bluuebunny/crossref_metadata_2025 huggingface dataset:
A Singular System with Precise Dosing and Spatiotemporal Control of CRISPR‐Cas9
Authors: Manna Debasish , Maji Basudeb , Gangopadhyay Soumyashree A. , Cox Kurt J. , Zhou Qingxuan , Law Benjamin K. , Mazitschek Ralph , Choudhary Amit
Published: March 2019

Several genome engineering applications of CRISPR‐Cas9, an RNA‐guided DNA endonuclease, require precision control of Cas9 activity over dosage, timing, and targeted site in an organism. While some control of Cas9 activity over dose and time have been achieved using small molecules, and spatial control using light, no singular system with control over all the three attributes exists. Furthermore, the reported small‐molecule systems lack wide dynamic range, have background activity in the absence of the small‐molecule controller, and are not biologically inert, while the optogenetic systems require prolonged exposure to high‐intensity light. We previously reported a small‐molecule‐controlled Cas9 system with some dosage and temporal control. By photocaging this Cas9 activator to render it biologically inert and photoactivatable, and employing next‐generation protein engineering approaches, we have built a system with a wide dynamic range, low background, and fast photoactivation using a low‐intensity light while rendering the small‐molecule activator biologically inert. We anticipate these precision controls will propel the development of practical applications of Cas9.
Iodine‐promoted Intermolecular Dehydrogenation Diamination: Synthesis of Unsymmetrical α,β‐Diamido Ketones
Authors: Zhang YongJian , Su Junyi , Niu Wenjie , Li Yujin
Published: March 2019

Iodine‐promoted direct diamination of α,β‐unsaturated ketone to form two C−N bonds has been developed starting from chalcone and secondary amine. This reaction was performed in THF at 50 °C in the presence of I2 and K2CO3. The protocol is metal‐free, operationally simple and carried out under mild conditions, providing an effective new way for directing diamination reactions.
Robust recursive linear quadratic regulator for wheeled mobile robots based on optical motion capture cameras
Authors: Inoue Roberto S. , Terra Marco H. , Leão Willian M. , Nakai Maurício E.
Published: March 2019

In this paper, we deal with nonholonomic wheeled mobile robots (WMR) modeled as uncertain nonlinear systems. Sources of uncertainties can be due to erroneous estimation of mass, inertia, and center of gravity and due to payload time‐varying. They also can be considered as external disturbances generated from unstructured environments. We are proposing the use of a robust linear quadratic regulator (RLQR) to deal with tracking problems of WMR. In order to guarantee the effectiveness of this control approach, the robot posture is measured through a high‐precision motion capture system. This RLQR encompasses in a unified framework all state and output uncertain parameters of the system and does not depend on any auxiliary parameter to be tuned. It is useful to be used in online applications. Experimental results are presented with a comparative study among the R‐LQR, the nonlinear
control via game theory, and the standard proportional‐derivative controller plus computed torque (PD+CT).
“It kind of fosters a culture of interdependence”: A participatory appraisal study exploring participants' experiences of the democratic processes of a peer‐led organisation
Authors: Budge Gemma , Mitchell Annie , Rampling Terry , Down Patrick ,   The Bridge Collective
Published: March 2019

Peer‐led mental health organisations operate through participatory democracy, enabling participants to take an active role in decision making about the running of these organisations. U.K. national policy recommends increased involvement of people accessing statutory mental health services in service development, for example, through co‐production. This study employed a participatory research method to explore participants' perspectives of the democratic processes of a U.K.‐based peer‐led mental health organisation, The Bridge Collective, and the influence of these processes on participant wellbeing. A range of data collection methods were used to gather the perspectives of 16 participants. Participatory thematic analysis identified how the organisations' democratic processes both nurtured and challenged participants' wellbeing. Three main themes captured the influences of the democratic processes on participant wellbeing: (a) negotiating relationships, (b) feeling the responsibility of involvement, and (c) sharing power. The findings identify the value of democratic processes in enabling meaningful social support and empowerment, and also identify the challenges of inclusion and workload management in participatory democracy. These insights may inform the development of co‐production methods and enable The Bridge Collective and other peer‐led organisations to further develop their processes.
Fluorinated Nanographite as a Cathode Material for Lithium Primary Batteries
Authors: Wang Li , Li Yanyan , Wang Shuo , Zhou Pengfei , Zhao Zengdian , Li Xiaowei , Zhou Jin , Zhuo Shuping
Published: March 2019

Lithium/fluorinated carbon (Li/CFx) batteries face the problems of low rate performance and initial voltage delay. Herein, we propose a novel type of fluorinated nanographite as a cathode material for Li/CFx batteries through the direct fluorination of nanographite. The structure of fluorinated nanographite, including crystalline phase, particle size, fluorine content, and the properties of C−F bonding, strongly depend on the fluorination temperature. The fluorinated nanographite prepared at 450 °C (FG‐450) shows the highest specific capacity, 837.4 mAh g−1 at 10 mA g−1, along with a discharge plateau of 2.54 V, responding to an energy density of 2004.5 Wh kg−1. The highlights of the fluorinated nanographite are to deliver high rate performance and overcome the initial voltage delay. FG‐450 can be discharged at a high rate of about 3.6 C, delivering a high power density of 5460 W kg−1 with a remaining energy density of 1030.5 Wh kg−1. The good electrochemical performance of the FG‐450 sample is ascribed to the combined effect of its nanoparticle size, large specific surface area, and continuous stacking porosity.
A Chemiluminescent Metal–Organic Framework
Authors: Rühle Bastian , Virmani Erika , Engelke Hanna , Hinterholzinger Florian M. , von Zons Tobias , Brosent Birte , Bein Thomas , Godt Adelheid , Wuttke Stefan
Published: March 2019

The synthesis and characterization of a chemiluminescent metal–organic framework with high porosity is reported. It consists of Zr6O6(OH)4 nodes connected by 4,4′‐(anthracene‐9,10‐diyl)dibenzoate as the linker and luminophore. It shows the topology known for UiO‐66 and is therefore denoted PAP‐UiO. The MOF was not only obtained as bulk material but also as a thin film. Exposure of PAP‐UiO as bulk or film to a mixture of bis‐(2,4,6‐trichlorophenyl) oxalate, hydrogen peroxide, and sodium salicylate in a mixture of dimethyl and dibutyl phthalate evoked strong and long lasting chemiluminescence of the PAP‐UiO crystals. Time dependent fluorescence spectroscopy on bulk PAP‐UiO and, for comparison, on dimethyl 4,4′‐(anthracene‐9,10‐diyl)dibenzoate provided evidence that the chemiluminescence originates from luminophores being part of the PAP‐UiO, including the luminophores inside the crystals.
An effective Sorensen‐single linkage clustering hybrid algorithm for cell formation problems in cellular manufacturing industry
Authors: S Sathish , AR Lakshmanan , P Karuppuswamy , C Bhagyanathan
Published: March 2019

The paper presented here entails technique that is based upon Sorensen's similarity coefficient as well as the Sorensen‐ Single Linkage Clustering (SLC) algorithm, which essentially is a hybrid clustering approach that has been deployed here to show issue related to cell formation during the process of cellular engineering. In the following paper and study that has been presented here, the suggested hybrid algorithm comparison has been drawn versus the existing clustering algorithms and their performances have been compared specifically the MOD‐SLC modified single linkage or SLC also known as the single linkage clustering algorithm. The Sorensen‐SLC technique and the inferences drawn on the same show that it performs comparatively better when compared with the MOD‐SLC and SLC algorithms. Additionally, the computation that is necessary for this hybrid algorithm is absolutely a bare minimal and the computation processing is effective and easy.
An efficient model for quantifying the interaction between structural properties of software and hardware in the ARM big.LITTLE architecture
Authors: Stepanovic Srboljub , Georgakarakos Georgios , Holmbacka Simon , Lilius Johan
Published: March 2019

Heterogeneous architectures offer the opportunity to achieve high performance and energy efficiency by selecting appropriate cores for the execution of ever‐changing software applications. Appropriate core selection depends on the interaction between the structural properties of the software and the hardware that influences the performance of the software. We propose a model for efficient core selection when executing software on ARM's big.LITTLE heterogeneous architecture. It features a metric based on the correlation between the performance and the number of last‐level data cache (LLC) misses on a big and a LITTLE core. Additionally, our model defines a soft threshold in terms of the number of LLC misses, which determines efficient core selection. We verify the model using stress and variable workload benchmarks as well as two popular high‐throughput applications for mutlicore targets, namely, HEVC and LDPC decoders, profiled with X‐Mem, Linux perf, and PMCTrack dynamic tools. Results show that our model can be used for efficient core selection with a relatively small error probability.
Direct and indirect effects of land‐use intensification on ant communities in temperate grasslands
Authors: Heuss Lisa , Grevé Michael E. , Schäfer Deborah , Busch Verena , Feldhaar Heike
Published: March 2019

Land‐use intensification is a major driver of local species extinction and homogenization. Temperate grasslands, managed at low intensities over centuries harbored a high species diversity, which is increasingly threatened by the management intensification over the last decades. This includes key taxa like ants. However, the underlying mechanisms leading to a decrease in ant abundance and species richness as well as changes in functional community composition are not well understood. We sampled ants on 110 grassland plots in three regions in Germany. The sampled grasslands are used as meadows or pastures, being mown, grazed or fertilized at different intensities. We analyzed the effect of the different aspects of land use on ant species richness, functional trait spaces, and community composition by using a multimodel inference approach and structural equation models. Overall, we found 31 ant species belonging to 8 genera, mostly open habitat specialists. Ant species richness, functional trait space of communities, and abundance of nests decreased with increasing land‐use intensity. The land‐use practice most harmful to ants was mowing, followed by heavy grazing by cattle. Fertilization did not strongly affect ant species richness. Grazing by sheep increased the ant species richness. The effect of mowing differed between species and was strongly negative for Formica species while Myrmica and common Lasius species were less affected. Rare species occurred mainly in plots managed at low intensity. Our results show that mowing less often or later in the season would retain a higher ant species richness—similarly to most other grassland taxa. The transformation from (sheep) pastures to intensively managed meadows and especially mowing directly affects ants via the destruction of nests and indirectly via loss of grassland heterogeneity (reduced plant species richness) and increased soil moisture by shading of fast‐growing plant species.
The basic examination of the magnetic shielding structure to use for a magnetic rotation angle sensor
Authors: Musha Takeshi , Inujima Hiroshi
Published: March 2019

The magnetic rotation angle sensor has more merits such as small‐sized, low‐cost, and the low‐power consumption than the optical sensor. But the magnetic rotation angle sensor has the demerit to be weak to the disturbance magnetic field applied from outside the sensor, so the magnetic rotation angle sensor needs magnetic shielding structure. We proposed the magnetic shielding structure of the parallel plate type that is the simpler technique to the magnetic shielding structure of enclosing the whole sensor with the magnetic substance. We confirmed that the parallel plate type has almost the same shielding performance as the magnetic shielding structure of enclosing the whole sensor with the magnetic substance at the magnetic detecting device. We have made a prototype and evaluated angle detection error with the disturbance magnetic field. As a result, we confirmed that the error is 0.06° when 10 mT disturbance magnetic fields hang over the sensor.
Pressure‐Induced Vapor Synthesis of Carbon‐Encapsulated SiOx/C Composite Spheres with Optimized Composition for Long‐Life, High‐Rate, and High‐Areal‐Capacity Lithium‐Ion Battery Anodes
Authors: Han Meisheng , Yu Jie
Published: March 2019

SiOx exhibits a high specific capacity as anode materials for lithium‐ion batteries. However, it is still a challenge to achieve long life, high rate performance, and high areal capacity for the SiOx materials. Herein, carbon‐encapsulated SiOx/C composite spheres are prepared by a high pressure caused by heating SiOx/C spheres in pure dimethylformamide in a sealed vessel. The SiOx/C spheres with different compositions are synthesized by pyrolysis of different liquid siloxanes and hexamethyldisilane in a sealed vessel and subsequent heat treatment. The electrochemical performances are strongly dependent on the composition of the SiOx/C spheres. The specific capacity and initial coulombic efficiency (ICE) greatly increase, and cyclability slightly decreases with a decrease in the x value from 1.28 to 0.59. However, the capacity, ICE, and cyclability greatly decrease with a further decrease in the x value because of the formation of SiC. The carbon‐encapsulated SiO0.59/C spheres exhibit a high reversible capacity (1561.3 mAh g−1), an outstanding cyclability (0.0332% capacity loss per cycle during 500 cycles at 1 A g−1), a good rate performance (245.3 mAh g−1 at 10 A g−1), and a high areal capacity (4.08 mAh cm−2). Formation of the spherical morphology and carbon‐encapsulating layers is a result of the high vapor pressure generated at a high temperature.
Propose and analysis of an integrated biomass gasification‐CHAT‐ST cycle as an efficient green power plant
Authors: Hosseinpour Saeed , Mehdipour Ramin , Mirzahosseini Alireza Haji Seyed , Hemmasi Amir Hooman , Ozgoli Hassan Ali
Published: March 2019

Advanced combined cycles using gas turbine and bottoming cycles have been developed to improve energy efficiency and output power of the conventional thermal power plants. In this study, integrated biomass gasification‐cascaded humidification advanced turbine and steam turbine cycle have been presented as a novel approach to reach out the sustainable energy vision. All generators of this comprehensive system operate by syngas produced from biomass gasification. Based on the technical consideration, modeling and simulation of the mentioned cycle have been performed, which results indicated more than 33.6 MW power generation and about 56.4% total efficiency in the base case. Moreover, parametric studies demonstrated the considerable dependency of the delivered power, specific fuel consumption, and heat rate to ambient temperature variations. In addition, principal parameters changes due to the fluctuation of the gasification temperature demonstrated an obvious increase in fuel consumption rate after crossing a turning point. Eventually, other achievements such as the negative effect of biomass moisture increase on cycle outputs, and also, advantages of turbine inlet temperature rise have obtained by plant analyzes. © 2019 American Institute of Chemical Engineers Environ Prog, 38:e13146, 2019
Rethinking Higher Education: Integration as a Framework for Change
Authors: Birx Donald L.
Published: March 2019

This chapter discusses the overhaul of Plymouth State University using a framework of integration in all matters of decision‐making. This is an example of whole system reorganization where traditional independent structures have been replaced by integrated structures representing new ways of working together and integral experiences for students.
Winebrenner Theological Seminary: From Oppositional to Creative Agenda
Authors: Sleasman Brent C.
Published: March 2019

This chapter provides insight into the challenges facing higher education and provides a rationale for redesign along with effective strategies and management approaches, based upon the case study experience of Winebrenner Theological Seminary in Findlay, Ohio.
Performance study on the evaporation and pressure drop of low‐temperature refrigerant blends in porous media
Authors: Tarawneh Mohammad
Published: March 2019

An experimental investigation on the performance of different low‐temperature refrigerant blends is presented in this work. Five different low‐temperature refrigerant blends are put on display to replace the R22 refrigerant, which has a high ozone depletion potential. These five blends are R404A, R407C, R410A, R417A, and R422A. Different performance studies have been performed on these alternative refrigerants to replace R22. A comparative experimental performance study is performed during the evaporation of these refrigerant blends in porous media. A porous metallic heat transfer medium is used with different porosities (40%, 43%, and 45%) in the evaporator during the test experiments. The evaporator superheat and the condenser subcool are maintained constant throughout the experiments at 8°C (±0.5°C) and 6°C (±0.5°C), respectively. The condensing temperature is kept constant at 38.5°C, and the mean evaporating temperatures were selected to be from −33 to −18°C. The effect of the above‐mentioned given operating conditions on the compressor discharge temperature, evaporation pressure drop, evaporation capacity, and coefficient of performance of these five low‐temperature refrigerant blends has been analyzed for different porosities. This experimental study showed that the refrigerant R422A can give a similar or greater performance to R22 and R404A with a global warming effect and zero ozone depleting potential.
Estimation of streamflow recession parameters: New insights from an analytic streamflow distribution model
Authors: Santos Ana Clara , Portela Maria Manuela , Rinaldo Andrea , Schaefli Bettina
Published: March 2019

Streamflow recession analysis characterizes the storage‐outflow relationship in catchments. This relationship, which typically follows a power law, summarizes all catchment‐scale subsurface hydrological processes and has long been known to be a key descriptor of the hydrologic response. In this paper, we tested a range of common recession analysis methods (RAMs) and propose the use of an analytic streamflow distribution model as an alternative method for recession parameter estimation and to objectively compare different RAMs. The used analytical model assumes power law recessions, in combination with a stochastic process for streamflow triggering rainfall events. This streamflow distribution model is used in the present framework to establish reference values for the recession parameters via maximum likelihood estimation. The model‐based method has two main advantages: (a) joint estimation of both power law recession parameters (coefficient and exponent), which are known to be strongly correlated, and (b) parameter estimation based on all available streamflow data (no recession selection). The approach is applied to five rainfall‐dominated catchments in Switzerland with 40 years of continuous streamflow observations. The results show that the estimated recession parameters are highly dependent on methodological choices and that some RAMs lead to biased estimates. The recession selection method is shown to be of prime importance for a reliable description of catchment‐scale recession behaviour, in particular in presence of short streamflow records. The newly proposed model‐based RAM yields robust results, which supports the further development of this method for comparative hydrology and opens new perspectives for understanding the recession behaviour of catchments.
Aluminium in glacial meltwater demonstrates an association with nutrient export (Werenskiöldbreen, Svalbard)
Authors: Stachnik Łukasz , Yde Jacob C. , Nawrot Adam , Uzarowicz Łukasz , Łepkowska Elżbieta , Kozak Katarzyna
Published: March 2019

The aluminium (Al) cycle in glacierised basins has not received a great deal of attention in studies of biogeochemical cycles. As Al may be toxic for biota, it is important to investigate the processes leading to its release into the environment. It has not yet been ascertained whether filterable Al (passing through a pore size of 0.45 μm) is incorporated into biogeochemical cycles in glacierised basins. Our study aims to determine the relationship between the processes bringing filterable Al and glacier‐derived filterable nutrients (particularly Fe and Si) into glacierised basins. We investigated the Werenskiöldbreen basin (44.1 km2, 60% glacierised) situated in SW Spitsbergen, Svalbard. In 2011, we collected meltwater from a subglacial portal at the glacier front and at a downstream hydrometric station throughout the ablation season. The Al concentration, unchanged between the subglacial system and proglacial zone, reveals that aluminosilicate weathering is a dominant source of filterable Al under subglacial conditions. By examining the Al:Fe ratio compared with pH and the sulphate mass fraction index, we found that the proton source for subglacial aluminosilicate weathering is mainly associated with sulphide oxidation and, to a lesser degree, with hydrolysis and carbonation. In subglacial outflows and in the glacial river, Al and Fe are primarily in the forms of Al(OH)4‐ and Fe(OH)3. The annual filterable Al yield (2.7 mmol m‐2) was of a magnitude similar to that of nutrients such as filterable Fe (3.0 mmol m‐2) and lower than that of dissolved Si (18.5 mmol m‐2). Our results show that filterable Al concentrations in meltwater are significantly correlated to filterable and dissolved glacier‐derived nutrients (Fe and Si, respectively) concentrations in glaciers worldwide. We conclude that a potential bioavailable Al pool derived from glacierised basins may be incorporated in biogeochemical cycles, as it is strongly related to the concentrations and yields of glacier‐derived nutrients.
Assessing qualitative similarities between financial reporting frameworks using visualization and rules: COREP vs. pillar 3
Authors: Yang Wenmei , Koshiyama Adriano S.
Published: March 2019

Financial institutions are struggling with larger volume, more specific and greater frequency of regulatory reporting after the global financial crisis in 2008, especially those that need to report to multiple jurisdictions. To help to improve reporting efficiency, this paper aims to assess the existence of similarities between templates related to credit and counter party credit risk of COREP and Pillar 3 regulatory reporting frameworks by applying Correspondence Analysis and Association Rules Mining. Our results suggest a high degree of overlap between these reporting frameworks, more prominently the three business functions as Front office, Finance and Risk. These patterns can be used as guidance for financial institutions to reshape their reporting architecture.
IGFBP7 contributes to epithelial‐mesenchymal transition of HPAEpiC cells in response to radiation
Authors: Zhong Yazhen , Lin Zechen , Lin Xianlei , Lu Jinhua , Wang Nan , Huang Siyu , Wang Yuanyuan , Zhu Yuan , Shen Yiwei , Jiang Jing , Lin Shengyou
Published: March 2019

Radiation‐induced lung injury (RILI) frequently occurs in patients with thoracic malignancies. In response to radiation, alveolar epithelial cells (AEC) undergo epithelial‐mesenchymal transition (EMT) and contribute to the pathogenesis of RILI. Insulin‐like growth factor binding protein 7 (IGFBP7) is reported as a downstream mediator of transforming growth factor‐β1 (TGF‐β1) pathway, which plays a crucial role in radiation‐induced EMT. In the present study, the levels of IGFBP7 and TGF‐β1 were simultaneously increased in experimental RILI models and radiation‐treated AEC (human pulmonary alveolar epithelial cells [HPAEpic]). The expression of IGFBP7 in radiation‐treated HPAEpic cells was obviously inhibited by the specific inhibitor of TGF‐β receptor antagonist SB431542 and TGF‐β1 neutralizing antibody, and time‐dependently enhanced by TGF‐β1 treatment. Moreover, IGFBP7 knockdown significantly attenuated the effects of radiation on morphology change, cell migration, expression of EMT‐related markers (E‐cadherin, α‐SMA, and Vimentin), and phosphorylation of extracellular‐signal‐regulated kinase (ERK). The effects of IGFBP7 overexpression on the expression of EMT‐related markers were partially reversed by the ERK inhibitor PD98059. In conclusion, IGFBP7, was enhanced by TGF‐β1, may be involved in radiation‐induced EMT of AEC via the ERK signaling pathway, thus contributing to the pathogenesis of RILI.
Predicting unintentional weight loss in patients with gastrointestinal cancer
Authors: Yoon Saunjoo L. , Kim Jung A , Kelly Debra Lynch , Lyon Debra , George Thomas J.
Published: March 2019

Background

Unintentional weight loss is a major problem for patients with gastrointestinal (GI) cancers because it affects treatment, survival outcomes, and quality of life. To date, little is known about the trajectory of weight loss and the relationship between baseline body mass index (BMI), location of the cancer, and outcomes. The aims of this study were to investigate patterns of weight loss over time in patients with GI cancer according to BMI groups (low, normal, and high) and location of cancer.

Methods

We examined de‐identified electronic medical record data of 801 adults (>21 years) with GI cancer using ICD‐9 codes (150–159). Descriptive statistics and linear mixed models were used to examine unintentional weight loss over time by BMI group (low, normal, and high) and to determine the effect of primary cancer site and patient characteristics on weight loss.

Results

The mean age of patients was 66.5 ± 11.9 years (21–95 years), with 58% male and 86% White. Mean weight loss over 3 years was 21.39 kg. At the first observation point, 7.8% were in the low BMI group, 30.1% were in the normal, and 62% were in the high group. At the end of observation, a majority of deaths (35.5%) occurred in the low BMI group (BMI < 20 kg/m2). Significant weight loss was observed in patients with gastric (t = −5.11, P < 0.001), oesophageal (t = −4.18, P < 0.001), and pancreatic (35.8%, t = −3.58, P < 0.001) cancers. Predictors of weight change were gender (F = 64.93, P < 0.001), cancer stage (F = 7.28, P < 0.001), and site by days (F = 8.24, P < 0.001). Weight loss rates were similar among the three BMI groups, but patterns were different based on primary cancer type as a function of days within each group.

Conclusions

Weight loss in patients with GI cancers has implications for survival. Patients with upper GI cancers experienced more weight loss and decreased survival rates compared with patients with lower GI cancers. Patients with a combination of upper GI cancer (oesophagogastric or pancreatic) and low baseline BMI had the fewest survival days and worst patient outcomes. Early intervention for weight management plays a critical role for improving the health outcomes and fatality rates of these patients.
Vesicovaginal Fistula: Ultrasound Delineation and Pathological Correlation
Authors: Carrington Bernadette M , Johnson Richard J.
Published: March 2019

Worldwide, the most common cause of vesicovaginal fistula (VVF) is obstructed labor causing bladder ischemia, but in Western countries it occurs most often as a complication of gynecological surgery, especially abdominal hysterectomy.1 It may also occur as a complication of urological procedures—urethral dilatation, plastic bladder repair, and papilloma fulguration. Less common causes are trauma, sepsis, radiotherapy, and malignancy. It is a recorded complication of a large bladder calculus.2 We present a patient with carcinoma of the cervix in whom a VVF occurred immediately postradiotherapy. Ultrasound examination clearly demonstrated the position and size of the fistula.
Antenatal Diagnosis of Diastematomyelia
Authors: Caspi Benjamin , Gorbacz Sheldon , Appelman Zvi , Elchalal Uri
Published: March 2019

Diastematomyelia is a rare condition comprised of saggital division of the spinal cord into halves by either cartilagenous or bony spurs at any level of the spinal cord. It is usually associated with anomalous development of the vertebrae. We present a case demonstrating prenatal ultrasonographic features of diastematomyelia that was confirmed later by autopsy.
A Case of Cystitis Glandularis with Associated Pelvic Lipomatosis: Ultrasound Evaluation
Authors: Duffis Alvaris W. , Weinberg Brighita , Diakoumakis Evangelos E.
Published: March 2019

Cystitis glandularis is an uncommon cystitis where chronic irritation to the bladder results in proliferation of the epithelium and replacement of the submucosa with glandular elements.1 This cystitis is more pronounced at the ureterovesical junction, thus causing ureteral obstruction with subsequent renal failure. Cystitis glandularis is known to be associated with pelvic lipomatosis, a benign proliferative process that involves the perivesicular retroperineum with varying effects upon the adjacent organs.2 The following case report is an example of the latter association.
Ultrasonography of Intestinal Ascaris
Authors: Peck R. J.
Published: March 2019

Ascariasis is an infection involving the large roundworm Ascaris lumbricoides. It is estimated that one‐quarter of the world's population is infected with ascaris.1 Clinical manifestations may result from the migration of larvae through the lungs and from the presence of adult worms in the small intestine, biliary ducts, and pancreatic ducts. The adult worms may measure up to 45 em in length.
A constitutive knockout of murine carbamoyl phosphate synthetase 1 results in death with marked hyperglutaminemia and hyperammonemia
Authors: Khoja Suhail , Nitzahn Matthew , Truong Brian , Lambert Jenna , Willis Brandon , Allegri Gabriella , Rüfenacht Véronique , Häberle Johannes , Lipshutz Gerald S.
Published: March 2019

The enzyme carbamoyl phosphate synthetase 1 (CPS1; EC 6.3.4.16) forms carbamoyl phosphate from bicarbonate, ammonia, and adenosine triphosphate (ATP) and is activated allosterically by N‐acetylglutamate. The neonatal presentation of bi‐allelic mutations of CPS1 results in hyperammonemia with reduced citrulline and is reported as the most challenging nitrogen metabolism disorder to treat. As therapeutic interventions are limited, patients often develop neurological injury or die from hyperammonemia. Survivors remain vulnerable to nitrogen overload, being at risk for repetitive neurological injury. With transgenic technology, our lab developed a constitutive Cps1 mutant mouse and reports its characterization herein. Within 24 hours of birth, all Cps1
−/− mice developed hyperammonemia and expired. No CPS1 protein by Western blot or immunostaining was detected in livers nor was Cps1 mRNA present. CPS1 enzymatic activity was markedly decreased in knockout livers and reduced in Cps1+/−mice. Plasma analysis found markedly reduced citrulline and arginine and markedly increased glutamine and alanine, both intermolecular carriers of nitrogen, along with elevated ammonia, taurine, and lysine. Derangements in multiple other amino acids were also detected. While hepatic amino acids also demonstrated markedly reduced citrulline, arginine, while decreased, was not statistically significant; alanine and lysine were markedly increased while glutamine was trending towards significance. In conclusion we have determined that this constitutive neonatal mouse model of CPS1 deficiency replicates the neonatal human phenotype and demonstrates the key biochemical features of the disorder. These mice will be integral for addressing the challenges of developing new therapeutic approaches for this, at present, poorly treated disorder.
Enzyme replacement therapy outcomes across the disease spectrum: Findings from the mucopolysaccharidosis VI Clinical Surveillance Program
Authors: Harmatz Paul R. , Lampe Christina , Parini Rossella , Sharma Reena , Teles Elisa L. , Johnson Julie , Sivam Debbie , Sisic Zlatko
Published: March 2019

The impact of galsulfase enzyme replacement therapy in patients with mucopolysaccharidosis (MPS) VI with phenotypes at either end of the disease spectrum was evaluated. The MPS VI Clinical Surveillance Program (CSP) was established to collect long‐term observational data from routine clinical and laboratory assessments. A subanalysis of the CSP was performed in patients with pretreatment urinary glycosaminoglycan (uGAG) levels <100 μg/mg and ≥200 μg/mg creatinine (low‐ and high‐uGAG) who had received galsulfase for ≥6 months. uGAG, 6‐minute walk test (6MWT), 3‐minute stair climb test (3MSCT), pulmonary function measures, height/growth, cardiac function, and safety were evaluated. Patients with a high‐uGAG level at pre‐treatment baseline (N = 68) showed greater impairments in endurance and pulmonary function than those with low‐baseline uGAG levels (N = 39). From pre‐treatment baseline, the distance walked on the 6MWT in the low‐ and high‐uGAG groups increased by a mean (±SD) of 49 (±151) meters and 42 (±165) meters (median follow‐up 5.5 and 7.7 years), respectively. The number of stairs/min climbed in the 3MSCT in the low‐ and high‐uGAG groups increased by a mean of 18 (±33) and 30 (±45) (median follow‐up 2.8 and 3.5 years), respectively. Overall, pulmonary function remained unchanged for both groups. No impact was seen on cardiac function. Galsulfase was generally well tolerated in both groups, with most adverse events being MPS‐related complications unrelated to galsulfase. Results of this CSP sub‐analysis suggest that galsulfase stabilizes MPS VI in the long‐term and has an acceptable safety profile, regardless of baseline disease severity.
Implementation of radiation therapist cylinder insertion for vaginal vault brachytherapy
Authors: Paterson Dean B. , Pearson Shelley M. , Johnson Carol A.
Published: March 2019

Vaginal vault brachytherapy is a common treatment for endometrial cancer. Historically, applicator insertion has been the domain of a radiation oncologist (RO). This commentary outlines a project to improve efficiency and workforce utilisation by introducing a competency framework and training module allowing entitled radiation therapists to perform single‐channel cylinder applicator insertions and treatment delivery under RO supervision for fraction one and without supervision for subsequent fractions. The rationale, relevant regulations, implementation process and barriers are explored.
Measurement and analysis on the accommodation responses to real‐mode, virtual‐mode, and focused‐mode integral imaging display
Authors: Chen Cong , Deng Huan , Wang Qiong‐Hua , Song Yu‐Tong
Published: March 2019

Integral imaging has three display modes including real mode, virtual mode, and focused mode, and each mode has unique display characteristics. In this paper, the accommodation responses to the three‐dimensional (3‐D) targets reconstructed by each mode of the integral imaging display were measured and statistically analyzed. Through the least square method, standard deviation analysis, and t‐test analysis, we found that the accommodation responses to the 3‐D target reconstructed by the focused mode was more similar to that of the real target on the same depth position. Moreover, the closer to the central depth plane was, the steadier accommodation response 3‐D targets could provide. These statistical analysis results are helpful to the design of integral imaging display device.
RASSF10 suppresses lung cancer proliferation and invasion by decreasing the level of phosphorylated LRP6
Authors: Han Xu , Dong Qianze , Wu Jingjing , Luo Yuan , Rong Xuezhu , Han Qiang , Zheng Xiaoying , Wang Enhua
Published: March 2019

Ras‐association domain family (RASSF) proteins exert distinct cellular functions. The expression of RASSF10 in non–small cell lung cancer and its underlying mechanism have not been reported. Herein, we explored the roles of RASSF10 in lung cancer cells and potential molecular mechanisms. We found low RASSF10 expression in lung cancer specimens, which was associated with low differentiation, advanced pTNM stage, positive lymph node metastasis, and poor prognosis in patients. Furthermore, RASSF10 overexpression inhibited the proliferation and invasion of lung cancer cells, which was the result of Wnt signaling suppression. However, we found that RASSF10 had no influence on Hippo signaling, while RASSF10 bound to LRP6 via the coiled‐coil domains and reduced p‐LRP6 level, eventually prohibiting β‐catenin nuclear translocation. However, deleting the coiled‐coil domains ablated this function. These findings expound the interaction between RASSF10 and LRP6 and uncover a potential link between N‐terminal RASSFs and the Wnt pathway.
Finite‐time synchronization of memristive neural networks with time‐varying delays via two control methods
Authors: Li Xiaofan , Fang Jian‐an , Li Huiyuan
Published: March 2019

In this paper, on the basis of the Lyapunov stability theory and finite‐time stability lemma, the finite‐time synchronization problem for memristive neural networks with time‐varying delays is studied by two control methods. First, the discontinuous state‐feedback control rule containing integral part for square sum of the synchronization error and the discontinuous adaptive control rule are designed for realizing synchronization of drive‐response memristive neural networks in finite time, respectively. Then, by using some important inequalities and defining suitable Lyapunov functions, some algebraic sufficient criteria guaranteeing finite‐time synchronization are deduced for drive‐response memristive neural networks in finite time. Furthermore, we give the estimation of the upper bounds of the settling time of finite‐time synchronization. Lastly, the effectiveness of the obtained sufficient criteria guaranteeing finite‐time synchronization is validated by simulation.
Oxidative Stress and Dysfunctional Intracellular Traffic Linked to an Unhealthy Diet Results in Impaired Cargo Transport in the Retinal Pigment Epithelium (RPE)
Authors: Keeling Eloise , Chatelet David S. , Johnston David A. , Page Anton , Tumbarello David A. , Lotery Andrew J. , Ratnayaka J. Arjuna
Published: March 2019

Scope

Oxidative stress and dysregulated intracellular trafficking are associated with an unhealthy diet which underlies pathology. Here, these effects on photoreceptor outer segment (POS) trafficking in the retinal pigment epithelium (RPE), a major pathway of disease underlying irreversible sight‐loss, are studied.

Methods and results

POS trafficking is studied in ARPE‐19 cells using an algorithm‐based quantification of confocal‐immunofluorescence data supported by ultrastructural studies. It is shown that although POS are tightly regulated and trafficked via Rab5, Rab7 vesicles, LAMP1/2 lysosomes and LC3b‐autophagosomes, there is also a considerable degree of variation and flexibility in this process. Treatment with H2O2 and bafilomycin A1 reveals that oxidative stress and dysregulated autophagy target intracellular compartments and trafficking in strikingly different ways. These effects appear limited to POS‐containing vesicles, suggesting a cargo‐specific effect.

Conclusion

The findings offer insights into how RPE cells cope with stress, and how mechanisms influencing POS transport/degradation can have different outcomes in the senescent retina. These shed new light on cellular processes underlying retinopathies such as age‐related macular degeneration. The discoveries reveal how diet and nutrition can cause fundamental alterations at a cellular level, thus contributing to a better understanding of the diet‐disease axis.
In situ postmortem ethanol quantification in the cerebrospinal fluid by non‐water‐suppressed proton MRS
Authors: Zoelch Niklaus , Hock Andreas , Steuer Andrea E. , Heimer Jakob , Kraemer Thomas , Thali Michael J. , Gascho Dominic
Published: March 2019

Determination of the ethanol concentration in corpses with MRS would allow a reproducible forensic assessment by which evidence is collected in a noninvasive manner. However, although MRS has been successfully used to detect ethanol in vivo, it has not been applied to postmortem ethanol quantification in situ. The present study examined the feasibility of the noninvasive measurement of the ethanol concentration in human corpses with MRS. A total of 15 corpses with suspected alcohol consumption before demise underwent examination in a 3 T whole body scanner. To address the partial overlap of the ethanol and lactate signal in the postmortem spectrum, non‐water‐suppressed single voxel spectra were recorded in the cerebrospinal fluid (CSF) of the left lateral ventricle via the metabolite cycling technique. The ethanol signals were quantified using the internal water as reference standard, as well as based on a reference signal acquired in a phantom. The measured values were compared with biochemically determined concentrations in the blood (BAC) and CSF (CSFAC). In 8 of the 15 corpses a BAC above zero was determined (range 0.03–1.68 g/kg). In all of these 8 corpses, ethanol was measured in CSF with the proposed MRS protocol. The two applied MRS calibration strategies resulted in similar concentrations. However, the MRS measurements generally overestimated the ethanol concentration by 0.09 g/kg (4%) to 0.72 g/kg (45%) as compared with the CSFAC value. The presented MRS protocol allows the measurement of ethanol in the CSF in human corpses and provides an estimation of the ethanol concentration prior to autopsy. Observed deviations from biochemically determined concentrations are mainly explained by the approximate correction of the relaxation attenuation of the ethanol signal.
The magnitude and predictors of therapy abandonment in pediatric central nervous system tumors in low‐ and middle‐income countries: Systematic review and meta‐analysis
Authors: Seah Tiffany , Zhang Chuer , Halbert Jay , Prabha Shashi , Gupta Sumit
Published: March 2019

Background

Outcomes of pediatric central nervous system (CNS) tumors in low‐ to middle‐income countries (LMIC) are poorer than their high‐income counterparts. Abandonment of therapy is increasingly recognized as a key contributor to this disparity, but has been poorly quantified. We performed a meta‐analysis to determine the magnitude of abandonment in pediatric CNS tumors in LMIC, and risk factors and interventions aimed at reducing this.

Patients and methods

We searched seven databases for pediatric CNS tumor cohorts followed up from diagnosis and treated in LMIC. All languages were included. Two reviewers independently selected articles and extracted data on abandonment rates (ARs) and predictors. The authors were contacted for additional information.

Results

Of 50 660 publications, 643 in five languages met criteria for full review; 131 met analysis inclusion criteria. ARs were not reported in the majority, and a small number were available from the authors. Available ARs ranged from 0% to 59%, from 38 studies (2497 children in 14 countries), and these were quantitatively analyzed. Lower‐middle‐income countries had higher ARs than upper‐middle‐income countries (27%, 95% confidence interval [CI] 20%–36% vs 9%, 95% CI 6%–14%, P < 0.0001), with significant heterogeneity within each (LMIC I2 = 78%, P < 0.00001, UMIC I2 = 85%, P < 0.00001). Common predictors for abandonment included distance to treatment centers, financial hardship, and prognostic misconceptions.

Conclusion

In LMICs, ARs are highest in lower‐MICs. However, the paucity of published data limits further evaluation. Given the increasing burden of pediatric CNS tumors in LMIC, addressing deficits in abandonment reporting is critical. Consistent reporting is needed for developing interventions to improve outcomes.
Oseltamivir phosphate—Lifting the restriction on its use to treat teenagers with influenza in Japan
Authors: Takeuchi Satoshi , Tetsuhashi Masashi , Sato Daisaku
Published: March 2019

Purpose

In 2007, Ministry of Health, Labour and Welfare (MHLW) warned to refrain from prescribing oseltamivir for teenagers when two Japanese teenagers with influenza fell from a high‐rise building after taking oseltamivir. Revisions of the warning texts of anti‐influenza drugs were discussed by the Subcommittee of Pharmaceutical Affairs and Food Sanitation Council, MHLW, based on the studies and trends of anti‐influenza medication over the last 10 years.

Method

The research group led by Dr Nobuhiko Okabe conducted nationwide survey since the 2007/2008 influenza season. The results of Japanese and foreign epidemiological and non‐clinical studies of abnormal behaviors in influenza patients since 2009 were reviewed.

Result

Severe abnormal behaviors have been reported in influenza patients taking all types of anti‐influenza drugs, as well as in untreated patients. There are some risks to patients whether treated with any anti‐influenza drug, or non‐treated though it is still not possible to rule out a potential causal relationship between abnormal behaviors and anti‐influenza drugs. 70% of abnormal behaviors occurred within two days after the onset of fever. No difference was found between anti‐influenza drugs treated and non‐treated patients. In patients receiving oseltamivir and other anti‐influenza drugs, the frequency of abnormal behaviors is not clearly different between teenagers and patients under 10 years old.

Conclusion

The specific “boxed warning” and the restriction only for oseltamivir that should not be used for teenagers was lifted. Therefore, the labeling of all anti‐influenza drugs carry a consistent warning about the potential for abnormal behaviors in Japan.
Flowering plant immune repertoires expand under mycorrhizal symbiosis
Authors: Kramer Eric M. , Statter Samantha A. , Yi Ho Jun , Carlson Joseph W. , McClelland Donald H. R.
Published: March 2019

Immune perception in flowering plants is mediated by a repertoire of cytoplasmic and cell‐surface receptors that detect invading microbes and their effects on cells. Here, we show that several large families of immune receptors exhibit size variations related to a plant's competence to host symbiotic root fungi (mycorrhiza). Plants that do not participate in mycorrhizal associations have significantly smaller immune repertoires, while the most promiscuous symbiotic hosts (ectomycorrhizal plant species) have significantly larger immune repertoires. By contrast, we find no significant increase in immune repertoire size among legumes competent to form a symbiosis with nitrogen‐fixing bacteria (rhizobia). To explain these observations, we hypothesize that plant immune repertoire size expands with symbiote species diversity.