bluuebunny/crossref_metadata_2025 huggingface dataset:
The Implications of Policy Stability for Renewable Energy Innovation in the United States, 1974–2009
Authors: Liang Jiaqi , Fiorino Daniel J.
Published: February 2013

Government support and commitment are of particular importance for renewable energy technology innovation activities, which are highly contingent on policy and market uncertainty. The research focus of this article is to examine the relationship between policy stability in public resource allocation and policy outcomes in renewable energy technologies. With time‐series cross‐sectional analyses, we test effects of both the stability and magnitude of federal R&D expenditures on patent applications in five renewable energy sectors (i.e., solar, wind, hydropower, geothermal, and bioenergy) from 1974 to 2009. The findings show that technology innovation is affected by both the magnitude and stability of government financial commitment. Nevertheless, when industries perceive government support over longer time frames, the magnitude effect loses explanatory power to the stability effect. In addition to federal R&D expenditures, policies pertaining to technology commercialization and marketization are a critical determinant of innovation activities. This study demonstrates that incremental, predictable, and credible expenditures facilitate renewable energy technology development. Conversely, a boom‐bust cycle of resource support fails to translate policy goals into intended results.
Reconceptualizing Major Policy Change in the Advocacy Coalition Framework: A Discourse Network Analysis of German Pension Politics
Authors: Leifeld Philip
Published: February 2013

How does major policy change come about? This article identifies and rectifies weaknesses in the conceptualization of innovative policy change in the Advocacy Coalition Framework. In a case study of policy belief change preceding an innovative reform in the German subsystem of old‐age security, important new aspects of major policy change are carved out. In particular, the analysis traces a transition from one single hegemonic advocacy coalition to another stable coalition, with a transition phase between the two equilibria. The transition phase is characterized (i) by a bipolarization of policy beliefs in the subsystem and (ii) by state actors with shifting coalition memberships due to policy learning across coalitions or due to executive turnover. Apparently, there are subsystems with specific characteristics (presumably redistributive rather than regulative subsystems) in which one hegemonic coalition is the default, or the “normal state.” In these subsystems, polarization and shifting coalition memberships seem to interact to produce coalition turnover and major policy change. The case study is based on discourse network analysis, a combination of qualitative content analysis and social network analysis, which provides an intertemporal measurement of advocacy coalition realignment at the level of policy beliefs in a subsystem.
Adult and early‐stage characters of Brassolini contain conflicting phylogenetic signal (Lepidoptera, Nymphalidae)
Authors: PENZ CARLA M. , FREITAS ANDRE V. L. , KAMINSKI LUCAS A. , CASAGRANDE MIRNA M. , DEVRIES PHILIP J.
Published: February 2013

This study examines the contribution of early‐stages and adult characters to the reconstruction of the phylogeny of Brassolini butterflies. Parsimony analyses used both equal weights and implied weights, and a series of analyses were performed. First, we analysed adult and early‐stages partitions independently and in combination for a subset of 27 species; in these cases the matrices were mostly complete. Whereas the adult partition alone produced a topology that was well resolved and congruent with previous studies, the early‐stages partition produced a poorly resolved tree under equal weights. Furthermore, implied weights produced a well‐resolved early‐stages topology that differed significantly from the adult topology. When both partitions were combined for 27 species, implied weights yielded a topology that resembled the adult tree except for the positions of Bia and Penetes, but statistical node support was generally lower. This suggests that stochastic noise increased when early‐stage characters were added to the adult partition, but the combined partitions topology was not statistically different from that based on adult characters alone. Second, given that preserved early stages are not as readily available as adults, we analysed a matrix including 45 species in which early‐stage data were missing for 18 species, and compared the topology to that produced by the adult partition alone. Results were similar to the analyses including fewer species; the combined partitions tree was similar to that from the adult partition except for the position of Bia and Penetes. We compare our findings to other genus‐level phylogenetic studies within Lepidoptera that have also used early‐stages and adult characters.
Direct Observations of Atmospheric Aerosol Nucleation
Authors: Kulmala Markku , Kontkanen Jenni , Junninen Heikki , Lehtipalo Katrianne , Manninen Hanna E. , Nieminen Tuomo , Petäjä Tuukka , Sipilä Mikko , Schobesberger Siegfried , Rantala Pekka , Franchin Alessandro , Jokinen Tuija , Järvinen Emma , Äijälä Mikko , Kangasluoma Juha , Hakala Jani , Aalto Pasi P. , Paasonen Pauli , Mikkilä Jyri , Vanhanen Joonas , Aalto Juho , Hakola Hannele , Makkonen Ulla , Ruuskanen Taina , Mauldin Roy L. , Duplissy Jonathan , Vehkamäki Hanna , Bäck Jaana , Kortelainen Aki , Riipinen Ilona , Kurtén Theo , Johnston Murray V. , Smith James N. , Ehn Mikael , Mentel Thomas F. , Lehtinen Kari E. J. , Laaksonen Ari , Kerminen Veli-Matti , Worsnop Douglas R.
Published: February 2013

Aerosol Formation

Most atmospheric aerosol particles result from a growth process that begins with atmospheric molecules and clusters, progressing to larger and larger sizes as they acquire other molecules, clusters, and particles. The initial steps of this process involve very small entities—with diameters of less than 2 nanometers—which have been difficult to observe.

Kulmala
et al.

(p.
943
; see the Perspective by

Andreae

) developed a sensitive observational protocol that allows these tiny seeds to be detected and counted, and they mapped out the process of aerosol formation in detail.
Using the Earth as a Polarized Electron Source to Search for Long-Range Spin-Spin Interactions
Authors: Hunter Larry , Gordon Joel , Peck Stephen , Ang Daniel , Lin Jung-Fu
Published: February 2013

In Search of Unparticles

The standard model of particle physics, which describes the basic building blocks of the universe and the interactions among them, is incomplete. Numerous theoretical extensions have been proposed, some of which predict long-range, spin-spin interactions. To test whether such interactions exist, a laboratory spin source is normally used.

Hunter
et al.

(p.
928
) used Earth as a polarized spin source and looked for these interactions by changing the geographical position and the orientation of the measurement apparatus. The polarized spins mainly come from the electrons in iron-containing minerals of Earth's mantle, which align in Earth's magnetic field. The large numbers of such polarized electrons allowed the extraction of upper bounds on some of the exotic spin-spin interactions far lower than those obtained in the laboratory.
Integrative Structural Biology
Authors: Ward Andrew B. , Sali Andrej , Wilson Ian A.
Published: February 2013

Integrative approaches using data from a wide variety of methods are yielding model structures of complex biological assemblies.
Mars Student Imaging Project: Real Research by Secondary Students
Authors: Klug Boonstra Sheri , Christensen Philip
Published: February 2013

The Mars Student Imaging Project, an IBI prize–winning module, provides student access to NASA scientists and spacecraft data.
Increases in Adult Life Expectancy in Rural South Africa: Valuing the Scale-Up of HIV Treatment
Authors: Bor Jacob , Herbst Abraham J. , Newell Marie-Louise , Bärnighausen Till
Published: February 2013

Cost-Benefit of ART

In the battle to control HIV, mass antiretroviral treatment (ART) costs $500 to $900 per person per year.

Bor
et al.

(p.
961
) calculated the impact of intensifying ART on the life expectancy of people living in rural KwaZulu Natal. The dates of death were collected from a population of about 100,000 people during 2000–2011: Four years before and 8 years after the scaling up of ART. Life expectancy of adults increased by more than 11 years after ART was expanded, and the economic value of the lifetimes gained were calculated to far exceed the cost of treatment.

Tanser
et al.

(p.
966
) followed nearly 17,000 HIV-uninfected individuals in KwaZulu-Natal over an 8-year period. Holding other HIV risk factors constant, individual HIV acquisition risk declined significantly with increasing ART coverage of HIV-infected people.
Lessons from Our Elders
The World Until Yesterday
What Can We Learn from Traditional Societies?

by Jared Diamond

Viking, New York, 2012. 543 pp. $36, C$38. ISBN 9780670024810. Allen Lane, London. £20. ISBN 9780713998986.
Authors: Runciman W. G.
Published: February 2013

Drawing on his experiences with the peoples of New Guinea and the anthropological literature about other traditional societies, Diamond considers practices of theirs that might help us improve our lives.
Optimizing Identification of Clinically Relevant Gram-Positive Organisms by Use of the Bruker Biotyper Matrix-Assisted Laser Desorption Ionization–Time of Flight Mass Spectrometry System
Authors: McElvania TeKippe Erin , Shuey Sunni , Winkler David W. , Butler Meghan A. , Burnham Carey-Ann D.
Published: February 2013

Matrix-assisted laser desorption ionization–time of flight mass spectrometry (MALDI-TOF MS) can be used as a method for the rapid identification of microorganisms. This study evaluated the Bruker Biotyper (MALDI-TOF MS) system for the identification of clinically relevant Gram-positive organisms. We tested 239 aerobic Gram-positive organisms isolated from clinical specimens. We evaluated 4 direct-smear methods, including “heavy” (H) and “light” (L) smears, with and without a 1-μl direct formic acid (FA) overlay. The quality measure assigned to a MALDI-TOF MS identification is a numerical value or “score.” We found that a heavy smear with a formic acid overlay (H+FA) produced optimal MALDI-TOF MS identification scores and the highest percentage of correctly identified organisms. Using a score of ≥2.0, we identified 183 of the 239 isolates (76.6%) to the genus level, and of the 181 isolates resolved to the species level, 141 isolates (77.9%) were correctly identified. To maximize the number of correct identifications while minimizing misidentifications, the data were analyzed using a score of ≥1.7 for genus- and species-level identification. Using this score, 220 of the 239 isolates (92.1%) were identified to the genus level, and of the 181 isolates resolved to the species level, 167 isolates (92.2%) could be assigned an accurate species identification. We also evaluated a subset of isolates for preanalytic factors that might influence MALDI-TOF MS identification. Frequent subcultures increased the number of unidentified isolates. Incubation temperatures and subcultures of the media did not alter the rate of identification. These data define the ideal bacterial preparation, identification score, and medium conditions for optimal identification of Gram-positive bacteria by use of MALDI-TOF MS.
High Prevalence of Asymptomatic Malaria in a Tribal Population in Eastern India
Authors: Ganguly Swagata , Saha Pabitra , Guha Subhasish K. , Biswas Asit , Das Sonali , Kundu Pratip K. , Maji Ardhendu K.
Published: February 2013

Asymptomatic infection by
Plasmodium falciparum
is an important obstacle to eliminating malaria. Asymptomatic carriers do not seek treatment for infection, and therefore they become a reservoir for the parasite. For this reason, these carriers pose a real public health risk. The systematic identification and treatment of asymptomatic infections should reduce the parasite reservoir. A large reduction in this pool will lower the chance of transmission of the disease. In this study, we screened a tribal population of 1,040 individuals in the Purulia district of West Bengal by using a dual-antigen rapid diagnostic kit (RDK), microscopy, and species-specific PCR. All positive individuals were treated with artemisinin-based combination therapy (ACT) (artesunate plus sulfadoxine-pyrimethamine) and followed for 42 days. Polymorphisms in candidate genes were screened by DNA sequencing. A significant proportion (8.4%) of the study population was infected with
P. falciparum
but showed no clinical manifestations. The PCR method was more sensitive in detecting infection than the RDK or microscopy. The efficacy of the ACT was 97%. In the
pfcrt
gene, the mutation K76T (the mutated amino acid is indicated by bold type) was found in 100% of the cases. In the
pfmdr1
gene, the mutations N86Y and Y184F were noted in 55.5% and 11% of the cases, respectively. Six different haplotypes were identified in the
pfdhfr-pfdhps
genes. Most importantly, the quintuple mutant A
16
I
51
R
59
N
108
I
164
-S
436
G
437
E
540
A
581
A
613
was found in 10% of the isolates, which is potentially important for the development of sulfadoxine-pyrimethamine resistance. A significant proportion of the study population harboring
P. falciparum
does not seek treatment and therefore serves as a reservoir for the parasite, maintaining the natural cycle. If the National Vector Borne Disease Control Programme (NVBDCP) of India is to eliminate malaria, then this hidden parasite burden needs to be addressed properly. Similar study in other parts of the country could help to determine the magnitude of the problem.
Herpes Simplex Virus 1 Infection Induces Activation and Subsequent Inhibition of the IFI16 and NLRP3 Inflammasomes
Authors: Johnson Karen E. , Chikoti Leela , Chandran Bala
Published: February 2013

Inflammasomes are multiprotein complexes that recognize pathogens and pathogen- or danger-associated molecular patterns. They induce the maturation and secretion of powerful proinflammatory interleukin-1B (IL-1β), IL-18, and IL-33 cytokines, which in turn activate expression of other immune genes and lymphocyte recruitment to the site of primary infection, thereby controlling invading pathogens. Inflammasomes are comprised of cytoplasmic sensor molecules, such as NLRP3 and AIM2 or nuclear sensor IFI16, the adaptor protein ASC (apoptosis-associated speck-like protein containing CARD), and the effector protein procaspase-1. Herpes simplex virus 1 (HSV-1), a ubiquitous virus that infects humans and establishes life-long latency, has evolved numerous mechanisms to evade host detection and immune responses. Here, we show that early duringin vitroinfection of human foreskin fibroblasts (2 to 4 h), HSV-1 induced the activation of the IFI16 and NLRP3 inflammasomes and maturation of IL-1β. Independent of viral gene expression, IFI16 recognized the HSV-1 genome in infected cell nuclei, relocalized, and colocalized with ASC in the cytoplasm. However, HSV-1 specifically targeted IFI16 for rapid proteasomic degradation at later times postinfection, which was dependent on the expression of ICP0, an immediate early protein of HSV-1. In contrast, NLRP3, AIM2, and ASC levels were not decreased. Also, caspase-1 was “trapped” in actin clusters at later time points that likely blocked the NLRP3/IFI16 inflammasome activity. In addition, the secretion of mature IL-1β was inhibited. These results suggest that though the host cell responds to HSV-1 infection by IFI16 and NLRP3 inflammasomes early during infection, HSV-1 has evolved mechanisms to shut down these responses to evade the proinflammatory consequences.
Very-Low-Density Lipoprotein (VLDL)-Producing and Hepatitis C Virus-Replicating HepG2 Cells Secrete No More Lipoviroparticles than VLDL-Deficient Huh7.5 Cells
Authors: Jammart Baptiste , Michelet Maud , Pécheur Eve-Isabelle , Parent Romain , Bartosch Birke , Zoulim Fabien , Durantel David
Published: February 2013

In the plasma samples of hepatitis C virus (HCV)-infected patients, lipoviroparticles (LVPs), defined as (very-) low-density viral particles immunoprecipitated with anti-β-lipoproteins antibodies are observed. This HCV-lipoprotein association has major implications with respect to our understanding of HCV assembly, secretion, and entry. However, cell culture-grown HCV (HCVcc) virions produced in Huh7 cells, which are deficient for very-low-density lipoprotein (VLDL) secretion, are only associated with and dependent on apolipoprotein E (apoE), not apolipoprotein B (apoB), for assembly and infectivity. In contrast to Huh7, HepG2 cells can be stimulated to produce VLDL by both oleic acid treatment and inhibition of the MEK/extracellular signal-regulated kinase (ERK) pathway but are not permissive for persistent HCV replication. Here, we developed a new HCV cell culture model to study the interaction between HCV and lipoproteins, based on engineered HepG2 cells stably replicating a blasticidin-tagged HCV JFH1 strain (JB). Control Huh7.5-JB as well as HepG2-JB cell lines persistently replicated viral RNA and expressed viral proteins with a subcellular colocalization of double-stranded RNA (dsRNA), core, gpE2, and NS5A compatible with virion assembly. The intracellular RNA replication level was increased in HepG2-JB cells upon dimethyl sulfoxide (DMSO) treatment, MEK/ERK inhibition, and NS5A overexpression to a level similar to that observed in Huh7.5-JB cells. Both cell culture systems produced infectious virions, which were surprisingly biophysically and biochemically similar. They floated at similar densities on gradients, contained mainly apoE but not apoB, and were not neutralized by anti-apoB antibodies. This suggests that there is no correlation between the ability of cells to simultaneously replicate HCV as well as secrete VLDL and their capacity to produce LVPs.
Hepatitis C Virus Replication Is Modulated by the Interaction of Nonstructural Protein NS5B and Fatty Acid Synthase
Authors: Huang Jing-Tang , Tseng Ching-Ping , Liao Mei-Huei , Lu Shao-Chun , Yeh Wei-Zhou , Sakamoto Naoya , Chen Chuan-Mu , Cheng Ju-Chien
Published: February 2013

Hepatitis C virus (HCV) nonstructural protein 5B (NS5B) is an RNA-dependent RNA polymerase (RdRp) that acts as a key player in the HCV replication complex. Understanding the interplay between the viral and cellular components of the HCV replication complex could provide new insight for prevention of the progression of HCV-associated hepatocellular carcinoma (HCC). In this study, the NS5B protein was used as the bait in a pulldown assay to screen for NS5B-interacting proteins that are present in Huh7 hepatoma cell lysates. After mass spectrophotometric analysis, fatty acid synthase (FASN) was found to interact with NS5B. Coimmunoprecipitation and double staining assays further confirmed the direct binding between NS5B and FASN. The domain of NS5B that interacts with FASN was also determined. Moreover, FASN was associated with detergent-resistant lipid rafts and colocalized with NS5B in active HCV replication complexes. In addition, overexpression of FASN enhanced HCV expression in Huh7/Rep-Feo cells, while transfection of FASN small interfering RNA (siRNA) or treatment with FASN-specific inhibitors decreased HCV replication and viral production. Notably, FASN directly increased HCV NS5B RdRp activity
in vitro
. These results together indicate that FASN interacts with NS5B and modulates HCV replication through a direct increase of NS5B RdRp activity. FASN may thereby serve as a target for the treatment of HCV infection and the prevention of HCV-associated HCC progression.
Isolation and Characterization of Current Human Coronavirus Strains in Primary Human Epithelial Cell Cultures Reveal Differences in Target Cell Tropism
Authors: Dijkman Ronald , Jebbink Maarten F. , Koekkoek Sylvie M. , Deijs Martin , Jónsdóttir Hulda R. , Molenkamp Richard , Ieven Margareta , Goossens Herman , Thiel Volker , van der Hoek Lia
Published: February 2013

The human airway epithelium (HAE) represents the entry port of many human respiratory viruses, including human coronaviruses (HCoVs). Nowadays, four HCoVs, HCoV-229E, HCoV-OC43, HCoV-HKU1, and HCoV-NL63, are known to be circulating worldwide, causing upper and lower respiratory tract infections in nonhospitalized and hospitalized children. Studies of the fundamental aspects of these HCoV infections at the primary entry port, such as cell tropism, are seriously hampered by the lack of a universal culture system or suitable animal models. To expand the knowledge on fundamental virus-host interactions for all four HCoVs at the site of primary infection, we used pseudostratified HAE cell cultures to isolate and characterize representative clinical HCoV strains directly from nasopharyngeal material. Ten contemporary isolates were obtained, representing HCoV-229E (n= 1), HCoV-NL63 (n= 1), HCoV-HKU1 (n= 4), and HCoV-OC43 (n= 4). For each strain, we analyzed the replication kinetics and progeny virus release on HAE cell cultures derived from different donors. Surprisingly, by visualizing HCoV infection by confocal microscopy, we observed that HCoV-229E employs a target cell tropism for nonciliated cells, whereas HCoV-OC43, HCoV-HKU1, and HCoV-NL63 all infect ciliated cells. Collectively, the data demonstrate that HAE cell cultures, which morphologically and functionally resemble human airwaysin vivo, represent a robust universal culture system for isolating and comparing all contemporary HCoV strains.
Delayed pneumothorax following an isolated clavicle injury
Authors: Gandham Surya , Nagar Anindyt
Published: February 2013

Isolated fractures of the clavicle have been rarely reported to be complicated by a pneumothorax. However, a delayed pneumothorax following this injury has not yet been reported in the literature. This case report describes a 19-year-old man who developed a left-sided apical pneumothorax from an ipsilateral fractured clavicle 5 days after his initial motorbike accident. Initial chest examination and radiographs showed no evidence of a pneumothorax in the accident and emergency department but a repeat radiograph in fracture clinic to assess the clavicle diagnosed an ipsilateral apical pneumothorax. He was then promptly treated with a chest drain which resolved the pneumothorax within 2 days. The clavicle fracture was treated non-operatively and after 6 weeks the patient had full function in his upper limb. Clinicians should therefore be aware of this rare complication from displaced clavicle fractures both immediately after the initial trauma and also on follow-up.
Adverse drug events in a paediatric intensive care unit: a prospective cohort
Authors: Silva Dafne C B , Araujo Orlei Ribeiro , Arduini Rodrigo G , Alonso Carolina F R , Shibata Audrey R O , Troster Eduardo J
Published: February 2013

Objectives

To describe adverse drug events (ADEs) in children under intensive care, identify risk factors and tools that can detect ADEs early, and the impact on length of stay (LOS).

Design

A prospective observational study.

Setting

Paediatric intensive care unit of a tertiary care teaching hospital.

Patients

239 patients with a mean age of 67.5 months representing 1818 days of hospitalisation in intensive care unit.

Interventions

Active search of charts and electronic patient records using triggers. The statistical analysis involved linear and logistic regression.

Measurements and main results

The average LOS was 7.6 days. There were 110 proven, probable and possible ADEs in 84 patients (35.1%). We observed 138 instances of triggers. The major classes of drugs associated with events were: antibiotics (n=41), diuretics (n=24), antiseizures (n=23), sedatives and analgesics (n=17) and steroids (n=18). The number of drugs administered was most related to the occurrence of ADEs and also to the LOS (p<0.001). The occurrence of an ADE may result in an increase in the LOS by 1.5 days per event, but this was not statistically significant in this sample. Patients aged less than 48 months also proved to be at a significant risk for ADEs, with an OR of 1.84 (95% CI 1.07 to 3.15, p=0.025). The number of drugs administered also correlated with the number of ADEs (p<0.0001). The chance of having at least one ADE increased linearly as the patient was administered more drugs.

Conclusions

The use of multiple drugs as well as lower patient age favours the occurrence of ADEs. The active search described here provides a systematic approach to this problem.
A practical technique for estimating service life of MSW leachate collection systems
Authors: Rowe R. Kerry , Yu Yan
Published: February 2013

The leachate characteristics and clogging of the leachate collection system at the Keele Valley Landfill is examined using the numerical model “BioClog”. The calculated effluent leachate concentrations (e.g., the chemical oxygen demand and calcium concentrations) and calculated calcium fraction in the clog material are in encouraging agreement with measured field data. A new practical model is developed and calibrated against the data from the sophisticated numerical model to estimate the service life of leachate collection systems in typical municipal solid waste (MSW) landfills. The procedures for using the new practical model are provided and illustrated by examples. Design charts are presented that may aid the design of leachate collection systems for typical MSW landfills.
Reliability-based load factors for blast design
Authors: Campidelli M. , Razaqpur A.G. , Foo S.
Published: February 2013

In this study the concepts of reliability are used to derive blast load factors. First, some objective criteria are proposed for the proper interpretation of pressure data gathered in arena tests. These criteria are applied to the pressure–time histories recorded during field tests involving live explosive detonated in contact with the ground. Three major shock wavefront parameters, including peak pressure, impulse, and positive phase duration are calculated. Next, statistical analysis is performed on these metrics to estimate their probability density functions and goodness-of-fit tests are carried out to gauge the appropriateness of each estimate. Using the best-fitting distribution for each wavefront metric, load factors are derived on the basis of two approaches. The first approach employs the percentiles of the three load metrics, each estimated using the pertinent probability distribution. The second approach uses concepts of reliability and presents load factors for low, medium, and high level of protection. The two sets of load factors are compared and the limitations of each approach are discussed.
Immune and oxidative stress trade-offs in four classes of Ruffs (Philomachus pugnax) with different reproductive strategies
Authors: Lozano George A. , Lank David B. , Addison Brianne
Published: February 2013

Immunity and resistance to oxidative stress are two mechanistically related aspects of self-maintenance that are usually not studied together in connection to ecological or evolutionary relevant variables. Whereas many studies compare two sexes, here we use Ruffs (Philomachus pugnax (L., 1758)), a species in which males have three alternative reproductive morphs: independents, satellites, and faeders. Previous work suggested that immune function in Ruffs depends on energetic constraints or potential of injuries. Based on their behaviour and life history, the three male morphs and females can be placed on an ordinal scale with independents at one end and females at the other, and these two explanations predict opposite patterns along this continuum. Innate and cell-mediated immunity decreased along this axis from independents to females, supporting a risk-of-injury explanation over the energetic constrains hypothesis. No such pattern was evident for oxidative stress or resistance, and no relationship was detected between immunity and oxidative resistance or stress. Hence, during the breeding season immunity reflected the risk of injury, with faeders located in the immunological continuum between females and other male morphs. Species with alternative reproductive strategies provide particularly useful systems in which to address the evolution and ecology behind physiological mechanisms.
Molecular, cellular, and muscle strip mechanics of the mdx mouse diaphragm
Authors: Bates Genevieve , Sigurdardottir Sara , Kachmar Linda , Zitouni Nedjma B. , Benedetti Andrea , Petrof Basil J. , Rassier Dilson , Lauzon Anne-Marie
Published: February 2013

Duchenne muscular dystrophy (DMD) is a lethal disorder caused by defects in the dystrophin gene, which leads to respiratory or cardiac muscle failure. Lack of dystrophin predisposes the muscle cell sarcolemmal membrane to mechanical damage. However, the role of myosin in this muscle weakness has been poorly addressed. In the current study, in addition to measuring the velocity of actin filament propulsion (υmax) of mdx myosin molecules purified from 3- and 12-mo-old control (C57Bl/10) and mdx (C57Bl/10 mdx) mouse diaphragms, we also measured myosin force production. Furthermore, we measured cellular and muscle strip force production at three mo of age. Stress (force/cross-sectional area) was smaller for mdx than control at the muscle strip level but was not different at the single fiber level. υmax of mdx myosin was not different from control at either 3 or 12 mo nor was their relative myosin force. The type I and IIb myosin heavy chain composition was not different between control and mdx diaphragms at 3 or 12 mo. These results suggest that the myosin function, as well as the single fiber mechanics, do not underlie the weakness of the mdx diaphragm. This weakness was only observed at the level of the intact muscle bundle and could not be narrowed down to a specific mechanical impairment of its individual fibers or myosin molecules.
TMEM16F is a component of a Ca2+-activated Cl− channel but not a volume-sensitive outwardly rectifying Cl− channel
Authors: Shimizu Takahiro , Iehara Takahiro , Sato Kaori , Fujii Takuto , Sakai Hideki , Okada Yasunobu
Published: February 2013

TMEM16 (transmembrane protein 16) proteins, which possess eight putative transmembrane domains with intracellular NH2- and COOH-terminal tails, are thought to comprise a Cl− channel family. The function of TMEM16F, a member of the TMEM16 family, has been greatly controversial. In the present study, we performed whole cell patch-clamp recordings to investigate the function of human TMEM16F. In TMEM16F-transfected HEK293T cells but not TMEM16K- and mock-transfected cells, activation of membrane currents with strong outward rectification was found to be induced by application of a Ca2+ ionophore, ionomycin, or by an increase in the intracellular free Ca2+ concentration. The free Ca2+ concentration for half-maximal activation of TMEM16F currents was 9.6 μM, which is distinctly higher than that for TMEM16A/B currents. The outwardly rectifying current-voltage relationship for TMEM16F currents was not changed by an increase in the intracellular Ca2+ level, in contrast to TMEM16A/B currents. The Ca2+-activated TMEM16F currents were anion selective, because replacing Cl− with aspartate− in the bathing solution without changing cation concentrations caused a positive shift of the reversal potential. The anion selectivity sequence of the TMEM16F channel was I− > Br− > Cl− > F− > aspartate−. Niflumic acid, a Ca2+-activated Cl− channel blocker, inhibited the TMEM16F-dependent Cl− currents. Neither overexpression nor knockdown of TMEM16F affected volume-sensitive outwardly rectifying Cl− channel (VSOR) currents activated by osmotic swelling or apoptotic stimulation. These results demonstrate that human TMEM16F is an essential component of a Ca2+-activated Cl− channel with a Ca2+ sensitivity that is distinct from that of TMEM16A/B and that it is not related to VSOR activity.
Inhibitory effects of omega-3 fatty acids on injury-induced epidermal growth factor receptor transactivation contribute to delayed wound healing
Authors: Turk Harmony F. , Monk Jennifer M. , Fan Yang-Yi , Callaway Evelyn S. , Weeks Brad , Chapkin Robert S.
Published: February 2013

Epidermal growth factor receptor (EGFR)-mediated signaling is required for optimal intestinal wound healing. Since n-3 polyunsaturated fatty acids (PUFA), specifically docosahexaenoic acid (DHA), alter EGFR signaling and suppress downstream activation of key signaling pathways, we hypothesized that DHA would be detrimental to the process of intestinal wound healing. Using a mouse immortalized colonocyte model, DHA uniquely reduced EGFR ligand-induced receptor activation, whereas DHA and its metabolic precursor eicosapentaenoic acid (EPA) reduced wound-induced EGFR transactivation compared with control (no fatty acid or linoleic acid). Under wounding conditions, the suppression of EGFR activation was associated with a reduction in downstream activation of cytoskeletal remodeling proteins (PLCγ1, Rac1, and Cdc42). Subsequently, DHA and EPA reduced cell migration in response to wounding. Mice were fed a corn oil-, DHA-, or EPA-enriched diet prior to intestinal wounding (2.5% dextran sodium sulfate for 5 days followed by termination after 0, 3, or 6 days of recovery). Mortality was increased in EPA-fed mice and colonic histological injury scores were increased in EPA- and DHA-fed mice compared with corn oil-fed (control) mice. Although kinetics of colonic EGFR activation and downstream signaling (PLCγ1, Rac1, and Cdc42) were delayed by both n-3 PUFA, colonic repair was increased in EPA- relative to DHA-fed mice. These results indicate that, during the early response to intestinal wounding, DHA and EPA uniquely delay the activation of key wound-healing processes in the colon. This effect is mediated, at least in part, via suppression of EGFR-mediated signaling and downstream cytoskeletal remodeling.
Loss of WNK3 is compensated for by the WNK1/SPAK axis in the kidney of the mouse
Authors: Mederle Katharina , Mutig Kerim , Paliege Alexander , Carota Isabel , Bachmann Sebastian , Castrop Hayo , Oppermann Mona
Published: February 2013

WNK3 kinase is expressed throughout the nephron and acts as a positive regulator of NKCC2 and NCC in vitro. Here we addressed the in vivo relevance of WNK3 using WNK3-deficient mice. WNK3−/− mice were viable and showed no gross abnormalities. The net tubular function was similar in wild-type (WT) and WNK3−/− mice as assessed by determination of 24-h urine output (1.63 ± .06 in WT and 1.55 ± .1 ml in WNK3−/−, n=16; P=0.42) and ambient urine osmolarity (1,804 ± 62 in WT vs. 1,819 ± 61 mosmol/kg in WNK3−/−, n=40; P=0.86). Water restriction (48 h) increased urine osmolarity similarly in both genotypes to 3,440 ± 220 and 3,200 ± 180 mosmol/kg in WT and WNK3−/− mice, respectively ( n=11; P=0.41). The glomerular filtration rate (343 ± 22 vs. 315 ± 13 ml/min), renal blood flow (1.35 ± 0.1 vs. 1.42 ± 0.04 ml), and plasma renin concentration (94 ± 18 vs. 80 ± 13 ng ANG I·ml−1·h−1) were similar between WT and WNK3−/− mice ( n=13; P=0.54). WNK1 was markedly upregulated in WNK3-deficient mice, whereas the expression of WNK4 was similar in both genotypes. When the mice were fed a salt-restricted diet [0.02% NaCl (wt/wt)] the levels of pSPAK/OSR1, pNKCC2, and pNCC were enhanced in both genotypes compared with the baseline conditions, with the levels in WNK3−/− exceeding those in WT mice. The upregulation of pSPAK/OSR1, pNKCC2, and pNCC in WNK3−/− mice relative to the levels in WT mice when fed a low-salt diet was paralleled by an increased diuresis in response to hydrochlorothiazide. In summary, the overall relevance of WNK3 for the renal reabsorption of NaCl appears to be limited and can be largely compensated for by the activation of WNK3-independent pathways. Consequently, our data suggest that WNK3 may serve as a member of a kinase network that facilitates the fine-tuning of renal transepithelial NaCl transport.
Impact of oral contraceptive use and menstrual phases on patellar tendon morphology, biochemical composition, and biomechanical properties in female athletes
Authors: Hansen Mette , Couppe Christian , Hansen Christina S. E. , Skovgaard Dorthe , Kovanen Vuokko , Larsen Jytte O. , Aagaard Per , Magnusson S. Peter , Kjaer Michael
Published: February 2013

Sex differences exist with regards to ligament and tendon injuries. Lower collagen synthesis has been observed in exercising women vs. men, and in users of oral contraceptives (OC) vs. nonusers, but it is unknown if OC will influence tendon biomechanics of women undergoing regular training. Thirty female athletes (handball players, 18–30 yr) were recruited: 15 long-term users of OC (7.0 ± 0.6 yr) and 15 nonusers (>5 yr). Synchronized values of patellar tendon elongation (obtained by ultrasonography) and tendon force were sampled during ramped isometric knee extensor maximum voluntary contraction to estimate mechanical tendon properties. Furthermore, tendon cross-sectional area and length were measured from MRI images, and tendon biopsies were obtained for analysis of tendon fibril characteristics and collagen cross-linking. Overall, no difference in tendon biomechanical properties, tendon fibril characteristics, or collagen cross-linking was observed between the OC users and nonusers, or between the different phases of the menstrual cycle. In athletes, tendon cross-sectional area in the preferred jumping leg tended to be larger than that in the contralateral leg ( P = 0.09), and a greater absolute ( P = 0.01) and normalized tendon stiffness ( P = 0.02), as well as a lower strain ( P = 0.04), were observed in the jumping leg compared with the contralateral leg. The results indicate that long-term OC use or menstrual phases does not influence structure or mechanical properties of the patellar tendon in female team handball athletes.
Ocular Surface Development and Gene Expression
Authors: Swamynathan Shivalingappa K.
Published: February 2013

The ocular surface—a continuous epithelial surface with regional specializations including the surface and glandular epithelia of the cornea, conjunctiva, and lacrimal and meibomian glands connected by the overlying tear film—plays a central role in vision. Molecular and cellular events involved in embryonic development, postnatal maturation, and maintenance of the ocular surface are precisely regulated at the level of gene expression by a well-coordinated network of transcription factors. A thorough appreciation of the biological characteristics of the ocular surface in terms of its gene expression profiles and their regulation provides us with a valuable insight into the pathophysiology of various blinding disorders that disrupt the normal development, maturation, and/or maintenance of the ocular surface. This paper summarizes the current status of our knowledge related to the ocular surface development and gene expression and the contribution of different transcription factors to this process.
Optimal Energy Control Strategy Design for a Hybrid Electric Vehicle
Authors: Zou Yuan , Shi-jie Hou , Dong-ge Li , Wei Gao , Hu Xiao-song
Published: February 2013

A heavy-duty parallel hybrid electric truck is modeled, and its optimal energy control is studied in this paper. The fundamental architecture of the parallel hybrid electric truck is modeled feed-forwardly, together with necessary dynamic features of subsystem or components. Dynamic programming (DP) technique is adopted to find the optimal control strategy including the gear-shifting sequence and the power split between the engine and the motor subject to a battery SOC-sustaining constraint. Improved control rules are extracted from the DP-based control solution, forming near-optimal control strategies. Simulation results demonstrate that a significant improvement on the fuel economy can be achieved in the heavy-duty vehicle cycle from the natural driving statistics.
Use of Near Infrared Spectroscopy to Asses Remote Ischemic Preconditioning in Skeletal Muscle
Authors: Ambrozic Jana , Lainscak Mitja , Podbregar Matej
Published: February 2013

Remote ischemic preconditioning (IPC) is a procedure during which brief periods of ischemia protect distant organ from ischemia-reperfusion injury. Appling IPC on an upper arm, this phenomenon has been demonstrated in several studies. Skeletal muscle tissue oxygenation at rest (StO2) and StO2 deoxygenation rate during vascular occlusion can be measured using near infrared spectroscopy (NIRS). We aimed to investigate the effects of remote upper arm IPC on StO2 and flow-mediated dilatation (FMD) in healthy male volunteers. In a randomized controlled crossover trial, resting StO2, StO2 deoxygenation rate, and FMD were measured on testing arm at baseline and after 60 minutes. After basal measurements IPC protocol on a contralateral arm was performed. StO2 deoxygenation rate was significantly lower after remote, the IPC cycles in comparison to deoxygenation rate at baseline (9.7±2.6 versus 7.5±2.5%, P=0.002). Comparison of deoxygenation rates showed a significant difference between the IPC and the control protocol (F=5.512, P=0.003). No differences were observed in FMD before and after remote IPC and in the control protocol. In healthy young adults, remote IPC reduces StO2 deoxygenation rate but has no significant impact on FMD. NIRS technique offers a novel approach to asses skeletal muscle adaptation in response to remote ischemic stimuli.
Arteriovenous Malformation in Temporal Lobe Presenting as Contralateral Ocular Symptoms Mimicking Carotid-Cavernous Fistula
Authors: Mohd-Tahir Fadzillah , Siti-Raihan Ishak , Wan Hazabbah W. H.
Published: February 2013

Aim. To report a rare case of arteriovenous malformation in temporal lobe presenting as contralateral orbital symptoms mimicking carotid-cavernous fistula.Method. Interventional case report.Results. A 31-year-old Malay gentleman presented with 2-month history of painful progressive exophthalmos of his left eye associated with recurrent headache, diplopia, and reduced vision. Ocular examination revealed congestive nonpulsating 7 mm exophthalmos of the left eye with no restriction of movements in all direction. There was diplopia in left lateral gaze. Left IOP was elevated at 29 mmHg. Left eye retinal vessels were slightly dilated and tortuous. CT scan was performed and showed right temporal arteriovenous malformation with a nidus of 3.8 cm × 2.5 cm with right middle cerebral artery as feeding artery. There was dilated left superior ophthalmic vein of 0.9 mm in diameter with enlarged left cavernous sinus. MRA and carotid angiogram confirmed right temporal arteriovenous malformation with no carotid-cavernous fistula. Most of the intracranial drainage was via left cavernous sinus. His signs and symptoms dramatically improved following successful embolisation, completely resolved after one year.Conclusion. Intracranial arteriovenous malformation is rarely presented with primary ocular presentation. Early intervention would salvage the eyes and prevent patients from more disaster morbidity or fatality commonly due to intracranial haemorrhage.
Analysis of Adaptive Fuzzy Technique for Multiple Crack Diagnosis of Faulty Beam Using Vibration Signatures
Authors: Dash Amiya Kumar
Published: February 2013

This paper discusses the multicrack detection of structure using fuzzy Gaussian technique. The vibration parameters derived from the numerical methods of the cracked cantilever beam are used to set several fuzzy rules for designing the fuzzy controller used to predict the crack location and depth. Relative crack locations and relative crack depths are the output parameters from the fuzzy inference system. The method proposed in the current analysis is used to evaluate the dynamic response of cracked cantilever beam. The results of the proposed method are in good agreement with the results obtained from the developed experimental setup.
Application of Asymptotic and Rigorous Techniques for the Characterization of Interferences Caused by a Wind Turbine in Its Neighborhood
Authors: Algar Maria Jesús , Lozano Lorena , Moreno Javier , González Iván , Cátedra Felipe
Published: February 2013

This paper presents a complete assessment to the interferences caused in the nearby radio systems by wind turbines. Three different parameters have been considered: the scattered field of a wind turbine, its radar cross-section (RCS), and the Doppler shift generated by the rotating movements of the blades. These predictions are very useful for the study of the influence of wind farms in radio systems. To achieve this, both high-frequency techniques, such as Geometrical Theory of Diffraction/Uniform Theory of Diffraction (GTD/UTD) and Physical Optics (PO), and rigorous techniques, like Method of Moments (MoM), have been used. In the analysis of the scattered field, conductor and dielectric models of the wind turbine have been analyzed. In this way, realistic results can be obtained. For all cases under analysis, the wind turbine has been modeled with NURBS (Non-Uniform Rational B-Spline) surfaces since they allow the real shape of the object to be accurately replicated with very little information.
Relationship between Maximum Principle and Dynamic Programming for Stochastic Recursive Optimal Control Problems and Applications
Authors: Shi Jingtao , Yu Zhiyong
Published: February 2013

This paper is concerned with the relationship between maximum principle and dynamic programming for stochastic recursive optimal control problems. Under certain differentiability conditions, relations among the adjoint processes, the generalized Hamiltonian function, and the value function are given. A linear quadratic recursive utility portfolio optimization problem in the financial engineering is discussed as an explicitly illustrated example of the main result.
Implementation of Stroke Dysphagia Screening in the Emergency Department
Authors: Daniels Stephanie K. , Anderson Jane A. , Petersen Nancy J.
Published: February 2013

Early detection of dysphagia is critical in stroke as it improves health care outcomes. Administering a swallowing screening tool (SST) in the emergency department (ED) appears most logical as it is the first point of patient contact. However, feasibility of an ED nurse-administered SST, particularly one involving trial water swallow administration, is unknown. The aims of this pilot study were to (1) implement an SST with a water swallow component in the ED and track nurses’ adherence, (2) identify barriers and facilitators to administering the SST through interviews, and (3) develop and implement a process improvement plan to address barriers. Two hundred seventy-eight individuals with stroke symptoms were screened from October 2009 to June 2010. The percentage of patients screened increased from 22.6 in October 2009 to a high of 80.8 in March 2010, followed by a decrease to 61.9% in June (Cochran-Armitage testz=-5.1042, P<0.0001). The odds of being screened were 4.0 times higher after implementation compared to two months before implementation. Results suggest that it is feasible for ED nurses to administer an SST with a water swallow component. Findings should facilitate improved quality of care for patients with suspected stroke and improve multidisciplinary collaboration in swallowing screening.