bluuebunny/crossref_metadata_2025 huggingface dataset:
Congenital Pulmonary Airway Malformation (CPAM): A Case Report
Authors: Ahmed Taslim Uddin , Roy Sudipta , Kabir ARM Luthful , Chowdhury Kona , Hassan Mahmuda , Mollah Md Abid Hossain , Noushin Rubaiya , Razzaque Mohammad Abdur , Khan Raihana Noor , Rahman Md Hamidur
Published: March 2018

Congenital pulmonary airway malformation (CPAM) is a very rare congenital cystic lung disease in children. Frequent respiratory tract infections (RTI) are major concerns in these patients. When a child having recurrent episodis of RTI, CPAM could be the underlying pathology. Surgical excision is recommended to make a definite diagnosis and exclude hidden malignancies and is also the treatment of choice. Here in, we report a 6 months old girl presenting with an acute respiratory infection for the first time. An routine USG of abdomen incidentally showed multiple cystic lessions in the left lower lung. CT scan of chest also revealed similar lessions in some area. After receiving treatment for pneumonia surgical excision was performed and she was doing well after surgeryBangladesh J Child Health 2017; VOL 41 (2) :129-134
Abstract from Current Literature Vol.41(2)
Authors: Editor -
Published: March 2018

Abstract not availableBangladesh J Child Health 2017; VOL 41 (2) :138
Probabilistic Sensitivity Amplification Control for Lower Extremity Exoskeleton
Authors: Wang Likun , Du Zhijiang , Dong Wei , Shen Yi , Zhao Guangyu
Published: March 2018

To achieve ideal force control of a functional autonomous exoskeleton, sensitivity amplification control is widely used in human strength augmentation applications. The original sensitivity amplification control aims to increase the closed-loop control system sensitivity based on positive feedback without any sensors between the pilot and the exoskeleton. Thus, the measurement system can be greatly simplified. Nevertheless, the controller lacks the ability to reject disturbance and has little robustness to the variation of the parameters. Consequently, a relatively precise dynamic model of the exoskeleton system is desired. Moreover, the human-robot interaction (HRI) cannot be interpreted merely as a particular part of the driven torque quantitatively. Therefore, a novel control methodology, so-called probabilistic sensitivity amplification control, is presented in this paper. The innovation of the proposed control algorithm is two-fold: distributed hidden-state identification based on sensor observations and evolving learning of sensitivity factors for the purpose of dealing with the variational HRI. Compared to the other state-of-the-art algorithms, we verify the feasibility of the probabilistic sensitivity amplification control with several experiments, i.e., distributed identification model learning and walking with a human subject. The experimental result shows potential application feasibility.
Micrometeorological Measurements Reveal Large Nitrous Oxide Losses during Spring Thaw in Alberta
Authors: Flesch Thomas , Baron Vern , Wilson John , Basarab John , Desjardins Raymond , Worth Devon , Lemke Reynald
Published: March 2018

Agricultural soils in Canada have been observed to emit a large pulse of nitrous oxide (N2O) gas during the spring thaw, representing a large percentage of the annual emissions. We report on three years of spring thaw N2O flux measurements taken at three Alberta agricultural sites: a crop production site (Crop), cattle winter-feeding site (WF), and a cattle winter-grazing site (WG). Soil fluxes were calculated with a micrometeorological technique based on the vertical gradient in N2O concentration above each site measured with an open-path (line-averaging) FTIR gas detector. The Crop and WG sites showed a clear N2O emission pulse lasting 10 to 25 days after thawing began. During this pulse there was a strong diurnal cycle in emissions that paralleled the cycle in near-surface soil temperature. The emission pulse was less pronounced at the WF site. The average spring thaw losses (over 25 to 31 days) were 5.3 (Crop), 7.0 (WF), and 8.0 (WG) kg N2O-N ha−1, representing 1 to 3.5% of the annual nitrogen input to the sites. These large losses are higher than found in most previous western Canadian studies, and generally higher than the annual losses estimated from the Intergovernmental Panel on Climate Change and Canadian National Inventory Report calculations. The high N2O losses may be explained by high soil nitrate levels which promoted rapid denitrification during thawing. The application of a high resolution (temporal) micrometeorological technique was critical to revealing these losses.
Dissecting the Mutational Landscape of Cutaneous Melanoma: An Omic Analysis Based on Patients from Greece
Authors: Kontogianni Georgia , Piroti Georgia , Maglogiannis Ilias , Chatziioannou Aristotelis , Papadodima Olga
Published: March 2018

Melanoma is a lethal type of skin cancer, unless it is diagnosed early. Formalin-fixed, paraffin-embedded (FFPE) tissue is a valuable source for molecular assays after diagnostic examination, but isolated nucleic acids often suffer from degradation. Here, for the first time, we examine primary melanomas from Greek patients, using whole exome sequencing, so as to derive their mutational profile. Application of a bioinformatic framework revealed a total of 10,030 somatic mutations. Regarding the genes containing putative protein-altering mutations, 73 were common in at least three patients. Sixty-five of these 73 top common genes have been previously identified in melanoma cases. Biological processes related to melanoma were affected by varied genes in each patient, suggesting differences in the components of a pathway possibly contributing to pathogenesis. We performed a multi-level analysis highlighting a short list of candidate genes with a probable causative role in melanoma.
A First Regional-Scale Estimate of Climate-Driven Terrestrial Carbon Export in Boreal Catchments
Authors: Diodato Nazzareno , Esposito Libera , Bellocchi Gianni
Published: March 2018

Highly dynamic hydro-geomorphic processes are known to drive exports of carbon (C) from river basins, but are not yet fully understood. Within this study, we simulated total organic carbon (TOC) exports at the outlet of Lake Simojärvi in the Gulf of Bothnia (Finland) with a parsimonious hydrological model. With thorough consideration of the dependence of erosion and sediment transport processes on seasonal precipitation rates, a satisfactory agreement was obtained between modelling and experimental observations (1962–2005). This provided confidence in the capability of the parsimonious model to represent temporal and spatial export dynamics. In the period 1860–2014, TOC export at the outlet of Lake Simojärvi was estimated to be highest on average (~5.5 Mg km−2·year−1) over 1974–2014 while the lowest TOC export (~2.5 Mg km−2·year−1) was estimated in 1860–1918 (with high levels of interannual-to-multidecadal variation). Regional simulations indicate that TOC increased in recent decades (on average, 4–5 Mg km−2·year−1 in 1974–2014 against ~3 Mg km−2·year−1 in 1940–1973) in northern Scandinavia and Finland. Warming-induced variability of TOC (which depends on precipitation patterns) may have altered the rates of C exchanges in aquatic ecosystems over recent years. TOC exports may continue to increase in boreal catchments with increasing temperatures as represented by future projections.
Associative Root–Pattern Data and Distribution in Arabic Morphology
Authors: Haddad Bassam , Awwad Ahmad , Hattab Mamoun , Hattab Ammar
Published: March 2018

This paper intends to present a large-scale dataset for Arabic morphology from a cognitive point of view considering the uniqueness of the root–pattern phenomenon. The center of attention is focused on studying this singularity in terms of estimating associative relationships between roots as a higher level of abstraction for words meaning, and all their potential occurrences with multiple morpho-phonetic patterns. A major advantage of this approach resides in providing a novel balanced large-scale language resource, which can be viewed as an instantiated global root–pattern network consisting of roots, patterns, stems, and particles, estimated statistically for studying the morpho-phonetic level of cognition of Arabic. In this context, this paper asserts that balanced root-distribution is an additional significant key criterion for evaluating topic coverage in an Arabic corpus. Furthermore, some additional novel probabilistic morpho-phonetic measures and their distribution have been estimated in the form of root and pattern entropies besides bi-directional conditional probabilities of bi-grams of stems, roots, and particles. Around 29.2 million webpages of ClueWeb were extracted, filtered from non-Arabic texts, and converted into a large textual dataset containing around 11.5 billion word forms and 9.3 million associative relationships. As this dataset is predominantly considering the root–pattern phenomenon in Semitic languages, the acquired data might be significant support for researchers interested in studying phenomena of Arabic such as visual word cognition, morpho-phonetic perception, morphological analysis, and cognitively motivated query expansion, spell-checking, and information retrieval. Furthermore, based on data distribution and frequencies, constructing balanced corpora will be easier.
Axiomatic Information Thermodynamics
Authors: Hulse Austin , Schumacher Benjamin , Westmoreland Michael
Published: March 2018

We present an axiomatic framework for thermodynamics that incorporates information as a fundamental concept. The axioms describe both ordinary thermodynamic processes and those in which information is acquired, used and erased, as in the operation of Maxwell’s demon. This system, similar to previous axiomatic systems for thermodynamics, supports the construction of conserved quantities and an entropy function governing state changes. Here, however, the entropy exhibits both information and thermodynamic aspects. Although our axioms are not based upon probabilistic concepts, a natural and highly useful concept of probability emerges from the entropy function itself. Our abstract system has many models, including both classical and quantum examples.
Analysis of Students’ Missed Organic Chemistry Quiz Questions that Stress the Importance of Prior General Chemistry Knowledge
Authors: Ealy Julie
Published: March 2018

A concern about students’ conceptual difficulties in organic chemistry prompted this study. It was found that prior knowledge from general chemistry was critical in organic chemistry, but what were some of the concepts that comprised that prior knowledge? Therefore an analysis of four years of organic chemistry quiz data was undertaken. Multiple general chemistry concepts were revealed that are essential prior knowledge in organic chemistry. The general chemistry concepts that were found pose a challenge to organic chemistry instructors who have identified those same concepts as ones they review or consider important in organic chemistry. A review of the literature provides recommendations that address the general chemistry students’ difficulties revealed in this study. Further research, however, is needed to follow through on those recommendations.
On the Distribution of Lightning Current among Interconnected Grounding Systems in Medium Voltage Grids
Authors: Ala Guido , Favuzza Salvatore , Francomano Elisa , Giglia Graziella , Zizzo Gaetano
Published: March 2018

This paper presents the results of a first investigation on the effects of lightning stroke on medium voltage installations’ grounding systems, interconnected with the metal shields of the Medium Voltage (MV) distribution grid cables or with bare buried copper ropes. The study enables us to evaluate the distribution of the lightning current among interconnected ground electrodes in order to estimate if the interconnection, usually created to reduce ground potential rise during a single-line-to-ground fault, can give place to dangerous situations far from the installation hit by the lightning stroke. Four different case studies of direct lightning stroke are presented and discussed: (1) two secondary substations interconnected by the cables’ shields; (2) two secondary substations interconnected by a bare buried conductor; (3) a high voltage/medium voltage station connected with a secondary substation by the medium voltage cables’ shields; (4) a high voltage/medium voltage station connected with a secondary substation by a bare buried conductor. The results of the simulations show that a higher peak-lowering action on the lighting-stroke current occurs due to the use of bare conductors as interconnection elements in comparison to the cables’ shields.
A Stackelberg Game Approach for Energy Outage-Aware Power Distribution of an Off-Grid Base Station over Multiple Retailers
Authors: Jeon Seung , Lee Joohyung , Park Hong-Shik
Published: March 2018

This paper investigates the problem of power distribution for an off-grid base station (BS) that operates sustainably without an electrical grid. We consider that multiple retailers with heterogeneous renewable energy sources (RESs) compete to maximize their revenues by individually setting the unit power price. Energy outages (EOs), which cause the power supply to fall below that which is sufficient for ensuring the traffic arrival rate required for the off-grid BS, critically affect the users’ service quality. To minimize EOs and operational expenditure (OPEX), the off-grid BS manages the power supply by reacting to the retailers’ pricing decisions. We analyze the economic benefits of power distribution to the off-grid BS from the perspective of the retailers’ pricing competition, by designing a hierarchical decision-making scheme as a multi-leader single-follower Stackelberg game. We derive a closed form expression for the optimal behavior of the off-grid BS and retailers, based on well-designed utility functions. Finally, numerical results demonstrate the proposed solution with its practical convergence time.
A Superconducting Induction Motor with a High Temperature Superconducting Armature: Electromagnetic Theory, Design and Analysis
Authors: Liu Bin , Badcock Rod , Shu Hang , Fang Jin
Published: March 2018

Large electric superconducting machines are being sought to solve emissions challenges in aircraft and provide a solution to >12 MW wind turbine electricity generation. Superconducting motors with only high temperature superconducting (HTS) armatures can offer advantages of high reliability, high power density, and high efficiency compared with conventional superconducting motors. In this paper, a novel HTS squirrel-cage induction motor is proposed for high speed operation, which adopts the structure of HTS windings with a certain inclination angle in the stator slots. Due to the limitation of curvature radius of superconducting tapes, the pitch of HTS windings can be only set to 1 and adopt the short pitch arrangement structure, which such design details of the HTS motor would ensure the superconducting coils can undertake larger current and reduce AC losses. In order to keep the HTS windings in superconducting state and larger current density, a special fixed cryogenic cooling system below 70 K with the method of gas extraction and decompression, which is made of aramid fiber, has been fabricated and the whole structure of the stator is placed in liquid nitrogen. According to the motor control principles and electromagnetic field theory, the electrical performances of the novel designed stator-HTS motor, which driven by the variable-voltage variable-frequency (VVVF) inverter, are analyzed including the flux density distributions, the torque, the induced electromotive force, losses and efficiency by using the finite element method. Finally, the components of HTS squirrel-cage induction motor have been manufactured according to the designed parameters. Next step, the motor will be assembled and tested.
Power Management of the DC Bus Connected Converters in a Hybrid AC/DC Microgrid Tied to the Main Grid
Authors: Salas-Puente Robert Antonio , Marzal Silvia , González-Medina Raúl , Figueres Emilio , Garcera Gabriel
Published: March 2018

In this paper, a centralized control strategy for the efficient power management of power converters composing a hybrid AC/DC microgrid is explained. The study is focused on the converters connected to the DC bus. The proposed power management algorithm is implemented in a microgrid central processor which is based on assigning several operation functions to each of the generators, loads and energy storage systems in the microgrid. The power flows between the DC and AC buses are studied in several operational scenarios to verify the proposed control. Experimental and simulation results demonstrate that the algorithm allows control of the power dispatch inside the microgrid properly by performing the following tasks: communication among power converters, the grid operator and loads; connection and disconnection of loads; control of the power exchange between the distributed generators and the energy storage system and, finally, supervision of the power dispatch limit set by the grid operator.
The Effects of Dynamic Root Distribution on Land–Atmosphere Carbon and Water Fluxes in the Community Earth System Model (CESM1.2.0)
Authors: Wang Yuanyuan , Jia Binghao , Xie Zhenghui
Published: March 2018

Roots are responsible for the uptake of water and nutrients by plants, and they have the plasticity to respond dynamically to different environmental conditions. However, currently, most climate models only prescribe rooting profiles as a function of the vegetation type of the land component, with no consideration of the surroundings. In this study, a dynamic rooting scheme describing root growth as a compromise between water and nitrogen availability in the subsurface was incorporated into the Community Earth System Model 1.2.0 (CESM1.2.0). The dynamic rooting scheme was incorporated to investigate the effects of land–atmosphere carbon and water fluxes, and their subsequent influences on climate. The modeling results of global land–atmosphere coupling simulations from 1982 to 2005 show that the dynamic rooting scheme can improve gross primary production (GPP) and evapotranspiration (ET) in most tropical regions, and in some high-latitude regions with lower mean biases (MBEs) and root mean square errors (RMSEs). Obvious differences in 2-m air temperature were found in low-latitude areas, with decreases of up to 2 °C. Under the influence of local land-surface feedback and large-scale moisture advection, total precipitation in the northeastern area of the Amazon and the west coast of Africa increased by 200 mm year−1, and that of South America, central Africa, and Indonesia increased by 50 to 100 mm year−1. Overall, the model incorporating the dynamic rooting scheme may reveal cooling and humidifying effects, especially for tropical regions.
The Human Tyrosyl-DNA Phosphodiesterase 1 (hTdp1) Inhibitor NSC120686 as an Exploratory Tool to Investigate Plant Tdp1 Genes
Authors: Macovei Anca , Pagano Andrea , Sabatini Maria , Grandi Sofia , Balestrazzi Alma
Published: March 2018

The hTdp1 (human tyrosyl-DNA phosphodiesterase 1) inhibitor NSC120686 has been used, along with topoisomerase inhibitors, as a pharmacophoric model to restrain the Tdp1 activity as part of a synergistic treatment for cancer. While this compound has an end-point application in medical research, in plants, its application has not been considered so far. The originality of our study consists in the use of hTdp1 inhibitor in Medicago truncatula cells, which, unlike human cells, contain two Tdp1 genes. Hence, the purpose of this study was to test the hTdp1 inhibitor NSC120686 as an exploratory tool to investigate the plant Tdp1 genes, since their characterization is still in incipient phases. To do so, M. truncatula calli were exposed to increasing (75, 150, 300 μM) concentrations of NSC120686. The levels of cell mortality and DNA damage, measured via diffusion assay and comet assay, respectively, were significantly increased when the highest doses were used, indicative of a cytotoxic and genotoxic threshold. In addition, the NSC120686-treated calli and untreated MtTdp1α-depleted calli shared a similar response in terms of programmed cell death (PCD)/necrosis and DNA damage. Interestingly, the expression profiles of MtTdp1α and MtTdp1β genes were differently affected by the NSC120686 treatment, as MtTdp1α was upregulated while MtTdp1β was downregulated. The NSC120686 treatment affected not only the MtTdp1 genes but also other genes with roles in alternative DNA repair pathways. Since the expression patterns of these genes were different than what was observed in the MtTdp1α-depleted plants, it could be hypothesized that the NSC120686 treatment exerts a different influence compared to that resulting from the lack of the MtTdp1α gene function.
Naturalistic Driving: A Framework and Advances in Using Big Data
Authors: Knoefel Frank , Wallace Bruce , Goubran Rafik , Marshall Shawn
Published: March 2018

Driving is an activity that facilitates physical, cognitive, and social stimulation in older adults, ultimately leading to better physical and cognitive health. However, aging is associated with declines in vision, physical health, and cognitive health, all of which can affect driving ability. One way of assessing driving ability is with the use of sensors in the older adult’s own vehicle. This paper provides a framework for driving assessment and addresses how naturalistic driving studies can assist in such assessments. The framework includes driving characteristics (how much driving, speed, position, type of road), actions and reactions (lane changes, intersections, passing, merging, traffic lights, pedestrians, other vehicles), destinations (variety and distance, sequencing and route planning), and driving conditions (time of day and season). Data from a subset of Ottawa drivers from the Candrive study is used to illustrate the use of naturalistic driving data. Challenges in using naturalistic driving big data and the changing technology in vehicles are discussed.
Water Quality in Surface Water: A Preliminary Assessment of Heavy Metal Contamination of the Mashavera River, Georgia
Authors: Withanachchi Sisira , Ghambashidze Giorgi , Kunchulia Ilia , Urushadze Teo , Ploeger Angelika
Published: March 2018

Water quality contamination by heavy metal pollution has severe effects on public health. In the Mashavera River Basin, an important agricultural area for the national food system in Georgia (e.g., vegetable, dairy and wine production), water contamination has multiple influences on the regional and country-wide health. With new industrial activities in the region, sediment extraction, and discharge of untreated wastewater into the river, its tributaries and irrigation canals, a comprehensive study of water quality was greatly needed. This study examined sediment and water samples from 17 sampling sites in the Mashavera River Basin during the high and low precipitation seasons. The results were characterized utilizing the Geo-accumulation Index (Igeo), Enrichment Factor (EF), Pollution Load index (PLI), Contamination Factor (CF) and Metal Index (MI). According to the CFs, Cu > Cd > Zn > Pb > Fe > Mn > Ni > Cr > Hg is the descending order for the content of all observed heavy metals in sediments collected in both seasons. Fe and As were additionally examined in water samples. Overall, As, Cd and Pb, all highly toxic elements, were found in high concentrations in downstream sample sites. According to these results, comprehensive monitoring with narrow intervals between sampling dates, more sample sites along all waterways, and proximate observation of multiple trace metal elements are highly recommended. Moreover, as the part of the water quality governance system, an immediate and sustainable collective action by all stakeholders to control the pollution level is highly recommended, as this issue is linked to the security of the national food system and poses a local public health risk.
Recurrent Renal Colic in a Patient with Munchausen Syndrome
Authors: Miconi Francesco , Rapaccini Valentina , Savarese Emanuela , Cabiati Gabriele , Pasini Augusto , Miconi Giovanni , Principi Nicola , Esposito Susanna
Published: March 2018

Background: In most of the cases regarding children, factitious disorders (FDs) are intentionally produced by parents. Less attention is paid to FDs in which a child or adolescent intentionally induces or falsifies the disease to attain a patient’s role. Case presentation: A 13-year-old immigrated and adopted boy previously underwent an operation for renal joint syndrome and was affected by recurrent episodes of renal colic. The boy was admitted reporting acute left flank pain with scars on the mucous face of his prepuce and had a recent previous hospitalization for the same reason. Laboratory tests and radiological findings did not reveal any morphological or functional alterations. Self-induced FD was suspected, and a psychiatric consultation was performed. After psychiatric consultation and remission of the symptoms with a placebo, a diagnosis of Munchausen syndrome was suspected. The patient’s uncle was not initially convinced of the diagnosis. Some videos clearly showed that the boy was handling his prepuce to excrete stones, explaining the scars. A therapeutic plan with psychiatrist support was later accepted with a positive outcome. No further signs and symptoms of renal colic were reported. Conclusions: It is recommended that paediatricians include FD in the differential diagnosis of a persistent and unexplained medical condition. If suspicion arises, confirmation and long-term therapy by a group of qualified specialists, including psychiatrists, should be planned.
PON-tstab: Protein Variant Stability Predictor. Importance of Training Data Quality
Authors: Yang Yang , Urolagin Siddhaling , Niroula Abhishek , Ding Xuesong , Shen Bairong , Vihinen Mauno
Published: March 2018

Several methods have been developed to predict effects of amino acid substitutions on protein stability. Benchmark datasets are essential for method training and testing and have numerous requirements including that the data is representative for the investigated phenomenon. Available machine learning algorithms for variant stability have all been trained with ProTherm data. We noticed a number of issues with the contents, quality and relevance of the database. There were errors, but also features that had not been clearly communicated. Consequently, all machine learning variant stability predictors have been trained on biased and incorrect data. We obtained a corrected dataset and trained a random forests-based tool, PON-tstab, applicable to variants in any organism. Our results highlight the importance of the benchmark quality, suitability and appropriateness. Predictions are provided for three categories: stability decreasing, increasing and those not affecting stability.
Silkworm Pupa Protein Hydrolysate Induces Mitochondria-Dependent Apoptosis and S Phase Cell Cycle Arrest in Human Gastric Cancer SGC-7901 Cells
Authors: Li Xiaotong , Xie Hongqing , Chen Yajie , Lang Mingzi , Chen Yuyin , Shi Liangen
Published: March 2018

Silkworm pupae (Bombyx mori) are a high-protein nutrition source consumed in China since more than 2 thousand years ago. Recent studies revealed that silkworm pupae have therapeutic benefits to treat many diseases. However, the ability of the compounds of silkworm pupae to inhibit tumourigenesis remains to be elucidated. Here, we separated the protein of silkworm pupae and performed alcalase hydrolysis. Silkworm pupa protein hydrolysate (SPPH) can specifically inhibit the proliferation and provoke abnormal morphologic features of human gastric cancer cells SGC-7901 in a dose- and time-dependent manner. Moreover, flow cytometry indicated that SPPH can induce apoptosis and arrest the cell-cycle in S phase. Furthermore, SPPH was shown to provoke accumulation of reactive oxygen species (ROS) and depolarization of mitochondrial membrane potential. Western blotting analysis indicated that SPPH inhibited Bcl-2 expression and promoted Bax expression, and subsequently induced apoptosis-inducing factor and cytochrome C release, which led to the activation of initiator caspase-9 and executioner caspase-3, cleavage of poly (ADP-ribose) polymerase (PARP), eventually caused cell apoptosis. Moreover, SPPH-induced S-phase arrest was mediated by up-regulating the expression of E2F1 and down-regulating those of cyclin E, CDK2 and cyclin A2. Transcriptome sequencing and gene set enrichment analysis (GSEA) also revealed that SPPH treatment could affect gene expression and pathway regulation related to tumourigenesis, apoptosis and cell cycle. In summary, our results suggest that SPPH could specifically suppress cell growth of SGC-7901 through an intrinsic apoptotic pathway, ROS accumulation and cell cycle arrest, and silkworm pupae have a potential to become a source of anticancer agents in the future.
EP4 as a Therapeutic Target for Aggressive Human Breast Cancer
Authors: Majumder Mousumi , Nandi Pinki , Omar Ahmed , Ugwuagbo Kingsley , Lala Peeyush
Published: March 2018

G-protein-coupled receptors (GPCRs, also called seven-transmembrane or heptahelical receptors) are a superfamily of cell surface receptor proteins that bind to many extracellular ligands and transmit signals to an intracellular guanine nucleotide-binding protein (G-protein). When a ligand binds, the receptor activates the attached G-protein by causing the exchange of Guanosine-5′-triphosphate (GTP) for guanosine diphosphate (GDP). They play a major role in many physiological functions, as well as in the pathology of many diseases, including cancer progression and metastasis. Only a few GPCR members have been exploited as targets for developing drugs with therapeutic benefit in cancer. Present review briefly summarizes the signaling pathways utilized by the EP (prostaglandin E receptor) family of GPCR, their physiological and pathological roles in carcinogenesis, with special emphasis on the roles of EP4 in breast cancer progression. We make a case for EP4 as a promising newer therapeutic target for treating breast cancer. We show that an aberrant over-expression of cyclooxygenase (COX)-2, which is an inflammation-associated enzyme, occurring in 40–50% of breast cancer patients leads to tumor progression and metastasis due to multiple cellular events resulting from an increased prostaglandin (PG) E2 production in the tumor milieu. They include inactivation of host anti-tumor immune cells, such as Natural Killer (NK) and T cells, increased immuno-suppressor function of tumor-associated macrophages, promotion of tumor cell migration, invasiveness and tumor-associated angiogenesis, due to upregulation of multiple angiogenic factors including Vascular Endothelial Growth Factor (VEGF)-A, increased lymphangiogenesis (due to upregulation of VEGF-C/D), and a stimulation of stem-like cell (SLC) phenotype in cancer cells. All of these events were primarily mediated by activation of the Prostaglandin (PG) E receptor EP4 on tumor or host cells. We show that selective EP4 antagonists (EP4A) could mitigate all of these events tested with cells in vitro as well as in vivo in syngeneic COX-2 expressing mammary cancer bearing mice or immune-deficient mice bearing COX-2 over-expressing human breast cancer xenografts. We suggest that EP4A can avoid thrombo-embolic side effects of long term use of COX-2 inhibitors by sparing cardio-protective roles of PGI2 via IP receptor activation or PGE2 via EP3 receptor activation. Furthermore, we identified two COX-2/EP4 induced oncogenic and SLC-stimulating microRNAs—miR526b and miR655, one of which (miR655) appears to be a potential blood biomarker in breast cancer patients for monitoring SLC-ablative therapies, such as with EP4A. We suggest that EP4A will likely produce the highest benefit in aggressive breast cancers, such as COX-2 expressing triple-negative breast cancers, when combined with other newer agents, such as inhibitors of programmed cell death (PD)-1 or PD-L1.
Crystal Structure of CYP2B6 in Complex with an Efavirenz Analog
Authors: Shah Manish , Zhang Qinghai , Halpert James
Published: March 2018

The over two dozen CYP2B structures of human, rabbit, and woodrat enzymes solved in the last decade have significantly enhanced our understanding of the structure-function relationships of drug metabolizing enzymes. More recently, an important role has emerged for halogen-π interactions in the CYP2B6 active site in substrate selectivity, explaining in part the preference for halogenated ligands as substrates. The mechanism by which such ligands interact with CYP2B enzymes involves conserved phenylalanine side chains, in particular F108, F115, or F297, in the active site, which form π bonds with halogens. To illustrate such halogen-π interactions using drugs that are major substrates of CYP2B6, we present here a crystal structure of CYP2B6 in complex with an analog of the widely used anti-HIV drug efavirenz, which contains a methyl group in place of the carbonyl oxygen. The chlorine of the efavirenz analog forms a π bond with the aromatic ring of F108, whereas the putative metabolism site on the distal end of the molecule is oriented towards the heme iron. The crystal structure showcases how CYP2B6 accommodates this important drug analog of considerable size in the active site by movement of various side chains without substantially increasing the active site volume. Furthermore, the CYP2B6-efavirenz analog complex provides a useful platform to investigate computationally as well as biophysically the effect of genetic polymorphisms on binding of the widely studied efavirenz.
Treatment of Arsenite Intoxication-Induced Peripheral Vasculopathy with Mesenchymal Stem Cells
Authors: Chiang Yi-Hung , Lin Chai-Chin , Chen Yen-Chung , Lee Oscar
Published: March 2018

Arsenite (As), a notorious toxic metal, is ubiquitously distributed in the earth and poses a serious threat to human health. Histopathological lesions of As intoxication are known as thromboangiitis obliterans, which are resistant to current treatment and often lead to lower limb amputation. In this study, we attempt to find that treatment with mesenchymal stem cells (MSCs) may be effective for As-induced vasculopathy. We first conducted an in vitro study with a co-culture system containing human MSCs and human umbilical vein endothelial cells (HUVECs) and treated individual and co-cultured cells with various concentrations of arsenite. We also designed an in vivo study in which Sprague Dawley (SD) rats received periodic intraperitoneal (IP) injections of 16 ppm arsenite for 12 weeks. MSCs were harvested from BALB/c mice that were transplanted via tail vein injection. We found that there was significantly higher cellular viability in human mesenchymal stem cells (hMSCs) than in HUVECs under concentrations of arsenite between 15 and 25 μM. The Annexin V apoptosis assay further confirmed this finding. Cytokine array assay for As-conditioned media revealed an elevated vascular endothelial growth factor (VEGF) level secreted by MSCs, which is crucial for HUVEC survival and was evaluated by an siRNA VEGF knockdown test. In the in vivo study, we demonstrated early apoptotic changes in the anterior tibial vessels of As-injected SD rats with a Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay, but these apoptotic changes were less frequently observed upon MSCs transplantation, indicating that the cytoprotective effect of MSCs successfully protected against As-induced peripheral vasculopathy. The feasibility of MSCs to treat and /or prevent the progression of As-induced vasculopathy is justified. Further clinical studies are required to demonstrate the therapeutic efficacy of MSCs in patients suffering from As intoxication with vasculopathy.
Towards a Novel Patch Material for Cardiac Applications: Tissue-Specific Extracellular Matrix Introduces Essential Key Features to Decellularized Amniotic Membrane
Authors: Becker Matthias , Maring Janita , Schneider Maria , Herrera Martin Aarón , Seifert Martina , Klein Oliver , Braun Thorsten , Falk Volkmar , Stamm Christof
Published: March 2018

There is a growing need for scaffold material with tissue-specific bioactivity for use in regenerative medicine, tissue engineering, and for surgical repair of structural defects. We developed a novel composite biomaterial by processing human cardiac extracellular matrix (ECM) into a hydrogel and combining it with cell-free amniotic membrane via a dry-coating procedure. Cardiac biocompatibility and immunogenicity were tested in vitro using human cardiac fibroblasts, epicardial progenitor cells, murine HL-1 cells, and human immune cells derived from buffy coat. Processing of the ECM preserved important matrix proteins as demonstrated by mass spectrometry. ECM coating did not alter the mechanical characteristics of decellularized amniotic membrane but did cause a clear increase in adhesion capacity, cell proliferation and viability. Activated monocytes secreted less pro-inflammatory cytokines, and both macrophage polarization towards the pro-inflammatory M1 type and T cell proliferation were prevented. We conclude that the incorporation of human cardiac ECM hydrogel shifts and enhances the bioactivity of decellularized amniotic membrane, facilitating its use in future cardiac applications.
Simulation of the Oxygen Permeability of a Composite Container
Authors: Defauchy Virginie , Le Corre Hélène , Colin Xavier
Published: March 2018

A kinetic model has been derived from the classical (Fick and Henry’s) laws of the gas theory for predicting the oxygen permeability of a closed composite container, initially filled by pure nitrogen under a pressure slightly higher than the atmospheric pressure. Its two main parameters, namely the coefficients of oxygen solubility and diffusion, were determined beforehand by routine laboratory tests of oxygen permeation at 20, 30, and 45 °C. It appears clearly that oxygen molecules will quickly cross the composite wall to progressively modify the gas composition inside the container. Several solutions are proposed for trying to reduce the oxygen permeability.
Characterization of Wood Derived Hierarchical Cellulose Scaffolds for Multifunctional Applications
Authors: Segmehl Jana , Studer Vanessa , Keplinger Tobias , Burgert Ingo
Published: March 2018

Functional materials of high porosity and hierarchical structure, based on renewable building blocks, are highly demanded for material applications. In this regard, substantial progress has been made by functionalizing micro- and nano-sized cellulose followed by its reassembly via bottom-up approaches. However, bottom-up assembly processes are still limited in terms of upscaling and the utilization of these building blocks presupposes the disassembly of the plant feedstock inherit hierarchical cellulose scaffold. To maintain the three-dimensional structure, delignification processes from pulp and paper production were recently adapted for the treatment of bulk wood. Yet, a detailed chemical analysis and the determination of macroscopic swelling/shrinkage parameters for the scaffolds, necessary for a systematic design of cellulose scaffold based materials, are still missing. Here, acidic bleaching and soda pulping were used for producing cellulose scaffolds, for functional materials under retention of their inherent hierarchical structure. Spatially resolved chemical investigations on thin sections by Raman microscopy provided detailed information on the induced alterations at the cell wall level, revealing significant differences in dependence of the chemistry of the pre-treatment. An adaption to bulk wood samples proved the applicability of these treatments at larger scales and volumetric alterations at different atmospheric conditions indicated the effect of the altered porosity of the scaffolds on their hygroscopic behaviour.
A New Breviane Spiroditerpenoid from the Marine-Derived Fungus Penicillium sp. TJ403-1
Authors: Yang Beiye , Sun Weiguang , Wang Jianping , Lin Shuang , Li Xiao-Nian , Zhu Hucheng , Luo Zengwei , Xue Yongbo , Hu Zhengxi , Zhang Yonghui
Published: March 2018

Marine-derived fungi are a promising and untapped reservoir for discovering structurally interesting and pharmacologically active natural products. In our efforts to identify novel bioactive compounds from marine-derived fungi, four breviane spiroditerpenoids, including a new compound, brevione O (1), and three known compounds breviones I (2), J (3), and H (4), together with a known diketopiperazine alkaloid brevicompanine G (5), were isolated and identified from an ethyl acetate extract of the fermented rice substrate of the coral-derived fungus Penicillium sp. TJ403-1. The absolute structure of 1 was elucidated by HRESIMS, one- and two-dimensional NMR spectroscopic data, and a comparison of its electronic circular dichroism (ECD) spectrum with the literature. Moreover, we confirmed the absolute configuration of 5 by single-crystal X-ray crystallography. All the isolated compounds were evaluated for isocitrate dehydrogenase 1 (IDH1) inhibitory activity and cytotoxicity, and compound 2 showed significant inhibitory activities against HL-60, A-549, and HEP3B tumor cell lines with IC50 values of 4.92 ± 0.65, 8.60 ± 1.36, and 5.50 ± 0.67 µM, respectively.
Production, Characterization and Biocompatibility Evaluation of Collagen Membranes Derived from Marine Sponge Chondrosia reniformis Nardo, 1847
Authors: Pozzolini Marina , Scarfì Sonia , Gallus Lorenzo , Castellano Maila , Vicini Silvia , Cortese Katia , Gagliani Maria , Bertolino Marco , Costa Gabriele , Giovine Marco
Published: March 2018

Collagen is involved in the formation of complex fibrillar networks, providing the structural integrity of tissues. Its low immunogenicity and mechanical properties make this molecule a biomaterial that is extremely suitable for tissue engineering and regenerative medicine (TERM) strategies in human health issues. Here, for the first time, we performed a thorough screening of four different methods to obtain sponge collagenous fibrillar suspensions (FSs) from C. reniformis demosponge, which were then chemically, physically, and biologically characterized, in terms of protein, collagen, and glycosaminoglycans content, viscous properties, biocompatibility, and antioxidant activity. These four FSs were then tested for their capability to generate crosslinked or not thin sponge collagenous membranes (SCMs) that are suitable for TERM purposes. Two types of FSs, of the four tested, were able to generate SCMs, either from crosslinking or not, and showed good mechanical properties, enzymatic degradation resistance, water binding capacity, antioxidant activity, and biocompatibility on both fibroblast and keratinocyte cell cultures. Finally, our results demonstrate that it is possible to adapt the extraction procedure in order to alternatively improve the mechanical properties or the antioxidant performances of the derived biomaterial, depending on the application requirements, thanks to the versatility of C. reniformis extracellular matrix extracts.
Catalytic Annulation of Epoxides with Heterocumulenes by the Indium-Tin System
Authors: Suzuki Itaru , Imakuni Akira , Baba Akio , Shibata Ikuya
Published: March 2018

In the synthesis of five-membered heterocycles by the annulation of epoxides with heterocumulenes such as carbon dioxide and isocyanates, we developed the indium-tin catalytic system and synthesized various cyclic adducts including novel types products under mild reaction conditions.
Comparative Evaluation of the Antioxidant and Anti-Alzheimer’s Disease Potential of Coumestrol and Puerarol Isolated from Pueraria lobata Using Molecular Modeling Studies
Authors: Koirala Prashamsa , Seong Su , Jung Hyun , Choi Jae
Published: March 2018

The current study assesses the antioxidant effects of two similar isoflavonoids isolated from Pueraria lobata, coumestrol and puerarol, along with the cholinergic and amyloid-cascade pathways to mitigate Alzheimer’s disease (AD). Antioxidant activity was evaluated via 1,1-diphenyl-2-picryhydrazyl (DPPH) and peroxynitrite (ONOO−) scavenging ability further screened via ONOO−-mediated nitrotyrosine. Similarly, acetyl- and butyrylcholinesterase (AChE/BChE) and β-site amyloid precursor protein cleaving enzyme 1 (BACE1) inhibitory activities were assessed together with docking and kinetic studies. Considering DPPH and ONOO− scavenging activity, coumestrol (EC50 values of 53.98 and 1.17 µM) was found to be more potent than puerarol (EC50 values of 82.55 and 6.99 µM) followed by dose dependent inhibition of ONOO−-mediated nitrotyrosine. Coumestrol showed pronounced AChE and BChE activity with IC50 values of 42.33 and 24.64 µM, respectively, acting as a dual cholinesterase (ChE) inhibitor. Despite having weak ChE inhibitory activity, puerarol showed potent BACE1 inhibition (28.17 µM). Kinetic studies of coumestrol showed AChE and BChE inhibition in a competitive and mixed fashion, whereas puerarol showed mixed inhibition for BACE1. In addition, docking simulations demonstrated high affinity and tight binding capacity towards the active site of the enzymes. In summary, we undertook a comparative study of two similar isoflavonoids differing only by a single aliphatic side chain and demonstrated that antioxidant agents coumestrol and puerarol are promising, potentially complementary therapeutics for AD.
ω-Methylsulfanylalkyl Glucosinolates: A General Synthetic Pathway
Authors: Mavratzotis Manolis , Cassel Stéphanie , Montaut Sabine , Rollin Patrick
Published: March 2018

A general pathway was devised to synthesize ω-methylsulfanylalkyl glucosinolates, which represent an important class of structurally homogeneous plant secondary metabolites. The required thiofunctionalized hydroximoyl chlorides were obtained from the corresponding α,ω-nitroalkyl methylsulfide precursors, involving as the key-step, a nitronate chlorination strategy. A coupling reaction with 1-thio-beta-d-glucopyranose, followed by O-sulfation of the intermediate thiohydroximate and final deprotection of the sugar moiety afforded the target compounds.
Antibacterial and Barrier Properties of Gelatin Coated by Electrospun Polycaprolactone Ultrathin Fibers Containing Black Pepper Oleoresin of Interest in Active Food Biopackaging Applications
Authors: Figueroa-Lopez Kelly , Castro-Mayorga Jinneth , Andrade-Mahecha Margarita , Cabedo Luis , Lagaron Jose
Published: March 2018

The present study evaluated the effect of using electrospun polycaprolactone (PCL) as a barrier coating and black pepper oleoresin (OR) as a natural extract on the morphology, thermal, mechanical, antimicrobial, oxygen, and water vapor barrier properties of solvent cast gelatin (GEL). The antimicrobial activity of the developed multilayer system obtained by the so-called electrospinning coating technique was also evaluated against Staphylococcus aureus strains for 10 days. The results showed that the multilayer system containing PCL and OR increased the thermal resistance, elongated the GEL film, and significantly diminished its permeance to water vapor. Active multilayer systems stored in hermetically closed bottles increased their antimicrobial activity after 10 days by inhibiting the growth of Staphylococcus aureus. This study demonstrates that addition of electrospun PCL ultrathin fibers and OR improved the properties of GEL films, which promoted its potential use in active food packaging applications.