bluuebunny/crossref_metadata_2025 huggingface dataset:
Plugging the skills gap: the vital role that women should play in cyber-security
Authors: Cobb Michelle Johnson
Published: January 2018

The past year has been dominated by cyber-security incidents in the news, including three of the biggest ransomware attacks ever to hit companies globally. Last September's massive Equifax breach continues to throw a spotlight on cyber-security and highlight how important it is for organisations to have protective cyber-security measures in place. Prior to the Apache Struts exploit, many organisations – including critical infrastructure firms – fell victim to WannaCry and NotPetya, increasing cyber-security concerns for nation states as well as businesses.

While headlines are full of high-profile breaches, organisations are struggling to find enough people with cyber-security skills. Yet women remain notable by their absence in the cyber-security world.

This isn't due to lack of qualifications. There are plenty of women with backgrounds in computer science and other technical and scientific fields who could meet this need. So why isn't this happening? Michelle Johnson Cobb of Skybox Security examines the hurdles that women face and, importantly, how they represent an untapped resource that could address serious issues faced by organisations.
Using the service desk to secure the organisation
Authors: Smith Kevin
Published: January 2018

Shadowy hackers and cyber-spies tend to dominate the public perception of online threats. Accompanied by clichéd stock images of grim-looking figures wearing face masks and oversized hoodies, they make for great headlines and an over-simplified metaphor to help the public understand the growing cyber-threat landscape. However, the more mundane reality is that – whether directly or indirectly – your everyday employees are the source of most threats to the organisation. The question is, what can we do to mitigate the risk of the insider threat

Your employees are the source of most threats to the organisation. The question is, what can we do to mitigate the risk?

The key is to bring together relevant IT and security teams united through the actions of an empowered service desk. You'll get better at detecting the early warning signs of a serious threat and proactively securing your endpoints. This kind of preventative approach could end up saving you millions in breach-related losses, argues Kevin Smith of Ivanti.
Indexes of Caring for Elderly in Earthquakes According to the Iranian Experience: A Qualitative Study
Authors: Khodadadi Hassan , Vatankhah Soudabeh , Sadeghi Tabandeh
Published: January 2018

Objective

The elderly are especially susceptible to death and injury in disasters. This study aimed to identify indexes of caring for elderly people in an earthquake according to the Iranian experience.

Methods

This qualitative study was conducted during 2014–2016 by use of the content analysis technique. Data were collected through individual deep interviews with the elderly and people with experience providing services to the elderly during earthquakes in an urban area of Iran. The data were analyzed by use of the Graneheim and Lundman method.

Results

Seven categories emerged: vulnerability of elderly people, physiological indexes, psychological indexes, economic indexes, religious and spiritual indexes, health indexes, and security indexes. There were 3 uncategorized issues: “There is no specific protocol for the elderly,” “The need to design plans based on age care,” and “Aid organizations.”

Conclusions

Implementing a comprehensive plan would not only save lives but decrease suffering and enable effective use of available resources. Due to the crucial role of the prehospital care system in disasters, there is a need for further investigation based on the results of this study to develop strategies for improving the system. (Disaster Med Public Health Preparedness. 2018;12:493–501)
Triage by Resource Allocation for INpatients: A Novel Disaster Triage Tool for Hospitalized Pediatric Patients
Authors: Lin Anna , Taylor Kristine , Cohen Ronald S.
Published: January 2018

Objective

To develop a disaster triage tool for the evacuation of hospitalized neonatal and pediatric populations.

Methods

We expanded an existing neonatal disaster triage tool for the evacuation of a children’s hospital. We assessed inpatients using bedside visual assessments and chart review to categorize patients transport level based on local emergency medical services protocols and expert opinion. The tool was refined by using multiple Plan Do Study Act cycles. Primary outcome was the number of each level of transport required for hospital evacuation. Secondary outcome was improved efficiency of obtaining information about specific transport needs for evacuation.

Results

We evaluated 1382 patients both visually and through electronic chart review over 10 random days. Accordance between visual assessment and electronic chart review reached 96.3%. During a 2 hour statewide disaster drill, no hospital units completed self-assessed transport needs for their patients; a single nurse used Triage by Resource Allocation in INpatients to determine transportation needs in less than 1 hour. (Disaster Med Public Health Preparedness. 2018;12:692-696)
Characterisation of the French ferret population, husbandry, reported medical care and feeding habits
Authors: Blanchard Géraldine , Marsot Maud , Bourassin Roselyne , Paragon Bernard-Marie , Benet Jean-Jacques , Linsart Adeline
Published: January 2018

Ferrets have become a common companion animal. But no data are available on the French population of ferrets. The goal of the survey was to characterise this population, including demographic characteristics, husbandry, reported medical care and feeding habits. Complete data were available for 1205 pet ferrets in 709 households. Most ferrets (86·1 %) lived indoors, 1 % received only artificial lighting, and 47 % chewed their cage. For 60 % of the ferrets, body weight was higher in winter and lower in summer. Neutered ferrets (58·5 % of males and 62·9 % of females) appeared lighter than intact ferrets of comparable age. A majority (52·4 %) of ferrets received a mix of commercial foods and fresh foods, but 28·6 % were offered no commercial foods. Data were analysed using several multivariable logistic regression models including age, sex, castration, food type and artificial lighting developed for four clinical outcome (lethargy and/or insulinoma, dental problems, diarrhoea and/or bird-seed stools and alopecia). Predictors of four clinical outcomes (lethargy, dental disease, diarrhoea and alopecia) were examined using multivariable logistic regression, with age, sex, neuter status, food type and artificial lighting as the exposure variables. Aged ferrets were more likely to have lethargy, insulinoma, dental problems and alopecia. Ferrets with artificial lighting were more likely to show alopecia. Additionally, ferrets fed commercial food only or a mixed diet (both commercial food and fresh food) were more likely to have lethargy, insulinoma, dental problems, diarrhoea and/or bird-seed stools compared with ferrets fed fresh food only. We also found a significant association between neutering and alopecia. It is to our knowledge the first description of the French population of the ferret as a companion animal.
Digital Islamic Law: Purpose and Prospects
Authors: Rabb Intisar A. , Tai Sharon
Published: January 2018

“Information wants to be free.” Although this sentiment dominates the current digital landscape, information about Islamic law and history often remains bound to its physical form and to the price of acquiring it. One should not have to travel to several countries or be associated with the handful of institutions with large collections in these fields to gain access to these sources (which can still be onerous once there). But this is precisely the case for those who aim to do serious, comparative, or otherwise broad-ranging work in Islamic law. For Islamic law, there is a persistent problem of access and ease of use.
“Tell Me Something I Don't Know!”: The Place and Politics of Digital Methods in the (Islamicate) Humanities
Authors: Miller Matthew Thomas , Savant Sarah Bowen
Published: January 2018

Debates about the value of digital methods often return to the nature of knowledge itself. Specifically, do not digital methods tell us what we intuitively already know? Or, if we do not know something yet, is it trivial or discoverable through other more traditional humanistic modes of analysis?
The Demands of Glory: Tocqueville and Terror in Algeria
Authors: Duong Kevin
Published: January 2018

It is now commonplace to acknowledge Alexis de Tocqueville's support for Algerian colonization. Less well understood, however, is why he also endorsed the French strategy of “total war” in the regency. How was Tocqueville's liberalism linked to the specific shape of violence in Algeria? By situating his Algerian writings in the intersecting intellectual contexts of the 1840s, this essay argues that Tocqueville endorsed total war in Africa because of his passion for glory. Far from an aristocratic anachronism, that passion was the product of contemporary scientific debates over voluntarism in France. It was also shaped by the lingering legacies of revolutionary republicanism and Bonapartism which defined glory in terms of national defense. By tethering modern liberty to this conception of glory, Tocqueville provided resources for rationalizing settlerism's exterminationist violence.
Variation in late L1 acquisition?
Authors: EMMOREY KAREN
Published: January 2018

Mayberry and Kluender review evidence that second language (L2) proficiency declines with age of acquisition (regardless of modality), but they also review evidence for variable L2 outcomes for individuals, with factors such as motivation, language aptitude, education, and L2 experience playing a role. They argue that if L2 outcomes were fully under the control of a critical period for language (CPL), these learning variables should not predict L2 outcome, and the outcome of L2 learning would not be consistently observed to be so variable. The questions raised in this commentary are whether there is variation in late L1 proficiency and whether such variation could provide insights into the CPL.
BORDERS AND BEYOND: CONTESTED POWER AND DISCOURSE AROUND SOUTHEAST COASTAL CHINA IN THE SIXTEENTH AND SEVENTEENTH CENTURIES
Authors: Chen Boyi
Published: January 2018

This article focuses on the mobile peoples who engaged in piracy on the borders beyond the territories negotiated by the imperial Chinese and colonial Spanish and Dutch powers, and by doing so, reframe our perception of early modern imperial and maritime history. In pre-modern times, the control of territory within the administrative borders was incomplete, and small pockets of territories with porous borders were beyond governmental rule. The people and the groups that lived along the coast of the northeastern South China Sea were, at different times, recognized differently and many of their activities were at times sanctioned and at other times outlawed. This article reveals a facet of how the non-stateless peoples lived on the borders beyond, claimed their own order in their own way, and worked and became naturalized or classified inside the strengthening borders in pre-modern societies according to the agenda and discourses of the dominant powers. I argue that the coastal societies had their own “order” that created groups “beyond control” or “being registered gradually.”
Trait-based responses of seven annual crops to elevated CO2and water limitation
Authors: McGranahan Devan Allen , Poling Brittany N.
Published: January 2018

By potentially disrupting crop production, climate change has been implicated as a threat to global food security. We focus on two elements of climate change: elevated atmospheric carbon dioxide concentration, or e[CO2], and reduced water availability, as caused by drought. Both variables have been shown to have effects on crop physiology, although there is considerable evidence of interactions and moderation by species-specific differences. Measuring traits helps scale environmental effects up to functional responses, and we focused on traits connected to photosynthesis, which has a close association with crop yield. We measured the response of four physiological traits—quantum photosynthetic yield, chlorophyll content, root:shoot ratio and leaf area—across a diverse set of seven annual crop species grown under three levels of e[CO2] (450, 575 and 700 ppm) and two levels of water availability (minimum ~45 and ~15% VWC) in a growth chamber. Species included barley, durum wheat, maize, oats, sorghum, pinto bean and sunflower. Our regression analysis focused on testing for interactions between e[CO2] and water limitation and determining relative effect sizes of climate change impacts across species, data that can be used for species-specific modeling or determining appropriate levels of environmental variables in free-air CO2enrichment studies designed to extend small-scale experimental results to the field. Across all species and all traits, the strongest effect of e[CO2] occurred from 450 to 575 ppm, with only marginal differences from 575 to 700 ppm. We found substantial declines in leaf area across all species as a result of e[CO2] and wide variability in leaf area responses to water limitation. Other traits showed weak and variable responses to both e[CO2] and water limitation. While our data confirm that elements of global change, especially increased atmospheric CO2concentration, do affect traits related to photosynthesis, we found no discernible pattern to suggest which crops might be more resistant to e[CO2].
Bias, insecurity and the level of trust in the judiciary: the case of Brazil
Authors: YEUNG LUCIANA L.
Published: January 2018

Are judges biased in their decisions? If so, what are the consequences? We propose a conceptual model that estimates the effects of judicial bias and insecurity on the trustworthiness of courts. Additionally, we empirically assess evidence of bias among justices at the Superior Court (STJ). For this purpose, we analyzed 1,412 decisions from 1998 to 2008. Results do not show consistent strong bias toward either the debtor or the creditor. We test a second hypothesis: that Brazilian courts are unpredictable, creating high levels of judicial insecurity. Empirical results corroborate this idea. Finally, we relate the empirical results found in this paper with the conceptual model initially developed, and provide evidence measured by a nationwide survey on the trustworthiness of the judiciary. As our model predicted, preliminary results indicate that citizens have lower levels of trust in the judicial system if courts and judges are biased and unpredictable.
Evidence of a one-dimensional thermodynamic phase diagram for simple glass-formers
Authors: Hansen H. W. , Sanz A. , Adrjanowicz K. , Frick B. , Niss K.
Published: January 2018

Glass formers show motional processes over an extremely broad range of timescales, covering more than ten orders of magnitude, meaning that a full understanding of the glass transition needs to comprise this tremendous range in timescales. Here we report simultaneous dielectric and neutron spectroscopy investigations of three glass-forming liquids, probing in a single experiment the full range of dynamics. For two van der Waals liquids, we locate in the pressure–temperature phase diagram lines of identical dynamics of the molecules on both second and picosecond timescales. This confirms predictions of the isomorph theory and effectively reduces the phase diagram from two to one dimension. The implication is that dynamics on widely different timescales are governed by the same underlying mechanisms.
Ultrafast current imaging by Bayesian inversion
Authors: Somnath S. , Law K. J. H. , Morozovska A. N. , Maksymovych P. , Kim Y. , Lu X. , Alexe M. , Archibald R. , Kalinin S. V. , Jesse S. , Vasudevan R. K.
Published: January 2018

Spectroscopic measurements of current–voltage curves in scanning probe microscopy is the earliest and one of the most common methods for characterizing local energy-dependent electronic properties, providing insight into superconductive, semiconductor, and memristive behaviors. However, the quasistatic nature of these measurements renders them extremely slow. Here, we demonstrate a fundamentally new approach for dynamic spectroscopic current imaging via full information capture and Bayesian inference. This general-mode I–V method allows three orders of magnitude faster measurement rates than presently possible. The technique is demonstrated by acquiring I–V curves in ferroelectric nanocapacitors, yielding >100,000 I–V curves in <20 min. This allows detection of switching currents in the nanoscale capacitors, as well as determination of the dielectric constant. These experiments show the potential for the use of full information capture and Bayesian inference toward extracting physics from rapid I–V measurements, and can be used for transport measurements in both atomic force and scanning tunneling microscopy.
Crystal structure reveals vaccine elicited bactericidal human antibody targeting a conserved epitope on meningococcal fHbp
Authors: López-Sagaseta Jacinto , Beernink Peter T. , Bianchi Federica , Santini Laura , Frigimelica Elisabetta , Lucas Alexander H. , Pizza Mariagrazia , Bottomley Matthew J.
Published: January 2018

Data obtained recently in the United Kingdom following a nationwide infant immunization program against serogroup B Neisseria meningitidis (MenB) reported >80% 4CMenB vaccine-mediated protection. Factor H-binding protein (fHbp) is a meningococcal virulence factor and a component of two new MenB vaccines. Here, we investigated the structural bases underlying the fHbp-dependent protective antibody response in humans, which might inform future antigen design efforts. We present the co-crystal structure of a human antibody Fab targeting fHbp. The vaccine-elicited Fab 1A12 is cross-reactive and targets an epitope highly conserved across the repertoire of three naturally occurring fHbp variants. The free Fab structure highlights conformational rearrangements occurring upon antigen binding. Importantly, 1A12 is bactericidal against MenB strains expressing fHbp from all three variants. Our results reveal important immunological features potentially contributing to the broad protection conferred by fHbp vaccination. Our studies fuel the rationale of presenting conserved protein epitopes when developing broadly protective vaccines.
Pro-metastatic collagen lysyl hydroxylase dimer assemblies stabilized by Fe2+-binding
Authors: Guo Hou-Fu , Tsai Chi-Lin , Terajima Masahiko , Tan Xiaochao , Banerjee Priyam , Miller Mitchell D. , Liu Xin , Yu Jiang , Byemerwa Jovita , Alvarado Sarah , Kaoud Tamer S. , Dalby Kevin N. , Bota-Rabassedas Neus , Chen Yulong , Yamauchi Mitsuo , Tainer John A. , Phillips George N. , Kurie Jonathan M.
Published: January 2018

Collagen lysyl hydroxylases (LH1-3) are Fe2+- and 2-oxoglutarate (2-OG)-dependent oxygenases that maintain extracellular matrix homeostasis. High LH2 levels cause stable collagen cross-link accumulations that promote fibrosis and cancer progression. However, developing LH antagonists will require structural insights. Here, we report a 2 Å crystal structure and X-ray scattering on dimer assemblies for the LH domain of L230 in Acanthamoeba polyphaga mimivirus. Loop residues in the double-stranded β-helix core generate a tail-to-tail dimer. A stabilizing hydrophobic leucine locks into an aromatic tyrosine-pocket on the opposite subunit. An active site triad coordinates Fe2+. The two active sites flank a deep surface cleft that suggest dimerization creates a collagen-binding site. Loss of Fe2+-binding disrupts the dimer. Dimer disruption and charge reversal in the cleft increase Km and reduce LH activity. Ectopic L230 expression in tumors promotes collagen cross-linking and metastasis. These insights suggest inhibitor targets for fibrosis and cancer.
Ub-ProT reveals global length and composition of protein ubiquitylation in cells
Authors: Tsuchiya Hikaru , Burana Daocharad , Ohtake Fumiaki , Arai Naoko , Kaiho Ai , Komada Masayuki , Tanaka Keiji , Saeki Yasushi
Published: January 2018

Protein ubiquitylation regulates diverse cellular processes via distinct ubiquitin chains that differ by linkage type and length. However, a comprehensive method for measuring these properties has not been developed. Here we describe a method for assessing the length of substrate-attached polyubiquitin chains, “ubiquitin chain protection from trypsinization (Ub-ProT).” Using Ub-ProT, we found that most ubiquitylated substrates in yeast-soluble lysate are attached to chains of up to seven ubiquitin molecules. Inactivation of the ubiquitin-selective chaperone Cdc48 caused a dramatic increase in chain lengths on substrate proteins, suggesting that Cdc48 complex terminates chain elongation by substrate extraction. In mammalian cells, we found that ligand-activated epidermal growth factor receptor (EGFR) is rapidly modified with K63-linked tetra- to hexa-ubiquitin chains following EGF treatment in human cells. Thus, the Ub-ProT method can contribute to our understanding of mechanisms regulating physiological ubiquitin chain lengths and composition.
Lymphocyte-specific protein 1 regulates mechanosensory oscillation of podosomes and actin isoform-based actomyosin symmetry breaking
Authors: Cervero Pasquale , Wiesner Christiane , Bouissou Anais , Poincloux Renaud , Linder Stefan
Published: January 2018

Subcellular fine-tuning of the actomyosin cytoskeleton is a prerequisite for polarized cell migration. We identify LSP (lymphocyte-specific protein) 1 as a critical regulator of actomyosin contractility in primary macrophages. LSP1 regulates adhesion and migration, including the parameters cell area and speed, and also podosome turnover, oscillation and protrusive force. LSP1 recruits myosin IIA and its regulators, including myosin light chain kinase and calmodulin, and competes with supervillin, a myosin hyperactivator, for myosin regulators, and for actin isoforms, notably β-actin. Actin isoforms are anisotropically distributed in myosin IIA-expressing macrophages, and contribute to the differential recruitment of LSP1 and supervillin, thus enabling an actomyosin symmetry break, analogous to the situation in cells expressing two myosin II isoforms. Collectively, these results show that the cellular pattern of actin isoforms builds the basis for the differential distribution of two actomyosin machineries with distinct properties, leading to the establishment of discrete zones of actomyosin contractility.
Biochemical mechanisms determine the functional compatibility of heterologous genes
Authors: Porse Andreas , Schou Thea S. , Munck Christian , Ellabaan Mostafa M. H. , Sommer Morten O. A.
Published: January 2018

Elucidating the factors governing the functional compatibility of horizontally transferred genes is important to understand bacterial evolution, including the emergence and spread of antibiotic resistance, and to successfully engineer biological systems. In silico efforts and work using single-gene libraries have suggested that sequence composition is a strong barrier for the successful integration of heterologous genes. Here we sample 200 diverse genes, representing >80% of sequenced antibiotic resistance genes, to interrogate the factors governing genetic compatibility in new hosts. In contrast to previous work, we find that GC content, codon usage, and mRNA-folding energy are of minor importance for the compatibility of mechanistically diverse gene products at moderate expression. Instead, we identify the phylogenetic origin, and the dependence of a resistance mechanism on host physiology, as major factors governing the functionality and fitness of antibiotic resistance genes. These findings emphasize the importance of biochemical mechanism for heterologous gene compatibility, and suggest physiological constraints as a pivotal feature orienting the evolution of antibiotic resistance.
Sensory deprivation in Staphylococcus aureus
Authors: Villanueva Maite , García Begoña , Valle Jaione , Rapún Beatriz , Ruiz de los Mozos Igor , Solano Cristina , Martí Miguel , Penadés José R. , Toledo-Arana Alejandro , Lasa Iñigo
Published: January 2018

Bacteria use two-component systems (TCSs) to sense and respond to environmental changes. The core genome of the major human pathogen Staphylococcus aureus encodes 16 TCSs, one of which (WalRK) is essential. Here we show that S. aureus can be deprived of its complete sensorial TCS network and still survive under growth arrest conditions similarly to wild-type bacteria. Under replicating conditions, however, the WalRK system is necessary and sufficient to maintain bacterial growth, indicating that sensing through TCSs is mostly dispensable for living under constant environmental conditions. Characterization of S. aureus derivatives containing individual TCSs reveals that each TCS appears to be autonomous and self-sufficient to sense and respond to specific environmental cues, although some level of cross-regulation between non-cognate sensor-response regulator pairs occurs in vivo. This organization, if confirmed in other bacterial species, may provide a general evolutionarily mechanism for flexible bacterial adaptation to life in new niches.
Acetylation accumulates PFKFB3 in cytoplasm to promote glycolysis and protects cells from cisplatin-induced apoptosis
Authors: Li Fu-Long , Liu Jin-Ping , Bao Ruo-Xuan , Yan GuoQuan , Feng Xu , Xu Yan-Ping , Sun Yi-Ping , Yan Weili , Ling Zhi-Qiang , Xiong Yue , Guan Kun-Liang , Yuan Hai-Xin
Published: January 2018

Abstract

Enhanced glycolysis in cancer cells has been linked to cell protection from DNA damaging signals, although the mechanism is largely unknown. The 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 3 (PFKFB3) catalyzes the generation of fructose-2,6-bisphosphate, a potent allosteric stimulator of glycolysis. Intriguingly, among the four members of PFKFB family, PFKFB3 is uniquely localized in the nucleus, although the reason remains unclear. Here we show that chemotherapeutic agent cisplatin promotes glycolysis, which is suppressed by PFKFB3 deletion. Mechanistically, cisplatin induces PFKFB3 acetylation at lysine 472 (K472), which impairs activity of the nuclear localization signal (NLS) and accumulates PFKFB3 in the cytoplasm. Cytoplasmic accumulation of PFKFB3 facilitates its phosphorylation by AMPK, leading to PFKFB3 activation and enhanced glycolysis. Inhibition of PFKFB3 sensitizes tumor to cisplatin treatment in a xenograft model. Our findings reveal a mechanism for cells to stimulate glycolysis to protect from DNA damage and potentially suggest a therapeutic strategy to sensitize tumor cells to genotoxic agents by targeting PFKFB3.
Afforestation neutralizes soil pH
Authors: Hong Songbai , Piao Shilong , Chen Anping , Liu Yongwen , Liu Lingli , Peng Shushi , Sardans Jordi , Sun Yan , Peñuelas Josep , Zeng Hui
Published: January 2018

Soil pH regulates soil biogeochemical processes and has cascading effects on terrestrial ecosystem structure and functions. Afforestation has been widely adopted to increase terrestrial carbon sequestration and enhance water and soil preservation. However, the effect of afforestation on soil pH is still poorly understood and inconclusive. Here we investigate the afforestation-caused soil pH changes with pairwise samplings from 549 afforested and 148 control plots in northern China. We find significant soil pH neutralization by afforestation—afforestation lowers pH in relatively alkaline soil but raises pH in relatively acid soil. The soil pH thresholds (TpH), the point when afforestation changes from increasing to decreasing soil pH, are species-specific, ranging from 5.5 (Pinus koraiensis) to 7.3 (Populus spp.) with a mean of 6.3. These findings indicate that afforestation can modify soil pH if tree species and initial pH are properly matched, which may potentially improve soil fertility and promote ecosystem productivity.
A microengineered vascularized bleeding model that integrates the principal components of hemostasis
Authors: Sakurai Yumiko , Hardy Elaissa T. , Ahn Byungwook , Tran Reginald , Fay Meredith E. , Ciciliano Jordan C. , Mannino Robert G. , Myers David R. , Qiu Yongzhi , Carden Marcus A. , Baldwin W. Hunter , Meeks Shannon L. , Gilbert Gary E. , Jobe Shawn M. , Lam Wilbur A.
Published: January 2018

Hemostasis encompasses an ensemble of interactions among platelets, coagulation factors, blood cells, endothelium, and hemodynamic forces, but current assays assess only isolated aspects of this complex process. Accordingly, here we develop a comprehensive in vitro mechanical injury bleeding model comprising an “endothelialized” microfluidic system coupled with a microengineered pneumatic valve that induces a vascular “injury”. With perfusion of whole blood, hemostatic plug formation is visualized and “in vitro bleeding time” is measured. We investigate the interaction of different components of hemostasis, gaining insight into several unresolved hematologic issues. Specifically, we visualize and quantitatively demonstrate: the effect of anti-platelet agent on clot contraction and hemostatic plug formation, that von Willebrand factor is essential for hemostasis at high shear, that hemophilia A blood confers unstable hemostatic plug formation and altered fibrin architecture, and the importance of endothelial phosphatidylserine in hemostasis. These results establish the versatility and clinical utility of our microfluidic bleeding model.
Cryo-EM structure of 5-HT3A receptor in its resting conformation
Authors: Basak Sandip , Gicheru Yvonne , Samanta Amrita , Molugu Sudheer Kumar , Huang Wei , Fuente Maria la de , Hughes Taylor , Taylor Derek J. , Nieman Marvin T. , Moiseenkova-Bell Vera , Chakrapani Sudha
Published: January 2018

Serotonin receptors (5-HT3AR) directly regulate gut movement, and drugs that inhibit 5-HT3AR function are used to control emetic reflexes associated with gastrointestinal pathologies and cancer therapies. The 5-HT3AR function involves a finely tuned orchestration of three domain movements that include the ligand-binding domain, the pore domain, and the intracellular domain. Here, we present the structure from the full-length 5-HT3AR channel in the apo-state determined by single-particle cryo-electron microscopy at a nominal resolution of 4.3 Å. In this conformation, the ligand-binding domain adopts a conformation reminiscent of the unliganded state with the pore domain captured in a closed conformation. In comparison to the 5-HT3AR crystal structure, the full-length channel in the apo-conformation adopts a more expanded conformation of all the three domains with a characteristic twist that is implicated in gating.
Multidimensional correlation of nuclear relaxation rates and diffusion tensors for model-free investigations of heterogeneous anisotropic porous materials
Authors: de Almeida Martins João P. , Topgaard Daniel
Published: January 2018

Despite their widespread use in non-invasive studies of porous materials, conventional MRI methods yield ambiguous results for microscopically heterogeneous materials such as brain tissue. While the forward link between microstructure and MRI observables is well understood, the inverse problem of separating the signal contributions from different microscopic pores is notoriously difficult. Here, we introduce an experimental protocol where heterogeneity is resolved by establishing 6D correlations between the individual values of isotropic diffusivity, diffusion anisotropy, orientation of the diffusion tensor, and relaxation rates of distinct populations. Such procedure renders the acquired signal highly specific to the sample’s microstructure, and allows characterization of the underlying pore space without prior assumptions on the number and nature of distinct microscopic environments. The experimental feasibility of the suggested method is demonstrated on a sample designed to mimic the properties of nerve tissue. If matched to the constraints of whole body scanners, this protocol could allow for the unconstrained determination of the different types of tissue that compose the living human brain.
Controlling motile disclinations in a thick nematogenic material with an electric field
Authors: Bhattacharjee Amit Kumar
Published: January 2018

Manipulating topological disclination networks that arise in a symmetry-breaking phase transformation in widely varied systems including anisotropic materials can potentially lead to the design of novel materials like conductive microwires, self-assembled resonators, and active anisotropic matter. However, progress in this direction is hindered by a lack of control of the kinetics and microstructure due to inherent complexity arising from competing energy and topology. We have studied thermal and electrokinetic effects on disclinations in a three-dimensional nonabsorbing nematic material with a positive and negative sign of the dielectric anisotropy. The electric flux lines are highly nonuniform in uniaxial media after an electric field below the Fréedericksz threshold is switched on, and the kinetics of the disclination lines is slowed down. In biaxial media, depending on the sign of the dielectric anisotropy, apart from the slowing down of the disclination kinetics, a nonuniform electric field filters out disclinations of different topology by inducing a kinetic asymmetry. These results enhance the current understanding of forced disclination networks and establish the presented method, which we call fluctuating electronematics, as a potentially useful tool for designing materials with novel properties in silico.
The reunion of two lineages of the Neotropical brown stink bug on soybean lands in the heart of Brazil
Authors: Soares Patricia L. , Cordeiro Erick M. G. , Santos Frederico N. S. , Omoto Celso , Correa Alberto S.
Published: January 2018

The rapid pace of conversion of natural areas to agricultural systems is highly concerning, and the consequences for conservation and pest management are not yet fully understood. We examined mitochondrial (COI and Cytb) and nuclear (ITS1) gene regions of 21 populations of the stink bug Euschistus heros, to investigate the genetic diversity, genetic structure, and demographic history of this emerging soybean pest in South America. Two deep lineages that diverged in the Pliocene (4.5 Myr) occur over wide areas of Brazil. Historical changes during the Plio-Pleistocene led to significant genetic differences between E. heros populations, which differentiated further in several biomes. The northern lineage is older, more diverse, and prevalent in the Amazon and Caatinga, while the southern lineage is younger, less diverse, and prevalent in the Atlantic Forest and Chaco biomes. Euschistus heros populations are expanding in size and range but at different rates, strongly affected by environmental variables. Secondary contact between the main lineages is now occurring, mainly in areas of intensive farming and particularly in the Cerrado, an important agricultural frontier. Individuals adapted to different environmental conditions and to large monocultures might currently be combining into a panmictic and hard-to-control pest population.
Novel non-periodic spoof surface plasmon polaritons with H-shaped cells and its application to high selectivity wideband bandpass filter
Authors: Gao Xin , Che Wenquan , Feng Wenjie
Published: January 2018

In this paper, one kind of novel non-periodic spoof surface plasmon polaritons (SSPPs) with H-shaped cells is proposed. As we all know, the cutoff frequency exists inherently for the conventional comb-shaped SSPPs, which is a kind of periodic groove shape structures and fed by a conventional coplanar waveguide (CPW). In this work, instead of increasing the depth of all the grooves, two H-shaped cells are introduced to effectively reduce the cutoff frequency of the conventional comb-shaped SSPPs (about 12 GHz) for compact design. More importantly, the guide waves can be gradually transformed to SSPP waves with high efficiency, and better impedance matching from 50 Ω to the novel SSPP strip is achieved. Based on the proposed non-periodic SSPPs with H-shaped cells, a wideband bandpass filter (the 3-dB fractional bandwidths 68%) is realized by integrating the spiral-shaped defected ground structure (DGS) etched on CPW. Specifically, the filter shows high passband selectivity (Δf3 dB/Δf20 dB = 0.91) and wide upper stopband with −20 dB rejection. A prototype is fabricated for demonstration. Good agreements can be observed between the measured and simulated results, indicating potential applications in the integrated plasmonic devices and circuits at microwave and even THz frequencies.
Fast and accurate detection of spread source in large complex networks
Authors: Paluch Robert , Lu Xiaoyan , Suchecki Krzysztof , Szymański Bolesław K. , Hołyst Janusz A.
Published: January 2018

Spread over complex networks is a ubiquitous process with increasingly wide applications. Locating spread sources is often important, e.g. finding the patient one in epidemics, or source of rumor spreading in social network. Pinto, Thiran and Vetterli introduced an algorithm (PTVA) to solve the important case of this problem in which a limited set of nodes act as observers and report times at which the spread reached them. PTVA uses all observers to find a solution. Here we propose a new approach in which observers with low quality information (i.e. with large spread encounter times) are ignored and potential sources are selected based on the likelihood gradient from high quality observers. The original complexity of PTVA is O(N
α
), where α ∈ (3,4) depends on the network topology and number of observers (N denotes the number of nodes in the network). Our Gradient Maximum Likelihood Algorithm (GMLA) reduces this complexity to O (N2log (N)). Extensive numerical tests performed on synthetic networks and real Gnutella network with limitation that id’s of spreaders are unknown to observers demonstrate that for scale-free networks with such limitation GMLA yields higher quality localization results than PTVA does.
Occupational Exposure to Polycyclic Aromatic Hydrocarbons and Elevated Cancer Incidence in Firefighters
Authors: Stec Anna A. , Dickens Kathryn E. , Salden Marielle , Hewitt Fiona E. , Watts Damian P. , Houldsworth Philip E. , Martin Francis L.
Published: January 2018

Cancer incidence appears to be higher amongst firefighters compared to the general population. Given that many cancers have an environmental component, their occupational exposure to products of carbon combustion such as polycyclic aromatic hydrocarbons (PAHs) is of concern. This is the first UK study identifying firefighters exposure to PAH carcinogens. Wipe samples were collected from skin (jaw, neck, hands), personal protective equipment of firefighters, and work environment (offices, fire stations and engines) in two UK Fire and Rescue Service Stations. Levels of 16 US Environmental Protection Agency (EPA) PAHs were quantified together with more potent carcinogens: 7,12-dimethylbenzo[a]anthracene, and 3-methylcholanthrene (3-MCA) (12 months post-initial testing). Cancer slope factors, used to estimate cancer risk, indicate a markedly elevated risk. PAH carcinogens including benzo[a]pyrene (B[a]P), 3-MCA, and 7,12-dimethylbenz[a]anthracene PAHs were determined on body surfaces (e.g., hands, throat), on PPE including helmets and clothing, and on work surfaces. The main exposure route would appear to be via skin absorption. These results suggest an urgent need to monitor exposures to firefighters in their occupational setting and conduct long-term follow-up regarding their health status.
The role of transposable elements in functional evolution of amphioxus genome: the case of opsin gene family
Authors: Pantzartzi Chrysoula N. , Pergner Jiri , Kozmik Zbynek
Published: January 2018

Transposable elements (TEs) are able to jump to new locations (transposition) in the genome, usually after replication. They constitute the so-called selfish or junk DNA and take over large proportions of some genomes. Due to their ability to move around they can change the DNA landscape of genomes and are therefore a rich source of innovation in genes and gene regulation. Surge of sequence data in the past years has significantly facilitated large scale comparative studies. Cephalochordates have been regarded as a useful proxy to ancestral chordate condition partially due to the comparatively slow evolutionary rate at morphological and genomic level. In this study, we used opsin gene family from three Branchiostoma species as a window into cephalochordate genome evolution. We compared opsin complements in terms of family size, gene structure and sequence allowing us to identify gene duplication and gene loss events. Furthermore, analysis of the opsin containing genomic loci showed that they are populated by TEs. In summary, we provide evidence of the way transposable elements may have contributed to the evolution of opsin gene family and to the shaping of cephalochordate genomes in general.
The PKA-C3 catalytic subunit is required in two pairs of interneurons for successful mating of Drosophila
Authors: Cassar Marlène , Sunderhaus Elizabeth , Wentzell Jill S. , Kuntz Sara , Strauss Roland , Kretzschmar Doris
Published: January 2018

Protein kinase A (PKA) has been shown to play a role in a plethora of cellular processes ranging from development to memory formation. Its activity is mediated by the catalytic subunits whereby many species express several paralogs. Drosophila encodes three catalytic subunits (PKA-C1–3) and whereas PKA-C1 has been well studied, the functions of the other two subunits were unknown. PKA-C3 is the orthologue of mammalian PRKX/Pkare and they are structurally more closely related to each other than to other catalytic subunits within their species. PRKX is expressed in the nervous system in mice but its function is also unknown. We now show that the loss of PKA-C3 in Drosophila causes copulation defects, though the flies are active and show no defects in other courtship behaviours. This phenotype is specifically due to the loss of PKA-C3 because PKA-C1 cannot replace PKA-C3. PKA-C3 is expressed in two pairs of interneurons that send projections to the ventro-lateral protocerebrum and the mushroom bodies and that synapse onto motor neurons in the ventral nerve cord. Rescue experiments show that expression of PKA-C3 in these interneurons is sufficient for copulation, suggesting a role in relaying information from the sensory system to motor neurons to initiate copulation.
Heterologous Expression of a Novel Drug Transporter from the Malaria Parasite Alters Resistance to Quinoline Antimalarials
Authors: Tindall Sarah M. , Vallières Cindy , Lakhani Dev H. , Islahudin Farida , Ting Kang-Nee , Avery Simon V.
Published: January 2018

Antimalarial drug resistance hampers effective malaria treatment. Critical SNPs in a particular, putative amino acid transporter were recently linked to chloroquine (CQ) resistance in malaria parasites. Here, we show that this conserved protein (PF3D7_0629500 in Plasmodium falciparum; AAT1 in P. chabaudi) is a structural homologue of the yeast amino acid transporter Tat2p, which is known to mediate quinine uptake and toxicity. Heterologous expression of PF3D7_0629500 in yeast produced CQ hypersensitivity, coincident with increased CQ uptake. PF3D7_0629500-expressing cultures were also sensitized to related antimalarials; amodiaquine, mefloquine and particularly quinine. Drug sensitivity was reversed by introducing a SNP linked to CQ resistance in the parasite. Like Tat2p, PF3D7_0629500-dependent quinine hypersensitivity was suppressible with tryptophan, consistent with a common transport mechanism. A four-fold increase in quinine uptake by PF3D7_0629500 expressing cells was abolished by the resistance SNP. The parasite protein localised primarily to the yeast plasma membrane. Its expression varied between cells and this heterogeneity was used to show that high-expressing cell subpopulations were the most drug sensitive. The results reveal that the PF3D7_0629500 protein can determine the level of sensitivity to several major quinine-related antimalarials through an amino acid-inhibitable drug transport function. The potential clinical relevance is discussed.
OPA1 gene therapy prevents retinal ganglion cell loss in a Dominant Optic Atrophy mouse model
Authors: Sarzi Emmanuelle , Seveno Marie , Piro-Mégy Camille , Elzière Lucie , Quilès Mélanie , Péquignot Marie , Müller Agnès , Hamel Christian P. , Lenaers Guy , Delettre Cécile
Published: January 2018

Dominant optic atrophy (DOA) is a rare progressive and irreversible blinding disease which is one of the most frequent forms of hereditary optic neuropathy. DOA is mainly caused by dominant mutation in the OPA1 gene encoding a large mitochondrial GTPase with crucial roles in membrane dynamics and cell survival. Hereditary optic neuropathies are commonly characterized by the degeneration of retinal ganglion cells, leading to the optic nerve atrophy and the progressive loss of visual acuity. Up to now, despite increasing advances in the understanding of the pathological mechanisms, DOA remains intractable. Here, we tested the efficiency of gene therapy on a genetically-modified mouse model reproducing DOA vision loss. We performed intravitreal injections of an Adeno-Associated Virus carrying the human OPA1 cDNA under the control of the cytomegalovirus promotor. Our results provide the first evidence that gene therapy is efficient on a mouse model of DOA as the wild-type OPA1 expression is able to alleviate the OPA1-induced retinal ganglion cell degeneration, the hallmark of the disease. These results displayed encouraging effects of gene therapy for Dominant Optic Atrophy, fostering future investigations aiming at clinical trials in patients.
Attention Gates the Selective Encoding of Duration
Authors: Maarseveen Jim , Hogendoorn Hinze , Verstraten Frans A. J. , Paffen Chris L. E.
Published: January 2018

The abundance of temporal information in our environment calls for the effective selection and utilization of temporal information that is relevant for our behavior. Here we investigated whether visual attention gates the selective encoding of relevant duration information when multiple sources of duration information are present. We probed the encoding of duration by using a duration-adaptation paradigm. Participants adapted to two concurrently presented streams of stimuli with different durations, while detecting oddballs in one of the streams. We measured the resulting duration after-effect (DAE) and found that the DAE reflects stronger relative adaptation to attended durations, compared to unattended durations. Additionally, we demonstrate that unattended durations do not contribute to the measured DAE. These results suggest that attention plays a crucial role in the selective encoding of duration: attended durations are encoded, while encoding of unattended durations is either weak or absent.