bluuebunny/crossref_metadata_2025 huggingface dataset:
CFD predicted pH gradients in lactic acid bacteria cultivations
Authors: Spann Robert , Glibstrup Jens , Pellicer‐Alborch Klaus , Junne Stefan , Neubauer Peter , Roca Christophe , Kold David , Lantz Anna Eliasson , Sin Gürkan , Gernaey Krist V. , Krühne Ulrich
Published: November 2018

The formation of pH gradients in a 700 L batch fermentation of Streptococcus thermophilus was studied using multi‐position pH measurements and computational fluid dynamics (CFD) modeling. To this end, a dynamic, kinetic model of
S. thermophilus and a pH correlation were integrated into a validated one‐phase CFD model, and a dynamic CFD simulation was performed. First, the fluid dynamics of the CFD model were validated with NaOH tracer pulse mixing experiments. Mixing experiments and simulations were performed whereas multiple pH sensors, which were placed vertically at different locations in the bioreactor, captured the response. A mixing time of about 46 s to reach 95% homogeneity was measured and predicted at an impeller speed of 242 rpm. The CFD simulation of the
S. thermophilus fermentation captured the experimentally observed pH gradients between a pH of 5.9 and 6.3, which occurred during the exponential growth phase. A pH higher than 7 was predicted in the vicinity of the base solution inlet. Biomass growth, lactic acid production, and substrate consumption matched the experimental observations. Moreover, the biokinetic results obtained from the CFD simulation were similar to a single‐compartment simulation, for which a homogeneous distribution of the pH was assumed. This indicates no influence of pH gradients on growth in the studied bioreactor. This study verified that the pH gradients during a fermentation in the pilot‐scale bioreactor could be accurately predicted using a coupled simulation of a biokinetic and a CFD model. To support the understanding and optimization of industrial‐scale processes, future biokinetic CFD studies need to assess multiple types of environmental gradients, like pH, substrate, and dissolved oxygen, especially at industrial scale.
Child Maltreatment in the Zhejiang Province of China: The Role of Parental Aggressive Tendency and a History of Maltreatment in Childhood
Authors: Ni Yanyan , Zhou Xudong , Li Leah , Hesketh Therese
Published: November 2018

This study aimed to explore the role of parental aggression and parental childhood maltreatment experience in the maltreatment of children in Zhejiang Province, eastern China. The study sites were two urban and two rural schools. Children aged ten to 16 years and their parents completed separate questionnaires, which included: parental childhood maltreatment; parental aggressive tendency; and maltreatment of children. Questionnaires were completed by 611 parents and 821 children. Fifty‐eight per cent of parents reported maltreatment of their children. Higher parental aggression scores were associated with an increased risk for all types of child maltreatment (relative risk ratios (RRRs) or odds ratios (ORs) ranged from 1.06–1.07 for each point higher on the aggression scale). Parental childhood maltreatment was significantly associated with an increased risk of moderate/severe physical maltreatment of children (OR = 1.80 (1.08, 3.00)); parental aggression was an explanatory factor for this association. Parental childhood maltreatment was positively associated with emotional maltreatment of children (OR = 1.89 (1.27, 2.83)). This was partly explained by parental aggression. In conclusion, high levels of child maltreatment were admitted by parents in China, suggesting the need for parenting education. Parents with a higher aggressive tendency were more likely to maltreat children. Parental aggressive tendency was an explanatory factor for the intergenerational transmission of maltreatment, indicating the possibility of identifying parents' aggressive tendencies for early prevention. © 2018 John Wiley & Sons, Ltd.

‘Explore[s] the role of parental aggression and parental childhood maltreatment experience in the maltreatment of children in Zhejiang Province’

Key Practitioner Messages

Child maltreatment of all types is common in China. What is especially striking is the finding that nearly a fifth of parents admitted to moderate/severe maltreatment of their children.

Parents with a higher aggressive tendency were more likely to use all types of maltreatment with their children.

Parental aggression was an explanatory factor for the intergenerational transmission of moderate/severe physical maltreatment and emotional maltreatment.

‘Child maltreatment of all types is common in China’
Build strong ties to campus through recruitment, multiple engagement points
Authors: Sutton Halley
Published: November 2018

Even after Paul Cooper retired from his position as the city of Claremont's police chief in 2016, he wasn't done with law enforcement. “I still enjoy law enforcement and the opportunity to make a difference and impact people's lives, so I stayed on as a volunteer reserve police officer with the Claremont Police Department and continue working as a reserve,” Cooper said. But in 2018, Cooper was hired as the assistant police chief at the University of California, Irvine.
Terminal Deoxynucleotidyl Transferase in the Synthesis and Modification of Nucleic Acids
Authors: Sarac Ivo , Hollenstein Marcel
Published: November 2018

The terminal deoxynucleotidyl transferase (TdT) belongs to the X family of DNA polymerases. This unusual polymerase catalyzes the template‐independent addition of random nucleotides on 3′‐overhangs during V(D)J recombination. The biological function and intrinsic biochemical properties of the TdT have spurred the development of numerous oligonucleotide‐based tools and methods, especially if combined with modified nucleoside triphosphates. Herein, we summarize the different applications stemming from the incorporation of modified nucleotides by the TdT. The structural, mechanistic, and biochemical properties of this polymerase are also discussed.
Utilization of Synthetic Calcium‐Phyllosilicates as Bifunctional Bases in the Matsuda‐Heck Reaction
Authors: Brunner Heiko , Vedder Lennart
Published: November 2018

Calcium‐phyllosilicates can successfully be used as novel bases in the Matsuda‐Heck reaction using methanol as solvent. The new experimental set‐up distinguishes itself by higher reactivity and better selectivity compared to other systems.
Class‐specific variable selection in high‐dimensional discriminant analysis through Bayesian Sparsity
Authors: Orlhac Fanny , Mattei Pierre‐Alexandre , Bouveyron Charles , Ayache Nicholas
Published: November 2018

Although the ongoing digital revolution in fields such as chemometrics, genomics, or personalized medicine gives hope for considerable progress in these areas, it also provides more and more high‐dimensional data to analyze and interpret. A common usual task in those fields is discriminant analysis, which however may suffer from the high dimensionality of the data. The recent advances, through subspace classification or variable selection methods, allowed to reach either excellent classification performances or useful visualizations and interpretations. Obviously, it is of great interest to have both excellent classification accuracies and a meaningful variable selection for interpretation. This work addresses this issue by introducing a subspace discriminant analysis method which performs a class‐specific variable selection through Bayesian sparsity. The resulting classification methodology is called sparse high‐dimensional discriminant analysis (sHDDA). Contrary to most sparse methods which are based on the Lasso, sHDDA relies on a Bayesian modeling of the sparsity pattern and avoids the painstaking and sensitive cross‐validation of the sparsity level. The main features of sHDDA are illustrated on simulated and real‐world data. In particular, an exemplar application to cancer characterization based on medical imaging using radiomic feature extraction is proposed.
T1 Population as the Driver of Excited‐State Proton‐Transfer in 2‐Thiopyridone
Authors: Eckert Sebastian , Norell Jesper , Jay Raphael M. , Fondell Mattis , Mitzner Rolf , Odelius Michael , Föhlisch Alexander
Published: November 2018

Excited‐state proton transfer (ESPT) is a fundamental process in biomolecular photochemistry, but its underlying mediators often evade direct observation. We identify a distinct pathway for ESPT in aqueous 2‐thiopyridone, by employing transient N 1s X‐ray absorption spectroscopy and multi‐configurational spectrum simulations. Photoexcitations to the singlet S2 and S4 states both relax promptly through intersystem crossing to the triplet T1 state. The T1 state, through its rapid population and near nanosecond lifetime, mediates nitrogen site deprotonation by ESPT in a secondary intersystem crossing to the S0 potential energy surface. This conclusively establishes a dominant ESPT pathway for the system in aqueous solution, which is also compatible with previous measurements in acetonitrile. Thereby, the hitherto open questions of the pathway for ESPT in the compound, including its possible dependence on excitation wavelength and choice of solvent, are resolved.
Neutrophil Elastase Promotes Linker Cleavage and Paclitaxel Release from an Integrin‐Targeted Conjugate
Authors: Raposo Moreira Dias André , Pina Arianna , Dean Amelia , Lerchen Hans‐Georg , Caruso Michele , Gasparri Fabio , Fraietta Ivan , Troiani Sonia , Arosio Daniela , Belvisi Laura , Pignataro Luca , Dal Corso Alberto , Gennari Cesare
Published: November 2018

This work takes advantage of one of the hallmarks of cancer, that is, the presence of tumor infiltrating cells of the immune system and leukocyte‐secreted enzymes, to promote the activation of an anticancer drug at the tumor site. The peptidomimetic integrin ligand cyclo(DKP‐RGD) was found to accumulate on the surface of αvβ3 integrin‐expressing human renal cell carcinoma 786‐O cells. The ligand was conjugated to the anticancer drug paclitaxel through a Asn‐Pro‐Val (NPV) tripeptide linker, which is a substrate of neutrophil‐secreted elastase. In vitro linker cleavage assays and cell antiproliferative experiments demonstrate the efficacy of this tumor‐targeting conjugate, opening the way to potential therapeutic applications.
Reproducible Measurement Results in Organic Solvent Nanofiltration with Ceramic Membranes
Authors: Lechner Kai , Brösigke Georg , Repke Jens‐Uwe
Published: November 2018

Ceramic membranes are still quite innovative to organic solvent nanofiltration. Nevertheless, flux and rejection results obtained in filtration measurements seem to depend largely on the experimental procedure, membrane production batch and setup. Therefore, an experimental approach is described, which proved to provide reproducible and reliable results that may be used as data set to derive parameters in model development.
Phase transition properties, chemical purity, and solubility of coniferyl alcohol and D‐mannose: Experimental and Cosmo‐RS predictions
Authors: Mohan Mood , Banerjee Tamal , Goud Vaibhav V.
Published: November 2018

The main objective of the study was to investigate the phase transition properties (melting temperature and heat of fusion) and chemical purity of coniferyl alcohol and D‐mannose by differential scanning calorimetry (DSC). The measurements have been performed at different heating rates from 1–20 °C/min under atmospheric inert gas. From the DSC analysis, the onset temperature, peak temperature, and the heat of fusion of both the compounds were measured. They were found to increase with an increase in the heating rate. The chemical purity of coniferyl alcohol and D‐mannose were determined based on the van't Hoff equation. The chemical purity of coniferyl alcohol was observed to be 99.54 mol% with a correction factor of 1.44 % at a 15 °C/min heating rate. The corresponding purity values for D‐mannose were 98.98 mol% at a correction factor of 6.76 % and 20 °C/min. The obtained results showed that the chemical purity of both the compounds was found to decrease with an increase in the correction factor. Furthermore, this study also focuses on the solubility of both substances in ionic liquids by applying the continuum solvation model (COSMO‐RS) using DSC measured melting properties as input.
Evolution of electronic conductivity in a Ni/YSZ electrode fabricated by electrophoretic deposition
Authors: Amiri Saeid , Hayes Robert E. , Sarkar Partha
Published: November 2018

The conductivity of a tubular micro solid oxide fuel cell (TμSOFC) anode is measured in‐situ. The Ni/YSZ composite anode was fabricated using the electrophoretic deposition (EPD) technique. The four‐probe method is used to measure the conductivity of several samples simultaneously under a reducing atmosphere during several cycles of heating, ∼100 h dwelling and cooling periods. Special attention is paid to maintaining similar fabrication and thermal histories among the samples. Despite all this, the measured conductivities show substantial variation and degradation from sample to sample and from one thermal cycle to the next. The most variations occur during the reduction of the cell, with significant oscillations in the measurements. Sample conductivities exhibit step‐like changes during the cooling and heat‐up cycles. A theory based on thermal expansion induced Ni particles connection formation and breakage within the YSZ backbone is proposed. Sample electron microscope micrographs are presented showing island‐like segregated Ni particles within a continuous YSZ structure. Eliminating such effects not only will reduce the cell performance variability but will also increase the peak power by 60 %, according to our simulation results.
Bio‐scouring of cotton fabric and enzymatic degumming of jute fibres by a thermo‐alkaline recombinant rhamnogalacturonan lyase, ctrglf from Clostridium thermocellum
Authors: Dhillon Arun , Rajulapati Vikky , Goyal Arun
Published: November 2018

In this study, the use of recombinant rhamnogalacturonan lyase CtRGLf in bio‐scouring of cotton and enzymatic degumming jute was evaluated. The best concentration for bio‐scouring of cotton and degumming of jute was found to be 12 mg/mL (3.2 U/mL) of crude CtRGLf. Cotton fabric treated with 12 mg/mL (3.2 U/mL) of crude CtRGLf took 30 s to absorb a drop of water while the CtRGLf untreated fabric took 40 min. The crude CtRGLf reduced the water absorption time of cotton fabric by 98 % after 45 min of treatment. FESEM images showed that crude CtRGLf (12 mg/mL; 3.2 U/mL), effectively removed the waxy compounds from the surface of jute fibres after 1 h of treatment. These results showed that CtRGLf is a potentially important enzyme for the textile industry.
Hybrid blind interference alignment in homogeneous cellular networks with limited coherence time
Authors: Bakhshi Ramin , İnce Erhan Aliriza
Published: November 2018

The work presented in this paper is inspired by the user grouping approach of topological blind interference alignment (top‐BIA), which is a semi‐blind IA scheme and the fact that the partially connected networks can be advantageous in terms of degree of freedom (DoF) and sum rate. The hybrid‐BIA scheme proposed in the paper uses top‐BIA to group users that are randomly distributed in a dense small‐cell network and aims to reduce the supersymbol length and overcome the DoF loss of the state‐of‐the‐art hierarchical BIA (h‐BIA) technique. The proposed scheme is very suitable for channels where coherence time is limited and also could attain a good DoF over a small number of symbol extensions. Both the sum‐DoF and the network throughput for hybrid‐BIA is greater than that of h‐BIA. By varying the number of user groups, the paper shows that h‐BIA constitutes a special case of hybrid‐BIA. Finally, the paper demonstrates the effect of changing the number of transmit antennas and number of small cells on the sum‐DoF gain of hybrid‐BIA over that of h‐BIA.
ADYTIA: Adaptive and Dynamic TCP Interface Architecture for heterogeneous networks
Authors: Vanzara Rakeshkumar , Sharma Priyanka , Bhatt Haresh S. , Tanwar Sudeep , Tyagi Sudhanshu , Kumar Neeraj , Obaidat Mohammad S.
Published: November 2018

Due to the widespread popularity and usage of Internet of things (IoT)‐enabled devices, there is an exponential increase in the data traffic generated from these IoT devices. Most of these devices communicate with each other using heterogeneous links having constraints such as latency, throughput, and interference from concurrent transmissions. This results in an extra burden on the underlying communication infrastructure to manage the traffic within these constraints between source and destination. However, most of the existing applications use different Transmission Control Protocol (TCP) variants for traffic management between these devices and are dependent on the stage of the sender, irrespective of the application types and link characteristics. Each operating system (OS) has different TCP variant for all applications, irrespective of path characteristics. Hence, a single TCP variant cannot select the best suitable link, which results in degradation in throughput compared to the existing default. Moreover, it cannot use the full capacity of the available link for different applications and network links, especially in heterogeneous network such as IoT. To cope up with these challenges, in this paper, we propose an Adaptive and Dynamic TCP Interface Architecture (ADYTIA). ADYTIA allows the usage of different TCP variants based on application and link characteristics, irrespective of the physical links of the entire path. It allows the usage of different TCP variants based on their design principle across heterogeneous technologies, platforms, and applications. ADYTIA is implemented on NS‐2 and Linux kernel for real testbed experiments. Its ability to select the best suitable TCP variant results in 20% to 80% improvement in throughput compared with the existing default and single TCP variant on Linux and Windows.
Ocean pollution assessment by integrating physical law and site‐specific data
Authors: Lang Y. , Christakos G.
Published: November 2018

This work introduces the Bayesian maximum entropy (BME) perspective in the space–time characterization and prediction of ocean pollution. The proposed approach can outperform the standard numerical techniques that can also solve the partial differential equation representing the ocean pollution law but either cannot integrate in the solution any case‐specific information (provided by the hard or soft data available) or they do not provide a complete stochastic characterization of the ocean pollution phenomenon. This happens because the BME‐based solution of the ocean pollution law can both take advantage of any case‐specific data available and derive the complete probability density function throughout the space–time domain of interest, which can be then used to derive more than one kind of ocean pollution predictors (including the mean, the median, and the mode) at every point of this domain. Valuable insight into the proposed approach is gained by means of a simulation (synthetic) experiment that considers the advection–reaction law in the light of hard data and three different types of soft information in a controlled environment so a useful sensitivity analysis of the results can be performed (which is not usually possible in a real‐world case study). The uncertainty assessment of this experiment demonstrated that BME leads to improved ocean pollution predictions compared with the standard numerical technique. In principle, the higher the quality and informativeness of the site‐specific data, the more realistic should be the BME solution of the ocean pollution law under conditions of in situ uncertainty (this result also points out the importance of collecting data as informative as possible to maximize prediction accuracy). Moreover, the uncertainty assessment of the pollutant concentration predictions demonstrated that the BME approach makes good use of the soft data leading to improved ocean pollution predictions compared with predictions that do not involve soft data.
Radical Reform Or Piecemeal Adjustments? The Case of Finnish Family Policy Reforms
Authors: Nyby Josefine , Nygård Mikael , Blum Sonja
Published: November 2018

Since the economic crisis, many welfare states reformed their social security systems to cut social expenditure, even in policy fields protecting the most vulnerable, such as family policy. Using qualitative content analysis, this article systematically examines reforms pursued in Finnish family policy 2007–2017, and establishes the direction and magnitude of these reforms. The result show that these fields were frequently reformed, containing both expanding and contracting policy adjustments, as well as contracting structural reforms. The result also show that the “Nordic” principle of universalism was slightly weakened and the principle of selectivity somewhat strengthened during this period.
Alcyonacea awakens: Palaeobiology and palaeoecology of Palaeozoic octocorals known from their sclerites
Authors: Fernández‐Martínez Esperanza , Coronado Ismael , Rodríguez Sergio , Tourneur Francis , Badpa Mahdi
Published: November 2018

Most Alcyonacea (subclass Octocorallia) have skeletons made up of small calcareous pieces called sclerites that are difficult to both preserve and recognize, which explains the scarce and irregular fossil record of the group. In this work, we study 56 geological samples bearing Syringoalcyon, a genus constituted by Alcyonacea represented by sclerites encrusting the outer walls and stolons of a syringoporoid coral. These samples come from 18 Silurian to mostly Carboniferous localities in Canada, USA, Mexico, Morocco, Algeria, Spain, Iran, and China. A morphological and numerical study was carried out to determine the main morphological and palaeobiological features of the sclerites and the Alcyonacea itself and to establish a new genus for these sclerites. The study facilitated distinguishing four sclerite morphotypes (spindle, elongate spindle, club, and arrowhead). Live sclerites can be attached through biotic or abiotic linkages to biotic substrate patches by insertion or cementation. Spindle sclerites arranged in vertical fences are the most common model, but other arrangements such as stacking or short horizontal fences have been observed even in a single specimen. The morphotypes, dimensions of the sclerites, substrates, and types of arrangement observed are well known in Recent Alcyonacea. According to the arrangements of the sclerites, the alcyonacean morphology was different depending on the shape and dimensions of the substrate. This Syringoporidae–Alcyonacea association is a good example of ecological engineering, but several data suggest that the relationship between these two corals was closer than hard substrate colonization.
Control of strike‐slip and pull‐apart processes to tectonic transition of the southern East China Sea Shelf Basin
Authors: Cui Xing , Dai Liming , Li Sanzhong , Guo Lingli , Suo Yanhui
Published: November 2018

The East China Sea Shelf Basin (ECSSB) lies among the Eurasian Plate, the Pacific Plate, and the Indian Plate. Its formation and evolution since the Mesozoic was controlled by the combined effect of westward subduction of the Pacific Plate and actions of the large‐scale ductile shear zone on the South China Plate—the Changle–Nan'ao Fault Zone. This paper selects the southern ECSSB with well‐developed Mesozoic strata as the study area. By analysing the basin architectures and structures of each structural unit, calculating the fault growth index, and referring to the sandbox modelling results, we consider that the Oujiang Sag belongs to a strike‐slip pull‐apart basin controlled by the Changle–Nan'ao Fault Zone, while the Minjiang Sag and the Jilong Sag are extensional basins without strike‐slip property. The Mesozoic evolutionary process of the ECSSB can be divided into three stages on the basis of the three main strike‐slip movements of the fault zone. In the Middle–Late Jurassic, the subduction of the Izanagi Plate induced the dextral shearing in a ENE direction of the Changle–Nan'ao Fault Zone, which then formed NW‐SE‐directed transpressional structures inside the ECSSB. In the Late Jurassic–Early Cretaceous, the motion sense of the Izanagi Plate gradually shifted to the northwestwards, inducing the sinistral‐thrusting of the fault zone. Following this, the initial NW‐SE‐directed compressional structures were stretched into the original sag. By the Late Cretaceous, the retreat of the subducting Paleo‐Pacific Plate led to the turning of the regional stress field from compression to transtension. Being influenced by the dextral strike‐slip‐related structures of the Changle–Nan'ao Fault Zone, the Oujiang Sag developed extensive strike slipping‐related structures and was assembled into a left‐stepping en echelon pattern. The Minjiang and Jilong sags, however, gradually grew into extensional depressions under successive extension due to the great distance from the strike‐slip fault zone.
The impact of financial incentives on health and health care: Evidence from a large wellness program
Authors: Einav Liran , Lee Stephanie , Levin Jonathan
Published: November 2018

Workplace wellness programs have become increasingly common in the United States, although there is not yet consensus regarding the ability of such programs to improve employees' health and reduce health care costs. In this paper, we study a program offered by a large U.S. employer that provides substantial financial incentives directly tied to employees' health. The program has a high participation rate among eligible employees, around 80%, and we analyze the data on the first 4 years of the program, linked to health care claims. We document robust improvements in employee health and a correlation between certain health improvements and reductions in health care cost. Despite the latter association, we cannot find direct evidence causally linking program participation to reduced health care costs, although it seems plausible that such a relationship will arise over longer horizons.
Molecular and cellular basis of mammary gland fibrosis and cancer risk
Authors: Wu Jianchun , Crowe David L.
Published: November 2018

Mammary gland luminal cells are maintained by the proliferation of ER− luminal progenitor (LP) cells. Human breast LP cells exhibit telomere DNA damage, which is associated with mammographic density and increased cancer risk. Telomeric repeat factor 2 (TRF2) protects telomeres from DNA damage response. TRF2 expression is reduced in human breast cancers. We deleted TRF2 expression in mammary gland epithelium. Mammary glands lacking TRF2 expression exhibited increased telomere DNA damage response, histopathological and functional degeneration, and prominent ductal fibrosis. TRF2‐deficient mammary tumors exhibited rapid onset and increased proliferation. Tumor derived LP cells failed to form tumors after transplantation. The MSC population was highly tumorigenic and maintained telomeres via the ALT mechanism. Telomere DNA damage response in mammary tumors resulted in p53 dependent ER+ cellular differentiation and sensitivity to anti‐estrogen therapy. Our results provide a new in vivo model of mammographic density, stem cell differentiation, cancer risk, and therapeutic sensitivity.
Improved biocompatibility of profiled sutures through lower macrophages adhesion
Authors: Eickhoff Roman M. , Bolle Tim , Kossel Klas , Heise Daniel , Kroh Andreas , Lambertz Andreas , Blaeser Andreas , Gries Thomas , Jockenhoevel Stefan , Neumann Ulf P. , Klink Christian D.
Published: November 2018

The biocompatibility of a textile implant is determined by various parameters, such as material composition and surface chemistry. However, little is known about the influence of geometry of sutures on biocompatibility. To elucidate this factor we focused on geometry‐modification resulting in ultrafine polyethylene terephthalate (UFPET) suture and a snowflake like shaped polyvenylidenfluorid (PVDF) suture.

Forty‐eight rats were divided into two observation periods. In each rat 3 out of 4 sutures (profiled UFPET, snowflake‐like profiled PVDF, reference Prolene and Mersilene suture) were randomly placed into the subcutaneous tissue. Rats were euthanized after 7 and 21 days and samples were explanted. Foreign body granuloma was measured and expression of CD68, TUNEL, Ki‐67 and Collagen I/III ratio were determined.

The profiled (snowflake) suture showed a significantly smaller FBG in comparison to standard sutures (p < 0.001). Both modified sutures showed a significant lower tissue remodeling by Ki‐67 and TUNEL expression (p < 0.03). Furthermore, profiled sutures caused a lower inflammatory reaction expressed in a significant lower amount of CD68 positive macrophages after 21 days (p < 0.001).

Modifications of suture geometry alter the foreign body granuloma and the inflammatory reaction. Therefore, profiled sutures might be a promising approach to improve biocompatibility of textile mesh prosthesis. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 107B: 1772–1778, 2019.
Role of miR‐142 in the pathogenesis of osteosarcoma and its potential as therapeutic approach
Authors: Shabani Parastoo , Izadpanah Sama , Aghebati‐Maleki Ali , Baghbani Elham , Baghbanzadeh Amir , Fotouhi Ali , Bakhshinejad Babak , Aghebati‐Maleki Leili , Baradaran Behzad
Published: November 2018

Osteosarcoma (OS) is the most common primary malignant tumor of the bone with a strong tendency to early metastasis, and occurs in growing bones more commonly in children and adolescents. Considering the limited therapeutic methods and lack of 100% success of these methods, developing innovative therapies with high efficacy and lower side effects is needed. Meanwhile, miRNAs and the studies indicating the involvement of miRNAs in OS development have attracted attentions as a result of the frequent abnormalities in expression of miRNAs in cancer. miRNAs are noncoding short sequences with lengths ranging from 18 to 25 nucleotides that play a very important role in cellular processes, such as proliferation, differentiation, migration, and apoptosis. MiRNAs can have either oncogenic or tumor suppressive role based on cellular function and targets. This review aimed to have overview on miR‐142 as a tumor suppressor in OS. Moreover, the genes involved in the disease, such as RAC1,
HMAG1,
MMP9,
MMP2, and
E‐cadherin, which have irregularities as a result of change in miR‐142 expression, and, thereby, result in increasing the proliferation, invasion, and metastasis of the cells in the tissues and OS cells will be discussed.
Wnt and BMP signaling pathways co‐operatively induce the differentiation of multiple myeloma mesenchymal stem cells into osteoblasts by upregulating EMX2
Authors: Wei Xiao‐Fang , Chen Qiao‐Lin , Fu Yuan , Zhang Qi‐Ke
Published: November 2018

Osteoblast differentiation, defined as the process whereby a relatively unspecialized cell acquires the specialized features of an osteoblast, is directly linked to multiple myeloma (MM) bone disease. Wnt and bone morphogenetic protein (BMP) are proved to be implicated in the pathological or defective osteoblast differentiation process. This study aims to test the involvement of Wnt, bone morphogenetic proteins (BMP) pathways, and empty spiracles homeobox 2 (EMX2) in osteoblast differentiation and MM development. Initially, differentially expressed genes in bone marrow mesenchymal stem cells (MSCs) from MM patients and healthy donors were identified using microarray‐based gene expression profiling. The functional role of Wnt and BMP in MM was determined. Next, we focused on the co‐operative effects of Wnt and BMP on calcium deposition, alkaline phosphatase (ALP) activity, the number of mineralized nodules, and osteocalcin (OCN) content in MSCs. The expression patterns of Wnt and BMP pathway–related genes, EMX2 and osteoblast differentiation‐related factors were determined to assess their effects on osteoblast differentiation. Furthermore, regulation of Wnt and BMP in ectopic osteogenesis was also investigated in vivo. An integrated genomic screen suggested that Wnt and BMP regularly co‐operate to regulate EMX2 and affect MM. EMX2 was downregulated in MSCs. The activated Wnt and BMP resulted in more calcium salt deposits, mineralized nodules, and a noted increased in ALP activity and OCN content by upregulating EMX2, leading to induced differentiation of MSCs into osteoblasts. Collectively, this study demonstrated that Wnt and BMP pathways could co‐operatively stimulate differentiation of MSCs into osteoblasts and inhibit MM progression, representing potential targets for MM treatment.
IGFBP7 regulates sepsis‐induced acute kidney injury through ERK1/2 signaling
Authors: Wang Xiaolin , Ma Teng , Wan Xiaojian , Meng Yan , Zhao Zhenzhen , Bian Jinjun , Bao Rui , Deng Xiaoming , Yang Tao
Published: November 2018

IGFBP7 as an early biomarker has been used to identify patients at risk of developing acute kidney injury (AKI). Nevertheless, its role in AKI remains obscure. The aim of our study is to determine the role and mechanism of IGFBP7 in lipopolysaccharide (LPS)‐induced HK‐2 cells in vitro and on sepsis‐induced AKI by cecal ligation and puncture (CLP) in vivo. Here, we identified that IGFBP7 expression was increased in patients with AKI and HK‐2 cells with LPS (1, 2, and 5 μg/mL) induction. HK‐2 cells with LPS induction showed cell cycle arrest at G1‐G0 phases and cell apoptosis and activated ERK1/2 parallel with the changes in the proteins belonging to the ERK1/2 pathway, including Cyclin D1, P21, Bax, and Bcl‐2, which were inhibited by the IGFBP7 knockdown. Moreover, IGFBP7 overexpression significantly induced cell cycle arrest at G1‐G0 phases and cell apoptosis of HK‐2 cells, which were inhibited by PD98509, an ERK1/2 signaling inhibitor. IGFBP7 knockdown effectively alleviated the severity of the renal injury, evidenced by decreases in the urinary levels of creatinine, blood urea nitrogen, and albumin, cell apoptosis, and activation of ERK1/2 signaling in CLP mice. Taken together, our findings indicate that IGFBP7 regulates sepsis‐induced AKI through ERK1/2 signaling.
Ab initio surface hopping excited‐state molecular dynamics approach on the basis of spin–orbit coupled states: An application to the A‐band photodissociation of CH3I
Authors: Kamiya Muneaki , Taketsugu Tetsuya
Published: November 2018

Ab initio molecular dynamics approach has been extended to multi‐state dynamics on the basis of the spin–orbit coupled electronic states that are obtained through diagonalization of the spin–orbit coupling matrix with the multi‐state second‐order multireference perturbation theory energies in diagonal elements and the spin–orbit coupling terms at the state‐averaged complete active space self‐consistent field level in off‐diagonal elements. Nonadiabatic transitions over the spin–orbit coupled states were taken into account explicitly by a surface hopping scheme with utilizing the nonadiabatic coupling terms calculated by numerical differentiation of the spin–orbit coupled wavefunctions and analytical nonadiabatic coupling terms. The present method was applied to the A‐band photodissociation of methyl iodide, CH3I + hv → CH3 + I (2P3/2)/I* (2P1/2), for which a pioneering theoretical work was reported by Amatatsu, Yabushita, and Morokuma. The present results reproduced well the experimental branching ratio and energy distributions in the dissociative products. © 2018 Wiley Periodicals, Inc.
Quantitative Modeling Analysis Demonstrates the Impact of CYP2C19 and CYP2D6 Genetic Polymorphisms on the Pharmacokinetics of Amitriptyline and Its Metabolite, Nortriptyline
Authors: Koh Ara , Pak Kwan Cheol , Choi Hee Youn , Ryu Sunae , Choi Seung‐eun , Kim Ki Soon , Bae Kyun‐Seop , Lim Hyeong‐Seok
Published: November 2018

Amitriptyline is a tricyclic antidepressant that is metabolized mainly by CYP2C19 and CYP2D6 enzymes. Higher plasma levels of amitriptyline and its active metabolite, nortriptyline, are associated with an increased risk of adverse events including anticholinergic effects. The aim of this study was to evaluate the effects of CYP2C19 and CYP2D6 genetic polymorphisms on amitriptyline and nortriptyline pharmacokinetics. Twenty‐four Korean healthy adult male volunteers were enrolled in the study after stratification by their CYP2C19 and CYP2D6 genotypes. Serial blood draws for pharmacokinetic analysis were made after a single oral 25‐mg dose of amitriptyline was administered. Plasma amitriptyline and nortriptyline concentrations were measured by a validated liquid chromatography with tandem mass spectrometry. Population pharmacokinetic modeling analysis was conducted using NONMEM, which evaluated the effects of CYP2C19 and CYP2D6 genotypes on amitriptyline and nortriptyline pharmacokinetics. The biotransformation of amitriptyline into nortriptyline was significantly different between subjects with the CYP2C19*2/*2, *2/*3, and *3/*3 genotypes and those with the other genotypes, with an estimated metabolic clearance of 17 and 61.5 L/h, respectively. Clearance of amitriptyline through pathways other than biotransformation into nortriptyline was estimated as 18.8 and 30.6 L/h for subjects with the CYP2D6*10/*10 and *10/*5 genotypes and those with the other genotypes, respectively. This study demonstrated a quantitative effect of the CYP2C19 and CYP2D6 genotypes on amitriptyline and nortriptyline pharmacokinetics. Production of nortriptyline from amitriptyline was associated with CYP2C19 genotypes, and clearance of amitriptyline through pathways other than biotransformation into nortriptyline was associated with CYP2D6 genotypes. These observations may be useful in developing individualized, optimal therapy with amitriptyline.
Retention in care among clinically stable antiretroviral therapy patients following a six‐monthly clinical consultation schedule: findings from a cohort study in rural Malawi
Authors: Wringe Alison , Cawley Caoimhe , Szumilin Elisabeth , Salumu Leon , Amoros Quiles Isabel , Pasquier Estelle , Masiku Charles , Nicholas Sarala
Published: November 2018

Introduction

Longer intervals between clinic consultations for clinically stable antiretroviral therapy (ART) patients may improve retention in care and reduce facility workload. We assessed long‐term retention among clinically stable ART patients attending six‐monthly clinical consultations (SMCC) with three‐monthly fast‐track drug refills, and estimated the number of consultations “saved” by this model of ART delivery in rural Malawi.

Methods

Stable patients (aged ≥18 years, on first‐line ART ≥12 months, CD4 count ≥300 cells/mL3, without opportunistic infections, not pregnant/breastfeeding) were eligible for SMCC, with three‐monthly drug refills from community health workers. Early enrollees were those starting SMCC within six months of eligibility, while late enrollees started at least 6 months after first eligibility. Kaplan–Meier methods were used to calculate cumulative probabilities of retention, stratified by timing of their enrolment and from first six‐monthly clinical consultation. Cox regression was used to measure attrition hazards from the first six‐monthly clinical consultation and risk factors for attrition, accounting for the time‐varying nature of their eligibility and enrolment in this model of care.

Results

From 2008 to 2015, 22,633 clinically stable patients from 11 facilities were eligible for SMCC for at least three months, contributing 74,264 person‐years of observation, and 18,363 persons (81%) initiated this model of care. The median time from eligibility to enrolment was 12 months and the median cumulative time on SMCC was 14.5 months. Five years after first SMCC eligibility, cumulative probabilities of retention were 85.5% (95% CI: 84.0% to 86.9%) among early enrollees and 93% (95% CI: 92.8% to 94.0%) among late enrollees. The cumulative probability of retention from first SMCC was 97.0% (95% CI: 96.7% to 97.3%) and 86% (95% CI: 85% to 87%) at one and five years respectively. Among eligible patients initiating SMCC, the adjusted hazards of attrition were 2.4 (95% CI: 2.0 to 2.8) times higher during periods of SMCC discontinuation compared to periods on SMCC. Male sex, younger age, more recent SMCC eligibility and WHO Stage 3/4 conditions in the past year were also independently associated with attrition from SMCC. Approximately 26,000 consultations were “saved” during 2014.

Conclusion

After five years, retention among patients attending SMCC was high, especially among women and older patients, and its scale‐up could facilitate universal access to ART.
Endometrial carcinoma: Evaluation using diffusion‐tensor imaging and its correlation with histopathologic findings
Authors: Yamada Ichiro , Wakana Kimio , Kobayashi Daisuke , Miyasaka Naoyuki , Oshima Noriko , Wakabayashi Akira , Saida Yukihisa , Tateishi Ukihide , Eishi Yoshinobu
Published: November 2018

Background

Although the prognosis of endometrial carcinoma (EMC) patients strictly depends on tumor invasion depth and its histologic grade, accurate preoperative assessment of these prognostic factors is often difficult.

Purpose

To determine the usefulness of diffusion‐tensor imaging (DTI) as a noninvasive method for evaluating tumor invasion depth and its histologic grade in patients with EMC.

Study Type

Prospective.

Population

Twenty‐five consecutive patients with histologically confirmed EMC who were surgically treated at our institution.

Field Strength/Sequence

DTI was performed with a 1.5T MRI system using a single‐shot echo‐planar imaging sequence with b values of 0 and 1000 s/mm2 and motion‐probing gradients in nine noncollinear directions.

Assessment

Fractional anisotropy (FA), mean diffusivity (MD), and axial diffusivity (AD) maps were analyzed by three observers and compared with histopathologic findings.

Statistical Tests

Dunnett's test, Spearman's rank correlation coefficient, and receiver operating characteristic (ROC) curve analyses.

Results

FA maps from all patients distinctly identified the junctional zone as a high‐FA zone (0.864 ± 0.037) that was significantly different from the endometrium and outer myometrium (0.251 ± 0.030 and 0.471 ± 0.091, respectively; P < 0.001). All EMCs were clearly depicted as hypointense areas on all DTI maps. AD maps provided the best tumor‐to‐uterus contrast, and EMCs (0.977 ± 0.120 × 10−3 mm2/s) had significantly lower AD values than all other layers of the normal uterine wall (2.166 ± 0.408, 2.010 ± 0.289, and 2.655 ± 0.203 × 10−3 mm2/s, respectively; P < 0.001). EMCs were clearly demarcated from the normal uterine wall, and DTI maps and histopathologic data yielded identical findings regarding tumor invasion depth. FA values showed a significant inverse correlation (r = –0.818; P < 0.001) with histologic grades 1, 2, and 3 of endometrioid adenocarcinomas.

Data Conclusion

In patients with EMC, DTI may be useful for evaluating tumor invasion depth and its histologic grade.

Level of Evidence: 1

Technical Efficacy: Stage 2

J. Magn. Reson. Imaging 2019;50:250–260.
The role of satellite glial cells in orofacial pain
Authors: Fan Wenguo , Zhu Xiao , He Yifan , Zhu Mengzhu , Wu Zhi , Huang Fang , He Hongwen
Published: November 2018

Some chronic pain conditions in the orofacial region are common, the mechanisms underlying which are unresolved. Satellite glial cells (SGCs) are the glial cells of the peripheral nervous system. In the sensory ganglia, each neuronal body is surrounded by SGCs forming distinct functional units. The unique structural organization enables SGCs to communicate with each other and with their enwrapped neurons via a variety of ways. There is a growing body of evidence that SGCs can influence the level of neuronal excitability and are involved in the development and/or maintenance of pain. The aim of this review was to summarize the latest advances made about the implication of SGCs in orofacial pain. It may offer new targets for the development of orofacial pain treatment.
Choice of reference climate conditions matters in impact studies: Case of bias‐corrected CORDEX data set
Authors: Dobor Laura , Hlásny Tomáš
Published: November 2018

Climate models have provided driving data for impact studies for decades. However, the uncertainties related to the use of such data have typically not been sufficiently considered. We investigate how CORDEX climate simulations, which were corrected for bias based on MESAN reanalysis data for the period of 1989–2010, match the gridded observational data set E‐OBS. Furthermore, we investigate whether the bias‐corrected simulations contain significant residual bias (RB), which we defined as the bias exceeding the range of the observational uncertainty (Uobs) that emerges from differences between the two data sets MESAN and E‐OBS. Because the reference period selected in climate change impact studies often differs from the period used for bias correction, we further investigated whether the RB and other performance metrics of the periods 1989–2010 and 1961–1990 differ. We conducted this assessment for whole Europe and for biogeographical zones.

Most of the used performance metrics show a good match of the simulations with MESAN in the period of 1989–2010. The comparison against E‐OBS yields worse results, indicating a significant difference between the two observational data sets. Minor bias exceeding the range of Uobs (RB) occurred over large land areas of Europe in this period. Based on the analysis conducted for the period of 1961–1990, the RB is several times larger than that of the period of 1989–2010; the other metrics also show worse performances.

Our findings imply that both the selection of the reference climate data set and reference period warrant greater attention in impact studies. In particular, we recommend researchers to use a bias correction period as reference period in their studies. Alternatively, a new bias correction should be applied if any different period is to be used as a reference.
Photothermal CH vibrational overtone detection by two‐color laser absorption
Authors: Diaz Marlon , Nyaupane Parashu R. , Diaz Ashley , Manzanares Carlos E.
Published: November 2018

In this experiment, the thermal lens technique is used with a modified arrangement of three lasers to induce a two‐color absorption. Two‐pump lasers, a variable wavelength orange dye laser (588–617 nm), a single line blue laser (488 nm), and a single line probe yellow laser (568 nm) are employed. A comparison is made between the magnitude of the thermal lens signal obtained with a one pump laser versus two pump lasers. The absorbing molecules are benzene and naphthalene in liquid n‐Hexane. The CH vibrational overtone spectra are obtained at room temperature for several concentrations. The molecules are excited to a high vibrational state (Δυ = 6) with the first laser and to an electronic level with a second laser (two‐color absorption). Using two pump lasers, the limit of detection of the molecule is several orders of magnitude more sensitive than using one pump laser. A nonlinear behavior of the integrated signal versus concentration is shown for the two‐color laser process. Linear behavior is shown for the one pump laser experiment. A model of signal amplification for a nonlinear absorption is presented to explain the results. The separation and identification of CH overtone bands in molecules and the sensitivity of the technique is emphasized to convey the potential use of CH overtone spectroscopy for imaging in thermal lens microscopy.