bluuebunny/crossref_metadata_2025 huggingface dataset:
Was maize domesticated in the Balsas Basin? Complex patterns of genetic divergence, gene flow and ancestral introgressions among Zea subspecies suggest an alternative scenario
Authors: Moreno-Letelier Alejandra , Aguirre-Liguori J.A. , Tenaillon Maud I. , Piñero Daniel , Gaut Brandon S. , Vázquez-Lobo Alejandra , Eguiarte Luis E.
Published: December 2017

The study of maize domestication has overlooked the genetic structure within maize’s wild relative teosinte. Prior to investigating the domestication history of maize (Zea mays subspecies mays), one should first understand the population history of teosintes and how they relate to maize. To achieve this, we used 32,739 SNPs obtained from a broad sampling of teosinte populations and 46 maize landraces and a) inferred current and past gene flow among teosinte populations and maize, b) analyzed the degree of introgression among Zea mays subspecies, and c) explored the putative domestication location of maize. We found geographic structure and introgression between Zea mays taxa. Teosinte subspecies have diverged significantly from maize, which indicates that current teosinte populations have evolved mainly independently from maize since the domestication. Our results further suggest that the likely ancestor of maize may maybe have come from Jalisco or the Pacific coast.

One Sentence Summary

Shared polymorphism in teosinte suggests a Jalisco origin of maize domestication.
Chromatin and nucleosome dynamics in DNA damage and repair
Authors: Hauer Michael H. , Gasser Susan M.
Published: December 2017

Chromatin is organized into higher-order structures that form subcompartments in interphase nuclei. Different categories of specialized enzymes act on chromatin and regulate its compaction and biophysical characteristics in response to physiological conditions. We present an overview of the function of chromatin structure and its dynamic changes in response to genotoxic stress, focusing on both subnuclear organization and the physical mobility of DNA. We review the requirements and mechanisms that cause chromatin relocation, enhanced mobility, and chromatin unfolding as a consequence of genotoxic lesions. An intriguing link has been established recently between enhanced chromatin dynamics and histone loss.
Framework for sustainable construction practices in Sri Lanka
Authors: Athapaththu Kushani Ishara , Karunasena Gayani
Published: December 2017

Purpose

Sustainability in construction is a challenging task for contractors due to diminishing natural resources and increasing energy costs. The purpose of this paper is to identify key issues that affect the adaptation of sustainable construction practices by Sri Lankan contracting organisations and propose a framework for successful adaptation.

Design/methodology/approach

Eight semi-structured interviews are conducted from three selected case studies to gather data on sustainable construction practices and related issues in contracting organisations in Sri Lanka. The proposed framework is validated and enhanced by interviews conducted with seven industry experts in Sri Lanka and the Persian Gulf region. A cross-case with code-based content analysis is used to analyse the data.

Findings

Gaps in the legal framework and weak enforcement of prevailing rules, less institutional intervention, less commitment of people especially key stakeholders, wrong perceptions on capital costs, and low levels of education and experience on sustainable construction are identified as key issues, similar to the Persian Gulf region. The proposed framework presents suggestions for successful adaptation of sustainable construction practices in the following eight key areas: legal framework, standards, guidelines or policies, design, procurement, technology, processes and innovations, people and organisational structure, education and training, and measurements and reporting.

Research limitations/implications

The scope of this research is limited to the data gathered from C1 category construction contractors in Sri Lanka and similar category in the United Arab Emirates of the Persian Gulf region.

Originality/value

The framework for the enhancement of sustainable construction practices via contracting organisations is proposed as an inaugural step to establishing a country-based and industry-specific model to achieve sustainability in the Sri Lankan construction industry.
Learning and usefulness stemming from collaboration in a maritime crisis management exercise in Northern Norway
Authors: Magnussen Leif Inge , Carlstrøm Eric , Sørensen Jarle Løwe , Torgersen Glenn-Egil , Hagenes Erlend Fritjof , Kristiansen Elsa
Published: December 2017

Purpose

This research investigates the perceived collaboration between public, private, and volunteer organisations during maritime crisis work, with an emphasis on learning and collaboration. The purpose of this paper is to investigate participants’ perceived collaboration training in relation to learning and usefulness.

Design/methodology/approach

The exercise studied in this research was run in the far North in Norway. It was estimated by the participants to be Europe’s most extensive exercise in 2016. Mixed methods research approach was applied, i.e. on-site observations, photos and interviews were conducted during the exercise. After the exercise, an online survey was distributed to emergency personnel holding different positions in conjunction with this exercise.

Findings

As reported, the exercise contributed to new insights on the relationship between collaboration and learning. The study showed that collaborative elements in exercises contribute to perceived learning (R=0.86, R2=0.74), and that learning in turn had a perceived beneficial effect on actual emergency work (R=0.79, R2=0.62).

Research limitations/implications

The possible research implications from this study include more focus on collaboration and new training schemes that could increase learning and usefulness.

Practical implications

Collaboration between actors seemed to suffer from the size of the exercise. A smaller exercise, less dependency on predetermined scripts, and more receptivity towards improvisation could improve collaboration.

Social implications

Increased awareness on the outcomes of collaboration exercise might increase their learning and usefulness, providing societies with improved rescue services.

Originality/value

This research implies that increased perceived collaboration has an effect on learning and usefulness in maritime exercises.
Achieving sustainability through integrating risk management into the architectural design process
Authors: Othman Ayman Ahmed Ezzat , Abdelwahab Nermeen Mohamed Amin
Published: December 2017

Purpose

The purpose of this paper is to develop a framework integrating risk management (RM) into the architectural design process (ADP) as an approach for delivering sustainable construction projects.

Design/methodology/approach

A research methodology, which consisted of literature review and field study, is designed to accomplish four objectives. First, to provide a comprehensive literature review of the concepts of sustainability, ADP and RM. Second, to present and synthesis the results of two relevant studies focused on identifying, quantifying and classifying the risks associated with ADP; and investigating the perception and application of Egyptian architectural design firms (ADFs) towards integrating RM into ADP as an approach for delivering sustainable construction projects. Third, to develop a framework that integrates RM into ADP towards delivering sustainable construction projects. Finally, to draw conclusions and recommendations to improve the practice of delivering sustainable construction projects among ADFs, construction professionals and governmental authorities.

Findings

ADP is a fundamental phase of the construction process because the decisions adopted during this phase affect the project performance throughout its life cycle. While RM is widely applied in different sectors of the construction industry, its application in ADP received scant attention in construction literature. The research identified 18 key risks that affect the sustainable delivery of construction projects during ADP. The architect, the client and the project manager are the highest ranked responsible parties for the occurrence of these key risks. The field study highlighted the need to develop a framework to facilitate integrating RM into ADP.

Research limitations/implications

This paper focused only on the integration of RM into ADP.

Originality/value

The conducted literature review and field study provided an in-depth understanding of the key risks that affect the sustainable delivery of construction projects during ADP. Through its five stages, the proposed framework is expected to serve as a foundation for integrating RM into ADP as an approach for delivering sustainable projects. This ideology has received scant attention in construction literature. The developed framework represents a synthesis that is novel and creative in thought and adds value to the knowledge in a manner that has not previously occurred.
Users’ perceptions of e-learning environments and services effectiveness
Authors: Haq Anwar ul , Magoulas George , Jamal Arshad , Majeed Asim , Sloan Diane
Published: December 2017

Purpose

E-learning environments and services (ELES) adoption and success rates challenge ELES designers, practitioners and organisations. Enterprise decision makers continue to seek effective instruments in launching such systems. The purpose of this paper is to understand users’ perceptions of ELES effectiveness and develop a theoretical framework which improves understanding of success factors for adoption.

Design/methodology/approach

Grounded theory method is used to reflect on the relationships between changing users’ requirements and expectations, technological advances and ELES effectiveness models. A longitudinal study collecting data from social media blogs over four years was authenticated based on the context evaluation, language structure and conversational constructs.

Findings

Identification of a new core dimension named “Concept Functionality” which can be used to understand the relationships between e-learning effectiveness factors including the relationships with other domains such as security. The findings are also used to validate major existing models for the success of ELES.

Practical implications

The new framework potentially improves system design process in the fields of education technology, enterprise systems, etc.

Originality/value

Concept functionality dimension can offer more insights to understand ELES effectiveness and further improve system design process in a variety of domains including enterprise systems, process modelling and education technology.
Implications of efficiency and productivity change over the season for setting MEY‐based trigger targets
Authors: Pascoe Sean , Hutton Trevor , Coglan Louisa , Nguyen Van Quang
Published: December 2017

The banana prawn component of Australia's Northern Prawn Fishery (NPF) is currently managed through the use of annually updated trigger catch rates as a means of achieving maximum economic yield (MEY) in the fishery, taking into account the estimated price and cost components for that season. The estimation of these target catch rates is based on the assumption of relative homogeneity of the fleet in terms of efficiency, productivity and cost structure. In this study, these assumptions are examined through the estimation of a stochastic production frontier. While technical efficiency varies between vessels, average efficiency is relatively constant over the fishing season. However, average productivity of the fleet increases, with smaller vessels (in terms of engine power) exiting the fishery earlier. This would likely increase the average cost of fishing towards the end of the season, with implications for setting the target catch rate. Based on a standard assumption as to the relationship between costs and vessel size, we find that the MEY target catch rates are most likely currently underestimated. However, the implementation of a precautionary minimum catch rate (which is above the MEY target catch rates for recent years) has maintained the fishery at a profitable level.
Can Your Network Make You Happy? Entrepreneurs’ Business Network Utilization and Subjective Well‐being
Authors: Newman Alexander , Mole Kevin F. , Ucbasaran Deniz , Subramanian Nachiappan , Lockett Andy
Published: December 2017

We draw on the conservation of resources theory to examine whether self‐efficacy and resilience mediate the relationship between entrepreneurs’ business network utilization and their subjective well‐being. Using socioemotional selectivity theory, we then examine the extent to which the mediating effects become stronger as entrepreneurs age. An analysis of data collected from 335 entrepreneurs in India reveals that business networks help entrepreneurs build resilience and self‐efficacy, which contribute to subjective well‐being. Furthermore, we find that the relationship between business network utilization and subjective well‐being strengthens as entrepreneurs age. Our findings attest to the importance of understanding how contextual resources in entrepreneurs’ work environments influence their subjective well‐being by enhancing their personal psychological resources.
Estimating the Cost of Providing Foundational Public Health Services
Authors: Mamaril Cezar Brian C. , Mays Glen P. , Branham Douglas Keith , Bekemeier Betty , Marlowe Justin , Timsina Lava
Published: December 2017

Objective

To estimate the cost of resources required to implement a set of Foundational Public Health Services (FPHS) as recommended by the Institute of Medicine.

Study Design

A stochastic simulation model was used to generate probability distributions of input and output costs across 11 FPHS domains. We used an implementation attainment scale to estimate costs of fully implementing FPHS.

Data Collection/Extraction Methods

We use data collected from a diverse cohort of 19 public health agencies located in three states that implemented the FPHS cost estimation methodology in their agencies during 2014–2015.

Principal Findings

The average agency incurred costs of $48 per capita implementing FPHS at their current attainment levels with a coefficient of variation (CV) of 16 percent. Achieving full FPHS implementation would require $82 per capita (CV=19 percent), indicating an estimated resource gap of $34 per capita.

Conclusions

Substantial variation in costs exists across communities in resources currently devoted to implementing FPHS, with even larger variation in resources needed for full attainment. Reducing geographic inequities in FPHS may require novel financing mechanisms and delivery models that allow health agencies to have robust roles within the health system and realize a minimum package of public health services for the nation.
The Impact of Enhanced Critical Care Training and 24/7 (Tele‐ICU) Support on Medicare Spending and Postdischarge Utilization Patterns
Authors: Trombley Matthew J. , Hassol Andrea , Lloyd Jennifer T. , Buchman Timothy G. , Marier Allison F. , White Alan , Colligan Erin
Published: December 2017

Objective

To estimate the effect of implementing a tele‐ICU and a critical care residency training program for advanced practice providers on service utilization and total Medicare episode spending.

Data Sources/Study Settings

Medicare claims data for fee‐for‐service beneficiaries at 12 large, inpatient hospitals in the Atlanta Hospital Referral Region.

Study Design

Difference‐in‐differences design where changes in spending and utilization for Medicare beneficiaries eligible for treatment in participating ICUs was compared to changes in a comparison group of clinically similar beneficiaries treated at similar hospitals’ ICUs in the same hospital referral region.

Extraction Methods

Using Medicare claims data from January 2010 through June 2015, we defined measures of Medicare episode spending during the ICU stay and subsequent 60 days after discharge, and utilization measures within 30 and 60 days after discharge.

Principal Findings

Implementation of the advanced practice provider residency program and tele‐ICU was associated with a significant reduction in average Medicare spending per episode, primarily driven by reduced readmissions within 60 days and substitution of home health care for institutional postacute care.

Conclusions

Innovations in workforce training and technology specific to the ICU may be useful in addressing the shortage of intensivist physicians, yielding benefits to patients and payers.
Digital Stratigraphy: Contextual Analysis of File System Traces in Forensic Science
Authors: Casey Eoghan
Published: December 2017

This work introduces novel methods for conducting forensic analysis of file allocation traces, collectively called digital stratigraphy. These in‐depth forensic analysis methods can provide insight into the origin, composition, distribution, and time frame of strata within storage media. Using case examples and empirical studies, this paper illuminates the successes, challenges, and limitations of digital stratigraphy. This study also shows how understanding file allocation methods can provide insight into concealment activities and how real‐world computer usage can complicate digital stratigraphy. Furthermore, this work explains how forensic analysts have misinterpreted traces of normal file system behavior as indications of concealment activities. This work raises awareness of the value of taking the overall context into account when analyzing file system traces. This work calls for further research in this area and for forensic tools to provide necessary information for such contextual analysis, such as highlighting mass deletion, mass copying, and potential backdating.
Biorefining of platinum group metals from model waste solutions into catalytically active bimetallic nanoparticles
Authors: Murray Angela J. , Zhu Ju , Wood Joe , Macaskie Lynne E.
Published: December 2017

Bacteria can fabricate platinum group metal (PGM) catalysts cheaply, a key consideration of industrial processes and waste decontaminations. Biorecovery of PGMs from wastes is promising but PGM leachates made from metallic scraps are acidic. A two‐step biosynthesis ‘pre‐seeds’ metallic deposits onto bacterial cells benignly; chemical reduction of subsequent metal from acidic solution via the seeds makes bioscaffolded nanoparticles (NPs). Cells of Escherichia coli were seeded using Pd(II) or Pt(IV) and exposed to a mixed Pd(II)/Pt(IV) model solution under H2 to make bimetallic catalyst. Its catalytic activity was assessed in the reduction of Cr(VI), with 2 wt% or 5 wt% preloading of Pd giving the best catalytic activity, while 1 wt% seeds gave a poorer catalyst. Use of Pt seeds gave less effective catalyst in the final bimetallic catalyst, attributed to fewer and larger initial seeds as shown by electron microscopy, which also showed a different pattern of Pd and Pt deposition. Bimetallic catalyst (using cells preloaded with 2 wt% Pd) was used in the hydrogenation of soybean oil which was enhanced by ~fourfold using the bimetallic catalyst made from a model waste solution as compared to 2 wt% Pd preloaded cells alone, with a similar selectivity to cis C18:1 product as found using a Pd‐Al2O3 commercial catalyst.
Simulation of Paleotectonic Stress Fields and Distribution Prediction of Tectonic Fractures at the Hudi Coal Mine, Qinshui Basin
Authors: FANG Huihuang , SANG Shuxun , WANG Jilin , LIU Shiqi , JU Wei
Published: December 2017

Study on tectonic fractures based on the inversion of tectonic stress fields is an effective method. In this study, a geological model was set up based on geological data from the Hudi Coal Mine, Qinshui Basin, a mechanical model was established under the condition of rock mechanics and geostress, and the finite element method was used to simulate the paleotectonic stress field. Based on the Griffith and Mohr‐Coulomb criterion, the distribution of tectonic fractures in the Shanxi Formation during the Indosinian, Yanshanian, and Himalayan period can be predicted with the index of comprehensive rupture rate. The results show that the acting force of the Pacific Plate and the India Plate to the North China Plate formed the direction of principal stress is N‐S, NW ‐ SE, and NE ‐ SW, respectively, in different periods in the study area. Changes in the direction and strength of the acting force led to the regional gradients of tectonic stress magnitude, which resulted in an asymmetrical distribution state of the stress conditions in different periods. It is suggested that the low‐stress areas are mainly located in the fault zones and extend along the direction of the fault zones. Furthermore, the high‐stress areas are located in the junction of fold belts and the binding site of multiple folds. The development of tectonic fractures was affected by the distribution of stress intensity and the tectonic position of folds and faults, which resulted in some developed areas with level I and II. There are obvious differences in the development of tectonic fractures in the fold and fault zones and the anticline and syncline structure at the same fold zones. The tectonic fractures of the Shanxi Formation during the Himalayan period are more developed than those during the Indosinian and Yanshanian period due to the superposition of the late tectonic movement to the early tectonic movement and the differences in the magnitude and direction of stress intensity.
p.X654R IDUA variant among Thai individuals with intermediate mucopolysaccharidosis type I and its residual activity as demonstrated in COS‐7 cells
Authors: Ngiwsara Lukana , Ketudat‐Cairns James R. , Sawangareetrakul Phannee , Charoenwattanasatien Ratana , Champattanachai Voraratt , Kuptanon Chulaluck , Pangkanon Suthipong , Tim‐Aroon Thipwimol , Wattanasirichaigoon Duangrurdee , Svasti Jisnuson
Published: December 2017

Background

Mucopolysaccharidosis type I (MPS I) is a rare autosomal‐recessive disorder caused by defects in alpha‐L‐iduronidase (IDUA), a lysosomal enzyme encoded by the IDUA gene. Herein, we characterized IDUA mutations underlying mucopolysaccharidosis type I intermediate form (Hurler–Scheie syndrome) and its molecular pathogenic mechanisms.

Methods

Clinical data, activity of the IDUA enzyme in leukocytes, and a mutation of the IDUA gene were analyzed. Pathogenesis associated with an IDUA mutation was further investigated by evaluating the mutant cDNA sequence, protein expression and activity in COS‐7 cells.

Results

Five unrelated patients were identified to have clinical diagnosis of intermediate form of MPS I (Hurler–Scheie) and exhibited low‐to‐absent levels of leukocyte IDUA activity. Genetic analysis revealed homozygous c.*1T>C (p.X654R) mutation in two patients and compound heterozygosity between the c.*1T>C and another allele including c.265G>A (p.R89Q), c.935G>A (p.W312X), or c.1138 C>T (p.Q380X), each in a single patient. Sequencing the 3′RACE product of the c.*1T>C (p.X654R) allele indicated a 38‐amino acids elongation of the mutant protein. COS‐7 cells expressing IDUA with the mutations exhibited extremely low levels or complete absence of enzyme activity compared to wild‐type IDUA. Western blot analysis detected no protein in p.W312X and p.Q380X samples, while an elevated molecular mass and a different pattern of protein bands were found in p.X654R specimen compared with the wild type IDUA.

Conclusions

Mutational spectrum underlying intermediate MPS I is expanded. Our data suggest that the p.X654R is an intermediate IDUA mutant allele with residual enzyme activity. It can lead to intermediate or milder form of MPS I depending on another associated allele.
The association of RAR‐related orphan receptor A (RORA) gene polymorphisms with the risk of asthma
Authors: Cai Xulong , Lin Mali , Cao Shan , Liu Yunguang , Lin Na
Published: December 2017

Asthma is a common, heterogeneous chronic respiratory disease characterized by chronic inflammation of the airway, airway hyperreactivity, and airway remodeling. The RAR‐related orphan receptor A (RORA) gene has been identified for the pathogenesis of asthma. The purpose of this research was to investigate the relationship between RORA gene polymorphisms and asthma susceptibility in the Chinese Zhuang population. This was a case–control study including 231 children with asthma and 343 healthy controls. The RORA gene polymorphisms were measured by the polymerase chain reaction–ligase detection reaction genotyping assays and confirmed by sequencing. The distribution of the genotype frequencies of the RORA rs11071559 C>T was significantly different in the group of cases and the healthy children (P < 0.05). By haplotype analyses, the haplotype TT (rs7164773/rs11071559) was statistically significant between asthmatics and nonasthmatics, but the association was not significant after correction for multiple comparisons. Our results provided evidence that the RORA rs11071559C>T polymorphism was associated with an elevated susceptibility to pediatric asthma in the Chinese Zhuang population.
“From One Shore to the Other”: Other Revolutions in the Interstices of the Revolution
Authors: Tazzioli Martina
Published: December 2017

This interview with Imed Soltani and Federica Sossi focuses on the campaign of the families of the missing Tunisian migrants, “From One Shore to the Other: Lives that Matter”. The campaign started in 2011 to demand that Italian and Tunisian institutions be held accountable for the disappearance of young Tunisian migrants who crossed the Mediterranean to Italy. The campaign brought together the families of Tunisian migrants and the Italian feminist collective “Le Venticinqueundici” as part of a migration struggle that involves the entire region but is rarely taken up as a cross‐shore militant campaign. The conversation between Soltani and Sossi illustrates the strengths of the campaign and the difficulties that arose in running it across shores, and offers a theoretical reflection on the notion of political recognition in an effort to decolonise the gaze on what counts as political subjectivity and political struggle.
Effect of chopping time and heating on 1H nuclear magnetic resonance and rheological behavior of meat batter matrix
Authors: Zhou Fen , Dong Hui , Shao Jun‐Hua , Zhang Jun‐Long , Liu Deng‐Yong
Published: December 2017

The effect of chopping time and heating on physicochemical properties of meat batters was investigated by low‐field nuclear magnetic resonance and rheology technology. Cooking loss and L* increased while texture profile analysis index decreased between chopping 5 and 6 min. The relaxation time T21 (bound water) and its peak area ratio decreased, while the ratio of T22 peak area (immobilized water) in raw meat batters gradually increased with the extension of chopping time. However, T22 was opposite after being heated and a new component T23 (free water) appeared (T2i is the spin – spin relaxation time for the ith component.). The initial damping factor (Tan δ) gradually decreased and there were significant difference between 4 and 5 min of chopping time. There were significantly positive correlations between the ratio of peak area of T22 and chopping time, the storage modulus (G′), cooking loss, and L*, respectively. Continued chopping time could improve the peak area proportion of T22 in raw meat batters. Further, the higher the peak area proportion of T22 in raw meat batters, the cooking loss of heated meat gel was higher. Also, the stronger the mobility of immobilized water in meat batter, the higher the L* of the fresh meat batters. Thus, it is revealed that the physicochemical properties of meat batter are significantly influenced by chopping time which further affects the water holding capacity and the texture of emulsification gel.
β‐adrenergic Receptor Blocker ICI 118,551 Selectively Increases Intermediate‐Conductance Calcium‐Activated Potassium Channel (IKCa)‐Mediated Relaxations in Rat Main Mesenteric Artery
Authors: Ozkan Melike Hacer , Uma Serdar
Published: December 2017

Endothelial IKCa and/or SKCa channels play an important role in the control of vascular tone by participating in endothelium‐dependent relaxation. Whether β‐AR antagonists, mainly used in hypertension, affect endothelial KCa channel function is unknown. In this study, we examined the effect of the β2‐AR antagonist and inverse agonist ICI 118,551 on the IKCa/SKCa channel activity by assessing functional relaxation responses to several agonists that stimulate these channels. Mesenteric arterial rings isolated from male Sprague Dawley mounted to organ baths. Acetylcholine elicited IKCa‐ and SKCa‐mediated relaxations that were abolished by TRAM‐34 and apamin, respectively. ICI 118,551, which did not dilate the arteries per se, increased the IKCa‐mediated relaxations, whereas SKCa‐mediated relaxations remained unaltered. Same potentiating effect was also detected on the IKCa‐mediated relaxations to carbachol and A23187, but not to NS309. Neither acetylcholine‐induced nitric oxide‐mediated relaxations nor SNP relaxations changed with ICI 118,551. The PKA inhibitor KT‐5720, the selective β2‐AR agonist salbutamol, the selective β2‐AR antagonist butoxamine, the non‐selective β‐AR antagonist propranolol, and the inverse agonists carvedilol or nadolol failed to affect the IKCa‐mediated relaxations. ICI 118,551‐induced increase was not reversed by salbutamol or propranolol as well. Besides, low potassium‐induced relaxations in endothelium‐removed arteries remained the same in the presence of ICI 118,551. These data demonstrate a previously unrecognized action of ICI 118,551, the ability to potentiate endothelial IKCa channel‐mediated vasodilation, through a mechanism independent of β2‐AR antagonistic or inverse agonistic action. Instead, the enhancement of acetylcholine relaxation seems likely to occur by a mechanism secondary to endothelial calcium increase.
Tanshinones that selectively block the collagenase activity of cathepsin K provide a novel class of ectosteric antiresorptive agents for bone
Authors: Panwar Preety , Law Simon , Jamroz Andrew , Azizi Pouya , Zhang Dongwei , Ciufolini Marco , Brömme Dieter
Published: December 2017

Background and Purpose

Attempts to generate active site‐directed cathepsin K (CatK) inhibitors for the treatment of osteoporosis have failed because of side effects. We have previously shown that an ectosteric tanshinone CatK inhibitor isolated from Salvia miltiorrhiza blocked, selectively, the collagenase activity of CatK, without affecting the active site and demonstrated its bone‐preserving activity in vivo. Here, we have characterize the antiresorptive potential of other tanshinones, which may provide a scaffold for side effect‐free CatK inhibitors.

Experimental Approach

Thirty‐one tanshinones were tested for their activity against CatK in enzymic and cell‐based assays. The inhibitory potency against triple helical and fibrillar collagen degradation was determined in enzymic assays, by scanning electron microscopy and mechanical strength measurements. Human osteoclast assays were used to determine the effects of the inhibitors on bone resorption, its reversibility and osteoclastogenesis. Binding sites were characterized by molecular docking.

Key Results

Twelve compounds showed highly effective anti‐collagenase activity and protected collagen against destruction and mechanical instability without inhibiting the hydrolysis of non‐collagenous substrates. Six compounds were highly effective in osteoclast bone resorption assays with IC50 values of <500 nM. None of these tanshinones had effects on cell viability, reversibility of bone resorption inhibition and osteoclastogenesis. The core pharmacophore of the tanshinones appears to be the three‐ring system with either a para‐ or ortho‐quinone entity.

Conclusions and Implications

Our study identified several potent ectosteric antiresorptive CatK inhibitors from the medicinal plant, S. miltiorrhiza, which may avoid side effects seen with active site‐directed inhibitors in clinical trials.
Our GIS is too small
Authors: Gahegan Mark
Published: December 2017

GIScience and GISystems have been successful in tackling many geographical problems over the last 30 years. But technologies and associated theory can become limiting if they end up defining how we see the world and what we believe are worthy and tractable research problems. This paper explores some of the limitations currently impacting GISystems and GIScience from the perspective of technology and community, contrasting GIScience with other informatics communities and their practices. It explores several themes: (i) GIScience and the informatics revolution; (ii) the lack of a community‐owned innovation platform for GIScience research; (iii) the computational limitations imposed by desktop computing and the inability to scale up analysis; (iv) the continued failure to support the temporal dimension, and especially dynamic processes and models with feedbacks; (v) the challenge of embracing a wider and more heterogeneous view of geographical representation and analysis; and (vi) the urgent need to foster an active software development community to redress some of these shortcomings. A brief discussion then summarizes the issues and suggests that GIScience needs to work harder as a community to become more relevant to the broader geographic field and meet a bigger set of representation, analysis, and modelling needs.
Bone marrow mesenchymal stem cells promote head and neck cancer progression through Periostin‐mediated phosphoinositide 3‐kinase/Akt/mammalian target of rapamycin
Authors: Liu Chuanxia , Feng Xiaoxia , Wang Baixiang , Wang Xinhua , Wang Chaowei , Yu Mengfei , Cao Guifen , Wang Huiming
Published: December 2017

Bone marrow mesenchymal stem cells (BMMSC) have been shown to be recruited to the tumor microenvironment and exert a tumor‐promoting effect in a variety of cancers. However, the molecular mechanisms related to the tumor‐promoting effect of BMMSC on head and neck cancer (HNC) are not clear. In this study, we investigated Periostin (POSTN) and its roles in the tumor‐promoting effect of BMMSC on HNC. In vitro analysis of HNC cells cultured in BMMSC‐conditioned media (MSC‐CM) showed that MSC‐CM significantly promoted cancer progression by enhancing cell proliferation, migration, epithelial‐mesenchymal transformation (EMT), and altering expression of cell cycle regulatory proteins and inhibition of apoptosis. Moreover, MSC‐CM promoted the expression of POSTN and POSTN promoted HNC progression through the activation of the phosphoinositide 3‐kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) signaling pathway. In a murine model of HNC, we found that BMMSC promoted tumor growth, invasion, metastasis and enhanced the expression of POSTN and EMT in tumor tissues. Clinical sample analysis further confirmed that the expression of POSTN and N‐cadherin were correlated with pathological grade and lymph node metastasis of HNC. In conclusion, this study indicated that BMMSC promoted proliferation, invasion, survival, tumorigenicity and migration of head and neck cancer through POSTN‐mediated PI3K/Akt/mTOR activation.
Pembrolizumab in Asia‐Pacific patients with advanced head and neck squamous cell carcinoma: Analyses from KEYNOTE‐012
Authors: Tahara Makoto , Muro Kei , Hasegawa Yasuhisa , Chung Hyun Cheol , Lin Chia‐Chi , Keam Bhumsuk , Takahashi Kenichi , Cheng Jonathan D. , Bang Yung‐Jue
Published: December 2017

KEYNOTE‐012 was a phase Ib, multicohort study designed to investigate efficacy and safety of pembrolizumab in advanced solid tumors. Results from the subset of patients with recurrent/metastatic head and neck squamous cell carcinoma (HNSCC) from the Asia‐Pacific region are reported. Patients with recurrent/metastatic HNSCC, measurable disease (RECIST version 1.1), and ECOG performance status (PS) 0‐1 were eligible for enrollment in the HNSCC expansion cohort. Patients received pembrolizumab 200 mg every 3 weeks. Response was assessed every 8 weeks. Co‐primary end‐points were safety and overall response rate (RECIST version 1.1, central review). Secondary end‐points included overall survival and response duration. Patients enrolled at any of the five centers throughout the Asia‐Pacific region were included in these analyses. Twenty‐six patients with HNSCC from the Asia‐Pacific region received pembrolizumab. The median age was 62 years, 65% of patients had ECOG PS 1, and 62% had received two or more prior therapies for recurrent/metastatic disease. Sixteen (62%) patients experienced a treatment‐related adverse event of any grade, including two (8%) patients who experienced one or more events of grade 3 severity. No treatment‐related deaths occurred. The overall response rate was 19% (95% confidence interval, 7%‐39%). After a median follow‐up of 12 months (range, 2‐21 months), a median response duration was not reached (range, 6 to 17+ months); four of five responses lasted ≥6 months. Median overall survival was 11.6 months (95% confidence interval, 4.7‐17.7 months). Pembrolizumab was well tolerated and had durable antitumor activity in patients with HNSCC from the Asia‐Pacific region. (Trial registration no. NCT01848834.)
Glucose-6-phosphate dehydrogenase inhibition attenuates acute lung injury through reduction in NADPH oxidase-derived reactive oxygen species
Authors: Nadeem A , Al-Harbi N O , Ahmad S F , Ibrahim K E , Siddiqui N , Al-Harbi M M
Published: December 2017

Acute lung injury (ALI) is a heterogeneous disease with the hallmarks of alveolar capillary membrane injury, increased pulmonary oedema and pulmonary inflammation. The most common direct aetiological factor for ALI is usually parenchymal lung infection or haemorrhage. Reactive oxygen species (ROS) generated by nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (NOX2) are thought to play an important role in the pathophysiology of ALI. Glucose-6-phosphate dehydrogenase (G6PD) plays an important role both in production of ROS as well as their removal through the supply of NADPH. However, how G6PD modulation affects NOX2-mediated ROS in the airway epithelial cells (AECs) during acute lung injury has not been explored previously. Therefore, we investigated the effect of G6PD inhibitor, 6-aminonicotinamide on G6PD activity, NOX2 expression, ROS production and enzymatic anti-oxidants in AECs in a mouse model of ALI induced by lipopolysaccharide (LPS). ALI led to increased G6PD activity in the AECs with concomitant elevation of NOX2, ROS, SOD1 and nitrotyrosine. G6PD inhibitor led to reduction of LPS-induced airway inflammation, bronchoalveolar lavage fluid protein concentration as well as NOX2-derived ROS and subsequent oxidative stress. Conversely, ALI led to decreased glutathione reductase activity in AECs, which was normalized by G6PD inhibitor. These data show that activation of G6PD is associated with enhancement of oxidative inflammation in during ALI. Therefore, inhibition of G6PD might be a beneficial strategy during ALI to limit oxidative damage and ameliorate airway inflammation.
Maternal Nanos‐Dependent RNA Stabilization in the Primordial Germ Cells of Drosophila Embryos
Authors: Sugimori Seiko , Kumata Yuji , Kobayashi Satoru
Published: December 2017

Nanos (Nos) is an evolutionary conserved protein expressed in the germline of various animal species. In Drosophila, maternal Nos protein is essential for germline development. In the germline progenitors, or the primordial germ cells (PGCs), Nos binds to the 3′ UTR of target mRNAs to repress their translation. In contrast to this prevailing role of Nos, here we report that the 3′ UTR of CG32425 mRNA mediates Nos‐dependent RNA stabilization in PGCs. We found that the level of mRNA expressed from a reporter gene fused to the CG32425 3′ UTR was significantly reduced in PGCs lacking maternal Nos (nos PGCs) as compared with normal PGCs. By deleting the CG32425 3′ UTR, we identified the region required for mRNA stabilization, which includes Nos‐binding sites. In normal embryos, CG32425 mRNA was maternally supplied into PGCs and remained in this cell type during embryogenesis. However, as expected from our reporter assay, the levels of CG32425 mRNA and its protein product expressed in nos PGCs were lower than in normal PGCs. Thus, we propose that Nos protein has dual functions in translational repression and stabilization of specific RNAs to ensure proper germline development.
A proposed framework of key activities and processes in the preparedness and recovery phases of disaster management
Authors: Oloruntoba Richard , Sridharan Ramaswami , Davison Graydon
Published: December 2017

This paper proposes an empirically grounded framework for examining the preparedness and recovery phases of disaster management activities and processes pertaining to predictable disasters within a developed country. The two‐stage framework provides a single model composed of important preparedness and recovery initiatives, as well as activities and processes derived from empirical data collected for case studies from Australia: the ‘Black Saturday’ bushfires in the state of Victoria in February 2009; and Cyclone Larry in March 2006. The framework enables a variety of analyses, including the generation of insights into disaster management preparedness and recovery in the context of events in wealthy developed countries. The paper combines two empirical examples, a series of bushfires and a severe tropical cyclone, to enhance understanding of, and to contribute to better, disaster preparedness and recovery in the future. The paper contributes to the growing literature on disasters, preparedness, recovery and associated logistics, and other issues.
Have cash transfers succeeded in reaching the poor in Latin America and the Caribbean?
Authors: Robles Marcos , Rubio Marcela G. , Stampini Marco
Published: December 2017

We present original estimates of the quality of targeting of conditional cash transfer (CCT) and non‐contributory pension (NCP) programmes in Latin America and the Caribbean. Our contribution is novel because we use both national and international poverty lines; provide differentiated estimates for urban and rural areas; and compare theCCTandNCPprogrammes. We show that leakage to the non‐poor coexists with pervasive under‐coverage of all poor, including the extreme poor. On average, theCCTs cover only 50.5% of the extreme poor in households with children under 18 years of age. Similarly, theNCPs cover only 50.9% of the extreme poor in households with elderly members who do not receive a contributory pension. At the same time, 40.4% ofCCTbeneficiaries and 50.1% ofNCPbeneficiaries are not poor, highlighting the potential need for re‐targeting and re‐certification. In most countries, re‐targeting could produce a substantial double benefit in terms of poverty reduction and fiscal savings.
Tooth injuries: Knowledge of parents of public school students from the city of Alfenas, Minas Gerais, Brazil
Authors: Cosme‐Silva Leopoldo , Fernandes Leandro A. , Rosselli Eliana R. , Poi Wilson R. , Martins Natália da Silva , de Lima Daniela C.
Published: December 2017

Background/Aims

The prognosis of traumatized teeth can be optimized if appropriate procedures are following at the time of the accident. The aim of this study was to evaluate the level of knowledge of students’ parents from a group of Brazilian schools regarding fracture and tooth avulsion in permanent teeth.

Methods

Parents of 802 students were interviewed using a pre‐tested questionnaire designed to explore how they would manage their child's dental avulsion or fracture.

Results

Among the parents, 8.6% reported their child had already suffered tooth injuries. Concerning dental fracture, 49.5% considered the possibility of bonding the tooth fragment and, for dental avulsion, 65.5% considered tooth replantation. Approximately 33.5% of parents would take the child to the dental office in case of fracture or dental avulsion, and of those, 66.2% would do so immediately. Further, 69.5% (for fracture) and 70.4% (for avulsion) would do so regardless of symptoms; only 24.2% and 21.3%, respectively, would seek care only if there was pain. In case of avulsion, 22.3% of those interviewed would store the tooth in liquid, such as saline solution (17.8%), water (16.4%) and fresh milk (12.2%).

Conclusion

Parents had partial and insufficient knowledge as to the proper approach to be adopted in cases of fracture and dental avulsion. Previous experience of dental trauma was not related to more appropriate behavior regarding these injuries.
The Great Famine in the county of Flanders (1315–17): the complex interaction between weather, warfare, and property rights
Authors: Geens Sam
Published: December 2017

The exceptional weather conditions and associated harvest failures of 1315–17 marked the beginning of the worst subsistence crisis in European history. Until now, historians have mainly viewed the Great Famine, and medieval famines in general, through theoretical models of the larger fourteenth‐century crisis. However, this article suggests that this approach is flawed and instead applies recent theories on contemporary famines to the crisis of 1315–17 in the county of Flanders. This new perspective not only leads to a re‐examination of existing explanations, such as the role of warfare, but also reveals the importance of property rights in entitlement to food: the power of elites, the relative number of large‐scale landowners, and the structure of household income all influenced peasants’ degree of vulnerability.
Characterizing synchrony patterns across cognitive task stages of associative recognition memory
Authors: Portoles Oscar , Borst Jelmer P. , van Vugt Marieke K.
Published: December 2017

Numerous studies seek to understand the role of oscillatory synchronization in cognition. This problem is particularly challenging in the context of complex cognitive behavior, which consists of a sequence of processing steps with uncertain duration. In this study, we analyzed oscillatory connectivity measures in time windows that previous computational models had associated with a specific sequence of processing steps in an associative memory recognition task (visual encoding, familiarity, memory retrieval, decision making, and motor response). The timing of these processing steps was estimated on a single‐trial basis with a novel hidden semi‐Markov model multivariate pattern analysis (HSMM‐MVPA) method. We show that different processing stages are associated with specific patterns of oscillatory connectivity. Visual encoding is characterized by a dense network connecting frontal, posterior, and temporal areas as well as frontal and occipital phase locking in the 4–9 Hz theta band. Familiarity is associated with frontal phase locking in the 9–14 Hz alpha band. Decision making is associated with frontal and temporo‐central interhemispheric connections in the alpha band. During decision making, a second network in the theta band that connects left‐temporal, central, and occipital areas bears similarity to the neural signature for preparing a motor response. A similar theta band network is also present during the motor response, with additionally alpha band connectivity between right‐temporal and posterior areas. This demonstrates that the processing stages discovered with the HSMM‐MVPA method are indeed linked to distinct synchronization patterns, leading to a closer understanding of the functional role of oscillations in cognition.