bluuebunny/crossref_metadata_2025 huggingface dataset:
On dynamic optimization sensitivity analysis
Authors: Hartono
Published: September 2019

This article describes a linear penalty method for getting sensitive information, i.e. the effect of variation on the constraint to the objective function. The dynamic optimization problem discussed here is a problem with state constraints. At first, the problem is formulated to unconstrained dynamic optimization problem by adding the constraints to the objective function as linear penalty terms. Then, the mathematical formulas to evaluate the change in the objective function and the optimal solution are derived if small perturbation introduced in the constraints. Lastly, the formulas are applied to some numerical examples. Comparison the result of numerical simulations to the numerical solutions obtained from reliable software, i.e. MISER 3.3, shows that the method in general is quite effective. The differences between two solutions are very small and insignificant.
Effectiveness of Non-monitored Green Roofs for Stormwater Management
Authors: Kasmin Hartini , Khalisha Khalidan Siti , Afnizan Wan Mohamed Wan , Syafira Razak Nur , Yacob Mohamad Norfekry Md.
Published: September 2019

A green roof is an alternative roofing system of any building or house that provides a better environment for urban areas. It has the potential to mitigate urban water problems. This study aims to investigate the rainfall runoff performance of two non-monitored green roofs with two different slopes. The experiment uses two types of non-monitored green roofs, namely flat roofs and sloped roofs that were exposed to climatic conditions in Parit Raja. The physical characteristics of the roofs were observed and rainfall runoff data was collected. The results showed that when 4 L of water was manually poured onto the roofs, an average of 60.4% of water was retained on sloped roofs whereas 48.4% was retained on flat roofs. Based on the 5-minute interval data, the retention ranges between 55.6% and 71.2% for both roofs. In terms of daily rainfall for a week, the average percentage was 69.2% for sloped roofs and 70.6% for flat roofs. All three approaches show that the green roofs produced less water runoff compared to normal roofs with both slopes retained water efficiently. Therefore, rainfall runoff performance for two types of green roof slopes was investigated and the available storage for the green roofs was recorded. In conclusion, with little maintenance, non-monitored green roofs can be efficiently used as a water mitigation system for urban areas
Water Quality Classification Using an Artificial Neural Network (ANN)
Authors: Sulaiman Khadijah , Hakim Ismail Lokman , Adib Mohammad Razi Mohd , Shalahuddin Adnan Mohd , Ghazali Rozaida
Published: September 2019

Malaysia is currently a rapidly developing country to achieve a 2020 vision. However the development that has been carried out contributed to a negative impact on the environment especially on water quality. Due to the deterioration of water quality, serious management efforts on water quality has been taken. Thus, the aim of this study is to investigate a technique that can automatically classify the water quality. The technique is based on the concept of Artificial Neural Network (ANN). Since the greater part of their methodologies depend on the idea of `pattern recognition’. Thus, it is convenient to inspect its ability in classify water quality. There are six environmental data were used in this study such as pH, total suspended solids (TSS), dissolved oxygen (DO), chemical oxygen demand (COD), biological oxygen demand (BOD), and ammonia. The data was obtained by in-site measurement and laboratory analysis. Then, the data was used as the feeder of input variables in the ANN database system. After training and testing the network of ANN, the result showed that 80.0% of accuracy classification with 0.468 of root mean square error (RMSE). This showed the encouraging results for classification.
Home Water Purification System in Malaysia: Qualitative and Quantitative Study
Authors: Shahirah Abd Rahim Nur , Othman Norzila
Published: September 2019

Concern over tap water quality has led to the expansion of water filtration system in Malaysia. This study is important to ensure that brands of water filters that have dominated the market in Malaysia do not exceed the quality of water released by safe water filters and no other pollutants leach from the machine. An exploratory study was undertaken to determine the pattern and selection factor of a home water filter system through a set of questionnaires. The survey results indicated that the most popular brands in Malaysia is Brand A from reverse osmosis filtration system. In the experimental study, five most frequently used brands of home water filters were evaluated and compared. Among the 27 parameters studied for each home water filter system, all parameter of physical, chemical and bacteriological quality is complied with the guideline values of the Ministry of Health Malaysia. Parameter of bacteriological quality shows absence bacteria parameter was detected in all samples tested. Meanwhile, physical quality parameter was given best performance removal from brand E and chemical water quality was efficient removal from brand C. In most cases user apply the home treatment of tap water to ensure that the quality of water physically look better and safe to be consumed.
Shear strength of FRP-Externally strengthened High Strength RC T-Beams
Authors: Ibrahim Basil , Leblouba Moussa , Al-Toubat Salah , Barakat Samer
Published: September 2019

This paper presents preliminary results of an extensive experimental program on the behavior of high-strength (HS) reinforced concrete (RC) T-beams strengthened with Carbon Fiber Reinforced Polymer (CFRP) sheets. The test program involves the fabrication and testing of 56 RC beams and many objectives to achieve. The objective of this paper is to investigate the effect of the number of CFRP layers on the shear strength of HS RC beams. To this end, three full-scale specimens were prepared and instrumented with displacement transducers and strain gauges: one control beam, one single-layer of CFRP sheets, and one double-layer of CFRP sheets. All beams were simply supported and subjected to a monotonically increasing load until failure. Preliminary results showed that in the absence of transverse steel reinforcements, the number of CFRP layers does not affect the ultimate strength of the HSC beams.
Calculation of clearances in twin screw compressors
Authors: Husak Ermin , Kovacevic Ahmed , Karabegovic Isak
Published: September 2019

Clearances between rotating and stationary parts in a screw compressor are set to ensure the efficient operation and allow for thermal deformation without unwanted contacts. The change in clearances is caused by both pressure and temperature changes within the machine. If clearances are too large, the increased leakage flows will reduce efficiency. However, if the nominal clearances are too small, contacts between the rotating and stationary parts can occur as a consequence of rotor and casing deformations. In order to determine the operational clearances, a numerical analysis of deformation of screw compressor rotors and casing has to be performed. This paper discusses how the temperature of rotor and casing surfaces calculated from the one-dimensional chamber model in the SCORG could be used as a boundary conditions for a steady state thermal and structural analysis of a screw compressor solid parts. Deformations of rotors and casing under temperature load were calculated using a commercial Finite Element Analysis code ANSYS. Operational clearance are estimated from these deformations and some recommendations for further work are proposed.
An improvement in the production flexibility and accuracy of rotor milling process employing Finger Cutters
Authors: Bergström A
Published: September 2019

Finger Cutters (FCs) are the recently SRM-developed rotor cutting technology which can be easily integrated into multi-axis flexible milling machines. Opposite to the traditional disc cutters, FC operates inside the rotor body and as a result of that requires much less torque. This opens a new possibility to utilize multi-axis machines in rotor milling process, bearing in mind that they generally have less torque than specialized milling machines. An introduction to FC technology including mathematical modeling, geometrical definition and cutter body grinding has been presented in ICSM2018 conference in Dortmund [2].

In this work, we will present the recent development in FC technology. In particular, we will focus on an innovative method to increase the production accuracy of the FC-cut rotor bodies. This method incorporates an iterative procedure of milling, measuring and adjusting. First, a theoretical target surface, so-called adjustment cut, is defined with a safety margin from the final finished surface. FC removes the material aiming to match the adjustment cut. Measuring the surface and comparing with the adjustment cut, a set of correction factors are calculated for the next iteration. Employing this iterative procedure, a notable improvement in the rotor manufacturing accuracy is achieved while risk for scrap rotors is reduced significantly.
Normal Rack Grid Generation Method for Screw Machines with Large Helix Angles
Authors: Yang Lu , Kovacevic Ahmed , Read Matthew
Published: September 2019

Improving the efficiency of the screw machine is highly significant for industry. Numerical simulation is an important tool in developing these machines. The 3D computational fluid dynamic simulation can give a valuable insight into the flow parameters of screw machines. However, it is currently difficult to generate high quality computational grids required for screw rotors with large helix angle. This is mainly due to the excessively high cell skewness of the rotors with large helix angel, which would introduce errors in numerical simulation. This paper presents a novel grid generation algorithm used for the screw rotors with large helix angel. This method is based on the principles developed for the grid generation in transverse cross-section. Such mesh is generated by SCORGTM using normal rack grid generation method which means numerical meshes are generated in a plane normal to the pitch helix line. The mesh lines are then parallel to the helix line and thus an orthogonal mesh will be produced. The main flow and leakage flow directions are orthogonal to the mesh, potentially reducing numerical diffusion. This developed algorithm could also be employed for single screw machines.
The development of the CS valve used to the variable swash plate compressor for a vehicle air-conditioning system
Authors: Taejin Le , Lee Bongsub , Lee Geonho , Kyeong-Ho Shin , Joo-Hyung Kim
Published: September 2019

Since the variable swash plate type compressor used in the vehicle air-conditioning system is mounted on the engine and uses the power of the vehicle, many studies have been conducted on improving the performance of the compressor in order to increase the fuel efficiency of the vehicle. This study was also carried to improve compressor performance through the control room & suction muffler (CS) valve which is an on-off valve located between the control room and suction muffler. The swash plate angle can be controlled by the control room pressure adjusted with control gas. The flow of control gas starts from compressed high-pressure gas which is in the discharge muffler, flows into the control room through the external control valve (ECV) and then flows out to suction muffler through the CS hole which is located between the control room and suction muffler. Such this control method is using the compressed discharge refrigerant so that the compressor power is increased when the amount of the control gas is increased. Therefore, in this study, the CS valve has been developed to reduce the compressor power by minimizing the amount of control gas and it has been confirmed that the compressor power was reduced about 5~10% by the compressor operation speed.
Study on the stress and deformation of a diaphragm compressor cylinder head under extreme conditions
Authors: Wang Ting , Tang Zhou , Jia Xiaohan
Published: September 2019

When a high-pressure diaphragm compressor applied in the hydrogen refueling station, the structure strength of the cylinder head are one of the most important evaluation criteria to guarantee the reliability and efficiency of the diaphragm compressor. Considering the thermal stress, this paper described a thermal-structural coupled analysis on the cylinder head of a diaphragm compressor, in which the thermal analysis was carried out, and then the structural analysis was performed based on temperature distribution. The stress and deformation of the cylinder head under high-temperature and high-pressure conditions were obtained. The experimental method was also conducted for the verification of thermal analysis. Results indicated that during the operation of the compressor, the temperature in the discharge holes was the highest, and the stress caused by high temperature and high working pressure in the discharge holes could reach a high level due to the restriction of the structure. As a result, the region where the discharge holes were opened on the cavity surface protruded into the diaphragm cavity, resulting in plastic deformation, and the plastic deformation would also result in hydrogen embrittlement, influencing the strength of the cylinder head.
Maritime security: the uncharted politics of the global sea
Authors: Bueger Christian , Edmunds Timothy , Ryan Barry J.
Published: September 2019

In this introduction to a special section of the September 2019 issue of International Affairs, we revisit the main themes and arguments of our article ‘Beyond seablindness: a new agenda for maritime security studies’, published in this journal in November 2017. We reiterate our call for more scholarly attention to be paid to the maritime environment in international relations and security studies. We argue that the contemporary maritime security agenda should be understood as an interlinked set of challenges of growing global, regional and national significance, and comprising issues of national, environmental, economic and human security. We suggest that maritime security is characterized by four main characteristics, including its interconnected nature, its transnationality, its liminality—in the sense of implicating both land and sea—and its national and institutional cross-jurisdictionality. Each of the five articles in the special section explores aspects of the contemporary maritime security agenda, including themes of geopolitics, international law, interconnectivity, maritime security governance and the changing spatial order at sea.
The oversecuritization of global health: changing the terms of debate
Authors: Wenham Clare
Published: September 2019

Linking health and security has become a mainstream approach to health policy issues over the past two decades. So much so that the discourse of global health security has become close to synonymous with global health, their meanings being considered almost interchangeable. While the debates surrounding the health–security nexus vary in levels of analysis from the global to the national to the individual, this article argues that the consideration of health as a security issue, and the ensuing path dependencies, have shifted in three ways. First, the concept has been broadened to the extent that a multitude of health issues (and others) are constructed as threats to health security. Second, securitizing health has moved beyond a rhetorical device to include the direct involvement of the security sector. Third, the performance of health security has become a security threat in itself. These considerations, the article argues, alter the remit of the global health security narrative; the global health community needs to recognize this shift and adapt its use of security-focused policies accordingly.
Antibacterial/Antifungal Activity of Extracted Chitosan From American Cockroach (Dictyoptera: Blattidae) and German Cockroach (Blattodea: Blattellidae)
Authors: Basseri Hamidreza , Bakhtiyari Ronak , Hashemi Sayed Jamal , Baniardelani Mojgan , Shahraki Hadi , Hosainpour Laila
Published: September 2019

We investigated bactericidal and fungicidal properties of chitosan extracted from adults and nymphs from both German cockroach, Blattella germanica (Blattodea: Blattellidae) and American cockroach, Periplaneta americana (Dictyoptera: Blattidae). The cuticle of adults and nymphs extracted from both cockroaches were dried and ground. The powders were demineralized and deproteinized followed by deacetylation using NaOH. Finally, the chitosan yields were examined for antibacterial and antifungal activities. The degree of deacetylation (DD) was different between adults and nymph stages. The antimicrobial effect of American cockroach chitosan (ACC) and German cockroach chitosan (GCC) was tested against four bacteria and four fungi. The extracted chitosans from American cockroach, Periplaneta americana and German Cockroach, Blattella germanica suppressed the growth of Gram-negative/positive bacteria except Micrococcus luteus. The growth of Aspergillus flavus and Aspergillus niger were notability inhibited by the extracted chitosans. The antimicrobial effect of the chitosan depended on the cockroach species, with chitosan of the American cockroach showing more inhibitory effect. This difference may be due to differences in the structure of chitin between the two cockroach species.
Highlights of Medical Entomology 2018: The Importance of Sustainable Surveillance of Vectors and Vector-Borne Pathogens
Authors: Connelly Roxanne
Published: September 2019

The theme of the 2018 Entomological Society of America, Entomological Society of Canada, and Entomological Society of British Columbia Joint Annual Meeting was Crossing Borders: Entomology in a Changing World. Following the theme of the meeting, papers selected for the 2018 ‘Highlights of Medical Entomology’ included reports of expanded ranges for Aedes albopictus (Skuse) (Diptera: Culicidae), Aedes japonicus japonicus (Theobald) (Diptera: Culicidae), Culex coronator Dyar and Knab (Diptera: Culicidae), Mansonia titillans (Walker) (Diptera: Culicidae), and Wyeomyia mitchellii (Theobald) (Diptera: Culicidae); a first report of mosquito feeding on earthworms and leeches; Cache Valley virus detection in Ae. j. japonicus; surveillance in high-risk areas of Canada for Lyme Disease; and increasing lone-star tick detections in Connecticut. The selection of papers served as a reminder of the increasingly difficult challenge of sustaining vector surveillance programs. Fluctuating funding and a decline in vector taxonomists and identification expertise contribute to the erosion of vector surveillance.
Interaction Between Psychiatric Symptoms and History of Mild TBI When Evaluating Postconcussion Syndrome in Veterans
Authors: Larsen Sadie E , Larson Eric R , Hunt Joshua C , Lorber William G , deRoon-Cassini Terri A
Published: September 2019

Introduction: Symptoms of postconcussive syndrome (PCS) after mild TBI (mTBI) have been shown to resolve quickly, yet new research raises questions about possible long-term effects of this condition. It is not clear how best to address assessment and treatment when someone reports lingering symptoms of PCS. One self-report measure used by the VA and the DoD is the Neurobehavioral Symptom Inventory (NSI), but this measure may be affected by underlying psychiatric symptoms. We investigated whether the NSI is sensitive to mTBI after considering a number of psychiatric and demographic factors. Methods: This study examined which factors are associated with NSI scores in a Veteran sample (n = 741) that had recently returned from deployment. Results: Post-traumatic stress disorder (PTSD) and depression accounted for most of the variance on the NSI. Although history of mTBI was initially related to NSI, this association was no longer significant after other covariates were considered. Conclusions: The NSI score was primarily explained by symptoms of PTSD and depression, suggesting that the NSI is not specific to the experience of a brain injury. We recommend cautious interpretation when this measure is used in the chronic phase after mTBI, especially among patients with comorbid depression or PTSD.
ZmPGIP3 Gene Encodes a Polygalacturonase-Inhibiting Protein that Enhances Resistance to Sheath Blight in Rice
Authors: Zhu Guang , Liang Enxing , Lan Xiang , Li Qian , Qian Jingjie , Tao Haixia , Zhang Mengjiao , Xiao Ning , Zuo Shimin , Chen Jianmin , Gao Yong
Published: September 2019

Plant polygalacturonase-inhibiting protein (PGIP) is a structural protein that can specifically recognize and bind to fungal polygalacturonase (PG). PGIP plays an important role in plant antifungal activity. In this study, a maize PGIP gene, namely ZmPGIP3, was cloned and characterized. Agarose diffusion assay suggested that ZmPGIP3 could inhibit the activity of PG. ZmPGIP3 expression was significantly induced by wounding, Rhizoctonia solani infection, jasmonate, and salicylic acid. ZmPGIP3 might be related to disease resistance. The gene encoding ZmPGIP3 was posed under the control of the ubiquitin promoter and constitutively expressed in transgenic rice. In an R. solani infection assay, ZmPGIP3 transgenic rice was more resistant to sheath blight than the wild-type rice regardless of the inoculated plant part (leaves or sheaths). Digital gene expression analysis indicated that the expression of some rice PGIP genes significantly increased in ZmPGIP3 transgenic rice, suggesting that ZmPGIP3 might activate the expression of some rice PGIP genes to resist sheath blight. Our investigation of the agronomic traits of ZmPGIP3 transgenic rice showed that ZmPGIP3 overexpression in rice did not show any detrimental phenotypic or agronomic effect. ZmPGIP3 is a promising candidate gene in the transgenic breeding for sheath blight resistance and crop improvement.
Training programs in communication skills to improve self-efficacy for health personnel
Authors: Mata Ádala Nayana de Sousa , Azevedo Kesley Pablo Morais de , Braga Liliane Pereira , Medeiros Gidyenne Christine Bandeira Silva de , Oliveira Segundo Victor Hugo de , Bezerra Isaac Newton Machado , Pimenta Isac Davidson Santiago Fernandes , Nicolás Ismael Martínez , Piuvezam Grasiela
Published: September 2019

Background:

Patient-centered care should be the focus of health services, where improvements in the communication skills of health professionals promote excellent health and quality care. Thus, this study is a protocol for a systematic review and meta-analysis to evaluate the effectiveness of training programs in communication skills to promote self-efficacy in the communication of health personnel.

Methods:

This systematic review protocol is conducted using the Preferred Reporting Items for Systematic Reviews and Meta-Analyzes (PRISMA) statement guidelines and the Cochrane Handbook of Systematic Reviews of Interventions. The review should include studies carried out with health professionals who have undergone training in communication skills aimed at promoting their self-efficacy. Clinical trials (randomized, non-randomized), community trials, and quasi-experimental studies should be included. Therefore, the comprehensive search strategy will be conducted in the following databases: PubMed/Medline, Scopus, Web of Science, EMBASE, Science Direct, CINAHL, PsycINFO, and the Cochrane Central Register of Controlled Trials (CENTRAL). Two independent reviewers will conduct all study selection procedures, data extraction, and methodological evaluation, and disagreements will be referred to a third reviewer. RevMan 5.3 software will be used to gather data and perform the meta-analysis if possible.

Results:

This systematic review will provide evidence on more effective programs for communication skills training and will consider information such as duration, educational strategies, assessment measures, and outcomes that promote health worker self-efficacy.

Discussion:

This systematic review should provide evidence for effective communication skills training for health professionals in order to guide new strategies for quality care.

Dissemination and ethics:

The findings of this scoping review will be disseminated in print, at conferences, or via peer-reviewed journals. Ethical approval is not necessary as this paper does not involve patient data.

Systematic review registration:

PROSPERO CRD42019129384.
GemSpot: A Pipeline for Robust Modeling of Ligands into CryoEM Maps
Authors: Robertson Michael J. , van Zundert Gydo C. P. , Borrelli Kenneth , Skiniotis Georgios
Published: September 2019

Producing an accurate atomic model of biomolecule-ligand interactions from maps generated by cryo-electron microscopy often presents challenges inherent to the methodology and the dynamic nature of ligand binding. Here we have developed GemSpot, a pipeline of computational chemistry methods that take into account EM map potentials, quantum mechanics energy calculations, and water molecule site prediction to generate candidate poses and provide a measure of the degree of confidence. The pipeline is validated through several published cryoEM structures of complexes in different resolution ranges and various types of ligands. In all cases, at least one identified pose produced both excellent interactions with the target and agreement with the map. GemSpot will be valuable for the robust identification of ligand poses and drug discovery efforts through cryoEM.
A supragranular nexus for the effects of neocortical beta events on human tactile perception
Authors: Law Robert G. , Pugliese Sarah , Shin Hyeyoung , Sliva Danielle , Lee Shane , Neymotin Samuel , Moore Christopher , Jones Stephanie R.
Published: September 2019

Transient neocortical events with high spectral power in the 15–29Hz beta band are among the most reliable predictors of sensory perception: High prestimulus beta event rates in primary somatosensory lead to sensory suppression, most effective at 100–300ms prestimulus latency. However, the synaptic and neuronal mechanisms inducing beta’s perceptual effects have not been completely localized. We combined human MEG with neural modeling designed to account for these macroscale signals to interpret the cellular and circuit mechanisms that underlie the influence of beta on tactile detection. Extending prior studies, we modeled the hypothesis that higher-order thalamic bursts, sufficient for beta event generation in cortex, recruit supragranular GABAB inhibition acting on a 300ms time scale to suppress sensory information. Consistency between model and MEG data supported this hypothesis and led to a further prediction, validated in our data, that stimuli are perceived when beta events occur simultaneously with tactile stimulation. The post-event suppressive mechanism explains an array of studies that associate beta with decreased processing, while the during-event mechanism may demand a reinterpretation of the role of beta events in the context of coincident timing.

Significance statement

Somatosensory beta events – transient 15-29Hz oscillations in electromagnetic recordings – are thought to be generated when “top-down” bursts of spikes presumably originating in higher-order thalamus arrive in upper layers of somatosensory cortex. Physiological evidence had shown that the immediate action of these top-down projections should be excitatory; however, after a beta event, sensory perception is noticeably inhibited for approximately 300ms. The source of this post-event sensory suppression, in particular, had been unresolved. Using a detailed computational model of somatosensory cortex, we find evidence for the hypothesis that these bursts couple indirectly to GABAB inhibition in upper layers of cortex, and that beta events first briefly disinhibit sensory relay before a longer period of inhibition.
The effects of postural threat induced by a virtual environment on performance of a walking balance task
Authors: Boroomand-Tehrani Amir , Huntley Andrew H. , Jagroop David , Campos Jennifer L. , Patterson Kara K. , Tremblay Luc , Mansfield Avril
Published: September 2019

Rapid motor learning may occur in situations where individuals perceive a threat of injury if they do not perform a task well. This rapid motor learning may be facilitated by improved motor performance and, consequently, more errorless practice. As a first step towards understanding the role of perceived threat on rapid motor learning, the purpose of this study was to determine how performance of a motor task is affected in situations where perceived threat of injury is high. We hypothesized that perceived threat of injury in a virtual environment would result in improved performance of a walking task (i.e., walking on a narrow beam). Results demonstrated that increased perceived threat of injury yielded slightly greater, but not statistically significant, balance performance in virtual environments (median percentage of successful steps: 78.8%, 48.3%, and 55.2% in the real low-threat, virtual low-threat, and virtual high-threat environments, respectively). These results may be partially attributed to habituation to threat over time and practice. If implemented carefully, virtual reality technology can be an effective tool for investigating walking balance in environments that are perceived as threatening.
Dimensionality changes actin network through lamin A and C and zyxin
Authors: Zonderland Jip , Moldero Ivan Lorenzo , Mota Carlos , Moroni Lorenzo
Published: September 2019

The actin cytoskeleton plays a key role in differentiation of human mesenchymal stromal cells (hMSCs), but its regulation in 3D tissue engineered scaffolds remains poorly studied. hMSCs cultured on 3D electrospun scaffolds made of a stiff material do not form actin stress fibers, contrary to hMSCs on 2D films of the same material. On 3D electrospun- and 3D additive manufactured scaffolds, hMSCs also displayed fewer focal adhesions, lower lamin A and C expression and less YAP1 nuclear localization. Together, this shows that dimensionality prevents the build-up of cellular tension, even on stiff materials. Knock down of either lamin A and C or zyxin resulted in fewer stress fibers in the cell center. Zyxin knock down reduced lamin A and C expression, but not vice versa, showing that this signal chain starts from the outside of the cell. Our study demonstrates that dimensionality changes the actin cytoskeleton through lamin A and C and zyxin, an important insight for future scaffold design, as the actin network, focal adhesions and nuclear stiffness are all critical for hMSC differentiation.
Pharmacological or genetic targeting of Transient Receptor Potential (TRP) channels can disrupt the planarian escape response
Authors: Sabry Ziad , Ho Alicia , Ireland Danielle , Rabeler Christina , Cochet-Escartin Olivier , Collins Eva-Maria S.
Published: September 2019

In response to noxious stimuli, planarians cease their typical ciliary gliding and exhibit an oscillatory type of locomotion called scrunching. We have previously characterized the biomechanics of scrunching and shown that it is induced by specific stimuli, such as amputation, noxious heat, and extreme pH. Because these specific inducers are known to activate Transient Receptor Potential (TRP) channels in other systems, we hypothesized that TRP channels control scrunching. We found that chemicals known to activate TRPA1 (allyl isothiocyanate (AITC) and hydrogen peroxide) and TRPV (capsaicin and anandamide) in other systems induce scrunching in the planarian species Dugesia japonica and, except for anandamide, in Schmidtea mediterranea. To confirm that these responses were specific to either TRPA1 or TRPV, respectively, we tried to block scrunching using selective TRPA1 or TRPV antagonists and RNA interference (RNAi) mediated knockdown. Unexpectedly, co-treatment with a mammalian TRPA1 antagonist, HC-030031, enhanced AITC-induced scrunching by decreasing the latency time, suggesting an agonistic relationship in planarians. We further confirmed that TRPA1 in both species is necessary for AITC-induced scrunching using RNAi. Conversely, while co-treatment of a mammalian TRPV antagonist, SB-366791, also enhanced capsaicin-induced reactions in D. japonica, combined knockdown of two previously identified D. japonica TRPV genes (DjTRPVa and DjTRPVb) did not inhibit capsaicin-induced scrunching. Surprisingly, RNAi of either DjTRPAa or DjTRPVa/DjTRPVb disrupted scrunching induced by the endocannabinoid and TRPV agonist, anandamide. Overall, our results show that although scrunching induction can involve different initial pathways for sensing stimuli, this behavior’s signature dynamical features are independent of the inducer, implying that scrunching is a stereotypical planarian escape behavior in response to various noxious stimuli that converge on a single downstream pathway. Understanding which aspects of nociception are conserved or not across different organisms can provide insight into the underlying regulatory mechanisms to better understand pain sensation.
Does rehearsal matter? Left anterior temporal alpha and theta band changes correlate with the beneficial effects of rehearsal on working memory
Authors: Plaska Chelsea Reichert , Ng Kenneth , Ellmore Timothy M.
Published: September 2019

Rehearsal during working memory (WM) maintenance facilitates retrieval. Less is known about how rehearsal modulates WM delay activity. In the present study, 44 participants completed a Sternberg Task with either intact novel scenes or phase-scrambled scenes, which had similar color and spatial frequency but lacked semantic content. During each condition participants generated a descriptive label and covertly rehearsed or suppressed (repeated “the”) during the delay. This was easy in the former but more difficult in the later condition where scenes lacked semantic content. Behavioral performance and EEG delay activity was analyzed as a function of maintenance strategy. Performance during WM revealed a benefit of rehearsal for phase-scrambled but not intact scenes. Examination of the absolute amplitude revealed three underlying sources of activity for rehearsal, including the left anterior temporal (TAL), left and midline parietal regions. Increases in alpha and theta activity in TAL were correlated with improvement in performance on WM with rehearsal only when labeling was not automatic (i.e. phase-scrambled scenes), which may reflect differences in labeling and rehearsal (i.e. semantic associations vs. shallow labels). We conclude that rehearsal only benefits memory for visual stimuli that lack semantic information, and that this is correlated with changes in alpha and theta rhythms.
Studying cellular functions in bipolar disorder: Are there specific predictors of lithium response?
Authors: Paul Pradip , Iyer Shruti , Nadella Ravi Kumar , Nayak Rashmitha , Chellappa Anirudh S. , Ambardar Sheetal , Sud Reeteka , Sukumaran Salil K. , Purushottam Meera , Jain Sanjeev ,   ADBS Consortium (ADBS: The Accelerator program for Discovery in Brain disorders using Stem cells), Viswanath Biju
Published: September 2019

Background

Lithiumis the first-line mood stabilizer for the treatment of bipolar disorder (BD). In order to interrogate cellular phenotypes related to disease and lithium treatment response, this study used neural precursor cells (NPCs) and lymphoblastoid cell lines (LCLs) from BD patients who are well characterized for clinical lithium response.

Methods

BDpatientsdiagnosed according to the DSM-IV criteria; were recruited from the outpatient services of the National Institute of Mental Health and Neurosciences (NIMHANS), Bangalore, India. Clinical lithium response was assessed using the “Alda scale” and “NIMH Retrospective Life chart method”. The controls were ethnically matched healthy subjects with no family history of neuropsychiatric illness. NPCs from two BD patients from the same family who clearly differed in their clinical response to lithium were chosen, and compared with healthy population controls. Whole transcriptome sequencing (RNA-Seq) and analysis were performed, with and withoutin vitrolithium (1mM for 7 days). In addition, mitochondrial membrane potential (MMP), cell viability and cell proliferation parameters were examined. Experiments were also performed in 25 LCLs from BD patients (16 lithium responders and 9 lithium non-responders), and 12 healthy control LCLs, to evaluate them in a system amenable to clinical translation.

Results

RNA-Sequencingand analysis did not reveal differences in NPCs onin vitrolithium treatment. MMP was lower in BD, both in NPCs and LCLs; reversal within vitrolithium happened only in LCLs and was unrelated to lithium response. Cell proliferation was higher in BD compared to controls, and there was no change on lithium addition. Cell viability assays indicated greater cell death in BD; which could only be rescued in LCLs of clinical lithium responders. The latter finding was associated with enhancedBCL2andGSK3Bexpression within vitrolithium.

Discussion

Overall, our study findings indicate that there are cellular phenotypes related to the disease (mitochondrial potential, cell proliferation) in NPCs and LCLs. We also observed clinical lithium response related phenotypes (cell viability,BCL2/ GSK3Bexpression) in LCLs. The next step would be to evaluate a larger set of PBMCs from clinical lithium response groups of BD to derive cellular phenotypes related to direct clinical application.
Morpho-anatomical variation and their phylogenetic implications in native and exotic species ofPinusgrowing in the Indian Himalayas
Authors: Singh Lav , Dixit Pooja , Srivastava Ravi Prakash , Pandey Shivaraman , Verma Praveen Chandra , Saxena Gauri
Published: September 2019

Pine is native to all continents and some oceanic islands of the northern hemisphere, chiefly in boreal, temperate or mountainous tropical regions; reaching its southernmost distribution below the equator in Southeast Asia.Pinusis divided into two subgenera,Strobus, andPinusby the number of vascular bundles present in the needles. Comprehensive and detailed anatomy of needles in ten species ofPinususing nine anatomical traits was carried out. These morphological and anatomical traits supported the classification of the genus up to section level. It was observed that number of needles per fascicle varied along with other related traits such as thickness and width of vascular bundles, the diameter of resin ducts, the thickness of epidermis and thickness and width of endodermal cells that show remarkable variations among different species selected for the present study. The data can be used as a tool for identification and classification ofPinusupto genus and species level. We also found that similarity and differences in leaf anatomical traits supported the molecular phylogeny ofPinusconducted by several researchers.
Loss of AUXIN RESPONSE FACTOR 4 function alters plant growth, stomatal function and improves tomato tolerance to salinity and osmotic stress
Authors: Bouzroud Sarah , Gasparini Karla , Hu Guojian , Machado Barbosa Maria Antonia , Rosa Bruno Luan , Fahr Mouna , Bendaou Najib , Bouzayen Mondher , Zsögön Agustin , Smouni Abdelaziz , Zouine Mohamed
Published: September 2019

Auxin controls multiple aspects of plant growth and development. However, its role in stress responses remains poorly understood. Auxin acts on the transcriptional regulation of target genes, mainly through Auxin Response Factors (ARF). This study focuses on the involvement of SlARF4 in tomato tolerance to salinity and osmotic stress. Using a reverse genetic approach, we found that the antisense down-regulation of SlARF4 promotes root development and density, increases soluble sugars content and maintains chlorophyll content at high levels under stress conditions. Furthermore, ARF4-as displayed higher tolerance to salt and osmotic stress through reduced stomatal conductance coupled with increased leaf relative water content and ABA content under normal and stressful conditions. This increase in ABA content was correlated with the activation of ABA biosynthesis genes and the repression of ABA catabolism genes. cat1, Cu/ZnSOD and mdhar genes were up-regulated in ARF4-as plants which can result in a better tolerance to salt and osmotic stress. A CRISPR/Cas9 induced SlARF4 mutant showed similar growth and stomatal responses as ARF4-as plants, which suggest that arf4-cr can tolerate salt and osmotic stresses. Our data support the involvement of ARF4 as a key factor in tomato tolerance to salt and osmotic stresses and confirm the use of CRISPR technology as an efficient tool for functional reverse genetics studies.
Plasmodium falciparumgrowth is regulated by Sphingosine 1 phosphate produced by Host Erythrocyte Membrane Sphingosine kinase 1
Authors: Sah Raj Kumar , Saini Monika , Pati Soumya , Singh Shailja
Published: September 2019

Sphingosine-1-phosphate (S1P) a bioactive lipid is produced in its primary reservoir, erythrocytes by an enzyme Sphingosine kinase-1 (SphK-1). The activation of such kinases and the subsequent S1P generation and secretion in the blood serum represent a major regulator of many cellular signaling cascades. Orthologue of sphingosine kinases 1 and 2 (SphK-1 and 2) that catalyze the phosphorylation of sphingosine generating S1P are not present in malaria parasite. The malaria parasite,Plasmodium falciparum, is an intracellular obligatory organism that reside in the human erythrocyte during its blood stage life cycle and orchestrates many metabolic interactions with host for its survival. Given the regulatory role of S1P, we targeted host SphK-1 by a generic pharmacological inhibitor N,N-Dimethyl-sphingosine (DMS) and analyzed growth of intra-erythrocytic parasite. We found that reducing S1P levels by inhibiting host SphK-1 activity led to halted parasite growth and ultimately cell death. Reduced intracellular S1P levels were attributed to decreased glycolysis marked by the low uptake of glucose by parasite and by less production of lactate, a byproduct of glycolysis. Reduced glycolysis was mediated by decrease translocation of the glycolytic enzyme, Glyceraldehyde 3-phosphate dehydrogenase (GAPDH) to the cytosol of infected erythrocytes and cell death. Knocking down of erythrocyte SphK-1 is not lethal to the host and being a host encoded enzyme, targeting it with safe and specific drugs will not lead to the problem of resistance; thus, SphK-1 represents a potent target for the development of therapeutics against intra-erythrocyticP. falciparum.

Author Summary

Erythrocytes membrane enzyme Sphingosine kinase-1 (SphK-1) produces Sphingosine-1-phosphate (S1P) a bioactive lipid by phosphorylation of Sphingosine (Sph). S1P generated by activation of SphK is prosurvival signal and regulate cell growth. The malaria parasite,Plasmodium falciparum, is an intracellular obligatory pathogen that reside in erythrocyte during its blood stage life cycle and orchestrates many metabolic interactions with its host erythrocytes for survival. Orthologue of SphK-1/ 2 are not present in malaria parasite, therefore treatment with SphK inhibitor targeted host SphK-1 and led to reduced S1P level. The reduction in host S1P led to halted parasite growth and cell death. Furthermore, reduced erythrocyte S1P levels led to decreased glycolysis marked by the low uptake of glucose by parasite and by less production of lactate. Erythrocyte SphK-1 being a host encoded enzyme, is resistance safe and represents a potent target for the development of therapeutics against intra-erythrocyticP. falciparum.
Programming for T-lymphocyte fates: modularity and mechanisms
Authors: Rothenberg Ellen V.
Published: September 2019

T-cell development in mammals is a model for lineage choice and differentiation from multipotent stem cells. Although T-cell fate choice is promoted by signaling in the thymus through one dominant pathway, the Notch pathway, it entails a complex set of gene regulatory network and chromatin state changes even before the cells begin to express their signature feature, the clonal-specific T-cell receptors (TCRs) for antigen. This review distinguishes three developmental modules for T-cell development, which correspond to cell type specification, TCR expression and selection, and the assignment of cells to different effector types. The first is based on transcriptional regulatory network events, the second is dominated by somatic gene rearrangement and mutation and cell selection, and the third corresponds to establishing a poised state of latent regulator priming through an unknown mechanism. Interestingly, in different lineages, the third module can be deployed at variable times relative to the completion of the first two modules. This review focuses on the gene regulatory network and chromatin-based kinetic constraints that determine activities of transcription factors TCF1, GATA3, PU.1, Bcl11b, Runx1, and E proteins in the primary establishment of T-cell identity.
Neurogenetic basis for circadian regulation of metabolism by the hypothalamus
Authors: Cedernaes Jonathan , Waldeck Nathan , Bass Joseph
Published: September 2019

Circadian rhythms are driven by a transcription–translation feedback loop that separates anabolic and catabolic processes across the Earth's 24-h light–dark cycle. Central pacemaker neurons that perceive light entrain a distributed clock network and are closely juxtaposed with hypothalamic neurons involved in regulation of sleep/wake and fast/feeding states. Gaps remain in identifying how pacemaker and extrapacemaker neurons communicate with energy-sensing neurons and the distinct role of circuit interactions versus transcriptionally driven cell-autonomous clocks in the timing of organismal bioenergetics. In this review, we discuss the reciprocal relationship through which the central clock drives appetitive behavior and metabolic homeostasis and the pathways through which nutrient state and sleep/wake behavior affect central clock function.
The 22q11 low copy repeats are characterized by unprecedented size and structural variability
Authors: Demaerel Wolfram , Mostovoy Yulia , Yilmaz Feyza , Vervoort Lisanne , Pastor Steven , Hestand Matthew S. , Swillen Ann , Vergaelen Elfi , Geiger Elizabeth A. , Coughlin Curtis R. , Chow Stephen K. , McDonald-McGinn Donna , Morrow Bernice , Kwok Pui-Yan , Xiao Ming , Emanuel Beverly S. , Shaikh Tamim H. , Vermeesch Joris R.
Published: September 2019

Low copy repeats (LCRs) are recognized as a significant source of genomic instability, driving genome variability and evolution. The Chromosome 22 LCRs (LCR22s) mediate nonallelic homologous recombination (NAHR) leading to the 22q11 deletion syndrome (22q11DS). However, LCR22s are among the most complex regions in the genome, and their structure remains unresolved. The difficulty in generating accurate maps of LCR22s has also hindered localization of the deletion end points in 22q11DS patients. Using fiber FISH and Bionano optical mapping, we assembled LCR22 alleles in 187 cell lines. Our analysis uncovered an unprecedented level of variation in LCR22s, including LCR22A alleles ranging in size from 250 to 2000 kb. Further, the incidence of various LCR22 alleles varied within different populations. Additionally, the analysis of LCR22s in 22q11DS patients and their parents enabled further refinement of the rearrangement site within LCR22A and -D, which flank the 22q11 deletion. The NAHR site was localized to a 160-kb paralog shared between the LCR22A and -D in seven 22q11DS patients. Thus, we present the most comprehensive map of LCR22 variation to date. This will greatly facilitate the investigation of the role of LCR variation as a driver of 22q11 rearrangements and the phenotypic variability among 22q11DS patients.