bluuebunny/crossref_metadata_2025 huggingface dataset:
The causal power of securitisation: an inquiry into the explanatory status of securitisation theory illustrated by the case of Somali piracy
Authors: Oliveira Gilberto Carvalho
Published: November 2017

This article joins the nascent debate on the causal status of securitisation theory. Relying on critical realist’s efforts to deepen and broaden the concept of cause – defined as ‘causal complex’ – and its insights to integrate discourse and constitutive relations into a non-positivist framework for causal explanation, the article aims to explore the explanatory status of securitisation theory, without downgrading its discursive core. To illustrate this argument, the article uses the securitisation of Somali piracy as an example of how the causal analysis of securitisation can contribute to explain some of the dynamics involved in security governance. From this perspective, securitisation works within a broader empirical framework of security, significantly implicated in causal relations, going beyond the Copenhagen School’s conception of securitisation as a non-causal constitutive theory merely defined as a formal framework for analysis. The article discusses, finally, the relevance and implications of introducing causal analysis in the study of securitisation.
Prolonged prostaglandin-E2-associated periosteal reaction and elevated C-reactive protein levels
Authors: Duggan Maria I. , MacLaren Andrew T. , Anand Dhullipala
Published: November 2017

This is a case review of two infants who received a prolonged course of prostaglandin-E2 therapy for congenital cardiac lesions while awaiting corrective surgery. These cases highlight an association between prolonged prostaglandin-E2 therapy with periosteal reactions and elevated C-reactive protein levels. Failure to recognise this association may lead to multiple courses of antibiotics for presumed sepsis and further prolongation of prostaglandin-E2 therapy.
Glyphosate plus 2,4-D Deposition, Absorption, and Efficacy on Glyphosate-Resistant Weed Species as Influenced by Broadcast Spray Nozzle
Authors: Legleiter Travis R. , Young Bryan G. , Johnson William G.
Published: November 2017

The introduction of 2,4-D–resistant soybean will provide an additional POST herbicide site of action for control of herbicide-resistant broadleaf weeds. The introduction of this technology also brings concern of off-site movement of 2,4-D onto susceptible crops such as sensitive soybean and tomato. The 2,4-D formulation approved for use in 2,4-D–resistant soybean restricts application of the herbicide to nozzles that produce very coarse to ultra-coarse droplet spectrums. The use of larger droplet spectrums for broadcast applications can reduce herbicide deposition onto target weeds and thus influence herbicide efficacy. Field experiments were conducted to evaluate the influence of nozzle design on herbicide deposition onto target plants and the resulting efficacy of a POST application of 280 g ha−1glyphosate plus 280 g ha−12,4-D. The TTI11004 nozzle produced an ultra-coarse droplet spectrum and reduced coverage and deposition density on spray cards as compared with the XR11004 and TT11004 nozzles that produced medium droplet spectrums. The AIXR11004 nozzle also reduced deposition density on spray cards but did not reduce coverage. Herbicide solution deposition onto glyphosate-resistant Palmer amaranth, tall waterhemp, giant ragweed, and horseweed ranged from 0.28 to 0.72 µl cm−2and was not influenced by nozzle design. Herbicide efficacy was reduced by the TTI11004 nozzle on Palmer amaranth and horseweed compared with the AIXR11004, TT11004, and XR11004 nozzles when applications were made to either high densities of plants or plants exceeding the labeled height. The use of the AIXR11004 and TTI11004 nozzles that are listed as approved nozzles for glyphosate plus 2,4-D applications on 2,4-D–resistant soybean did not reduce herbicide deposition onto four of the most troublesome broadleaves and did not reduce herbicide efficacy when applied in conjunction with lower weed densities and smaller weeds.
Enhanced "Train and Hope" for Scalable, Cost-Effective Professional Development in Youth Suicide Prevention
Authors: Adrian Molly , Lyon Aaron R. , Nicodimos Semret , Pullmann Michael D. , McCauley Elizabeth
Published: November 2017

Abstract. Background: The knowledge base surrounding how to most effectively prepare and sustain practitioner knowledge and skills for suicide risk assessment and management is limited. Aims: This study examined the impact of a 6-hr continuing education training, and the effect of a posttraining reminder system, on mental health practitioners' knowledge, attitudes, and behavior surrounding suicide assessment and intervention. Method: Data were obtained prior to the training, immediately after the training, and at the 3-month follow-up. Medical record data were abstracted for a subsample of practitioners. Participants were randomly assigned to an e-mail reminder condition or no reminder condition that provided information related to the training. Results: All practitioners demonstrated increase s in suicide assessment knowledge and attitudes for engaging in suicide risk assessments from pre- to posttest, and gains were maintained at the 3-month follow-up. There was no effect of the e-mail reminder on practitioner knowledge, attitudes, or behaviors compared with the condition without the e-mail reminder. The use of e-mail reminders was not associated with any additional changes. Limitations: Limitations include predominantly self-report and small sample. Conclusion: Strategies to effectively change practitioner knowledge, attitudes, and behaviors toward suicidal clients may include continuing education. Efficient and effective designs of reminder systems for augmenting and supporting suicide assessment management training are needed.
Telephone Crisis Support Workers' Intentions to Use Recommended Skills While Experiencing Functional Impairment
Authors: Kitchingman Taneile A. , Wilson Coralie J. , Woodward Alan , Caputi Peter , Wilson Ian
Published: November 2017

Abstract. Background: Empathic engagement with distressed others can lead to elevated symptoms of psychological distress and functional impairment, which preclude helping professionals' delivery of optimal patient care. Whether telephone crisis support workers are impacted in a similar way is not currently reported in the literature. Aims: This study examined the relationship between functional impairment and intentions to use recommended support skills in a representative national sample of 210 telephone crisis support workers. Method: Participants completed an online survey including measures of functional impairment and intentions to use recommended telephone crisis support skills with callers reporting suicidal ideation, symptoms of depression, and anxiety. Results: As a group, participants who experienced greater functional impairment during the past month reported significantly lower intentions to use recommended support skills with callers than those who reported lower functional impairment. Limitations: Future research is needed to clarify the extent to which results generalize to telephone crisis support workers from other organizations. Conclusion: Results warrant further research to (a) identify determinants of telephone crisis support workers' functional impairment, and (b) for the deliberate management of telephone crisis support workers' functional impairment through developing and/or modifying existing service strategies to optimize workers' psychological well-being and delivery of support to callers.
Assessing Test-Retest Reliability of Psychological	Measures
Authors: Aldridge Victoria K. , Dovey Terence M. , Wade Angie
Published: November 2017

Abstract. Psychological research and clinical practice rely heavily on psychometric testing for measuring psychological constructs that represent symptoms of psychopathology, individual difference characteristics, or cognitive profiles. Test-retest reliability assessment is crucial in the development of psychometric tools, helping to ensure that measurement variation is due to replicable differences between people regardless of time, target behavior, or user profile. While psychological studies testing the reliability of measurement tools are pervasive in the literature, many still discuss and assess this form of reliability inappropriately with regard to the specified aims of the study or the intended use of the tool. The current paper outlines important factors to consider in test-retest reliability analyses, common errors, and some initial methods for conducting and reporting reliability analyses to avoid such errors. The paper aims to highlight a persistently problematic area in psychological assessment, to illustrate the real-world impact that these problems can have on measurement validity, and to offer relatively simple methods for improving the validity and practical use of reliability statistics.
A mouse model of the schizophrenia-associated 1q21.1 microdeletion syndrome exhibits altered mesolimbic dopamine transmission
Authors: Nielsen Jacob , Fejgin Kim , Sotty Florence , Nielsen Vibeke , Mørk Arne , Christoffersen Claus T. , Yavich Leonid , Lauridsen Jes B. , Clausen Dorte , Larsen Peter H. , Egebjerg Jan , Werge Thomas M. , Kallunki Pekka , Christensen Kenneth V. , Didriksen Michael
Published: November 2017

1q21.1 hemizygous microdeletion is a copy number variant leading to eightfold increased risk of schizophrenia. In order to investigate biological alterations induced by this microdeletion, we generated a novel mouse model (Df(h1q21)/+)and characterized it in a broad test battery focusing on schizophrenia-related assays.Df(h1q21)/+mice displayed increased hyperactivity in response to amphetamine challenge and increased sensitivity to the disruptive effects of amphetamine and phencyclidine hydrochloride (PCP) on prepulse inhibition. Probing of the direct dopamine (DA) pathway using the DA D1 receptor agonist SKF-81297 revealed no differences in induced locomotor activity compared to wild-type mice, butDf(h1q21)/+mice showed increased sensitivity to the DA D2 receptor agonist quinpirole and the D1/D2 agonist apomorphine. Electrophysiological characterization of DA neuron firing in the ventral tegmental area revealed more spontaneously active DA neurons and increased firing variability inDf(h1q21)/+mice, and decreased feedback reduction of DA neuron firing in response to amphetamine. In a range of other assays,Df(h1q21)/+mice showed no difference from wild-type mice: gross brain morphology and basic functions such as reflexes, ASR, thermal pain sensitivity, and motor performance were unaltered. Similarly, anxiety related measures, baseline prepulse inhibition, and seizure threshold were unaltered. In addition to the central nervous system-related phenotypes,Df(h1q21)/+mice exhibited reduced head-to tail length, which is reminiscent of the short stature reported in humans with 1q21.1 deletion. With aspects of both construct and face validity, theDf(h1q21)/+model may be used to gain insight into schizophrenia-relevant alterations in dopaminergic transmission.
Genome-wide analysis in UK Biobank identifies four loci associated with mood instability and genetic correlation with major depressive disorder, anxiety disorder and schizophrenia
Authors: Ward Joey , Strawbridge Rona J. , Bailey Mark E. S. , Graham Nicholas , Ferguson Amy , Lyall Donald M. , Cullen Breda , Pidgeon Laura M. , Cavanagh Jonathan , Mackay Daniel F. , Pell Jill P. , O’Donovan Michael , Escott-Price Valentina , Smith Daniel J.
Published: November 2017

Abstract

Mood instability is a core clinical feature of affective and psychotic disorders. In keeping with the Research Domain Criteria approach, it may be a useful construct for identifying biology that cuts across psychiatric categories. We aimed to investigate the biological validity of a simple measure of mood instability and evaluate its genetic relationship with several psychiatric disorders, including major depressive disorder (MDD), bipolar disorder (BD), schizophrenia, attention deficit hyperactivity disorder (ADHD), anxiety disorder and post-traumatic stress disorder (PTSD). We conducted a genome-wide association study (GWAS) of mood instability in 53,525 cases and 60,443 controls from UK Biobank, identifying four independently associated loci (on chromosomes 8, 9, 14 and 18), and a common single-nucleotide polymorphism (SNP)-based heritability estimate of ~8%. We found a strong genetic correlation between mood instability and MDD (rg = 0.60, SE = 0.07, p = 8.95 × 10−17) and a small but significant genetic correlation with both schizophrenia (rg = 0.11, SE = 0.04, p = 0.01) and anxiety disorders (rg = 0.28, SE = 0.14, p = 0.04), although no genetic correlation with BD, ADHD or PTSD was observed. Several genes at the associated loci may have a role in mood instability, including the DCC netrin 1 receptor (DCC) gene, eukaryotic translation initiation factor 2B subunit beta (eIF2B2), placental growth factor (PGF) and protein tyrosine phosphatase, receptor type D (PTPRD). Strengths of this study include the very large sample size, but our measure of mood instability may be limited by the use of a single question. Overall, this work suggests a polygenic basis for mood instability. This simple measure can be obtained in very large samples; our findings suggest that doing so may offer the opportunity to illuminate the fundamental biology of mood regulation.
Fluoxetine treatment is effective in a rat model of childhood-induced post-traumatic stress disorder
Authors: Ariel Lior , Inbar Sapir , Edut Schachaf , Richter-Levin Gal
Published: November 2017

Although selective serotonin reuptake inhibitors (SSRIs) are first-line treatment for post-traumatic stress disorder (PTSD) patients, their therapeutic efficacy is limited. Childhood adversities are considered a risk factor for developing PTSD in adulthood but may trigger PTSD without additional trauma in some individuals. Nevertheless, just as childhood is considered a vulnerable period it may also be an effective period for preventive treatment. Using a rat model of childhood-induced PTSD, pre-pubertal stress (juvenile stress, JVS), we compared the therapeutic effects of fluoxetine and examined the effectiveness of 1 month of fluoxetine treatment following JVS and into adulthood compared to treatment in adulthood. Since not all individuals develop PTSD following a trauma, comparing only group means is not the adequate type of analysis. We employed a behavioral profiling approach, which analyzes individual differences compared to the normal behavior of a control group. Animals exposed to JVS exhibited a higher proportion of affected animals as measured using the elevated plus maze 8 weeks after JVS. Fluoxetine treatment following the JVS significantly decreased the proportion of affected animals as measured in adulthood. Fluoxetine treatment in adulthood was not effective. The results support the notion that childhood is not only a vulnerable period but also an effective period for preventive treatment.
Publisher Correction: Ellipticity dependence of high-harmonic generation in solids originating from coupled intraband and interband dynamics
Authors: Tancogne-Dejean Nicolas , Mücke Oliver D. , Kärtner Franz X. , Rubio Angel
Published: November 2017

The published version of this Article contained an error in the second sentence of the fourth paragraph of the subheaded section “Ellipticity and helicity of the emitted harmonics”. The final exponent in this sentence should read:
inπ/2. This has now been corrected in the PDF and HTML versions of the Article.
Laboratory layered latte
Authors: Xue Nan , Khodaparast Sepideh , Zhu Lailai , Nunes Janine K. , Kim Hyoungsoo , Stone Howard A.
Published: November 2017

Inducing thermal gradients in fluid systems with initial, well-defined density gradients results in the formation of distinct layered patterns, such as those observed in the ocean due to double-diffusive convection. In contrast, layered composite fluids are sometimes observed in confined systems of rather chaotic initial states, for example, lattes formed by pouring espresso into a glass of warm milk. Here, we report controlled experiments injecting a fluid into a miscible phase and show that, above a critical injection velocity, layering emerges over a time scale of minutes. We identify critical conditions to produce the layering, and relate the results quantitatively to double-diffusive convection. Based on this understanding, we show how to employ this single-step process to produce layered structures in soft materials, where the local elastic properties vary step-wise along the length of the material.
Neuronal signals regulate obesity induced β-cell proliferation by FoxM1 dependent mechanism
Authors: Yamamoto Junpei , Imai Junta , Izumi Tomohito , Takahashi Hironori , Kawana Yohei , Takahashi Kei , Kodama Shinjiro , Kaneko Keizo , Gao Junhong , Uno Kenji , Sawada Shojiro , Asano Tomoichiro , Kalinichenko Vladimir V. , Susaki Etsuo A. , Kanzaki Makoto , Ueda Hiroki R. , Ishigaki Yasushi , Yamada Tetsuya , Katagiri Hideki
Published: November 2017

Under insulin-resistant conditions such as obesity, pancreatic β-cells proliferate to prevent blood glucose elevations. A liver–brain–pancreas neuronal relay plays an important role in this process. Here, we show the molecular mechanism underlying this compensatory β-cell proliferation. We identify FoxM1 activation in islets from neuronal relay-stimulated mice. Blockade of this relay, including vagotomy, inhibits obesity-induced activation of the β-cell FoxM1 pathway and suppresses β-cell expansion. Inducible β-cell-specific FoxM1 deficiency also blocks compensatory β-cell proliferation. In isolated islets, carbachol and PACAP/VIP synergistically promote β-cell proliferation through a FoxM1-dependent mechanism. These findings indicate that vagal nerves that release several neurotransmitters may allow simultaneous activation of multiple pathways in β-cells selectively, thereby efficiently promoting β-cell proliferation and maintaining glucose homeostasis during obesity development. This neuronal signal-mediated mechanism holds potential for developing novel approaches to regenerating pancreatic β-cells.
Exploration of pyrazine-embedded antiaromatic polycyclic hydrocarbons generated by solution and on-surface azomethine ylide homocoupling
Authors: Wang Xiao-Ye , Richter Marcus , He Yuanqin , Björk Jonas , Riss Alexander , Rajesh Raju , Garnica Manuela , Hennersdorf Felix , Weigand Jan J. , Narita Akimitsu , Berger Reinhard , Feng Xinliang , Auwärter Willi , Barth Johannes V. , Palma Carlos-Andres , Müllen Klaus
Published: November 2017

Nanographenes, namely polycyclic aromatic hydrocarbons (PAHs) with nanoscale dimensions (>1 nm), are atomically precise cutouts from graphene. They represent prime models to enhance the scope of chemical and physical properties of graphene through structural modulation and functionalization. Defined nitrogen doping in nanographenes is particularly attractive due to its potential for increasing the number of π-electrons, with the possibility of introducing localized antiaromatic ring elements. Herein we present azomethine ylide homocoupling as a strategy to afford internally nitrogen-doped, non-planar PAH in solution and planar nanographene on surfaces, with central pyrazine rings. Localized antiaromaticity of the central ring is indicated by optical absorption spectroscopy in conjunction with theoretical calculations. Our strategy opens up methods for chemically tailoring graphene and nanographenes, modified by antiaromatic dopants.
The interdomain flexible linker of the polypeptide GalNAc transferases dictates their long-range glycosylation preferences
Authors: de las Rivas Matilde , Lira-Navarrete Erandi , Daniel Earnest James Paul , Compañón Ismael , Coelho Helena , Diniz Ana , Jiménez-Barbero Jesús , Peregrina Jesús M. , Clausen Henrik , Corzana Francisco , Marcelo Filipa , Jiménez-Osés Gonzalo , Gerken Thomas A. , Hurtado-Guerrero Ramon
Published: November 2017

The polypeptide GalNAc-transferases (GalNAc-Ts), that initiate mucin-typeO-glycosylation, consist of a catalytic and a lectin domain connected by a flexible linker. In addition to recognizing polypeptide sequence, the GalNAc-Ts exhibit unique long-range N- and/or C-terminal prior glycosylation (GalNAc-O-Ser/Thr) preferences modulated by the lectin domain. Here we report studies on GalNAc-T4 that reveal the origins of its unique N-terminal long-range glycopeptide specificity, which is the opposite of GalNAc-T2. The GalNAc-T4 structure bound to a monoglycopeptide shows that the GalNAc-binding site of its lectin domain is rotated relative to the homologous GalNAc-T2 structure, explaining their different long-range preferences. Kinetics and molecular dynamics simulations on several GalNAc-T2 flexible linker constructs show altered remote prior glycosylation preferences, confirming that the flexible linker dictates the rotation of the lectin domain, thus modulating the GalNAc-Ts' long-range preferences. This work for the first time provides the structural basis for the different remote prior glycosylation preferences of the GalNAc-Ts.
Mechanistic insight into TRIP13-catalyzed Mad2 structural transition and spindle checkpoint silencing
Authors: Brulotte Melissa L. , Jeong Byung-Cheon , Li Faxiang , Li Bing , Yu Eric B. , Wu Qiong , Brautigam Chad A. , Yu Hongtao , Luo Xuelian
Published: November 2017

The spindle checkpoint maintains genomic stability and prevents aneuploidy. Unattached kinetochores convert the latent open conformer of the checkpoint protein Mad2 (O-Mad2) to the active closed conformer (C-Mad2), bound to Cdc20. C-Mad2–Cdc20 is incorporated into the mitotic checkpoint complex (MCC), which inhibits the anaphase-promoting complex/cyclosome (APC/C). The C-Mad2-binding protein p31comet and the ATPase TRIP13 promote MCC disassembly and checkpoint silencing. Here, using nuclear magnetic resonance (NMR) spectroscopy, we show that TRIP13 and p31comet catalyze the conversion of C-Mad2 to O-Mad2, without disrupting its stably folded core. We determine the crystal structure of human TRIP13, and identify functional TRIP13 residues that mediate p31comet–Mad2 binding and couple ATP hydrolysis to local unfolding of Mad2. TRIP13 and p31comet prevent APC/C inhibition by MCC components, but cannot reactivate APC/C already bound to MCC. Therefore, TRIP13–p31comet intercepts and disassembles free MCC not bound to APC/C through mediating the local unfolding of the Mad2 C-terminal region.
Network dynamics-based cancer panel stratification for systemic prediction of anticancer drug response
Authors: Choi Minsoo , Shi Jue , Zhu Yanting , Yang Ruizhen , Cho Kwang-Hyun
Published: November 2017

Cancer is a complex disease involving multiple genomic alterations that disrupt the dynamic response of signaling networks. The heterogeneous nature of cancer, which results in highly variable drug response, is a major obstacle to developing effective cancer therapy. Previous studies of cancer therapeutic response mostly focus on static analysis of genome-wide alterations, thus they are unable to unravel the dynamic, network-specific origin of variation. Here we present a network dynamics-based approach to integrate cancer genomics with dynamics of biological network for drug response prediction and design of drug combination. We select the p53 network as an example and analyze its cancer-specific state transition dynamics under distinct anticancer drug treatments by attractor landscape analysis. Our results not only enable stratification of cancer into distinct drug response groups, but also reveal network-specific drug targets that maximize p53 network-mediated cell death, providing a basis to design combinatorial therapeutic strategies for distinct cancer genomic subtypes.
Reduced anxiety is associated with the accumulation of six serotonin reuptake inhibitors in wastewater treatment effluent exposed goldfish Carassius auratus
Authors: Simmons D. B. D. , McCallum E. S. , Balshine S. , Chandramouli B. , Cosgrove J. , Sherry J. P.
Published: November 2017

Pharmaceuticals and personal care products (PPCPs) have been found in wastewater treatment plant (WWTP) effluents and their recipient watersheds. To assess the potential of WWTP effluents to alter fish behaviour, we caged male goldfish (Carassius auratus) for 21-days at three sites along a contamination gradient downstream from a WWTP which discharges into Cootes Paradise Marsh, on the western tip of Lake Ontario. We also included a fourth caging site as an external reference site within Lake Ontario at the Jordan Harbour Conservation Area. We then measured concentrations of PPCPs and monoamine neurotransmitters in caged goldfish plasma, and conducted behavioural assays measuring activity, startle response, and feeding. We detected fifteen different PPCPs in goldfish plasma including six serotonin reuptake inhibitors (amitriptyline, citalopram, fluoxetine/norfluoxetine, sertraline, venlafaxine, and diphenhydramine). Plasma concentrations of serotonin were significantly greater in plasma of fish caged closer to the WWTP effluent outfall site. The fish caged near and downstream of the WWTP effluent were bolder, more exploratory, and more active overall than fish caged at the reference site. Taken together, our results suggest that fish downstream of WWTPs are accumulating PPCPs at levels sufficient to alter neurotransmitter concentrations and to also impair ecologically-relevant behaviours.
A novel bioreactor system for biaxial mechanical loading enhances the properties of tissue-engineered human cartilage
Authors: Meinert Christoph , Schrobback Karsten , Hutmacher Dietmar W. , Klein Travis J.
Published: November 2017

The ex vivo engineering of autologous cartilage tissues has the potential to revolutionize the clinical management of joint disorders. Yet, high manufacturing costs and variable outcomes associated with tissue-engineered implants are still limiting their application. To improve clinical outcomes and facilitate a wider use of engineered tissues, automated bioreactor systems capable of enhancing and monitoring neotissues are required. Here, we developed an innovative system capable of applying precise uni- or biaxial mechanical stimulation to developing cartilage neotissues in a tightly controlled and automated fashion. The bioreactor allows for simple control over the loading parameters with a user-friendly graphical interface and is equipped with a load cell for monitoring tissue maturation. Applying our bioreactor, we demonstrate that human articular chondrocytes encapsulated in hydrogels composed of gelatin methacryloyl (GelMA) and hyaluronic acid methacrylate (HAMA) respond to uni- and biaxial mechanical stimulation by upregulation of hyaline cartilage-specific marker genes. We further demonstrate that intermittent biaxial mechanostimulation enhances accumulation of hyaline cartilage-specific extracellular matrix. Our study underlines the stimulatory effects of mechanical loading on the biosynthetic activity of human chondrocytes in engineered constructs and the need for easy-to-use, automated bioreactor systems in cartilage tissue engineering.
Immune tuning scaffold for the local induction of a pro-regenerative environment
Authors: Corradetti Bruna , Taraballi Francesca , Corbo Claudia , Cabrera Fernando , Pandolfi Laura , Minardi Silvia , Wang Xin , Van Eps Jeffrey , Bauza Guillermo , Weiner Bradley , Tasciotti Ennio
Published: November 2017

In mammals, tissue regeneration is accomplished through a well-regulated, complex cascade of events. The disruption of the cellular and molecular processes involved in tissue healing might lead to scar formation. Most tissue engineering approaches have tried to improve the regenerative outcome following an injury, through the combination of biocompatible materials, stem cells and bioactive factors. However, implanted materials can cause further healing impairments due to the persistent inflammatory stimuli that trigger the onset of chronic inflammation. Here, it is described at the molecular, cellular and tissue level, the body response to a functionalized biomimetic collagen scaffold. The grafting of chondroitin sulfate on the surface of the scaffold is able to induce a pro-regenerative environment at the site of a subcutaneous implant. The early in situ recruitment, and sustained local retention of anti-inflammatory macrophages significantly reduced the pro-inflammatory environment and triggered a different healing cascade, ultimately leading to collagen fibril re-organization, blood vessel formation, and scaffold integration with the surrounding native tissue.
Multiplex three-dimensional optical mapping of tumor immune microenvironment
Authors: Lee Steve Seung-Young , Bindokas Vytautas P. , Kron Stephen J.
Published: November 2017

Recent developments in optical tissue clearing and microscopic imaging have advanced three-dimensional (3D) visualization of intact tissues and organs at high resolution. However, to expand applications to oncology, critical limitations of current methods must be addressed. Here we describe transparent tissue tomography (T3) as a tool for rapid, three-dimensional, multiplexed immunofluorescent tumor imaging. Cutting tumors into sub-millimeter macrosections enables simple and rapid immunofluorescence staining, optical clearing, and confocal microscope imaging. Registering and fusing macrosection images yields high resolution 3D maps of multiple tumor microenvironment components and biomarkers throughout a tumor. The 3D maps can be quantitatively evaluated by automated image analysis. As an application of T3, 3D mapping and analysis revealed a heterogeneous distribution of programmed death-ligand 1 (PD-L1) in Her2 transgenic mouse mammary tumors, with high expression limited to tumor cells at the periphery and to CD31+ vascular endothelium in the core. Also, strong spatial correlation between CD45+ immune cell distribution and PD-L1 expression was revealed by T3 analysis of the whole tumors. Our results demonstrate that a tomographic approach offers simple and rapid access to high-resolution three-dimensional maps of the tumor immune microenvironment, offering a new tool to examine tumor heterogeneity.
Dynamical system with plastic self-organized velocity field as an alternative conceptual model of a cognitive system
Authors: Janson Natalia B. , Marsden Christopher J.
Published: November 2017

It is well known that architecturally the brain is a neural network, i.e. a collection of many relatively simple units coupled flexibly. However, it has been unclear how the possession of this architecture enables higher-level cognitive functions, which are unique to the brain. Here, we consider the brain from the viewpoint of dynamical systems theory and hypothesize that the unique feature of the brain, the self-organized plasticity of its architecture, could represent the means of enabling the self-organized plasticity of its velocity vector field. We propose that, conceptually, the principle of cognition could amount to the existence of appropriate rules governing self-organization of the velocity field of a dynamical system with an appropriate account of stimuli. To support this hypothesis, we propose a simple non-neuromorphic mathematical model with a plastic self-organized velocity field, which has no prototype in physical world. This system is shown to be capable of basic cognition, which is illustrated numerically and with musical data. Our conceptual model could provide an additional insight into the working principles of the brain. Moreover, hardware implementations of plastic velocity fields self-organizing according to various rules could pave the way to creating artificial intelligence of a novel type.
Beyond the Michaelis-Menten equation: Accurate and efficient estimation of enzyme kinetic parameters
Authors: Choi Boseung , Rempala Grzegorz A. , Kim Jae Kyoung
Published: November 2017

Examining enzyme kinetics is critical for understanding cellular systems and for using enzymes in industry. The Michaelis-Menten equation has been widely used for over a century to estimate the enzyme kinetic parameters from reaction progress curves of substrates, which is known as the progress curve assay. However, this canonical approach works in limited conditions, such as when there is a large excess of substrate over enzyme. Even when this condition is satisfied, the identifiability of parameters is not always guaranteed, and often not verifiable in practice. To overcome such limitations of the canonical approach for the progress curve assay, here we propose a Bayesian approach based on an equation derived with the total quasi-steady-state approximation. In contrast to the canonical approach, estimates obtained with this proposed approach exhibit little bias for any combination of enzyme and substrate concentrations. Importantly, unlike the canonical approach, an optimal experiment to identify parameters with certainty can be easily designed without any prior information. Indeed, with this proposed design, the kinetic parameters of diverse enzymes with disparate catalytic efficiencies, such as chymotrypsin, fumarase, and urease, can be accurately and precisely estimated from a minimal amount of timecourse data. A publicly accessible computational package performing such accurate and efficient Bayesian inference for enzyme kinetics is provided.
High Resolution AMS Dates from Shubayqa 1, northeast Jordan Reveal Complex Origins of Late Epipalaeolithic Natufian in the Levant
Authors: Richter Tobias , Arranz-Otaegui Amaia , Yeomans Lisa , Boaretto Elisabetta
Published: November 2017

The Late Epipalaeolithic Natufian (~14,600 − 11,500 cal BP) is a key period in the prehistory of southwest Asia. Often described as a complex hunting and gathering society with increased sedentism, intensive plant exploitation and associated with an increase in artistic and symbolic material culture, it is positioned between the earlier Upper- and Epi-Palaeolithic and the early Neolithic, when plant cultivation and subsequently animal domestication began. The Natufian has thus often been seen as a necessary pre-adaptation for the emergence of Neolithic economies in southwest Asia. Previous work has pointed to the Mediterranean woodland zone of the southern Levant as the ‘core zone’ of the Early Natufian. Here we present a new sequence of 27 AMS radiocarbon dates from the Natufian site Shubayqa 1 in northeast Jordan. The results suggest that the site was occupied intermittently between ~14,600 − 12,000 cal BP. The dates indicate the Natufian emerged just as early in eastern Jordan as it did in the Mediterranean woodland zone. This suggests that the origins and development of the Natufian were not tied to the ecological conditions of the Mediterranean woodlands, and that the evolution of this hunting and gathering society was more complex and heterogeneous than previously thought.
Similarity-based Regularized Latent Feature Model for Link Prediction in Bipartite Networks
Authors: Wang Wenjun , Chen Xue , Jiao Pengfei , Jin Di
Published: November 2017

Link prediction is an attractive research topic in the field of data mining and has significant applications in improving performance of recommendation system and exploring evolving mechanisms of the complex networks. A variety of complex systems in real world should be abstractly represented as bipartite networks, in which there are two types of nodes and no links connect nodes of the same type. In this paper, we propose a framework for link prediction in bipartite networks by combining the similarity based structure and the latent feature model from a new perspective. The framework is called Similarity Regularized Nonnegative Matrix Factorization (SRNMF), which explicitly takes the local characteristics into consideration and encodes the geometrical information of the networks by constructing a similarity based matrix. We also develop an iterative scheme to solve the objective function based on gradient descent. Extensive experiments on a variety of real world bipartite networks show that the proposed framework of link prediction has a more competitive, preferable and stable performance in comparison with the state-of-art methods.
The necessity to choose causes the effects of reward on saccade preparation
Authors: Wolf Christian , Heuer Anna , Schubö Anna , Schütz Alexander C.
Published: November 2017

When humans have to choose between different options, they can maximize their payoff by choosing the option that yields the highest reward. Information about reward is not only used to optimize decisions but also for movement preparation to minimize reaction times to rewarded targets. Here, we show that this is especially true in contexts in which participants additionally have to choose between different options. We probed eye movement preparation by measuring saccade latencies to differently rewarded single targets (single-trial) appearing left or right from fixation. In choice-trials, both targets were displayed and participants were free to decide for one target to receive the corresponding reward. In blocks without choice-trials, single-trial latencies were not or only weakly affected by reward. With choice-trials present, the influence of reward increased with the proportion and difficulty of choices and decreased when a cue indicated that no choice will be necessary. Choices caused a delay in subsequent single-trial responses to the non-chosen option. Taken together, our results suggest that reward affects saccade preparation mainly when the outcome is uncertain and depends on the participants’ behavior, for instance when they have to choose between targets differing in reward.
Feeding type and development drive the ingestion of microplastics by freshwater invertebrates
Authors: Scherer Christian , Brennholt Nicole , Reifferscheid Georg , Wagner Martin
Published: November 2017

Microscopic plastic items (microplastics) are ubiquitously present in aquatic ecosystems. With decreasing size their availability and potential to accumulate throughout food webs increase. However, little is known on the uptake of microplastics by freshwater invertebrates. To address this, we exposed species with different feeding strategies to 1, 10 and 90 µm fluorescent polystyrene spheres (3–3 000 particles mL−1). Additionally, we investigated how developmental stages and a co-exposure to natural particles (e.g., food) modulate microplastic ingestion. All species ingested microplastics in a concentration-dependent manner with Daphnia magna consuming up to 6 180 particles h−1, followed by Chironomus riparius (226 particles h−1), Physella acuta (118 particles h−1), Gammarus pulex (10 particles h−1) and Lumbriculus variegatus (8 particles h−1). D. magna did not ingest 90 µm microplastics whereas the other species preferred larger microplastics over 1 µm in size. In C. riparius and D. magna, size preference depended on the life stage with larger specimens ingesting more and larger microplastics. The presence of natural particles generally reduced the microplastics uptake. Our results demonstrate that freshwater invertebrates have the capacity to ingest microplastics. However, the quantity of uptake depends on their feeding type and morphology as well as on the availability of microplastics.
Algae associated with coral degradation affects risk assessment in coral reef fishes
Authors: McCormick Mark I. , Barry Randall P. , Allan Bridie J. M.
Published: November 2017

Habitat degradation alters the chemical landscape through which information about community dynamics is transmitted. Olfactory information is crucial for risk assessment in aquatic organisms as predators release odours when they capture prey that lead to an alarm response in conspecific prey. Recent studies show some coral reef fishes are unable to use alarm odours when surrounded by dead-degraded coral. Our study examines the spatial and temporal dynamics of this alarm odour-nullifying effect, and which substratum types may be responsible. Field experiments showed that settlement-stage damselfish were not able to detect alarm odours within 2 m downcurrent of degraded coral, and that the antipredator response was re-established 20–40 min after transferral to live coral. Laboratory experiments indicate that the chemicals from common components of the degraded habitats, the cyanobacteria, Okeania sp., and diatom, Pseudo-nitzschia sp.prevented an alarm odour response. The same nullifying effect was found for the common red algae, Galaxauria robusta, suggesting that the problem is of a broader nature than previously realised. Those fish species best able to compensate for a lack of olfactory risk information at key times will be those potentially most resilient to the effects of coral degradation that operate through this mechanism.
Motor cortical activity changes during neuroprosthetic-controlled object interaction
Authors: Downey John E. , Brane Lucas , Gaunt Robert A. , Tyler-Kabara Elizabeth C. , Boninger Michael L. , Collinger Jennifer L.
Published: November 2017

Brain-computer interface (BCI) controlled prosthetic arms are being developed to restore function to people with upper-limb paralysis. This work provides an opportunity to analyze human cortical activity during complex tasks. Previously we observed that BCI control became more difficult during interactions with objects, although we did not quantify the neural origins of this phenomena. Here, we investigated how motor cortical activity changed in the presence of an object independently of the kinematics that were being generated using intracortical recordings from two people with tetraplegia. After identifying a population-wide increase in neural firing rates that corresponded with the hand being near an object, we developed an online scaling feature in the BCI system that operated without knowledge of the task. Online scaling increased the ability of two subjects to control the robotic arm when reaching to grasp and transport objects. This work suggests that neural representations of the environment, in this case the presence of an object, are strongly and consistently represented in motor cortex but can be accounted for to improve BCI performance.
Microdroplet-based On-Demand Drawing of High Aspect-Ratio Elastomeric Micropillar and Its Contact Sensing Application
Authors: Li Qiang , Dhakal Rabin , Kim Jaeyoun
Published: November 2017

High aspect-ratio elastomeric micropillars play important roles as the platform for microscale sensing and actuation. Many soft-lithographic techniques have been developed for their facile realization but most of the techniques are limited to build the micropillars only on totally flat, widely accessible substrate areas with the micropillar’s structural characteristics completely predetermined, leaving little room for in situ control. Here we demonstrate a new technique which overcomes these limitations by directly drawing micropillars from pipette-dispensed PDMS microdroplets using vacuum-chucked microspheres. The combined utilization of PDMS microdroplets and microspheres not only enables the realization of microsphere-tipped PDMS micropillars on non-flat, highly space-constrained substrate areas at in situ controllable heights but also allows arraying of micropillars with dissimilar heights at a close proximity. To validate the new technique’s utility and versatility, we realize PDMS micropillars on various unconventional substrate areas in various configurations. We also convert one of them, the optical fiber/micropillar hybrid, into a soft optical contact sensor. Both the fabrication technique and the resulting sensing scheme will be useful for future biomedical microsystems.
Attraction of Halyomorpha halys (Hemiptera: Pentatomidae) haplotypes in North America and Europe to baited traps
Authors: Morrison William R. , Milonas Panos , Kapantaidaki Despoina Evr. , Cesari Michele , Di Bella Emanuele , Guidetti Roberto , Haye Tim , Maistrello Lara , Moraglio Silvia T. , Piemontese Lucia , Pozzebon Alberto , Ruocco Giulia , Short Brent D. , Tavella Luciana , Vétek Gábor , Leskey Tracy C.
Published: November 2017

Halyomorpha halysis a global invasive species, native to Southeast Asia, that is threatening agriculture in invaded regions. Our objectives were to: 1) establish the attractiveness of semiochemical stimuli paired with field-deployed traps in Europe (Greece, Hungary, Italy, and Switzerland), compared with Maryland, USA, and 2) identifyH. halyshaplotypes recovered from traps at each location. We found qualitatively identical patterns of capture between sites located across Europe and in Maryland, USA. In both regions, captures ofH. halysadults indicated a synergistic response to traps baited with the two componentH. halysaggregation pheromone, and pheromone synergist, methyl (2E, 4E, 6Z)-decatrienoate when compared with either individually. Haplotype diversity in Europe based on trapped specimens was much greater than the USA, with five new haplotypes described here, probably indicating ongoing invasion and re-introduction ofH. halys. By contrast, a single, previously identified haplotype was trapped in Maryland, USA, representing a single introduction. AllH. halyshaplotypes responded to each semiochemical in apparent proportion to their frequency in the overall population based on independently derived information from prior work. Taken together, these data suggest that pheromone-based technology will be of global utility for the monitoring of this important invasive species.
Disturbed blood flow worsens endothelial dysfunction in moderate-severe chronic obstructive pulmonary disease
Authors: Barak Otto F. , Mladinov Suzana , Hoiland Ryan L. , Tremblay Joshua C. , Thom Stephen R. , Yang Ming , Mijacika Tanja , Dujic Zeljko
Published: November 2017

The aims of this study were: (1) to test whether oscillatory shear stress further exacerbates endothelial dysfunction in patients with moderate-severe COPD, and (2) to test whether low flow oxygen administration improves endothelial function and is protective against oscillatory shear stress-induced endothelial dysfunction in patients with moderate-severe COPD. In 17 patients and 10 age-matched non-smoking control subjects we examined brachial artery flow-mediated dilation (FMD) and circulating microparticles before and after 20 minutes of experimentally-induced oscillatory shear stress. COPD patients performed this intervention a second time following a 20-minute wash in period of low flow supplemental oxygen to normalize arterial oxygen saturation. COPD patients had ~six-fold greater baseline retrograde shear rate (P < 0.05) and lower FMD (P < 0.05). The oscillatory shear stress intervention induced significant decreases in brachial artery FMD of all groups (P < 0.05). Oscillatory shear stress elevated circulating markers of endothelial cell apoptosis (CD31+/CD41b− microparticles) in COPD patients, but not age-matched controls. Supplemental oxygen administration abrogated the oscillatory shear stress-induced increase in CD31+/CD41b− microparticles, and improved FMD after accounting for the shear stress stimulus. We have demonstrated that acutely disturbed blood flow with increased retrograde shear stress further deteriorates the already impaired endothelial function with attendant endothelial apoptosis in patients with moderate-severe COPD.