bluuebunny/crossref_metadata_2025 huggingface dataset:
A Simplified Computational Model for the Location of Depth Average Velocity in a Rectangular Irrigation Channel
Authors: Ma Zhuangzhuang , Wu Zhangsheng , Li Tongshu , Han Yu , Chen Jian , Zhang Liangpei
Published: August 2019

Flow measurements in open channels have often utilized velocity-area methods. Thus, estimations of the average velocity in a cross-section of rural canals play an important role in the flow measurement of an irrigation district. This paper derives a model for calculating depth average velocity. This model considers the classical logarithmic formula describing the velocity distribution and flow partitioning theory, which is aimed at finding out a location that represents the depth average velocity (LDAV) along the vertical line from boundary to water surface. Subsequently, the average flow velocity of the whole channel can be further determined by using the velocity-area method in different regions. Moreover, the LDAV has different expressions in different sub-regions according to flow partitioning theory under various aspect ratios. The results are verified by experiments under different experimental conditions, and the formula is highly applicable and has a high theoretical significance and practical value.
Dependency Analysis based Approach for Virtual Machine Placement in Software-Defined Data Center
Authors: Narantuya Jargalsaikhan , Ha Taejin , Bae Jaewon , Lim Hyuk
Published: August 2019

In data centers, cloud-based services are usually deployed among multiple virtual machines (VMs), and these VMs have data traffic dependencies on each other. However, traffic dependency between VMs has not been fully considered when the services running in the data center are expanded by creating additional VMs. If highly dependent VMs are placed in different physical machines (PMs), the data traffic increases in the underlying physical network of the data center. To reduce the amount of data traffic in the underlying network and improve the service performance, we propose a traffic-dependency-based strategy for VM placement in software-defined data center (SDDC). The traffic dependencies between the VMs are analyzed by principal component analysis, and highly dependent VMs are grouped by gravity-based clustering. Each group of highly dependent VMs is placed within an appropriate PM based on the Hungarian matching method. This strategy of dependency-based VM placement facilitates reducing data traffic volume of the data center, since the highly dependent VMs are placed within the same PM. The results of the performance evaluation in SDDC testbed indicate that the proposed VM placement method efficiently reduces the amount of data traffic in the underlying network and improves the data center performance.
A Displacement Controlled Fatigue Test Method for Additively Manufactured Materials
Authors: Parvez Mohammad Masud , Chen Yitao , Karnati Sreekar , Coward Connor , Newkirk Joseph W. , Liou Frank
Published: August 2019

A novel adaptive displacement-controlled test setup was developed for fatigue testing on mini specimens. In property characterization of additive manufacturing materials, mini specimens are preferred due to the specimen preparation, and manufacturing cost but mini specimens demonstrate higher fatigue strength than standard specimens due to the lower probability of material defects resulting in fatigue. In this study, a dual gauge section Krouse type mini specimen was designed to conduct fatigue tests on additively manufactured materials. The large surface area of the specimen with a constant stress distribution and increased control volume as the gauge section may capture all different types of surface and microstructural defects of the material. A fully reversed bending (R = −1) fatigue test was performed on simply supported specimens. In the displacement-controlled mechanism, the variation in the control signal during the test due to the stiffness variation of the specimen provides a unique insight into identifying the nucleation and propagation phase. The fatigue performance of the wrought 304 and additively manufactured 304L stainless steel was compared applying a control signal monitoring (CSM) method. The test results and analyses validate the design of the specimen and the effective implementation of the test bench in fatigue testing of additively manufactured materials.
Insights into the Variations of Hao-Dependent Nitrifying and Nir-Dependent Denitrifying Microbial Communities in Ammonium-Graduated Lake Environments
Authors: Zhao Ruojin , Chen Yinyan , Qu Jin , Jin Peng , Zheng Zhanwang , Cui Zhiwen
Published: August 2019

Biological nitrification and denitrification play significant roles in nitrogen-associated biogeochemical cycles. However, our understanding of the spatial scales at which microbial communities act and vary is limited. We used gene-specific metagenomic PCR to explore changes in nitrifying and denitrifying microbial communities within pristine lake and its branches, where the ammonium and dissolved organic carbon (DOC) concentrations form a gradient. The biomarkers hydroxylamine oxidoreductase and nitrite reductase genes indicated that strong relationships exist between the diversities and community structures of denitrifiers and ammonium gradients. It showed that the Nitrosomonas oligotropha cluster dominates the nitrifying bacteria in low-nutrition environments, while a new Nitrosomonas ureae cluster accounted for nearly 80% of the nitrifying bacteria in high-nitrogen environments. The distribution and diversity of nirS/K-dependent denitrifiers in the various habitats were similar, but predominantly affiliated with unknown clusters. Moreover, the abundance of all the hao genes dramatically outnumbered that of nir genes. The relative abundance of hao was clearly higher during eutrophication (13.60%) than during oligotrophy (5.23%), whereas that of nirS showed opposite tendencies. Overall, this study provides valuable comparative insights into the shifts in nitrifying and denitrifying microbial populations in lake environments with ammonium gradients, suggesting that unique dominant denitrifiers probably play an important role in the nitrogen cycle.
Electron-Impact Dissociation of Vibrationally-Excited Molecular Hydrogen into Neutral Fragments
Authors: Scarlett Liam , Savage Jeremy , Fursa Dmitry , Zammit Mark , Bray Igor
Published: August 2019

We present convergent close-coupling (CCC) calculations of electron-impact dissociation of vibrationally-excited molecular hydrogen into neutral fragments. This work follows from our previous results for dissociation of molecular hydrogen in the ground vibrational level [Scarlett et al., Eur. Phys. J. D 72, 34 (2018)], which were obtained from calculations performed in a spherical coordinate system. The present calculations, performed utilizing a spheroidal formulation of the molecular CCC method, reproduce the previous dissociation cross sections for the ground vibrational level, while allowing the extension to scattering on excited levels.
From Stochastic Optics to the Wigner Formalism: The Role of the Vacuum Field in Optical Quantum Communication Experiments
Authors: Casado Alberto , Guerra Santiago , Plácido José
Published: August 2019

The Wigner formalism in the Heisenberg picture constitutes a bridge that connects Quantum Optics to Stochastic Optics. The vacuum field appears explicitly in the formalism, and the wavelike aspects of light are emphasised. In addition, the zeropoint intensity as a threshold for detection is a common denominator in both theories. In this paper, after summarising the basic rules of the Wigner approach and its application to parametric down-conversion, some new results are presented that delve into the physical meaning of the zeropoint field in optical quantum communication. Specifically, the relationship between Bell-state distinguishability and the number of sets of zeropoint modes that take part in the experiment is analysed in terms of the coupling between the phases of the different fields involved and the subtraction of the zeropoint intensity at the detectors. Additionally, the connection between the compatibility theorem in quantum cryptography and zeropoint field is stressed.
Impact of Four Protein Additives in Cryogels on Osteogenic Differentiation of Adipose-Derived Mesenchymal Stem Cells
Authors: Häussling Victor , Deninger Sebastian , Vidoni Laura , Rinderknecht Helen , Ruoß Marc , Arnscheidt Christian , Athanasopulu Kiriaki , Kemkemer Ralf , Nussler Andreas K. , Ehnert Sabrina
Published: August 2019

Human adipose-derived mesenchymal stem/stromal cells (Ad-MSCs) have great potential for bone tissue engineering. Cryogels, mimicking the three-dimensional structure of spongy bone, represent ideal carriers for these cells. We developed poly(2-hydroxyethyl methacrylate) cryogels, containing hydroxyapatite to mimic inorganic bone matrix. Cryogels were additionally supplemented with different types of proteins, namely collagen (Coll), platelet-rich plasma (PRP), immune cells-conditioned medium (CM), and RGD peptides (RGD). The different protein components did not affect scaffolds’ porosity or water-uptake capacity, but altered pore size and stiffness. Stiffness was highest in scaffolds with PRP (82.3 kPa), followed by Coll (55.3 kPa), CM (45.6 kPa), and RGD (32.8 kPa). Scaffolds with PRP, CM, and Coll had the largest pore diameters (~60 µm). Ad-MSCs were osteogenically differentiated on these scaffolds for 14 days. Cell attachment and survival rates were comparable for all four scaffolds. Runx2 and osteocalcin levels only increased in Ad-MSCs on Coll, PRP and CM cryogels. Osterix levels increased slightly in Ad-MSCs differentiated on Coll and PRP cryogels. With differentiation alkaline phosphatase activity decreased under all four conditions. In summary, besides Coll cryogel our PRP cryogel constitutes as an especially suitable carrier for bone tissue engineering. This is of special interest, as this scaffold can be generated with patients’ PRP.
Molecular Characterization of Twenty-Five Marine Cyanobacteria Isolated from Coastal Regions of Ireland
Authors: Shiels Katie , Browne Norma , Donovan Fiona , Murray Patrick , Saha Sushanta Kumar
Published: August 2019

Twenty-five marine cyanobacteria isolated from Irish coasts were characterized based on their morphological characters and 16S rRNA gene sequence analysis. In addition, superoxide dismutase (SOD) and malate dehydrogenase (MDH) isoenzyme banding patterns were used to differentiate two morphologically ambiguous isolates. In this study, six new cyanobacteria-specific primers were designed, and a 16S rRNA gene of twenty-five morphologically diverse cyanobacteria was successfully PCR amplified (1198–1396 bps). Assembled 16S rRNA sequences were used both for a basic local alignment search tool (BLAST) analysis for genus-level identification and to generate a phylogenetic tree, which yielded two major clusters: One with morphologically homogenous cyanobacteria and the other with morphologically very diverse cyanobacteria. Kamptonema okenii and Tychonema decoloratum were isolated from a single field sample of Ballybunion and were originally identified as the same ‘Oscillatoria sp.’ based on preliminary morphological observations. However, an alignment of 16S rRNA gene sequences and SOD and MDH isoenzyme banding pattern analyses helped in differentiating the morphologically-indistinguishable ‘Oscillatoria sp.’. Finally, after a re-evaluation of their morphological characters using modern taxonomic publications, the originally identified ‘Oscillatoria sp.’ were re-identified as Kamptonema okenii and Tychonema decoloratum, thus supporting the polyphasic approach of cyanobacteria characterization.
The Impact of Salts on the Ice Recrystallization Inhibition Activity of Antifreeze (Glyco)Proteins
Authors: Surís-Valls Romà , Voets Ilja
Published: August 2019

Antifreeze (glyco)proteins (AF(G)Ps) have received increasing attention as potential cryopreservation agents since their discovery in the 1970s. While cryopreservation strategies for specific cells (such as red blood cells) are successful and widely implemented, preservation of other cell types, tissues and whole organs remains challenging. This is due to the multifactorial nature of the freeze-thaw damage, the complexity of preserving biological matter and the (country-to-country) variability of the employed procedures and regulations. AF(G)Ps are well-known for their ability to modulate ice crystal growth morphology and ice recrystallization inhibition (IRI), both of which are considered key contributors to freeze-thaw damage. To date, however, the impact of AF(G)Ps on cell survival remains at best partially understood as conflicting results on the benefits or disadvantages of including AF(G)P in cryopreservation strategies remain unelucidated. We hypothesize that variability in the additives in the cryopreservation media contributes to the observed discrepancies. To critically examine this idea, we monitored the inhibition of ice recrystallization by AF(G)P in the presence of various salts using a quantitative analysis of optical microscopy images via the Lifshitz-Slyozov-Wagner (LSW) theory for Oswald ripening. We found that the addition of salts, which are used in culture and cryopreservation media, enhances the IRI activity of AF(G)Ps, and that the magnitude of the enhancement was in line with the Hofmeister series. The size of ice crystals grown in AFGP1–5 and type III AFP samples containing chloride, phosphate and citrate ions were statistically smaller after 90 min of incubation than crystals grown in the absence of these salts. The ice recrystallization rates (kd) of AFGP1–5 and type III AFP samples prepared at a fixed overall ionic strength of 100 mM progressively decreased following the Hofmeister series for anions. Our results demonstrate that the performance of AF(G)Ps is significantly influenced by additives present in common cryopreservation media. It is thus important to conduct excipient compatibility experiments to identify potential incompatibilities between additives and AF(G)Ps in cryopreservation formulations.
Microparticles as Potential Mediators of High Glucose-Induced Renal Cell Injury
Authors: Ravindran Sreenithya , Pasha Mazhar , Agouni Abdelali , Munusamy Shankar
Published: August 2019

Diabetic nephropathy (DN) is the most common cause of chronic kidney disease worldwide. Activation of signaling pathways such as the mammalian target of rapamycin (mTOR), extracellular signal-regulated kinases (ERK), endoplasmic reticulum (ER) stress, transforming growth factor-beta (TGF-β), and epithelial-mesenchymal transition (EMT), are thought to play a significant role in the etiology of DN. Microparticles (MPs), the small membrane vesicles containing bioactive signals shed by cells upon activation or during apoptosis, are elevated in diabetes and were identified as biomarkers in DN. However, their exact role in the pathophysiology of DN remains unclear. Here, we examined the effect of MPs shed from renal proximal tubular cells (RPTCs) exposed to high glucose conditions on naïve RPTCs in vitro. Our results showed significant increases in the levels of phosphorylated forms of 4E-binding protein 1 and ERK1/2 (the downstream targets of mTOR and ERK pathways), phosphorylated-eIF2α (an ER stress marker), alpha smooth muscle actin (an EMT marker), and phosphorylated-SMAD2 and nuclear translocation of SMAD4 (markers of TGF-β signaling). Together, our findings indicate that MPs activate key signaling pathways in RPTCs under high glucose conditions. Pharmacological interventions to inhibit shedding of MPs from RPTCs might serve as an effective strategy to prevent the progression of DN.
Comparison of Transcranial Direct Current Stimulation Electrode Montages for the Lower Limb Motor Cortex
Authors: Patel Radhika , Madhavan Sangeetha
Published: August 2019

Transcranial direct current stimulation (tDCS) has been widely explored as a neuromodulatory adjunct to modulate corticomotor excitability and improve motor behavior. However, issues with the effectiveness of tDCS have led to the exploration of empirical and experimental alternate electrode placements to enhance neuromodulatory effects. Here, we conducted a preliminary study to compare a novel electrode montage (which involved placing 13 cm2 electrodes anterior and posterior to the target location) to the traditionally used electrode montage (13 cm2 stimulating electrode over the target area and the 35 cm2 reference electrode over the contralateral orbit). We examined the effects of tDCS of the lower limb motor area (M1) by measuring the corticomotor excitability (CME) of the tibialis anterior muscle using transcranial magnetic stimulation in twenty healthy participants. We examined behavioral effects using a skilled motor control task performed with the ankle. We did not find one electrode montage to be superior to the other for changes in the CME or motor control. When the group was dichotomized into responders and non-responders (based on upregulation in CME), we found that the responders showed significant upregulation from baseline after tDCS for both montages. However, only the responders in the traditional montage group showed significant changes in motor control after tDCS. These results do not support the superiority of the new anterior–posterior montage over the traditional montage. Further work with a larger cohort and multiple cumulative sessions may be necessary to confirm our results.
NPM-ALK Is a Key Regulator of the Oncoprotein FOXM1 in ALK-Positive Anaplastic Large Cell Lymphoma
Authors: Haque Moinul , Li Jing , Huang Yung-Hsing , Almowaled Meaad , Barger Carter J. , Karpf Adam R. , Wang Peng , Chen Will , Turner Suzanne D. , Lai Raymond
Published: August 2019

Forkhead Box M1 (FOXM1) is an oncogenic transcription factor implicated in the pathogenesis of solid and hematologic cancers. In this study, we examined the significance of FOXM1 in NPM-ALK-positive anaplastic large cell lymphoma (NPM-ALK + ALCL), with a focus on how it interacts with NPM-ALK, which is a key oncogenic driver in these tumors. FOXM1 was expressed in NPM-ALK + ALCL cell lines (5/5), patient samples (21/21), and tumors arising in NPM-ALK transgenic mice (4/4). FOXM1 was localized in the nuclei and confirmed to be transcriptionally active. Inhibition of FOXM1 in two NPM-ALK + ALCL cells using shRNA and pharmalogic agent (thiostrepton) resulted in reductions in cell growth and soft-agar colony formation, which were associated with apoptosis and cell-cycle arrest. FOXM1 is functionally linked to NPM-ALK, as FOXM1 enhanced phosphorylation of the NPM-ALK/STAT3 axis. Conversely, DNA binding and transcriptional activity of FOXM1 was dependent on the expression of NPM-ALK. Further studies showed that this dependency hinges on the binding of FOXM1 to NPM1 that heterodimerizes with NPM-ALK, and the phosphorylation status of NPM-ALK. In conclusion, we identified FOXM1 as an important oncogenic protein in NPM-ALK+ ALCL. Our results exemplified that NPM-ALK exerts oncogenic effects in the nuclei and illustrated a novel role of NPM1 in NPM-ALK pathobiology.
The Histone Demethylase Enzymes KDM3A and KDM4B Co-Operatively Regulate Chromatin Transactions of the Estrogen Receptor in Breast Cancer
Authors: Jones Dominic , Wilson Laura , Thomas Huw , Gaughan Luke , Wade Mark A.
Published: August 2019

Many estrogen receptor (ER)-positive breast cancers develop resistance to endocrine therapy but retain canonical receptor signalling in the presence of selective ER antagonists. Numerous co-regulatory proteins, including enzymes that modulate the chromatin environment, control the transcriptional activity of the ER. Targeting ER co-regulators has therefore been proposed as a novel therapeutic approach. By assessing DNA-binding dynamics in ER-positive breast cancer cells, we have identified that the histone H3 lysine 9 demethylase enzymes, KDM3A and KDM4B, co-operate to regulate ER activity via an auto-regulatory loop that facilitates the recruitment of each co-activating enzyme to chromatin. We also provide evidence that suggests that KDM3A primes chromatin for deposition of the ER pioneer factor FOXA1 and recruitment of the ER-transcriptional complex, all prior to ER recruitment, therefore establishing an important mechanism of chromatin regulation involving histone demethylases and pioneer factors, which controls ER functionality. Importantly, we show via global gene-expression analysis that a KDM3A/KDM4B/FOXA1 co-regulated gene signature is enriched for pro-proliferative and ER-target gene sets, suggesting that abrogation of this network could be an efficacious therapeutic strategy. Finally, we show that depletion of both KDM3A and KDM4B has a greater inhibitory effect on ER activity and cell growth than knockdown of each individual enzyme, suggesting that targeting both enzymes represents a potentially efficacious therapeutic option for ER-driven breast cancer.
Interphase Cytogenetic Analysis of Micronucleated and Multinucleated Cells Supports the Premature Chromosome Condensation Hypothesis as the Mechanistic Origin of Chromothripsis
Authors: Pantelias Antonio , Karachristou Ioanna , Georgakilas Alexandros G. , Terzoudi Georgia I.
Published: August 2019

The discovery of chromothripsis in cancer genomes challenges the long-standing concept of carcinogenesis as the result of progressive genetic events. Despite recent advances in describing chromothripsis, its mechanistic origin remains elusive. The prevailing conception is that it arises from a massive accumulation of fragmented DNA inside micronuclei (MN), whose defective nuclear envelope ruptures or leads to aberrant DNA replication, before main nuclei enter mitosis. An alternative hypothesis is that the premature chromosome condensation (PCC) dynamics in asynchronous micronucleated cells underlie chromosome shattering in a single catastrophic event, a hallmark of chromothripsis. Specifically, when main nuclei enter mitosis, premature chromatin condensation provokes the shattering of chromosomes entrapped inside MN, if they are still undergoing DNA replication. To test this hypothesis, the agent RO-3306, a selective ATP-competitive inhibitor of CDK1 that promotes cell cycle arrest at the G2/M boundary, was used in this study to control the degree of cell cycle asynchrony between main nuclei and MN. By delaying the entrance of main nuclei into mitosis, additional time was allowed for the completion of DNA replication and duplication of chromosomes inside MN. We performed interphase cytogenetic analysis using asynchronous micronucleated cells generated by exposure of human lymphocytes to γ-rays, and heterophasic multinucleated Chinese hamster ovary (CHO) cells generated by cell fusion procedures. Our results demonstrate that the PCC dynamics during asynchronous mitosis in micronucleated or multinucleated cells are an important determinant of chromosome shattering and may underlie the mechanistic origin of chromothripsis.
Predicting Visual Acuity Deterioration and Radiation-Induced Toxicities after Brachytherapy for Choroidal Melanomas
Authors: Espensen Charlotte A. , Appelt Ane L. , Fog Lotte S. , Gothelf Anita B. , Thariat Juliette , Kiilgaard Jens F.
Published: August 2019

Ruthenium-106 (Ru-106) brachytherapy is an established modality for eye-preserving treatment of choroidal melanoma. To achieve optimal treatment outcomes, there should be a balance between tumour control and the risk of healthy tissue toxicity. In this retrospective study, we examined normal tissue complication probability (NTCP) for visual acuity deterioration and late complications to aid the understanding of dose-dependence after Ru-106 treatments. We considered consecutive patients diagnosed with choroidal melanoma and primarily treated at a single institution from 2005–2014. Treatment plans were retrospectively recreated using dedicated software and image guidance to contour the tumour and determine the actual plaque position. Dose distributions were extracted from each plan for all relevant anatomical structures. We considered visual acuity deterioration and late complications (maculopathy, optic neuropathy, ocular hypertension, vascular obliteration, cataract and retinal detachment). Lasso statistics were used to select the most important variables for each analysis. Outcomes were related to dose and clinical characteristics using multivariate Cox regressions analysis. In total, 227 patients were considered and 226 of those were eligible for analysis. Median potential follow-up time was 5.0 years (95% CI: 4.5–6.0). Visual acuity deterioration was related to optic disc-tumour distance and dose metrics from the retina and the macula, with retina V10Gy showing the strongest correlation. Macula V10Gy was the only dose metric impacting risk of maculopathy, while optic disc-tumour distance also proved important. Optic disc V50Gy had the largest impact on optic neuropathy along with optic disc-tumour distance. Optic disc V20Gy was the only variable associated with vascular obliteration. Lens D2% had the largest impact on the risk of cataract along with older age and the largest base dimension. We found no variables associated with the risk of ocular hypertension and retinal detachment. Visual acuity deterioration and most late complications demonstrated dependence on dose delivered to healthy structures in the eye after Ru-106 brachytherapy for choroidal melanomas.
MicroRNA-361: A Multifaceted Player Regulating Tumor Aggressiveness and Tumor Microenvironment Formation
Authors: Xu Daozhi , Dong Peixin , Xiong Ying , Yue Junming , Ihira Kei , Konno Yosuke , Kobayashi Noriko , Todo Yukiharu , Watari Hidemichi
Published: August 2019

MicroRNA-361-5p (miR-361) expression frequently decreases or is lost in different types of cancers, and contributes to tumor suppression by repressing the expression of its target genes implicated in tumor growth, epithelial-to-mesenchymal transition (EMT), metastasis, drug resistance, glycolysis, angiogenesis, and inflammation. Here, we review the expression pattern of miR-361 in human tumors, describe the mechanisms responsible for its dysregulation, and discuss how miR-361 modulates the aggressive properties of tumor cells and alter the tumor microenvironment by acting as a novel tumor suppressor. Furthermore, we describe its potentials as a promising diagnostic or prognostic biomarker for cancers and a promising target for therapeutic development.
Isoliquiritigenin Suppresses E2-Induced Uterine Leiomyoma Growth through the Modulation of Cell Death Program and the Repression of ECM Accumulation
Authors: Lin Po-Han , Kung Hsiang-Lin , Chen Hsin-Yuan , Huang Ko-Chieh , Hsia Shih-Min
Published: August 2019

Uterine leiomyomas, also known as fibroids, are common and prevalent in women of reproductive age. In this study, the effect of Isoliquiritigenin (ISL), a licorice flavonoid, on the anti-proliferation of uterine leiomyoma was investigated. We found that the survival of uterine leiomyoma ELT3 cells and primary uterine smooth muscle (UtSMC) cells was reduced by treatment with ISL alone or with ISL plus estradiol (E2). Cell cycles were arrested through the reduction of G2/M- and S-phase populations in ELT3 and UtSMC cells, respectively. Furthermore, increased sub-G1 phase and nucleus condensation were observed in ELT3 cells but not in UtSMC cells. Co-treatment of ELT3 cells with E2 and ISL inhibited ERK1/2 activation, whereas p38 and c-Jun N-terminal kinase (JNK) activation was enhanced. Moreover, ISL-induced apoptosis and autophagy cell death in ELT3 cells were observed. Serum E2 and P4 levels were reduced in a E2-enhanced uterine myometrium hyperplasia mouse model by ISL treatment, which contributed to the downregulation of the expression of extracellular matrix (ECM) associated proteins and matrix metalloproteinase (MMPs). Taken together, these results showed that ISL exerted a higher effect on the inhibition of estrogen-induced uterine leiomyoma growth for both in vitro and in vivo ECM accumulation, demonstrating its potential as a new option for treatment of uterine leiomyoma.
HLA Expression in Uveal Melanoma: An Indicator of Malignancy and a Modifiable Immunological Target
Authors: Souri Zahra , Wierenga Annemijn P.A. , Mulder Arend , Jochemsen Aart G. , Jager Martine J.
Published: August 2019

Uveal melanoma (UM) is the most common primary intraocular malignancy in adults, and gives rise to metastases in 50% of cases. The presence of an inflammatory phenotype is a well-known risk factor for the development of metastases. This inflammatory phenotype is characterized by the presence of high numbers of lymphocytes and macrophages, and a high expression of the HLA Class I and II antigens. An abnormal expression of HLA Class I may influence cytotoxic T lymphocyte (CTL) as well as Natural Killer (NK) cell responses. We provide a comprehensive review regarding the inflammatory phenotype in UM and the expression of locus- and allele-specific HLA Class I and of Class II antigens in primary UM and its metastases. Furthermore, we describe the known regulators and the role of genetics (especially chromosome 3 and BRCA-Associated Protein 1 (BAP1 status)), and, last but not least, the effect of putative therapeutic treatments on HLA expression.
Microbial Phosphotriesterase: Structure, Function, and Biotechnological Applications
Authors: Latip Wahhida , Knight Victor Feizal , Abdul Halim Norhana , Ong Keat Khim , Mohd Kassim Noor Azilah , Wan Yunus Wan Md Zin , Mohd Noor Siti Aminah , Mohamad Ali Mohd Shukuri
Published: August 2019

The role of phosphotriesterase as an enzyme which is able to hydrolyze organophosphate compounds cannot be disputed. Contamination by organophosphate (OP) compounds in the environment is alarming, and even more worrying is the toxicity of this compound, which affects the nervous system. Thus, it is important to find a safer way to detoxify, detect and recuperate from the toxicity effects of this compound. Phosphotriesterases (PTEs) are mostly isolated from soil bacteria and are classified as metalloenzymes or metal-dependent enzymes that contain bimetals at the active site. There are three separate pockets to accommodate the substrate into the active site of each PTE. This enzyme generally shows a high catalytic activity towards phosphotriesters. These microbial enzymes are robust and easy to manipulate. Currently, PTEs are widely studied for the detection, detoxification, and enzyme therapies for OP compound poisoning incidents. The discovery and understanding of PTEs would pave ways for greener approaches in biotechnological applications and to solve environmental issues relating to OP contamination.
Two-Step Production of Neofructo-Oligosaccharides Using Immobilized Heterologous Aspergillus terreus 1F-Fructosyltransferase Expressed in Kluyveromyces lactis and Native Xanthophyllomyces dendrorhous G6-Fructosyltransferase
Authors: Burghardt Jan Philipp , Baas Markus , Gerlach Doreen , Czermak Peter
Published: August 2019

Fructo-oligosaccharides (FOS) are prebiotic low-calorie sweeteners that are synthesized by the transfer of fructose units from sucrose by enzymes known as fructosyltransferases. If these enzymes generate β-(2,6) glycosidic bonds, the resulting oligosaccharides belong to the neoseries (neoFOS). Here, we characterized the properties of three different fructosyltransferases using a design of experiments approach based on response surface methodology with a D-optimal design. The reaction time, pH, temperature, and substrate concentration were used as parameters to predict three responses: The total enzyme activity, the concentration of neoFOS and the neoFOS yield relative to the initial concentration of sucrose. We also conducted immobilization studies to establish a cascade reaction for neoFOS production with two different fructosyltransferases, achieving a total FOS yield of 47.02 ± 3.02%. The resulting FOS mixture included 53.07 ± 1.66 mM neonystose (neo-GF3) and 20.8 ± 1.91 mM neo-GF4.
MiR-200-3p Is Potentially Involved in Cell Cycle Arrest by Regulating Cyclin A during Aestivation in Apostichopus japonicus
Authors: Wang Shanshan , Chen Muyan , Yin Yingchao , Storey Kenneth B.
Published: August 2019

The sea cucumber (Apostichopus japonicus) has become a good model organism for studying environmentally induced aestivation in marine invertebrates. We hypothesized that mechanisms that arrest energy-expensive cell cycle activity would contribute significantly to establishing the hypometabolic state during aestivation. Cyclin A is a core and particularly interesting cell cycle regulator that functions in both the S phase and in mitosis. In the present study, negative relationships between miR-200-3p and AjCA expressions were detected at both the transcriptional and the translational levels during aestivation in A. japonicus. Dual-luciferase reporter assays confirmed the targeted location of the miR-200-3p binding site within the AjCA gene transcript. Furthermore, gain- and loss-of-function experiments were conducted in vivo with sea cucumbers to verify the interaction between miR-200-3p and AjCA in intestine tissue by qRT-PCR and Western blotting. The results show that the overexpression of miR-200-3p mimics suppressed AjCA transcript levels and translated protein production, whereas transfection with a miR-200-3p inhibitor enhanced both AjCA mRNA and AjCA protein in A. japonicus intestine. Our findings suggested a potential mechanism that reversibly arrests cell cycle progression during aestivation, which may center on miR-200-3p inhibitory control over the translation of cyclin A mRNA transcripts.
Clinical Protocol to Prevent Thrombogenic Effect of Liver-Derived Mesenchymal Cells for Cell-Based Therapies
Authors: Coppin Louise , Najimi Mustapha , Bodart Julie , Rouchon Marie-Sophie , van der Smissen Patrick , Eeckhoudt Stéphane , Dahlqvist Géraldine , Castanares-Zapatero Diego , Komuta Mina , Brouns Sanne L. , Baaten Constance C. , Heemskerk Johan W. M. , Horman Sandrine , Belmonte Nathalie , Sokal Etienne , Stéphenne Xavier
Published: August 2019

The efficacy of mesenchymal stem cell infusion is currently tested in numerous clinical trials. However, therapy-induced thrombotic consequences have been reported in several patients. The aim of this study was to optimize protocols for heterologous human adult liver-derived progenitor cell (HHALPC) infusion, in order to eliminate acute thrombogenesis in liver-based metabolic or acute decompensated cirrhotic (ADC) patients. In rats, thrombotic effects were absent when HHALPCs were infused at low cell dose (5 × 106 cells/kg), or at high cell dose (5 × 107 cells/kg) when combined with anticoagulants. When HHALPCs were exposed to human blood in a whole blood perfusion assay, blocking of the tissue factor (TF) coagulation pathway suppressed fibrin generation and platelet activation. In a Chandler tubing loop model, HHALPCs induced less explosive activation of coagulation with blood from ADC patients, when compared to blood from healthy controls, without alterations in coagulation factor levels other than fibrinogen. These studies confirm a link between TF and thrombogenesis, when TF-expressing cells are exposed to human blood. This phenomenon however, could be controlled using either a low, or a high cell dose combined with anticoagulants. In clinical practice, this points to the suitability of a low HHALPC dose infusion to cirrhotic patients, provided that platelet and fibrinogen levels are monitored.
HLA-E Polymorphism Determines Susceptibility to BK Virus Nephropathy after Living-Donor Kidney Transplant
Authors: Rohn Hana , Michita Rafael Tomoya , Schramm Sabine , Dolff Sebastian , Gäckler Anja , Korth Johannes , Heinemann Falko M. , Wilde Benjamin , Trilling Mirko , Horn Peter A. , Kribben Andreas , Witzke Oliver , Rebmann Vera
Published: August 2019

Human leukocyte antigen (HLA)-E is important for the regulation of anti-viral immunity. BK polyomavirus (BKPyV) reactivation after kidney transplant is a serious complication that can result in BKPyV-associated nephropathy (PyVAN) and subsequent allograft loss. To elucidate whether HLA-E polymorphisms influence BKPyV replication and nephropathy, we determined the HLA-E genotype of 278 living donor and recipient pairs. A total of 44 recipients suffered from BKPyV replication, and 11 of these developed PyVAN. Homozygosity of the recipients for the HLA-E*01:01 genotype was associated with the protection against PyVAN after transplant (p = 0.025, OR 0.09, CI [95%] 0.83–4.89). Considering the time course of the occurrence of nephropathy, recipients with PyVAN were more likely to carry the HLA-E*01:03 allelic variant than those without PyVAN (Kaplan–Meier analysis p = 0.03; OR = 4.25; CI (95%) 1.11–16.23). Our findings suggest that a predisposition based on a defined HLA-E genotype is associated with an increased susceptibility to develop PyVAN. Thus, assessing HLA-E polymorphisms may enable physicians to identify patients being at an increased risk of this viral complication.
The Ubiquitin Moiety of Ubi1 Is Required for Productive Expression of Ribosomal Protein eL40 in Saccharomyces cerevisiae
Authors: Martín-Villanueva Sara , Fernández-Pevida Antonio , Kressler Dieter , de la Cruz Jesús
Published: August 2019

Ubiquitin is a highly conserved small eukaryotic protein. It is generated by proteolytic cleavage of precursor proteins in which it is fused either to itself, constituting a polyubiquitin precursor of head-to-tail monomers, or as a single N-terminal moiety to ribosomal proteins. Understanding the role of the ubiquitin fused to ribosomal proteins becomes relevant, as these proteins are practically invariably eS31 and eL40 in the different eukaryotes. Herein, we used the amenable yeast Saccharomyces cerevisiae to study whether ubiquitin facilitates the expression of the fused eL40 (Ubi1 and Ubi2 precursors) and eS31 (Ubi3 precursor) ribosomal proteins. We have analyzed the phenotypic effects of a genomic ubi1∆ub-HA ubi2∆ mutant, which expresses a ubiquitin-free HA-tagged eL40A protein as the sole source of cellular eL40. This mutant shows a severe slow-growth phenotype, which could be fully suppressed by increased dosage of the ubi1∆ub-HA allele, or partially by the replacement of ubiquitin by the ubiquitin-like Smt3 protein. While expression levels of eL40A-HA from ubi1∆ub-HA are low, eL40A is produced practically at normal levels from the Smt3-S-eL40A-HA precursor. Finally, we observed enhanced aggregation of eS31-HA when derived from a Ubi3∆ub-HA precursor and reduced aggregation of eL40A-HA when expressed from a Smt3-S-eL40A-HA precursor. We conclude that ubiquitin might serve as a cis-acting molecular chaperone that assists in the folding and synthesis of the fused eL40 and eS31 ribosomal proteins.
Environmental and Economic Evaluation of Fuel Choices for Short Sea Shipping
Authors: Spoof-Tuomi Kirsi , Niemi Seppo
Published: August 2019

The shipping industry is looking for strategies to comply with increasingly stringent emission regulations. Fuel has a significant impact on emissions, so a switch to alternative fuels needs to be evaluated. This study investigated the emission performances of liquefied natural gas (LNG) and liquefied biogas (LBG) in shipping and compared them to conventional marine diesel oil (MDO) combined with selective catalytic reduction (SCR). For assessing the complete global warming potential of these fuels, the life-cycle approach was used. In addition, the study evaluated the local environmental impacts of combustion of these fuels, which is of particular importance for short sea shipping operations near coastal marine environment and residential areas. All three options examined are in compliance with the most stringent emission control area (ECA) regulations currently in force or entering into force from 2021. In terms of local environmental impacts, the two gaseous fuels had clear advantages over the MDO + SCR combination. However, the use of LNG as marine fuel achieved no significant CO2-equivalent reduction, thus making little progress towards the International Maritime Organization’s (IMO’s) visions of decarbonizing shipping. Major life cycle GHG emission benefits were identified by replacing fossil fuels with LBG. The most significant challenge facing LBG today is fuel availability in volumes needed for shipping. Without taxation or subsidies, LBG may also find it difficult to compete with the prices of fossil fuels.
Investigation of Micro-Hardness, Wear Resistance, and Defects of 316L Stainless Steel and TiC Composite Coating Fabricated by Laser Engineered Net Shaping
Authors: Lian Guofu , Zhao Chenmin , Zhang Yang , Huang Xu , Chen Changrong , Jiang Jibin
Published: August 2019

The influence of processing parameters in laser engineered net shaping (LENS) on the properties of 316L stainless steel and titanium carbide (TiC) composite coating was studied. The key processing parameters were laser power, scanning speed, TiC powder ratio, and powder feed rate. Mathematical models were developed to investigate the micro-hardness, wear volume, and defect area of the coating. The accuracy of the models was examined by analysis of variance and experimental validation. Results showed that micro-hardness was positively correlated with TiC powder ratio. Increasing TiC powder ratio could reduce the wear volume. In addition, the wear volume displayed an increase then decrease with increasing laser power and decreasing scanning speed. Both scanning speed and TiC powder ratio showed a recognizable impact on the defect area. Reducing the scanning speed and TiC powder ratio can effectively reduce the defect area. The targets for the processing parameters optimization were set to maximize micro-hardness, minimize wear volume, and defect area. The difference between the model prediction value and experimental validation result for micro-hardness, wear volume, and defect area were 0.46%, 4.54%, and 8.82%, respectively. These results provide guidance for the LENS processing parameters optimization in controlling and predicting of 316L/TiC composite coating properties.
Study on Local Residual Stress in a Nanocrystalline Cr2O3 Coating by Micro-Raman Spectroscopy
Authors: Li Qiu , Gou Yanrong , Wang Tie-Gang , Gu Tingyi , Yu Qiang , Wang Lijie
Published: August 2019

Residual stress in coatings often affects the service performance of coatings, and the residual stresses in some local areas even lead to premature failure of coatings. In this work, we characterized the residual stress of local micro-areas of a nanocrystalline Cr2O3 coating deposited on a Si wafer through micro-Raman spectroscopy, including the depositional edge zone where the electrode was placed, the micro-area containing Cr2O3 macroparticles, and other micro-areas vulnerable to cracks. To accurately measure the thickness of the coating, we combined optical interferometry and direct measurement by a profilometer. The results indicate the existence of in-plane tensile residual stress on the Cr2O3 coating. In thick coatings, the residual stress is independent of the coating thickness and is stable between 0.55 GPa and 0.75 GPa. As the coating thickness is less than 0.8 μm, the residual stress is directly related to the coating thickness. This in-plane tensile stress is considered as the origin of the observed microcrack, which can partially release the stress.
Thermodynamic, Dynamic, and Transport Properties of Quantum Spin Liquid in Herbertsmithite from an Experimental and Theoretical Point of View
Authors: Shaginyan Vasily R. , Msezane Alfred Z. , Amusia Miron Ya. , Clark John W. , Japaridze George S. , Stephanovich Vladimir A. , Leevik Yulya S.
Published: August 2019

In our review, we focus on the quantum spin liquid (QSL), defining the thermodynamic, transport, and relaxation properties of geometrically frustrated magnet (insulators) represented by herbertsmithite ZnCu 3 ( OH ) 6 Cl 2 . The review mostly deals with an historical perspective of our theoretical contributions on this subject, based on the theory of fermion condensation closely related to the emergence (due to geometrical frustration) of dispersionless parts in the fermionic quasiparticle spectrum, so-called flat bands. QSL is a quantum state of matter having neither magnetic order nor gapped excitations even at zero temperature. QSL along with heavy fermion metals can form a new state of matter induced by the topological fermion condensation quantum phase transition. The observation of QSL in actual materials such as herbertsmithite is of fundamental significance both theoretically and technologically, as it could open a path to the creation of topologically protected states for quantum information processing and quantum computation. It is therefore of great importance to establish the presence of a gapless QSL state in one of the most prospective materials, herbertsmithite. In this respect, the interpretation of current theoretical and experimental studies of herbertsmithite are controversial in their implications. Based on published experimental data augmented by our theoretical analysis, we present evidence for the the existence of a QSL in the geometrically frustrated insulator herbertsmithite ZnCu 3 ( OH ) 6 Cl 2 , providing a strategy for unambiguous identification of such a state in other materials. To clarify the nature of QSL in herbertsmithite, we recommend measurements of heat transport, low-energy inelastic neutron scattering, and optical conductivity σ ¯ in ZnCu 3 ( OH ) 6 Cl 2 crystals subject to an external magnetic field at low temperatures. Our analysis of the behavior of σ ¯ in herbertsmithite justifies this set of measurements, which can provide a conclusive experimental demonstration of the nature of its spinon-composed quantum spin liquid. Theoretical study of the optical conductivity of herbertsmithite allows us to expose the physical mechanisms responsible for its temperature and magnetic field dependence. We also suggest that artificially or spontaneously introducing inhomogeneity at nanoscale into ZnCu 3 ( OH ) 6 Cl 2 can both stabilize its QSL and simplify its chemical preparation, and can provide for tests that elucidate the role of impurities. We make predictions of the results of specified measurements related to the dynamical, thermodynamic, and transport properties in the case of a gapless QSL.
A Comparison of Systematic Quadrat and Capture-Mark-Recapture Sampling Designs for Assessing Freshwater Mussel Populations
Authors: Carey Caitlin S. , Jones Jess W. , Butler Robert S. , Kelly Marcella J. , Hallerman Eric M.
Published: August 2019

Our study objective was to compare the relative effectiveness and efficiency of quadrat and capture-mark-recapture (CMR) sampling designs for monitoring mussels. We collected data on a recently reintroduced population of federally endangered Epioblasma capsaeformis and two nonlisted, naturally occurring species—Actinonaias pectorosa and Medionidus conradicus—in the Upper Clinch River, Virginia, over two years using systematic quadrat and CMR sampling. Both sampling approaches produced similar estimates of abundance; however, precision of estimates varied between approaches, years, and among species, and further, quadrat sampling efficiency of mussels detectable on the substrate surface varied among species. CMR modeling revealed that capture probabilities for all three study species varied by time and were positively associated with shell length, that E. capsaeformis detection was influenced by sex, and that year-to-year apparent survival was high (>96%) for reintroduced E. capsaeformis. We recommend that monitoring projects use systematic quadrat sampling when the objective is to estimate and detect trends in abundance for species of moderate to high densities (>0.2/m2), whereas a CMR component should be incorporated when objectives include assessing reintroduced populations, obtaining reliable estimates of survival and recruitment, or producing unbiased population estimates for species of low to moderate densities (≤0.2/m2).