bluuebunny/crossref_metadata_2025 huggingface dataset:
Overcoming Remote Workforce Cyber Threats: A Comprehensive Ransomware and Bot Net Defense Strategy Utilizing VPN Networks
Authors: Ogungbemi Olumide Samuel , Ezeugwa Favour Amarachi , Olaniyi Oluwaseun Oladeji , Akinola Oluwaseun Ibrahim , Oladoyinbo Oluseun Babatunde
Published: July 2024

This study investigates endpoint security strategies for remote workforces utilizing VPN networks, focusing on mitigating ransomware and botnet attacks. A mixed-methods approach was employed, analyzing the effectiveness of existing endpoint solutions and simulating network segmentation strategies. The study highlights the enhanced effectiveness of traditional endpoint security solutions when augmented with advanced technologies with specific applications including email filtering to block phishing attempts, MFA to verify user identities, EDR systems to detect and block unauthorized access tools, and encryption to secure data during cloud services. The introduction of network segmentation and zero-trust architectures further secured data centers by limiting lateral movements and requiring continuous re-authentication. Results demonstrate that while traditional endpoint security solutions remain essential, their effectiveness can be enhanced through a multi-layered approach incorporating advanced technologies with this research showing quick response times, high containment efficiency, and fast recovery speeds across all segments, with the Finance Department notably achieving a response time of 5 minutes and containment efficiency of 95%. Specifically, our cost-benefit analysis of network segmentation strategies shows that Strategy 1, despite a higher cost, offers superior improvements in throughput and latency reduction, providing more value per dollar spent. These results underscore the plan’s capability in rapidly detecting, containing, and recovering from attacks. User education significantly improved cybersecurity awareness and reduced susceptibility to attacks. This research provides practical recommendations for organizations to strengthen their endpoint security posture and protect their remote workforce through a combination of advanced technologies, proactive measures, and continuous user education.
Optimization of Radiation Protection for Companions in Pediatric Chest Radiography
Authors: Cassol Luísa Vargas , Bail Felipe Arboitte Torrel de , Rodrigues Thays Bandeira , Müller Maurício Alves , Santos Rafael Rimoli , Favarin Nataly Nogueira , Nogueira Laura Pizarro Trojahn , Claus Thiago Victorino
Published: July 2024

Aims: The objective of this study is to optimize the positioning of the companion during pediatric chest radiographic exams by analyzing the scattered radiation dose measured with an ionization chamber.
Place and Duration of Study: The experimental study was conducted between February 2024 and April 2024, in the radiodiagnosis laboratory belonging to the Medical Physics and Radiology Technology courses at the Franciscan University (UFN) in the city of Santa Maria, Rio Grande do Sul.
Methodology: A fixed conventional X-ray device and a phantom (simulating object) filled with 15 cm of water to represent a pediatric chest were used. The parameters of voltage (kV) and the product of current and time (mA.s) were kept constant. Measurements of the air KERMA (KAIR) were performed by positioning the dosimetric system at four points around the phantom (0º, 90º, 180º, and 270º), simulating the exposure conditions of the companion.
Results: The results showed that the lowest radiation dose received by the companion at the gonadal level occurred at 90º around the table (cathode side), while the lowest dose at the lens level was at 270º (anode side). The highest dose at the gonadal level was observed at 180º, and the highest dose at the lens level was at 90º.
Conclusion: It was concluded that the companion should position themselves on the anode side (270º), as the lens does not have lead protection, while protection is available for the rest of the body. This recommendation aims to optimize radiological safety for the companion.
Western Pacific atmospheric nutrient deposition fluxes, their impact on surface ocean productivity
Authors: Martino M. , Hamilton D. , Baker A. R. , Jickells T. D. , Bromley T. , Nojiri Y. , Quack B. , Boyd P. W.
Published: June 2014

The atmospheric deposition of both macronutrients and micronutrients plays an important role in driving primary productivity, particularly in the low‐latitude ocean. We report aerosol major ion measurements for five ship‐based sampling campaigns in the western Pacific from ~25°N to 20°S and compare the results with those from Atlantic meridional transects (~50°N to 50°S) with aerosols collected and analyzed in the same laboratory, allowing full incomparability. We discuss sources of the main nutrient species (nitrogen (N), phosphorus (P), and iron (Fe)) in the aerosols and their stoichiometry. Striking north–south gradients are evident over both basins with the Northern Hemisphere more impacted by terrestrial dust sources and anthropogenic emissions and the North Atlantic apparently more impacted than the North Pacific. We estimate the atmospheric supply rates of these nutrients and the potential impact of the atmospheric deposition on the tropical western Pacific. Our results suggest that the atmospheric deposition is P deficient relative to the needs of the resident phytoplankton. These findings suggest that atmospheric supply of N, Fe, and P increases primary productivity utilizing some of the residual excess phosphorus (P*) in the surface waters to compensate for aerosol P deficiency. Regional primary productivity is further enhanced via the stimulation of nitrogen fixation fuelled by the residual atmospheric iron and P*. Our stoichiometric calculations reveal that a P* of 0.1 µmol L−1 can offset the P deficiency in atmospheric supply for many months. This study suggests that atmospheric deposition may sustain ~10% of primary production in both the western tropical Pacific.
Characterizing the annual cycle of African dust transport to the Caribbean Basin and South America and its impact on the environment and air quality
Authors: Prospero Joseph M. , Collard François‐Xavier , Molinié Jack , Jeannot Alexis
Published: June 2014

Decades of aerosol measurements on Barbados have yielded a detailed picture of African mineral dust transport to the Caribbean Basin that shows a strong seasonal cycle with a maximum in boreal summer and a minimum in winter. Satellite aerosol products suggest that in spring, there is a comparable transport to northeastern South America. Here we characterize the complete annual cycle of dust transport to the western Atlantic by linking the Barbados record to multiyear records of airborne particulate matter less than 10 µm diameter (PM10) measured in air quality programs at Cayenne (French Guiana) and Guadeloupe. Comparisons of PM10 at these sites with concurrent dust measurements at Barbados demonstrate that high PM10 levels are almost entirely due to dust. Cayenne PM10 peaks in spring in a cycle which is consistent with satellite aerosol optical depth and suggests that the Sahel is the dominant source. The persistent transport of dust during much of the year could impact a wide range of environmental processes over a broad region that extends from the southern United States to the Amazon Basin. Finally, the average 24 h PM10 concentrations at Cayenne and Guadeloupe frequently exceed the World Health Organization air quality guideline. Thus soil dust PM10 could be a significant, but generally unrecognized, health factor at western Atlantic sites and also in other relatively remote regions affected by long‐range dust from Africa. Because dust emissions and transport are highly sensitive to climate variability, climate change in coming decades could greatly affect a wide range of biogeochemical processes and human health in this region.
Soil nitrogen dynamics within profiles of a managed moist temperate forest chronosequence consistent with long‐term harvesting‐induced losses
Authors: Kellman Lisa , Kumar Sanjeev , Diochon Amanda
Published: June 2014

This study investigates whether clear‐cut forest harvesting leads to alterations in the decadal‐scale biogeochemical nitrogen (N) cycles of moist temperate forest ecosystems. Using a harvested temperate red spruce (Picea rubens Sarg.) forest chronosequence in Nova Scotia, Canada, representing <1 to >80 year old postharvest conditions, alongside a reference old‐growth (125+ year old) site with no documented history of disturbance, we examine harvesting‐related changes in soil N pools and fluxes. Specifically, we quantify soil N storage with depth and age across the forest chronosequence, examine changes in physical fractions and δ15N of soil N through depth and time, and quantify gross soil N transformation rates through depth and time using a 15N isotope dilution technique. Our findings point to a large loss of total N in the soil pool, particularly within the deep soil (>20 cm) and organomineral fractions. A pulse of available mineralized N (as ammonium) was observed following harvesting (mean residence time (MRT) > 6 days), but its MRT dropped to <1 day 80 years following harvesting, in contrast to the MRT of 2–3 days observed in the reference old‐growth forest site. These mineralization patterns coupled with inferred leaching losses to groundwater are consistent with storage estimates that suggest soil N may not reaccrue for almost a century following this disturbance.
Effects of productivity, glaciation, and ventilation on late Quaternary sedimentary redox and trace element accumulation on the Vancouver Island margin, western Canada
Authors: Chang Alice S. , Pedersen Thomas F. , Hendy Ingrid L.
Published: June 2014

Variations in chalcophile and redox‐sensitive trace elements are examined at high‐resolution intervals from a ~50 kyr long sediment core (MD02‐2496) from the Vancouver Island margin. Enrichments of Ag, Cd, Re, U, and Mo above lithogenous levels, signifying sedimentary suboxia and anoxia, occurred during the early Holocene and Bølling/Allerød, and during warm interstadial events of Marine Isotope Stage (MIS) 3. Down‐core trace element profiles co‐vary with productivity proxy records (opal, CaCO3, and marine organic carbon), and with sedimentary nitrogen isotope ratios, which reflect variably enriched nitrate upwelled from intermediate waters that were transported northward from the Eastern Tropical North Pacific. The similarity of the MD02‐2496 record with records from the southern portion of the California Current System (CCS), and to the Greenland ice core oxygen isotope record during warm climate intervals, suggests that sedimentary redox conditions along the California Current responded to local productivity, to North Atlantic climate change and to tropical Pacific surface water processes via long‐distance teleconnections. Concentrations of trace elements and productivity proxies were relatively depleted during the Younger Dryas, cool stadial events of MIS 3, and in two episodes of glaciomarine sedimentation from ~14.7 to 30.5 kyr BP (last glacial maximum, LGM), and from 44 to 50.4 kyr BP. Cordilleran Ice Sheet advancement onto the Vancouver Island continental shelf during the LGM led to intervals of increased terrigenous sedimentation and greatly reduced productivity not seen in the southern portion of the CCS, and along with ventilation of North Pacific Intermediate Waters, resulted in brief sedimentary oxic conditions.
Principal Component Geostatistical Approach for large‐dimensional inverse problems
Authors: Kitanidis P. K. , Lee J.
Published: June 2014

The quasi‐linear geostatistical approach is for weakly nonlinear underdetermined inverse problems, such as Hydraulic Tomography and Electrical Resistivity Tomography. It provides best estimates as well as measures for uncertainty quantification. However, for its textbook implementation, the approach involves iterations, to reach an optimum, and requires the determination of the Jacobian matrix, i.e., the derivative of the observation function with respect to the unknown. Although there are elegant methods for the determination of the Jacobian, the cost is high when the number of unknowns, m, and the number of observations, n, is high. It is also wasteful to compute the Jacobian for points away from the optimum. Irrespective of the issue of computing derivatives, the computational cost of implementing the method is generally of the order of m2n, though there are methods to reduce the computational cost. In this work, we present an implementation that utilizes a matrix free in terms of the Jacobian matrix Gauss‐Newton method and improves the scalability of the geostatistical inverse problem. For each iteration, it is required to perform K runs of the forward problem, where K is not just much smaller than m but can be smaller that n. The computational and storage cost of implementation of the inverse procedure scales roughly linearly with m instead of m2 as in the textbook approach. For problems of very large m, this implementation constitutes a dramatic reduction in computational cost compared to the textbook approach. Results illustrate the validity of the approach and provide insight in the conditions under which this method perform best.
Increased evaporation following widespread tree mortality limits streamflow response
Authors: Biederman J. A. , Harpold A. A. , Gochis D. J. , Ewers B. E. , Reed D. E. , Papuga S. A. , Brooks P. D.
Published: June 2014

A North American epidemic of mountain pine beetle (MPB) has disturbed over 5 million ha of forest containing headwater catchments crucial to water resources. However, there are limited observations of MPB effects on partitioning of precipitation between vapor loss and streamflow, and to our knowledge these fluxes have not been observed simultaneously following disturbance. We combined eddy covariance vapor loss (V), catchment streamflow (Q), and stable isotope indicators of evaporation (E) to quantify hydrologic partitioning over 3 years in MPB‐impacted and control sites. Annual control V was conservative, varying only from 573 to 623 mm, while MPB site V varied more widely from 570 to 700 mm. During wet periods, MPB site V was greater than control V in spite of similar above‐canopy potential evapotranspiration (PET). During a wet year, annual MPB V was greater and annual Q was lower as compared to an average year, while in a dry year, essentially all water was partitioned to V. Ratios of 2H and 18O in stream and soil water showed no kinetic evaporation at the control site, while MPB isotope ratios fell below the local meteoric water line, indicating greater E and snowpack sublimation (Ss) counteracted reductions in transpiration (T) and sublimation of canopy‐intercepted snow (Sc). Increased E was possibly driven by reduced canopy shading of shortwave radiation, which averaged 21 W m−2 during summer under control forest as compared to 66 W m−2 under MPB forest. These results show that abiotic vapor losses may limit widely expected streamflow increases.
Large‐scale hydraulic tomography and joint inversion of head and tracer data using the Principal Component Geostatistical Approach (PCGA)
Authors: Lee J. , Kitanidis P. K.
Published: June 2014

The stochastic geostatistical inversion approach is widely used in subsurface inverse problems to estimate unknown parameter fields and corresponding uncertainty from noisy observations. However, the approach requires a large number of forward model runs to determine the Jacobian or sensitivity matrix, thus the computational and storage costs become prohibitive when the number of unknowns, m, and the number of observations, n increase. To overcome this challenge in large‐scale geostatistical inversion, the Principal Component Geostatistical Approach (PCGA) has recently been developed as a “matrix‐free” geostatistical inversion strategy that avoids the direct evaluation of the Jacobian matrix through the principal components (low‐rank approximation) of the prior covariance and the drift matrix with a finite difference approximation. As a result, the proposed method requires about K runs of the forward problem in each iteration independently of m and n, where K is the number of principal components and can be much less than m and n for large‐scale inverse problems. Furthermore, the PCGA is easily adaptable to different forward simulation models and various data types for which the adjoint‐state method may not be implemented suitably. In this paper, we apply the PCGA to representative subsurface inverse problems to illustrate its efficiency and scalability. The low‐rank approximation of the large‐dimensional dense prior covariance matrix is computed through a randomized eigen decomposition. A hydraulic tomography problem in which the number of observations is typically large is investigated first to validate the accuracy of the PCGA compared with the conventional geostatistical approach. Then the method is applied to a large‐scale hydraulic tomography with 3 million unknowns and it is shown that underlying subsurface structures are characterized successfully through an inversion that involves an affordable number of forward simulation runs. Lastly, we present a joint inversion of head and tracer test data using MODFLOW and MT3DMS as coupled black‐box forward simulation solvers. These applications demonstrate the advantages of the PCGA, i.e., the scalability to high‐dimensional inverse problems and the ability to utilize multiple forward models as black boxes.
Kinetic parameter estimation of HDPE slurry process from molecular weight distribution: Estimability analysis and multistep methodology
Authors: Zhang Chen , Shao Zhijiang , Chen Xi , Yao Zhen , Gu Xueping , Biegler Lorenz T.
Published: June 2014

This study addresses kinetic parameter estimation for a high‐density polyethylene (HDPE) slurry process based on fitting molecular weight distributions (MWDs). From the process model, we conduct an estimability analysis by assessing the relative sensitivity between output variables and kinetic parameters as well as confidence intervals. This determines which parameters can be estimated. Conversely, a major challenge remains with the solution of an ill‐conditioned parameter estimation problem with MWD as the output variable. To overcome the convergence difficulties with the associated problem, we develop a novel multistep methodology where we first obtain MWD parameters by matching to data and then estimate kinetic parameters by matching to the regressed MWD parameters. Computational results and eigenvalue analysis show this multistep methodology separates an ill‐conditioned problem into two well‐conditioned subproblems. Moreover, we consider simulation‐based and industrial HDPE case studies. These results demonstrate the applicability, potential, and efficiency of this solution procedure. © 2014 American Institute of Chemical Engineers AIChE J, 60: 3442–3459, 2014
Regime transition in viscous and pseudo viscous systems: A comparative study
Authors: Rabha Swapna , Schubert Markus , Hampel Uwe
Published: June 2014

A comprehensive quantitative study on the effect of liquid viscosity (1 ≤ µL ≤ 1149 mPa‐s) on the local flow phenomena of the gas phase in a small diameter bubble column is performed using ultrafast electron beam X‐ray tomography. The internal dynamic flow structure and the bubble size distribution shows a dual role of the liquid viscosity on the hydrodynamics. Further, the effect of solid concentration (Cs = 0.05, 0.20) on the local flow behavior of the gas phase is studied for the pseudo slurry viscosities similar to the liquid viscosities of the gas–liquid systems. The effects of liquid and pseudo slurry viscosities on flow structure, bubble size distribution, and gas phase distribution are compared. The bubble coalescence is significantly enhanced with the addition of particles as compared to the system without particles for apparently same viscosity. The superficial gas velocity at which transition from homogeneous bubbly to slug flow regime occurs is initiated by the addition of particles as compared to the particle free system for apparently same viscosity. © 2014 American Institute of Chemical Engineers AIChE J, 60: 3079–3090, 2014
A method for scale‐up of co‐electrospun nanofibers via flat core‐shell structure spinneret
Authors: Wu Huihui , Zheng Yuansheng , Zeng Yongchun
Published: June 2014

An approach to the scale‐up of co‐electrospinning via a flat core‐shell structure spinneret has been developed in this study. The spinneret with a flat surface involves shell‐holes and core‐needles. Electric field simulation reveals that the flat core‐shell spinneret configuration creates a more uniform electric field gradient. Experimental study shows that in comparison with the conventional needle co‐electrospinning, core‐shell nanofibers produced by this new designed setup are finer and of better morphology. Composite nanofibers with special morphologies can be fabricated by modifying the structure of this spinneret. The production rate of the core‐shell nanofibers can be enhanced by increasing the hole and needle number of the spinneret. This novel design is expected to provide a promising method towards the massive production of core‐shell nanofibers. © 2014 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2014, 131, 41027.
Comparison of rigid divinylbenzene with flexible 1,7‐octadiene crosslinks in acrylic acid resins—effects on kinetics of swelling and loading of heavy metal ions from water
Authors: Wasim Ali Syed , Malik Muhammad Arif , Jan Saida , Naeem Kashif
Published: June 2014

Acrylic acid–1,7‐octadiene resin was synthesized in beaded form by a two‐step process: suspension polymerization of ethylacrylate and 1,7‐octadiene monomers, followed by hydrolysis using either 98% H2SO4 or 10 M NaOH. Acrylic acid–divinylbenzene resins were also synthesized by the same process for the purpose of comparing a rigid divinylbenzene with a flexible 1,7‐octadiene crosslinkage in the acrylic acid resins. Swelling of the resins in distilled water shows that replacing divinylbenzenes with 1,7‐octadiene makes the resin achieve greater swelling in a significantly shorter time. 1,7‐Octadiene also allowed for an increase in crosslinkage to 20% compared to 4% in the case of divinylbenzene, without compromising the loading rates of toxic heavy metal ions like Pb2+, Cu2+, and Cr3+ from water samples. The acrylic acid–1,7‐octadine resin was found useful for removal of the toxic heavy metal ions from wastewater samples. © 2014 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2014, 131, 41038.
Influence of the excystment time on the breeding success of juvenile freshwater pearl mussels (Margaritifera margaritifera)
Authors: Eybe Tanja , Thielen Frankie , Bohn Torsten , Sures Bernd
Published: June 2014

Freshwater pearl mussel (Margaritifera margaritifera L.) is an endangered species. Rearing in captivity for eventual release is one possible method of increasing the likelihood of persistence in different rivers. As rearing is a time‐consuming procedure, knowledge about conditions that increase survival and growth rates and decrease the period of the parasitic stage would be advantageous.

Experiments with two excystment periods (one preterm in January, induced by artificially raising the water temperature, and a natural one in May) were performed, and the growth and survival rates of juvenile mussels were determined. Furthermore, meristic parameters of the host fish (brown trout, Salmo trutta) infested with glochidia in August the year before were investigated before and after both juvenile collection periods.

In January the mean intensity was 151.5 glochidia per fish (±260.6) and 80% of host fish were infested. In May, the mean intensity was 142.7 glochidia per fish (±177.0) with 30% of fish infested with glochidia. Although the condition factors of the fish decreased during the experiments to 0.8 ± 0.1 (January) and 0.7 ± 0.2 (May), no apparent influence on the growth or survival rate of the juvenile mussels was obvious.

The output of juvenile mussels was higher in the January excystment period (2854 compared with 2310).

During both excystment periods, the length of the freshly excysted juveniles increased slightly from the first to the last day of collection. Mussels excysted with a mean length of 0.32–0.33 mm (at the beginning of the excystment period) and 0.38 mm (at the end).

Individuals collected after the first few days of the January excystment period were the most suitable for culture. Growth up to a minimum of 1 mm in 110 days and a survival rate of 62–98% were observed. Juvenile survival from the May excystment period was lower (7–38%) presumably owing to poor water quality in the river.

Copyright © 2014 John Wiley & Sons, Ltd.
Site fidelity, survival and conservation options for the threatened flapper skate (Dipturus cf. intermedia)
Authors: Neat Francis , Pinto Cecilia , Burrett Ian , Cowie Lewis , Travis Justin , Thorburn James , Gibb Fiona , Wright Peter J.
Published: June 2014

In order to evaluate if marine protected areas (MPAs) can be expected to confer conservation benefits to large, mobile marine species it is important to assess their site fidelity and habitat ranging patterns. The flapper skate (Dipterus cf. intermedia) is a large, threatened elasmobranch for which MPAs are being considered on the west coast of Scotland. To inform MPA establishment, a multiannual mark–recapture programme, a year‐long static array acoustic study and an archival tagging study of flapper skate were undertaken.

Capture–mark–recapture (CMR) modelling of 280 individuals indicated significant heterogeneity in the recapture rate suggesting the region contained a mixture of site‐attached (resident) and vagrant (transient) individuals. The analysis estimated that 100–400 resident individuals were present in the study area. The number of transient individuals was estimated at around 25% of all those tagged. The average annual survival probability of resident individuals was estimated to be 0.64.

The acoustic study of 20 individuals demonstrated that over half were resident on a day‐by‐day basis for months at a time. Three individuals were detected over the entire year. Two individuals moved away immediately after tagging and over half moved out of the study area in the springtime.

Three data storage tags revealed that resident individuals utilized most of the available depth habitat (6–205 m) in the area and occasionally visited deeper areas outside the immediate study area.

The results indicate that the establishment of a MPA would confer conservation benefits to flapper skate in the area. Management should consider all depths in the study area, areas beyond the study site, and alternative conservation measures such as technical gear measures for fisheries. This study has implications for the conservation and management of similar long‐lived, mobile marine species.

© 2014 Crown copyright. Aquatic Conservation: Marine and Freshwater Ecosystems © 2014 John Wiley & Sons, Ltd.
Small proteins, big roles: The signaling protein Apela extends the complexity of developmental pathways in the early zebrafish embryo
Authors: Reichman‐Fried Michal , Raz Erez
Published: June 2014

The identification of molecules controlling embryonic patterning and their functional analysis has revolutionized the fields of Developmental and Cell Biology. The use of new sequence information and modern bioinformatics tools has enriched the list of proteins that could potentially play a role in regulating cell behavior and function during early development. The recent application of efficient methods for gene knockout in zebrafish has accelerated the functional analysis of many proteins, some of which have been overlooked due to their small size. Two recent publications report on the identification of one such protein and its role in zebrafish embryogenesis. The protein, currently designated Apela, was shown to act as a secreted protein whose absence adversely affected various early developmental processes. Additional signaling proteins that have been identified in one of the studies are likely to open the way to unraveling hitherto unknown developmental pathways and have the potential to provide a more comprehensive understanding of known developmental processes.
Zinc, magnesium, and calcium ion supplementation confers tolerance to acetic acid stress in industrial Saccharomyces cerevisiae utilizing xylose
Authors: Ismail Ku Syahidah Ku , Sakamoto Takatoshi , Hasunuma Tomohisa , Zhao Xin‐Qing , Kondo Akihiko
Published: June 2014

Lignocellulosic biomass is a potential substrate for ethanol production. However, pretreatment of lignocellulosic materials produces inhibitory compounds such as acetic acid, which negatively affect ethanol production by Saccharomyces cerevisiae. Supplementation of the medium with three metal ions (Zn2+, Mg2+, and Ca2+) increased the tolerance of S. cerevisiae toward acetic acid compared to the absence of the ions. Ethanol production from xylose was most improved (by 34%) when the medium was supplemented with 2 mM Ca2+, followed by supplementation with 3.5 mM Mg2+ (29% improvement), and 180 μM Zn2+ (26% improvement). Higher ethanol production was linked to high cell viability in the presence of metal ions. Comparative transcriptomics between the supplemented cultures and the control suggested that improved cell viability resulted from the induction of genes controlling the cell wall and membrane. Only one gene, FIT2, was found to be up‐regulated in common between the three metal ions. Also up‐regulation of HXT1 and TKL1 might enhance xylose consumption in the presence of acetic acid. Thus, the addition of ionic nutrients is a simple and cost‐effective method to improve the acetic acid tolerance of S. cerevisiae.
Platinum‐Catalyzed Asymmetric Ring‐opening Reaction of Oxabenzonorbornadiene with Terminal Alkynes
Authors: Long Yuhua , Jiang Han , Zou Zhifu , Chen Kaixuan , Fang Yali
Published: June 2014

A novel platinum‐catalyzed asymmetric ring‐opening reaction of oxabenzonorbornadiene with terminal alkynes is described. The reaction affords optically active cis‐2‐alkynyl‐1,2‐dihydronaphthalen‐1‐ols in moderate yields with good enantioselectivity in the presence of catalytic amounts of Pt(COD)Cl2/(S)‐BINAP and an excess of zinc powder. The products were obtained exclusively with the relative cis‐configuration of the ring substituents and the prevalent (1R,2S)‐configuration of the stereocenters, as determined by single crystal X‐ray diffraction analysis.
Highly Efficient Dye‐sensitized Solar Cells by Co‐sensitization of Organic Dyes and Co‐adsorbent Chenodeoxycholic Acid
Authors: Wei Yinni , Wu Zhisheng , An Zhongwei , Chen Xinbing , Chen Pei , Liu Qianfeng
Published: June 2014

Approach to highly efficient dye‐sensitized solar cells (DSSCs) by co‐sensitization of organic dyes, AZ6+AZ5 with co‐adsorbent chenodeoxycholic acid (CDCA) is presented. The power conversion efficiencies (PCEs) of 8.55% and 8.31% are obtained from DSSCs co‐sensitized by AZ6 (0.3 mmol/L)+AZ5 (0.1 mmol/L) with CDCA concentration of 5 and 20 mmol/L in one step cocktail, respectively. The latter shows high stability in a period of 653 h under ambient conditions.
High‐fat diet induces early‐onset diabetes in heterozygous Pax6 mutant mice
Authors: Chen Yuanyuan , Feng Ruopeng , Wang Hong , Wei Rui , Yang Jin , Wang Liang , Wang Haining , Zhang Lin , Hong Tian‐pei , Wen Jinhua
Published: June 2014

Background

Type 2 diabetes is caused by interactions between genetic and environmental factors. Our previous studies reported that paired box 6 mutation heterozygosity (Pax6m/+) led to defective proinsulin processing and subsequent abnormal glucose metabolism in mice at 6 months of age. However, high‐fat diet exposure could be an important incentive for diabetes development. In this study, we aimed to develop a novel diabetic model imitating human type 2 diabetes by exposing Pax6m/+ mice to high‐fat diet and to explore the underlying mechanism of diabetes in this model.

Methods

Over 300 Pax6m/+ and wild‐type male weanling mice were randomly divided into two groups and were fed an high‐fat diet or chow diet for 6–10 weeks. Blood glucose and glucose tolerance levels were monitored during this period. Body weights, visceral adipose weights, blood lipid profiles and insulin sensitivity (determined with an insulin tolerance test) were used to evaluate obesity and insulin resistance. Proinsulin processing and insulin secretion levels were used to evaluate pancreatic β cell function.

Results

After 6 weeks of high‐fat diet exposure, only the Pax6m/+ mice showed dramatic postloading hyperglycaemia. These mice exhibited significant high‐fat diet‐induced visceral obesity and insulin resistance and displayed defective prohormone convertase 1/3 production, an increased proinsulin:total insulin ratio and impaired early‐phase insulin secretion, because of the Pax6 mutation. Hyperglycaemia worsened progressively over time with the high‐fat diet, and most Pax6m/+ mice on high‐fat diet developed diabetes or impaired glucose tolerance after 10 weeks. Furthermore, high‐fat diet withdrawal partly improved blood glucose levels in the diabetic mice.

Conclusions

By combining the Pax6m/+ genetic background with an high‐fat diet environment, we developed a novel diabetic model to mimic human type 2 diabetes. This model is characterized by impaired insulin secretion, caused by the Pax6 mutation, and high‐fat diet‐induced insulin resistance and therefore provides an ideal tool for research on type 2 diabetes pathogenesis and therapies. Copyright © 2014 John Wiley & Sons, Ltd.
Seasonal water use by deciduous and evergreen woody species in a scrub community is based on water availability and root distribution
Authors: Ellsworth Patrick Z. , Sternberg Leonel S. L.
Published: June 2014

In a seasonally dry plant community of central Florida, USA, that experiences water limitation in the dry season and high water availability in the wet season, we first tested whether evergreen woody species shift from shallow water in the wet season to deep water in the dry season. Second, we tested whether deciduous woody species restrict water uptake to the shallow soil during the wet season and cease water uptake during the dry season. To address these questions, we measured water source use of two deciduous and three evergreen species over 13 months using stable isotopes. As hypothesized in previous studies, we showed that leaflessness in deciduous plants is an important source of stem water isotopic fractionation. Therefore, we compared stable isotope ratios of stem water only when deciduous species had leaves and found that all species, except the evergreen Lyonia ferruginea, used proportionally the same water sources. Early dry season water use was based on water availability for all species except L. ferruginea, and deep soil (50–150 cm) was the most important water source. During the late dry and wet seasons, water uptake from each soil layer was based on its respective proportion of fine roots. Nevertheless, deep water remained an important water source throughout the year. This study clearly demonstrates the limitations of using stable isotopes of stem water when comparing deciduous versus evergreen species. Further, this study is the first to directly quantify depth of water uptake via isotope analysis and couple these findings with root distribution. Copyright © 2014 John Wiley & Sons, Ltd.
Mono‐ and Dinuclear Complexes of Tricarbonylrhenium(I) with 4‐Methyl‐2,2′‐bipyridine‐4′‐carbonitrile
Authors: Mecchia Ortiz Juan H. , Morán Vieyra Faustino E. , Borsarelli Claudio D. , Romero Isabel , Fontrodona Xavier , Parella Teodor , Lis de Katz Noemí D. , Fagalde Florencia , Katz Néstor E.
Published: June 2014

Novel mono‐ and dinuclear tricarbonylrhenium(I) complexes of formula [Re(Mebpy‐CN)(CO)3Cl] (1), [Re(Mebpy‐CN)(CO)3(CH3CN)](PF6) (2), and [(CH3CN)(CO)3Re(Mebpy‐CN)Ru(NH3)5](PF6)3 (3), in which Mebpy‐CN = 4‐methyl‐2,2′‐bipyridine‐4′‐carbonitrile, were prepared and characterized by spectroscopic, photophysical, and computational techniques. The complete structure of complex 2 was determined by X‐ray diffraction. The increased conjugation in the bipyridyl ring owing to the nitrile substituent increases the emission quantum yields of the 3MLCT (metal‐to‐ligand charge‐transfer) lowest‐lying excited states of 1 and 2 with respect to the corresponding bpy complexes (bpy = 2,2′‐bipyridine). The mixed‐valent species of formula [(CH3CN)(CO)3Re(Mebpy‐CN)Ru(NH3)5]4+ (4) was prepared in situ and as a mixed salt; the charge recombination from its metal‐to‐metal charge‐transfer (MMCT) excited state is predicted to lie in the Marcus inverted region. The electronic structures and optical properties of all the reported complexes calculated by DFT and TD‐DFT methods agree reasonably well with experimental results.
DSPC or DPPC as main shell component influences ligand distribution and binding area of lipid‐coated targeted microbubbles
Authors: Kooiman Klazina , Kokhuis Tom J. A. , van Rooij Tom , Skachkov Ilya , Nigg Alex , Bosch Johannes G. , van der Steen Antonius F. W. , van Cappellen Wiggert A. , de Jong Nico
Published: June 2014

Ultrasound contrast agents (UCA) consist of gas‐filled coated microbubbles with diameters of 1–10 µm. Targeted UCA can bind to biomarkers associated with disease through coating‐incorporated ligands, making ultrasound molecular imaging possible. The aim of our research was to compare the ligand distribution, binding area, and bound microbubble shape of 1,2‐distearoyl‐sn‐glycero‐3‐phosphocholine (DSPC) based and 1,2‐dipalmitoyl‐sn‐glycero‐3‐phosphocholine (DPPC) based lipid‐coated microbubbles using super‐resolution microscopy. Ligand distribution was studied by conjugating the fluorescent streptavidin Oregon Green 488 to the biotinylated microbubbles. An inhomogeneous streptavidin distribution was found when DSPC was the main coating lipid. When DSPC was replaced by DPPC, a more homogeneous streptavidin distribution was observed. Binding area of targeted microbubbles was studied using biotinylated microbubbles bound to a streptavidin‐coated surface. DSPC microbubbles had a significantly smaller binding area than DPPC microbubbles. Whereas the bound DSPC microbubbles remained spherical, the DPPC microbubbles were dome‐shaped. This study reveals that lipid‐coated microbubbles differ in ligand distribution, binding area, and bound microbubble shape solely on the basis of their main lipid component.

Practical applications: A homogeneous ligand distribution, larger binding area and domed shape upon binding could be advantageous for binding of targeted microbubbles, thereby favoring DPPC over DSPC as main lipid for UCA for ultrasound molecular imaging. The findings of the present study can be used for the design of targeted microbubbles with improved binding capabilities and for the ongoing research to acoustically distinguish bound from unbound microbubbles.

Targeted biotinylated DSPC and DPPC‐based microbubbles bound to streptavidin‐coated surface. Left graph: binding area; right panels: microbubbles (red fluorescent) bound to streptavidin‐coated surface (green fluorescent).
Dihydrophytol and phytol isomers as marker substances for hydrogenated and refined vegetable oils
Authors: Schröder Markus , Lehnert Katja , Hammann Simon , Vetter Walter
Published: June 2014

Edible vegetable oils are an important part of the human diet. Products with different levels of processing are marketed for this purpose. Key‐products are virgin oils, refined oils, and partly or fully hydrogenated oils. In this study we explored whether compounds derived from trans‐phytol, i.e. the natural constituent of chlorophyll, could serve as marker compounds for identifying the processing type of oils, spreads and margarines. The evaluation was based on the contribution of the native trans‐phytol along with its transformation products cis‐ and iso‐phytol as well as dihydrophytol. Gas chromatography with mass spectrometry operated in the selected ion monitoring mode enabled the detection of these compounds at >0.01 mg/100 g oil or fat. In virgin vegetable oils trans‐phytol was the principle phytol related compound while cis‐phytol was generally <0.05% and iso‐phytol and dihydrophytol were not detected at all. Refined vegetable oils contained trans‐, cis‐, and iso‐phytol but no dihydrophytol. Partly and totally hydrogenated vegetable oils contained dihydrophytol if at least 5% hydrogenated fat were present in the oil. The occurrence of cis‐ and iso‐phytol in vegetable oils can be used as indicators for refined oils while the presence of dihydrophytol in vegetable oils is an indication for hydrogenation.

Practical applications: The analysis of trans‐phytol, cis‐phytol, iso‐phytol, and dihydrophytol can be used in food control for oil authentication. In this context iso‐phytol can serve as an additional marker for refined vegetable oils and dihydrophytol as a marker for hydrogenated vegetable oils.

Native vegetable oils are containing trans‐phytol in the unsaponifiable matter. During the refining of vegetable oils measurable amounts of cis‐phytol and iso‐phytol are formed from trans‐phytol. In addition, hydrogenation of oils leads to formation of dihydrophytol from trans‐phytol and cis‐phytol, and these four compounds can be used to authenticate different qualities of vegetable oils.
Activation of the developmental pathway neurogenin-3/microRNA-7a regulates cholangiocyte proliferation in response to injury
Authors: Marzioni Marco , Agostinelli Laura , Candelaresi Cinzia , Saccomanno Stefania , De Minicis Samuele , Maroni Luca , Mingarelli Eleonora , Rychlicki Chiara , Trozzi Luciano , Banales Jesus M. , Benedetti Antonio , Baroni Gianluca Svegliati
Published: June 2014

The activation of the biliary stem-cell signaling pathway hairy and enhancer of split 1/pancreatic duodenal homeobox-1 (Hes-1/PDX-1) in mature cholangiocytes determines cell proliferation. Neurogenin-3 (Ngn-3) is required for pancreas development and ductal cell neogenesis. PDX-1-dependent activation of Ngn-3 initiates the differentiation program by inducing microRNA (miR)−7 expression. Here we investigated the role Ngn-3 on cholangiocyte proliferation. Expression levels of Ngn-3 and miR-7 isoforms were tested in cholangiocytes from normal and cholestatic human livers. Ngn-3 was knocked-down in vitro in normal rat cholangiocytes by short interfering RNA (siRNA). In vivo, wild-type and Ngn-3-heterozygous (+/−) mice were subjected to 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC) feeding (a model of sclerosing cholangitis) or bile duct ligation (BDL). In the liver, Ngn-3 is expressed specifically in cholangiocytes of primary sclerosing cholangitis (PSC) patients and in mice subjected to DDC or BDL, but not in normal human and mouse livers. Expression of miR-7a-1 and miR-7a-2 isoforms, but not miR-7b, was increased in DDC cholangiocytes compared to normal ones. In normal rat cholangiocytes, siRNA against Ngn-3 blocked the proliferation stimulated by exendin-4. In addition, Ngn-3 knockdown neutralized the overexpression of insulin growth factor-1 (IGF1; promitotic effector) observed after exposure to exendin-4, but not that of PDX-1 or VEGF-A/C. Oligonucleotides anti-miR-7 inhibited the exendin-4-induced proliferation in normal rat cholangiocytes, but did not affect Ngn-3 synthesis. Biliary hyperplasia and collagen deposition induced by DDC or BDL were significantly reduced in Ngn-3+/− mice compared to wild-type. Conclusion: Ngn-3-dependent activation of miR-7a is a determinant of cholangiocyte proliferation. These findings indicate that the reacquisition of a molecular profile typical of organ development is essential for the biological response to injury by mature cholangiocytes. (Hepatology 2014;60:1324–1335)
Discovery and validation of urinary metabotypes for the diagnosis of hepatocellular carcinoma in West Africans
Authors: Ladep Nimzing G. , Dona Anthony C. , Lewis Matthew R. , Crossey Mary M.E. , Lemoine Maud , Okeke Edith , Shimakawa Yusuke , Duguru Mary , Njai Harr F. , Fye Haddy K.S. , Taal Makie , Chetwood John , Kasstan Ben , Khan Shahid A. , Garside Deborah A. , Wijeyesekera Anisha , Thillainayagam Andrew V. , Banwat Edmund , Thursz Mark R. , Nicholson Jeremy K. , Njie Ramou , Holmes Elaine , Taylor-Robinson Simon D.
Published: June 2014

There is no clinically applicable biomarker for surveillance of hepatocellular carcinoma (HCC), because the sensitivity of serum alpha-fetoprotein (AFP) is too low for this purpose. Here, we determined the diagnostic performance of a panel of urinary metabolites of HCC patients from West Africa. Urine samples were collected from Nigerian and Gambian patients recruited on the case-control platform of the Prevention of Liver Fibrosis and Cancer in Africa (PROLIFICA) program. Urinary proton nuclear magnetic resonance (1H-NMR) spectroscopy was used to metabolically phenotype 290 subjects: 63 with HCC; 32 with cirrhosis (Cir); 107 with noncirrhotic liver disease (DC); and 88 normal control (NC) healthy volunteers. Urine samples from a further cohort of 463 subjects (141 HCC, 56 Cir, 178 DC, and 88 NC) were analyzed, the results of which validated the initial cohort. The urinary metabotype of patients with HCC was distinct from those with Cir, DC, and NC with areas under the receiver operating characteristic (AUROC) curves of 0.86 (0.78–0.94), 0.93 (0.89–0.97), and 0.89 (0.80–0.98) in the training set and 0.81 (0.73–0.89), 0.96 (0.94–0.99), and 0.90 (0.85–0.96), respectively, in the validation cohort. A urinary metabolite panel, comprising inosine, indole-3-acetate, galactose, and an N-acetylated amino acid (NAA), showed a high sensitivity (86.9% [75.8–94.2]) and specificity (90.3% [74.2–98.0]) in the discrimination of HCC from cirrhosis, a finding that was corroborated in a validation cohort (AUROC: urinary panel = 0.72; AFP = 0.58). Metabolites that were significantly increased in urine of HCC patients, and which correlated with clinical stage of HCC, were NAA, dimethylglycine, 1-methylnicotinamide, methionine, acetylcarnitine, 2-oxoglutarate, choline, and creatine. Conclusion: The urinary metabotyping of this West African cohort identified and validated a metabolite panel that diagnostically outperforms serum AFP. (Hepatology 2014;60:1291–1301)
Serum mitochondrial biomarkers and damage-associated molecular patterns are higher in acetaminophen overdose patients with poor outcome
Authors: McGill Mitchell R. , Staggs Vincent S. , Sharpe Matthew R. , Lee William M. , Jaeschke Hartmut
Published: June 2014

Acetaminophen (APAP) overdose is a major cause of acute liver failure (ALF). Numerous studies have shown that APAP hepatotoxicity in mice involves mitochondrial dysfunction, and recent data suggest that this is also the case in humans. We have previously shown that glutamate dehydrogenase (GDH), mitochondrial DNA (mtDNA), and nuclear DNA (nDNA) fragments can be measured in circulation of overdose patients as mechanistic biomarkers of mitochondrial damage and damage-associated molecular patterns. In the present study, our aim was to determine whether these biomarkers are higher in serum from nonsurvivors of APAP-induced ALF (AALF), compared to survivors. GDH, mtDNA, and nDNA fragments were measured in serum from AALF patients who did (n = 34) or did not (n = 35) recover. Importantly, all three were significantly increased in patients who died, compared to those who survived (GDH: 450 ± 73 vs. 930 ± 145 U/L; mtDNA: 21 ± 6 vs. 48 ± 13 and 33 ± 10 vs. 43 ± 7 ng/mL for two different genes; nDNA fragments: 148 ± 13 vs. 210 ± 13% of control). Receiver operating characteristic (ROC) curve analyses revealed that nDNA fragments, GDH, and mtDNA were predictive of outcome (area under the curve [AUC], study admission: 0.73, 0.70, and 0.71 or 0.76, respectively, P < 0.05; AUC, time of peak ALT: 0.78, 0.71, and 0.71 or 0.76, respectively, P < 0.05), and the results were similar to those from the Model for End-Stage Liver Disease (MELD; AUC, peak MELD: 0.77; P < 0.05). Conclusions: Our data suggest that patients with more mitochondrial damage are less likely to survive, demonstrating that mitochondria are central in the mechanisms of APAP hepatotoxicity in humans. Clinically, serum nDNA fragments, GDH, and mtDNA could be useful as part of a panel of biomarkers to predict patient outcome. (Hepatology 2014;60:1336–1345)