bluuebunny/crossref_metadata_2025 huggingface dataset:
Robust semiglobal swarm tracking of coupled harmonic oscillators with input saturation and external disturbance
Authors: Wang Xiaoling , Su Housheng , Wang Xiaofan , Chen Guanrong
Published: October 2017

The robust semiglobal swarm tracking problem of N coupled harmonic oscillators and 1 actual leader with input saturation and external disturbance on a directed communication topology is considered, in which the N coupled harmonic oscillators are referred to followers. First, the low‐and‐high gain feedback technique is introduced to construct a relative state‐dependent control algorithm. Then, an observer‐based control algorithm is designed based on the low‐and‐high gain feedback technique and the high‐gain observer design methodology. Sufficient conditions are derived to guarantee robust semiglobal swarm tracking for state‐feedback control and output‐feedback control, respectively. Numerical simulations are finally provided to verify the theoretic results.
Concise Review: Induced Pluripotent Stem Cell Models for Neuropsychiatric Diseases
Authors: Adegbola Abidemi , Bury Luke A. , Fu Chen , Zhang Meixiang , Wynshaw-Boris Anthony
Published: October 2017

The major neuropsychiatric conditions of schizophrenia, affective disorders, and infantile autism are characterized by chronic symptoms of episodic, stable, or progressive nature that result in significant morbidity. Symptomatic treatments are the mainstay but do not resolve the underlying disease processes, which are themselves poorly understood. The prototype psychotropic drugs are of variable efficacy, with therapeutic mechanisms of action that are still uncertain. Thus, neuropsychiatric disorders are ripe for new technologies and approaches with the potential to revolutionize mechanistic understanding and drive the development of novel targeted treatments. The advent of methods to produce patient-derived stem cell models and three-dimensional organoids with the capacity to differentiate into neurons and the various neuronal cellular lineages mark such an advance. We discuss numerous techniques involved, their applications, and areas that require further optimization.
Dissecting gene‐environment interactions: A penalized robust approach accounting for hierarchical structures
Authors: Wu Cen , Jiang Yu , Ren Jie , Cui Yuehua , Ma Shuangge
Published: October 2017

Identification of gene‐environment (G × E) interactions associated with disease phenotypes has posed a great challenge in high‐throughput cancer studies. The existing marginal identification methods have suffered from not being able to accommodate the joint effects of a large number of genetic variants, while some of the joint‐effect methods have been limited by failing to respect the “main effects, interactions” hierarchy, by ignoring data contamination, and by using inefficient selection techniques under complex structural sparsity. In this article, we develop an effective penalization approach to identify important G × E interactions and main effects, which can account for the hierarchical structures of the 2 types of effects. Possible data contamination is accommodated by adopting the least absolute deviation loss function. The advantage of the proposed approach over the alternatives is convincingly demonstrated in both simulation and a case study on lung cancer prognosis with gene expression measurements and clinical covariates under the accelerated failure time model.
Decision theory for comparing institutions
Authors: Longford Nicholas T.
Published: October 2017

Various forms of performance assessment are applied to public service institutions, such as hospitals, schools, police units, and local authorities. Difficulties arise in the interpretation of the results presented in some established formats because they require a good understanding and appreciation of the uncertainties involved. Usually the results have to be adapted to the perspectives of the users—managers of the assessed units, a consumer, or a central authority (a watchdog) that dispenses awards and sanctions. We present a decision‐theoretical approach to these and related problems in which the perspectives are integrated in the analysis and its results are choices from a finite list of options (alternative courses of action).
Drug Delivery to the Brain across the Blood–Brain Barrier Using Nanomaterials
Authors: Tsou Yung‐Hao , Zhang Xue‐Qing , Zhu He , Syed Sahla , Xu Xiaoyang
Published: October 2017

A major obstacle facing brain diseases such as Alzheimer's disease, multiple sclerosis, brain tumors, and strokes is the blood–brain barrier (BBB). The BBB prevents the passage of certain molecules and pathogens from the circulatory system into the brain. Therefore, it is nearly impossible for therapeutic drugs to target the diseased cells without the assistance of carriers. Nanotechnology is an area of growing public interest; nanocarriers, such as polymer‐based, lipid‐based, and inorganic‐based nanoparticles can be engineered in different sizes, shapes, and surface charges, and they can be modified with functional groups to enhance their penetration and targeting capabilities. Hence, understanding the interaction between nanomaterials and the BBB is crucial. In this Review, the components and properties of the BBB are revisited and the types of nanocarriers that are most commonly used for brain drug delivery are discussed. The properties of the nanocarriers and the factors that affect drug delivery across the BBB are elaborated upon in this review. Additionally, the most recent developments of nanoformulations and nonconventional drug delivery strategies are highlighted. Finally, challenges and considerations for the development of brain targeting nanomedicines are discussed. The overall objective is to broaden the understanding of the design and to develop nanomedicines for the treatment of brain diseases.
Sequential Coalescence Enabled Two‐Step Microreactions in Triple‐Core Double‐Emulsion Droplets Triggered by an Electric Field
Authors: Jia Yankai , Ren Yukun , Hou Likai , Liu Weiyu , Deng Xiaokang , Jiang Hongyuan
Published: October 2017

Advances in microfluidic emulsification have enabled the generation of exquisite multiple‐core droplets, which are promising structures to accommodate microreactions. An essential requirement for conducting reactions is the sequential coalescence of the multiple cores encapsulated within these droplets, therefore, mixing the reagents together in a controlled sequence. Here, a microfluidic approach is reported for the conduction of two‐step microreactions by electrically fusing three cores inside double‐emulsion droplets. Using a microcapillary glass device, monodisperse water‐in‐oil‐in‐water droplets are fabricated with three compartmented reagents encapsulated inside. An AC electric field is then applied through a polydimethylsiloxane chip to trigger the sequential mixing of the reagents, where the precise sequence is guaranteed by the discrepancy of the volume or conductivity of the inner cores. A two‐step reaction in each droplet is ensured by two times of core coalescence, which totally takes 20–40 s depending on varying conditions. The optimal parameters of the AC signal for the sequential fusion of the inner droplets are identified. Moreover, the capability of this technique is demonstrated by conducting an enzyme‐catalyzed reaction used for glucose detection with the double‐emulsion droplets. This technique should benefit a wide range of applications that require multistep reactions in micrometer scale.
Non‐Fullerene Acceptors With A2 = A1‐D‐A1 = A2 Skeleton Containing Benzothiadiazole and Thiazolidine‐2,4‐Dione for High‐Performance P3HT‐Based Organic Solar Cells
Authors: Xiao Bo , Tang Ailing , Cheng Linxiu , Zhang Jianqi , Wei Zhixiang , Zeng Qingdao , Zhou Erjun
Published: October 2017

Two new planar small molecule acceptors (SMAs) with A2 = A1‐D‐A1 = A2 skeleton are designed and synthesized, where indacenodithiophene (IDT), benzothiadiazole (BT), and thiazolidine‐2,4‐dione (TD) are used as the central donor unit of D, the bridged group of A1 and the end group of A2, respectively. The final SMAs of BT2 and BT2b reveal high‐lying the lowest unoccupied molecular orbital (LUMO) in comparison with that of rhodanine (R) based analogs, which can increase the open‐circuit voltage (VOC) of P3HT‐based solar cells. In addition, by modulating the side chains in the middle IDT unit, BT2b with octyl side chain has an obvious red‐shifted absorption spectrum and stronger crystallinity than that of BT2 with 4‐hexylphenyl side chain. Meanwhile, the different monomolecular packing of two SMAs can be further proven from STM images, where only BT2b can form a regular texture. P3HT:BT2 and P3HT:BT2b blend solar cells upon thermal annealing shows power conversion efficiencies (PCEs) of 4.93 and 6.08% with open‐circuit voltage (VOC) of 0.97 and 0.92 V, respectively. The results indicate that TD is a promising end‐caped segment to up‐shift the LUMO of BT‐based SMAs and could simultaneously realize high VOC and PCE. In addition, the different side chains attached in IDT unit can strongly affect the intermolecular interaction and photovoltaic performance. These results provide important guideline for the design of SMAs to combine with P3HT.
Learning from ancient water management: Archeology's role in modern‐day climate change adaptations
Authors: Kaptijn Eva
Published: October 2017

Climate change is altering our environment and societies worldwide have to devise adaptation strategies. Water management strategies are becoming especially important. In the past, societies had to adapt in order to survive as well. Communities often practised long‐term sustainable agriculture. By understanding the ways in which ancient communities were successful at or failed in attaining social‐ecological resilience through water management archeologists can provide important information for modern communities facing similar problems. Archeology's long time perspective is very valuable. However, archeologists are confronted with a number of issues. Archeology can only study the material remains of past societies, not the living communities. Not all human activity translates into material residue and not all materials survive. Moreover, people will not demonstrate completely rational cause‐and‐effect behavior, but ideology and beliefs, which archeology can only poorly attest, will also have influenced decisions. Nevertheless, archeology can bring a unique perspective to the debate on climate change adaptation: archeology can falsify or corroborate sustainability claims, ancient water management techniques may still be a resilient mode of subsistence and ancient techniques often rely on relatively simple technology allowing for easier adoption. When transposing ancient water management techniques to modern situations it is important to involve stakeholders from an early stage, to incorporate traditional knowledge systems as much as possible and most importantly to ascertain whether physical and socio‐cultural circumstances are comparable. Archeological knowledge on ancient sustainability and water management is not a panacea for all climate related aridification, but can contribute a unique longue durée perspective. WIREs Water 2018, 5:e1256. doi: 10.1002/wat2.1256

This article is categorized under:

Human Water > Water as Imagined and Represented
On the origins and industrial applications of Saccharomyces cerevisiae × Saccharomyces kudriavzevii hybrids
Authors: Peris David , Pérez‐Torrado Roberto , Hittinger Chris Todd , Barrio Eladio , Querol Amparo
Published: October 2017

Companies based on alcoholic fermentation products, such as wine, beer and biofuels, use yeasts to make their products. Each industrial process utilizes different media conditions, which differ in sugar content, the presence of inhibitors and fermentation temperature. Saccharomyces cerevisiae has traditionally been the main yeast responsible for most fermentation processes. However, the market is changing due to consumer demand and external factors such as climate change. Some processes, such as biofuel production or winemaking, require new yeasts to solve specific challenges, especially those associated with sustainability, novel flavours and altered alcohol content. One of the proposed solutions is the application of yeast hybrids. The lager beer market has been dominated by S. cerevisiae × S. eubayanus hybrids. However, several less thoroughly studied hybrids have been isolated from other diverse industrial processes. Here we focus on S. cerevisiae × S. kudriavzevii hybrids, which have been isolated from diverse industrial conditions that include wine, ale beer, cider and dietary supplements. Emerging data suggest an extended and complex story of adaptation of these hybrids to traditional industrial conditions. S. cerevisiae × S. kudriavzevii hybrids are also being explored for new industrial applications, such as biofuels. This review describes the past, present and future of S. cerevisiae × S. kudriavzevii hybrids. Copyright © 2017 John Wiley & Sons, Ltd.
A Trichosporonales genome tree based on 27 haploid and three evolutionarily conserved ‘natural’ hybrid genomes
Authors: Takashima Masako , Sriswasdi Sira , Manabe Ri‐Ichiroh , Ohkuma Moriya , Sugita Takashi , Iwasaki Wataru
Published: October 2017

To construct a backbone tree consisting of basidiomycetous yeasts, draft genome sequences from 25 species of Trichosporonales (Tremellomycetes, Basidiomycota) were generated. In addition to the hybrid genomes of Trichosporon coremiiforme and Trichosporon ovoides that we described previously, we identified an interspecies hybrid genome in Cutaneotrichosporon mucoides (formerly Trichosporon mucoides). This hybrid genome had a gene retention rate of ~55%, and its closest haploid relative was Cutaneotrichosporon dermatis. After constructing the C. mucoides subgenomes, we generated a phylogenetic tree using genome data from the 27 haploid species and the subgenome data from the three hybrid genome species. It was a high‐quality tree with 100% bootstrap support for all of the branches. The genome‐based tree provided superior resolution compared with previous multi‐gene analyses. Although our backbone tree does not include all Trichosporonales genera (e.g. Cryptotrichosporon), it will be valuable for future analyses of genome data. Interest in interspecies hybrid fungal genomes has recently increased because they may provide a basis for new technologies. The three Trichosporonales hybrid genomes described in this study are different from well‐characterized hybrid genomes (e.g. those of Saccharomyces pastorianus and Saccharomyces bayanus) because these hybridization events probably occurred in the distant evolutionary past. Hence, they will be useful for studying genome stability following hybridization and speciation events. Copyright © 2017 John Wiley & Sons, Ltd.
Evaluation of Prognostic Factors for Esophageal Squamous Cell Carcinoma Treated with Neoadjuvant Chemoradiotherapy Followed by Surgery
Authors: Hamai Yoichi , Hihara Jun , Emi Manabu , Furukawa Takaoki , Murakami Yuji , Nishibuchi Ikuno , Ibuki Yuta , Yamakita Ichiko , Kurokawa Tomoaki , Nagata Yasushi , Okada Morihito
Published: October 2017

Background

Intensive trimodality therapy is needed for locally advanced esophageal squamous cell carcinoma (ESCC). However, some patients develop recurrence and die of cancer even after trimodality therapy.

Methods

We evaluated prognostic factors based on data from 125 patients with ESCC who underwent neoadjuvant chemoradiotherapy (NCRT) comprising concurrent chemotherapy and 40 Gy of radiation, followed by curative‐intent esophagectomy.

Results

Thirty‐four (27.2%) patients achieved a pathological complete response (pCR) after NCRT. The 5‐year recurrence‐free (RFS) and overall survival (OS) rates of all patients were 49.2 and 52.9%, respectively, and were significantly better for patients with pCR than without pCR (p = 0.01 and 0.02, respectively). Univariate and multivariate analyses selected performance status [PS 0 vs. 1: hazard ratio (HR) 2.05; 95% confidence interval (CI) 1.30–4.84; p = 0.01] and ypN (0 vs. 1: HR 2.33; 95% CI 1.12–4.84; p = 0.02; 0 vs. 2/3: HR 3.73; 95% CI 1.68–8.28; p = 0.001) as independent covariates for RFS. Furthermore, PS (0 vs. 1; HR 2.94; 95% CI 1.51–5.72; p = 0.002) and ypN (0 vs. 1; HR 2.26; 95% CI 1.09–4.69; p = 0.03; 0 vs. 2/3: HR 3.90; 95% CI 1.79–8.48; p = 0.001) were also independent covariates for OS.

Conclusions

Performance status 1 and ypN+ were significantly associated with a poor prognosis after trimodality therapy for ESCC.
Carnosinase, diabetes mellitus and the potential relevance of carnosinase deficiency
Authors: Peters Verena , Zschocke Johannes , Schmitt Claus P.
Published: October 2017

Carnosinase (CN1) is a dipeptidase, encoded by the CNDP1 gene, that degrades histidine‐containing dipeptides, such as carnosine, anserine and homocarnosine. Loss of CN1 function (also called carnosinase deficiency or aminoacyl‐histidine dipeptidase deficiency) has been reported in a small number of patients with highly elevated blood carnosine concentrations, denoted carnosinaemia; it is unclear whether the variety of clinical symptoms in these individuals is causally related to carnosinase deficiency. Reduced CN1 function should increase serum carnosine concentrations but the genetic basis of carnosinaemia has not been formally confirmed to be due to CNDP1 mutations. A CNDP1 polymorphism associated with low CN1 activity correlates with significantly reduced risk for diabetic nephropathy, especially in women with type 2 diabetes, and may slow progression of chronic kidney disease in children with glomerulonephritis. Studies in rodents demonstrate antiproteinuric and vasculoprotective effects of carnosine, the precise molecular mechanisms, however, are still incompletely understood. Thus, carnosinemia due to CN1 deficiency may be a non‐disease; in contrast, carnosine may potentially protect against long‐term sequelae of reactive metabolites accumulating, e.g. in diabetes and chronic renal failure.
Emigration Rates From Sample Surveys: An Application to Senegal
Authors: Willekens Frans , Zinn Sabine , Leuchter Matthias
Published: October 2017

What is the emigration rate of a country, and how reliable is that figure? Answering these questions is not at all straightforward. Most data on international migration are census data on foreign-born population. These migrant stock data describe the immigrant population in destination countries but offer limited information on the rate at which people leave their country of origin. The emigration rate depends on the number leaving in a given period and the population at risk of leaving, weighted by the duration at risk. Emigration surveys provide a useful data source for estimating emigration rates, provided that the estimation method accounts for sample design. In this study, emigration rates and confidence intervals are estimated from a sample survey of households in the Dakar region in Senegal, which was part of the Migration between Africa and Europe survey. The sample was a stratified two-stage sample with oversampling of households with members abroad or return migrants. A combination of methods of survival analysis (time-to-event data) and replication variance estimation (bootstrapping) yields emigration rates and design-consistent confidence intervals that are representative for the study population.
Size, shape, and topology optimization of planar and space trusses using mutation-based improved metaheuristics
Authors: Tejani Ghanshyam G. , Savsani Vimal J. , Patel Vivek K. , Savsani Poonam V.
Published: October 2017

In this study, simultaneous size, shape, and topology optimization of planar and space trusses are investigated. Moreover, the trusses are subjected to constraints for element stresses, nodal displacements, and kinematic stability conditions. Truss Topology Optimization (TTO) removes the superfluous elements and nodes from the ground structure. In this method, the difficulties arise due to unacceptable and singular topologies; therefore, the Grubler's criterion and the positive definiteness are used to handle such issue. Moreover, the TTO is challenging due to its search space, which is implicit, non-convex, non-linear, and often leading to divergence. Therefore, mutation-based metaheuristics are proposed to investigate them. This study compares the performance of four improved metaheuristics (viz. Improved Teaching–Learning-Based Optimization (ITLBO), Improved Heat Transfer Search (IHTS), Improved Water Wave Optimization (IWWO), and Improved Passing Vehicle Search (IPVS)) and four basic metaheuristics (viz. TLBO, HTS, WWO, and PVS) in order to solve structural optimization problems.

Highlights Improvements in four recently designed metaheuristics. Use of random mutation-based search technique. Applications on challenging/benchmark problems of simultaneous size, shape, and topology optimization of truss structures. Improvements effective over basic metaheuristics.
Legal Consciousness and Workers’ Resistance in Đồng Nai Province, Vietnam
Authors: NGUYEN Tu Phuong
Published: October 2017

This article examines how labour law contributes to labour resistance in Vietnam through an empirical case study of the ‘core workers’ in Đồng Nai Province. These core workers are factory workers who have undergone legal training and who provide legal aid to factory workers in need. They have, at the same time, deployed their legal knowledge to demand access to justice for themselves and the factory workers. This article demonstrates that the core workers’ legal consciousness is shaped by their mobilization of the law and their own workplace experiences. It then investigates in detail a core worker’s engagements with individual and collective disputes, and discusses his views on legal aid, labour law, and workplace relationships. This article argues that the core workers’ resistance is not only a fight against illegal practices, but that it also embodies a call for the management’s moral obligations towards its workers.
One Step Forward, Two Steps Back? The New U.S. Regulatory Budgeting Rules in Light of the International Experience
Authors: Renda Andrea
Published: October 2017

Executive Order (EO) 13771 on “Reducing Regulation and Controlling Regulatory Costs” introduces a new regulatory budgeting system in the U.S. federal rulemaking process. International experience suggests that the new rule, aimed both at reducing the number of regulations and the volume of regulatory costs, will focus on a subset of regulatory impacts, most certainly the direct costs imposed by regulation on businesses, or even a subset thereof. The paper discusses possible ways to make sense of the new rule, without undermining the soundness of benefit-cost analysis mandated by EO12866. The paper concludes that the new system, while potentially promoting more retrospective regulatory reviews, will risk fundamentally affecting the quality of regulation in the United States, generating frictions and inefficiencies throughout the administration, to the detriment of social welfare.
On the propagation of gravity currents over and through a submerged array of circular cylinders
Authors: Zhou Jian , Cenedese Claudia , Williams Tim , Ball Megan , Venayagamoorthy Subhas K. , Nokes Roger I.
Published: October 2017

The propagation of full-depth lock-exchange bottom gravity currents past a submerged array of circular cylinders is investigated using laboratory experiments and large eddy simulations. Firstly, to investigate the front velocity of gravity currents across the whole range of array density $\unicode[STIX]{x1D719}$ (i.e. the volume fraction of solids), the array is densified from a flat bed ($\unicode[STIX]{x1D719}=0$) towards a solid slab ($\unicode[STIX]{x1D719}=1$) under a particular submergence ratio $H/h$, where $H$ is the flow depth and $h$ is the array height. The time-averaged front velocity in the slumping phase of the gravity current is found to first decrease and then increase with increasing $\unicode[STIX]{x1D719}$. Next, a new geometrical framework consisting of a streamwise array density $\unicode[STIX]{x1D707}_{x}=d/s_{x}$ and a spanwise array density $\unicode[STIX]{x1D707}_{y}=d/s_{y}$ is proposed to account for organized but non-equidistant arrays ($\unicode[STIX]{x1D707}_{x}\neq \unicode[STIX]{x1D707}_{y}$), where $s_{x}$ and $s_{y}$ are the streamwise and spanwise cylinder spacings, respectively, and $d$ is the cylinder diameter. It is argued that this two-dimensional parameter space can provide a more quantitative and unambiguous description of the current–array interaction compared with the array density given by $\unicode[STIX]{x1D719}=(\unicode[STIX]{x03C0}/4)\unicode[STIX]{x1D707}_{x}\unicode[STIX]{x1D707}_{y}$. Both in-line and staggered arrays are investigated. Four dynamically different flow regimes are identified: (i) through-flow propagating in the array interior subject to individual cylinder wakes ($\unicode[STIX]{x1D707}_{x}$: small for in-line array and arbitrary for staggered array; $\unicode[STIX]{x1D707}_{y}$: small); (ii) over-flow propagating on the top of the array subject to vertical convective instability ($\unicode[STIX]{x1D707}_{x}$: large; $\unicode[STIX]{x1D707}_{y}$: large); (iii) plunging-flow climbing sparse close-to-impermeable rows of cylinders with minor streamwise intrusion ($\unicode[STIX]{x1D707}_{x}$: small; $\unicode[STIX]{x1D707}_{y}$: large); and (iv) skimming-flow channelized by an in-line array into several subcurrents with strong wake sheltering ($\unicode[STIX]{x1D707}_{x}$: large; $\unicode[STIX]{x1D707}_{y}$: small). The most remarkable difference between in-line and staggered arrays is the non-existence of skimming-flow in the latter due to the flow interruption by the offset rows. Our analysis reveals that as $\unicode[STIX]{x1D719}$ increases, the change of flow regime from through-flow towards over- or skimming-flow is responsible for increasing the gravity current front velocity.
Heritage as War
Authors: Bsheer Rosie
Published: October 2017

The construction of heritage can be a violent process. Authorizing state-sanctioned narratives and the spaces that materialize them are belligerent acts. Crafting and territorializing a singular history out of many entangled ones necessarily relies on the destruction, containment, and/or silencing of the evidentiary terrain—of people, places, and things. In this sense, the construction of the past—to play on Carl von Clausewitz's well-known maxim—is the continuation of war by other means. As networks of knowledge production and transmission, “lieux de mémoire” are everyday sites of violence that embody ongoing social relations and the attendant struggles over power. In times of peace as in war, they are terrains of symbolic and material contestation whose creative destruction can be deployed as political spectacles and projections of power. Examples of such dynamics abound, whether in the Standing Rock Sioux reservation in North America or Palmyra, Baghdad, and Mecca in the Middle East. In its varied forms, then, heritage is as much a cause for celebration for some as it is a cause of injury for others. Heritage reflects the power to subjugate the past to the politics of the present and to dictate the future, both of which are intrinsic to state and subject formation.
RESPONSE TO JEFF D. COLGAN’S REVIEW OF DYING TO FORGET: OIL, POWER, PALESTINE AND THE FOUNDATIONS OF US POLICY IN THE MIDDLE EAST (IJMES 49 [2017]: 360–62)
Authors: Gendzier Irene L.
Published: October 2017

I appreciate the effort of Jeff D. Colgan to grapple with the material presented in my study of the formative years of US policy in Palestine and Israel given his interest in oil policy. However, the analysis of the origin of the US–Israel oil connection is not designed as a warning to oil companies or as a preface to oil nationalizations in the Arab world, which sometimes appears to be Colgan's prime concern in his review. The analysis offered in Dying to Forget: Oil, Power, Palestine and the Foundations of US Policy in the Middle East is about the transformation of Palestine at a time that coincided with the decolonization struggles across North Africa and the Middle East in which US officials recognized the importance of Palestine and its potential through the period including and following Israel's emergence.
Two glutathione transferase isoforms isolated from juvenile cysts ofTaenia crassiceps: identification, purification and characterization
Authors: Maldonado G. , Nava G. , Plancarte A.
Published: October 2017

We identified and characterized the first two glutathione transferases (GSTs) isolated from juvenile cysts ofTaenia crassiceps(EC 2.5.1.18). The two glutathione transferases (TcGST1 and TcGST2) were purified in a single-step protocol using glutathione (GSH)-sepharose chromatography in combination with a GSH gradient. The specific activities of TcGST1 and TcGST2 were 26 U mg−1and 19 U mg−1, respectively, both at 25°C and pH 6.5 with 1-chloro-2,4-dinitrobenzene (CDNB) and GSH as substrates. TheKm(CDNB)andKcat(CDNB)values for TcGST1 and TcGST2 (0.86 μmand 62 s−1; 1.03 μmand 1.97 s−1, respectively) andKm(GSH)andKcat(GSH)values for TcGST1 and TcGST2 (0.55 μmand 11.61 s−1; 0.3 μmand 32.3 s−1, respectively) were similar to those reported for mammalian and helminth GSTs. Mass spectrometry analysis showed that eight peptides from each of the two parasite transferases were a match for gi|29825896 glutathione transferase (Taenia solium), confirming that both enzymes are GSTs. The relative molecular masses were 54,000 ± 0.9 for the native enzymes and 27,500 ± 0.5 for the enzyme subunits. Thus, TcGST1 and TcGST2 are dimeric proteins. Optimal TcGST1 and TcGST2 activities were observed at pH 8.5 in the range of 20–55°C and pH 7.5 at 35–40°C, respectively. TcGST1 and TcGST2 were inhibited by cibacron blue (CB), bromosulphophthalein (BST), rose bengal (RB), indomethacin and haematin (Hm) with 50% inhibitory concentrations (IC50) in the μmrange. TcGST1 was inhibited in a non-competitive manner by all tested inhibitors with the exception of indomethacin, which was uncompetitive. The discovery of these new GSTs facilitates the potential use ofT. crassicepsas a model to investigate multifunctional GSTs.
Buying through your teeth: traditional currency and conservation of flying foxesPteropusspp. in Solomon Islands
Authors: Lavery Tyrone H. , Fasi John
Published: October 2017

Globally, island bats are vulnerable to subsistence hunting, with widespread population declines, local extirpations and extinctions. Bats are important to the ecological functioning of remote oceanic islands, and thus the sustainable management of hunting of flying foxesPteropusspp. is a conservation priority in the Pacific. In Solomon Islands people hunt flying foxes for bushmeat and their canine teeth, which are used as traditional currency. The value of teeth potentially increases hunting pressure on species ofPteropus. We interviewed 197 people on Makira Island to determine the nature of this use and how it may influence flying-fox populations. We asked questions to gather information about hunting practices, the value of canine teeth, utilization of traditional currency, and population trends ofPteropus. Flying-fox teeth remain highly valued on Makira. It is primarily the teeth ofP. tonganusthat are used rather than those of the smallerP. cognatus. Although flying foxes are not targeted solely for their teeth, this added value seemingly drives hunters to focus onP. tonganus. Hunting varied across five regions of Makira and high hunting pressure corresponded with perceived rarity ofP. tonganus. Regions with low hunting pressure may be opportune locations to initiate flying-fox conservation on Makira.
The effects of snow and salt on ice table stability in University Valley, Antarctica
Authors: Williams K.E. , Heldmann J.L. , McKay Christopher P. , Mellon Michael T.
Published: October 2017

The Antarctic Dry Valleys represent a unique environment where it is possible to study dry permafrost overlaying an ice-rich permafrost. In this paper, two opposing mechanisms for ice table stability in University Valley are addressed: i) diffusive recharge via thin seasonal snow deposits and ii) desiccation via salt deposits in the upper soil column. A high-resolution time-marching soil and snow model was constructed and applied to University Valley, driven by meteorological station atmospheric measurements. It was found that periodic thin surficial snow deposits (observed in University Valley) are capable of drastically slowing (if not completely eliminating) the underlying ice table ablation. The effects of NaCl, CaCl2 and perchlorate deposits were then modelled. Unlike the snow cover, however, the presence of salt in the soil surface (but no periodic snow) results in a slight increase in the ice table recession rate, due to the hygroscopic effects of salt sequestering vapour from the ice table below. Near-surface pore ice frequently forms when large amounts of salt are present in the soil due to the suppression of the saturation vapour pressure. Implications for Mars high latitudes are discussed.
Neuropsychological Recovery Trajectories in Moderate to Severe Traumatic Brain Injury: Influence of Patient Characteristics and Diffuse Axonal Injury
Authors: Rabinowitz Amanda R. , Hart Tessa , Whyte John , Kim Junghoon
Published: October 2017

Objectives: The goal of the present study was to elucidate the influence of demographic and neuropathological moderators on the longitudinal trajectory neuropsychological functions during the first year after moderate to severe traumatic brain injury (TBI). In addition to examining demographic moderators such as age and education, we included a measure of whole-brain diffuse axonal injury (DAI), and examined measures of processing speed (PS), executive function (EF), and verbal learning (VL) separately. Methods: Forty-six adults with moderate to severe TBI were examined at 3, 6, and 12 months post-injury. Participants underwent neuropsychological evaluation and neuroimaging including diffusion tensor imaging. Using linear mixed effects modeling, we examined longitudinal trajectories and moderating factors of cognitive outcomes separately for three domains: PS, VL, and EF. Results: VL and EF showed linear improvements, whereas PS exhibited a curvilinear trend characterized by initial improvements that plateaued or declined, depending on age. Age moderated the recovery trajectories of EF and PS. Education and DAI did not influence trajectory but were related to initial level of functioning for PS and EF in the case of DAI, and all three cognitive domains in the case of education. Conclusions: We found disparate recovery trajectories across cognitive domains. Younger age was associated with more favorable recovery of EF and PS. These findings have both clinical and theoretical implications. Future research with a larger sample followed over a longer time period is needed to further elucidate the factors that may influence cognitive change over the acute to chronic period after TBI. (JINS, 2018, 24, 237–246)
Russian Federation – Measures on the Importation of Live Pigs, Pork and Other Pig Products from the European Union (Russia–Pigs (EU)), DS475
Authors: Alcover Maria
Published: October 2017

This dispute arose after African Swine Fever (ASF), a highly contagious disease of pigs, was detected in four member States of the European Union (EU) and Russia stopped accepting imports of pigs and pig products from the EU. The EU presented claims with respect to two measures: (i) the ‘EU-wide ban’, consisting of Russia's ban on the importation of the products at issue from the entire EU; and (ii) the ‘country-specific import bans’ imposed by Russia on imports from the four EU member States – Estonia, Latvia, Lithuania, and Poland. There were two categories of products at issue: ‘treated products’ (finished products subject to a treatment that ensures destruction of ASF) and ‘non-treated products’ (products including live pigs, and raw meat preparations). Treated products were not subject to the EU-wide ban. The EU brought multiple claims under the Agreement on the Application of Sanitary and Phytosanitary Measures (SPS Agreement).
Michael Katz, Urban Optimist
Authors: O'Mara Margaret
Published: October 2017

“It is hard to capture the sense in which life in the past, especially in cities, differed from living today,” Michael B. Katz wrote in the conclusion of his first book-length work of urban history, The People of Hamilton, Canada West (Katz 1975: 311). “For the recognizable components of past urban life lull one into imagining a continuity greater than that which exists. In fundamental ways the patterns and texture of urban existence have changed.”
Cyanophage-encoded lipid desaturases: oceanic distribution, diversity and function
Authors: Roitman Sheila , Hornung Ellen , Flores-Uribe José , Sharon Itai , Feussner Ivo , Béjà Oded
Published: October 2017

Cyanobacteria are among the most abundant photosynthetic organisms in the oceans; viruses infecting cyanobacteria (cyanophages) can alter cyanobacterial populations, and therefore affect the local food web and global biochemical cycles. These phages carry auxiliary metabolic genes (AMGs), which rewire various metabolic pathways in the infected host cell, resulting in increased phage fitness. Coping with stress resulting from photodamage appears to be a central necessity of cyanophages, yet the overall mechanism is poorly understood. Here we report a novel, widespread cyanophage AMG, encoding a fatty acid desaturase (FAD), found in two genotypes with distinct geographical distribution. FADs are capable of modulating the fluidity of the host’s membrane, a fundamental stress response in living cells. We show that both viral FAD (vFAD) families are Δ9 lipid desaturases, catalyzing the desaturation at carbon 9 in C16 fatty acid chains. In addition, we present a comprehensive fatty acid profiling for marine cyanobacteria, which suggests a unique desaturation pathway of medium- to long-chain fatty acids no longer than C16, in accordance with the vFAD activity. Our findings suggest that cyanophages are capable of fiddling with the infected host’s membranes, possibly leading to increased photoprotection and potentially enhancing viral-encoded photosynthetic proteins, resulting in a new viral metabolic network.
Calmodulin dissociates the STIM1-Orai1 complex and STIM1 oligomers
Authors: Li Xin , Wu Guangyan , Yang Yin , Fu Shijuan , Liu Xiaofen , Kang Huimin , Yang Xue , Su Xun-Cheng , Shen Yuequan
Published: October 2017

Store-operated calcium entry (SOCE) is a major pathway for calcium ions influx into cells and has a critical role in various cell functions. Here we demonstrate that calcium-bound calmodulin (Ca2+-CaM) binds to the core region of activated STIM1. This interaction facilitates slow Ca2+-dependent inactivation after Orai1 channel activation by wild-type STIM1 or a constitutively active STIM1 mutant. We define the CaM-binding site in STIM1, which is adjacent to the STIM1–Orai1 coupling region. The binding of Ca2+-CaM to activated STIM1 disrupts the STIM1–Orai1 complex and also disassembles STIM1 oligomer. Based on these results we propose a model for the calcium-bound CaM-regulated deactivation of SOCE.
The giant protein titin regulates the length of the striated muscle thick filament
Authors: Tonino Paola , Kiss Balazs , Strom Josh , Methawasin Mei , Smith John E. , Kolb Justin , Labeit Siegfried , Granzier Henk
Published: October 2017

The contractile machinery of heart and skeletal muscles has as an essential component the thick filament, comprised of the molecular motor myosin. The thick filament is of a precisely controlled length, defining thereby the force level that muscles generate and how this force varies with muscle length. It has been speculated that the mechanism by which thick filament length is controlled involves the giant protein titin, but no conclusive support for this hypothesis exists. Here we show that in a mouse model in which we deleted two of titin’s C-zone super-repeats, thick filament length is reduced in cardiac and skeletal muscles. In addition, functional studies reveal reduced force generation and a dilated cardiomyopathy (DCM) phenotype. Thus, regulation of thick filament length depends on titin and is critical for maintaining muscle health.
An integrative method to decode regulatory logics in gene transcription
Authors: Yan Bin , Guan Daogang , Wang Chao , Wang Junwen , He Bing , Qin Jing , Boheler Kenneth R. , Lu Aiping , Zhang Ge , Zhu Hailong
Published: October 2017

Modeling of transcriptional regulatory networks (TRNs) has been increasingly used to dissect the nature of gene regulation. Inference of regulatory relationships among transcription factors (TFs) and genes, especially among multiple TFs, is still challenging. In this study, we introduced an integrative method, LogicTRN, to decode TF–TF interactions that form TF logics in regulating target genes. By combiningcis-regulatory logics and transcriptional kinetics into one single model framework, LogicTRN can naturally integrate dynamic gene expression data and TF-DNA-binding signals in order to identify the TF logics and to reconstruct the underlying TRNs. We evaluated the newly developed methodology using simulation, comparison and application studies, and the results not only show their consistence with existing knowledge, but also demonstrate its ability to accurately reconstruct TRNs in biological complex systems.
Staphylococcus aureus interaction with Pseudomonas aeruginosa biofilm enhances tobramycin resistance
Authors: Beaudoin T. , Yau Y. C. W. , Stapleton P. J. , Gong Y. , Wang P. W. , Guttman D. S. , Waters V.
Published: October 2017

Antimicrobial resistance is a significant threat to the treatment of infectious disease. Multiple mechanisms of resistance to different classes of antibiotics have been identified and well-studied. However, these mechanisms are studied with bacteria in isolation, whereas often, infections have a polymicrobial basis. Using a biofilm slide chamber model, we visualized the formation and development of clinical Pseudomonas aeruginosa biofilms in the presence of secreted Staphylococcus aureus exoproducts, two bacteria that commonly co-infect pediatric patients with cystic fibrosis. We showed that, over time, certain isolates of P. aeruginosa can form different biofilm architecture in the presence of S. aureus exoproducts. We further determined that this interaction was dependent on Psl produced by P. aeruginosa and staphylococcal protein A from S. aureus. Importantly, we identified a mechanism of antibiotic resistance to tobramycin that is dependent on the polymicrobial interactions between these two bacteria. This interaction occurred in isolates of P. aeruginosa recovered from children with cystic fibrosis who failed to clear P. aeruginosa following inhaled tobramycin treatment.
Myosin X is recruited to nascent focal adhesions at the leading edge and induces multi-cycle filopodial elongation
Authors: He Kangmin , Sakai Tsuyoshi , Tsukasaki Yoshikazu , Watanabe Tomonobu M. , Ikebe Mitsuo
Published: October 2017

Filopodia protrude from the leading edge of cells and play important roles in cell motility. Here we report the mechanism of myosin X (encoded by Myo10)-induced multi-cycle filopodia extension. We found that actin, Arp2/3, vinculin and integrin-β first accumulated at the cell’s leading edge. Myosin X was then gathered at these sites, gradually clustered by lateral movement, and subsequently initiated filopodia formation. During filopodia extension, we found the translocation of Arp2/3 and integrin-β along filopodia. Arp2/3 and integrin-β then became localized at the tip of filopodia, from where myosin X initiated the second extension of filopodia with a change in extension direction, thus producing long filopodia. Elimination of integrin-β, Arp2/3 and vinculin by siRNA significantly attenuated the myosin-X-induced long filopodia formation. We propose the following mechanism. Myosin X accumulates at nascent focal adhesions at the cell’s leading edge, where myosin X promotes actin convergence to create the base of filopodia. Then myosin X moves to the filopodia tip and attracts integrin-β and Arp2/3 for further actin nucleation. The tip-located myosin X then initiates the second cycle of filopodia elongation to produce the long filopodia.
Effect of Specific Mutations in Cd300 Complexes Formation; Potential Implication of Cd300f in Multiple Sclerosis
Authors: Martínez-Barriocanal Águeda , Arcas-García Andrea , Magallon-Lorenz Miriam , Ejarque-Ortíz Aroa , Negro-Demontel María Luciana , Comas-Casellas Emma , Schwartz Simo , Malhotra Sunny , Montalban Xavier , Peluffo Hugo , Martín Margarita , Comabella Manuel , Sayós Joan
Published: October 2017

Herein, we have used bioinformatics tools to predict five clusters defining ligand-binding sites on the extracellular domain of human CD300b receptor, presumably involved in the formation of both homodimers and heterodimers with other CD300 family members. Site-directed mutagenesis revealed residues glutamic acid 28 and glutamine 29 in cluster 5 to be necessary for the formation of CD300b complexes. Surprisingly, the disruption of cluster 2 and 4 reconstituted the binding capability lost by the mutation of residues glutamic acid 28 to alanine, glutamine 29 to alanine (E28A-Q29G). We identified a missense mutation arginine 33 to glutamine (R33Q) in CD300f by direct sequencing of exon 2 in peripheral blood samples from 50 patients with multiple sclerosis (MS). Levels of expression of CD300f were almost undetectable on monocytes from the patient bearing the R33Q mutation compared with healthy individuals. Whereas R33Q mutation had no effect in the formation of CD300f complexes, the inhibition of protein synthesis with cycloheximide indicated that CD300f R33Q is less stable than native CD300f. Finally, we report that the levels of expression of CD300f on the surface of classical and intermediate monocytes from MS patients are significantly lower when compared to the same cell populations in healthy individuals.
Racial disparities in patient survival and tumor mutation burden, and the association between tumor mutation burden and cancer incidence rate
Authors: Zhang Wensheng , Edwards Andrea , Flemington Erik K. , Zhang Kun
Published: October 2017

The causes underlying racial disparities in cancer are multifactorial. In addition to socioeconomic issues, biological factors may contribute to these inequities, especially in disease incidence and patient survival. To date, there have been few studies that relate the disparities in these aspects to genetic aberrations. In this work, we studied the impacts of race on the patient survival and tumor mutation burden using the data released by the Cancer Genome Atlas (TCGA). The potential relationship between mutation burden and disease incidence is further inferred by an integrative analysis of TCGA data and the data from the Surveillance, Epidemiology, and End Results (SEER) Program. The results show that disparities are present (p < 0.05) in patient survival of five cancers, such as head and neck squamous cell carcinoma. The numbers of tumor driver mutations are differentiated (p < 0.05) over the racial groups in five cancers, such as lung adenocarcinoma. By treating a specific cancer type and a racial group as an “experimental unit”, driver mutation numbers demonstrate a significant (r = 0.46, p < 0.002) positive correlation with cancer incidence rates, especially when the five cancers with mutational disparities are exclusively focused (r = 0.88, p < 0.00002). These results enrich our understanding of racial disparities in cancer and carcinogenic process.