bluuebunny/crossref_metadata_2025 huggingface dataset:
Neutralization of Clostridium difficile Toxin B Mediated by Engineered Lactobacilli That Produce Single-Domain Antibodies
Authors: Andersen Kasper Krogh , Strokappe Nika M. , Hultberg Anna , Truusalu Kai , Smidt Imbi , Mikelsaar Raik-Hiio , Mikelsaar Marika , Verrips Theo , Hammarström Lennart , Marcotte Harold
Published: November 2015

Clostridium difficile
is the primary cause of nosocomial antibiotic-associated diarrhea in the Western world. The major virulence factors of
C. difficile
are two exotoxins, toxin A (TcdA) and toxin B (TcdB), which cause extensive colonic inflammation and epithelial damage manifested by episodes of diarrhea. In this study, we explored the basis for an oral antitoxin strategy based on engineered
Lactobacillus
strains expressing TcdB-neutralizing antibody fragments in the gastrointestinal tract. Variable domain of heavy chain-only (VHH) antibodies were raised in llamas by immunization with the complete TcdB toxin. Four unique VHH fragments neutralizing TcdB
in vitro
were isolated. When these VHH fragments were expressed in either secreted or cell wall-anchored form in
Lactobacillus paracasei
BL23, they were able to neutralize the cytotoxic effect of the toxin in an
in vitro
cell-based assay. Prophylactic treatment with a combination of two strains of engineered
L. paracasei
BL23 expressing two neutralizing anti-TcdB VHH fragments (VHH-B2 and VHH-G3) delayed killing in a hamster protection model where the animals were challenged with spores of a TcdA
−
TcdB
+
strain of
C. difficile
(
P
< 0.05). Half of the hamsters in the treated group survived until the termination of the experiment at day 5 and showed either no damage or limited inflammation of the colonic mucosa despite having been colonized with
C. difficile
for up to 4 days. The protective effect in the hamster model suggests that the strategy could be explored as a supplement to existing therapies for patients.
Formation of an Intramolecular Periplasmic Disulfide Bond in TcpP Protects TcpP and TcpH from Degradation in Vibrio cholerae
Authors: Morgan Sarah J. , French Emily L. , Thomson Joshua J. , Seaborn Craig P. , Shively Christian A. , Krukonis Eric S.
Published: November 2015

TcpP and ToxR coordinately regulate transcription of
toxT
, the master regulator of numerous virulence factors in
Vibrio cholerae
. TcpP and ToxR are membrane-localized transcription factors, each with a periplasmic domain containing two cysteines. In ToxR, these cysteines form an intramolecular disulfide bond and a cysteine-to-serine substitution affects activity. We determined that the two periplasmic cysteines of TcpP also form an intramolecular disulfide bond. Disruption of this intramolecular disulfide bond by mutation of either cysteine resulted in formation of intermolecular disulfide bonds. Furthermore, disruption of the intramolecular disulfide bond in TcpP decreased the stability of TcpP. While the decreased stability of TcpP-C207S resulted in a nearly complete loss of
toxT
activation and cholera toxin (CT) production, the second cysteine mutant, TcpP-C218S, was partially resistant to proteolytic degradation and maintained ∼50%
toxT
activation capacity. TcpP-C218S was also TcpH independent, since deletion of
tcpH
did not affect the stability of TcpP-C218S, whereas wild-type TcpP was degraded in the absence of TcpH. Finally, TcpH was also unstable when intramolecular disulfides could not be formed in TcpP, suggesting that the single periplasmic cysteine in TcpH may assist with disulfide bond formation in TcpP by interacting with the periplasmic cysteines of TcpP. Consistent with this finding, a TcpH-C114S mutant was unable to stabilize TcpP and was itself unstable. Our findings demonstrate a periplasmic disulfide bond in TcpP is critical for TcpP stability and virulence gene expression.

IMPORTANCE
The
Vibrio cholerae
transcription factor TcpP, in conjunction with ToxR, regulates transcription of
toxT
, the master regulator of numerous virulence factors in
Vibrio cholerae
. TcpP is a membrane-localized transcription factor with a periplasmic domain containing two cysteines. We determined that the two periplasmic cysteines of TcpP form an intramolecular disulfide bond and disruption of the intramolecular disulfide bond in TcpP decreased the stability of TcpP and reduced virulence gene expression. Normally TcpH, another membrane-localized periplasmic protein, protects TcpP from degradation. However, we found that TcpH was also unstable when intramolecular disulfides could not be formed in TcpP, indicating that the periplasmic cysteines of TcpP are required for functional interaction with TcpH and that this interaction is required for both TcpP and TcpH stability.
The Gonococcal NlpD Protein Facilitates Cell Separation by Activating Peptidoglycan Cleavage by AmiC
Authors: Stohl Elizabeth A. , Lenz Jonathan D. , Dillard Joseph P. , Seifert H. Steven
Published: November 2015

Key steps in bacterial cell division are the synthesis and subsequent hydrolysis of septal peptidoglycan (PG), which allow efficient separation of daughter cells. Extensive studies in the Gram-negative, rod-shaped bacteriumEscherichia colihave revealed that this hydrolysis is highly regulated spatially and temporally.Neisseria gonorrhoeaeis an obligate Gram-negative, diplococcal pathogen and is the only causative agent of the sexually transmitted infection gonorrhea. We investigated how cell separation proceeds in this diplococcal organism. We demonstrated that deletion of thenlpDgene in strain FA1090 leads to poor growth and to an altered colony and cell morphology. An isopropyl-beta-d-galactopyranoside (IPTG)-regulatednlpDcomplemented construct can restore these defects only when IPTG is supplied in the growth medium. Thin-section transmission electron microscopy (TEM) revealed that thenlpDmutant strain grew in large clumps containing live and dead bacteria, which was consistent with deficient cell separation. Biochemical analyses of purified NlpD protein showed that it was able to bind purified PG. Finally, we showed that, although NlpD has no hydrolase activity itself, NlpD potentiates the hydrolytic activity of AmiC. These results indicate thatN. gonorrhoeaeNlpD is required for proper cell growth and division through its interactions with the amidase AmiC.

IMPORTANCEN. gonorrhoeaeis the sole causative agent of the sexually transmitted infection gonorrhea. The incidence of antibiotic-resistant gonococcal infections has risen sharply in recent years, andN. gonorrhoeaehas been classified as a “superbug” by the CDC. Since there is a dearth of new antibiotics to combat gonococcal infections, elucidating the essential cellular process ofN. gonorrhoeaemay point to new targets for antimicrobial therapies. Cell division and separation is one such essential process. We identified and characterized the gonococcalnlpDgene and showed that it is essential for cell separation. In contrast to other pathogenic bacteria, the gonococcal system is streamlined and does not appear to have any redundancies.
Cyclic Di-GMP Regulates Multiple Cellular Functions in the Symbiotic Alphaproteobacterium Sinorhizobium meliloti
Authors: Schäper Simon , Krol Elizaveta , Skotnicka Dorota , Kaever Volkhard , Hilker Rolf , Søgaard-Andersen Lotte , Becker Anke
Published: November 2015

Sinorhizobium meliloti
undergoes major lifestyle changes between planktonic states, biofilm formation, and symbiosis with leguminous plant hosts. In many bacteria, the second messenger 3′,5′-cyclic di-GMP (c-di-GMP, or cdG) promotes a sessile lifestyle by regulating a plethora of processes involved in biofilm formation, including motility and biosynthesis of exopolysaccharides (EPS). Here, we systematically investigated the role of cdG in
S. meliloti
Rm2011 encoding 22 proteins putatively associated with cdG synthesis, degradation, or binding. Single mutations in 21 of these genes did not cause evident changes in biofilm formation, motility, or EPS biosynthesis. In contrast, manipulation of cdG levels by overproducing endogenous or heterologous diguanylate cyclases (DGCs) or phosphodiesterases (PDEs) affected these processes and accumulation of
N
-Acyl-homoserine lactones in the culture supernatant. Specifically, individual overexpression of the
S. meliloti
genes
pleD
,
SMb20523
,
SMb20447
,
SMc01464
, and
SMc03178
encoding putative DGCs and of
SMb21517
encoding a single-domain PDE protein had an impact and resulted in increased levels of cdG. Compared to the wild type, an
S. meliloti
strain that did not produce detectable levels of cdG (cdG
0
) was more sensitive to acid stress. However, it was symbiotically potent, unaffected in motility, and only slightly reduced in biofilm formation. The
SMc01790-SMc01796
locus, homologous to the
Agrobacterium tumefaciens
uppABCDEF
cluster governing biosynthesis of a unipolarly localized polysaccharide, was found to be required for cdG-stimulated biofilm formation, while the single-domain PilZ protein McrA was identified as a cdG receptor protein involved in regulation of motility.

IMPORTANCE
We present the first systematic genome-wide investigation of the role of 3′,5′-cyclic di-GMP (c-di-GMP, or cdG) in regulation of motility, biosynthesis of exopolysaccharides, biofilm formation, quorum sensing, and symbiosis in a symbiotic alpha-rhizobial species. Phenotypes of an
S. meliloti
strain unable to produce cdG (cdG
0
) demonstrated that this second messenger is not essential for root nodule symbiosis but may contribute to acid tolerance. Our data further suggest that enhanced levels of cdG promote sessility of
S. meliloti
and uncovered a single-domain PilZ protein as regulator of motility.
A systematic review of stroke recognition instruments in hospital and prehospital settings
Authors: Rudd Matthew , Buck Deborah , Ford Gary A , Price Christopher I
Published: November 2015

Background

We undertook a systematic review of all published stroke identification instruments to describe their performance characteristics when used prospectively in any clinical setting.

Methods

A search strategy was applied to Medline and Embase for material published prior to 10 August 2015. Two authors independently screened titles, and abstracts as necessary. Data including clinical setting, reported sensitivity, specificity, positive predictive value, negative predictive value were extracted independently by two reviewers.

Results

5622 references were screened by title and or abstract. 18 papers and 3 conference abstracts were included after full text review. 7 instruments were identified; Face Arm Speech Test (FAST), Recognition of Stroke in the Emergency Room (ROSIER), Los Angeles Prehospital Stroke Screen (LAPSS), Melbourne Ambulance Stroke Scale (MASS), Ontario Prehospital Stroke Screening tool (OPSS), Medic Prehospital Assessment for Code Stroke (MedPACS) and Cincinnati Prehospital Stroke Scale (CPSS). Cohorts varied between 50 and 1225 individuals, with 17.5% to 92% subsequently receiving a stroke diagnosis. Sensitivity and specificity for the same instrument varied across clinical settings. Studies varied in terms of quality, scoring 13–31/36 points using modified Standards for the Reporting of Diagnostic accuracy studies checklist. There was considerable variation in the detail reported about patient demographics, characteristics of false-negative patients and service context. Prevalence of instrument detectable stroke varied between cohorts and over time. CPSS and the similar FAST test generally report the highest level of sensitivity, with more complex instruments such as LAPSS reporting higher specificity at the cost of lower detection rates.

Conclusions

Available data do not allow a strong recommendation to be made about the superiority of a stroke recognition instrument. Choice of instrument depends on intended purpose, and the consequences of a false-negative or false-positive result.
Effects of an acute bout of moderate-intensity exercise on postprandial lipemia and airway inflammation
Authors: Johnson Ariel M. , Kurti Stephanie P. , Smith Joshua R. , Rosenkranz Sara K. , Harms Craig A.
Published: November 2015

A high-fat meal (HFM) induces an increase in blood lipids (postprandial lipemia; PPL), systemic inflammation, and acute airway inflammation. While acute exercise has been shown to have anti-inflammatory and lipid-lowering effects, it is unknown whether exercise prior to an HFM will translate to reduced airway inflammation post-HFM. Our purpose was to determine the effects of an acute bout of exercise on airway inflammation post-HFM and to identify whether any protective effect of exercise on airway inflammation was associated with a reduction in PPL or systemic inflammation. In a randomized cross-over study, 12 healthy, 18- to 29-year-old men (age, 23.0 ± 3.2 years; height, 178.9 ± 5.5 cm; weight, 78.5 ± 11.7 kg) consumed an HFM (1 g fat/1 kg body weight) 12 h following exercise (EX; 60 min at 60% maximal oxygen uptake) or without exercise (CON). Fractional exhaled nitric oxide (FENO; measure of airway inflammation), triglycerides (TG), and inflammatory markers (high-sensitivity C-reactive protein, tumor-necrosis factor-alpha, and interleukin-6) were measured while fasted at 2 h and 4 h post-HFM. FENOincreased over time (2 h: CON, p = 0.001; EX, p = 0.002, but not by condition (p = 0.991). TG significantly increased 2 and 4 h post-HFM (p < 0.001), but was not significant between conditions (p = 0.256). Inflammatory markers did not significantly increase by time or condition (p > 0.05). There were no relationships between FENOand TG or systemic inflammatory markers for any time point or condition (p > 0.05). In summary, an acute bout of moderate-intensity exercise performed 12 h prior to an HFM did not change postprandial airway inflammation or lipemia in healthy, 18- to 29-year-old men.
Influence of cross correlation between soil parameters on probability of failure of simple cohesive and c-ϕ slopes
Authors: Javankhoshdel Sina , Bathurst Richard J.
Published: November 2015

This paper focuses on the calculation of probability of failure of simple unreinforced slopes and the influence of the magnitude of cross correlation between soil parameters on numerical outcomes. A general closed-form solution for cohesive slopes with cross correlation between cohesion and unit weight was investigated and results compared with cases without cross correlation. Negative cross correlations between cohesion and friction angle and positive cross correlations between cohesion and unit weight, and friction angle and unit weight were considered in the current study. The factors of safety and probabilities of failure for the slopes with uncorrelated soil properties were obtained using probabilistic slope stability design charts previously reported by the writers. Results for cohesive soil slopes and positive cross correlation between cohesion and unit weight are shown to decrease probability of failure. Probability of failure also decreased for increasing negative cross correlation between cohesion and friction angle, and increasing positive correlation between cohesion and unit weight, and friction angle and unit weight. Probabilistic slope stability design charts presented by the writers in an earlier publication are extended to include cohesive-frictional (c-[Formula: see text]) soil slopes with and without cross correlation between soil input parameters. An important outcome of the work presented here is that cross correlation between random values of soil properties can reduce the probability of failure for simple slope cases. Hence, previous probabilistic design charts by the writers for simple soil slopes with uncorrelated soil properties are conservative (safe) for design. This study also provides one explanation why slope stability analyses using uncorrelated soil properties can predict unreasonably high probabilities of failure when conventional estimates of factor of safety suggest a stable slope.
Juvenile life-history diversity and population stability of spring Chinook salmon in the Willamette River basin, Oregon
Authors: Schroeder R. Kirk , Whitman Luke D. , Cannon Brian , Olmsted Paul
Published: November 2015

Migratory and rearing pathways of juvenile spring Chinook salmon (Oncorhynchus tshawytscha) were documented in the Willamette River basin to identify life histories and estimate their contribution to smolt production and population stability. We identified six primary life histories that included two phenotypes for early migratory tactics: fry that migrated up to 140–200 km shortly after emergence (movers) and fish that reared for 8–16 months in natal areas (stayers). Peak emigration of juvenile salmon from the Willamette River was in June–July (subyearling smolts), March–May (yearling smolts), and November–December (considered as “autumn smolts”). Alternative migratory behaviors of juvenile salmon were associated with extensive use of diverse habitats that eventually encompassed up to 400 rkm of the basin, including tributaries in natal areas and large rivers. Juvenile salmon that reared in natal reaches and migrated as yearlings were the most prevalent life history and had the lowest temporal variability. However, the total productivity of the basin was increased by the contribution of fish with dispersive life histories, which represented over 50% of the total smolt production. Life-history diversity reduced the variability in the total smolt population by 35% over the weighted mean of individual life histories, providing evidence of a considerable portfolio effect through the asynchronous contributions of life histories. Protecting and restoring a diverse suite of connected habitats in the Willamette River basin will promote the development and expression of juvenile life histories, thereby providing stability and resilience to native salmon populations.
SERVICE REALIZATION AND DETERMINANTS IN AGRICULTURAL COOPERATIVES IN CHINA: EVIDENCE FROM ZHEJIANG, SICHUAN AND HEILONGJIANG PROVINCES
Authors: GAO YULING , HUANG ZUHUI , LIANG QIAO
Published: November 2015

In the past decade, China has begun to develop the agricultural cooperatives. The service function is the most important reason for cooperatives’ existence. This paper formulates an analytical framework regarding the realization of services in cooperatives from the perspective of agricultural industrialization. Firstly, the definition, measurement and determinants of service realization are analyzed theoretically. Then, the realization of services, as well as influencing the service realization are examined empirically regarding grain, vegetable, fruit, livestock and chicken in the Zhejiang, Sichuan and Heilongjiang provinces. The paper concludes that product characteristics, resources owned by members, entrepreneurship of managers and incentives to managers have significant and positive impacts on the service realization.
A review of WIMP baryogenesis mechanisms
Authors: Cui Yanou
Published: November 2015

It was recently proposed that weakly interacting massive particles (WIMP) may provide new ways of generating the observed baryon asymmetry in the early universe, as well as addressing the cosmic coincidence between dark matter (DM) and baryon abundances. This suggests a new possible connection between weak scale new particle physics and modern cosmology. This review summarizes the general ideas and simple model examples of the two recently proposed WIMP baryogenesis mechanisms: baryogenesis from WIMP DM annihilation during thermal freeze-out, and baryogenesis from metastable WIMP decay after thermal freeze-out. This review also discusses the interesting phenomenology of these models, in particular, the experimental signals that can be probed in the intensity frontier experiments and the large hadron collider (LHC) experiments.
NUMERICAL SIMULATIONS OF A NONLINEAR STOCHASTIC PARTIAL DIFFERENTIAL EQUATION MODELING PHYTOPLANKTON AGGREGATION
Authors: EL SAADI NADJIA , BAH ALASSANE
Published: November 2015

In this paper, we are interested in the numerical simulation of a nonlinear stochastic partial differential equation (SPDE) arising as a model of phytoplankton aggregation. This SPDE consists of a diffusion equation with a chemotaxis term and a branching noise. We develop and implement a numerical scheme to solve this SPDE and present its numerical solutions for parameter values corresponding to real conditions in nature. Further, a comparison is made with two deterministic versions of the SPDE, that are advection–diffusion equations with linear and nonlinear reaction terms, to emphasize the efficiency of the stochastic equation in modeling the aggregation behavior in phytoplankton.
How Information from Taiwan-based Enterprises in China Influences Investment Decisions of China-based Service Enterprises in Taiwan
Authors: Lin Chun Ju
Published: November 2015

This study yielded insights based on eight China-based service enterprises that entered the overseas Chinese market through greenfield investment. We found that some of the China-based service enterprises explore the internationalization information from Taiwan-based enterprises in China, which operated through trade, outsourcing and joint ventures. Most cases of SOEs, including airlines, wholesale & retail, restaurant and banking, the investment decision was made in full awareness of the institutional driving factor of ECFA. China-based service enterprises owned by local government and venturing in Taiwan are more likely to depend on personal or partner networks of Taiwan-based enterprises in China, than on due diligence process. They intend to venture into the overseas Chinese market for their outward FDI. Our findings and propositions are important for China-based service enterprises’ outward FDI. Asian host countries can improve their understanding of how to influence the FDI of China-based service enterprises through their home-country-based enterprises in China, helping to mitigate their liability of foreignness by means of personal or partner networks.
BIOMECHANICAL STABILITY OF THE CERVICAL SPINE AFTER UNCINATE PROCESS RESECTION: A FINITE ELEMENT ANALYSIS
Authors: BO XUEFENG , MEI XI , WANG HUI , WANG WEIDA , CHEN ZAN , LIU ZHICHENG
Published: November 2015

When performing anterolateral foraminotomy for the treatment of cervical spondylotic radiculopathy, the extent of uncinate process resection affects the stability of the cervical spine. The aim of this study was to determine the stability of the cervical spine after resection of various amounts of the uncinate process. Based on computed tomography (CT) scans of an adult male volunteer, a three-dimensional geometric model of the cervical spine (C4-C6) was established using Mimics 13.1, SolidWorks 2012, and ANSYS 15.0 software packages. Next, the mechanical parameters of the tissues were assigned according to their different material characteristics. Using the tetrahedral mesh method, a three-dimensional finite element model of the cervical spine was then established. In modeling uncinated process resection, two excision protocols were compared. The first excision protocol, protocol A, mimicked the extent of resection used in current clinical surgical practice. The second excision protocol, protocol B, employed an optimal resection extent as predicted by the finite element model. Protocols A and B were then used to resect the left uncinate process of the C5 vertebra to either 50% or 60% of the total height of the uncinate process. The stability of the cervical spine was assessed by evaluating values of deformation and maximum equivalent stress during extension, flexion, lateral bending, and rotation. After protocol A resection, the total deformation was increased as was the maximum equivalent stress during left and right rotation. After protocol B resection, the total deformation was little changed and the maximum equivalent stress was visibly decreased during left and right rotation. As evidenced by these results, protocol B resection had relatively little effect on the stability of the cervical spine, suggesting that resection utilizing the limits proposed in protocol B appears to better maintain the stability of the cervical spine when compared with current clinical surgical practice as replicated in protocol A.
THE INTERACTION POTENTIAL BETWEEN MICRO/NANO CURVED SURFACE BODY WITH NEGATIVE GAUSS CURVATURE AND AN OUTSIDE PARTICLE
Authors: WANG DAN , YIN YAJUN , WU JIYE , ZHONG ZHENG
Published: November 2015

Based on the negative exponential pair potential ([Formula: see text]), the interaction potential between curved surface body with negative Gauss curvature and an outside particle is proved to be of curvature-based form, i.e., it can be written as a function of curvatures. Idealized numerical experiments are designed to test the accuracy of the curvature-based potential. Compared with the previous results, it is confirmed that the interaction potential between curved surface body and an outside particle has a unified expression of curvatures regardless of the sign of Gauss curvature. Further, propositions below are confirmed: Highly curved surface body may induce driving forces, curvatures and the gradient of curvatures are the essential factors forming the driving forces.
Coherent states, vacuum structure and infinite component relativistic wave equations
Authors: Cirilo-Lombardo Diego Julio
Published: November 2015

It is commonly claimed in the recent literature that certain solutions to wave equations of positive energy of Dirac-type with internal variables are characterized by a non-thermal spectrum. As part of that statement, it was said that the transformations and symmetries involved in equations of such type corresponded to a particular representation of the Lorentz group. In this paper, we give the general solution to this problem emphasizing the interplay between the group structure, the corresponding algebra and the physical spectrum. This analysis is completed with a strong discussion and proving that: (i) the physical states are represented by coherent states; (ii) the solutions in [Yu. P. Stepanovsky, Nucl. Phys. B (Proc. Suppl.) 102 (2001) 407–411; 103 (2001) 407–411] are not general, (iii) the symmetries of the considered physical system in [Yu. P. Stepanovsky, Nucl. Phys. B (Proc. Suppl.) 102 (2001) 407–411; 103 (2001) 407–411] (equations and geometry) do not correspond to the Lorentz group but to the fourth covering: the Metaplectic group [Formula: see text].
ENTREPRENEURSHIP EDUCATION IN THE CONTEXT OF DEVELOPING COUNTRIES: STUDY OF THE STATUS AND THE MAIN BARRIERS IN MOZAMBICAN HIGHER EDUCATION INSTITUTIONS
Authors: LIBOMBO DAMBUSSE B. , DINIS ANABELA
Published: November 2015

This study focuses on the issue of entrepreneurship education and the role of Higher Education Institutions (HEI) in the context of developing countries. More specifically it aims to understand how entrepreneurship education is being implemented in Mozambique and to identify the main barriers to the creation of companies promoted by/incubated in HEI with entrepreneurship education in their curricula. The paper includes theoretical discussion and the presentation of a case study. It begins with a literature review about the relationship between entrepreneurship and development followed by a discussion about entrepreneurship education in the context of developing countries and entrepreneurship education provided by HEI. The empirical study is focused in Mozambique. After a contextualization of entrepreneurship education in Mozambique, Mozambican HEI with entrepreneurship education are identified and their situation and difficulties concerning the implementation of entrepreneurship education are discussed. Data collection includes documental sources and interviews with HEI representatives of a sample of ten establishments of the universe of five public and private HEI with entrepreneurship education in Mozambique. Results indicate that lack of resources, trained/qualified teachers and cooperation networks with the business community and other relevant actors are the main barriers.
HOW MUCH CARBON PRICING IS IN COUNTRIES’ OWN INTERESTS? THE CRITICAL ROLE OF CO-BENEFITS
Authors: PARRY IAN , VEUNG CHANDARA , HEINE DIRK
Published: November 2015

This paper calculates, for the top 20 emitting countries, how much pricing of carbon dioxide (CO2) emissions would be in their own national interests due to domestic co-benefits (leaving aside the global climate benefits). On average, second-best domestic prices are substantial, $57.5 per ton of CO2 (for year 2010), reflecting primarily health co-benefits from reduced air pollution at coal plants and, in some cases, reductions in automobile externalities net of fuel taxes/subsidies. Pricing co-benefits reduces CO2 emissions from the top 20 emitters by 13.5%. However, co-benefits vary dramatically across countries (e.g., with population exposure to pollution) and differentiated pricing of CO2 emissions therefore yields higher net benefits (by 23%) than uniform pricing. Importantly, the efficiency case for pricing carbon’s co-benefits hinges critically on weak prospects (for the foreseeable future) for comprehensive internalization of other externalities through other (more efficient) pricing instruments.
China’s Industrialization and the Pathway of Industrial CO2 Emissions
Authors: CHEN Zi , LIU Changyi , QU Shenning
Published: November 2015

Industrial sector is the largest CO2 emission sector in China, thus the peak of China’s total CO2 emissions relies heavily on its industrial sector. After rapid industrialization during the last three decades, China now is between the intermediate and the late industrialization stage in general. Looking at the production and emission structures of China’s industries, especially the heavy and chemical industrial sectors which are energy- and emission-intensive industries, we claim that the output of these heavy and chemical industries will peak at around 2020, the industrialization process will complete at around 2025 and after that, China will enter the post-industrialization era. According to the CO2 emission pathways of developed countries during their industrialization, i.e. the so-called “Carbon Kuznets Curve”, and based on the characteristics of China’s industrialization and urbanization process, it is estimated that the CO2 emissions from the industrial sector will keep rising over time and reach its peak at around the year 2040 in the business-as-usual scenario; while in the low-carbon scenario, it will peak between 2025 and 2030 and decline after the year 2040.
Layer‐by‐Layer Self‐Assembled Ferrite Multilayer Nanofilms for Microwave Absorption
Authors: Heo Jiwoong , Choi Daheui , Hong Jinkee
Published: November 2015

We demonstrate a simple method for fabricating multilayer thin films containing ferrite (Co0.5Zn0.5Fe2O4) nanoparticles, using layer‐by‐layer (LbL) self‐assembly. These films have microwave absorbing properties for possible radar absorbing and stealth applications. To demonstrate incorporation of inorganic ferrite nanoparticles into an electrostatic‐interaction‐based LbL self‐assembly, we fabricated two types of films: (1) a blended three‐component LbL film consisting of a sequential poly(acrylic acid)/oleic acid‐ferrite blend layer and a poly(allylamine hydrochloride) layer and (2) a tetralayer LbL film consisting of sequential poly(diallyldimethylammonium chloride), poly(sodium‐4‐sulfonate), bPEI‐ferrite, and poly(sodium‐4‐sulfonate) layers. We compared surface morphologies, thicknesses, and packing density of the two types of ferrite multilayer film. Ferrite nanoparticles (Co0.5Zn0.5Fe2O4) were prepared via a coprecipitation method from an aqueous precursor solution. The structure and composition of the ferrite nanoparticles were characterized by X‐ray diffraction, energy dispersive X‐ray spectroscopy, transmission electron microscopy, and scanning electron microscopy. X‐ray diffraction patterns of ferrite nanoparticles indicated a cubic spinel structure, and energy dispersive X‐ray spectroscopy revealed their composition. Thickness growth and surface morphology were measured using a profilometer, atomic force microscope, and scanning electron microscope.
Extracellular Polyhydroxyalkanoate Depolymerase by Acidovorax sp. DP5
Authors: Vigneswari S. , Lee T. S. , Bhubalan Kesaven , Amirul A. A.
Published: November 2015

Bacteria capable of degrading polyhydroxyalkanoates (PHA) by secreting extracellular depolymerase enzymes were isolated from water and soil samples collected from various environments in Malaysia. A total of 8 potential degraders exhibited clear zones on poly(3-hydroxybutyrate) [P(3HB)] based agar, indicating the presence of extracellular PHA depolymerase. Among the isolates, DP5 exhibited the largest clearing zone with a degradation index of 6.0. The highest degradation activity of P(3HB) was also observed with depolymerase enzyme of DP5 in mineral salt medium containing P(3HB). Based on biochemical characterization and 16S rRNA cloning and sequencing, isolate DP5 was found to belong to the genus Acidovorax and subsequently named as Acidovorax sp. DP5. The highest extracellular depolymerase enzyme activity was achieved when 0.25% (w/v) of P(3HB) and 1 g/L of urea were used as carbon and nitrogen source, respectively, in the culture media. The most suitable assay condition of the depolymerase enzyme in response to pH and temperature was tested. The depolymerase produced by strain Acidovorax sp. DP5 showed high percentage of degradation with P(3HB) films in an alkaline condition with pH 9 and at a temperature of 40°C.
Synthesis, Characterization, andIn VitroDrug Delivery Capabilities of (Zn, Al)-Based Layered Double Hydroxide Nanoparticles
Authors: Nagaraj Vinay J. , Sun Xiaodi , Mehta Jiten , Martin Mac , Ngo Thi , Dey Sandwip K.
Published: November 2015

There is an urgent need for the development of alternative strategies for effective drug delivery to improve the outcome of patients suffering from deadly diseases such as cancer. Nanoparticles, in particular layered double hydroxide (LDH) nanoparticles, have great potential as nanocarriers of chemotherapeutic molecules. In this study, we synthesized (Zn, Al)-LDH nanoparticles and report their enhanced pH-dependent stability in comparison to the commonly used (Mg, Al)-LDH nanoparticles. Fluorescein isothiocyanate (FITC) and valproate (VP) were intercalated into (Zn, Al)-LDH nanoparticles to study cellular uptake, biocompatibility, and drug delivery capabilities using cultured pancreatic adenocarcinoma BxPC3 cells. Fluorescence measurements indicated that FITC-intercalated LDH nanoparticles showed a greater degree of energy-dependent uptake rather than passive uptake by BxPC3 cells, especially at high concentrations of nanoparticles. Tetrazolium-based colorimetric assays indicated that BxPC3 cells treated with VP-intercalated LDH nanoparticles showed a significant reduction in cell viability along with about 30-fold reduction in IC50compared to the drug alone. In contrast, the non-drug-intercalated LDH nanoparticles did not affect the cell viability indicating very low innate cytotoxicity. Our research indicates that the superior properties of (Zn, Al)-LDH nanoparticles make them ideal candidates for further development asin vivochemotherapy drug delivery agents.
Histological and Biochemical Evaluation of the Kidney following Chronic Consumption of Hibiscus sabdariffa
Authors: Ukoha U. U. , Mbagwu S. I. , Ndukwe G. U. , Obiagboso C.
Published: November 2015

Hibiscus sabdariffa L. has been used traditionally as herbal medicine and has been documented to have a broad range of therapeutic effects. The present study aimed to investigate the effects of chronic administration of aqueous extract of flowers of Hibiscus sabdariffa on the histology of the kidney and some biochemical indices of renal function in male Wistar rats. Twenty (20) Wistar rats were randomly divided into four (4) groups of five rats each. The extract was administered orally in doses 200, 500, and 800 mg/kg body weight for 21 days. The kidney was harvested and processed histologically and blood samples were taken for biochemical assays. The histological results showed dose dependent pathological states and the biochemical analysis revealed a dose dependant variation in renal indices. These results suggest that chronic administration of aqueous extract of Hibiscus sabdariffa may be toxic to the kidney.
Graphene Nanoplatelets in Epoxy System: Dispersion, Reaggregation, and Mechanical Properties of Nanocomposites
Authors: Wei Jiacheng , Atif Rasheed , Vo Thuc , Inam Fawad
Published: November 2015

The use of graphene nanocomposites in advanced applications has attracted much attention in recent years. However, in order to substitute traditional epoxy reinforcements with graphene, there are still some issues like dispersion, homogenization, and reaggregation. In this paper, graphene bundles dispersed in two‐component epoxy system by bath sonication, dispersion state, and reaggregation behavior of graphene in this system have been studied. Light transmittance in ultraviolet‐visible spectroscopy has been used to quantify the reaggregation by a series of controlled experiments. After 18 mins sonication of 0.005 wt% graphene dispersion at 20°C, the light transmittance decreased from 68.92% to 54.88% in liquid epoxy and decreased from 72.80% to 46.42% in hardener; while increasing the temperature from 20°C to 60°C, the light transmittance in liquid epoxy decreased from 65.96% to 53.21% after 6 mins sonication. With the incorporation of 0.3 wt% graphene, the tensile strength of nanocomposites increased from 57.2 MPa to 64.4 MPa and the storage modulus increased from 1.66 GPa to 2.16 GPa. The results showed that the dispersion state depends on the function of sonication time and temperature, and graphene has a significant reinforcement effect on epoxy.
Cytogenotoxicity of Abattoir Effluent in Clarias gariepinus (Burchell, 1822) Using Micronucleus Test
Authors: Alimba Chibuisi G. , Ajayi Ebenezer O. , Hassan Titilayo , Sowunmi Akindayo A. , Bakare Adekunle A.
Published: November 2015

The cytogenotoxic potential of abattoir effluent from Bodija, Nigeria, was investigated using micronucleus test in Clarias gariepinus. Fish was exposed to five different concentrations: 0.2, 0.4, 0.8, 1.6, and 3.1% of the effluent for 7, 14, and 28 days. Tap water and 0.02 mL/L of benzene were used as negative and positive controls, respectively. Physicochemical parameters and heavy metals were analyzed in the effluent in accordance with standard methods. After exposure, blood was collected from the treated and control fish and slides were prepared for micronuclei (MN) and nuclear abnormality evaluation in the peripheral erythrocytes. The effluent induced significant (p<0.05) increase in the frequency of MN in a time dependent manner. Similarly, the frequency of total nuclear abnormalities (blebbing, notch, bud, binucleation, and vacuolation) was higher in the exposed fish than the negative control. Electrical conductivity, nitrate, biochemical oxygen demand, chemical oxygen demand, arsenic, and copper analyzed in the effluent may have provoked the observed cytogenetic damage. The findings herein suggest the presence of clastogens and cytotoxins in Bodija abattoir wastewater which are capable of increasing genomic instability in aquatic biota.
In Vitro Hemocompatibility and Cytotoxicity Evaluation of Halloysite Nanotubes for Biomedical Application
Authors: Liu Hao-Yang , Du Lei , Zhao Yan-Teng , Tian Wei-Qun
Published: November 2015

Halloysite nanotubes (HNTs), due to their unique structures and properties, may play an important role in biomedical applications. In vitro test is usually conducted as a preliminary screening evaluation of the hemocompatibility and cytotoxicity of HNTs for its short term consuming, convenience, and less expense. In this work, HNTs were processed with anticoagulated rabbit blood to detect its blood compatibility. The result of hemolysis test shows that the hemolysis ratios are below 0.5%, indicating nonhemolysis of HNTs. Plasma recalcification time suggests that HNTs are dose‐dependently contributing to blood coagulation in platelet poor plasma (PPP). The effect of platelet activation caused by HNTs was also examined by scanning electron microscopy (SEM). Meanwhile, HNTs were labeled with fluorescein isothiocyanate (FITC) to observe its intracellular distribution in A549 cells under confocal microscopy. CCK‐8 test and TUNEL test of HNTs at different concentration levels were performed in vitro, respectively. Therefore, the potential usage of HNTs in medicine may be very meaningful in oral dosing, dermal application, dental uses, or medical implants.
Serological Survey for Avian Influenza in Turkeys in Three States of Southwest Nigeria
Authors: Oluwayelu Daniel Oladimeji , Aiki-Raji Comfort Oluladun , Adigun Oladunni Taiwo , Olofintuyi Opeyemi Kazeem , Adebiyi Adebowale Idris
Published: November 2015

Since the first outbreak of avian influenza (AI) in Nigeria in 2006, there has been continuous monitoring of the disease in chickens with little attention given to turkeys. As part of on-going surveillance for AI in southwest Nigeria, we used a competitive ELISA to detect anti-AI virus antibodies in 520 turkey sera obtained from poultry farms in Oyo, Osun, and Ondo states while haemagglutination inhibiting antibodies against low pathogenic AI viruses (LPAIVs) were detected using H3N8 and H5N2 subtype-specific antigens. The overall seroprevalence obtained by ELISA was 4.4% (23/520). Of the 23 ELISA-positive samples, 18 were positive for anti-AIV H3N8 antibodies only and four were positive for both anti-AIV H3N8 and H5N2 antibodies indicating a mixed infection, while five were negative for antibodies to either of the two AIV subtypes. Considering that turkeys have been implicated as a mixing vessel for generating influenza virus reassortants of human and avian origin, the detection of antibodies to LPAIV H3N8 and H5N2 in these turkeys is of public health concern. We advocate further studies to determine the potential role of turkeys in the zoonotic transmission of AIVs in Nigeria. Additionally, the practice of rearing turkeys with chickens should be discouraged.
Delayed Ego Strength Development in Opioid Dependent Adolescents and Young Adults
Authors: Abramoff Benjamin A. , Lange Hannah L. H. , Matson Steven C. , Cottrill Casey B. , Bridge Jeffrey A. , Abdel-Rasoul Mahmoud , Bonny Andrea E.
Published: November 2015

Objective. To evaluate ego strengths, in the context of Erikson’s framework, among adolescents and young adults diagnosed with opioid dependence as compared to non-drug using youth.Methods. Opioid dependent (n=51) and non-drug using control (n=31) youth completed the self-administered Psychosocial Inventory of Ego Strengths (PIES). The PIES assesses development in the framework of Erikson’s ego strength stages. Multivariate linear regression modeling assessed the independent association of the primary covariate (opioid dependent versus control) as well as potential confounding variables (e.g., psychiatric comorbidities, intelligence) with total PIES score.Results. Mean total PIES score was significantly lower in opioid dependent youth (231.65±30.39opioid dependent versus270.67±30.06control;p<0.01). Evaluation of the PIES subscores found significant (p<0.05) delays in all ego strength areas (hope, will, purpose, competence, fidelity, love, care, and wisdom). When adjusting for potential confounders, opioid dependence remained a significant (p<0.001) independent predictor of total PIES score.Conclusion. Adolescents with opioid dependence demonstrated significant delays in ego strength development. A treatment approach acknowledging this delay may be needed in the counseling and treatment of adolescents with opioid dependence.
Hyperthermia Selectively Targets Human Papillomavirus in Cervical Tumors via p53-Dependent Apoptosis
Authors: Oei Arlene L. , van Leeuwen Caspar M. , ten Cate Rosemarie , Rodermond Hans M. , Buist Marrije R. , Stalpers Lukas J.A. , Crezee Johannes , Kok H. Petra , Medema Jan Paul , Franken Nicolaas A.P.
Published: November 2015

Human papillomavirus (HPV) is associated with cervical cancer, the third most common cancer in women. The high-risk HPV types 16 and 18 are found in over 70% of cervical cancers and produce the oncoprotein, early protein 6 (E6), which binds to p53 and mediates its ubiquitination and degradation. Targeting E6 has been shown to be a promising treatment option to eliminate HPV-positive tumor cells. In addition, combined hyperthermia with radiation is a very effective treatment strategy for cervical cancer. In this study, we examined the effect of hyperthermia on HPV-positive cells using cervical cancer cell lines infected with HPV 16 and 18, in vivo tumor models, and ex vivo–treated patient biopsies. Strikingly, we demonstrate that a clinically relevant hyperthermia temperature of 42°C for 1 hour resulted in E6 degradation, thereby preventing the formation of the E6–p53 complex and enabling p53-dependent apoptosis and G2-phase arrest. Moreover, hyperthermia combined with p53 depletion restored both the cell-cycle distribution and apoptosis to control levels. Collectively, our findings provide new insights into the treatment of HPV-positive cervical cancer and suggest that hyperthermia therapy could improve patient outcomes. Cancer Res; 75(23); 5120–9. ©2015 AACR.
M-CSF and GM-CSF Receptor Signaling Differentially Regulate Monocyte Maturation and Macrophage Polarization in the Tumor Microenvironment
Authors: Van Overmeire Eva , Stijlemans Benoît , Heymann Felix , Keirsse Jiri , Morias Yannick , Elkrim Yvon , Brys Lea , Abels Chloé , Lahmar Qods , Ergen Can , Vereecke Lars , Tacke Frank , De Baetselier Patrick , Van Ginderachter Jo A. , Laoui Damya
Published: November 2015

Tumors contain a heterogeneous myeloid fraction comprised of discrete MHC-IIhi and MHC-IIlo tumor-associated macrophage (TAM) subpopulations that originate from Ly6Chi monocytes. However, the mechanisms regulating the abundance and phenotype of distinct TAM subsets remain unknown. Here, we investigated the role of macrophage colony-stimulating factor (M-CSF) in TAM differentiation and polarization in different mouse tumor models. We demonstrate that treatment of tumor-bearing mice with a blocking anti-M-CSFR monoclonal antibody resulted in a reduction of mature TAMs due to impaired recruitment, extravasation, proliferation, and maturation of their Ly6Chi monocytic precursors. M-CSFR signaling blockade shifted the MHC-IIlo/MHC-IIhi TAM balance in favor of the latter as observed by the preferential differentiation of Ly6Chi monocytes into MHC-IIhi TAMs. In addition, the genetic and functional signatures of MHC-IIlo TAMs were downregulated upon M-CSFR blockade, indicating that M-CSFR signaling shapes the MHC-IIlo TAM phenotype. Conversely, granulocyte macrophage (GM)-CSFR had no effect on the mononuclear tumor infiltrate or relative abundance of TAM subsets. However, GM-CSFR signaling played an important role in fine-tuning the MHC-IIhi phenotype. Overall, our data uncover the multifaceted and opposing roles of M-CSFR and GM-CSFR signaling in governing the phenotype of macrophage subsets in tumors, and provide new insight into the mechanism of action underlying M-CSFR blockade. Cancer Res; 76(1); 35–42. ©2015 AACR.
Antibody-Dependent Phagocytosis of Tumor Cells by Macrophages: A Potent Effector Mechanism of Monoclonal Antibody Therapy of Cancer
Authors: Gül Nuray , van Egmond Marjolein
Published: November 2015

Nowadays, it is impossible to imagine modern cancer treatment without targeted therapies, such as mAbs, that bind to tumor-associated antigens. Subsequently, mAbs can use a wide range of effector functions that mostly engage the immune system. mAbs can bridge immune effector cells with tumor cells, which can result in antibody-dependent cytotoxicity. Increasing evidence, however, identified macrophages as prominent effector cells and induction of antibody-dependent cell phagocytosis as one of the primary mechanisms of action mediated by mAbs. Macrophages are extremely effective in eliminating tumor cells from the circulation. Several immunosuppressive mechanisms may, however, hamper their function, particularly in solid malignancies. In this review, we discuss the evolving insight of macrophages as effector cells in mAb therapy and address novel (co)therapeutic strategies that may be used to fully unleash their cytotoxic capacity for the treatment of cancer. Cancer Res; 75(23); 5008–13. ©2015 AACR.