bluuebunny/crossref_metadata_2025 huggingface dataset:
Evaluation of the RealTime HIV-1, Xpert HIV-1, and Aptima HIV-1 Quant Dx Assays in Comparison to the NucliSens EasyQ HIV-1 v2.0 Assay for Quantification of HIV-1 Viral Load
Authors: Mor Orna , Gozlan Yael , Wax Marina , Mileguir Fernando , Rakovsky Avia , Noy Bina , Mendelson Ella , Levy Itzchak
Published: September 2015

HIV-1 RNA monitoring, both before and during antiretroviral therapy, is an integral part of HIV management worldwide. Measurements of HIV-1 viral loads are expected to assess the copy numbers of all common HIV-1 subtypes accurately and to be equally sensitive at different viral loads. In this study, we compared for the first time the performance of the NucliSens v2.0, RealTime HIV-1, Aptima HIV-1 Quant Dx, and Xpert HIV-1 viral load assays. Plasma samples (
n
= 404) were selected on the basis of their NucliSens v2.0 viral load results and HIV-1 subtypes. Concordance, linear regression, and Bland-Altman plots were assessed, and mixed-model analysis was utilized to compare the analytical performance of the assays for different HIV-1 subtypes and for low and high HIV-1 copy numbers. Overall, high concordance (>83.89%), high correlation values (Pearson
r
values of >0.89), and good agreement were observed among all assays, although the Xpert and Aptima assays, which provided the most similar outputs (estimated mean viral loads of 2.67 log copies/ml [95% confidence interval [CI], 2.50 to 2.84 log copies/ml] and 2.68 log copies/ml [95% CI, 2.49 to 2.86 log copies/ml], respectively), correlated best with the RealTime assay (89.8% concordance, with Pearson
r
values of 0.97 to 0.98). These three assays exhibited greater precision than the NucliSens v2.0 assay. All assays were equally sensitive for subtype B and AG/G samples and for samples with viral loads of 1.60 to 3.00 log copies/ml. The NucliSens v2.0 assay underestimated A1 samples and those with viral loads of >3.00 log copies/ml. The RealTime assay tended to underquantify subtype C (compared to the Xpert and Aptima assays) and subtype A1 samples. The Xpert and Aptima assays were equally efficient for detection of all subtypes and viral loads, which renders these new assays most suitable for clinical HIV laboratories.
Clonal Diversification and Changes in Lipid Traits and Colony Morphology in Mycobacterium abscessus Clinical Isolates
Authors: Park In Kwon , Hsu Amy P. , Tettelin Hervé , Shallom Shamira J. , Drake Steven K. , Ding Li , Wu Un-In , Adamo Nick , Prevots D. Rebecca , Olivier Kenneth N. , Holland Steven M. , Sampaio Elizabeth P. , Zelazny Adrian M.
Published: September 2015

The smooth-to-rough colony morphology shift in
Mycobacterium abscessus
has been implicated in loss of glycopeptidolipid (GPL), increased pathogenicity, and clinical decline in cystic fibrosis (CF) patients. However, the evolutionary phenotypic and genetic changes remain obscure. Serial isolates from nine non-CF patients with persistent
M. abscessus
infection were characterized by colony morphology, lipid profile via thin-layer chromatography and matrix-assisted laser desorption ionization–time of flight mass spectrometry (MALDI-TOF MS), sequencing of eight genes in the GPL locus, and expression level of
fadD23
, a key gene involved in the biosynthesis of complex lipids. All 50 isolates were typed as
M. abscessus
subspecies
abscessus
and were clonally related within each patient. Rough isolates, all lacking GPL, predominated at later disease stages, some showing variation within rough morphology. While most (77%) rough isolates harbored detrimental mutations in
mps1
and
mps2
, 13% displayed previously unreported mutations in
mmpL4a
and
mmpS4
, the latter yielding a putative GPL precursor. Two isolates showed no deleterious mutations in any of the eight genes sequenced. Mixed populations harboring different GPL locus mutations were detected in 5 patients, demonstrating clonal diversification, which was likely overlooked by conventional acid-fast bacillus (AFB) culture methods. Our work highlights applications of MALDI-TOF MS beyond identification, focusing on mycobacterial lipids relevant in virulence and adaptation. Later isolates displayed accumulation of triacylglycerol and reduced expression of
fadD23
, sometimes preceding rough colony onset. Our results indicate that clonal diversification and a shift in lipid metabolism, including the loss of GPL, occur during chronic lung infection with
M. abscessus
. GPL loss alone may not account for all traits associated with rough morphology.
Stationary-Phase Persisters to Ofloxacin Sustain DNA Damage and Require Repair Systems Only during Recovery
Authors: Völzing Katherine G. , Brynildsen Mark P.
Published: September 2015

Chronic infections are a serious health care problem, and bacterial persisters have been implicated in infection reoccurrence. Progress toward finding antipersister therapies has been slow, in part because of knowledge gaps regarding the physiology of these rare phenotypic variants. Evidence shows that growth status is important for survival, as nongrowing cultures can have 100-fold more persisters than growing populations. However, additional factors are clearly important, as persisters remain rare even in nongrowing populations. What features, beyond growth inhibition, allow persisters to survive antibiotic stress while the majority of their kin succumb to it remains an open question. To investigate this, we used stationary phase as a model nongrowing environment to study
Escherichia coli
persistence to ofloxacin. Given that the prevailing model of persistence attributes survival to transient dormancy and antibiotic target inactivity, we anticipated that persisters would suffer less damage than their dying kin. However, using genetic mutants, flow cytometry, fluorescence-activated cell sorting, and persistence assays, we discovered that nongrowing ofloxacin persisters experience antibiotic-induced damage that is indistinguishable from that of nonpersisters. Consistent with this, we found that these persisters required DNA repair for survival and that repair machinery was unnecessary until the posttreatment recovery period (after ofloxacin removal). These findings suggest that persistence to ofloxacin is not engendered solely by reduced antibiotic target corruption, demonstrate that what happens following antibiotic stress can be critical to the persistence phenotype, and support the notion that inhibition of DNA damage repair systems could be an effective strategy to eliminate fluoroquinolone persisters.

IMPORTANCE
In the absence of resistant mutants, infection reoccurrences can still occur because of persisters, rare bacterial cells that survive antibiotic treatments to repopulate infection sites. Persister survival is attributed to a transient state of dormancy in which a cell's growth and metabolism are significantly reduced and many essential processes are thought to be inactive. Thus, dormancy is believed to protect persisters from antibiotic-induced damage and death. In this work, we show that in nongrowing populations, persisters to ofloxacin experience the same level of antibiotic-induced damage as cells that succumb to the treatment and that their survival critically depends on repair of this damage after the conclusion of treatment. These findings reveal that persistence to ofloxacin is not engendered solely by reduced antibiotic target corruption and highlight that processes following antibiotic stress are important to survival. We hypothesize that effective antipersister therapies may be developed on the basis of this knowledge.
Selective Sweeps and Parallel Pathoadaptation Drive Pseudomonas aeruginosa Evolution in the Cystic Fibrosis Lung
Authors: Diaz Caballero Julio , Clark Shawn T. , Coburn Bryan , Zhang Yu , Wang Pauline W. , Donaldson Sylva L. , Tullis D. Elizabeth , Yau Yvonne C. W. , Waters Valerie J. , Hwang David M. , Guttman David S.
Published: September 2015

Pulmonary infections caused by
Pseudomonas aeruginosa
are a recalcitrant problem in cystic fibrosis (CF) patients. While the clinical implications and long-term evolutionary patterns of these infections are well studied, we know little about the short-term population dynamics that enable this pathogen to persist despite aggressive antimicrobial therapy. Here, we describe a short-term population genomic analysis of 233
P. aeruginosa
isolates collected from 12 sputum specimens obtained over a 1-year period from a single patient. Whole-genome sequencing and antimicrobial susceptibility profiling identified the expansion of two clonal lineages. The first lineage originated from the coalescence of the entire sample less than 3 years before the end of the study and gave rise to a high-diversity ancestral population. The second expansion occurred 2 years later and gave rise to a derived population with a strong signal of positive selection. These events show characteristics consistent with recurrent selective sweeps. While we cannot identify the specific mutations responsible for the origins of the clonal lineages, we find that the majority of mutations occur in loci previously associated with virulence and resistance. Additionally, approximately one-third of all mutations occur in loci that are mutated multiple times, highlighting the importance of parallel pathoadaptation. One such locus is the gene encoding penicillin-binding protein 3, which received three independent mutations. Our functional analysis of these alleles shows that they provide differential fitness benefits dependent on the antibiotic under selection. These data reveal that bacterial populations can undergo extensive and dramatic changes that are not revealed by lower-resolution analyses.

IMPORTANCE
Pseudomonas aeruginosa
is a bacterial opportunistic pathogen responsible for significant morbidity and mortality in cystic fibrosis (CF) patients. Once it has colonized the lung in CF, it is highly resilient and rarely eradicated. This study presents a deep sampling examination of the fine-scale evolutionary dynamics of
P. aeruginosa
in the lungs of a chronically infected CF patient. We show that diversity of
P. aeruginosa
is driven by recurrent clonal emergence and expansion within this patient and identify potential adaptive variants associated with these events. This high-resolution sequencing strategy thus reveals important intraspecies dynamics that explain a clinically important phenomenon not evident at a lower-resolution analysis of community structure.
Function of the CRISPR-Cas System of the Human Pathogen Clostridium difficile
Authors: Boudry Pierre , Semenova Ekaterina , Monot Marc , Datsenko Kirill A. , Lopatina Anna , Sekulovic Ognjen , Ospina-Bedoya Maicol , Fortier Louis-Charles , Severinov Konstantin , Dupuy Bruno , Soutourina Olga
Published: September 2015

Clostridium difficile
is the cause of most frequently occurring nosocomial diarrhea worldwide. As an enteropathogen,
C. difficile
must be exposed to multiple exogenous genetic elements in bacteriophage-rich gut communities. CRISPR (clustered regularly interspaced short palindromic repeats)-Cas (CRISPR-associated) systems allow bacteria to adapt to foreign genetic invaders. Our recent data revealed active expression and processing of CRISPR RNAs from multiple type I-B CRISPR arrays in
C. difficile
reference strain 630. Here, we demonstrate active expression of CRISPR arrays in strain R20291, an epidemic
C. difficile
strain. Through genome sequencing and host range analysis of several new
C. difficile
phages and plasmid conjugation experiments, we provide evidence of defensive function of the CRISPR-Cas system in both
C. difficile
strains. We further demonstrate that
C. difficile
Cas proteins are capable of interference in a heterologous host,
Escherichia coli
. These data set the stage for mechanistic and physiological analyses of CRISPR-Cas-mediated interactions of important global human pathogen with its genetic parasites.

IMPORTANCE
Clostridium difficile
is the major cause of nosocomial infections associated with antibiotic therapy worldwide. To survive in bacteriophage-rich gut communities, enteropathogens must develop efficient systems for defense against foreign DNA elements. CRISPR-Cas systems have recently taken center stage among various anti-invader bacterial defense systems. We provide experimental evidence for the function of the
C. difficile
CRISPR system against plasmid DNA and bacteriophages. These data demonstrate the original features of active
C. difficile
CRISPR system and bring important insights into the interactions of this major enteropathogen with foreign DNA invaders during its infection cycle.
Primary pancreatic hydatid cyst: an unexpected differential diagnosis
Authors: Hiremath Bharati , Subramaniam Narayana , Boggavarapu Manobhiram
Published: September 2015

Hydatid disease, caused by the cystic stage ofEchinococcus granulosus, most commonly involves the liver (59–75%) and lung (27%), and rarely involves the kidney (3%), bone (1–4%) and brain (1–2%). Even rarer sites include the heart and spleen, and skeletal muscle, with virtually no site being immune. The pancreas is an exceedingly rare site for primary disease (without concomitant involvement of the liver or peritoneum), with less than 20 reported cases in the literature. This case report describes a 48-year-old woman presenting with a solitary cystic lesion arising from the neck of the pancreas, which was ultimately determined to be a hydatid cyst on histopathological examination. It also discusses the difficulties in preoperative and postoperative management and includes a review of the literature.
Background to some of the seismic design provisions of the 2015 National Building Code of Canada
Authors: Humar Jagmohan
Published: September 2015

The last version of the National Building Code of Canada was issued in 2010. The next version will be issued in 2015. In the code cycle between 2010 and 2015 significant changes have taken place in the seismic design provision. The main factor that drives these changes is an improved understanding of the seismic hazard across the country. Changes have also been introduced in the site effect factors. The structural design provisions have been appropriately adjusted to respond to changes in the estimates of hazard and the new site effect factors. There are also new provisions related to design in regions of low hazard, buildings with flexible diaphragms, buildings with inclined columns, passive energy dissipation systems, base isolation, rocking foundations, glazing systems, racks, and elevators. Some of the changes are briefly discussed. The main focus of the paper is, however, on the revisions to the structural design provisions.
Tracking the fidelity of Atlantic bluefin tuna released in Canadian waters to the Gulf of Mexico spawning grounds
Authors: Wilson Steven G. , Jonsen Ian D. , Schallert Robert J. , Ganong James E. , Castleton Michael R. , Spares Aaron D. , Boustany Andre M. , Stokesbury Michael J.W. , Block Barbara A.
Published: September 2015

The objective of this study was to advance the use of pop-up satellite archival tags to track the migrations of Atlantic bluefin tuna (Thunnus thynnus) to their spawning grounds. Deployment of tags occurred in the Gulf of St. Lawrence, Canada, during fall months from 2007 to 2013. Pop-up satellite archival tags (n = 135) were attached to 125 Atlantic bluefin tuna (curved fork length (CFL) = 268 ± 20 cm (mean ± SD)) with the objective of keeping tags on until visitation to a spawning area or longer. A dataset of 18 800 days was acquired, which included 5800 days of time-series data from 19 recovered satellite tags. Many Atlantic bluefin tuna visited the Gulf of Mexico spawning grounds (74%), the mean size of which was 275 ± 14 cm (CFL ± SD, n = 49), with a measured CFL of 243 to 302 cm. These fish had a mean entry date into the Gulf of Mexico of 14 January ± 42 days (SD). The mean residency period for fish that had tracks with entrance and exit from the Gulf of Mexico was 123 ± 49 days (SD) (n = 22). Atlantic bluefin tuna that moved into the Gulf of Mexico during the spawning season remained west of the 45°W meridian for the duration of the track. Electronic tagging datasets from two fish were obtained before, during, and after the Deepwater Horizon oil spill. Both fish utilized habitat in the vicinity of the Macondo Well on 20 April 2010 when the Deepwater Horizon oil drilling rig accident occurred. Spawning hotspots are identified in the Gulf of Mexico using kernel density analyses and compared with the newly established closed areas.
Dendroclimatic analysis of red pine affected by Diplodia shoot blight in different latitudinal regions in Michigan
Authors: Chhin Sophan , O’Brien Joseph
Published: September 2015

Drought and intraspecific competition in red pine (Pinus resinosa Ait.) stands in Michigan have been implicated as predisposing factors for increased shoot blight risk caused by Diplodia pinea Desm. The overall objective of this study is to examine the interactive effects of drought, other climatic factors, and biotic factors (intraspecific competition) on productivity and growth of red pine forests affected by Diplodia shoot blight. This study incorporates a dendroclimatic approach that allows the retrospective examination of past annual diameter growth in relation to historical climate and the assessment of the potential impacts of future climate change. A total of 20 red pine stands were sampled in two latitudinal regions (the Upper Peninsula (UP) and the Lower Peninsula (LP) regions) of Michigan across two levels of initial stand density (low vs. high) and two levels of forest health condition (healthy vs. D. pinea affected). The full dendroclimatic relationships revealed in this study indicated that other climatic factors, in addition to summer drought stress, impacted red pine radial growth. Overall, red pine radial growth was generally more affected by precipitation and moisture index than solely by temperature variables. The radial growth response to climate depended on latitudinal region: summer moisture stress was more influential in the LP; cold spring and early summer temperatures negatively impacted growth more in the UP; and the degree of winter harshness was more of a factor in the UP. Crown damage caused by winter damage may have predisposed red pine stands to D. pinea affection by providing an easier entry point for fungal infection. Negative relations with precipitation in D. pinea affected stands may be due to increased dispersal of spores in D. pinea affected stands with significant rain and any increased storm and wind activity. Projections of radial growth under future scenarios of climate change indicate that climate warming has the potential to increase growth mainly in red pine stands in the UP region where growth has historically been limited by cool temperatures early in the growing season. Under the moisture index model, growth of red pine under the drier (A2) climate change scenario, only the D. pinea impacted high-density stands in the LP region are projected to show a significant decrease in growth by the middle (2041–2070) and final (2071–2100) projection periods. Model-based projections of forest growth in Michigan generally do not account for forest health issues such as invasive pathogens. The current study therefore provides a new understanding of the role of forest pathogens under future climate change.
Comparison of the growth kinetics and proteolytic activities of Chryseobacterium species and Pseudomonas fluorescens
Authors: Bekker A. , Steyn L. , Charimba G. , Jooste P. , Hugo C.
Published: September 2015

The effect of temperature on the growth kinetics and proteolytic activity of Chryseobacterium joostei and Chryseobacterium bovis was determined during this study. The results were compared with the activities of Pseudomonas fluorescens, which is regarded to be a major food spoilage psychrotolerant microorganism. For the growth studies, cultures were incubated in nutrient broth in a temperature gradient incubator (from 9 to 50 °C) and separately at 4 °C, and the optical density was measured at different time intervals. Growth temperature profiles for each organism were constructed. For determination of proteolytic activity, the cultures were incubated in fat-free ultra-high temperature processed milk in the temperature gradient incubator for 72 h (temperature range as above). Cell-free extracts were used to determine the proteolytic activity using the azocasein method. Results of the growth studies showed that C. joostei had the ability to grow over a wider temperature range than C. bovis and P. fluorescens without being affected by changes in the temperature. For the proteolytic activity, C. joostei had significantly (p < 0.001) higher activity per milligram of protein at 15.5 °C, followed by C. bovis and P. fluorescens. The results showed that C. joostei potentially has an even greater spoilage capacity in milk on the basis of growth rate and proteolytic activity than did P. fluorescens.
THE EFFECTS OF SUBSIDIES FOR CHILDBEARING ON MIGRATION AND FERTILITY: EVIDENCE FROM KOREA
Authors: HONG SUNG HYO , SULLIVAN RYAN
Published: September 2015

This study examines the effects of a fertility subsidy that was instituted in specific regions in Korea in 2004. The value of the subsidy ranged from $4000 to $9000 (2004 US$) depending on the area of residence. Using a difference-in-differences estimation strategy, we measure the effects of the policy on childbearing and migration in and out of the subsidized areas. Our estimates for migration suggest that the policy significantly increased the net inflow of females into the subsidized areas. This effect is driven roughly equally by a decrease in the outflow from and an increase into the subsidized areas. Our estimated effects on fertility are in line with previous results from the literature; we find that a $1000 increase in fertility subsidies leads to a 0.108% increase in the chance of bearing a child for all age groups (21 to 45). Our results show that the policy increased total births in 2005 by 11,000 and that the vast majority of this increase was from the 21 to 33 cohort.
PUBLIC INVESTMENT FINANCED BY CONSUMPTION TAX IN AN AGING SOCIETY
Authors: WATANABE MINORU , MIYAKE YUSUKE , YASUOKA MASAYA
Published: September 2015

Earlier papers have examined endogenous growth models including public investment financed by an income tax. However, public capital with such financing has not been reported. Aging societies are developing rapidly in economically developed countries. Consumption taxes to finance government expenditures are attractive to alleviate intergenerational inequality. In this paper, we demonstrate that, for public investment financing, a consumption tax is better than an income tax for income growth. If a future generation’s utility is not discounted greatly in social welfare, a consumption tax is superior. A government-set income growth rate target makes income tax financing desirable by providing more social welfare.
ECONOMIC IMPACT ASSESSMENT OF PUBLIC–PRIVATE MATCHING FUND PROGRAMS USING FIRM-LEVEL DATA
Authors: KIM YOUNGKYU , OH INHA , LEE JEONG-DONG
Published: September 2015

In the intermediate goods industry, largely made up of small and medium enterprises (SMEs), a government can use a matching fund to execute policies that, for example, provide funds to promote and support firms' innovative activities. This study performs an empirical analysis to investigate the additional effects when a government uses a matching fund in this way and, in particular, to analyze the growth of firms. Methodologically, to deal with the selectivity issue, we adopt a propensity score matching (PSM) estimator. We also investigate the performance of the matching fund according to changes in private shares. Our findings show that supported firms invested larger amounts in R&D and procured external financing through an overall improvement in their level of reliability. However, the results also show that this was not connected to further improvements in business performance. Moreover, although our results show some positive impact on assets and R&D expenditure from private investment in the matching fund, the relationship between sales and fixed assets was non-significant.
Theoretical investigation of elastic and phononic properties of Zn1−xBexO alloys
Authors: Elhamra F. , Lakel S. , Ibrir M. , Almi K. , Meradji H.
Published: September 2015

Our calculations were conducted within density functional theory (DFT) and density functional perturbation theory (DFPT) using norm-conserving pseudo-potential and the local density approximation. The elastic constants of [Formula: see text] were calculated, [Formula: see text], [Formula: see text] and [Formula: see text] increase with the increase of Be content, whereas the [Formula: see text] shows a non-monotonic variation and [Formula: see text] decreases when Be concentration increases. The values of bulk modulus [Formula: see text], Young’s modulus [Formula: see text] and shear modulus [Formula: see text] increase with the increase of Be content. Poisson’s ratio [Formula: see text] decreases with increased Be concentration. The ductility decreases with increasing Be concentration and the compressibility for [Formula: see text] along [Formula: see text]-axis is smaller than along [Formula: see text]-axis. Phonon dispersion curves show that [Formula: see text] is dynamically stable (no soft modes). Quantities such as refractive index, Born effective charge, dielectric constants and optical phonon frequencies were calculated as a function of the Be molar fraction [Formula: see text]. The agreement between the present results and the known data that are available only for ZnO and BeO is generally satisfactory. Our results for [Formula: see text] [Formula: see text] are predictions.
Hyundai Motor Company in the Indian Market
Authors: Park Young-Eun , Rhee Dong-Kee
Published: September 2015

This case study describes the strategies of Hyundai Motor Company for entering and working in India, as part of its global management strategies. With its huge potential in market development, India attracted worldwide attention and was a place of fierce competition among global corporations. In the automobile industry, Hyundai Motor India (HMI) went into the production of national vehicles for India's citizens through localization of products and marketing as well as standardization of manpower and organization. This study will examine the strategies and role of HMI as the future leader of domestic markets and outpost for global exportation.
Nanostructured Perovskite LaCo1-xMnxO3 as Bifunctional Catalysts for Rechargeable Metal–Air Batteries
Authors: Ge Xiaoming , Li Bing , Wuu Delvin , Sumboja Afriyanti , An Tao , Hor T. S. Andy , Zong Yun , Liu Zhaolin
Published: September 2015

Bifunctional catalyst that is active for both oxygen reduction reaction (ORR) and oxygen evolution reaction (OER) is one of the most important components of rechargeable metal–air batteries. Nanostructured perovskite bifunctional catalysts comprising La , Co and Mn ( LaCo 1-x Mn x O 3, LCMO ) are synthesized by hydrothermal methods. The morphology, structure and electrochemical activity of the perovskite bifunctional catalysts are characterized by scanning electron microscopy (SEM), X-ray diffraction (XRD) and rotating disk electrode (RDE) techniques. Nanorod, nanodisc and nanoparticle are typical morphologies of LCMO . The electrocatalytic activity of LCMO is significantly improved by the addition of conductive materials such as carbon nanotube. To demonstrate the practical utilization, LCMO in the composition of LaCo 0.8 Mn 0.2 O 3( LCMO82 ) is used as air cathode catalysts for rechargeable zinc–air batteries. The battery prototype can sustain 470 h or 40 discharge–charge cycles equivalent.
Breached Initiations: Sociopolitical Resources and Conflicts in Emergent Adulthood
Authors: Mendoza-Denton Norma , Boum Aomar
Published: September 2015

Work theorizing youth subcultures, especially of the spectacular kind, has provided an influential approach for understanding the lives of young people for the past 40 years in anthropology and sociology. In this review, we frame current literature through a lens we call “breached initiations.” We motivate our organization of the literature into processes we term “delaying,” “hopscotching,” and “opting out,” referring to ways in which youth engage sociopolitical resources and chronotopes to alter the sequencing and clustering of their expected progress through milestones of adulthood. In many cases, youth delay or refuse entry into a world that is considered “normal” and demand a reconsideration of its very premises. We highlight symbolic, material, and networked resources; by considering the commonalities in the structural situations of different youth groups, we do not view them as islands, but instead assert their embeddedness in common change.
Inclusive Wealth as a Metric of Sustainable Development
Authors: Polasky Stephen , Bryant Benjamin , Hawthorne Peter , Johnson Justin , Keeler Bonnie , Pennington Derric
Published: September 2015

Inclusive wealth is a measure designed to address whether society is on a sustainable development trajectory. Inclusive wealth is defined as the aggregate value of all capital assets. Increases in inclusive wealth indicate an improved productive base capable of supporting a higher standard of living in the future. To be truly inclusive, measures of inclusive wealth must include the value of all forms of capital that contribute to human well-being: human capital, manufactured capital, natural capital, and social capital. Sustainability concerns have increased attention on the ways of measuring the value of natural capital. We review various attempts to measure natural capital and to incorporate these into inclusive wealth including estimates using national wealth accounts and integrated ecological and economic models used to estimate ecosystem services. Empirically measuring the value of various types of capital in terms of a common metric is hugely challenging, and no current attempt to date can be said to be fully inclusive. Despite the empirical challenges, inclusive wealth provides a clear, coherent, and systematic framework for addressing sustainable development. Combining measures of semi-inclusive wealth that capture forms of capital that can be relatively easily measured in monetary terms with a set of biophysical metrics capturing important aspects of natural capital that are difficult to measure in monetary terms may provide a good set of signals of whether society is proceeding along a sustainable development trajectory.
Rewilding: Science, Practice, and Politics
Authors: Lorimer Jamie , Sandom Chris , Jepson Paul , Doughty Chris , Barua Maan , Kirby Keith J.
Published: September 2015

Rewilding is being promoted as an ambitious alternative to current approaches to nature conservation. Interest is growing in popular and scientific literatures, and rewilding is the subject of significant comment and debate, outstripping scientific research and conservation practice. Projects and research are found the world over, with concentrations in Europe, North America, and on tropical islands. A common aim is to maintain, or increase, biodiversity, while reducing the impact of present and past human interventions through the restoration of species and ecological processes. The term rewilding has been applied to diverse concepts and practices. We review the historical emergence of the term and its various overlapping meanings, aims, and approaches, and illustrate this through a description of four flagship rewilding case studies. The science of rewilding has centered on three different historical baselines: the Pleistocene, the Holocene, and novel contemporary ecosystems. The choice of baseline has differing implications for conservation in a variety of contexts. Rewilding projects involve a range of practical components—such as passive management, reintroduction, and taxon substitution—some of which have attracted criticism. They also raise a series of political, social, and ethical concerns where they conflict with more established forms of environmental management. In conclusion, we summarize the different goals, approaches, tools, and contexts that account for the variations in rewilding and identify priorities for future research and practice.
Cerebrospinal Fluid Mechanics and Its Coupling to Cerebrovascular Dynamics
Authors: Linninger Andreas A. , Tangen Kevin , Hsu Chih-Yang , Frim David
Published: September 2015

Cerebrospinal fluid (CSF) is not stagnant but displays fascinating oscillatory flow patterns inside the ventricular system and reversing fluid exchange between the cranial vault and spinal compartment. This review provides an overview of the current knowledge of pulsatile CSF motion. Observations contradicting classical views about its bulk production and clearance are highlighted. A clinical account of diseases of abnormal CSF flow dynamics, including hydrocephalus, syringomyelia, Chiari malformation type 1, and pseudotumor cerebri, is also given. We survey medical imaging modalities used to observe intracranial dynamics in vivo. Additionally, we assess the state of the art in predictive models of CSF dynamics. The discussion addresses open questions regarding CSF dynamics as they relate to the understanding and management of diseases.
Empirical Comparative Law
Authors: Spamann Holger
Published: September 2015

I review the empirical comparative law literature with an emphasis on quantitative work. After situating the field and surveying its main applications to date, I turn to methodological issues. I discuss at length the obstacles to causal inference from comparative data, and caution against inappropriate use of instrumental variables and other techniques. Even if comparative data cannot identify any single causal theory, however, they are extremely important in narrowing down the set of plausible theories. I report progress in measurement design and suggest improvements in data analysis and interpretation using techniques from other fields, particularly growth econometrics.
Management of Benign Prostatic Hyperplasia
Authors: Kim Eric H. , Larson Jeffrey A. , Andriole Gerald L.
Published: September 2015

Benign prostatic hyperplasia (BPH) and associated lower urinary tract symptoms (LUTS) commonly affect older men. Age-related changes associated with metabolic disturbances, changes in hormone balance, and chronic inflammation may cause BPH development. The diagnosis of BPH hinges on a thorough medical history and focused physical examination, with attention to other conditions that may be causing LUTS. Digital rectal examination and urinalysis should be performed. Other testing may be considered depending on presentation of symptoms, including prostate-specific antigen, serum creatinine, urine cytology, imaging, cystourethroscopy, post-void residual, and pressure-flow studies. Many medical and surgical treatment options exist. Surgery should be reserved for patients who either have failed medical management or have complications from BPH, such as recurrent urinary tract infections, refractory urinary retention, bladder stones, or renal insufficiency as a result of obstructive uropathy.
Media Effects: Theory and Research
Authors: Valkenburg Patti M. , Peter Jochen , Walther Joseph B.
Published: September 2015

This review analyzes trends and commonalities among prominent theories of media effects. On the basis of exemplary meta-analyses of media effects and bibliometric studies of well-cited theories, we identify and discuss five features of media effects theories as well as their empirical support. Each of these features specifies the conditions under which media may produce effects on certain types of individuals. Our review ends with a discussion of media effects in newer media environments. This includes theories of computer-mediated communication, the development of which appears to share a similar pattern of reformulation from unidirectional, receiver-oriented views, to theories that recognize the transactional nature of communication. We conclude by outlining challenges and promising avenues for future research.
Biogeography of Viruses in the Sea
Authors: Chow Cheryl-Emiliane T. , Suttle Curtis A.
Published: September 2015

Viral ecology is a rapidly progressing area of research, as molecular methods have improved significantly for targeted research on specific populations and whole communities. To interpret and synthesize global viral diversity and distribution, it is feasible to assess whether macroecology concepts can apply to marine viruses. We review how viral and host life history and physical properties can influence viral distribution in light of biogeography and metacommunity ecology paradigms. We highlight analytical approaches that can be applied to emerging global data sets and meta-analyses to identify individual taxa with global influence and drivers of emergent properties that influence microbial community structure by drawing on examples across the spectrum of viral taxa, from RNA to ssDNA and dsDNA viruses.
Virus-Host Interactions: From Unbiased Genetic Screens to Function
Authors: Ramage Holly , Cherry Sara
Published: September 2015

Deciphering the many interactions that occur between a virus and host cell over the course of infection is paramount to understanding mechanisms of pathogenesis and to the future development of antiviral therapies. Over the past decade, researchers have started to understand these complicated relationships through the development of methodologies, including advances in RNA interference, proteomics, and the development of genetic tools such as haploid cell lines, allowing high-throughput screening to identify critical contact points between virus and host. These advances have produced a wealth of data regarding host factors hijacked by viruses to promote infection, as well as antiviral factors responsible for subverting viral infection. This review highlights findings from virus-host screens and discusses our thoughts on the direction of screening strategies moving forward.
Revisiting the adipocyte: a model for integration of cytokine signaling in the regulation of energy metabolism
Authors: Rodríguez Amaia , Ezquerro Silvia , Méndez-Giménez Leire , Becerril Sara , Frühbeck Gema
Published: September 2015

Adipose tissue constitutes an extremely active endocrine organ with a network of signaling pathways enabling the organism to adapt to a wide range of different metabolic challenges, such as starvation, stress, infection, and short periods of gross energy excess. The functional pleiotropism of adipose tissue relies on its ability to synthesize and release a huge variety of hormones, cytokines, complement and growth factors, extracellular matrix proteins, and vasoactive factors, collectively termed adipokines. Obesity is associated with adipose tissue dysfunction leading to the onset of several pathologies including type 2 diabetes, dyslipidemia, nonalcoholic fatty liver, or hypertension, among others. The mechanisms underlying the development of obesity and its associated comorbidities include the hypertrophy and/or hyperplasia of adipocytes, adipose tissue inflammation, impaired extracellular matrix remodeling, and fibrosis together with an altered secretion of adipokines. Recently, the potential role of brown and beige adipose tissue in the protection against obesity has been also recognized. In contrast to white adipocytes, which store energy in the form of fat, brown and beige fat cells display energy-dissipating capacity through the promotion of triacylglycerol clearance, glucose disposal, and generation of heat for thermogenesis. Identification of the morphological and molecular changes in white, beige, and brown adipose tissue during weight gain is of utmost relevance for the identification of pharmacological targets for the treatment of obesity and its associated metabolic diseases.
Morning and evening physical exercise differentially regulate the autonomic nervous system during nocturnal sleep in humans
Authors: Yamanaka Yujiro , Hashimoto Satoko , Takasu Nana N. , Tanahashi Yusuke , Nishide Shin-ya , Honma Sato , Honma Ken-ichi
Published: September 2015

Effects of daily physical exercise in the morning or in the evening were examined on circadian rhythms in plasma melatonin and core body temperature of healthy young males who stayed in an experimental facility for 7 days under dim light conditions (<10 lux). Sleep polysomnogram (PSG) and heart rate variability (HRV) were also measured. Subjects performed 2-h intermittent physical exercise with a bicycle ergometer at ZT3 or at ZT10 for four consecutive days, where zeitgeber time 0 (ZT0) was the time of wake-up. The rising phase of plasma melatonin rhythm was delayed by 1.1 h without exercise. Phase-delay shifts of a similar extent were detected by morning and evening exercise. But the falling phase shifted only after evening exercise by 1.0 h. The sleep PSG did not change after morning exercise, while Stage 1+2 sleep significantly decreased by 13.0% without exercise, and RE sleep decreased by 10.5% after evening exercise. The nocturnal decline of rectal temperature was attenuated by evening exercise, but not by morning exercise. HRV during sleep changed differentially. Very low frequency (VLF) waves increased without exercise. VLF, low frequency (LF), and high frequency (HF) waves increased after morning exercise, whereas HR increased after evening exercise. Morning exercise eventually enhanced the parasympathetic activity, as indicated by HRV, while evening exercise activated the sympathetic activity, as indicated by increase in heart rate in the following nocturnal sleep. These findings indicated differential effects of morning and evening exercise on the circadian melatonin rhythm, PSG, and HRV.
Effects of dynamic shear and transmural pressure on wall shear stress sensitivity in collecting lymphatic vessels
Authors: Kornuta Jeffrey A. , Nepiyushchikh Zhanna , Gasheva Olga Y. , Mukherjee Anish , Zawieja David C. , Dixon J. Brandon
Published: September 2015

Given the known mechanosensitivity of the lymphatic vasculature, we sought to investigate the effects of dynamic wall shear stress (WSS) on collecting lymphatic vessels while controlling for transmural pressure. Using a previously developed ex vivo lymphatic perfusion system (ELPS) capable of independently controlling both transaxial pressure gradient and average transmural pressure on an isolated lymphatic vessel, we imposed a multitude of flow conditions on rat thoracic ducts, while controlling for transmural pressure and measuring diameter changes. By gradually increasing the imposed flow through a vessel, we determined the WSS at which the vessel first shows sign of contraction inhibition, defining this point as the shear stress sensitivity of the vessel. The shear stress threshold that triggered a contractile response was significantly greater at a transmural pressure of 5 cmH2O (0.97 dyne/cm2) than at 3 cmH2O (0.64 dyne/cm2). While contraction frequency was reduced when a steady WSS was applied, this inhibition was reversed when the applied WSS oscillated, even though the mean wall shear stresses between the conditions were not significantly different. When the applied oscillatory WSS was large enough, flow itself synchronized the lymphatic contractions to the exact frequency of the applied waveform. Both transmural pressure and the rate of change of WSS have significant impacts on the contractile response of lymphatic vessels to flow. Specifically, time-varying shear stress can alter the inhibition of phasic contraction frequency and even coordinate contractions, providing evidence that dynamic shear could play an important role in the contractile function of collecting lymphatic vessels.
Do ASARM peptides play a role in nephrogenic systemic fibrosis?
Authors: Rowe Peter S. N. , Zelenchuk Lesya V. , Laurence Jennifer S. , Lee Phil , Brooks William M. , McCarthy Ellen T.
Published: September 2015

Nephrogenic systemic fibrosis (NSF) is a devastating condition associated with gadolinium (Gd3+)-based contrast agents (GBCAs) in patients with kidney disease. The release of toxic Gd3+ from GBCAs likely plays a major role in NSF pathophysiology. The cause and etiology of Gd3+ release from GBCAs is unknown. Increased Acidic Serine Aspartate Rich MEPE-associated peptides (ASARM peptides) induce bone mineralization abnormalities and contribute to renal phosphate-handling defects in inherited hypophosphatemic rickets and tumor-induced osteomalacia. The proteolytic cleavage of related bone matrix proteins with ASARM motifs results in release of ASARM peptide into bone and circulation. ASARM peptides are acidic, reactive, phosphorylated inhibitors of mineralization that bind Ca2+ and hydroxyapatite. Since the ionic radius of Gd3+ is close to that of Ca2+, we hypothesized that ASARM peptides increase the risk of NSF by inducing release of Gd3+ from GBCAs. Here, we show 1) ASARM peptides bind and induce release of Gd3+ from GBCAs in vitro and in vivo; 2) A bioengineered peptide (SPR4) stabilizes the Gd3+-GBCA complex by specifically binding to ASARM peptide in vitro and in vivo; and 3) SPR4 peptide infusion prevents GBCA-induced NSF-like pathology in a murine model with increased ASARM peptide (Hyp mouse). We conclude ASARM peptides may play a role in NSF and SPR4 peptide is a candidate adjuvant for preventing or reducing risk of disease.
Functional differentiation of cholinergic and noradrenergic modulation in a biophysical model of olfactory bulb granule cells
Authors: Li Guoshi , Linster Christiane , Cleland Thomas A.
Published: September 2015

Olfactory bulb granule cells are modulated by both acetylcholine (ACh) and norepinephrine (NE), but the effects of these neuromodulators have not been clearly distinguished. We used detailed biophysical simulations of granule cells, both alone and embedded in a microcircuit with mitral cells, to measure and distinguish the effects of ACh and NE on cellular and microcircuit function. Cholinergic and noradrenergic modulatory effects on granule cells were based on data obtained from slice experiments; specifically, ACh reduced the conductance densities of the potassium M current and the calcium-dependent potassium current, whereas NE nonmonotonically regulated the conductance density of an ohmic potassium current. We report that the effects of ACh and NE on granule cell physiology are distinct and functionally complementary to one another. ACh strongly regulates granule cell firing rates and afterpotentials, whereas NE bidirectionally regulates subthreshold membrane potentials. When combined, NE can regulate the ACh-induced expression of afterdepolarizing potentials and persistent firing. In a microcircuit simulation developed to investigate the effects of granule cell neuromodulation on mitral cell firing properties, ACh increased spike synchronization among mitral cells, whereas NE modulated the signal-to-noise ratio. Coapplication of ACh and NE both functionally improved the signal-to-noise ratio and enhanced spike synchronization among mitral cells. In summary, our computational results support distinct and complementary roles for ACh and NE in modulating olfactory bulb circuitry and suggest that NE may play a role in the regulation of cholinergic function.