced order models (ROMs) which are specifically designed to capture Coulomb friction (combined with micro- and macroslip). To demonstrate the proposed approach, a simplified hula seal is placed between two very rigid plates (which relate to the transition piece and the liner). For validation, contact elements are used to model the interface between the plates and the hula seal. Transient dynamic analysis (TDA) in ansys is applied to the full-order model. The model is shown to exhibit softening nonlinearity and microslip at all levels of prestress. To show that ROMs for this system are possible (i.e., they exist), we use proper orthogonal decomposition (POD) to show that the dynamics is dominated by a low number of spatial coherences. For a variety of frequency ranges and prestress levels, we show that a single such coherence is dominant. Next, low order models are proposed and their parameters are identified. A systematic method to identify these parameters is developed. Particular attention is paid to the amount of calculations needed for obtaining these parameters. Finally, the ROMs are validated by comparing their predictions with results from TDA for the full-order model. We show that these ROMs can accurately predict the nonlinear response of the system.
Investigation on Constraint Effect of a Reactor Pressure Vessel Subjected to Pressurized Thermal Shocks
Authors: Qian Guian , Niffenegger Markus
Published: July 2014

The integrity of a reactor pressure vessel (RPV) related to pressurized thermal shocks (PTSs) has been extensively studied. This paper introduces the method of using fracture mechanics for the integrity analysis of a RPV subjected to PTS transients. A 3-D finite element (FE) model is used to perform thermal and fracture mechanics analyses by considering both elastic and elastic–plastic material models. The results show that the linear elastic analysis leads to a more conservative result than the elastic–plastic analysis. The variation of the T-stress and Q-stress (crack tip constraint loss) of a surface crack in a RPV subjected to PTSs is studied. A shallow crack is assumed in the RPV and the corresponding constraint effect on fracture toughness of the material is quantified by the K–T method. The safety margin of the RPV is larger based on the K–T approach than based only on the K approach. The J–Q method with the modified boundary layer formulation (MBL) is used for the crack tip constraint analysis by considering elastic–plastic material properties. For all transient times, the real stress is lower than that calculated from small scale yielding (SSY) due to the loss of crack tip constraint.
Preventing infection of osseointegrated transcutaneous implants: Incorporation of silver into preconditioned fibronectin-functionalized hydroxyapatite coatings suppresses Staphylococcus aureus colonization while promoting viable fibroblast growth in vitro
Authors: Chimutengwende-Gordon Mukai , Pendegrass Catherine , Bayston Roger , Blunn Gordon
Published: July 2014

The success of transcutaneous implants depends on the achievement of a soft tissue seal by enabling fibroblasts to win the race for the surface against bacteria. Fibronectin-functionalized hydroxyapatite coatings (HAFn) have been shown to improve dermal tissue ingrowth and attachment. However, during the early postoperative period before a soft tissue seal has formed, bacterial colonization may occur. This study explored the incorporation of silver, a broad spectrum antimicrobial agent, into HAFn coatings with the aim of reducing bacterial colonization. Silver is known to have dose-dependent cytotoxic effects. Therefore, the effects of silver incorporation into HAFn coatings on both in vitro human dermal fibroblast viability and Staphylococcus aureus colonization were assessed. An electrochemical deposition technique was used to codeposit hydroxyapatite and silver (HAAg) and fibronectin was adsorbed onto this to produce HAAgFn coatings. Surfaces were preconditioned with serum to mimic the in vivo environment. Nonpreconditioned HAAg and HAAgFn coatings suppressed bacterial colonization but were cytotoxic. After serum-preconditioning, more than 90% of fibroblasts that grew on all HAAg and HAAgFn coatings were viable. The highest silver content coatings tested (HAAg100 and HAAgFn100) resulted in a greater than 99% reduction in biofilm and planktonic bacterial numbers compared to HA and HAFn controls. Although HAAg100 had greater antibacterial activity than HAAgFn100, the findings of this study indicate that fibroblasts would win the race for the surface against S aureus on both HAAg100 and HAAgFn100 after serum-preconditioning.
A method for tracking time-evolving sound speed profiles using Kalman filters
Authors: Huang Jiamin , Li Jianlong , Xu Wen
Published: July 2014

This paper implements a weighted ensemble Kalman filter for tracking time-evolving sound speed profiles. The approach first updates the particles following the procedure of the ensemble Kalman filter and then resamples the updated particles according to their importance weights. The weights are evaluated by the classical geoacoustic inversion likelihood obtained from the Bartlett power objective functions. Example illustrates that the new method outperforms the ensemble with a comparable computational load.
Movement Kinematics as an Index of the Level of Motor Skill: The Case of Indian Craftsmen Stone Knapping
Authors: Biryukova Elena V. , Bril Blandine , Frolov Alexander A. , Koulikov Mikhail A.
Published: July 2014

What are the differences between the movements of an expert exhibiting superior performance compared with those of a novice or even an experienced person? Adopting a functional approach to tool use, this study presents results from experimental field research on stone knapping from Indian craftsmen of different levels of skill. The results showed that the differences in the levels of motor skill appeared in movement variability rather than in particular kinematic content. The higher is the level of motor skill, the more kinematic solutions are used, the more stable are the functional and the more variable the nonfunctional joint loadings. This study strongly suggests that to really understand learning processes and motor expertise, naturalistic challenging activities that require years of practice need to be elicited.
Delineating Wnt Pathways in Pain
Authors: Ferrarelli Leslie K.
Published: July 2014

Targeting two branches of Wnt signaling might alleviate pain associated with cancer.
In Vivo
Assessment of SMT19969 in a Hamster Model of Clostridium difficile Infection
Authors: Weiss William , Pulse Mark , Vickers Richard
Published: July 2014

SMT19969 [2,2′-bis(4-pyridyl)3
H
,3′-
H
5,5-bibenzimidazole] is a novel narrow-spectrum nonabsorbable antibiotic currently in development for the treatment of
Clostridium difficile
infection. The comparative activities of SMT19969 and vancomycin against nonepidemic and epidemic strains of
C. difficile
were studied in an established hamster model. Against nonepidemic (VA11) strains, the survival rates of SMT19969-treated animals ranged from 80% to 95%. Vancomycin exhibited 100% protection during treatment, with relapse observed starting on day 9 and 50% survival at day 20. At 50 mg/kg of body weight, SMT19969 administered orally once daily for 5 days provided full protection of treated animals on the dosing days and through day 12 against epidemic strains. Vancomycin also protected during the dosing interval, but apparent relapse occurred earlier, starting on day 11. SMT19969 exhibited excellent
in vitro
activity, with MICs of 0.25 μg/ml for all isolates. The MICs for vancomycin were 2- to 4-fold higher at ≤0.5 to 1 μg/ml. All plasma sample concentrations of SMT19969 were below the limit of quantification (25 ng/ml) at all time points, consistent with the reported lack of bioavailability of the compound. Cecal concentrations were significantly above the MIC (ranging from 96 μg/ml to 172 μg/ml).
Asymptomatic Carriage of Group A Streptococcus Is Associated with Elimination of Capsule Production
Authors: Flores Anthony R. , Jewell Brittany E. , Olsen Randall J. , Shelburne Samuel A. , Fittipaldi Nahuel , Beres Stephen B. , Musser James M.
Published: July 2014

Humans commonly carry pathogenic bacteria asymptomatically, but despite decades of study, the underlying molecular contributors remain poorly understood. Here, we show that a group A streptococcus carriage strain contains a frameshift mutation in the
hasA
gene resulting in loss of hyaluronic acid capsule biosynthesis. This mutation was repaired by allelic replacement, resulting in restoration of capsule production in the isogenic derivative strain. The “repaired” isogenic strain was significantly more virulent than the carriage strain in a mouse model of necrotizing fasciitis and had enhanced growth
ex vivo
in human blood. Importantly, the repaired isogenic strain colonized the mouse oropharynx with significantly greater bacterial burden and had significantly reduced ability to internalize into cultured epithelial cells than the acapsular carriage strain. We conducted full-genome sequencing of 81 strains cultured serially from 19 epidemiologically unrelated human subjects and discovered the common theme that mutations negatively affecting capsule biosynthesis arise
in vivo
in the
has
operon. The significantly decreased capsule production is a key factor contributing to the molecular détente between pathogen and host. Our discoveries suggest a general model for bacterial pathogens in which mutations that downregulate or ablate virulence factor production contribute to carriage.
CysK2 from Mycobacterium tuberculosis Is an
O
-Phospho-
l
-Serine-Dependent
S
-Sulfocysteine Synthase
Authors: Steiner Eva Maria , Böth Dominic , Lössl Philip , Vilaplana Francisco , Schnell Robert , Schneider Gunter
Published: July 2014

Mycobacterium tuberculosis
is dependent on cysteine biosynthesis, and reduced sulfur compounds such as mycothiol synthesized from cysteine serve in first-line defense mechanisms against oxidative stress imposed by macrophages. Two biosynthetic routes to
l
-cysteine, each with its own specific cysteine synthase (CysK1 and CysM), have been described in
M. tuberculosis
, but the function of a third putative sulfhydrylase in this pathogen, CysK2, has remained elusive. We present biochemical and biophysical evidence that CysK2 is an
S
-sulfocysteine synthase, utilizing
O
-phosphoserine (OPS) and thiosulfate as substrates. The enzyme uses a mechanism via a central aminoacrylate intermediate that is similar to that of other members of this pyridoxal phosphate-dependent enzyme family. The apparent second-order rate of the first half-reaction with OPS was determined as
k
max
/

K
s

= (3.97 × 10
3
) ± 619 M
−1
s
−1
, which compares well to the OPS-specific mycobacterial cysteine synthase CysM with a
k
max
/

K
s

of (1.34 × 10
3
) ± 48.2. Notably, CysK2 does not utilize thiocarboxylated CysO as a sulfur donor but accepts thiosulfate and sulfide as donor substrates. The specificity constant
k
cat
/

K
m

for thiosulfate is 40-fold higher than for sulfide, suggesting an annotation as
S
-sulfocysteine synthase. Mycobacterial CysK2 thus provides a third metabolic route to cysteine, either directly using sulfide as donor or indirectly via
S
-sulfocysteine. Hypothetically,
S
-sulfocysteine could also act as a signaling molecule triggering additional responses in redox defense in the pathogen upon exposure to reactive oxygen species during dormancy.
Biological Cost of Pyocin Production during the SOS Response in Pseudomonas aeruginosa
Authors: Penterman Jon , Singh Pradeep K. , Walker Graham C.
Published: July 2014

LexA and two structurally related regulators, PrtR and PA0906, coordinate the
Pseudomonas aeruginosa
SOS response. RecA-mediated autocleavage of LexA induces the expression of a protective set of genes that increase DNA damage repair and tolerance. In contrast, RecA-mediated autocleavage of PrtR induces antimicrobial pyocin production and a program that lyses cells to release the newly synthesized pyocin. Recently, PrtR-regulated genes were shown to sensitize
P. aeruginosa
to quinolones, antibiotics that elicit a strong SOS response. Here, we investigated the mechanisms by which PrtR-regulated genes determine antimicrobial resistance and genotoxic stress survival. We found that induction of PrtR-regulated genes lowers resistance to clinically important antibiotics and impairs the survival of bacteria exposed to one of several genotoxic agents. Two distinct mechanisms mediated these effects. Cell lysis genes that are induced following PrtR autocleavage reduced resistance to bactericidal levels of ciprofloxacin, and production of extracellular R2 pyocin was lethal to cells that initially survived UV light treatment. Although typically resistant to R2 pyocin,
P. aeruginosa
becomes transiently sensitive to R2 pyocin following UV light treatment, likely because of the strong downregulation of lipopolysaccharide synthesis genes that are required for resistance to R2 pyocin. Our results demonstrate that pyocin production during the
P. aeruginosa
SOS response carries both expected and unexpected costs.
Repetitive Sequence Variations in the Promoter Region of the Adhesin-Encoding Gene
sabA
of Helicobacter pylori Affect Transcription
Authors: Harvey Vivian C. , Acio Catherine R. , Bredehoft Amy K. , Zhu Laurence , Hallinger Daniel R. , Quinlivan-Repasi Vanessa , Harvey Samuel E. , Forsyth Mark H.
Published: July 2014

The pathogenesis of diseases elicited by the gastric pathogen
Helicobacter pylori
is partially determined by the effectiveness of adaptation to the variably acidic environment of the host stomach. Adaptation includes appropriate adherence to the gastric epithelium via outer membrane protein adhesins such as SabA. The expression of
sabA
is subject to regulation via phase variation in the promoter and coding regions as well as repression by the two-component system ArsRS. In this study, we investigated the role of a homopolymeric thymine [poly(T)] tract −50 to −33 relative to the
sabA
transcriptional start site in
H. pylori
strain J99. We quantified
sabA
expression in
H. pylori
J99 by quantitative reverse transcription-PCR (RT-PCR), demonstrating significant changes in
sabA
expression associated with experimental manipulations of poly(T) tract length. Mimicking the length increase of this tract by adding adenines instead of thymines had similar effects, while the addition of other nucleotides failed to affect
sabA
expression in the same manner. We hypothesize that modification of the poly(T) tract changes DNA topology, affecting regulatory protein interaction(s) or RNA polymerase binding efficiency. Additionally, we characterized the interaction between the
sabA
promoter region and ArsR, a response regulator affecting
sabA
expression. Using recombinant ArsR in electrophoretic mobility shift assays (EMSA), we localized binding to a sequence with partial dyad symmetry −20 and +38 relative to the
sabA
+1 site. The control of
sabA
expression by both ArsRS and phase variation at two distinct repeat regions suggests the control of
sabA
expression is both complex and vital to
H. pylori
infection.
Emerging Roles for Anionic Non-Bilayer Phospholipids in Fortifying the Outer Membrane Permeability Barrier
Authors: Bishop Russell E.
Published: July 2014

Lately, researchers have been actively investigating
Escherichia coli
lptD
mutants, which exhibit reduced transport of lipopolysaccharide to the cell surface. In this issue of the
Journal of Bacteriology
, Sutterlin et al. (
H. A. Sutterlin, S. Zhang, and T. J. Silhavy, J. Bacteriol. 196:3214–3220
, 2014) now reveal an important functional role for phosphatidic acid in fortifying the outer membrane permeability barrier in certain
lptD
mutant backgrounds. These findings come on the heels of the first reports of two LptD crystal structures, which now provide a structural framework for interpreting
lptD
genetics.
‘My body's falling apart.’ Understanding the experiences of patients with advanced multimorbidity to improve care: serial interviews with patients and carers
Authors: Mason Bruce , Nanton Veronica , Epiphaniou Eleni , Murray Scott A , Donaldson Anne , Shipman Cathy , Daveson Barbara A , Harding Richard , Higginson Irene J , Munday Dan , Barclay Stephen , Dale Jeremy , Kendall Marilyn , Worth Allison , Boyd Kirsty
Published: July 2014

Objective

Multimorbidity is increasingly common in the last year of life, and associated with frequent hospital admissions. The epidemiology is well described, but patient perspectives are less understood. We report the experiences and perceptions of people with advanced multimorbidity to inform improvements in palliative and end-of-life care.

Design

Multicentre study including serial, multiperspective interviews with patients and their family carers; an interpretive analysis of experiences and understanding of living with advanced multimorbidity.

Participants

We recruited patients and their family carers using established UK clinical guidance for the identification of people anticipated to be in their last year of life.

Settings

An acute admissions unit in a Scottish regional hospital; a large English general practice; a London respiratory outpatient clinic.

Results

We analysed 87 interviews with 37 patients and 17 carers. They struggled with multiple changing medications, multiple services better aligned with single conditions such as cancer, and a lack of coordination and continuity of care. Family carers spoke of physical, mental and emotional exhaustion and feeling undervalued by professionals. Patients and carers frequently saw deteriorating health as part of ‘growing old’. Many used a ‘day-to-day’ approach to self-management that hindered engagement with advance care planning and open discussions about future care. ‘Palliative care’ and ‘dying soon’ were closely related concepts for many patients, carers and professionals, so rarely discussed.

Conclusions

Patients with advanced multimorbidity received less care than their illness burden would appear to merit. Some people did restrict their interactions with care providers to preserve autonomy, but many had a limited understanding of their multiple conditions, medications and available services, and found accessing support impersonal and challenging. Greater awareness of the needs associated with advanced multimorbidity and the coping strategies adopted by these patients and carers is necessary, together with more straightforward access to appropriate care.