bluuebunny/crossref_metadata_2025 huggingface dataset:
Mathematical Analysis of Hepatitis B Virus Transmission Dynamics in the Absence of Therapy with Atangana-Baleanu Fractional -Order SPQWXY Model
Authors: Bamigwojo Otugene Victor , Ezike Mbah Christopher Godwin , Alemoh Paul Owhenagbo , Idoko(OP) Idoko Peter , Adedoyin Jeremiah Damilola , Enyejo Lawrence Anebi , Chikaedum Agina Precious
Published: October 2024

This paper presents an innovative fractional order network model aimed at elucidating the transmission dynamics of Hepatitis B Virus (HBV). Incorporating fractional calculus enables the model to capture the intricate, memory-dependent mechanisms inherent in HBV spread, thereby overcoming the constraints of conventional integer order models. The primary objective of the study is to develop a more precise depiction of HBV transmission, encompassing both vertical and horizontal routes in the absence of vaccination strategies. Furthermore, the paper assesses the existence and uniqueness of solutions utilizing the Banach fixed point theory with the Picard-Lindelf approach. Numerical simulations conducted across various fractional orders reveal that as the fractional order decreases from 1, the rate of endemic spread decelerates.
Eddy‐induced carbon transport across the Antarctic Circumpolar Current
Authors: Moreau Sébastien , Penna Alice Della , Llort Joan , Patel Ramkrushnbhai , Langlais Clothilde , Boyd Philip W. , Matear Richard J. , Phillips Helen E. , Trull Thomas W. , Tilbrook Bronte , Lenton Andrew , Strutton Peter G.
Published: August 2017

The implications of a mesoscale eddy for relevant properties of the Southern Ocean carbon cycle are examined with in situ observations. We explored carbon properties inside a large (~190 km diameter) cyclonic eddy that detached from the Subantarctic Front (SAF) south of Tasmania in March 2016. Based on remote sensing, the eddy was present for ~2 months in the Subantarctic Zone (SAZ), an important region of oceanic carbon dioxide (CO2) uptake throughout the annual cycle and carbon subduction (i.e., where mode and intermediate waters form), before it was reabsorbed into the SAF. The eddy was sampled during the middle of its life, 1 month after it spawned. Comparatively, the eddy was ~3°C colder, 0.5 practical salinity unit fresher, and less biologically productive than surrounding SAZ waters. The eddy was also richer in dissolved inorganic carbon (DIC) and had lower saturation states of aragonite and calcite than the surrounding SAZ waters. As a consequence, it was a strong source of CO2 to the atmosphere (with fluxes up to +25 mmol C m−2 d−1). Compared to the SAF waters, from which it originated, DIC concentration in the eddy was ~20 μmol kg−1 lower, indicating lateral mixing, small‐scale recirculation, or eddy stirring with lower‐DIC SAZ waters by the time the eddy was observed. As they are commonly spawned from the Antarctic Circumpolar Current, and as 50% of them decay in the SAZ (the rest being reabsorbed by the SAF‐N), these types of eddies may represent a significant south‐north transport pathway for carbon across the ACC and may alter the carbon properties of SAZ waters.
Vegetation masking effect on future warming and snow albedo feedback in a boreal forest region of northern Eurasia according to MIROC‐ESM
Authors: Abe Manabu , Takata Kumiko , Kawamiya Michio , Watanabe Shingo
Published: August 2017

The Earth system model, Model for Interdisciplinary Research on Climate‐Earth system model (MIROC‐ESM), in which the leaf area index (LAI) is calculated interactively with an ecological land model, simulated future changes in the snow water equivalent under the scenario of global warming. Using MIROC‐ESM, the effects of the snow albedo feedback (SAF) in a boreal forest region of northern Eurasia were examined under the possible climate future scenario RCP8.5. The simulated surface air temperature (SAT) in spring greatly increases across Siberia and the boreal forest region, whereas the snow cover decreases remarkably only in western Eurasia. The large increase in SAT across Siberia is attributed to strong SAF, which is caused by both the reduced snow‐covered fraction and the reduced surface albedo of the snow‐covered portion due to the vegetation masking effect in those grid cells. A comparison of the future changes with and without interactive LAI changes shows that in Siberia, the vegetation masking effect increases the spring SAF by about two or three times and enhances the spring warming by approximately 1.5 times. This implies that increases in vegetation biomass in the future are a potential contributing factor to warming trends and that further research on the vegetation masking effect is needed for reliable future projection.
Scaling properties of observed and simulated satellite visible radiances
Authors: Barker Howard W. , Qu Zhipeng , Bélair Stéphane , Leroyer Sylvie , Milbrandt Jason A. , Vaillancourt Paul A.
Published: August 2017

Structure functions Sq, which are related to power spectra and used to study turbulence, were computed for GOES‐13 visible radiances measured on 16 May 2015 over French Guiana and adjacent Atlantic Ocean. The nested Global Environmental Multiscale (GEM) numerical weather prediction (NWP) model was run for the same time and area. Cloud data generated by GEM over (300 km)2 domains, with one‐way nesting ending at horizontal grid‐spacing of 0.25 km, were operated on by a 3‐D solar radiative transfer model with resulting radiances degraded to GOES‐13 resolution (~1 km) and Sq computed for them, too. For GOES‐13 radiances, scaling exponents ζ(2) associated with S2, for separation distances between 5 km and 25 km, were typically >0.6 for deep convective and marine boundary layer clouds and <0.4 for shallow cumuli over land. ζ(2) for GEM agreed well with GOES‐13 for deep convective clouds. This suggests that the self‐organizing properties of deep convection in GEM exhibit realistic geometric features, a potentially important point given the link between cloud structure and precipitation, with the latter being much more difficult to measure and assess than visible radiances. Regarding radiances for GEM's marine boundary layer clouds, their Sq differed markedly from GOES‐13's; better resembling fair‐weather cumulus. Likewise, GEM's shallow cumuli over land appear to have bypassed the “scattered” fair‐weather stage and went straight into more organized convection. Thus, it appears that comparing time series of Sq for geostationary satellite data and corresponding modeled radiances has the potential to benefit assessment of cloud system‐resolving models.
Terrain controls on the occurrence of coastal retrogressive thaw slumps along the Yukon Coast, Canada
Authors: Ramage Justine L. , Irrgang Anna M. , Herzschuh Ulrike , Morgenstern Anne , Couture Nicole , Lantuit Hugues
Published: August 2017

Retrogressive thaw slumps (RTSs) are among the most active landforms in the Arctic; their number has increased significantly over the past decades. While processes initiating discrete RTSs are well identified, the major terrain controls on the development of coastal RTSs at a regional scale are not yet defined. Our research reveals the main geomorphic factors that determine the development of RTSs along a 238 km segment of the Yukon Coast, Canada. We (1) show the current extent of RTSs, (2) ascertain the factors controlling their activity and initiation, and (3) explain the spatial differences in the density and areal coverage of RTSs. We mapped and classified 287 RTSs using high‐resolution satellite images acquired in 2011. We highlighted the main terrain controls over their development using univariate regression trees model. Coastal geomorphology influenced both the activity and initiation of RTSs: active RTSs and RTSs initiated after 1972 occurred primarily on terrains with slope angles greater than 3.9° and 5.9°, respectively. The density and areal coverage of RTSs were constrained by the volume and thickness of massive ice bodies. Differences in rates of coastal change along the coast did not affect the model. We infer that rates of coastal change averaged over a 39 year period are unable to reflect the complex relationship between RTSs and coastline dynamics. We emphasize the need for large‐scale studies of RTSs to evaluate their impact on the ecosystem and to measure their contribution to the global carbon budget.
Human neural stem cell transplantation into the corpus callosum of Alzheimer's mice
Authors: McGinley Lisa M. , Kashlan Osama N. , Chen Kevin S. , Bruno Elizabeth S. , Hayes John M. , Backus Carey , Feldman Seth , Kashlan Bader N. , Johe Karl , Feldman Eva L.
Published: August 2017

The hippocampus has been the target of stem cell transplantations in preclinical studies focused on Alzheimer's disease, with results showing improvements in histological and behavioral outcomes. The corpus callosum is another structure that is affected early in Alzheimer's disease. Therefore, we hypothesize that this structure is a novel target for human neural stem cell transplantation in transgenic Alzheimer's disease mouse models. This study demonstrates the feasibility of targeting the corpus callosum and identifies an effective immunosuppression regimen for transplanted neural stem cell survival. These results support further preclinical development of the corpus callosum as a therapeutic target in Alzheimer's disease.
Transition Metal‐Catalysed Intramolecular Carbenoid C−H Insertion for Pyrrolidine Formation by Decomposition of α‐Diazoesters
Authors: Solé Daniel , Amenta Arianna , Mariani Francesco , Bennasar M.‐Lluïsa , Fernández Israel
Published: August 2017

The use of Pd‐, Rh(II)‐ and Ru(II)‐based catalysts has been explored in the transition metal‐catalysed intramolecular carbenoid C−H insertion of α‐diazoesters leading to pyrrolidines. Although the outcome of the reaction was highly substrate‐dependent, in general, it was possible to control the chemoselectivity of the process towards pyrrolidines by adequate catalyst selection. The Pd(0)‐catalysts were as efficient as [Rh(Ph3CCO2)2]2 in promoting the C(sp3)−H insertion of ortho‐substituted anilines. In contrast, for anilines bearing meta‐ and para‐substituents, the Rh(II)‐catalyst provided the best chemoselectivities and reaction yields. On the other hand, [Ru(p‐cymene)Cl2]2 was the most efficient catalyst for the insertion reaction of the N‐benzyl‐N‐phenyl and N,N‐dibenzyl α‐diazoesters, while the C(sp3)−H insertion of the N‐benzylsulfonamide substrate was only promoted by [Rh(Ph3CCO2)2]2. According to density functional theory (DFT) calculations, the mechanism involved in the Pd(0)‐ and Ru(II)‐catalysed C(sp3)−H insertions differs considerably from that typically proposed for the Rh(II)‐catalysed transformation. Whereas the Pd(0)‐catalysed reaction involves a Pd‐mediated 1,5‐H migration from the C(sp3)−H bond to the carbenoid carbon atom leading to the formal oxidation of the transition metal, a Ru(II)‐promoted Mannich type reaction involving a zwitterionic intermediate seems to be operative in the Ru(II)‐catalysed transformation.

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Heritability and genetic integration of tooth size in the South Carolina Gullah
Authors: Stojanowski Christopher M. , Paul Kathleen S. , Seidel Andrew C. , Duncan William N. , Guatelli‐Steinberg Debbie
Published: August 2017

Objectives

This article provides estimates of narrow‐sense heritability and genetic pleiotropy for mesiodistal tooth dimensions for a sample of 20th century African American individuals. Results inform biological distance analysis and offer insights into patterns of integration in the human dentition.

Materials and Methods

Maximum mesiodistal crown dimensions were measured using Hillson‐FitzGerald calipers on 469 stone dental casts from the Menegaz‐Bock Collection. Narrow‐sense heritability estimates and genetic and phenotypic correlations were estimated using SOLAR 8.1.1 with covariate screening for age, sex, age*sex interaction, and birth year.

Results

Heritability estimates were moderate (∼0.10 – 0.90;h2mean = 0.51) for most measured variables with sex as the only significant covariate. Patterns of genetic correlation indicate strong integration across tooth classes, except molars. Comparison of these results to previously published work suggests lower overall heritability relative to other human populations and much stronger genetic integration across tooth classes than obtained from nonhuman primate genetic pleiotropy estimates.

Conclusions

These results suggest that the high heritabilities previously published may reflect overestimates inherent in previous study designs; as such the standard estimate of 0.55 used in biodistance analyses may not be appropriate. For the Gullah, isolation and endogamy coupled with elevated levels of physiological and economic stress may suppress narrow‐sense heritability estimates. Pleiotropy analyses suggest a more highly integrated dentition in humans than in other mammals.
Occurrence of osteon banding in adult human cortical bone
Authors: Andronowski Janna M. , Pratt Isaac V. , Cooper David M. L.
Published: August 2017

Objectives

Differentiating human from nonhuman fragmented bone is often accomplished using histological methods if the observation of gross morphology proves insufficient. Linearly oriented primary and/or secondary osteonal systems, commonly referred to as osteon bands, are described as a strong indicator of nonhuman bone, particularly the occurrence of multiple bands. This phenomenon has been conventionally documented using two‐dimensional (2D) histology, but such analyses are destructive and typically limited to a single cross‐section. Progressive developments in high‐resolution X‐ray imaging, however, allow for the nondestructive three‐dimensional (3D) visualization of bone microarchitecture. The primary objective of the current research was to visualize and document the occurrence of osteon banding in adult human cortical bone using high‐resolution synchrotron radiation‐based micro‐Computed Tomography (SR micro‐CT).

Materials and methods

Synchrotron radiation‐based micro‐CT scanning was carried out at the Canadian Light Source (CLS) national synchrotron facility. The presence or absence of osteon banding was visualized in human skeletal elements from three adult males with representative samples from all regions of the skeleton (n = 129). If present, osteon banding was described and quantified.

Results

Results indicated that 23 of 129 human cortical bone specimens exhibited osteon banding, representing 18% of the sample. Linear arrangements of primary and/or secondary osteons were observed in the following skeletal elements: temporal, parietal, frontal, occipital, clavicle, mandible, femur, tibia, ulna, second metatarsal, and sacrum.

Discussion

The present work represents the first 3D examination of inter‐element variation in osteon banding in adult human cortical bone. Findings indicate that the presence of multiple osteon bands in a single specimen is not diagnostic of nonhuman bone. As such, osteon banding categorically should not be taken as evidence of nonhuman bone in forensic and archaeological contexts.
Variation in human gape cycle kinematics and occlusal topography
Authors: Laird Myra F.
Published: August 2017

Objectives

This study tested hypotheses relating intraspecific variation in occlusal morphology and intraspecific variation in jaw movements during feeding. Gape cycle kinematic variation was hypothesized to correlate with gape cycle number within a chewing sequence as well as with food toughness and stiffness. Gape cycle kinematic variation was also hypothesized to correlate with variation in occlusal area, slope, and volume.

Methods and Materials

Twenty‐six adult human subjects chewed four foods with varying material properties while their jaw movements were recorded using three‐dimensional coordinates of facial markers captured with a Vicon camera system. Post‐canine occlusal morphology of each subject was quantified in ArcGIS using dental topographic analysis of dental casts.

Results

Gape cycle duration did not vary with gape cycle number, food toughness, or food stiffness. Gape cycle vertical and lateral displacement correlated negatively with gape cycle number, while foods with higher toughness and Young's modulus had greater jaw vertical and lateral displacement. Subjects with steeper occlusal slopes had longer gape cycle durations and greater amounts of vertical displacement during the slow closing phase of the gape cycle.

Discussion

The results suggest that gape cycle durations are relatively consistent despite changes in food properties and gape cycle number, while occlusal slope affects gape cycle duration and vertical displacement during inferred occlusal contact. However, gape cycle number and bolus properties explain greater amounts of kinematic variation than does occlusal morphology.
A test of the optimal iron hypothesis among breastfeeding Ariaal mothers in northern Kenya
Authors: Fujita Masako , Wander Katherine
Published: August 2017

Objective

The optimal iron hypothesis posits a trade‐off in iron nutrition—iron deficiency restricts iron available to infectious agents, protecting against severe infection, but also compromises immune defense—such that mild‐to‐moderate iron deficiency may be more adaptive than either iron‐replete or severe deficiency in environments with high infectious disease load. This hypothesis has not been tested among adults.

Materials and Methods

A secondary analysis of data and specimens from 220 lactating mothers in northern Kenya was conducted. Elevated serum C‐reactive protein (CRP > 2 or >5 mg/l) was utilized to identify prevalent subclinical infection/inflammation. Iron deficiency was identified with transferrin receptor in archived dried blood spots (TfR > 5.0 mg/l). The absence of iron deficiency or anemia (Hemoglobin < 12 g/l) defined the iron replete state. Iron‐deficient erythropoiesis (IDE, mild‐to‐moderate iron deficiency) was defined as iron deficiency without anemia; iron deficiency anemia (IDA, severe iron deficiency) as iron deficiency with anemia; and noniron‐deficiency anemia (NIDA) as anemia without iron deficiency.

Results

The prevalence of elevated inflammation (subclinical infection) was lowest in IDE. In logistic regression, IDE was inversely associated with inflammation (for CRP > 2 mg/l: adjusted odds ratio, aOR = 0.30; p = 0.02; for CRP > 5 mg/l: aOR = 0.27; p = 0.10), compared to the iron replete state. The protective effect of IDE differed in the presence of vitamin A deficiency or underweight.

Conclusions

We interpret these patterns as tentative support for the optimal iron hypothesis in breastfeeding women in the infectious disease ecology of northern Kenya. Iron deficiency may interact in important ways with other forms of malnutrition that are known to affect immune protection.
Perspectives of Aboriginal issues among non‐Aboriginal residents of rural Victorian communities
Authors: Bourke Lisa , Malatzky Christina , Terry Daniel , Nixon Raelene , Ferguson Karyn , Ferguson Peter
Published: August 2017

Racism, in various forms, remains a dominant feature in Australian society. Aboriginal Australians are commonly targets of racial discrimination. However, understanding racism is difficult given that racial attitudes vary towards particular groups of people, across place and time and are difficult to measure. This paper presents responses of residents across four rural shires in Victoria to questions about attitudes towards Aboriginal people/issues. Responses indicated that attitudes towards Aboriginal people were diverse and that individuals varied in their attitudes on specific items. There were subtle differences between the four sites and association between demographic characteristics and some items in particular sites. This suggests that respondents are inconsistent in their attitudes relating to Aboriginal people/issues and that there are place‐based influences on these attitudes. We conclude that the many varied understandings of racism and Aboriginal Australians allow the discourses of exclusion, disempowerment and othering to be maintained.
Uneven Integration: Local Government Integration Policies and Filipino Residents in Nagoya City, Japan
Authors: Sioson Erica Paula
Published: August 2017

The failure at the national level to address foreign resident integration has highlighted the need for local governments to implement policies and provide social services to foreign residents to promote multicultural co‐existence. How such policies impact the integration of foreign residents given the specific context by which they migrated and settled is what this article seeks to investigate. Indices measuring integration policies tend to assess only what policies are intended to measure, leaving out unintended outcomes that can help better understand policy impact. This study is based on a mixed‐methods study of Filipino residents in Nagoya City. Using a multidimensional approach to understand the extent of integration, I found that the Filipino residents are experiencing an uneven integration, brought about by a conflation of the approach of the local government to integration that prioritizes structural integration and the specific context of the Filipino residents in Japan.
Millimeter‐wave emissivity as a metric for the non‐contact diagnosis of human skin conditions
Authors: Owda Amani Yousef , Salmon Neil , Harmer Stuart William , Shylo Sergiy , Bowring Nicholas John , Rezgui Nacer Ddine , Shah Mamta
Published: August 2017

A half‐space electromagnetic model of human skin over the band 30–300 GHz was constructed and used to model radiometric emissivity. The model showed that the radiometric emissivity rose from 0.4 to 0.8 over this band, with emission being localized to a layer approximately one millimeter deep in the skin. Simulations of skin with differing water contents associated with psoriasis, eczema, malignancy, and thermal burn wounds indicated radiometry could be used as a non‐contact technique to detect and monitor these conditions. The skin emissivity of a sample of 30 healthy volunteers, measured using a 95 GHz radiometer, was found to range from 0.2 to 0.7, and the experimental measurement uncertainty was ±0.002. Men on average were found to have an emissivity 0.046 higher than those of women, a measurement consistent with men having thicker skin than women. The regions of outer wrist and dorsal forearm, where skin is thicker, had emissivities 0.06–0.08 higher than the inner wrist and volar forearms where skin is generally thinner. Recommendations are made to develop a more sophisticated model of the skin and to collect larger data sets to obtain a deeper understanding of the signatures of human skin in the millimeter wave band. Bioelectromagnetics. 38:559–569, 2017. © 2017 The Authors. Bioelectromagnetics published by Wiley Periodicals, Inc.
Strain Breeding Enhanced Heterologous Cellobiohydrolase Secretion by Saccharomyces cerevisiae in a Protein Specific Manner
Authors: Kroukamp Heinrich , den Haan Riaan , la Grange Daniël C. , Sibanda Ntsako , Foulquié‐Moreno Maria R. , Thevelein Johan M. , van Zyl Willem H.
Published: August 2017

The yeast Saccharomyces cerevisiae has a long association with alcoholic fermentation industries and has received renewed interest as a biocatalyst for second‐generation bioethanol production. Rational engineering strategies are used to create yeast strains for consolidated bioprocessing of lignocellulosic biomass. Although significant progress is made in this regard with the expression of different cellulolytic activities in yeast, cellobiohydrolase (CBH) titers remain well below ideal levels. Through classical breeding, S. cerevisiae strains with up to twofold increased CBH secretion titers is obtained in strains expressing a single gene copy. An increase of up to 3.5‐fold in secreted cellobiohydrolase activity is subsequently shown for strains expressing the heterologous gene on a high copy episomal vector. To our knowledge, this is the first report of classical breeding being used to enhance heterologous protein secretion and also the most significant enhancement of CBH secretion in yeast yet reported. This enhanced secretion phenotype is specific for cellobiohydrolase I secretion, indicating that reporter protein properties might be a major determining factor for efficient protein secretion in yeast. By exploring the latent potential of different S. cerevisiae strains, the authors show that the allele pool of various strains is a valuable engineering resource to enhance secretion in yeast.
A metabolic engineering strategy for producing free fatty acids by the Yarrowia lipolytica yeast based on impairment of glycerol metabolism
Authors: Yuzbasheva Evgeniya Y. , Mostova Elizaveta B. , Andreeva Natalia I. , Yuzbashev Tigran V. , Fedorov Alexander S. , Konova Irina A. , Sineoky Sergey P.
Published: August 2017

In recent years, bio‐based production of free fatty acids from renewable resources has attracted attention for their potential as precursors for the production of biofuels and biochemicals. In this study, the oleaginous yeast Yarrowia lipolytica was engineered to produce free fatty acids by eliminating glycerol metabolism. Free fatty acid production was monitored under lipogenic conditions with glycerol as a limiting factor. Firstly, the strain W29 (Δgpd1), which is deficient in glycerol synthesis, was obtained. However, W29 (Δgpd1) showed decreased biomass accumulation and glucose consumption in lipogenic medium containing a limiting supply of glycerol. Analysis of substrate utilization from a mixture of glucose and glycerol by the parental strain W29 revealed that glycerol was metabolized first and glucose utilization was suppressed. Thus, the Δgpd1Δgut2 double mutant, which is deficient also in glycerol catabolism, was constructed. In this genetic background, growth was repressed by glycerol. Oleate toxicity was observed in the Δgpd1Δgut2Δpex10 triple mutant strain which is deficient additionally in peroxisome biogenesis. Consequently, two consecutive rounds of selection of spontaneous mutants were performed. A mutant released from growth repression by glycerol was able to produce 136.8 mg L−1 of free fatty acids in a test tube, whereas the wild type accumulated only 30.2 mg L−1. Next, an isolated oleate‐resistant strain produced 382.8 mg L−1 of free fatty acids. Finely, acyl‐CoA carboxylase gene (ACC1) over‐expression resulted to production of 1436.7 mg L−1 of free fatty acids. The addition of dodecane promoted free fatty acid secretion and enhanced the level of free fatty acids up to 2033.8 mg L−1 during test tube cultivation.
Comparative analysis of plant‐produced, recombinant dimeric IgA against cell wall β‐glucan of pathogenic fungi
Authors: Capodicasa Cristina , Catellani Marcello , Moscetti Ilaria , Bromuro Carla , Chiani Paola , Torosantucci Antonella , Benvenuto Eugenio
Published: August 2017

Immunoglobulins A (IgA) are crucially involved in protection of human mucosal surfaces from microbial pathogens. In this work, we devised and expressed in plants recombinant chimeric antifungal antibodies (Abs) of isotype A (IgA1, IgA2, and scFvFcA1), derived from a murine mAb directed to the fungal cell wall polysaccharide β‐glucan which had proven able to confer protection against multiple pathogenic fungi. All recombinant IgA (rIgA) were expressed and correctly assembled in dimeric form in plants and evaluated for yield, antigen‐binding efficiency and antifungal properties in vitro, in comparison with a chimeric IgG1 version. Production yields and binding efficiency to purified β‐glucans showed significant variations not only between Abs of different isotypes but also between the different IgA formats. Moreover, only the dimeric IgA1 was able to strongly bind cells of the fungal pathogen Candida albicans and to restrain its adhesion to human epithelial cells. Our data indicate that IgG to IgA switch and differences in molecular structure among different rIgA formats can impact expression in plant and biological activity of anti‐β‐glucans Abs and provide new insights for the design of recombinant IgA as anti‐infective immunotherapeutics, whose potential is still poorly investigated.
Codelivery of anti‐cancer agents via double‐walled polymeric microparticles/injectable hydrogel: A promising approach for treatment of triple negative breast cancer
Authors: Davoodi Pooya , Ng Wei Cheng , Srinivasan Madapusi P. , Wang Chi‐Hwa
Published: August 2017

Triple negative breast cancer (TNBC) is an aggressive sub‐type of breast cancer that rarely responds to conventional chemotherapy. Therefore, novel agents or new routes need to be developed to improve treatment efficacy and diminish severe side‐effects of anti‐cancer agents in TNBC patients. This study explores a novel localized co‐delivery platform with potential application against TNBC. Uniform core‐shell microparticles encapsulating cisplatin (Cis‐DDP) and paclitaxel (PTX) are fabricated using coaxial electrohydrodynamic atomization technique and subsequently are embedded into an injectable hydrogel. The hydrogel provides an additional diffusion barrier against Cis‐DDP and confines premature release of drugs. In addition, the hydrogel can provide a versatile tool for retaining particles in the tumor resected cavity during the injection following debulking surgery and prevent surgical site infection due to its inherent antibacterial properties. The combination of Cis‐DDP and PTX demonstrates a synergistic effect against MDA‐MB‐231 cell line assigned to three different mechanisms of action, including denaturation of DNA strands, stabilization of microtubules, and amplification of intracellular reactive oxygen species (ROS) and activation of caspase‐3 pathways. The results show a significant accumulation of mitochondrial ROS insults in cells upon treatment that consequently causes programmed cells death. The performance of microparticles/hydrogel carrier is evaluated against three‐dimensional MDA‐MB‐231 (breast cancer) 3D spheroids, where a superior efficacy and a greater reduction in spheroid growth are observed over 14 days, as compared with free‐drug treatment. Overall, drug‐loaded core‐shell microparticles embedded into injectable hydrogel provides a promising strategy to treat aggressive cancers and a modular platform for a broad range of localized multidrug therapies customizable to the cancer type.
Dynamic monitoring of p53 translocation to mitochondria for the analysis of specific inhibitors using luciferase‐fragment complementation
Authors: Noda Natsumi , Awais Raheela , Sutton Robert , Awais Muhammad , Ozawa Takeaki
Published: August 2017

Intracellular protein translocation plays a pivotal role in regulating complex biological processes, including cell death. The tumor suppressor p53 is a transcription factor activated by DNA damage and oxidative stress that also translocates from the cytosol into the mitochondrial matrix to facilitate necrotic cell death. However, specific inhibitors of p53 mitochondrial translocation are largely unknown. To explore the inhibitors of p53, we developed a bioluminescent probe to monitor p53 translocation from cytosol to mitochondria using luciferase fragment complementation assays. The probe is composed of a novel pair of luciferase fragments, the N‐terminus of green click beetle luciferase CBG68 (CBGN) and multiple‐complement luciferase fragment (McLuc1). The combination of luciferase fragments showed significant luminescence intensity and high signal‐to‐background ratio. When the p53 connected with McLuc1 translocates from cytosol into mitochondrial matrix, CBGN in mitochondrial matrix enables to complement with McLuc1, resulting in the restoration of the luminescence. The luminescence intensity was significantly increased under hydrogen peroxide‐induced oxidative stress following the complementation of CBGN and McLuc1. Pifithrin‐μ, a selective inhibitor of p53 mitochondrial translocation, prevented the mitochondrial translocation of the p53 probe in a concentration‐dependent manner. Furthermore, the high luminescence intensity made it easier to visualize the p53 translocation at a single cell level under a bioluminescence microscope. This p53 mitochondrial translocation assay is a new tool for high‐throughput screening to identify novel p53 inhibitors, which could be developed as drugs to treat diseases in which necrotic cell death is a major contributor.
Simultaneous determination of morphine‐6‐d‐glucuronide, morphine‐3‐d‐glucuronide and morphine in human plasma and urine by ultra‐performance liquid chromatography–tandem mass spectrometry: Application to M6G injection pharmacokinetic study
Authors: Xu Wen , Zhuang Quankun , Chen Xia , Jiang Ji , Hu Pei , Wang Hongyun
Published: August 2017

A robust ultra‐performance liquid chromatography–tandem mass spectrometry (UPLC–MS/MS) method for the determination of morphine‐6‐d‐glucuronide (M6G), morphine‐3‐d‐glucuronide (M3G) and morphine (MOR) in human plasma and urine has been developed and validated. The analytes of interest were extracted from plasma by protein precipitation. The urine sample was prepared by dilution. Both plasma and urine samples were chromatographed on an Acquity UPLC HSS T3 column using gradient elution. Detection was performed on a Xevo TQ‐S tandem mass spectrometer in multiple reaction monitoring mode using positive electrospray ionization. Matrix interferences were not observed at the retention time of the analytes and internal standard, naloxone‐D5. The lower limits of quantitation of plasma and urine were 2/0.5/0.5 and 20/4/2 ng/mL for M6G/M3G/MOR, respectively. Calibration curves were linear over the concentration ranges of 2–2000/0.5–500/0.5–500 and 20–20,000/4–4000/2–2000 ng/mL for M6G/M3G/MOR in plasma and urine samples, respectively. The precision was <7.14% and the accuracy was within 85–115%. Furthermore, stability of the analytes at various conditions, dilution integrity, extraction recovery and matrix effect were assessed. Finally, this quantitative method was successfully applied to the pharmacokinetic study of M6G injection in Chinese noncancer pain patients.
Quantitative analysis of clofazimine (Lamprene®), an antileprosy agent, in human dried blood spots using liquid chromatography–tandem mass spectrometry
Authors: Li Wenkui , Doherty John , Fu Yunlin , Flarakos Jimmy
Published: August 2017

An LC–MS/MS method was developed and validated for bioanalysis of clofazimine in human dried blood spot (DBS) samples in support of a clinical study on multidrug‐resistant tuberculosis in developing countries. The validated assay dynamic range was from 10.0 to 2000 ng/mL using a 1/8 inch DBS punch. The accuracy and precision of the assay were ±11.0% (bias) and ≤13.5% (CV) for the LLOQs (10.0 ng/mL) and ±15% (bias) and ≤15% (CV) for all other QC levels. The assay was proved to be free from the possible impact owing to spot size and storage temperature (e.g. at 60°C, ≤ − 60°C). The validated assay is well suited for the intended clinical study where conventional pharmacokinetic sample collection is not feasible.
Employment of modified Fe3O4 nanoparticles using thermo‐sensitive polymer for extraction and pre‐concentration of cefexime in biological samples
Authors: Naghibi Saman , Sahebi Hamed
Published: August 2017

Cefexime is a useful antibiotic that can be prescribed to treat bacterial infections. Nanoparticles have been widely marketed as a universal solution among scientists. Many studies have been performed to modify nanoparticles to make them functional as extraction and pre‐concentration agents and drug carriers. Temperature‐sensitive polymers belong to a group of substances that undergo a major change in their physical features in response to temperature. Recently developed polymers can be used in many different areas, including modification of nanoparticles. In order to modify this nanoparticle, grafting copolymerization of Fe3O4 nanoparticles was performed using poly (N‐vinylcaprolactam) and 3‐allyloxy‐1,2‐propanediol. The optimum conditions for pre‐concentration of cefexime were studied. Under these optimum conditions, extraction recovery of biological samples in the range of 71–89% was obtained. The limit of detection and precision of proposed method were 4.5 × 10−4 μg mL−1 and <4.11% (relative standard deviation), respectively. Based on the results from analysis of cefexime, in biological samples using the proposed method, the ability of this method to extract and pre‐concentrate cefexime was confirmed. Also, satisfactory results from an in vitro study on drug release in simulated intestine media were obtained.
β‐Acrolein‐Substituted Corroles: A Route to the Preparation of Functionalized Polyacrolein Microspheres for Chemical Sensor Applications
Authors: Savoldelli Andrea , Magna Gabriele , Di Natale Corrado , Catini Alexandro , Nardis Sara , Fronczek Frank R. , Smith Kevin M. , Paolesse Roberto
Published: August 2017

An efficient β‐functionalization of [5,10,15‐tris‐(4‐methylphenyl)corrolato]cobalt derivatives through a Vilsmeier‐type reaction allows the introduction of an acrolein substituent, which is subsequently copolymerized with pure acrolein. The obtained hybrid microspheres are exploited as nanogravimetric chemical sensors. The sensing properties of the developed sensors are tested through exposure to different volatile organic compounds chosen as model analytes. The results show improved sensor sensitivity of the resulting devices for all the tested analytes with respect to sensors functionalized with either corrole or polyacrolein. The enhanced properties are attributed to the accurate and tunable merging of the properties of both exploited materials.
Robust Macroscopic 3D Sponges of Manganese Oxide Molecular Sieves
Authors: Liu Zhenxin , Wu Depeng , Guo Xuehui , Fang Shaoming , Wang Lizhen , Xing Yu , Suib Steven L.
Published: August 2017

The construction of macroscopic 3D sponges is of great technological importance for various applications. An outstanding challenge is the facile fabrication of sponges with the desirable combination of good stability, high electrical conductivity, and absorption ability. Here free‐standing 3D OMS‐2 sponges are demonstrated, with various densities, which possess a combination of desirable physical properties including high porosity, robustness, permeability, recyclability, high electrical conductivity, and selective water absorption in preference to oil. Some of these properties have systematic trends with various densities. The stress of the OMS‐2 sponge, made by nanowire‐based freeze‐drying process, is four orders of magnitude higher than that made by calcination‐related process. These new materials should find practical applications in environmental, catalysis, sensing, absorption, and energy storage, particularly in the removal of water spill cleanup, and beyond.
Two New Preyssler‐Type Polyoxometalate‐Based Coordination Polymers and Their Application in Horseradish Peroxidase Immobilization
Authors: Du Jing , Cao Mei‐Da , Feng Shu‐Li , Su Fang , Sang Xiao‐Jing , Zhang Lan‐Cui , You Wan‐Sheng , Yang Mei , Zhu Zai‐Ming
Published: August 2017

Enzyme immobilization is of increasing importance for biocatalysis, for which good supports are critical. Herein, two new Preyssler‐type polyoxometalate (POM)‐based coordination polymers, namely, {[Cu(H2biim)2][{Cu(H2biim)2(μ‐H2O)}2Cu(H2biim)(H2O)2]H[({Cu(H2biim)(H2O)2}0.5)2((μ‐C3HN2Cl2){Cu(H2biim)}2){Z(H2O)P5W30O110}]⋅x H2O}n (1: Z=Na, x=9; 2: Z=Ag, x=10; H2biim=2,2′‐biimidazole) were designed and synthesized. Compounds 1 and 2 exhibit the same skeletons, which contain multiple CuII complex fragments and penta‐supported {ZP5W30} (Z=Na, Ag) clusters. They were first employed to immobilize horseradish peroxidase (HRP). Results show that compounds 1 and 2 are good supports for HRP immobilization, and exhibit higher enzyme loading, lower loading times, and excellent reusability. The immobilized HRP (HRP/1 or HRP/2) was further applied to detect H2O2, and good sensitivity, wide linear range, low detection limit, and fast response were achieved. This work shows that POM‐based hybrid materials are a new kind of promising support for enzyme immobilization.
Opioid Tripeptides Hybridized with trans‐1‐Cinnamylpiperazine as Proliferation Inhibitors of Pancreatic Cancer Cells in Two‐ and Three‐Dimensional in vitro Models
Authors: Laskowska Anna K. , Puszko Anna K. , Sosnowski Piotr , Różycki Krzysztof , Kosson Piotr , Matalińska Joanna , Durlik Marek , Misicka Aleksandra
Published: August 2017

According to the World Health Organization, the mortality rate among patients with pancreatic cancer will increase in the upcoming years. Gemcitabine is the first choice for treatment of pancreatic malignancy, but increasing resistance to this drug is decreasing its overall efficacy. Studies on new therapies that target metabolic pathways, growth factor inhibitors, and tumor stroma or tumor stem cells are currently underway in many research groups. Herein we report the bioactive properties (cytotoxicity and hemolytic activity) of synthetic peptidomimetics containing an opioid tripeptide fragment (Tyr‐R1‐R2‐; where R1 is d‐Ala or d‐Thr, and R2 is Phe or Trp) hybridized with trans‐1‐cinnamylpiperazine. These compounds are stable in plasma up to 96 h and exhibit low hemotoxicity and good inhibitory effects on cancer cell growth in two‐ and three‐dimensional in vitro models of pancreatic cancer.
Analyses of Complex Mixtures by F1 Homo‐Decoupled Diagonal Suppressed Total Correlation Spectroscopy
Authors: Verma Ajay , Parihar Rashmi , Bhattacharya Subrato , Baishya Bikash
Published: August 2017

A diagonal suppressed F1 decoupled total correlation spectroscopy(TOCSY) experiment is developed for analyses of complex mixtures. In 2D homonuclear correlation, assignment of the cross peaks is crucial for structure elucidation. However, when cross peaks are close to the diagonal peaks in overcrowded spectral regions, their assignment becomes tedious. In complex mixtures, the presence of multiple spectra along with broad and complex proton multiplets owing to homonuclear scalar couplings degrade the resolution to the extent that assignment of various cross peaks becomes tedious or impossible. Herein, a diagonal suppressed total correlation technique with F1 decoupling is presented to improve the resolution of the cross peaks. The resolution of the cross peaks is improved by both diagonal suppression as well as the collapse of the multiplets to singlets. Application of the method to a few mixtures of organic compounds reveals better identification of the cross peaks relative to other TOCSY variants.
Risk of type 2 diabetes in patients with insomnia: A population‐based historical cohort study
Authors: Lin Chia‐Ling , Chien Wu‐Chien , Chung Chi‐Hsiang , Wu Fei‐Ling
Published: August 2017

Background

We investigated the risk of type 2 diabetes mellitus (T2DM) in patients with and without insomnia.

Methods

In this historical cohort study, we performed a secondary analysis of data from 2001 to 2010, which was obtained from Taiwan's National Health Insurance Database. We developed a Cox proportional hazard regression model to estimate the effects of insomnia on T2DM risk. Kaplan‐Meier survival analysis was applied to compare the differences in the cumulative incidence of T2DM between the groups with and without insomnia.

Results

During the follow‐up period, the T2DM incidence rate of patients with insomnia was significantly higher than that of patients without insomnia (34.7 vs 24.3 per 1000 person‐years). Overall, patients with insomnia had a higher risk of T2DM than did patients without insomnia (adjusted hazard ratio, 1.16; 95% confidence interval [CI], 1.10‐1.19). Among patients aged younger than 40 years, those with insomnia had a higher risk of T2DM than did the comparison cohort (adjusted hazard ratio, 1.31; 95% CI, 1.14‐1.55). Compared with patients without insomnia, the risk tended to increase with the duration of follow‐up in patients with insomnia; when the insomnia duration was <4 years, 4 to 8 years, and >8 years, the risk of T2DM increased by 1.14, 1.38, and 1.51 times (95% CI, 1.03‐1.17, 1.15‐1.49, and 1.20‐1.86), respectively. Patients with insomnia had a higher risk of T2DM, and this risk was particularly pronounced among the younger (≤40 years) population.

Conclusion

Chronic insomnia could be an important risk factor for T2DM.
Fins into limbs: Recent insights from sarcopterygian fish
Authors: Amaral Danielson B. , Schneider Igor
Published: August 2017

Limbs with digits evolved as sarcopterygian fish transitioned to a terrestrial life, giving rise to modern tetrapods. Since the Devonian, most of the sarcopterygian fish diversity became extinct, with the only surviving representatives being two coelacanth and six lungfish species. As the sister group of tetrapods, sarcopterygian fish constitute the ideal models to address questions regarding the transition of vertebrates from water to land. However, distantly related yet experimentally amenable teleost fish species have instead become the organisms of choice for geneticists and developmental biologists. Comparative studies using teleosts, such as zebrafish, have greatly enriched our knowledge on the genetic and regulatory mechanisms underlying fin development. However, their highly derived fin anatomy provides limited insights on the origin of limbs and the teleost‐specific whole‐genome duplication represents a further complication to comparisons of gene function and regulation. In recent years, refined morphological and behavioral studies and access to lungfish embryos and availability of genetic resources have underscored the value of nontetrapod sarcopterygians as model organisms. Here we review recent studies using lungfishes and coelacanths that shed light on various aspects of the evolution of the tetrapod limb, including the origin of the tetrapod pelvis, limb musculature, digits, locomotion, and regenerative capacity.
Alterations in anterior–posterior patterning and its accompanying changes along the proximal‐distal axis during the fin‐to‐limb transition
Authors: Tanaka Mikiko
Published: August 2017

The evolution from fins to limbs was one of the most successful innovations for vertebrates, allowing them to vastly expand their behaviors and habitats. Fossil records suggest that morphological changes occurred not only along the proximal‐distal axis included appearance of the autopod, but also occurred along the anterior‐posterior axis included reductions in the size and number of basal bones and digits. This review focuses on recent progress in developmental and genetic studies aimed at elucidating the mechanisms underlying alteration of anterior‐posterior patterning and its accompanying changes along the proximal‐distal axis during the fin‐to‐limb transition.