bluuebunny/crossref_metadata_2025 huggingface dataset:
The Design and Application of a Track-type Autonomous Inspection Robot for Electrical Distribution Room
Authors: Cheng Min , Xiang Dao
Published: May 2019

Electrical distribution equipment inspection is crucial for the electric power industry. With the rapid increase in the number of electrical distribution rooms, an unattended inspection method, for example, autonomous inspection robot, is eagerly desired by the industry to make up for the deficiencies of traditional manual inspection in effectiveness and validity. Existing inspection robots designed for indoor substations are generally lack of practicality, due to the factors such as inspection requirements and robot weight. To bridge the gap between prototype and practicality, in this work, we design the first completely autonomous robotic system, LongSword, which provides a satisfying technical solution for equipment inspection with an optical zoom camera, a thermal imaging camera or a partial discharge detector. Firstly, we design a novel and flexible hardware architecture which allows the robot to move, lift, and rotate in the station to reach any desired position. Secondly, we develop an intelligent software framework which consists of several modules to achieve accurate equipment recognition and reliable failure diagnosis. Thirdly, we achieve an apposite integration of the existing technologies to implement an applicable robotic system that can fulfill the requirements of indoor equipment inspection. There are over 200 LongSwords currently serving about 160 electrical distribution rooms, some of which have been working for more than 1 year. The average precision of device status recognition is up to 99.70%, and the average inspection time of a single device is as short as 13.5 s. The feedback from workers shows that LongSword can significantly improve the efficiency and reliability of equipment inspection, which accelerates the process of setting up unmanned stations.
A Study on Vibrations of Hexarot-Based High-G Centrifugal Simulators
Authors: Pedrammehr Siamak , Asadi Houshyar , Nahavandi Saeid
Published: May 2019

This paper investigates the vibrations of hexarot simulators. The generalized modeling of kinematics and dynamics formulation of a hexarot mechanism is addressed. This model considers the flexible manipulator with the base motion. The dynamic formulation has been developed based on the principle of virtual work. The dynamic model consists of the stiffness of the different parts of the mechanism, the effects of gravity and inertia, torque and force related to the joints viscous friction. Finally, the response of the end effector at various frequencies has been presented, and the vibrations of the mechanism and the dynamic stability index have been investigated.
Remote sensing of the Tay Estuary using visible and near-infrared data: mapping of the inter-tidal zone
Authors: Cracknell A. P. , Hayes L. W. B. , Keltie G. F.
Published: May 2019

Synopsis

The coastal zone is being seen increasingly as a major resource requiring the planning of its use to accommodate the many and frequently conflicting demands placed upon it. In the U.K. this planning is complicated by the difficulties arising from the scale, map projection and quality of information provided by the different mapping agencies. These difficulties are compounded because the representation of information concerning the littoral is quickly outdated by the dynamic coastal processes operating in this zone. This paper presents the results of an investigation of the use of digital remote sensing and mapping techniques, using data from a set of LANDSAT MSS scenes corresponding to different tidal states, for mapping within the coastal zone where regular and possibly cyclic map revision is required.
The nature and distribution of the suspended load of the middle Tay Estuary
Authors: Hubbard Fred H. , Hashim Majid H. A.
Published: May 2019

Synopsis

The suspended loads at three stations in the middle estuary of the River Tay have been analysed monthly, at low and high water of the spring tides, over the period June 1983 to May 1984. Major mineral modal analyses were derived from bulk and mineral oxide analyses. The concentrations in the suspended loads of the trace metals Cr, Cu, Pb and Zn were determined. An efficient circulatory system operates within the middle estuary which largely retains the suspended loads acquired from the inner estuary, even at seasonal periods of high influx. The major mineral assemblage is quartz, chlorite, illite and kaolinite. There is some preferential landward return of quartz and chlorite. Chromium has an association with chlorite, while copper, lead and zinc seem linked with suspended particulate organic matter which, at least in part, is derived from sewage disposal into the estuary. Dissolved zinc is associated with dissolved organic matter.
The physical geography and geology of the estuary and Firth of Forth, Scotland
Authors: Browne Michael A. E.
Published: May 2019

Synopsis

The Upper Palaeozoic bedrock, which is of sedimentary and volcanic origin, is briefly described. The origin of the Forth as a series of depressions in the bedrock surface probably owes much to erosion of a pre-existing Tertiary landscape during phases of Quaternary glaciation. The late Quaternary history of the area is described, relating the distribution of the sediments deposited in the Forth to climatic events and changes in relative sea-level. Since the acme of the last main glaciation about 20,000 years ago, late Devensian marine and estuarine sediments have been deposited on the underlying glacial till sheet at altitudes ranging from more than 120 m below O.D. to at least 46 m above O.D. Similarly, raised and buried beaches and their deposits occur at altitudes from 40 m above O.D. down to around 10 m below O.D. in the estuary. During the Flandrian, sea-level has fluctuated, reaching its maximum (about 11 to 15 m above O.D.) about 6500 years ago. The typical deposit of this period is the carse clay which forms a series of extensive, fertile raised mudflats around the estuary. The calcareous marine faunas of the carse clay and older deposits are outlined.
Water circulation in the Firth of Forth, Scotland
Authors: Dyke P. P. G.
Published: May 2019

Synopsis

The Firth of Forth, in terms of physical oceanography, is part of the North Sea. The general circulation pattern in the firth must be regarded as largely speculative. There have been insufficient measurements of insufficient quality, and what evidence exists leads to the view that what circulation there is, is sluggish and varies from season to season and from year to year.

A description is given of the three principal mechanisms that contribute to circulation. Tides, due initially to astronomical forces, manifest themselves in the Firth of Forth through the rise and fall of the adjacent open sea. This rise and fall, periodic in mid ocean, is no longer strictly so in the firth and neither are the tidal currents. The wind-driven currents in the sea are influenced by the earth's rotation. In the Firth of Forth, some of this influence is retained. Naturally, wind-driven currents are larger near the surface. Finally, when water of different densities meets, overturning causes convection currents. All of these effects are present to some extent in the Firth of Forth. In addition, specific account has to be taken of complicated coastal and bottom topography and river outflow. Some attempt to bring together these effects and available measurements is made in this paper. Lastly, several theoretical models are proposed which account for the magnitudes and directions of the observed steady circulation. Mathematical details are given in appendices.
Contamination and effects of hydrocarbons on the Forth ecosystem, Scotland
Authors: Elliott M. , Griffiths A. H.
Published: May 2019

Synopsis

Since 1924 the Forth has received effluent from Scotland's major petrochemical industry and refinery in addition to hydrocarbon inputs from many other sources. The firth shows no major effects of this, but the history of inputs, together with the estuary's physical characteristics, have created a large residue of hydrocarbon contaminants especially in its sediments. This paper gives the degree and gradients of contamination in several components and describes the effect of hydrocarbon contaminants on the ecosystem structure.

The major inputs have produced localised lethal effects, in that productive estuarine intertidal habitat has been lost or its functioning altered. The changes are primarily due to organic enrichment with only very near-field toxic effects. Some of the effects result from historical contamination, but existing discharges continue to have a deleterious effect. New petrochemical discharges in both firth and estuary appear to have a minimal impact, although the historical contamination makes it difficult to assess their effects.
The intertidal benthos and sediments of particulate shores in the Firth of Forth, Scotland, with particular reference to waste water discharges
Authors: Read Paul
Published: May 2019

Synopsis

The paper summarises and briefly discusses published and unpublished data relating to the physicochemical characteristics of the sediments and the occurrence and distribution of the intertidal macrobenthos of paniculate shores in the Firth of Forth. In general, the shores described are poor faunistically and in some areas this results partly from the influence of waste water discharges. Detailed information is available for only a limited number of the numerous beaches in the Firth of Forth. In consequence, this paper focusses attention on the results of a long term study of four beaches along the south shore of the firth which was undertaken as part of an environmental impact assessment in relation to the introduction of improved sewage treatment and disposal for the City of Edinburgh. Edinburgh Sewage Scheme and the firth into which it discharges are briefly described and data pertaining to changes in the intertidal sediments and the intertidal macrobenthic communities, which occurred in the Seafield Bay area of the firth following pollution abatement, are presented and discussed.
Fishery studies in the estuary and Firth of Forth, Scotland
Authors: Poxton M. G.
Published: May 2019

Synopsis

Recent fishery studies in the estuary and Firth of Forth stem from the late 1970s and have largely been carried out by the Institute of Terrestrial Ecology, the Forth River Purification Board and Heriot-Watt University. This paper briefly reviews these studies, which may loosely be divided into work done at power stations, general demersal and pelagic studies of the estuarine fish populations, studies on particular species (lamprey, eelpout, whiting, cod and flatfish, especially the plaice), pollution- orientated studies (hydrocarbons in flatfish and mercury in eelpout) and more general work including ichthyoplankton surveys. Most work has been done on the ecology of flatfish, especially the plaice and it is examined in most detail.

A total of fifty species of fish have been recorded of which thirty-six occurred in the estuary and thirty-nine in the firth. Others are however known to occur. Of the twenty-eight species entrained into the intakes of local power stations, the sprat, herring, whiting and sand goby were most numerous, while other common species were sandeels, eelpout and pogge. Sand gobies, whiting, common dabs and sprats were the most numerous species taken by Agassiz trawling with herring, cod, eelpout, butterfish, pogge, flounders and plaice also commonly taken. Only herring, sprat, whiting, cod and fatherlasher were recorded using a midwater trawl and only the clupeoids occurred in all the catches. The catches of the 2 m beam trawl used in sandy bays in the firth were dominated by plaice, common dabs, sand gobies and sandeels. The ichthyoplankton surveys undertaken in 1986 have caught twenty-three species as eggs and twelve species as larvae. The majority of the eggs were those of the common dab, whiting, flounder, rock ling and sprat, while the majority of larvae were sandeels and clupeoids.
Selection and management of sites of nature conservation importance in the Forth estuary and Firth, Scotland
Authors: Gordon Nancy J.
Published: May 2019

Synopsis

The Forth is of great importance for nature conservation. More than half of the coastline of the estuary and the Firth of Forth is assessed to be sufficiently important for designation as Sites of Special Scientific Interest (SSSIs). The basis of the selection of these sites is discussed. The SSSIs are then described, including those which are managed as nature reserves. Wider aspects of conservation in the Forth are referred to. The main threats to wildlife sites and species are indicated, together with possible solutions, and opportunities for conservation.
Scotland's energy demands
Authors: Miller D. J.
Published: May 2019

Synopsis

The main features of energy demand in Scotland are described and compared, in respect of total energy use and the shares supplied by the different fuels, with the figures for the United Kingdom and other countries. Recent trends in demand are examined to illustrate how the present position has been reached and factors likely to influence each fuel's share in the future are outlined. The role of the energy industries themselves is discussed and the scope for new initiatives by these industries indicated.
The availability of gas
Authors: Probert W. R.
Published: May 2019

Synopsis

This paper considers market fundamentals rather than privatisation, which is largely about organisation. During the last ten years there has been significant growth in the size of the world's remaining proven gas reserves. The proven reserve production ratio has been growing and is now sixty years. Beyond proven reserves there are reserves in the “probable” and “possible” categories. Within Western Europe, gas reserves are principally located in Norway, the Netherlands and the United Kingdom. Additional reserves are accessible to Western Europe. For the United Kingdom, gas supplies are probably ample in the short to medium term. In the longer term there is likely to be a need for imports but there are various potential suppliers. At the Church House debate in 1976 many were obsessed with “energy gaps”; today's conventional wisdom is “market forces”. Energy forecasts have proved inaccurate, but gas demand has been fairly close to projections. Over the last ten years the role of gas in energy markets has been growing, such that gas is now the major fuel in non-transport energy demand. Gas now dominates the domestic market for energy in Britain. Growth in customers continues in Scotland and the rest of Britain. Nevertheless, there is fierce competition in the domestic market with millions of decisions taken on acquiring and replacing appliances each year. The growing role of gas in Scottish and British industrial and commercial markets is discussed, with faster growth overall in demand in Scotland than Britain as a whole. The recession has had its effect but gas suffered less than some other fuels. Growth in gas demand from industry has resumed. Great emphasis is placed upon improving the efficiency of gas use. Used wisely, an availability of gas is foreseen on a long term basis.
Radiation studies
Authors: Curran Samuel
Published: May 2019

Our President, Sir Alwyn Williams, asked me to act for him in this last element of our Symposium and he stressed that I should tell you how unhappy he was to be absent today.

I found myself reflecting on some possible reasons for the invitation to me to deputise. The most obvious is perhaps my seniority as a Fellow of the Royal Society of Edinburgh. I have been a Fellow for almost forty years. In addition, and more pertinent to my immediate task, for over fifty years I have been involved in research, or close to research, in nuclear science and particularly concerned with research on penetrating radiation. I trust this qualifies me to discuss some important trends.
ACCURATE, ENERGY-EFFICIENT CLASSIFICATION WITH SPIKING RANDOM NEURAL NETWORK
Authors: Hussain Khaled F. , Bassyouni Mohamed Yousef , Gelenbe Erol
Published: May 2019

Artificial Neural Networks (ANNs)-based techniques have dominated state-of-the-art results in most problems related to computer vision, audio recognition, and natural language processing in the past few years, resulting in strong industrial adoption from all leading technology companies worldwide. One of the major obstacles that have historically delayed large-scale adoption of ANNs is the huge computational and power costs associated with training and testing (deploying) them. In the mean-time, Neuromorphic Computing platforms have recently achieved remarkable performance running the bio-realistic Spiking Neural Networks at high throughput and very low power consumption making them a natural alternative to ANNs. Here, we propose using the Random Neural Network, a spiking neural network with both theoretical and practical appealing properties, as a general purpose classifier that can match the classification power of ANNs on a number of tasks while enjoying all the features of being a spiking neural network. This is demonstrated on a number of real-world classification datasets.
SCHEDULING IN A SINGLE-SERVER QUEUE WITH STATE-DEPENDENT SERVICE RATES
Authors: Ayesta Urtzi , Prabhu Balakrishna , Righter Rhonda
Published: May 2019

We consider single-server scheduling to minimize holding costs where the capacity, or rate of service, depends on the number of jobs in the system, and job sizes become known upon arrival. In general, this is a hard problem, and counter-intuitive behavior can occur. For example, even with linear holding costs the optimal policy may be something other than SRPT or LRPT, it may idle, and it may depend on the arrival rate. We first establish an equivalence between our problem of deciding which jobs to serve when completed jobs immediately leave, and a problem in which we have the option to hold on to completed jobs and can choose when to release them, and in which we always serve jobs according to SRPT. We thus reduce the problem to determining the release times of completed jobs. For the clearing, or transient system, where all jobs are present at time 0, we give a complete characterization of the optimal policy and show that it is fully determined by the cost-to-capacity ratio. With arrivals, the problem is much more complicated, and we can obtain only partial results.
Comparison of contrast sensitivity in macaque monkeys and humans
Authors: Ridder William H. , Zhang Kai Ming , Karsolia Apoorva , Engles Michael , Burke James
Published: May 2019

Contrast sensitivity functions reveal information about a subject’s overall visual ability and have been investigated in several species of nonhuman primates (NHPs) with experimentally induced amblyopia and glaucoma. However, there are no published studies comparing contrast sensitivity functions across these species of normal NHPs. The purpose of this investigation was to compare contrast sensitivity across these primates to determine whether they are similar. Ten normal humans and eight normal NHPs (Macaca fascicularis) took part in this project. Previously published data from Macaca mulatta and Macaca nemestrina were also compared. Threshold was operationally defined as two misses in a row for a descending method of limits. A similar paradigm was used for the humans except that the descending method of limits was combined with a spatial, two-alternative forced choice (2-AFC) technique. The contrast sensitivity functions were fit with a double exponential function. The averaged peak contrast sensitivity, peak spatial frequency, acuity, and area under the curve for the humans were 268.9, 3.40 cpd, 27.3 cpd, and 2345.4 and for the Macaca fascicularis were 99.2, 3.93 cpd, 26.1 cpd, and 980.9. A two-sample t-test indicated that the peak contrast sensitivities (P = 0.001) and areas under the curve (P = 0.010) were significantly different. The peak spatial frequencies (P = 0.150) and the extrapolated visual acuities (P = 0.763) were not different. The contrast sensitivities for the Macaca fascicularis, Macaca mulatta, and Macaca nemestrina were qualitatively and quantitatively similar. The contrast sensitivity functions for the NHPs had lower peak contrast sensitivities and areas under the curve than the humans. Even though different methods have been used to measure contrast sensitivity in different species of NHP, the functions are similar. The contrast sensitivity differences and similarities between humans and NHPs need to be considered when using NHPs to study human disease.
Excitability and irritability in preschoolers predicts later psychopathology: The importance of positive and negative emotion dysregulation
Authors: Vogel Alecia C. , Jackson Joshua J. , Barch Deanna M. , Tillman Rebecca , Luby Joan L.
Published: May 2019

Emotion dysregulation is a risk factor for the development of a variety of psychopathologic outcomes. In children, irritability, or dysregulated negative affect, has been the primary focus, as it predicts later negative outcomes even in very young children. However, dysregulation of positive emotion is increasingly recognized as a contributor to psychopathology. Here we used an exploratory factor analysis and defined four factors of emotion dysregulation: irritability, excitability, sadness, and anhedonia, in the preschool-age psychiatric assessment collected in a sample of 302 children ages 3–5 years enriched for early onset depression. The irritability and excitability factor scores defined in preschoolers predicted later diagnosis of mood and externalizing disorders when controlling for other factor scores, social adversity, maternal history of mood disorders, and externalizing diagnoses at baseline. The preschool excitability factor score predicted emotion lability in late childhood and early adolescence when controlling for other factor scores, social adversity, and maternal history. Both excitability and irritability factor scores in preschoolers predicted global functioning into the teen years and early adolescence, respectively. These findings underscore the importance of positive, as well as negative, affect dysregulation as early as the preschool years in predicting later psychopathology, which deserves both further study and clinical consideration.
Integration: What Do We Mean?
Authors: Thomas David
Published: May 2019

It is now 18 years since Lloyd Dunn (1968) wrote his seminal paper “Special Education for the Mildly Retarded: Is much of it justified?” In the meantime, there has been major legislation in USA in the form of Public Law 94-142 (1975) which has been widely interpreted as a blueprint for improved services for the handicapped and for their integration into ordinary schools. In Britain, Section 10 of the Education Act (1976), the Warnock Report (1978) and the Education Act (1981) have provided, in varying degrees, official encouragement for integration.
A Language Proposal to Maximize Communication for an Echolalic Responding Adult
Authors: Spinks Tony
Published: May 2019

The theme of the 11th National Conference of the Australian Association of Special Education was Responding to Expectations. Responding to expectations requires anticipation of correct educational directions and proper teaching strategies to accommodate such directions. All decisions that result from responding to expectations are fundamentally controversial and should be challenged. Through the process of challenge, expectations change, and this has been the case in the development of teaching strategies to improve communication for those who have a limited response repertoire.
Predictors of early childhood undernutrition in Nigeria: the role of maternal autonomy
Authors: Agu Ngozichukwuka , Emechebe Nnadozie , Yusuf Korede , Falope Oluyemisi , Kirby Russell S
Published: May 2019

Objective:

To investigate the relationship between maternal autonomy and various indices of child undernutrition among children aged <2 years in Nigeria, considering the cultural context and sociodemographic factors.

Design:

Population-based, cross-sectional study. Associations between various indices of maternal autonomy and child undernutrition (specifically stunting, underweight and wasting) were determined using weighted bivariate and multivariable logistic regression modelling.

Setting:

2013 Nigerian Demographic Health Survey.

Participants:

Children aged between 3 and 24 months (n 7532).

Results:

Overall, 31·4 % (n 2270), 29·8 % (n 2060) and 25·0 % (n 1755) of children in the sample were stunted, underweight and wasted, respectively. Women with acceptance of domestic violence (low autonomy) were approximately 18 and 14 % less likely to have stunted (OR = 0·82; 95 % CI 0·71, 0·94) and underweight children (OR = 0·86; 95 % CI 0·75, 0·99), respectively. Similarly, women with low power in their couple relations were 17 % less likely to have children who were wasted (OR = 0·83; 95 % CI 0·72, 0·97). Sociodemographic predictors of all indices of undernutrition included maternal education and Hausa ethnicity. Additionally, stunting was predicted by lack of exclusive breast-feeding, low income and being of Fulani ethnicity; wasting by having mothers with low BMI; and underweight by breast-feeding initiation within 1 h hour of birth, polygamous homes, mothers with low BMI and being of Fulani ethnicity.

Conclusions:

Women with acceptance of domestic violence and low power in couple relations were found to be less likely to have children with indices of undernutrition. This unexpected finding calls for future exploratory research, and policies and interventions that target at-risk subgroups.
Plasma Sheath Formation at Craters on Airless Bodies
Authors: Wang X. , Robertson S. , Horányi M.
Published: May 2019

The surfaces of airless planetary bodies directly interact with the solar wind plasma and ultraviolet radiation, resulting in surface charging and formation of a sheath above the surface. These interactions are further complicated by the presence of craters with characteristic sizes spanning over orders of magnitude from centimeters to kilometers. Here we present laboratory results to show that the plasma sheath formed in a crater varies significantly, depending on the radius of the crater compared to the Debye length of ambient plasma. When the Debye length is much smaller than the radius of the crater, the plasma expands into the crater and forms a sheath along the crater wall and floor. When the Debye length is comparable to or larger than the radius of the crater, the potential in the crater becomes more homogenous with a largely reduced electric field. A double layer is formed between the crater and ambient plasma. It is likely that the electrons slowed down by the sheath cannot be efficiently reflected back to the plasma due to the reduced electric field and pile up within the crater, causing an increased electron density that crosses over the density of the ions.
Response of a Rheologically Stratified Lithosphere to Subduction of an Indenter‐Shaped Plate: Insights Into Localized Exhumation at Orogen Syntaxes
Authors: Koptev Alexander , Ehlers Todd A. , Nettesheim Matthias , Whipp David M.
Published: May 2019

This study investigates the influence of the 3‐D geometry of a down‐going plate, the rheological structure of the upper plate, and the migration of the overriding plate toward the trench in relation to the overall subduction velocity on the exhumation pattern in orogen syntaxes. Using a thermomechanical numerical code (DOUAR), we analyze the strain localization, rock uplift, and exhumation response of a rheologically stratified continental lithosphere to subduction of a convex‐upward‐shaped indenter. The models consider three thermorheological lithospheric profiles that determine the degree of mechanical coupling between the upper crust and lithospheric mantle. These models include a strong, cratonic lithosphere; a weaker, younger (and hotter) continental plate; and an intermediate case. The strongly coupled case predicts a localization of high rock uplift rates along narrow linear bands crossing the entire model domain parallel to the trench. In contrast, in a weakly coupled lithosphere, rock uplift is concentrated within a curved ellipse region of anomalously high exhumation rates located above the indenter apex. The aspect ratio of the localized area of rapid rock uplift is controlled by the initial width of the rigid indenter and the relationship between boundary velocities. In particular, the combination of little or no upper plate migration with a narrow indenter causes a nearly circular region (~100‐km diameter) of rapid exhumation that resembles the pattern of thermochronometer ages observed in orogen syntaxes such as the Southeast Alaska and the Olympic Mountains of the Cascadia subduction zone (western USA).
Impressive near-infrared brightness and singlet oxygen generation from strategic lanthanide–porphyrin double-decker complexes in aqueous solution
Authors: Zhang Jing-Xiang , Chan Wai-Lun , Xie Chen , Zhou Yan , Chau Ho-Fai , Maity Partha , Harrison George T. , Amassian Aram , Mohammed Omar F. , Tanner Peter A. , Wong Wai-Kwok , Wong Ka-Leung
Published: May 2019

Although lanthanide double-decker complexes with hetero-macrocyclic ligands as functional luminescent and magnetic materials have promising properties, their inferior water solubility has negated their biomedical applications. Herein, four water-soluble homoleptic lanthanide (Ln = Gd, Er, Yb and La) sandwiches with diethylene-glycol-disubstituted porphyrins (DD) are reported, with their structures proven by both quantum chemical calculations and scanning tunneling microscopy. Our findings demonstrate that the near-infrared emission intensity and singlet oxygen (1O2) quantum yields of YbDD and GdDD in aqueous media are higher than those of the reported capped lanthanide monoporphyrinato analogues, YbN and GdN; the brightness and luminescence lifetime in water of YbDD are greater than those of YbN. This work provides a new dimension for the future design and development of molecular theranostics-based water-soluble double-decker lanthanide bisporphyrinates.
Prosurvival autophagy is regulated by protein kinase CK1 alpha in multiple myeloma
Authors: Carrino Marilena , Quotti Tubi Laura , Fregnani Anna , Canovas Nunes Sara , Barilà Gregorio , Trentin Livio , Zambello Renato , Semenzato Gianpietro , Manni Sabrina , Piazza Francesco
Published: May 2019

Multiple myeloma (MM) is a tumor of plasma cells (PCs). Due to the intense immunoglobulin secretion, PCs are prone to endoplasmic reticulum stress and activate several stress-managing pathways, including autophagy. Indeed, autophagy deregulation is maladaptive for MM cells, resulting in cell death. CK1α, a pro-survival kinase in MM, has recently been involved as a regulator of the autophagic flux and of the transcriptional competence of the autophagy-related transcription factor FOXO3a in several cancers. In this study, we investigated the role of CK1α in autophagy in MM. To study the autophagic flux we generated clones of MM cell lines expressing the mCherry-eGFP-LC3B fusion protein. We observed that CK1 inhibition with the chemical ATP-competitive CK1 α/δ inhibitor D4476 resulted in an impaired autophagic flux, likely due to an alteration of lysosomes acidification. However, D4476 caused the accumulation of the transcription factor FOXO3a in the nucleus, and this was paralleled by the upregulation of mRNA coding for autophagic genes. Surprisingly, silencing of CK1α by RNA interference triggered the autophagic flux. However, FOXO3a did not shuttle into the nucleus and the transcription of autophagy-related FOXO3a-dependent genes was not observed. Thus, while the chemical inhibition with the dual CK1α/δ inhibitor D4476 induced cell death as a consequence of an accumulation of ineffective autophagic vesicles, on the opposite, CK1α silencing, although it also determined apoptosis, triggered a full activation of the early autophagic flux, which was then not supported by the upregulation of autophagic genes. Taken together, our results indicate that the family of CK1 kinases may profoundly influence MM cells survival also through the modulation of the autophagic pathway.
Development of human cGAS-specific small-molecule inhibitors for repression of dsDNA-triggered interferon expression
Authors: Lama Lodoe , Adura Carolina , Xie Wei , Tomita Daisuke , Kamei Taku , Kuryavyi Vitaly , Gogakos Tasos , Steinberg Joshua I. , Miller Michael , Ramos-Espiritu Lavoisier , Asano Yasutomi , Hashizume Shogo , Aida Jumpei , Imaeda Toshihiro , Okamoto Rei , Jennings Andy J. , Michino Mayako , Kuroita Takanobu , Stamford Andrew , Gao Pu , Meinke Peter , Glickman J. Fraser , Patel Dinshaw J. , Tuschl Thomas
Published: May 2019

Cyclic GMP-AMP synthase (cGAS) is the primary sensor for aberrant intracellular dsDNA producing the cyclic dinucleotide cGAMP, a second messenger initiating cytokine production in subsets of myeloid lineage cell types. Therefore, inhibition of the enzyme cGAS may act anti-inflammatory. Here we report the discovery of human-cGAS-specific small-molecule inhibitors by high-throughput screening and the targeted medicinal chemistry optimization for two molecular scaffolds. Lead compounds from one scaffold co-crystallize with human cGAS and occupy the ATP- and GTP-binding active site. The specificity and potency of these drug candidates is further documented in human myeloid cells including primary macrophages. These novel cGAS inhibitors with cell-based activity will serve as probes into cGAS-dependent innate immune pathways and warrant future pharmacological studies for treatment of cGAS-dependent inflammatory diseases.
Potentially large post-1505 AD earthquakes in western Nepal revealed by a lake sediment record
Authors: Ghazoui Z. , Bertrand S. , Vanneste K. , Yokoyama Y. , Nomade J. , Gajurel A. P. , van der Beek P. A.
Published: May 2019

According to paleoseismological studies, the last earthquake that ruptured the Main Frontal Thrust in western Nepal occurred in 1505 AD. No evidence of large earthquakes has been documented since, giving rise to the concept of a seismic gap in the central Himalaya. Here, we report on a new record of earthquake-triggered turbidites from Lake Rara, western Nepal. Our lake-sediment record contains eight possibly moderate-to-large earthquake-triggered turbidites during the last 800 years, three of which overlap in age with previously reportedMw ≥ 7 events in western Nepal. Shaking intensity modelling, together with instrumental records, suggests that near-field earthquakes (≤15 km) should have a minimumMw  5.6, and regional earthquakes (≤80 km) aMw > ~ 6.5, to trigger turbidites. We present a likely scenario that western Nepal may be as seismically active as central Nepal; however, more data are needed to revaluate the seismic risk in the central Himalaya.
Diverse MR1-restricted T cells in mice and humans
Authors: Koay Hui-Fern , Gherardin Nicholas A. , Xu Calvin , Seneviratna Rebecca , Zhao Zhe , Chen Zhenjun , Fairlie David P. , McCluskey James , Pellicci Daniel G. , Uldrich Adam P. , Godfrey Dale I.
Published: May 2019

Mucosal-associated invariant T (MAIT) cells express an invariant TRAV1/TRAJ33 TCR-α chain and are restricted to the MHC-I-like molecule, MR1. Whether MAIT cell development depends on this invariant TCR-α chain is unclear. Here we generateTraj33-deficient mice and show that they are highly depleted of MAIT cells; however, a residual population remains and can respond to exogenous antigen in vitro or pulmonaryLegionellachallenge in vivo. These residual cells include some that expressTrav1+TCRs with conservativeTraj-gene substitutions, and others that expressTrav1-TCRs with a broad range ofTrajgenes. We further report that human TRAV1-2-MR1-restricted T cells contain both MAIT-like and non-MAIT-like cells, as judged by their TCR repertoire, antigen reactivity and phenotypic features. These include a MAIT-like population that expresses a public, canonical TRAV36+TRBV28+TCR. Our findings highlight the TCR diversity and the resulting potential impact on antigen recognition by MR1-restricted T cells.
Author Correction: Towards a data-integrated cell
Authors: Malod-Dognin Noël , Petschnigg Julia , Windels Sam F. L. , Povh Janez , Hemingway Harry , Ketteler Robin , Pržulj Nataša
Published: May 2019

The original version of this Article contained an error in the spelling of the author Harry Hemingway, which was incorrectly given as Harry Hemmingway. This has been corrected in both the PDF and HTML versions of the Article.
Evaluation of Aminolevulinic Acid-Derived Tumor Fluorescence Yields Disparate Results in Murine and Spontaneous Large Animal Models of Lung Cancer
Authors: Predina Jarrod D. , Runge Jeffrey , Newton Andrew , Mison Michael , Xia Leilei , Corbett Christopher , Shin Michael , Sulyok Lydia Frenzel , Durham Amy , Nie Shuming , Singhal Sunil , Holt David
Published: May 2019

Fluorescence guided surgery is an emerging technology that may improve accuracy of pulmonary resection for non-small cell lung cancer (NSCLC). Herein we explore optical imaging for NSCLC surgery using the well-studied protoporphyrin IX (PPIX)/5-aminiolevulinic acid (5-ALA) system. More specifically, we evaluate fluorescent patterns observed when using (1) commonly utilized in vitro and murine NSCLC models and with (2) spontaneous canine NSCLCs, which closely mimic human disease. Using flow cytometry and fluorescent microscopy, we confirmed that NSCLC models fluoresce after exposure to 5-ALA in vitro. High levels of fluorescence were similarly observed in murine tumors within 2 hours of systemic 5-ALA delivery. When evaluating this approach in spontaneous canine NSCLC, tumor fluorescence was observed in 6 of 7 canines. Tumor fluorescence, however, was heterogenous owing to intratumoral variations in cellularity and necrosis. Margin and lymph node detection was inaccurate. These data demonstrate the importance of incorporating reliable cancer models into preclinical evaluations of optical agents. Utilization of spontaneous large animal models of cancer may further provide an important intermediate in the path to human translation of optical contrast agents.
Quantitative synchrotron X-ray tomography of the material-tissue interface in rat cortex implanted with neural probes
Authors: Böhm Thomas , Joseph Kevin , Kirsch Matthias , Moroni Riko , Hilger André , Osenberg Markus , Manke Ingo , Johnston Midori , Stieglitz Thomas , Hofmann Ulrich G. , Haas Carola A. , Thiele Simon
Published: May 2019

Neural probes provide many options for neuroscientific research and medical purposes. However, these implantable micro devices are not functionally stable over time due to host-probe interactions. Thus, reliable high-resolution characterization methods are required to understand local tissue changes upon implantation. In this work, synchrotron X-ray tomography is employed for the first time to image the interface between brain tissue and an implanted neural probe, showing that this 3D imaging method is capable of resolving probe and surrounding tissue at a resolution of about 1 micrometer. Unstained tissue provides sufficient contrast to identify electrode sites on the probe, cells, and blood vessels within tomograms. Exemplarily, we show that it is possible to quantify characteristics of the interaction region between probe and tissue, like the blood supply system. Our first-time study demonstrates a way for simultaneous 3D investigation of brain tissue with implanted probe, providing information beyond what was hitherto possible.
Pt nanoparticles decorated heterostructured g-C3N4/Bi2MoO6 microplates with highly enhanced photocatalytic activities under visible light
Authors: Jia Z. , Lyu F. , Zhang L. C. , Zeng S. , Liang S. X. , Li Y. Y. , Lu J.
Published: May 2019

Exploring an efficient and photostable heterostructured photocatalyst is a pivotal scientific topic for worldwide energy and environmental concerns. Herein, we reported that Pt decorated g-C3N4/Bi2MoO6heterostructured composites with enhanced photocatalytic performance under visible light were simply synthesized by one-step hydrothermal method for methylene blue (MB) dye degradation. Results revealed that the synthetic Pt decorated g-C3N4/Bi2MoO6composites with Bi2MoO6contents of 20 wt.% (Pt@CN/20%BMO) presented the highest photocatalytic activity, exhibiting 7 and 18 times higher reactivity than the pure g-C3N4and Bi2MoO6, respectively. Structural analyses showed that Bi2MoO6microplates were anchored on the wrinkled flower-like g-C3N4matrix with Pt decoration, leading to a large expansion of specific surface area from 10.79 m2/g for pure Bi2MoO6to 46.09 m2/g for Pt@CN/20%BMO. In addition, the Pt@CN/20%BMO composites exhibited an improved absorption ability in the visible light region, presenting a promoted photocatalytic MB degradation. Quenching experiments were also conducted to provide solid evidences for the production of hydroxyl radicals (•OH), electrons (e−), holes (h+) and superoxide radicals (•O2−) during dye degradation. The findings in this critical work provide insights into the synthesis of heterostructured photocatalysts with the optimization of band gaps, light response and photocatalytic performance in wastewater remediation.
Leukocyte telomere length is associated with elevated plasma glucose and HbA1c in young healthy men independent of birth weight
Authors: Grunnet L. G. , Pilgaard K. , Alibegovic A. , Jensen C. B. , Hjort L. , Ozanne S. E. , Bennett M. , Vaag A. , Brøns C.
Published: May 2019

Telomeres are protein-bound regions of repetitive nucleotide sequences (TTAGGG) at the end of human chromosomes, and their length is a marker of cellular aging. Intrauterine growth restriction is associated with shorter blood cell telomeres at birth and individuals with type 2 diabetes have shorter telomeres. Individuals with a low birth weight (LBW) have an increased risk of metabolic disease and type 2 diabetes. Therefore, we aimed to investigate the relationship between birth weight and telomere length and the association between birth weight, telomere length and cardiometabolic phenotype in adulthood. Young, healthy men with LBW (n = 55) and normal birth weight (NBW) (n = 65) were examined including blood pressure, blood samples and body composition. Leukocyte telomere length was determined using a high-throughput qPCR method. The LBW men were more insulin resistant as determined by the HOMA-IR index. There was no difference in telomere length between LBW and NBW subjects. When adjusting for birth weight and cohort effect, significant negative associations between telomere length and fasting glucose (P = 0.003) and HbA1c (P = 0.0008) were found. In conclusion, no significant difference in telomere length was found between LBW and NBW men. The telomere length was negatively associated with glucose concentrations and HbA1c levels within the normal non-diabetic range independent of birth weight.
TGFβ-induced cytoskeletal remodeling mediates elevation of cell stiffness and invasiveness in NSCLC
Authors: Gladilin E. , Ohse S. , Boerries M. , Busch H. , Xu C. , Schneider M. , Meister M. , Eils R.
Published: May 2019

Importance of growth factor (GF) signaling in cancer progression is widely acknowledged. Transforming growth factor beta (TGFβ) is known to play a key role in epithelial-to-mesenchymal transition (EMT) and metastatic cell transformation that are characterized by alterations in cell mechanical architecture and behavior towards a more robust and motile single cell phenotype. However, mechanisms mediating cancer type specific enhancement of cell mechanical phenotype in response to TGFβ remain poorly understood. Here, we combine high-throughput mechanical cell phenotyping, microarray analysis and gene-silencing to dissect cytoskeletal mediators of TGFβ-induced changes in mechanical properties of on-small-cell lung carcinoma (NSCLC) cells. Our experimental results show that elevation of rigidity and invasiveness of TGFβ-stimulated NSCLC cells correlates with upregulation of several cytoskeletal and motor proteins including vimentin, a canonical marker of EMT, and less-known unconventional myosins. Selective probing of gene-silenced cells lead to identification of unconventional myosin MYH15 as a novel mediator of elevated cell rigidity and invasiveness in TGFβ-stimulated NSCLC cells. Our experimental results provide insights into TGFβ-induced cytoskeletal remodeling of NSCLC cells and suggest that mediators of elevated cell stiffness and migratory activity such as unconventional cytoskeletal and motor proteins may represent promising pharmaceutical targets for restraining invasive spread of lung cancer.
Thermal Stabilization of Viral Vaccines in Low-Cost Sugar Films
Authors: Leung Vincent , Mapletoft Jonathan , Zhang Ali , Lee Amanda , Vahedi Fatemeh , Chew Marianne , Szewczyk Alexandra , Jahanshahi-Anbuhi Sana , Ang Jann , Cowbrough Braeden , Miller Matthew S. , Ashkar Ali , Filipe Carlos D. M.
Published: May 2019

Most currently available vaccines, particularly live vaccines, require the cold chain, as vaccine efficacy can be significantly hampered if they are not stored in a temperature range of 2–8 °C at all times. This necessity places a tremendous financial and logistical burden on vaccination programs, particularly in the developing world. The development of thermally stable vaccines can greatly alleviate this problem and, in turn, increase vaccine accessibility worldwide. In this paper, we detail a simple and cost-effective method for stabilizing live vaccines that uses FDA-approved materials. To this end, we dried enveloped DNA (Herpes Simplex Virus type 2) and RNA (Influenza A virus) viral vaccines in a pullulan and trehalose mixture. The results of these studies showed that the live-attenuated HSV-2 vaccine retained its efficacy for at least 2 months of storage at 40 °C, while the inactivated influenza vaccine was able to retain its immunogenicity for at least 3 months of storage at 40 °C. This work presents a simple approach that allows thermo-sensitive vaccines to be converted into thermo-stable vaccines that do not require refrigeration, thus contributing to the improvement of vaccine deployment throughout the world.
Chromosomal integration of aldo-keto-reductase and short-chain dehydrogenase/reductase genes in Clostridium beijerinckii NCIMB 8052 enhanced tolerance to lignocellulose-derived microbial inhibitory compounds
Authors: Okonkwo Christopher Chukwudi , Ujor Victor , Ezeji Thaddeus Chukwuemeka
Published: May 2019

In situ detoxification of lignocellulose-derived microbial inhibitory compounds is an economical strategy for the fermentation of lignocellulose-derived sugars to fuels and chemicals. In this study, we investigated homologous integration and constitutive expression of Cbei_3974 and Cbei_3904, which encode aldo-keto reductase and previously annotated short chain dehydrogenase/reductase, respectively, in Clostridium beijerinckii NCIMB 8052 (Cb), resulting in two strains: Cb_3974 and Cb_3904. Expression of Cbei_3974 led to 2-fold increase in furfural detoxification relative to Cb_3904 and Cb_wild type. Correspondingly, butanol production was up to 1.2-fold greater in furfural-challenged cultures of Cb_3974 relative to Cb_3904 and Cb_wild type. With 4-hydroxybezaldehyde and syringaldehyde supplementation, Cb_3974 showed up to 2.4-fold increase in butanol concentration when compared to Cb_3904 and Cb_wild type. Syringic and vanillic acids were considerably less deleterious to all three strains of Cb tested. Overall, Cb_3974 showed greater tolerance to furfural, 4-hydroxybezaldehyde, and syringaldehyde with improved capacity for butanol production. Hence, development of Cb_3974 represents a significant progress towards engineering solventogenic Clostridium species that are tolerant to lignocellulosic biomass hydrolysates as substrates for ABE fermentation.