bluuebunny/crossref_metadata_2025 huggingface dataset:
Riverscape genetic variation, migration patterns, and morphological variation of the threatened Round Rocksnail, Leptoxis ampla
Authors: Whelan Nathan V. , Galaska Matthew P. , Sipley Breanna N. , Weber Jennifer M. , Johnson Paul D. , Halanych Kenneth M. , Helms Brian S.
Published: January 2019

Within riverine systems, headwater populations are hypothesized to harbour higher amounts of genetic distinctiveness than populations in the main stem of a river and display increased genetic diversity in large, downstream habitats. However, these hypotheses were mostly developed with insects and fish, and they have not been tested on many invertebrate lineages. Pleuroceridae gastropods are of particular ecological importance to rivers of eastern North America, sometimes comprising over 90% of macroinvertebrate biomass. Yet, virtually nothing is known of pleurocerid landscape genetics, including whether genetic diversity follows predictions made by hypotheses developed on more mobile species. Moreover, the commonly repeated hypothesis that intraspecific morphological variation in gastropods results from ecophenotypic plasticity has not been well tested on pleurocerids. Using 2bRAD‐seq to discover single nucleotide polymorphisms, we show that the threatened, Cahaba River endemic pleurocerid, Leptoxis ampla, has limited gene flow among populations and that migration is downstream‐biased, conflicting with previous hypotheses. Both tributary and main stem populations harbour unique genomic profiles, and genetic diversity was highest in downstream populations. Furthermore, L. ampla shell morphology was more correlated with genetic differences among individuals and populations than habitat characteristics. We anticipate similar genetic and demographic patterns to be seen in other pleurocerids, and hypotheses about gene flow and population demographics that were based on more mobile taxa often, but not always, apply to freshwater gastropods. From a conservation standpoint, genetic structure of L. ampla populations suggests distinctive genetic diversity is lost with localized extirpation, a phenomenon common across the range of Pleuroceridae.
Diagnostic accuracy of the Thai version of the Mini‐Addenbrooke's Cognitive Examination as a mild cognitive impairment and dementia screening test
Authors: Charernboon Thammanard
Published: January 2019

Aim

To examine the diagnostic accuracy of the Thai version of the Mini‐Addenbrooke's Cognitive Examination (MACE‐T) for detecting mild cognitive impairment and dementia.

Methods

Participants consisted of 60 controls, 40 people with mild cognitive impairment (MCI) and 48 people with dementia. All participants completed the Thai version of the Addenbrooke's Cognitive Examination – III (ACE‐T) and the MACE‐T scores were obtained from items within the ACE‐T.

Results

A cut‐off score of 21/22 detected MCI with a sensitivity of 95% (95% confidence interval (CI): 86.1–100) and specificity of 85% (95% CI: 77.8–93.4). A cut‐off score of 16/17 detected dementia with a sensitivity and specificity of 95.8% (95% CI: 88.2–100) and 85% (95% CI: 76.4–89.7), respectively. Using Bayes theorem, the MACE‐T demonstrated high negative predictive values (> 94%) for diagnosing MCI and dementia, independent of their prevalence rates. Education was the only significant predictor of performance in the MACE‐T.

Conclusion

The MACE‐T is a good short cognitive screening test with high diagnostic accuracy for screening for MCI and dementia.
Urban voices: The hybrid figure of the street singer in Renaissance Italy
Authors: Degl’Innocenti Luca , Rospocher Massimo
Published: January 2019

This essay aims to investigate from a combined historical and literary perspective the protean and elusive figures of early modern Italian street singers, or cantastorie, showing the advantages and challenges of an interdisciplinary approach. Both textual analysis and archival investigation, we argue, are of crucial importance in order to shed some light on their social identity as well as on their cultural background. Cantastorie are in fact so multifaceted that the same figure is often known to different scholars in a variety of roles. Depending on a scholar’s discipline, or on the sources used, a single face emerges, making them appear either as poets or as singers, or as musicians, actors, jugglers, barkers, publishers, booksellers, entertainers, news‐reporters, public lecturers, medical charlatans and many other things. By focusing on three paradigmatic examples (and on several minor ones), we show that in order to draw an all‐round portrait of these itinerant performers we have to combine as many different perspectives as possible: Jacopo Coppa was a charlatan, Niccolò Zoppino a publisher, and Cristoforo the Altissimo a poet, but all of them – like most cantastorie – were also several other things at the same time. Therefore, in analysing street performers it is difficult to employ traditional social, literary and cultural categories, but we need to adopt – and sometimes create – more comprehensive and truly interdisciplinary paradigms. It is essential to combine different methodologies, scales of analysis, and sources; in a nutshell, it often means reading the same texts with different eyes.
Associations of fitness and physical activity with orthostatic responses of heart rate and blood pressure at midlife
Authors: Oksanen Päivi , Tulppo Mikko P. , Auvinen Juha , Niemelä Maisa , Jämsä Timo , Puukka Katri , Huikuri Heikki V. , Korpelainen Raija , Venojärvi Mika , Kiviniemi Antti M.
Published: January 2019

Cardiorespiratory fitness (CRF) and physical activity (PA) are associated with autonomic function, but their associations to orthostatic autonomic responses are unclear in epidemiological setting. We hypothesized that higher CRF and PA would associate with higher immediate vagal responses and lower incidence of adverse findings during orthostatic test. At age of 46, 787 men and 938 women without cardiorespiratory diseases and diabetes underwent an orthostatic test (3‐minutes sitting, 3‐minutes standing) with recording of RR intervals (RRi) and blood pressure (BP) by finger plethysmography. Acute responses of RRi (30:15 ratio) and BP were calculated. CRF was measured by a submaximal step test and daily amount of moderate‐to‐vigorous PA (MVPA) for 2 weeks by wrist‐worn accelerometer. Lifelong PA was based on questionnaires at ages of 14, 31, and 46. High CRF was significantly associated with higher RRi 30:15 ratio (adjusted standardized β = 0.17, P < 0.001) and milder acute decrease of systolic BP while standing (β = 0.10, P = 0.001), while MVPA was not (β = 0.04 for RRi 30:15 ratio and β = 0.05 for systolic BP acute response). High lifelong PA was significantly associated with higher RRi 30:15 ratio (β = 0.08, P = 0.002) but not with acute systolic BP response. Those in the lowest tertile of CRF had 9.2‐fold risk (P = 0.002) of having postural orthostatic tachycardia syndrome compared to more fit. Cardiorespiratory fitness and lifelong physical activity, but not current physical activity, were independently associated with higher cardiac vagal response to orthostasis. The present results underscore the importance fitness and lifelong physical activity in prevention of abnormal autonomic function and related cardiovascular risk.
The Impact of Globalization on Women's and Non‐Women's Protest*
Authors: Bell Sam R. , Murdie Amanda , Peksen Dursun
Published: January 2019

Objectives

We advance hypotheses on the extent to which the three main aspects of globalization—economic, political, and social—fuel mass protest and delineate how these effects can be especially instrumental in understanding collective mass mobilization among a historically disadvantaged group, women.

Methods

We use new and updated data on anti‐government protest to examine the covariates of protest intensity cross‐nationally over time.

Results

Results from the data analysis indicate that while political globalization is associated with reduced women's protest, social globalization is associated with increased women's and non‐women's protest. Further, economic globalization has somewhat divergent effects on women's and non‐women's protest.

Conclusions

Results from our thorough analysis of the three main aspects of globalization highlight the varying effects that different dimensions of globalization have on political protest. Our study offers a unique analysis of the factors associated with protest by women and compares it to other types of protest.
Placental histopathological abnormalities and poor perinatal outcomes
Authors: Thirumalaikumar Lakshmi , Ramalingam Kalaivani , Marton Tamas
Published: January 2019

Key content

Examination of the placenta is important and must be correlated with the clinical conditions.

Placental histology can yield valuable information in cases of adverse perinatal outcome.

Information obtained from the placenta is vital to formulate an appropriate plan of care in subsequent pregnancy.

Learning objectives

To understand the correlation between placental histology and pregnancy outcome.

To identify the clinical conditions that will benefit from placental histology.

To understand the process of storing the placenta for different examination techniques.

Ethical issues

Should the placenta be sent for histology in all cases of growth restriction and stillbirth?

Is it cost effective to undertake universal placental histology?
ZooScatR—An r package for modelling the scattering properties of weak scattering targets using the distorted wave Born approximation
Authors: Gastauer Sven , Chu Dezhang , Cox Martin J.
Published: January 2019

A thorough understanding of the scattering characteristics of marine organisms is a prerequisite for robust quantitative fisheries acoustic data processing or interpretation. Target strength models, such as the distorted wave Born approximation (DWBA) can be used to improve the understanding of field recordings of weakly scattering targets. With acoustic methods now being used by a wide audience, allowing access to such models becomes a necessity. To ease access to the DWBA model, an r package (zooscatr) which includes a web application and the ability to parameterise the model either through the web application, text files, or pure scripting has been developed and is now freely available on Github.
Effect of Skill Level on Allocation of Visual Attention in Volleyball Blocking
Authors: Laffer Jason C. , Coutts Aaron J. , Fransen Job
Published: January 2019

Dynamic motor skills such as volleyball blocking rely on efficient perception–action coupling and are influenced by individual, environmental, and task constraints. However, limited research studies have assessed the effect of an individual constraint such as blocking skill on visual attention during anin-situvolleyball blocking task. Therefore, this study used a cross-sectional, observational design to investigate the gaze behavior of 18 male volleyball players (25.6 ± 4.9 years), of two different levels of blocking skill determineda prioriaccording to success during an on-court blocking task. When compared to relatively unsuccessful players (RUS), the gaze of relatively successful players (RS) was observed to fixate more often (RUS: 0.7 ± 0.7 n, RS: 1.3 ± 0.3 n) and dwell for longer (Total; RUS: 12.2 ± 18.4%, RS: 48.0 ± 37.2%, Phase 4; RUS: 6.6 ± 8.8%, RS: 16.9 ± 12.4%) on the opposition spiker, demonstrating that important perceptual information about an opposing team’s attack lies within the behavior of the opposition spiker. More successful blockers were also observed to be taller (RUS: 181.8 ± 6.6 cm, RS: 192.6 ± 3.9 cm), longer in arm-span (RUS: 185.7 ± 5.6 cm, RS: 195.2 ± 5.6 cm), and heavier (RUS: 78.6 ± 11.4 kg, RS: 90.5 ± 8.5 kg). These results can consequently be used to develop a profile of the visual attention and physical attributes of successful blockers for use in developing talented players.
Robot learning—Beyond imitation
Authors: Yang Guang-Zhong
Published: January 2019

This special issue covers many aspects and applications of robot learning, including current progress, opportunities, and challenges.
Impact of an Antimicrobial Stewardship Intervention on Within- and Between-Patient Daptomycin Resistance Evolution in Vancomycin-Resistant Enterococcus faecium
Authors: Kinnear Clare L. , Patel Twisha S. , Young Carol L. , Marshall Vincent , Newton Duane W. , Read Andrew F. , Woods Robert J.
Published: January 2019

Vancomycin-resistant
Enterococcus
(VRE) is a leading cause of hospital-acquired infection, with limited treatment options. Resistance to one of the few remaining drugs, daptomycin, is a growing clinical problem and has previously been described in this hospital.
Nearly Complete Genome Sequence of a Human Norovirus GII.P17-GII.17 Strain Isolated from Brazil in 2015
Authors: Santiso-Bellón Cristina , Fuentes-Trillo Azahara , da Silva Ribeiro de Andrade Juliana , Monzó Carolina , Vila-Vicent Susana , Gozalbo Rovira Roberto , Buesa Javier , Chaves Felipe J. , Miagostovich Marize Pereira , Rodríguez-Díaz Jesús
Published: January 2019

Human noroviruses are the most common cause of nonbacterial acute gastroenteritis worldwide. We report here the nearly complete genome sequence (7,551 nucleotides) of a human norovirus GII.P17-GII.17 strain detected in July 2015 in the stool sample from an adult with acute gastroenteritis in Brazil.
Complete Genome Sequence of Microbacterium foliorum NRRL B-24224, a Host for Bacteriophage Discovery
Authors: Russell Daniel A. , Garlena Rebecca A. , Hatfull Graham F.
Published: January 2019

We report the complete annotated genome sequence of
Microbacterium foliorum
NRRL B-24224, a type strain isolated from the phyllosphere of grasses and a commonly used host for bacteriophage discovery. The genome contains no identifiable prophage or CRISPR or restriction-modification system, which suggests that it may continue to be a fruitful host for phage discovery.
Complete Genome Sequence of the Marine Hydrocarbon Degrader Alcaligenes aquatilis QD168, Isolated from Crude Oil-Polluted Sediment of Quintero Bay, Central Chile
Authors: Durán Roberto E. , Barra-Sanhueza Bárbara , Salvà-Serra Francisco , Méndez Valentina , Jaén-Luchoro Daniel , Moore Edward R. B. , Seeger Michael
Published: January 2019

Alcaligenes aquatilis
strain QD168 (= CCUG 69566) is a marine hydrocarbon-degrading bacterium isolated from crude oil-polluted sediment from Quintero Bay, Central Chile. Here, we present the 4.32-Mb complete genome sequence of strain QD168, with 3,892 coding sequences, 58 tRNAs, and a 56.3% G+C content.
sRNA Target Prediction Organizing Tool (SPOT) Integrates Computational and Experimental Data To Facilitate Functional Characterization of Bacterial Small RNAs
Authors: King Alisa M. , Vanderpool Carin K. , Degnan Patrick H.
Published: January 2019

Small RNAs (sRNAs) regulate gene expression in diverse bacteria by interacting with mRNAs to change their structure, stability, or translation. Hundreds of sRNAs have been identified in bacteria, but characterization of their regulatory functions is limited by difficulty with sensitive and accurate identification of mRNA targets. Thus, new robust methods of bacterial sRNA target identification are in demand. Here, we describe our
s
mall RNA target
p
rediction
o
rganizing
t
ool (SPOT), which streamlines the process of sRNA target prediction by providing a single pipeline that combines available computational prediction tools with customizable results filtering based on experimental data. SPOT allows the user to rapidly produce a prioritized list of predicted sRNA-target mRNA interactions that serves as a basis for further experimental characterization. This tool will facilitate elucidation of sRNA regulons in bacteria, allowing new discoveries regarding the roles of sRNAs in bacterial stress responses and metabolic regulation.
A Translational Pharmacokinetic Rat Model of Cerebral Spinal Fluid and Plasma Concentrations of Cefepime
Authors: Avedissian Sean N. , Pais Gwendolyn , Joshi Medha D. , Rhodes Nathaniel J. , Scheetz Marc H.
Published: January 2019

This study defines the transit of cefepime between plasma and cerebral spinal fluid (CSF) in a rat model. Male Sprague-Dawley rats received cefepime intravenously. Plasma samples were obtained via a second dedicated intravenous catheter. CSF sampling occurred via an intracisternal catheter. Drug exposures and transfer from the plasma to the CSF during the first 24 h were calculated. The median CSF/blood percentage of penetration was 19%. Cefepime transit to the CSF is rapid and predictable in the rat model. This model will be highly useful for understanding the therapeutic window for cefepime and neurotoxicity.
Importance of diagnostics in epidemic and pandemic preparedness
Authors: Kelly-Cirino Cassandra D , Nkengasong John , Kettler Hannah , Tongio Isabelle , Gay-Andrieu Françoise , Escadafal Camille , Piot Peter , Peeling Rosanna W , Gadde Renuka , Boehme Catharina
Published: January 2019

Diagnosticsare fundamental for successful outbreak containment. In this supplement, ‘Diagnostic preparedness for WHO Blueprint pathogens’, we describe specific diagnostic challenges presented by selected priority pathogens most likely to cause future epidemics.

Some challenges to diagnostic preparedness are common to all outbreak situations, as highlighted by recent outbreaks of Ebola, Zika and yellow fever. In this article, we review these overarching challenges and explore potential solutions. Challenges include fragmented and unreliable funding pathways, limited access to specimens and reagents, inadequate diagnostic testing capacity at both national and community levels of healthcare and lack of incentives for companies to develop and manufacture diagnostics for priority pathogens during non-outbreak periods. Addressing these challenges in an efficient and effective way will require multiple stakeholders—public and private—coordinated in implementing a holistic approach to diagnostics preparedness. All require strengthening of healthcare system diagnostic capacity (including surveillance and education of healthcare workers), establishment of sustainable financing and market strategies and integration of diagnostics with existing mechanisms. Identifying overlaps in diagnostic development needs across different priority pathogens would allow more timely and cost-effective use of resources than a pathogen by pathogen approach; target product profiles for diagnostics should be refined accordingly. We recommend the establishment of a global forum to bring together representatives from all key stakeholders required for the response to develop a coordinated implementation plan. In addition, we should explore if and how existing mechanisms to address challenges to the vaccines sector, such as Coalition for Epidemic Preparedness Innovations and Gavi, could be expanded to cover diagnostics.
A novel vegetated three-layer landfill cover system using recycled construction wastes without geomembrane
Authors: Ng Charles W.W. , Chen R. , Coo J.L. , Liu J. , Ni J.J. , Chen Y.M. , Zhan L.-t. , Guo H.W. , Lu B.W.
Published: January 2019

To promote environmental protection and sustainability, the use of plants and recycled wastes in geotechnical construction such as landfill covers is recommended. A landfill cover field test was conducted at the Shenzhen Xiaping landfill site, located in a humid climatic region of China. The main objective was to validate the field performance of a novel vegetated three-layer landfill cover system using recycled construction waste without the need of geomembrane. Unsieved completely decomposed granite and coarsely crushed concrete was used for the top and intermediate layers while sieved completely decomposed granite was used as the lowest layer. One section was transplanted with Bermuda grass while the other section was left bare. To assess the landfill cover performance, pore-water pressure, volumetric water content, percolation, and atmospheric parameters were measured for a period of 13 months under natural climatic conditions. The cumulative rainfall depth was about 2950 mm over the entire monitoring period. During rainfall, the presence of grass led to lower pore-water pressure (or higher suction) and volumetric water content in the three-layer landfill cover system. At the end of monitoring, the cumulative percolation was about 27 and 20 mm for the bare and grass-covered landfill covers, respectively. It is evident that the vegetated three-layer landfill cover system using recycled concrete without geomembrane can be effective in minimizing percolation in humid climates.
Quantum Hall devices for the primary resistance standard based on the GaAs/AlxGa1−x As heterostructure
Authors: Wang Xueshen , Zhong Qing , Li Jinjin , Zhong Yuan , Zhao Mengke
Published: January 2019

Quantum Hall devices for primary resistance metrology based on the GaAs/Al[Formula: see text]Ga[Formula: see text]As heterostructure were fabricated and compared with the devices from international metrology organization International Bureau of Weights and Measures (BIPM) by calibrating the same 100 [Formula: see text] transfer standard resistor with a cryogenic current comparator. Relative deviation between NIM-made device NIM-C1 and BIPM-made device BIPM-1 was −4.49 parts in 109 with an uncertainty of 3.63 parts in 109 which indicated NIM-C1 satisfied the requirement for the primary resistance standard.
2.4 GHz Real-Time Prototyping Tool for OFDM Channel Estimation using USRP2 and LabVIEW
Authors: Küçük Kerem
Published: January 2019

Wireless local area networks (WLANs) are currently playing an important role in serving the indoor traffic demand. Therefore, there is a need for software-defined radio platforms (SDRs) that can enable the solutions used in these systems to be tested in real environments as well as simulated results. In this paper, we present the SDR-based wireless receiver platform for determining the real-time WLANs performance and provide the comparison of the different channel estimation methods for IEEE 802.11g based on orthogonal frequency division multiplexing (OFDM) operations. The implementation of the receiver comprises the universal software radio peripheral and National Instruments LabVIEW. To determine the real-time receiver tool performance, we emphasized necessary signal processing techniques and different channel estimation methods with varying experimental parameters in real wireless environments. Experimental results report that the SDR-based receiver tool with the LabVIEW in real-time provides the throughput of the OFDM wireless network. The captured throughput performance concerning frame error rate by the receiver is also scrutinized with different channel estimation methods.
Population-based incremental learning for the prediction of Homo sapiens’ protein secondary structure
Authors: Chen Ye , Yuan Xiaoping , Cang Xiaohui
Published: January 2019

Protein structure prediction is the prediction of the 3D structure of a protein based on its amino acid sequence. It is a key component in disciplines such as medicine, biology, and biochemistry. The prediction of the protein secondary structure of Homo sapiens is one of the more important domains. Many methods have been used to feed forward neural networks or SVMs combined with a sliding window. This method’s mechanisms are too complex to be able to extract clear and straightforward physical meanings from it. This paper explores population-based incremental learning (PBIL), which is a method that combines the mechanisms of a generational genetic algorithm with simple competitive learning. The result shows that its accuracies are particularly associated with the Homo species. This new perspective reveals a number of different possibilities for the purposes of performance improvements.
Iridium Satellite Signals: A Case Study in Interference Characterization and Mitigation for Radio Astronomy Observations
Authors: Deshpande Avinash A. , Lewis B. M.
Published: January 2019

Several post-detection approaches to the mitigation of radio-frequency interference (RFI) are compared by applying them to the strong RFI from the Iridium satellites. These provide estimates for the desired signal in the presence of RFI, by exploiting distinguishing characteristics of the RFI, such as its polarization, statistics, and periodicity. Our data are dynamic spectra with full Stokes parameters and 1[Formula: see text]ms time resolution. Moreover, since most man-made RFI is strongly polarized, we use the data to compare its unpolarized component with its Stokes I. This approach on its own reduces the RFI intensity by many tens of dBs. A comprehensive approach that also recognizes non-Gaussian statistics, and the time and frequency structure inherent in the RFI, permits exceedingly effective post-detection excision provided full Stokes intensity data are available.
Light Shapes
Authors: Kartashova Tatiana , Pas Susan F. Te , Ridder Huib De , Pont Sylvia C.
Published: January 2019

In computer graphics, illuminating a scene is a complex task, typically consisting of cycles of adjusting and rendering the scene to see the effects. We propose a technique for visualization of light as a tensor field via extracting its properties (i.e., intensity, direction, diffuseness) from (virtual) radiance measurements and showing these properties as a grid of shapes over a volume of a scene. Presented in the viewport, our visualizations give an understanding of the illumination conditions in the measured volume for both the local values and the global variations of light properties. Additionally, they allow quick inferences of the resulting visual appearance of (objects in) scenes without the need to render them. In our evaluation, observers performed at least as well using visualizations as using renderings when they were comparing illumination between parts of a scene and inferring the final appearance of objects in the measured volume. Therefore, the proposed visualizations are expected to help lighting artists by providing perceptually relevant information about the structure of the light field and flow in a scene.
A General Framework for Spectrum Sensing Using Dedicated Spectrum Sensor Networks
Authors: Liu Yunhuai , Zhang Qian , Ni Lionel
Published: January 2019

Efficient spectrum sensing is essential for the successful application of the Dynamic Spectrum Assignment (DSA) technology in Cognitive Radio Networks (CRNs). In conventional spectrum sensing schemes, secondary users (SUs) have to intelligently schedule their sensing and accessing so that the spectrum opportunities are thoroughly exploited while the primary users are not harmed. In this article, we propose a new sensing service model in which a Spectrum Sensor Network (SSN) is employed for spectrum sensing tasks. We will describe the general framework for this SSN-enabled CRN and present the major challenges in such an architecture. We will address one of these challenges and formulate it as a boundary detection problem with unknown erroneous inputs. A novel cooperative boundary detection algorithm is designed which explores recent advances in Support Vector Machines (SVM) and computational geometry. We prove that cooperative spectrum sensing can asymptotically approach the optimal solution. Real testbed as well as comprehensive simulation experiments are conducted, and the results show that, compared with the traditional schemes, cooperative boundary detection can dramatically reduce the spectrum sensing overhead and improve the effectiveness of DSA.
Split Manufacturing-Based Register Transfer-Level Obfuscation
Authors: Cui Xiaotong , Zhang Jeff (Jun) , Wu Kaijie , Garg Siddharth , Karri Ramesh
Published: January 2019

Fabrication-less integrated circuit (IC) design houses outsource fabrication to third-party foundries to reduce cost of manufacturing. The outsourcing of IC fabrication, beyond our expectation, raises concerns regarding intellectual property (IP) piracy and theft by rogue elements in the third-party foundries. Obfuscation techniques have been proposed to increase resistance to reverse engineering, IP recovery, IP theft, and piracy. However, prior work on obfuscation for IP protection has primarily applied to the gate level or the layout level. As a result, it can significantly impact the performance of the original design in addition to requiring redesign of standard cells.

In this article, we propose a high-level synthesis and analysis (HLSA)-based obfuscation approach for IP protection. The proposed method is based on split manufacturing. Additional dummy units and MUXes can be added to further obfuscate the design. The proposed technique aligns with the standard-cell-based design methodologies and does not significantly impact the performance of the original design. Our experimental results confirm that the proposed approach can provide high levels of IC obfuscation with moderate area cost.
Solving the Structure and Dynamics of Metal Nanoparticles by Combining X-Ray Absorption Fine Structure Spectroscopy and Atomistic Structure Simulations
Authors: Timoshenko J. , Duan Z. , Henkelman G. , Crooks R.M. , Frenkel A.I.
Published: January 2019

Extended X-ray absorption fine structure (EXAFS) spectroscopy is a premiere method for analysis of the structure and structural transformation of nanoparticles. Extraction of analytical information about the three-dimensional structure and dynamics of metal–metal bonds from EXAFS spectra requires special care due to their markedly non-bulk-like character. In recent decades, significant progress has been made in the first-principles modeling of structure and properties of nanoparticles. In this review, we summarize new approaches for EXAFS data analysis that incorporate particle structure modeling into the process of structural refinement.
CRISPR-Based Tools in Immunity
Authors: Simeonov Dimitre R. , Marson Alexander
Published: January 2019

CRISPR technology has opened a new era of genome interrogation and genome engineering. Discovered in bacteria, where it protects against bacteriophage by cleaving foreign nucleic acid sequences, the CRISPR system has been repurposed as an adaptable tool for genome editing and multiple other applications. CRISPR's ease of use, precision, and versatility have led to its widespread adoption, accelerating biomedical research and discovery in human cells and model organisms. Here we review CRISPR-based tools and discuss how they are being applied to decode the genetic circuits that control immune function in health and disease. Genetic variation in immune cells can affect autoimmune disease risk, infectious disease pathogenesis, and cancer immunotherapies. CRISPR provides unprecedented opportunities for functional mechanistic studies of coding and noncoding genome sequence function in immunity. Finally, we discuss the potential of CRISPR technology to engineer synthetic cellular immunotherapies for a wide range of human diseases.
Using T Cell Receptor Repertoires to Understand the Principles of Adaptive Immune Recognition
Authors: Bradley Philip , Thomas Paul G.
Published: January 2019

Adaptive immune recognition is mediated by antigen receptors on B and T cells generated by somatic recombination during lineage development. The high level of diversity resulting from this process posed technical limitations that previously limited the comprehensive analysis of adaptive immune recognition. Advances over the last ten years have produced data and approaches allowing insights into how T cells develop, evolutionary signatures of recombination and selection, and the features of T cell receptors that mediate epitope-specific binding and T cell activation. The size and complexity of these data have necessitated the generation of novel computational and analytical approaches, which are transforming how T cell immunology is conducted. Here we review the development and application of novel biological, theoretical, and computational methods for understanding T cell recognition and discuss the potential for improved models of receptor:antigen interactions.
Acute kidney injury induces dramatic p21 upregulation via a novel, glucocorticoid-activated, pathway
Authors: Zager Richard A. , Johnson Ali C. M.
Published: January 2019

The cyclin kinase inhibitor p21 is acutely upregulated during acute kidney injury (AKI) and exerts cytoprotective effects. A proposed mechanism is oxidant stress-induced activation of p53, the dominant p21 transcription factor. Glycerol-induced rhabdomyolysis induces profound renal oxidant stress. Hence, we studied this AKI model to determine whether p53 activation corresponds with p21 gene induction and/or whether alternative mechanism(s) might be involved. CD-1 mice were subjected to glycerol-induced AKI. After 4 or 18 h, plasma, urinary, and renal cortical p21 protein and mRNA levels were assessed. Renal p53 activation was gauged by measurement of both total and activated (Ser15-phosphorylated) p53 and p53 mRNA levels. Glycerol evoked acute, progressive increases in renal cortical p21 mRNA and protein levels. Corresponding plasma (~25-fold) and urinary (~75-fold) p21 elevations were also observed. Renal cortical ratio of total to phosphorylated (Ser15) p53 rose three- to fourfold. However, the p53 inhibitor pifithrin-α failed to block glycerol-induced p21 gene induction, suggesting that an alternative p21 activator might also be at play. To this end, it was established that glycerol-induced AKI 1) dramatically increased plasma (~5-fold) and urinary (~75-fold) cortisol levels, 2) the glucocorticoid receptor antagonist mifepristone blocked glycerol-induced p21 mRNA and protein accumulation, and 3) dexamethasone or cortisol injections markedly increased p21 protein and mRNA in both normal and glycerol-treated mice, although no discernible p53 protein or mRNA increases were observed. We conclude that AKI-induced “systemic stress” markedly increases plasma and urinary cortisol, which can then activate renal p21 gene expression, at least in part, via a glucocorticoid receptor-dependent signaling pathway. Discernible renal cortical p53 increases are not required for this dexamethasone-mediated p21 response.
Processing of object motion and self-motion in the lateral subdivision of the medial superior temporal area in macaques
Authors: Sasaki Ryo , Angelaki Dora E. , DeAngelis Gregory C.
Published: January 2019

Multiple areas of macaque cortex are involved in visual motion processing, but their relative functional roles remain unclear. The medial superior temporal (MST) area is typically divided into lateral (MSTl) and dorsal (MSTd) subdivisions that are thought to be involved in processing object motion and self-motion, respectively. Whereas MSTd has been studied extensively with regard to processing visual and nonvisual self-motion cues, little is known about self-motion signals in MSTl, especially nonvisual signals. Moreover, little is known about how self-motion and object motion signals interact in MSTl and how this differs from interactions in MSTd. We compared the visual and vestibular heading tuning of neurons in MSTl and MSTd using identical stimuli. Our findings reveal that both visual and vestibular heading signals are weaker in MSTl than in MSTd, suggesting that MSTl is less well suited to participate in self-motion perception than MSTd. We also tested neurons in both areas with a variety of combinations of object motion and self-motion. Our findings reveal that vestibular signals improve the separability of coding of heading and object direction in both areas, albeit more strongly in MSTd due to the greater strength of vestibular signals. Based on a marginalization technique, population decoding reveals that heading and object direction can be more effectively dissociated from MSTd responses than MSTl responses. Our findings help to clarify the respective contributions that MSTl and MSTd make to processing of object motion and self-motion, although our conclusions may be somewhat specific to the multipart moving objects that we employed.

NEW & NOTEWORTHY Retinal image motion reflects contributions from both the observer’s self-motion and the movement of objects in the environment. The neural mechanisms by which the brain dissociates self-motion and object motion remain unclear. This study provides the first systematic examination of how the lateral subdivision of area MST (MSTl) contributes to dissociating object motion and self-motion. We also examine, for the first time, how MSTl neurons represent translational self-motion based on both vestibular and visual cues.
Adrenergic agonist induces rhythmic firing in quiescent cardiac preganglionic neurons in nucleus ambiguous via activation of intrinsic membrane excitability
Authors: Aiba Isamu , Noebels Jeffrey L.
Published: January 2019

Cholinergic vagal nerves projecting from neurons in the brain stem nucleus ambiguus (NAm) play a predominant role in cardiac parasympathetic pacemaking control. Central adrenergic signaling modulates the tone of this vagal output; however, the exact excitability mechanisms are not fully understood. We investigated responses of NAm neurons to adrenergic agonists using in vitro mouse brain stem slices. Preganglionic NAm neurons were identified by ChAT-tdTomato fluorescence in young adult transgenic mice, and their cardiac projection was confirmed by retrograde dye tracing. Juxtacellular recordings detected sparse or absent spontaneous action potentials (AP) in NAm neurons. However, bath application of epinephrine or norepinephrine strongly and reversibly activated most NAm neurons regardless of their basal firing rate. Epinephrine was more potent than norepinephrine, and this activation largely depends on α1-adrenoceptors. Interestingly, adrenergic activation of NAm neurons does not require an ionotropic synaptic mechanism, because postsynaptic excitatory or inhibitory receptor blockade did not occlude the excitatory effect, and bath-applied adrenergic agonists did not alter excitatory or inhibitory synaptic transmission. Instead, adrenergic agonists significantly elevated intrinsic membrane excitability to facilitate generation of recurrent action potentials. T-type calcium current and hyperpolarization-activated current are involved in this excitation pattern, although not required for spontaneous AP induction by epinephrine. In contrast, pharmacological blockade of persistent sodium current significantly inhibited the adrenergic effects. Our results demonstrate that central adrenergic signaling enhances the intrinsic excitability of NAm neurons and that persistent sodium current is required for this effect. This central balancing mechanism may counteract excessive peripheral cardiac excitation during increased sympathetic tone.

NEW & NOTEWORTHY Cardiac preganglionic cholinergic neurons in the nucleus ambiguus (NAm) are responsible for slowing cardiac pacemaking. This study identified that adrenergic agonists can induce rhythmic action potentials in otherwise quiescent cholinergic NAm preganglionic neurons in brain stem slice preparation. The modulatory influence of adrenaline on central parasympathetic outflow may contribute to both physiological and deleterious cardiovascular regulation.
On Best Proximity Results for a Generalized Modified Ishikawa’s Iterative Scheme Driven by Perturbed 2-Cyclic Like-Contractive Self-Maps in Uniformly Convex Banach Spaces
Authors: De la Sen M. , Abbas Mujahid
Published: January 2019

This paper proposes a generalized modified iterative scheme where the composed self-mapping driving can have distinct step-dependent composition order in both the auxiliary iterative equation and the main one integrated in Ishikawa’s scheme. The self-mapping which drives the iterative scheme is a perturbed 2-cyclic one on the union of two sequences of nonempty closed subsets Ann=0∞ and Bnn=0∞ of a uniformly convex Banach space. As a consequence of the perturbation, such a driving self-mapping can lose its cyclic contractive nature along the transients of the iterative process. These sequences can be, in general, distinct of the initial subsets due to either computational or unmodeled perturbations associated with the self-mapping calculations through the iterative process. It is assumed that the set-theoretic limits below of the sequences of sets Ann=0∞ and Bnn=0∞ exist. The existence of fixed best proximity points in the set-theoretic limits of the sequences to which the iterated sequences converge is investigated in the case that the cyclic disposal exists under the asymptotic removal of the perturbations or under its convergence of the driving self-mapping to a limit contractive cyclic structure.
traG Gene Is Conserved across Mesorhizobium spp. Able to Nodulate the Same Host Plant and Expressed in Response to Root Exudates
Authors: Paço A. , da-Silva J. R. , Eliziário F. , Brígido C. , Oliveira S. , Alexandre A.
Published: January 2019

Evidences for an involvement of the bacterial type IV secretion system (T4SS) in the symbiotic relationship between rhizobia and legumes have been pointed out by several recent studies. However, information regarding this secretion system in Mesorhizobium is still very scarce. The aim of the present study was to investigate the phylogeny and expression of the traG gene, which encodes a substrate receptor of the T4SS. In addition, the occurrence and genomic context of this and other T4SS genes, namely, genes from tra/trb and virB/virD4 complexes, were also analyzed in order to unveil the structural and functional organization of T4SS in mesorhizobia. The location of the T4SS genes in the symbiotic region of the analyzed rhizobial genomes, along with the traG phylogeny, suggests that T4SS genes could be horizontally transferred together with the symbiosis genes. Regarding the T4SS structural organization in Mesorhizobium, the virB/virD4 genes were absent in all chickpea (Cicer arietinum L.) microsymbionts and in the Lotus symbiont Mesorhizobium japonicum MAFF303099T. Interestingly, the presence of genes belonging to another secretion system (T3SS) was restricted to these strains lacking the virB/virD4 genes. The traG gene expression was detected in M. mediterraneum Ca36T and M. ciceri LMS-1 strains when exposed to chickpea root exudates and also in the early nodules formed by M. mediterraneum Ca36T, but not in older nodules. This study contributes to a better understanding of the importance of T4SS in mutualistic symbiotic bacteria.
Impact of Serum Uric Acid Levels on Outcomes following Renal Artery Revascularization in Patients with Renovascular Disease
Authors: Chen Xiao-jun , Eirin Alfonso , Kane Garvan C. , Misra Sanjay , Textor Stephen C. , Lerman Amir , Lerman Lilach O.
Published: January 2019

Background. Percutaneous transluminal renal angioplasty (PTRA) improves blood pressure (BP) and renal function only in selected patients with atherosclerotic renovascular disease (ARVD). Hyperuricemia is associated with elevated risk for hypertension and chronic renal disease, but its role in renovascular hypertension is unclear. We hypothesized that hyperuricemia negatively impacts renal and BP outcomes among patients with ARVD undergoing PTRA. Methods. This retrospective, observational cohort study included 94 patients with ARVD and preserved systolic cardiac function, who underwent PTRA at Mayo Clinic, Rochester, Minnesota. Renal, BP, and mortality outcomes were compared among patients according to their serum uric acid (SUA) levels. Multivariate analysis was used to determine significant predictors of renal, BP, and mortality outcomes after PTRA. Results. Compared to patients with normal basal SUA levels (≤5.7 mg/dl), patients with very high SUA (≥8.7 mg/dl) had lower baseline estimated glomerular filtration rate (eGFR), more extensive use of antihypertensive and diuretic drugs, increased baseline systolic blood pressure (SBP), and elevated left ventricular mass index. After PTRA, multiple logistic regression analysis showed that, compared to normal SUA, very high SUA was associated with decreased odds ratio (OR) of change in eGFR (adjusted OR=0.90; 95% confidence interval [CI], 0.86-0.95), but not of change in SBP. In multivariate linear analysis SUA independently predicted delta urine protein/creatinine ratio (β: 26.0; 95% confidence interval, 13.9 to 38.1). Conclusion. Severe hyperuricemia in patients with AVRD may have a negative impact on outcomes of renal revascularization.
Spontaneous Osteonecrosis of the Tarsal Navicular: A Report of Two Cases
Authors: Kitaura Yukie , Nishimura Akinobu , Nakazora Shigeto , Fukuda Aki , Senga Yoshiyuki , Kato Ko , Sudo Akihiro
Published: January 2019

Spontaneous osteonecrosis of the tarsal navicular, called the Mueller-Weiss syndrome, is an uncommon disease. Patients who are resistant to conservative treatment require operative treatment. However, there is no established operative treatment. Two cases of spontaneous osteonecrosis of the tarsal navicular with double (talonavicular and naviculocuneiform joints) arthrodeses with different locking plates are presented. Removal of necrotic areas from the tarsal navicular and replacement with autologous bone graft procured from the iliac crest followed by arthrodesis using a locking plate were performed. Case 1 was fixed with an LCP Distal Radius Plate (SYNTHES) and 6 2.4 mm locking screws. Case 2 was fixed with a Cervical Spine Locking Plate Variable Angle (SYNTHES) and 4 4.0 mm locking screws. Case 2 achieved solid fusion of the talonavicular-cuneiform joints, but case 1 resulted in nonunion of the talonavicular joint. This difference in internal fixation strength might have caused the difference in the results. Performance of double arthrodeses from the medial aspect using a locking plate is a reasonable operative procedure to treat spontaneous osteonecrosis of the tarsal navicular. Strong primary fixation using a thick plate with large-thread screws was important to obtain joint fusions.
First Record Mutations in the Genes ASPA and ARSA Causing Leukodystrophy in Jordan
Authors: Froukh Tawfiq
Published: January 2019

Leukodystrophies (LDs) are heterogeneous genetic disorders characterized by abnormal white matter in the central nervous system. Some of the LDs are progressive and often fatal. In general, LD is primarily diagnosed based on the neuroimaging; however, definitive diagnosis of the LD type is done using genetic testing such as next-generation sequencing. The aim of this study is to identify the genetic causes of LD in two independent Jordanian cases that exhibit MRI findings confirming LD with no definitive diagnosis using whole exome sequencing (WES). The most likely causative variants were identified. In one case, the homozygous pathogenic variant NM_000049.2:c.914C>A;p.Ala305Glu, which is previously reported in ClinVar, in the gene ASPA was identified causing Canavan disease. In the second case, the homozygous novel variant NM_000487.5:c.256C>G;p.Arg86Gly in the gene ARSA was identified causing metachromatic leukodystrophy. The two variants segregate in their families. The phenotypes of the two studied cases overlap with assigned diseases. The present study raises the importance of using WES to identify the precise neurodevelopmental diseases in Jordan.