bluuebunny/crossref_metadata_2025 huggingface dataset:
Stationary Expansion Shocks for a Regularized Boussinesq System
Authors: El Gennady A. , Hoefer Mark A. , Shearer Michael
Published: September 2017

Stationary expansion shocks have been identified recently as a new type of solution to hyperbolic conservation laws regularized by nonlocal dispersive terms that naturally arise in shallow‐water theory. These expansion shocks were studied previously for the Benjamin‐Bona‐Mahony (BBM) equation using matched asymptotic expansions. In this paper, we extend the BBM analysis to the regularized Boussinesq system by using Riemann invariants of the underlying dispersionless shallow‐water equations. The extension for a system is nontrivial, requiring a combination of small amplitude, long‐wave expansions with high order matched asymptotics. The constructed asymptotic solution is shown to be in excellent agreement with accurate numerical simulations of the Boussinesq system for a range of appropriately smoothed Riemann data.
Comparison of one commercial and two in‐house TaqMan multiplex real‐time PCR assays for detection of enteropathogenic, enterotoxigenic and enteroaggregative Escherichia coli
Authors: Hahn Andreas , Luetgehetmann Marc , Landt Olfert , Schwarz Norbert Georg , Frickmann Hagen
Published: September 2017

Objective

Enteropathogenic, enterotoxigenic and enteroaggregative Escherichia coli (EPEC, ETEC, EAEC) are among the most frequent causes of diarrhoea during travel or on military deployments. Cost‐efficient and reliable real‐time multiplex PCR (mPCR) assays are desirable for surveillance or point prevalence studies in remote and resource‐limited tropical settings. We compared one commercial PCR kit and two in‐house assays without using a gold standard to estimate sensitivity and specificity of each assay.

Methods

Residual materials from nucleic acid extractions of stool samples from two groups with presumably different prevalences and increased likelihood of being infected or colonised by diarrhoeagenic E. coli were included in the assessment. One group comprised samples from returnees from tropical deployments, the second group was of migrants and study participants from high‐endemicity settings. Each sample was assessed with all of the PCR assays. Cycle threshold (Ct) values were descriptively compared.

Results

The calculated sensitivities for the commercial test vs. the in‐house tests were for EPEC 0.84 vs. 0.89 and 0.96, for ETEC 0.83 vs. 0.76 and 0.61, and for EAEC 0.69 vs. 0.54 and 0.69. False positive results were rare – specificity was 0.94 and 0.97 for two EPEC tests and 1.0 for all other tests. Most positive samples had late Ct values corresponding to low quantities of pathogens. Discordant test results were associated with late Ct values.

Conclusions

As commercial and in‐house assays showed comparable results, in‐house tests can be assumed to be safe while affording considerable savings, making them a valuable alternative for surveillance testing in resource‐limited tropical areas.
Cryopreserved platelets demonstrate reduced activation responses and impaired signaling after agonist stimulation
Authors: Waters Lauren , Padula Matthew P. , Marks Denese C. , Johnson Lacey
Published: September 2017

BACKGROUND

Room temperature–stored (20‐24°C) platelets (PLTs) have a shelf life of 5 days, making it logistically challenging to supply remote medical centers with PLT products. Cryopreservation of PLTs in dimethyl sulfoxide (DMSO) and storage at –80°C enables an extended shelf life up to 2 years. Although cryopreserved PLTs have been widely characterized under resting conditions, their ability to undergo agonist‐induced activation is yet to be fully explored.

STUDY DESIGN AND METHODS

Buffy coat PLTs were cryopreserved at –80°C with 5% to 6% DMSO and sampled before freezing and after thawing. PLTs were analyzed under resting conditions and after agonist stimulation with adenosine diphosphate, collagen, or thrombin receptor–activating peptide‐6. The expression of activation markers, microparticle formation, and calcium mobilization were analyzed by flow cytometry. Soluble PLT proteins present in the PLT supernatant were examined by enzyme‐linked immunosorbent assay. Protein phosphorylation was investigated with Western blotting.

RESULTS

After cryopreservation, PLTs displayed increased surface activation markers and higher basal calcium levels. Cryopreserved PLTs demonstrated diminished aggregation responses. Additionally, cryopreserved PLTs showed a limited ability to become activated (as measured by CD62P and phosphatidylserine exposure and cytokine release) after agonist stimulation. A reduction in the abundance and phosphorylation of key signaling proteins (Akt, Src, Lyn, ERK, and p38) was seen in cryopreserved PLTs.

CONCLUSIONS

Cryopreservation of PLTs induces dramatic changes to the basal PLT phenotype and renders them largely nonresponsive to agonist stimulation, likely due to the alterations in signal transduction. Therefore, further efforts are required to understand how cryopreserved PLTs achieve their hemostatic effect once transfused.
Transmission and immunopathology of the avian influenza virus A/Anhui/1/2013 (H7N9) human isolate in three commonly commercialized avian species
Authors: Vidaña B. , Dolz R. , Busquets N. , Ramis A. , Sánchez R. , Rivas R. , Valle R. , Cordón I. , Solanes D. , Martínez J. , Majó N.
Published: September 2017

H7N9 virus infection is a global concern, given that it can cause severe infection and mortality in humans. However, the understanding of H7N9 epidemiology, animal reservoir species and zoonotic risk remains limited. This work evaluates the pathogenicity, transmissibility and local innate immune response of three avian species harbouring different respiratory distribution of α2,6 and α2,3 SA receptors. Muscovy ducks, European quails and SPF chickens were intranasally inoculated with 105 embryo infectious dose (EID)50 of the human H7N9 (A/Anhui/1/2013) influenza isolate. None of the avian species showed clinical signs or macroscopic lesions, and only mild microscopic lesions were observed in the upper respiratory tract of quail and chickens. Quail presented more severe histopathologic lesions and avian influenza virus (AIV) positivity by immunohistochemistry (IHC), which correlated with higher IL‐6 responses. In contrast, Muscovy ducks were resistant to disease and presented higher IFNα and TLR7 response. In all species, viral shedding was higher in the respiratory than in the digestive tract. Higher viral shedding was observed in quail, followed by chicken and ducks, which presented similar viral titres. Efficient transmission was observed in all contact quail and half of the Muscovy ducks, while no transmission was observed between chicken. All avian species showed viral shedding in drinking water throughout infection.
Reviewer Acknowledgements
Authors: Smith Robert
Published: September 2017

Journal of Education and Training Studies (JETS) would like to acknowledge the following reviewers for their assistance with peer review of manuscripts for this issue. Many authors, regardless of whether JETS publishes their work, appreciate the helpful feedback provided by the reviewers. Their comments and suggestions were of great help to the authors in improving the quality of their papers. Each of the reviewers listed below returned at least one review for this issue.Reviewers for Volume 5, Number 9Angel H. Y. Lai, Hong Kong Baptist University, Hong KongCengiz Alyilmaz, TurkeyCharlotte Alverson, University of Oregon, USAChris Prince Udochukwu Njoku, University of Nigeria, NigeriaCynthia M. Compton, Wingate University, USAEbru Temiz, Niğde Ömer Halis Demir University, TurkeyElena Jerves, University of Cuenca, EcuadorErkan Atalmış, Kahramanmaras Imam University, TurkeyErkut Tutkun, TurkeyFethi Kayalar, Erzincan University, TurkeyHalide Nur Ozudogru Erdogan, Abant Izzet Baysal University, TurkeyHalil Erdem Çocuk, Mersin University, TurkeyHatice Irem Ozteke Kozan, Necmettin Erbakan University, TurkeyIbrahim Can, TurkeyIoannis Syrmpas, University of Thessaly, GreeceJohn Cowan, Edinburgh Napier University, UKJosé D Badia, University of Valencia, SpainKun-Hsi Liao, Taiwan Shoufu University, TaiwanKürşad Çağrı Bozkirli, TurkeyLaima Kyburiene, Kaunas University of Applied Sciences, LithuaniaLisa Marie Portugal, Grand Canyon University, USALorna T. Enerva, Polytechnic University of the Philippines, PhilippinesM. Fatih Karahuseyinoglu, Firat Universitesi, TurkeyMan-fung Lo, The Hong Kong Polytechnic University, Hong KongMarcie Zaharee, The MITRE Corporation, USAMarco Antonio Catussi Paschoalotto, University of São Paulo, BrazilMehmet Akif Ziyagil, TurkeyMehmet Inan, Marmara University, TurkeyMeral Seker, Alanya Alaaddin Keykubat University, TurkeyMichail Kalogiannakis, University of Crete, GreeceMin Gui, Wuhan University, ChinaMustafa Çakır, Marmara Üniversity, TurkeyMustafa Önder, Şekeroğlu-Muş Alparslan University, TurkeyNele Kampa, Leibniz-Institute for Science and Mathematics Education (IPN), GermanyNerina Fernanda Sarthou, Universidad Nacional del Centro de la Provincia de Buenos Aires, ArgentinaNurşat Biçer, TurkeyÖnder Dağlıoğlu, TurkeyÖzgür Ulubey, Muğla Sıtkı Koçman University, TurkeyRichard H. Martin, Mercer University, USARichard Penny, University of Washington Bothell, USARui Manuel Carreteiro, National Institute of Psychology and Neurosciences, PortugalSadia Batool, Preston University Islamabad, PakistanSelloane Pitikoe, University of Kwazulu-Natal, South AfricaSenem Seda Şahenk Erkan, Marmara University, TurkeyStamatis Papadakis, University of Crete, GreeceThomas K. F. Chiu, The University of Hong Kong, Hong KongYakup Koç, Erzincan University, TurkeyYi Lu, American Institute for Research, USAZeki Coskuner, Firat Universitesi, Turkey                            Robert SmithEditorial AssistantOn behalf of,The Editorial Board of Journal of Education and Training StudiesRedfame Publishing9450 SW Gemini Dr. #99416Beaverton, OR 97008, USAURL: http://jets.redfame.com
Heteromeric α/β glycine receptors regulate excitability in parvalbumin‐expressing dorsal horn neurons through phasic and tonic glycinergic inhibition
Authors: Gradwell M. A. , Boyle K. A. , Callister R. J. , Hughes D. I. , Graham B. A.
Published: September 2017

Key points

Spinal parvalbumin‐expressing interneurons have been identified as a critical source of inhibition to regulate sensory thresholds by gating mechanical inputs in the dorsal horn.

This study assessed the inhibitory regulation of the parvalbumin‐expressing interneurons, showing that synaptic and tonic glycinergic currents dominate, blocking neuronal or glial glycine transporters enhances tonic glycinergic currents, and these manipulations reduce excitability.

Synaptically released glycine also enhanced tonic glycinergic currents and resulted in decreased parvalbumin‐expressing interneuron excitability.

Analysis of the glycine receptor properties mediating inhibition of parvalbumin neurons, as well as single channel recordings, indicates that heteromeric α/β subunit‐containing receptors underlie both synaptic and tonic glycinergic currents.

Our findings indicate that glycinergic inhibition provides critical control of excitability in parvalbumin‐expressing interneurons in the dorsal horn and represents a pharmacological target to manipulate spinal sensory processing.

The dorsal horn (DH) of the spinal cord is an important site for modality‐specific processing of sensory information and is essential for contextually relevant sensory experience. Parvalbumin‐expressing inhibitory interneurons (PV+ INs) have functional properties and connectivity that enables them to segregate tactile and nociceptive information. Here we examine inhibitory drive to PV+ INs using targeted patch‐clamp recording in spinal cord slices from adult transgenic mice that express enhanced green fluorescent protein in PV+ INs. Analysis of inhibitory synaptic currents showed glycinergic transmission is the dominant form of phasic inhibition to PV+ INs. In addition, PV+ INs expressed robust glycine‐mediated tonic currents; however, we found no evidence for tonic GABAergic currents. Manipulation of extracellular glycine by blocking either, or both, the glial and neuronal glycine transporters markedly decreased PV+ IN excitability, as assessed by action potential discharge. This decreased excitability was replicated when tonic glycinergic currents were increased by electrically activating glycinergic synapses. Finally, we show that both phasic and tonic forms of glycinergic inhibition are mediated by heteromeric α/β glycine receptors. This differs from GABAA receptors in the dorsal horn, where different receptor stoichiometries underlie phasic and tonic inhibition. Together these data suggest both phasic and tonic glycinergic inhibition regulate the output of PV+ INs and contribute to the processing and segregation of tactile and nociceptive information. The shared stoichiometry for phasic and tonic glycine receptors suggests pharmacology is unlikely to be able to selectively target each form of inhibition in PV+ INs.
Monitoring program for mammals in a protected area of Colombia
Authors: Jiménez Germán , López-Cepeda Natalia , Delgado Andrea , Guevara Ana María , Lozano Laura
Published: September 2017

Between the second semester of 2009 and the first semester of 2011, camera traps were set up in conserved and disturbed habitats in the Otún Quimbaya Flora and Fauna Sanctuary. From a sampling effort of 2,066 camera-days, 673 photographs of 157 independent events were obtained for eight species of wild mammals and a domestic one. Their activity patterns were mainly nocturnal even for those species reported as diurnal. The impact of human interference and exotic species was evident for two species: Tapirus pinchaque and Cerdocyon thous. The former was observed below its altitudinal range with activity patterns mainly crepuscular and nocturnal. The second was observed in the same habitats where domestic dogs were found, with activity patterns mainly crepuscular and nocturnal. These findings suggest that both species have altered their activity patterns. Actions must be focused on decreasing the interaction of these mammals with humans and domestic dogs.
Peri-Ultrasound Modeling of Dynamic Response of an Interface Crack Showing Wave Scattering and Crack Propagation
Authors: Hadi Hafezi Mohammad , Kundu Tribikram
Published: September 2017

A cracked structure made of two different elastic materials having a Griffith crack at the interface is analyzed when it is subjected to pure shear loading and ultrasonic loading. The waves generated by the applied load and the crack propagation resulted from the shear loading are investigated. Peri-ultrasound modeling tool is used for this analysis. A comparison between experimental results and numerical predictions shows a very good matching between the two. Furthermore, the increase in nonlinear ultrasonic response in presence of the interface crack could also be modeled by this technique. The computed results show that when the interface crack propagates, then it breaks the interface at one end of the crack and breaks the material with lower elastic modulus at the other end. The unique feature of this peridynamics-based modeling tool is that it gives a complete picture of the structural response when it is loaded—it shows how elastic waves propagate in the structure and are scattered by the crack, how the crack surfaces open up, and then how crack starts to propagate. Different modeling tools are not needed to model these various phenomena.
A Perspective Evaluation Methodology for Economic Feasibility of Low Temperature Sustainable Energy Source in Heating Mode Technology
Authors: Tarrad Ali H.
Published: September 2017

The economical and clean environment issues for a sustainable energy source at low temperature (LT) were considered and compared to natural gas technology as a fossil fuel source. The friendly environment refrigerants R410A, R407C, R717, R134a, and R600a were analyzed in an approximately 500 kW heating load output cascade heat pump. The heat pump was investigated at an intermediate temperature of 35 °C, high temperature (HT) cycle condenser at 70 °C, and compressors isentropic efficiency of 70%. All analyzed refrigerant pairs exhibited high heating season performance factor (HSPF), and it was ranged between 7 and 8.5. The thermal performance comparison revealed that the HSPF for R717/R600a showed the highest values among other refrigerant pairs. The results showed that at LT cycle evaporator temperature range of −10 to −2 °C, the natural gas technology revealed a higher season heating cost values than that of the heat pump plant by up to 10%. On the contrary at lower LT evaporator temperature, the heat pump plant technology exhibited a higher season heating cost lied in the range of 4–13.6% than that of the natural gas system. At compressors isentropic efficiency of 90%, the seasonal heating cost of the heat pump plant was lower than that of the natural gas technology by the range of 9–25% at test conditions. The mean seasonal CO2 amount released by the natural gas firing technology from all tested refrigerant pairs ranged between 2.1 and 2.5 times that of the heat pump plant technology for the investigated LT evaporator temperature range.
An investigation into the variability between different shear wave elastography systems in muscle
Authors: Alfuraih Abdulrahman M. , O'Connor Philip , Tan Ai Lyn , Hensor Elizabeth , Emery Paul , Wakefield Richard J.
Published: September 2017

Aims: The reliability and agreement between shear wave elastography (SWE) systems using different acquisition methods in muscles is not yet established. The objectives were to determine the reliability of a new SWE system on normal resting muscles using different acquisition methods and to compare its performance to an established state-of-the-art system.Material and methods: Small, medium and large ROI sizes in addition to longitudinal, oblique and transverse orientations over five different locations within the rectus femoris muscle were tested using the new system. Results were compared to the established system to test for inter-system reproducibility.Results: Lowest within-subject coefficient of variance (4.3%) andshear wave velocity (1.83 m/s) were associated with the medium ROI and longitudinal orientation from the lateral location. This combination resulted in a strong internal agreement of intra-class correlation of 0.76 (0.57–0.89) for the new system and an almost perfect agreement of 0.92 (0.82–0.97) for the established. Inter-system reproducibility for the best combination was 0.71 (0.48–1) with a mean velocity difference ±95% limits of agreement of 0.07±0.49 m/s.Conclusions: Altering SWE acquisition methods can produce variable results. The new system produced reliable results that are comparable with but not as reliable as the established.
HSP105 prevents depression-like behavior by increasing hippocampal brain-derived neurotrophic factor levels in mice
Authors: Hashikawa Naoya , Utaka Yuta , Ogawa Takumi , Tanoue Ryo , Morita Yuna , Yamamoto Sayumi , Yamaguchi Satoru , Kayano Masafumi , Zamami Yoshito , Hashikawa-Hobara Narumi
Published: September 2017

The gastric ulcer drug teprenone has central nervous system effects, specifically reducing depression-like behavior in mice.
The empty primordial asteroid belt
Authors: Raymond Sean N. , Izidoro Andre
Published: September 2017

The asteroid belt may be a cosmic refugee camp that formed empty but was populated by objects from across the solar system.
Earthquake forecasting during the complex Amatrice-Norcia seismic sequence
Authors: Marzocchi Warner , Taroni Matteo , Falcone Giuseppe
Published: September 2017

Prospective earthquake forecasts yield probabilities consistent with the space-time-magnitude evolution of a complex sequence.
Size effects resolve discrepancies in 40 years of work on low-temperature plasticity in olivine
Authors: Kumamoto Kathryn M. , Thom Christopher A. , Wallis David , Hansen Lars N. , Armstrong David E. J. , Warren Jessica M. , Goldsby David L. , Wilkinson Angus J.
Published: September 2017

When deforming by low-temperature plasticity, the strength of the mantle mineral olivine is controlled by its grain size.
Pay up or retract? Drug survey spurs conflict
Authors: Marcus Adam
Published: September 2017

Researchers' zealous effort to protect intellectual property has included legal threats.
PETA targets early-career wildlife researcher
Authors: Grimm David
Published: September 2017

Critics say animal rights organization is trying to intimidate vulnerable scientists.
Potential role of intratumor bacteria in mediating tumor resistance to the chemotherapeutic drug gemcitabine
Authors: Geller Leore T. , Barzily-Rokni Michal , Danino Tal , Jonas Oliver H. , Shental Noam , Nejman Deborah , Gavert Nancy , Zwang Yaara , Cooper Zachary A. , Shee Kevin , Thaiss Christoph A. , Reuben Alexandre , Livny Jonathan , Avraham Roi , Frederick Dennie T. , Ligorio Matteo , Chatman Kelly , Johnston Stephen E. , Mosher Carrie M. , Brandis Alexander , Fuks Garold , Gurbatri Candice , Gopalakrishnan Vancheswaran , Kim Michael , Hurd Mark W. , Katz Matthew , Fleming Jason , Maitra Anirban , Smith David A. , Skalak Matt , Bu Jeffrey , Michaud Monia , Trauger Sunia A. , Barshack Iris , Golan Talia , Sandbank Judith , Flaherty Keith T. , Mandinova Anna , Garrett Wendy S. , Thayer Sarah P. , Ferrone Cristina R. , Huttenhower Curtis , Bhatia Sangeeta N. , Gevers Dirk , Wargo Jennifer A. , Golub Todd R. , Straussman Ravid
Published: September 2017

In model systems, bacteria present in human pancreatic tumors confer resistance to the anticancer drug gemcitabine.
The form and function of channelrhodopsin
Authors: Deisseroth Karl , Hegemann Peter
Published: September 2017

From biophysics to neuroscience tools

The channelrhodopsins and their distinctive light-activated ion channels have emerged as major tools in modern biological research. Deisseroth and Hegemann review the structural and functional properties of these protein photoreceptors. Mutagenesis and modeling studies, coupled with the reintroduction of modified channels into living systems, offer a profound understanding of how these channels work. The insights into the underlying basic science provide foundations for developing further applications in biology and medicine.

Science
, this issue p.
eaan5544
A cargo-sorting DNA robot
Authors: Thubagere Anupama J. , Li Wei , Johnson Robert F. , Chen Zibo , Doroudi Shayan , Lee Yae Lim , Izatt Gregory , Wittman Sarah , Srinivas Niranjan , Woods Damien , Winfree Erik , Qian Lulu
Published: September 2017

Sorting molecules with DNA robots

Single-stranded DNA robots can move over the surface of a DNA origami sheet and sort molecular cargoes. Thubagere
et al.
developed a simple algorithm for recognizing two types of molecular cargoes and their drop-off destinations on the surface (see the Perspective by Reif). The DNA robot, which has three modular functional domains, repeatedly picks up the two types of molecules and then places them at their target destinations. No additional power is required because the DNA robot does this by random walking across the origami surface.

Science
, this issue p.
eaan6558
; see also p.
1095
DNA robots sort as they walk
Authors: Reif John H.
Published: September 2017

Multiple DNA robots perform parallel tasks on a self-assembled DNA origami surface
Characterization of Antigenic Relatedness between GII.4 and GII.17 Noroviruses by Use of Serum Samples from Norovirus-Infected Patients
Authors: Dai Ying-Chun , Xia Ming , Huang Qiong , Tan Ming , Qin Lin , Zhuang Ya-Li , Long Yan , Li Jian-Dong , Jiang Xi , Zhang Xu-Fu
Published: September 2017

A novel GII.17 norovirus variant caused major gastroenteritis epidemics in China in 2014 to 2016. To explore the host immune factors in selection of the emergence of this new variant, we characterized its antigenic relatedness with the GII.4 noroviruses that have dominated in China for decades. Through an enzyme-linked immunosorbent assay (ELISA) and a histo-blood group antigen (HBGA) blocking assay using sera from GII.4 and the GII.17 variant-infected patients, respectively, we observed limited cross-immune reactivity by the ELISA but little reactivity by the HBGA blocking assay between GII.4 norovirus and the new GII.17 variant. Our data suggest that, among other possible factors, GII.4-specific herd immunity had little role in the emergence of the new GII.17 variant. Thus, GII.17 may be an important active antigenic type or immunotype that needs to be considered for future vaccine strategies against human noroviruses.
Finegoldia magna Isolated from Orthopedic Joint Implant-Associated Infections
Authors: Söderquist Bo , Björklund Sanna , Hellmark Bengt , Jensen Anders , Brüggemann Holger
Published: September 2017

The anaerobic Gram-positive coccus
Finegoldia magna
is a rare cause of infections of bone and joints. The aim of this study was to describe the microbiological and clinical characteristics of orthopedic implant-associated infections caused by
F. magna
. We retrospectively analyzed samples consisting of anaerobic Gram-positive cocci and samples already identified as
F. magna
from patients with orthopedic infections. The isolates found were determined to the species level using matrix-assisted laser desorption ionization–time of flight mass spectrometry (MALDI-TOF MS). The antibiotic susceptibility pattern was determined by Etest. Whole-genome sequencing (WGS) was performed. Clinical data were extracted from each patient's journal. In nine patients, orthopedic joint implant-associated infections were identified as being caused by
F. magna
. The isolates were susceptible to most of the antibiotics tested, with the exception of rifampin and moxifloxacin in a few cases. Five of the nine infections were monomicrobial. The most common antibiotic used to treat the infection was penicillin V, but five of the nine patients received a combination of antibiotics. Eight patients underwent surgical treatment, with extraction of the implant performed in seven cases and reimplantation in only two cases. The WGS showed a relatively small core genome, with 126,647 single nucleotide polymorphisms identified within the core genome. A phylogenomic analysis revealed that the isolates clustered into two distinct clades. Orthopedic implant-associated infections caused by
F. magna
are rare, but the bacteria are generally susceptible to antibiotics. Despite this, surgical treatment combined with long-term antibiotics is often necessary. The WGS analysis revealed a high heterogeneity and suggested the existence of at least two different
Finegoldia
species.
The TB Portals: an Open-Access, Web-Based Platform for Global Drug-Resistant-Tuberculosis Data Sharing and Analysis
Authors: Rosenthal Alex , Gabrielian Andrei , Engle Eric , Hurt Darrell E. , Alexandru Sofia , Crudu Valeriu , Sergueev Eugene , Kirichenko Valery , Lapitskii Vladzimir , Snezhko Eduard , Kovalev Vassili , Astrovko Andrei , Skrahina Alena , Taaffe Jessica , Harris Michael , Long Alyssa , Wollenberg Kurt , Akhundova Irada , Ismayilova Sharafat , Skrahin Aliaksandr , Mammadbayov Elcan , Gadirova Hagigat , Abuzarov Rafik , Seyfaddinova Mehriban , Avaliani Zaza , Strambu Irina , Zaharia Dragos , Muntean Alexandru , Ghita Eugenia , Bogdan Miron , Mindru Roxana , Spinu Victor , Sora Alexandra , Ene Catalina , Vashakidze Sergo , Shubladze Natalia , Nanava Ucha , Tuzikov Alexander , Tartakovsky Michael
Published: September 2017

The TB Portals program is an international consortium of physicians, radiologists, and microbiologists from countries with a heavy burden of drug-resistant tuberculosis working with data scientists and information technology professionals. Together, we have built the TB Portals, a repository of socioeconomic/geographic, clinical, laboratory, radiological, and genomic data from patient cases of drug-resistant tuberculosis backed by shareable, physical samples. Currently, there are 1,299 total cases from five country sites (Azerbaijan, Belarus, Moldova, Georgia, and Romania), 976 (75.1%) of which are multidrug or extensively drug resistant and 38.2%, 51.9%, and 36.3% of which contain X-ray, computed tomography (CT) scan, and genomic data, respectively. The top
Mycobacterium tuberculosis
lineages represented among collected samples are Beijing, T1, and H3, and single nucleotide polymorphisms (SNPs) that confer resistance to isoniazid, rifampin, ofloxacin, and moxifloxacin occur the most frequently. These data and samples have promoted drug discovery efforts and research into genomics and quantitative image analysis to improve diagnostics while also serving as a valuable resource for researchers and clinical providers. The TB Portals database and associated projects are continually growing, and we invite new partners and collaborations to our initiative. The TB Portals data and their associated analytical and statistical tools are freely available at
https://tbportals.niaid.nih.gov/
.
Genomic Characterization of Urethritis-Associated Neisseria meningitidis Shows that a Wide Range of N. meningitidis Strains Can Cause Urethritis
Authors: Ma Kevin C. , Unemo Magnus , Jeverica Samo , Kirkcaldy Robert D. , Takahashi Hideyuki , Ohnishi Makoto , Grad Yonatan H.
Published: September 2017

Neisseria meningitidis
, typically a resident of the oro- or nasopharynx and the causative agent of meningococcal meningitis and meningococcemia, is capable of invading and colonizing the urogenital tract. This can result in urethritis, akin to the syndrome caused by its sister species,
N. gonorrhoeae
, the etiologic agent of gonorrhea. Recently, meningococcal strains associated with outbreaks of urethritis were reported to share genetic characteristics with the gonococcus, raising the question of the extent to which these strains contain features that promote adaptation to the genitourinary niche, making them gonococcus-like and distinguishing them from other
N. meningitidis
strains. Here, we analyzed the genomes of 39 diverse
N. meningitidis
isolates associated with urethritis, collected independently over a decade and across three continents. In particular, we characterized the diversity of the nitrite reductase gene (
aniA
), the factor H-binding protein gene (
fHbp
), and the capsule biosynthetic locus, all of which are loci previously suggested to be associated with urogenital colonization. We observed notable diversity, including frameshift variants, in
aniA
and
fHbp
and the presence of intact, disrupted, and absent capsule biosynthetic genes, indicating that urogenital colonization and urethritis caused by
N. meningitidis
are possible across a range of meningococcal genotypes. Previously identified allelic patterns in urethritis-associated
N. meningitidis
strains may reflect genetic diversity in the underlying meningococcal population rather than novel adaptation to the urogenital tract.
Three Conserved Regions in Baculovirus Sulfhydryl Oxidase P33 Are Critical for Enzymatic Activity and Function
Authors: Kuang Wenhua , Zhang Huanyu , Wang Manli , Zhou Ning-Yi , Deng Fei , Wang Hualin , Gong Peng , Hu Zhihong
Published: September 2017

Baculoviruses encode a conserved sulfhydryl oxidase, P33, which is necessary for budded virus (BV) production and multinucleocapsid occlusion-derived virus (ODV) formation. Here, the structural and functional relationship of P33 was revealed by X-ray crystallography, site-directed mutagenesis, and functional analysis. Based on crystallographic characterization and structural analysis, a series of P33 mutants within three conserved regions, i.e., the active site, the dimer interface, and the R127-E183 salt bridge, were constructed.
In vitro
experiments showed that mutations within the active site and dimer interface severely impaired the sulfhydryl oxidase activity of P33, while the mutations in the salt bridge had a relatively minor influence. Recombinant viruses containing mutated P33 were constructed and assayed
in vivo
. Except for the active-site mutant AXXA, all other mutants produced infectious BVs, although certain mutants had a decreased BV production. The active-site mutant H114A, the dimer interface mutant H227D, and the salt bridge mutant R127A-E183A were further analyzed by electron microscopy and bioassays. The occlusion bodies (OBs) of mutants H114A and R127A-E183A had a ragged surface and contained mostly ODVs with a single nucleocapsid. The OBs of all three mutants contained lower numbers of ODVs and had a significantly reduced oral infectivity in comparison to control virus. Crystallographic analyses further revealed that all three regions may coordinate with one another to achieve optimal function of P33. Taken together, our data revealed that all the three conserved regions are involved in P33 activity and are crucial for virus morphogenesis and peroral infectivity.

IMPORTANCE
Sulfhydryl oxidase catalyzes disulfide bond formation of substrate proteins. P33, a baculovirus-encoded sulfhydryl oxidase, is different from other cellular and viral sulfhydryl oxidases, bearing unique features in tertiary and quaternary structure organizations. In this study, we found that three conserved regions, i.e., the active site, dimer interface, and the R127-E183 salt bridge, play important roles in the enzymatic activity and function of P33. Previous observations showed that deletion of
p33
results in a total loss of budded virus (BV) production and in morphological changes in occlusion-derived virus (ODV). Our study revealed that certain P33 mutants lead to occlusion bodies (OBs) with a ragged surface, decreased embedded ODVs, and reduced oral infectivity. Interestingly, some P33 mutants with impaired ODV/OB still retained BV productivity, indicating that the impacts on BV and on ODV/OB are two distinctly different functions of P33, which are likely to be performed via different substrate proteins.
14-3-3 Regulates Actin Filament Formation in the Deep-Branching Eukaryote Giardia lamblia
Authors: Krtková Jana , Xu Jennifer , Lalle Marco , Steele-Ogus Melissa , Alas Germain C. M. , Sept David , Paredez Alexander R.
Published: September 2017

Giardia
lacks canonical actin-binding proteins. Gl-14-3-3 was identified as an actin interactor, but the significance of this interaction was unknown. Loss of Gl-14-3-3 results in ectopic short actin filaments, indicating that Gl-14-3-3 is an important regulator of the actin cytoskeleton in
Giardia
. Drug studies indicate that Gl-14-3-3 complex formation is in part phospho-regulated. We demonstrate that complex formation is downstream of
Giardia
’s sole Rho family GTPase, Gl-Rac. This result provides the first mechanistic connection between Gl-Rac and Gl-actin in
Giardia
. Native gels and overlay assays indicate intermediate proteins are required to support the interaction between Gl-14-3-3 and Gl-actin, suggesting that Gl-14-3-3 is regulating multiple Gl-actin complexes.
Managing problematic severe asthma: beyond the guidelines
Authors: Pike Katharine C , Levy Mark L , Moreiras John , Fleming Louise
Published: September 2017

This review discusses issues related to managing problematic severe asthma in children and young people. A small minority of children have genuinely severe asthma symptoms which are difficult to control. Children with genuinely severe asthma need investigations and treatments beyond those described within conventional guidelines. However, the majority of children with poor symptom control despite high-intensity treatment achieve improvement in their asthma control once attention has been paid to the basics of asthma management. Basic asthma management requires optimisation of inhaler technique and treatment adherence, avoidance of environmental triggers and self-management education. It is also important that clinicians recognise risk factors that predispose patients to asthma exacerbations and potentially life-threatening attacks. These correctable issues need to be tackled in partnership with children and young people and their families. This requires a coordinated approach between professionals across healthcare settings. Establishing appropriate infrastructure for coordinated asthma care benefits not only those with problematic severe asthma, but also the wider asthma population as similar correctable issues exist for children with asthma of all severities. Investigation and management of genuine severe asthma requires specialist multidisciplinary expertise and a systematic approach to characterising patients’ asthma phenotypes and delivering individualised care. While inhaled corticosteroids continue to play a leading role in asthma therapy, new treatments on the horizon might further support phenotype-specific therapy.
Hearing the voices of children and young people to develop and test a patient-reported experience measure in a specialist paediatric setting
Authors: Wray Jo , Hobden Sylvie , Knibbs Sarah , Oldham Geralyn
Published: September 2017

Objective

To develop and test patient-reported experience measures (PREMs) for children and young people in a specialist paediatric hospital setting.

Design

Six PREMs were developed and tested by children and young people for children and young people aged 8–11, 12–13 and 14–16 years in inpatient and outpatient settings. A week-long pilot was implemented across inpatient wards and outpatient clinics to identify facilitators and barriers to the routine use of PREMs in a real-time setting across our organisation.

Setting

Tertiary paediatric hospital.

Main outcome measures

Final PREMs; identified facilitators and barriers to implementation.

Participants

543 children and young people aged 8–16 years attending outpatient clinics or inpatient wards across a range of specialties.

Results

Three key themes about hospital experience were identified during focus groups: facilities, treatment and tests and people working at the hospital, and these provided the structure for the questionnaires. During cognitive testing the questionnaires were generally understood but some revisions to language and length of the questionnaires were required. Two designs were selected for the final PREMs. During acceptability and feasibility testing it was evident that children and young people liked the PREMs and wanted to give feedback on their hospital experience. Particular challenges for routine use of the PREMs focused on sustainability and resources.

Conclusions

The new PREMs will provide children and young people receiving care in specialist paediatric hospitals with the opportunity to provide feedback on their experience. Sustainability and ensuring that feedback results in improvements need to be addressed in future work.
Health system effects of implementing integrated community case management (iCCM) intervention in private retail drug shops in South Western Uganda: a qualitative study
Authors: Kitutu Freddy Eric , Mayora Chrispus , Johansson Emily White , Peterson Stefan , Wamani Henry , Bigdeli Maryam , Shroff Zubin Cyrus
Published: September 2017

Background

Intervening in private drug shops to improve quality of care and enhance regulatory oversight may have health system effects that need to be understood before scaling up any such interventions. We examine the processes through which a drug shop intervention culminated in positive unintended effects and other dynamic interactions within the underlying health system.

Methods

A multifaceted intervention consisting of drug seller training, supply of diagnostics and subsidised medicines, use of treatment algorithms, monthly supervision and community sensitisation was implemented in drug shops in South Western Uganda, to improve paediatric fever management. Focus group discussions and in-depth interviews were conducted with stakeholders (drug sellers, government officials and community health workers) at baseline, midpoint and end-line between September 2013 and September 2015. Using a health market and systems lens, transcripts from the interviews were analysed to identify health system effects associated with the apparent success of the intervention.

Findings

Stakeholders initially expressed caution and fears about the intervention’s implications for quality, equity and interface with the regulatory framework. Over time, these stakeholders embraced the intervention. Most respondents noted that the intervention had improved drug shop standards, enabled drug shops to embrace patient record keeping, parasite-based treatment of malaria and appropriate medicine use. There was also improved supportive supervision, and better compliance to licensing and other regulatory requirements. Drug seller legitimacy was enhanced from the community and client perspective, leading to improved trust in drug shops.

Conclusion

The study showed how effectively using health technologies and the perceived efficacy of medicines contributed to improved legitimacy and trust in drug shops among stakeholders. The study also demonstrated that using a combination of appropriate incentives and consumer empowerment strategies can help harmonise common practices with medicine regulations and safeguard public health, especially in mixed health market contexts.
ROS1-1
Authors: Pal Prodipto , Khan Zanobia
Published: September 2017

ROS1 is a receptor tyrosine kinase that has recently been shown to undergo gene rearrangements in~1%–2% of non-small cell lung carcinoma (NSCLC) and in a variety of other tumours including cholangiocarcinoma, gastric carcinoma, colorectal carcinoma and in spitzoid neoplasms, glioblastoma and inflammatory myofibroblastic tumours. The ROS1 gene fusion undergoes constitutive activation, regulates cellular proliferation and is implicated in carcinogenesis. ROS1 fusions can be detected by fluorescence in situ hybridisation, real-time PCR, sequencing-based techniques and immunohistochemistry-based methods in clinical laboratories. The small molecule tyrosine kinase inhibitor, crizotinib has been shown to be an effective inhibitor of ROS1 and has received Food and Drug Administration approval for treatment of advanced NSCLC. The current review is an update on the clinical findings and detection methods of ROS1 in clinical laboratories in NSCLC and other tumours.
Statefinder diagnostic for a generalized Proca model
Authors: Xi Ping , Jing Yun-Long , Lü Wen-Dong , Zhai Xiang-Hua
Published: September 2017

In this paper, we apply the statefinder diagnostic on the cosmology in the framework of the generalized Proca theories with derivative self-interactions possessing three propagating physical degrees of freedom. We discuss the evolving trajectories of the statefinder parameters with the parameter n of this model recently fitted as n = 0.254 and n = 0.16 by use of the current observational data and find that some typical characteristic of the evolution of statefinder parameters makes the model distinguishable between n = 0.254 case and n = 0.16 case and also from other dark energy models.
Exact solutions for scalar field cosmology in f(R) gravity
Authors: Maharaj S. D. , Goswami R. , Chervon S. V. , Nikolaev A. V.
Published: September 2017

We study scalar field FLRW cosmology in the content of f(R) gravity. Our consideration is restricted to the spatially flat Friedmann universe. We derived the general evolution equations of the model, and showed that the scalar field equation is automatically satisfied for any form of the f(R) function. We also derived representations for kinetic and potential energies, as well as for the acceleration in terms of the Hubble parameter and the form of the f(R) function. Next we found the exact cosmological solutions in modified gravity without specifying the f(R) function. With negligible acceleration of the scalar curvature, we found that the de Sitter inflationary solution is always attained. Also we obtained new solutions with special restrictions on the integration constants. These solutions contain oscillating, accelerating, decelerating and even contracting universes. For further investigation, we selected special cases which can be applied with early or late inflation. We also found exact solutions for the general case for the model with negligible acceleration of the scalar curvature in terms of special Airy functions. Using initial conditions which represent the universe at the present epoch, we determined the constants of integration. This allows for the comparison of the scale factor in the new solutions with that for current stage of the universe evolution in the [Formula: see text]CDM model.
Does the diffraction cone shrinkage with energy originate from unitarity?
Authors: Troshin S. M. , Tyurin N. E.
Published: September 2017

We note that the diffraction cone shrinkage might result from unitarization only, i.e. there is no need to introduce it into an input amplitude ab initio.
The gas sensing properties of hafnium oxide thin films depending on the annealing environment
Authors: Karaduman Irmak , Acar Selim
Published: September 2017

The main focus of this study is to investigate the NO2 gas-sensing properties of HfO2 thin films, taking into the account the importance of the annealing environment and temperature. HfO2 films were produced with 10 nm and 20 nm thicknesses by atomic layer deposition (ALD). They were annealed under N2 and O2 environment with rapid thermal annealing system at two different temperatures. It was found that the NO2 responses of annealed in N2 environment were higher than annealed in O2 environment. The response of 10 nm thickness HfO2 thin film was calculated 22% for N2 environment whereas, it was calculated 18% for O2 environment. The highest gas response is obtained for 10 nm thickness of HfO2 thin film annealed in N2 environment. The performance of the HfO2 thin films reveals that the gas responses rely on annealing temperature as well as annealing atmosphere. The linear dependences of the sensitivity were also observed as the NO2 gas concentrations varied from 10 ppm to 30 ppm in logarithmic forms, indicating that HfO2 thin films offer promising potential for future practical applications in monitoring the NO2 gas.
BBR-Based Iteration-Free CORDIC Algorithm
Authors: Yao Yafeng , Feng Zhongxiu
Published: September 2017

Coordinate rotation digital computer (CORDIC) algorithm has been widely used in modern digital communication systems such as all-digital phase-locked loop, fast Fourier transform and direct digital frequency synthesizers. Precision of the CORDIC algorithm implemented using pipelined architecture has to be guaranteed by increasing the number of iterations, which leads to large delay, excessive consumption of hardware resource and other problems, unfavorable for applications calling for high real-time performance and low power consumption. In this paper, through integrated use of binary to bipolar recoding, angle domain folding, merging iteration and optimized lookup table, an iteration-free CORDIC algorithm was proposed, with which it takes only two clock cycles to get the output, and it enables certain improvements in hardware consumption and output precision when compared with other basic implementation methods.
Bound-free electron–positron pair production mechanism at an electron-ion collider
Authors: Şengül M. Y.
Published: September 2017

The aims of building electron-ion colliders (EICs) are to reach high collision luminosity and polarization, to search on the structure and the interactions of gluon-matter, to investigate the spin structure of matter, to probe the behavior of parton densities in the nuclear medium, and to study and to test quantum chromodynamics (QCD). In this work, we have calculated the cross-sections of the ion beam loss mechanism at EICs via bound-free pair production (BFPP) mechanism. The BFPP is important for the detector design because of its large cross-sections that will give rise to decrease the luminosity of the accelerators. We have done the cross-section calculations for BFPP in the framework of quantum electrodynamics (QED) by using the lowest-order perturbation theory for three different EICs that are mentioned below.