bluuebunny/crossref_metadata_2025 huggingface dataset:
APOCALYPSES NOW: MODERN SCIENCE AND BIBLICAL MIRACLES: THE BOYLE LECTURE 2018
Authors: Harris Mark
Published: November 2018

I explore an intriguing area that has crept under the radar of today's science‐and‐theology conversation, namely, scientific studies of the big miracle and catastrophe stories of the Bible (e.g., Noah's flood, or the plagues of Egypt). These studies have proposed naturalistic explanations for some of the most spectacular and unlikely of the biblical miracles. While the scientists believe their naturalistic interpretations represent a major advance in understanding the stories, professional biblical scholars show little interest, or are openly disdainful. I will point out the striking parallels with the foundational “catastrophism‐uniformitarianism” controversy in nineteenth‐century geology, and will suggest that the debate also takes us toward a novel kind of natural theology when we consider the biblical miracle and catastrophe texts. Here, the spectacular scientific explanations do not deny the miraculous character of the biblical stories so much as provide a uniquely modern purchase on their transcendent quality.
RELOCATING THE CONFLICT BETWEEN SCIENCE AND RELIGION AT THE FOUNDATIONS OF THE HISTORY OF SCIENCE
Authors: Ungureanu James C.
Published: November 2018

Historians of science and religion usually trace the origins of the “conflict thesis,” the notion that science and religion have been in perennial “conflict” or “warfare,” to the late nineteenth century, particularly to the narratives of New York chemist John William Draper and historian Andrew Dickson White. In this essay, I argue against that convention. Their narratives should not be read as stories to debunk, but rather as primary sources reflecting themes and changes in religious thought during the late nineteenth century. I contend that Draper and White were part of a long liberal Protestant heritage that emphasized history, reason, and religious emancipation against ecclesiastical authority. As an alternative source of origins, however, I suggest that the real “conflict thesis” is to be found in the fledgling discipline of the history of science as it emerged during the late nineteenth and first half of the twentieth century. The real origin of the “conflict thesis” is found in the very discipline that now seeks to condemn it.
Precursor Selection for Carbon Membrane Fabrication: A Review
Authors: Sazali N. , Salleh W. N. W. , Nur Izwanne M. , Harun Z. , Kadirgama K.
Published: November 2018

The rapid expansion of gas separation technology since it was first introduced is promoted by the beneficial selective permeability capability of the polymeric membranes. Up to the currently available information, a large number of studies have reported polymeric membranes permeability and selectivity performances for a different type of gasses. However, trends showed that separation of gases using as per in synthesized polymers had reached a bottlenecks performance limits. Due to this reason, membranes in the form of asymmetric and composite structures is seen as an interesting option of membrane modification to improve the performance and economic value of the membranes alongside with an introduction of new processes to the field. An introduction of new polymers during membrane fabrication leads to a formation of its unique structure depending on the polymers. Thus, structured studies are needed to determine the kinetic behavior of the new addition to membrane structures. This review examines the ongoing progress made in understanding the effects of the different polymers additives to the structural modification and the gas separation performances of the carbon membranes. A reduction of defects consisted of pore holes, and cracks on carbon membranes could be minimized with the right selection of polymer precursor.
Effect of Take-up Speed on the Fabrication of Cellulose Acetate Hollow Fibre Membrane in CO2 Separation from N2 and CH4
Authors: Mubashir M. , Yeong Y. F. , Chew T. L , Lau K. K.
Published: November 2018

Over the past decades, hollow fibre membranes (HFMs) have attracted much interest of the researchers due to their extensive industrial usage in CO2 separation processes. In the current study, we have reported the effect of take-up speed on the fabrication of cellulose acetate (CA) HFMs in gas separation. The morphology of the resultant HFMs was examined by using field emission scanning electron microscopy (FESEM). The gas permeation results obtained in this work revealed that, when take-up speed increased from free fall to 12.2 m/min, CO2, N2 and CH4 permeances of the resultant CA HFM were reduced 55.68%, 87.25% and 82.00%, respectively. Meanwhile, gas pair selectivities were increased 146.18% and 247.76% respectively. These results were mainly due to the increment of polymer orientation and chain packing which suppressed the macro-voids in the HFMs and thus, the gas pair selectivities were improved. Furthermore, it was found that CA HFM spun at take-up speed of 12.2 m/min showed highest CO2/CH4 and CO2/N2 ideal selectivities of 3.9 and 3.6, respectively.
A Cloud-based Conceptual Framework for Multi-Objective Virtual Machine Scheduling using Whale Optimization Algorithm
Authors: Rana Nadim , Abd Latiff Muhammad Shafie , Muhammad Abdulhamid Shafi'i
Published: November 2018

Virtual machine scheduling in the cloud is considered one of the major issue to solve optimal resource allocation problem on the heterogeneous datacenters. With respect to that, the key concern is to map the virtual machines (VMs) with physical machines (PMs) in a way that maximum resource utilization can be achieved with minimum cost. Due to the fact that scheduling is an NP-hard problem, a metaheuristic approach is proven to achieve a better optimal solution to solve this problem. In a rapid changing heterogeneous environment, where millions of resources can be allocated and deallocate in a fraction of the time, modern metaheuristic algorithms perform well due to its immense power to solve the multidimensional problem with fast convergence speed. This paper presents a conceptual framework for solving multi-objective VM scheduling problem using novel metaheuristic Whale optimization algorithm (WOA). Further, we present the problem formulation for the framework to achieve multi-objective functions.
The Supplemental Nutrition Assistance Program as a Source of Social Welfare – Reflections and Recommendations
Authors: Li Yuyang
Published: November 2018

This paper discusses the Supplemental Nutrition Assistance Program, which aid those in need via food stamps. First the author introduces the program, including its coverage. Then, the author discusses criticisms of the program—that it has high costs and may reduce incentives for work. Finally, recommendations are given in light of the shortcomings.
An Integrated Approach to the Study of Ethnicity and Its Relevance to Ethiopia
Authors: Nigusie Alemu Asfaw
Published: November 2018

Despite decades old study of ethnicity, scholars have largely failed to answer basic questions that are pertinent to the topic because they study it from a single perspective (primordialism, constructivism, and instrumentalism) and such an isolated study could not fully elaborate the phenomenon. Consequently, as a remedy to this problem, an integrated approach to the study of ethnicity has been formulated by Philip Q. Yang. Thus, the central objective of this paper was to examine this approach and test its relevance to the Ethiopian case, where ethnic identity has been playing a major role since the middle of twentieth century. Scholars in the field of political science have identified the problem of instrumentalization of ethnic identity by political elites and parties for their political gains but have insufficiently analyzed the problem due to overreliance on a single theory. To this effect, primary and secondary data were collected through literature and document review. The integrated approach of ethnicity includes the central arguments of primordialism, constructivism, and instrumentalism and hence is found to be very crucial to understand and explain past and present Ethiopian socio-political systems, their concomitant ethnic policies and the political struggles thereof. This work thus concludes that, with all its limitations, studying such complex and dynamic issue as ethnicity requires adopting an integrated or holistic approach so that one could have a better picture of the issue at hand.
Archimedes’ Principle Using Energy Considerations
Authors: Goh Ker Liang
Published: November 2018

Archimedes’ principle states the buoyant force is equal to the weight of fluid displaced by the object. In this work, we will develop this principle using energy considerations.
Fundamental-frequency discrimination based on temporal-envelope cues: Effects of bandwidth and interference
Authors: Mehta Anahita H. , Oxenham Andrew J.
Published: November 2018

Both music and speech perception rely on hearing out one pitch in the presence of others. Pitch discrimination of narrowband sounds based only on temporal-envelope cues is rendered nearly impossible by introducing interferers in both normal-hearing listeners and cochlear-implant (CI) users. This study tested whether performance improves in normal-hearing listeners if the target is presented over a broad spectral region. The results indicate that performance is still strongly affected by spectrally remote interferers, despite increases in bandwidth, suggesting that envelope-based pitch is unlikely to allow CI users to perceive pitch when multiple harmonic sounds are presented at once.
Vocal emotion recognition performance predicts the quality of life in adult cochlear implant users
Authors: Luo Xin , Kern Ashley , Pulling Kathryn R.
Published: November 2018

Clinical tests of cochlear implant (CI) outcomes in sentence recognition cannot fully reflect CI users' self-reported quality of life (QoL). Here, vocal emotion recognition scores, speech reception thresholds (SRTs), and demographic factors were tested as predictors of QoL scores assessed with the Nijmegen Cochlear Implant Questionnaire in postlingually deafened adult CI users. After correction for multiple comparisons, vocal emotion recognition scores were significantly correlated with QoL scores in all subdomains (social interaction, self-esteem, etc.), while SRTs and duration of CI use were not. Vocal emotion recognition may thus be used in clinic to accurately and broadly predict QoL with CIs.
Streptavidin-conjugated gold nanoclusters as ultrasensitive fluorescent sensors for early diagnosis of HIV infection
Authors: Kurdekar Aditya Dileep , Avinash Chunduri L. A. , Manohar C. Sai , Haleyurgirisetty Mohan Kumar , Hewlett Indira K. , Venkataramaniah Kamisetti
Published: November 2018

GNCIA allows a sensitive and selective detection of HIV-1 infections with a sensitivity of 5 pg/ml.
HIV-1 vaccine design through minimizing envelope metastability
Authors: He Linling , Kumar Sonu , Allen Joel D. , Huang Deli , Lin Xiaohe , Mann Colin J. , Saye-Francisco Karen L. , Copps Jeffrey , Sarkar Anita , Blizard Gabrielle S. , Ozorowski Gabriel , Sok Devin , Crispin Max , Ward Andrew B. , Nemazee David , Burton Dennis R. , Wilson Ian A. , Zhu Jiang
Published: November 2018

A coherent HIV-1 vaccine strategy addresses envelope stabilization, nanoparticle display, antibody response, and manufacture.
Situated experimental agents for scientific discovery
Authors: Stanton Samuel C.
Published: November 2018

Integrating robotic collaborators into experimental practice may give rise to an exciting new paradigm.
CASE: A HAL 9000 for 2021
Authors: Bonasso Pete
Published: November 2018

CASE can plan and manage activities for a planetary base and interact with users through a dialog management system.
Two recombinant human monoclonal antibodies that protect against lethal Andes hantavirus infection in vivo
Authors: Garrido Jose L. , Prescott Joseph , Calvo Mario , Bravo Felipe , Alvarez Raymond , Salas Alexis , Riquelme Raul , Rioseco Maria L. , Williamson Brandi N. , Haddock Elaine , Feldmann Heinz , Barria Maria I.
Published: November 2018

Post-exposure highly potent human monoclonal antibodies target Andes hantavirus glycoprotein in a hamster hantavirus cardiopulmonary syndrome model.
Not just uninhibited: Interneurons and seizure onset
Authors: Andreae Laura C.
Published: November 2018

Optogenetic study in vivo demonstrates that different types of interneurons show consistently elevated but distinct firing patterns in the period preceding seizure onset in a rodent model of epilepsy.
Direct Identification of 80 Percent of Bacteria from Blood Culture Bottles by Matrix-Assisted Laser Desorption Ionization–Time of Flight Mass Spectrometry Using a 10-Minute Extraction Protocol
Authors: Simon Loïc , Ughetto Estelle , Gaudart Alice , Degand Nicolas , Lotte Romain , Ruimy Raymond
Published: November 2018

Matrix-assisted laser desorption ionization–time of flight mass spectrometry is not widely used to identify bacteria directly from positive blood culture bottles (BCBs) because of overlong protocols. The objective of this work was to develop and evaluate a simple extraction protocol for reliable identification from BCBs.
Multicenter Evaluation of NeuMoDx Group B
Streptococcus
Assay on the NeuMoDx 288 Molecular System
Authors: Emery C. L. , Relich R. F. , Davis T. H. , Young S. A. , Sims M. D. , Boyanton B. L.
Published: November 2018

Group B
Streptococcus
(GBS) is the leading cause of neonatal sepsis and meningitis in developed countries. Recommendations for antepartum GBS detection include enriched culture with several options for identifying GBS, some of which are time-consuming.
Oncogenic Kaposi’s Sarcoma-Associated Herpesvirus Upregulates Argininosuccinate Synthase 1, a Rate-Limiting Enzyme of the Citrulline-Nitric Oxide Cycle, To Activate the STAT3 Pathway and Promote Growth Transformation
Authors: Li Tingting , Zhu Ying , Cheng Fan , Lu Chun , Jung Jae U. , Gao Shou-Jiang
Published: November 2018

We have previously shown that Kaposi’s sarcoma-associated herpesvirus (KSHV)-transformed cells depend on glutamine rather than glucose for energy production and amino acid and nucleotide syntheses. In this study, we have further examined how the KSHV-reprogramed metabolic pathways are regulated and discovered that KSHV hijacks the citrulline-nitric oxide (NO) cycle to promote growth proliferation and transformation. Multiple KSHV-encoded microRNAs upregulate argininosuccinate synthase 1 (ASS1), a key enzyme in the citrulline-NO cycle.
ASS1
is required for KSHV-induced proliferation, colony formation in soft agar, and NO generation of KSHV-transformed cells, which also depends on inducible nitric oxide synthase. By maintaining intracellular NO levels,
ASS1
mediates KSHV activation of the STAT3 pathway, which is essential for KSHV-induced abnormal cell proliferation and transformation. These results illustrate a novel mechanism by which an oncogenic virus hijacks a key metabolic pathway to promote growth transformation and reveal a potential novel therapeutic target for KSHV-induced malignancies.
A Novel Type of Influenza A Virus-Derived Defective Interfering Particle with Nucleotide Substitutions in Its Genome
Authors: Kupke Sascha Young , Riedel Dietmar , Frensing Timo , Zmora Pawel , Reichl Udo
Published: November 2018

Defective interfering particles (DIPs) typically contain a highly deleted form of the viral genome, rendering them defective in virus replication. Yet upon complementation through coinfection with fully infectious standard virus (STV), interference with the viral life cycle can be observed, leading to suppressed STV replication and the release of mainly noninfectious DIPs. Interestingly, recent research indicates that DIPs may serve as an antiviral agent. Here we report the discovery of a yet-unknown type of influenza A virus-derived DIP (termed “OP7” virus) that contains numerous point mutations instead of large deletions in its genome. Furthermore, the underlying principles that render OP7 virions interfering and apparently defective seem to differ from those of conventional DIPs. In conclusion, we believe that OP7 virus might be a promising candidate for antiviral therapy. Moreover, it exerts strong effects, both on virus replication and on the host cell response, and may have been overlooked in other IAV preparations.
A Human Gain-of-Function STING Mutation Causes Immunodeficiency and Gammaherpesvirus-Induced Pulmonary Fibrosis in Mice
Authors: Bennion Brock G. , Ingle Harshad , Ai Teresa L. , Miner Cathrine A. , Platt Derek J. , Smith Amber M. , Baldridge Megan T. , Miner Jonathan J.
Published: November 2018

A variety of human rheumatologic disease-causing mutations have recently been identified. Some of these mutations are found in viral nucleic acid-sensing proteins, but whether viruses can influence the onset or progression of these human diseases is less well understood. One such autoinflammatory disease, called STING-associated vasculopathy with onset in infancy (SAVI), affects children and leads to severe lung disease. We generated mice with a SAVI-associated STING mutation and infected them with γHV68, a common DNA virus that is related to human Epstein-Barr virus. Mice with the human disease-causing STING mutation were more vulnerable to infection than wild-type littermate control animals. Furthermore, the STING mutant mice developed lung fibrosis similar to that of patients with SAVI. These findings reveal that a human STING mutation creates severe immunodeficiency, leading to virus-induced lung disease in mice.
Packaging of the Influenza Virus Genome Is Governed by a Plastic Network of RNA- and Nucleoprotein-Mediated Interactions
Authors: Bolte Hardin , Rosu Miruna E. , Hagelauer Elena , García-Sastre Adolfo , Schwemmle Martin
Published: November 2018

The genome of influenza A virus is organized into eight viral ribonucleoproteins (vRNPs); this provides evolutionary advantages but complicates genome packaging. Although it has been shown that RNA packaging sequences and specific amino acids in the viral nucleoprotein (NP), both components of each vRNP, ensure selective packaging of one copy of each vRNP per virus particle, the required RNA-RNA and RNA-NP interactions remain largely elusive. We identified that the genome packaging mechanism tolerates the mutation of certain individual RNA packaging sequences, while their combined mutation provokes distinct genome packaging defects. Moreover, we found that seven specific amino acid substitutions in NP impair the function of RNA packaging sequences and that this defect is partially restored by another NP amino acid change. Collectively, our data indicate that packaging of the influenza A virus genome is controlled by a redundant and plastic network of RNA/protein interactions, which may facilitate natural reassortment processes.
Reducing inappropriate antibiotic prescribing in upper respiratory tract infection in a primary care setting in Kolkata, India
Authors: Dehn Lunn Amy
Published: November 2018

Inappropriate antibiotic use is a key factor in the emergence of antibiotic resistance. The majority of antibiotics are prescribed in primary care, where upper respiratory tract infection (URTI) is a common presentation. Inappropriate antibiotic prescribing in URTI is common globally and has increased markedly in developing and transitional countries. Antibiotic stewardship is crucial to prevent the emergence and spread of resistant microbes. This project aimed to reduce inappropriate antibiotic prescribing in URTI in a non-governmental organisation’s primary care outreach clinics in Kolkata, India, from 62.6% to 30% over 4 months. A multifaceted intervention to reduce inappropriate antibiotic use in non-specific URTI was implemented. This consisted of a repeated process of audit and feedback, interactive training sessions, one-to-one case-based discussion, antibiotic guideline development and coding updates. The primary outcome measure was antibiotic prescribing rates. A baseline audit of all patients presenting with non-specific URTI over 8 weeks in November and December 2016 (n=222) found that 62.6% were prescribed antibiotics. Postintervention audit over 4 weeks in April 2017 (n=69) showed a marked reduction in antibiotic prescribing to 7.2%. An increase in documentation of examination findings was also observed, from 52.7% to 95.6%. This multifaceted intervention was successful at reducing inappropriate antibiotic prescribing, with sustained reductions demonstrated over the 4 months of the project. This suggests that approaches previously used in Europe can successfully be applied to different settings.
Immediate postnatal contraception: what women know and think
Authors: Thwaites Annette , Logan Louise , Nardone Anthony , Mann Sue
Published: November 2018

Introduction

Postpartum women are at risk of rapid repeat, unplanned pregnancy with associated adverse outcomes for mother and child. We aimed to better understand their contraceptive needs to improve delivery of services and prevent unplanned pregnancies.

Methods

A cross-sectional survey of women on the postnatal ward of an inner-city hospital was administered over a 6-week period in June and July 2017 to determine their level of knowledge, intentions and preferences regarding postnatal contraception.

Results

272 women were surveyed: 86% of all women on the postnatal ward during the study period. 10% (26/272) had never used any method of contraception previously and 22% (59/272) had ever used a long-acting reversible contraception (LARC) method. 18% (48/272) recalled a health professional speaking to them about contraception at any point during their pregnancy and 32% (87/272) said they needed more information to decide on their postnatal contraceptive method. 54% (147/272) of women did not think any LARC methods were safe immediately postnatally, rising to 71% (194/272) if breastfeeding. However, 47% (129/272) of women said that they would prefer to get their contraception from the ward before discharge and 46% (126/272) were likely to accept LARC, if safe, in this setting.

Conclusions

Almost half the women in our survey would welcome provision of postnatal contraception, including LARC, on the postnatal ward but the women surveyed currently lack the knowledge to make informed choices in this setting. There is therefore a need for effective, tailored contraceptive choices discussions with every woman during pregnancy, as well as integrated planning for postnatal provision of the woman’s chosen method.
Modified approach to fibrinogen replacement in the setting of dysfibrinogenaemia
Authors: Chandler Jocelyn B , Siddon Alexa J , Bahel Parveen , Torres Richard , Rinder Henry M , Tormey Christopher A
Published: November 2018

Most fibrinogen replacement strategies focus on quantitative deficiencies. A thrombin time (TT) mixing study helped to assess qualitative defects caused by dysfibrinogens. Plasma samples were collected from non-anticoagulated subjects (n=6) meeting laboratory criteria for suspected dysfibrinogenaemia (TT > 22 s; fibrinogen activity <180) and from a control group. TT mixing studies were performed on subject plasma with increasing volumes of pooled normal plasma at 1:2, 1:4 and 1:5 dilutions. No subjects with dysfibrinogenaemia demonstrated a complete TT correction at 1:2, but 50% corrected at 1:4 and 100% at 1:5 dilution. Based on these data, a correction factor (CF), defined as the reciprocal dilution yielding complete correction, was incorporated into our clinical practice formula for fibrinogen dosing in patients with dysfibrinogenaemias. Our study incorporates TT mixing studies for assessment of dysfibrinogens. The addition of a mix-derived CF to classical formulae may better approximate dosing in patients with dysfibrinogenaemia.
Fluoxetine oral treatment discloses 5-HT1D receptor as vagoinhibitor of the cardiac cholinergic neurotransmission in rat
Authors: López Cristina , Gómez-Roso Miriam , García-Pedraza José Ángel , Martín María Luisa , Morán Asunción , García-Domingo Mónica
Published: November 2018

Although depression and cardiovascular diseases are related, the role of antidepressants such as fluoxetine (increasing serotonin levels) within cardiac regulation remains unclear. We aimed to determine whether fluoxetine modifies the pharmacological profile of serotonergic influence on vagal cardiac outflow. Rats were treated with fluoxetine (10 mg/kg per day; p.o.) for 14 days or equivalent volumes of drinking water (control group); then, they were pithed and prepared for vagal stimulation. Bradycardic responses were obtained by electrical stimulation of the vagal fibers (3, 6, and 9 Hz) or i.v. acetylcholine (ACh; 1, 5, and 10 μg/kg). The i.v. administration of 5-hydroxytryptamine (5-HT; 10 and 50 μg/kg) inhibited the vagally induced bradycardia. 5-CT (5-HT1/7 agonist) and L-694,247 (5-HT1D agonist) mimicked the serotonin inhibitory effect while α-methyl-5-HT (5-HT2 agonist) was devoid of any action. SB269970 (5-HT7 antagonist) did not abolish 5-CT inhibitory action on the electrically induced bradycardia. Pretreatment with LY310762 (5-HT1D antagonist) blocked the effects induced by L-694,247 and 5-CT. 5-HT and 5-CT failed to modify the bradycardia induced by exogenous ACh. Our outcomes suggest that fluoxetine treatment modifies 5-HT modulation on heart parasympathetic neurotransmission in rats, evoking inhibition of the bradycardia via prejunctional 5-HT1D in pithed rats.
Software design of the smart antenna in the connectivity infotainment system
Authors: Jiang Xiaoyan
Published: November 2018

This paper designs a smart antenna system for the connective vehicle infotainment. It provides a whole software solution for the Vehicle Head Unit independent with OS system. It includes worldwide analog and digital radio and TV, full radio stacks, FM to DAB on web radio seamlessly, vehicle networking management. This paper is to define the interface between the smart antenna module and the Head Unit. The physical link between the smart antenna and the Head Unit is Ethernet, the interface is based on several protocols based on IP protocol such as UPnP, HTTP to receive a radio signal and use it. Thanks to the open source structures and integrating all the radio stacks, this system is much easier for OEM vehicle companies and Tier one suppliers to adopt the smart antenna into the infotainment Head Unit. It saves them a lot of developing time and cost.
Establishment and optimization of packet transport network core bearer network oriented to long-term evolution business
Authors: Luo Hongyan , Qian Tao , Zhu Xiangxian , Wang Huiyin , Yang Jinwen
Published: November 2018

The modern telecommunication has come into the Long-Term Evolution (LTE) era. The whole transmission network gradually has evolved to the IP network. The overall network organization is likewise becoming more and more similar to the metropolitan data network. A mobile Packet Transport Network (PTN) transmission network construction is investigated. The specific bearing requirements of time division long-term evolution (TD-LTE) are analyzed. The topology structures of L3 and L2/L3 and the equipment applications in different network levels of the PTN network are discussed. The existing problems concerning the circuit scheduling, disaster tolerance requirement, security connection and business pressure are analyzed in detail. Their corresponding optimization strategies are presented. Finally, the network level having a clear, robust and complete coverage is reached. It proves that the optimized network can meet the third level of the disaster tolerance international standard SHARE 78.
WHEN TO CALL THE CUSTOMER? TIMING OF CUSTOMER INVOLVEMENT IN THE DEVELOPMENT OF NEW PRODUCTS AND SERVICES
Authors: VESELAJ SABIT , TORFASON MAGNUS THOR
Published: November 2018

Involving customers in the development of new products and services helps firms understand customer needs, increasing the likelihood of meeting those needs and expectations. Although a large body of literature addresses the implications of customer involvement for project performance, the results of previous research are somewhat inconsistent. This paper explores this issue by examining the differing impact of customer involvement on the development of new products and new services. We propose that the role of customer involvement differs for these two types of innovations, with involvement in the early stages more important for products and involvement in the launch stage more important for services. Our results, based on a comprehensive dataset on customer involvement in innovation, are consistent with such a pattern, suggesting that more attention should be paid to the conditional benefits of customer involvement in different types of solution development.
Sedimentology, architecture and depositional setting of the fluvial Spireslack Sandstone of the Midland Valley, Scotland: insights from the Spireslack surface coal mine
Authors: Ellen R. , Browne M. A. E. , Mitten A. J. , Clarke S. M. , Leslie A. G. , Callaghan E.
Published: November 2018

The Spireslack surface coal mine exposes a section in the Carboniferous Lawmuir Formation (Brigantian) into the Upper Limestone Formation (Arnsbergian). This paper describes the stratigraphy exposed at Spireslack and, in so doing, names for the first time the Spireslack Sandstone, a distinctive erosively based, sandstone-dominated unit in the Upper Limestone Formation. The Spireslack Sandstone consists of two fluvial sandstone channel sets and an upper, possibly fluvio-estuarine, succession. From an analysis of their internal architectural elements, the channel sets are interpreted as a low-sinuosity, sand-dominated, mixed-load fluvial system in which avulsion and variations in sediment load played a significant part. The lower channel set appears to be confined to erosional palaeovalleys of limited lateral extent and significant relief. The upper channel set is much more laterally extensive and shows evidence of a generally lower sediment load with a greater degree of lateral accretion and flooding. Consequently, the Spireslack Sandstone may represent a system responding to base level changes of higher magnitude and longer duration than the glacio-eustatic scale commonly attributed to Carboniferous fluvio-deltaic cycles. The Spireslack Sandstone may represent an important correlative marker in the Carboniferous of the Midland Valley and may provide an alternative analogue for some Carboniferous fluvial sandstone stratigraphic traps.
Uncertainty in current and future health wearables
Authors: Knowles Bran , Smith-Renner Alison , Poursabzi-Sangdeh Forough , Lu Di , Alabi Halimat
Published: November 2018

Expect inherent uncertainties in health-wearables data to complicate future decision making concerning user health.
How to implement any concurrent data structure
Authors: Calciu Irina , Sen Siddhartha , Balakrishnan Mahesh , Aguilera Marcos K.
Published: November 2018

We propose a method called Node Replication (NR) to implement any concurrent data structure. The method takes a single-threaded implementation of a data structure and automatically transforms it into a concurrent (thread-safe) implementation. The result is designed to work well with and harness the power of modern servers, which are complex Non-Uniform Memory Access (NUMA) machines with many processor sockets and subtle performance characteristics. Using NR requires no expertise in concurrent data structure design, and the result is free of concurrency bugs. NR represents a paradigm shift of how concurrent algorithms are developed: rather than designing for a data structure, we design for the architecture.
Learning to see
Authors: Edwards Chris
Published: November 2018

Machine learning turns the spotlight on elusive viruses.
Anxa2 gene silencing attenuates obesity-induced insulin resistance by suppressing the NF-κB signaling pathway
Authors: Wang Yong , Cheng Yun-Sheng , Yin Xiao-Qiang , Yu Gang , Jia Ben-Li
Published: November 2018

Insulin resistance (IR) continues to pose a major threat to public health due to its role in the pathogenesis of metabolic syndrome and its ever-increasing prevalence on a global scale. The aim of the current study was to investigate the efficacy of Anxa2 in obesity-induced IR through the mediation of the NF-κB signaling pathway. Microarray analysis was performed to screen differentially expressed genes associated with obesity. To verify whether Anxa2 was differentially expressed in IR triggered by obesity, IR mouse models were established in connection with a high-fat diet (HFD). In the mouse IR model, the role of differentially expressed Anxa2 in glycometabolism and IR was subsequently detected. To investigate the effect of Anxa2 on IR and its correlation with inflammation, a palmitic acid (PA)-induced IR cell model was established, with the relationship between Anxa2 and the NF-κB signaling pathway investigated accordingly. Anxa2 was determined to be highly expressed in IR. Silencing Anxa2 was shown to inhibit IR triggered by obesity. When Anxa2 was knocked down, elevated expression of phosphorylated insulin receptor substrate 1 (IRS1), IRS1 and peroxisome proliferator-activated receptor coactivator-1a, and glucose tolerance and insulin sensitivity along with 2-deoxy-d-glucose uptake was detected, whereas decreased expression of suppressor of cytokine signaling 3, IL-6, IL-1β, TNF-α, and p50 was observed. Taken together, the current study ultimately demonstrated that Anxa2 may be a novel drug strategy for IR disruption, indicating that Anxa2 gene silencing is capable of alleviating PA or HFD-induced IR and inflammation through its negative regulatory role in the process of p50 nuclear translocation of the NF-κB signaling pathway.
The role of coagulation and platelets in colon cancer-associated thrombosis
Authors: Mitrugno Annachiara , Tassi Yunga Samuel , Sylman Joanna L. , Zilberman-Rudenko Jevgenia , Shirai Toshiaki , Hebert Jessica F. , Kayton Robert , Zhang Ying , Nan Xiaolin , Shatzel Joseph J. , Esener Sadik , Duvernay Matthew T. , Hamm Heidi E. , Gruber András , Williams Craig D. , Takata Yumie , Armstrong Randall , Morgan Terry K. , McCarty Owen J. T.
Published: November 2018

Cancer-associated thrombosis is a common first presenting sign of malignancy and is currently the second leading cause of death in cancer patients after their malignancy. However, the molecular mechanisms underlying cancer-associated thrombosis remain undefined. In this study, we aimed to develop a better understanding of how cancer cells affect the coagulation cascade and platelet activation to induce a prothrombotic phenotype. Our results show that colon cancer cells trigger platelet activation in a manner dependent on cancer cell tissue factor (TF) expression, thrombin generation, activation of the protease-activated receptor 4 (PAR4) on platelets and consequent release of ADP and thromboxane A2. Platelet-colon cancer cell interactions potentiated the release of platelet-derived extracellular vesicles (EVs) rather than cancer cell-derived EVs. Our data show that single colon cancer cells were capable of recruiting and activating platelets and generating fibrin in plasma under shear flow. Finally, in a retrospective analysis of colon cancer patients, we found that the number of venous thromboembolism events was 4.5 times higher in colon cancer patients than in a control population. In conclusion, our data suggest that platelet-cancer cell interactions and perhaps platelet procoagulant EVs may contribute to the prothrombotic phenotype of colon cancer patients. Our work may provide rationale for targeting platelet-cancer cell interactions with PAR4 antagonists together with aspirin and/or ADP receptor antagonists as a potential intervention to limit cancer-associated thrombosis, balancing safety with efficacy.
Modulating GLUT1 expression in retinal pigment epithelium decreases glucose levels in the retina: impact on photoreceptors and Müller glial cells
Authors: Swarup Aditi , Samuels Ivy S. , Bell Brent A. , Han John Y. S. , Du Jianhai , Massenzio Erik , Abel E. Dale , Boesze-Battaglia Kathleen , Peachey Neal S. , Philp Nancy J.
Published: November 2018

The retina is one of the most metabolically active tissues in the body and utilizes glucose to produce energy and intermediates required for daily renewal of photoreceptor cell outer segments. Glucose transporter 1 (GLUT1) facilitates glucose transport across outer blood retinal barrier (BRB) formed by the retinal pigment epithelium (RPE) and the inner BRB formed by the endothelium. We used conditional knockout mice to study the impact of reducing glucose transport across the RPE on photoreceptor and Müller glial cells. Transgenic mice expressing Cre recombinase under control of the Bestrophin1 ( Best1) promoter were bred with Glut1flox/flox mice to generate Tg-Best1-Cre:Glut1flox/flox mice ( RPEΔGlut1). The RPEΔGlut1 mice displayed a mosaic pattern of Cre expression within the RPE that allowed us to analyze mice with ~50% ( RPEΔGlut1m) recombination and mice with >70% ( RPEΔGlut1h) recombination separately. Deletion of GLUT1 from the RPE did not affect its carrier or barrier functions, indicating that the RPE utilizes other substrates to support its metabolic needs thereby sparing glucose for the outer retina. RPEΔGlut1m mice had normal retinal morphology, function, and no cell death; however, where GLUT1 was absent from a span of RPE greater than 100 µm, there was shortening of the photoreceptor cell outer segments. RPEΔGlut1h mice showed outer segment shortening, cell death of photoreceptors, and activation of Müller glial cells. The severe phenotype seen in RPEΔGlut1h mice indicates that glucose transport via the GLUT1 transporter in the RPE is required to meet the anabolic and catabolic requirements of photoreceptors and maintain Müller glial cells in a quiescent state.
Synergy between sacubitril and valsartan leads to hemodynamic, antifibrotic, and exercise tolerance benefits in rats with preexisting heart failure
Authors: Maslov Mikhail Y. , Foianini Stephan , Mayer Dita , Orlov Michael V. , Lovich Mark A.
Published: November 2018

Simultaneous neprilysin inhibition (NEPi) and angiotensin receptor blockade (ARB) with sacubitril/valsartan improves cardiac function and exercise tolerance in patients with heart failure. However, it is not known whether these therapeutic benefits are primarily due to NEPi with sacubitril or ARB with valsartan or their combination. Therefore, the aim of the present study was to investigate the potential contribution of sacubitril and valsartan to the benefits of the combination therapy on left ventricular (LV) function and exercise tolerance. Heart failure was induced by volume overload via partial disruption of the aortic valve in rats. Therapy began 4 wk after valve disruption and lasted through 8 wk. Drugs were administered daily via oral gavage [sacubitril/valsartan (68 mg/kg), valsartan (31 mg/kg), and sacubitril (31 mg/kg)]. Hemodynamic assessments were conducted using Millar technology, and an exercise tolerance test was conducted using a rodent treadmill. Therapy with sacubitril/valsartan improved load-dependent indexes of LV contractility (dP/d tmax) and relaxation (dP/d tmin), exercise tolerance, and mitigated myocardial fibrosis, whereas monotherapies with valsartan, or sacubitril did not. Both sacubitril/valsartan and valsartan similarly improved a load-independent index of contractility [slope of the end-systolic pressure-volume relationship ( Ees)]. Sacubitril did not improve Ees. First, synergy of NEPi with sacubitril and ARB with valsartan leads to the improvement of load-dependent LV contractility and relaxation, exercise tolerance, and reduction of myocardial collagen content. Second, the improvement in load-independent LV contractility with sacubitril/valsartan appears to be solely due to ARB with valsartan constituent.

NEW & NOTEWORTHY Our data suggest the following explanation for the effects of sacubitril/valsartan: 1) synergy of sacubitril and valsartan leads to the improvement of load-dependent left ventricular contractility and relaxation, exercise tolerance, and reduction of myocardial fibrosis and 2) improvement in load-independent left ventricular contractility is solely due to the valsartan constituent. The findings offer a better understanding of the outcomes observed in clinical studies and might facilitate the continuing development of the next generations of angiotensin receptor neprilysin inhibitors.
Effects of altered pyruvate dehydrogenase activity on contracting skeletal muscle bioenergetics
Authors: Kasper Jonathan D. , Meyer Ronald A. , Beard Daniel A. , Wiseman Robert W.
Published: November 2018

During aerobic exercise (>65% of maximum oxygen consumption), the primary source of acetyl-CoA to fuel oxidative ATP synthesis in muscle is the pyruvate dehydrogenase (PDH) reaction. This study investigated how regulation of PDH activity affects muscle energetics by determining whether activation of PDH with dichloroacetate (DCA) alters the dynamics of the phosphate potential of rat gastrocnemius muscle during contraction. Twitch contractions were induced in vivo over a broad range of intensities to sample submaximal and maximal aerobic workloads. Muscle phosphorus metabolites were measured in vivo before and after DCA treatment by phosphorus nuclear magnetic resonance spectroscopy. At rest, DCA increased PDH activation compared with control (90 ± 12% vs. 23 ± 3%, P < 0.05), with parallel decreases in inorganic phosphate (Pi) of 17% (1.4 ± 0.2 vs. 1.7 ± 0.1 mM, P < 0.05) and an increase in the free energy of ATP hydrolysis (ΔGATP) (−66.2 ± 0.3 vs. −65.6 ± 0.2 kJ/mol, P < 0.05). During stimulation DCA increased steady-state phosphocreatine (PCr) and the magnitude of ΔGATP, with concomitant reduction in Piand ADP concentrations. These effects were not due to kinetic alterations in PCr hydrolysis, resynthesis, or glycolytic ATP production and altered the flow-force relationship between mitochondrial ATP synthesis rate and ΔGATP. DCA had no significant effect at 1.0- to 2.0-Hz stimulation because physiological mechanisms at these high stimulation levels cause maximal activation of PDH. These data support a role of PDH activation in the regulation of the energetic steady state by altering the phosphate potential (ΔGATP) at rest and during contraction.
Neuromuscular junction abnormalities in a zebrafish loss-of-function model of TDP-43
Authors: Bose Poulomee , Armstrong Gary A. B. , Drapeau Pierre
Published: November 2018

Almost 90% of amyotrophic lateral sclerosis (ALS) cases are characterized by the presence of aggregates of insoluble, misfolded cytoplasmic TAR DNA binding protein of 43 kDa (TDP-43). Distal axonopathy with impaired neuromuscular junctions (NMJs) before motor neuron degeneration or clinical onset of symptoms has been hypothesized as an early pathology in ALS. However, synaptic defects at the NMJ caused by TDP-43 mutations have not been characterized. In this study, we examined a previously reported zebrafish line expressing the tardbpY220X/Y220Xvariant, which results in an unstable and degraded protein. These tardbp−/−larvae, however, mature normally due to the upregulated expression of an alternative splice variant of the tardbp paralog tardbp-like, or tardbpl. We generated a mutant line with a CRISPR/Cas9-mediated 5-base pair deletion encompassing the ATG start codon of tardbpl and in-crossed these with tardbp−/−mutants to obtain tardbp−/−and tardbpl−/−double mutants, herein referred to as hom/hom. We subsequently characterized morphological, coiling, locomotor, synaptic, and NMJ structural abnormalities in the hom/hom mutants and in their genotypic controls. We observed that hom/hom mutants displayed gross morphological defects, early lethality, reduced locomotor function, aberrant quantal transmission, and perturbed synapse architecture at the NMJ. We further employed pharmacological manipulations in an effort to rescue phenotypic defects and observed that tardbp+/−; tardbpl−/−(herein referred to as het/hom) mutants, but not hom/hom mutants, were sensitive to chronic treatments of BAY K 8644, an L-type calcium channel agonist. This result highlights the importance of partial vs. complete loss of allelic functions of TDP-43.

NEW & NOTEWORTHY This study highlights the importance of partial vs. complete loss of allelic functions of TDP-43 in a zebrafish loss of function model, thus making it an attractive tool for drug screening approaches.
Temporal and spatial asymmetries during stationary cycling cause different feedforward and feedback modifications in the muscular control of the lower limbs
Authors: Zych Magdalena , Rankin Ian , Holland Donal , Severini Giacomo
Published: November 2018

Motor adaptations are useful for studying the way in which the lower limbs are controlled by the brain. However, motor adaptation paradigms for the lower limbs are typically based on locomotion tasks, where the necessity of maintaining postural stability is the main driver of adaptation and could possibly mask other underlying processes. In this study we investigated whether small temporal or spatial asymmetries can trigger motor adaptations during stationary cycling, where stability is not directly compromised. Fourteen healthy individuals participated in two experiments: in one of the experiments, the angle between the crank arms of the pedals was altered by 10° to induce a temporal asymmetry; in the other experiment, the length of the right pedal was shortened by 2.4 cm to induce a spatial asymmetry. We recorded the acceleration of the crank arms and the electromographic signals of 16 muscles (8 per leg). The analysis of the accelerometer data was used to investigate the presence of motor adaptations. Muscle synergy analysis was performed on each side to quantify changes in neuromuscular control. We found that motor adaptations are present in response to temporal asymmetries and are obtained by progressively shifting the activation patterns of two synergies on the right leg. Spatial asymmetries, on the other hand, appear to trigger a feedback-driven response that does not present an aftereffect. This response is characterized by a steplike decrease in activity in the right gastrocnemius when the asymmetry is present and likely reflects the altered task demands.

NEW & NOTEWORTHY The processes driving lower limb motor adaptations are not fully clear, and previous research appears to indicate that adaptations are mainly driven by stability. We show that lower limb adaptations can be obtained also in the absence of an explicit balance threat. We also show that adaptations are present when kinematic error cannot be compensated for, suggesting the presence of intrinsic error measures regulating the timing of activation of the two legs.