bluuebunny/crossref_metadata_2025 huggingface dataset:
Proper orthogonal decomposition of primary breakup and spray in co-axial airblast atomizers
Authors: Charalampous Georgios , Hadjiyiannis Constantinos , Hardalupas Yannis
Published: April 2019

The primary atomization of a liquid jet by a coaxial stream of high speed gas is analyzed by means of Proper Orthogonal Decomposition (POD) for gas to liquid momentum ratios (MR) from 182 to 727 and Weber numbers, We, from 22 to 88. The continuous liquid core is visualized by the optical connectivity technique. The full spray in the near nozzle region is visualized using shadowgraphy. It is found that universal POD modes exist for the continuous liquid core and the near nozzle full spray across all considered flow conditions. The universal POD modes are related to physical structures of the flow. The complexity of the flow, as determined by the energy of the POD modes, is found to be constant for the liquid core across the examined range of flow MR. On the contrary, the complexity of the full spray is inversely proportional to the flow MR. Correlations are established between the spatial and temporal scales of primary atomization. In addition, a novel method to extrapolate the spatial and temporal scales of the atomization process beyond the limits of the current measurement resolution is described and demonstrated. Estimates are provided on the number of samples and the sampling rate that are required to fully resolve the flow to specific temporal and spatial scales.
Inducing out-of-plane precession of magnetization for microwave-assisted magnetic recording with an oscillating polarizer in a spin-torque oscillator
Authors: Zhou W. , Sepehri-Amin H. , Taniguchi T. , Tamaru S. , Sakuraba Y. , Kasai S. , Kubota H. , Hono K.
Published: April 2019

The dynamics of a simple design of a spin-torque oscillator (STO) compatible with microwave-assisted magnetic recording were investigated. The STO with Ni80Fe20 (NiFe) used as a polarizer and Fe67Co33 (FeCo) used as a field generating layer was fabricated and measured. As the bias voltage increased, the magnetization reversal of NiFe occurred, then, multiple signals appeared in the power spectra. The signals reflected out-of-plane precession (OPP) mode oscillation of both the FeCo and NiFe layers, as well as the magnetoresistance effect of the STO, which had a frequency equal to the difference between the oscillation frequencies of the NiFe and FeCo layers. Such dynamics were reproduced by micromagnetic simulation. The results of the experiment and simulation demonstrate the merit of realizing OPP mode oscillation with a simple and thin structure suitable for a narrow gap recording head. In particular, the experimental results obtained with this STO design revealed that the cone angle for OPP mode oscillation of the FeCo layer (estimated by using the macrospin model) was large, namely, ∼70°.
Simple non-galvanic flip-chip integration method for hybrid quantum systems
Authors: Satzinger K. J. , Conner C. R. , Bienfait A. , Chang H.-S. , Chou Ming-Han , Cleland A. Y. , Dumur É. , Grebel J. , Peairs G. A. , Povey R. G. , Whiteley S. J. , Zhong Y. P. , Awschalom D. D. , Schuster D. I. , Cleland A. N.
Published: April 2019

A challenge faced by experimenters exploring hybrid quantum systems is how to integrate and interconnect different materials and different substrates in a quantum-coherent fashion. Here, we present a simple and inexpensive flip-chip bonding process, suitable for integrating hybrid quantum devices on chips from different substrates. The process only requires equipment and materials used routinely for contact photolithography, and it is possible to undo the bonding and reuse the chips. The technique requires minimal compressive force, so it is compatible with a wide range of different substrates. Unlike indium-based bonding, this process does not establish a galvanic connection between the two chips, but as we show, in some situations this is not necessary. We demonstrate the technique using lithographically patterned quarter-wave coplanar waveguide resonators, fabricated on one chip, and couple these inductively to a transmission line patterned lithographically on a separate chip. The two chips have a vertical interchip gap of about 7 μm, and we can repeatedly achieve lateral alignments of better than 2 μm. We measure electromagnetic resonances with low-power (∼1 photon) internal quality factors Qi around 5 × 105, comparable to single-chip performances, with as-designed coupling quality factors Qc ranging from 2 × 102 to 5 × 105.
Piezo-impedance response of carbon nanotube/polydimethylsiloxane nanocomposites
Authors: Jeon Dae-Young , Kim Heeju , Lee Min Wook , Park So Jeong , Kim Gyu-Tae
Published: April 2019

Advanced physical sensors based on carbon nanotube/polydimethylsiloxane (CNT/PDMS) nanocomposites have recently attracted much attention for potential applications such as wearable and flexible electronic devices. In this work, a CNT/PDMS sponge was fabricated and their capacitive as well as resistive response was investigated by impedance characterization with an equivalent circuit model. The newly defined gauge factor, which considers simultaneously both the piezocapacitive and piezoresistive effects of CNT/PDMS sponge sensors, showed a significantly improved sensitivity. This work provides important information for a better understanding of CNT/PDMS nanocomposites and their sensing performance.
A fiber-integrated nanobeam single photon source emitting at telecom wavelengths
Authors: Lee Chang-Min , Buyukkaya Mustafa Atabey , Aghaeimeibodi Shahriar , Karasahin Aziz , Richardson Christopher J. K. , Waks Edo
Published: April 2019

Fiber-coupled single photon sources are considered important components of photonics-based quantum information processors. Most fiber-coupled single photon sources require careful alignment between fibers and quantum emitters. In this work, we present an alignment-free fiber-integrated single photon source based on an InAs/InP quantum dot emitting at telecom wavelengths. We designed a nanobeam containing the quantum dots attached to a fiber taper. The adiabatic tapered coupler of the nanobeam enables efficient light coupling to the fiber taper. Using a tungsten probe in a focused ion beam system, we transferred the nanobeam to the fiber taper. The observed fiber-coupled single photon emission occurs with a brightness of 1.4% and a purity of 83%. This device provides a building block for fiber-optic quantum circuits that have various applications, such as quantum communication and distributed quantum computing.
Over 100% magnetoresistance ratio at room temperature in magnetic tunnel junctions with CuGaSe2 spacer layer
Authors: Mukaiyama K. , Jung J. W. , Sepehri-Amin H. , Kasai S. , Furubayashi T. , Ohkubo T. , Hono K.
Published: April 2019

We investigated the structure and magneto-transport properties of magnetic tunnel junctions (MTJs) consisting of half-metallic Co2FeGa0.5Ge0.5 ferromagnetic electrodes and a semiconductive CuGaSe2 interlayer. The magnetoresistance (MR) ratio reaches more than 100% at room temperature and nearly 250% at 30 K with the resistance area product (RA) smaller than 1 Ω μm2. Microstructural analysis clarified that Co and Fe atoms diffuse into the CuGaSe2 layer, which can be a possible reason for the scattering of RA values but poorly affect the MR ratio itself. Our findings stress the potential of semiconductor barriers in MTJs for spintronics application that requires low RA.
Effect of poling temperature on piezoelectric and dielectric properties of 0.7Pb(Mg1/3Nb2/3)O3-0.3PbTiO3 single crystals under alternating current poling
Authors: Wan Haotian , Luo Chengtao , Chang Wei-Yi , Yamashita Yohachi , Jiang Xiaoning
Published: April 2019

In this work, the piezoelectric and dielectric properties of [001]-oriented 0.7Pb(Mg1/3Nb2/3)O3-0.3PbTiO3 single crystals under alternating current poling (ACP) at different temperatures were studied. The piezoelectric coefficients (d33 ∼ 1930 pC/N, d31 ∼ −850 pC/N) and free dielectric permittivity (εT33/ε0 ∼ 7570) reached their highest values when the poling temperature (Tpoling) was 70 °C. Compared with traditional direct current electric field poling at 20 °C, 70 °C-ACP samples showed an enhancement of 40%, 35%, and 49% for d33, d31, and εT33/ε0, respectively. Meanwhile, d33 and εT33/ε0 were enhanced by about 9% when Tpoling increased from 20 °C to 70 °C under ACP, while d31 remained the same value and the dielectric loss was lowered from 0.29% to 0.22%. Moreover, ACP samples with different Tpoling have similar electromechanical coupling factors (k31 ∼ 0.44, kt ∼ 0.60). A discussion of the mechanism for the ACP enhancement was based on the domain observation using piezoresponse force microscopy, and the results showed that the domain densities of ACP samples with different Tpoling were positively correlated with their piezoelectric properties. This work demonstrated the enormous potential of ACP optimization for relaxor-PT single crystal applications.
Characterisation of bovine embryos following prolonged culture in embryonic stem cell medium containing leukaemia inhibitory factor
Authors: Hosoe Misa , Furusawa Tadashi , Hayashi Ken-Go , Takahashi Toru , Hashiyada Yutaka , Kizaki Keiichiro , Hashizume Kazuyoshi , Tokunaga Tomoyuki , Matsuyama Shuichi , Sakumoto Ryosuke
Published: April 2019

In order to help elucidate the process of epiblast and trophoblast cell differentiation in bovine embryos invitro, we attempted to develop a suitable culture medium to allow extended embryo culture. Day 7 bovine blastocysts developed in conventional medium were cultured further in embryonic stem cell medium with or without leukaemia inhibitory factor (LIF) until Day 23. At Day 14, the expression of octamer-binding transcription factor 3/4 (OCT3/4) and VIMENTIN was significantly higher in embryos cultured with than without LIF, but embryonic disc formation was not observed. Although expression of SRY (sex determining region Y)-box 17 (SOX17) mRNA was significantly lower in Day 14 embryos cultured with and without LIF than in invivo embryos, hypoblast cells formed just inside the trophoblast cells of the invitro-cultured embryos. On Day 23, expression of placental lactogen (PL) and prolactin-related protein 1 (PRP1) was not affected by LIF in invitro-cultured embryos, levels of both genes were significantly lower in the invitro than invivo embryos. Similar to invivo embryos, binucleate cell clusters seen in Day 23invitro-cultured embryos were composed of PL-negative and -positive cells. These results suggest that our culture system partially reproduced the differentiation process of trophoblast cells invivo.
Accelerated Immunodeficiency-associated Vaccine-derived Poliovirus Serotype 3 Sequence Evolution Rate in an 11-week-old Boy With X-linked Agammaglobulinemia and Perinatal Human Immunodeficiency Virus Exposure
Authors: Jallow Sabelle , Wilmshurst Jo M , Howard Wayne , Copelyn Julie , Seakamela Lerato , Chan Koon-Wing , Sebunya Robert , Sibiya Rosinah , Du Plessis Heleen , Jacobs Charlene , Berkowitz Natacha , Blumberg Lucille , McCarthy Kerrigan , Maseti Elizabeth , Kamupira Mercy , Dlamini Nonhlanhla , Gumede Nicksy , Diop Ousmane M , Lau Yu Lung , Moonsamy Shelina , Eley Brian , Suchard Melinda
Published: April 2019

Primary B-cell immunodeficiencies are risk factors for the generation of vaccine-derived polioviruses. We report immunodeficiency-associated vaccine-derived poliovirus serotype 3 in an 11-week-old boy with X-linked agammaglobulinemia. Unique characteristics of this case include early age of presentation, high viral evolutionary rate, and the child’s perinatal exposure to human immunodeficiency virus.
Reconciling Antimicrobial Susceptibility Testing and Clinical Response in Antimicrobial Treatment of Chronic Cystic Fibrosis Lung Infections
Authors: Waters Valerie J , Kidd Timothy J , Canton Rafael , Ekkelenkamp Miquel B , Johansen Helle Krogh , LiPuma John J , Bell Scott C , Elborn J Stuart , Flume Patrick A , VanDevanter Donald R , Gilligan Peter ,   Antimicrobial Resistance International Working Group in Cystic Fibrosis, Bullington Wendy , Burgel Pierre-Regis , Byrnes Catherine , Drevinek Pavel , Holmes Alison , Kahl Barbara , Maples Holly , Martiniano Stacey , McColley Susanna , Morris Andrew , Muhlebach Marianne , Parkins Michael , Ratjen Felix , Roberts Jason , Saiman Lisa , Shah Anand , Smyth Alan , Somayaji Ranjani , Taccetti Giovanni , Tunney Michael , Winthrop Kevin , Zemanick Edith
Published: April 2019

Median cystic fibrosis (CF) survival has increased dramatically over time due to several factors, including greater availability and use of antimicrobial therapies. During the progression of CF lung disease, however, the emergence of multidrug antimicrobial resistance can limit treatment effectiveness, threatening patient longevity. Current planktonic-based antimicrobial susceptibility testing lacks the ability to predict clinical response to antimicrobial treatment of chronic CF lung infections. There are numerous reasons for these limitations including bacterial phenotypic and genotypic diversity, polymicrobial interactions, and impaired antibiotic efficacy within the CF lung environment. The parallels to other chronic diseases such as non-CF bronchiectasis are discussed as well as research priorities for moving forward.
A ruptured penetrating atherosclerotic ulcer of the ascending aorta: a case report of an endovascular repair with extending the length of the aortic coverage by debranching the innominate artery
Authors: Chenesseau Josephine , Barral Pierre-Antoine , Piquet Philippe , Gaudry Marine
Published: April 2019

Background

An endovascular approach to the management of a ruptured plaque in the ascending aorta may be an alternative to open surgery in high-risk patients. This option may become inevitable due to the number of elderly patients unfit for open cardiac surgery. There are very few stent grafts able to fit the ascending aorta and in emergency cases, most medical teams have been limited to current thoracic aortic endografts, the shortest of which measure 10 cm.

Case summary

We report a case of an endovascular repair of a ruptured penetrating atherosclerotic ulcer of the ascending aorta. The patient was considered for open cardiac surgery but was evaluated at a high mortality risk based on his age, his medical history, and significant calcifications on his aorta. Our vascular surgical team decided then to perform an endovascular repair with extending the length of the aortic coverage by debranching the innominate artery.

Discussion

Endovascular treatment of an acute ruptured aorta is feasible in high-risk patients with thoracic endovascular stent grafts and coverage of the innominate artery. Endovascular treatment of the ascending aorta is at its infancy and in need of further research. New stent grafts designed for the ascending aorta are in progress and should increase the numbers of interventions in the years to come.
EuroGTP II: a tool to assess risk, safety and efficacy of substances of human origin
Authors: Trias Esteve , Lomas Richard , Tabera Jaime , Piteira A Rita , Tilleman Kelly , Casaroli-Marano Ricardo P , Chandrasekar Akila ,   EuroGTP II Study Group
Published: April 2019

A systematic methodology, able to assess risk and predict clinical safety and efficacy of Substances of Human Origin’ (SoHO) has been developed. The model consists of a risk based approach taking into account factors such as novelty of the product, preparation process, clinical indication, and its technical complexity.
Microcirculatory Free Flap Failure With Patent Anastomosis Salvaged by In Situ Thrombolysis in Vulnerable Phase Burn
Authors: Coeugniet Edouard , Al Yafi Mohamed Nazhat , Lafrance Dominique , Danino Michel Alain , Soulez Gilles , Nguyen Quynh , Harris Patrick
Published: April 2019

Free flap reconstruction in acute burns has high failure rates, relating mainly to a systemic inflammatory state. The “vulnerable phase” can last for 6 weeks after burn and can cause thrombosis of the flap microcirculation with patent arterial and venous anastomoses. Revision surgery alone may be unsuccessful, but thrombolysis can lead to flap salvage. We describe a case of successful flap salvage with thrombolysis after unsuccessful revision surgery by permeable arterial and venous anastomoses in a patient in the acute burn phase suffering from microcirculatory thrombosis. Thrombolysis in these cases has not been described to date, but it could contribute to salvaging flaps by radiological intervention alone. A 23-year-old man was admitted with a 38% TBSA burn, including loss of all eyelid skin. The right eye was reconstructed in a satisfactory manner, but the left eye required urgent corneal coverage on day 32 with a dorsalis pedis fasciocutaneous free flap. The flap was hypo-perfused postoperatively, but anastomoses were found to be permeable on exploration. Angiography performed postoperatively after revision confirmed anastomotic patency, but failed to demonstrate small vessel beds within the flap. Thus, r-tPa was given at the anastomosis site and immediately the flap recovered completely. However, a total of 10 packed red blood cell transfusions were needed over the next 9 days. Thrombolysis in the context of free flap microvascular compromise may improve the overall success rates, especially in acute-phase burn patients where this etiology may be found, due to a vulnerable inflammatory period.
On the Possibility of Informative Equilibria in Futures Markets with Feedback
Authors: Lieli Robert P , Nieto-Barthaburu Augusto
Published: April 2019

We study the existence of equilibria and the information content of prices in futures markets where the probability of future payoffs can be altered by an intervening agent who acts in response to the market price, hence creating a feedback effect. We focus on the market with the simplest possible structure: traders betting on the occurrence of a future event by buying or selling Arrow-Debreu securities (one dollar claims contingent on a binary outcome). We find that in the presence of feedback: (i) a rational expectations equilibrium may not exist; (ii) the market price may decline in response to information that is ex-ante more favorable to the occurrence of the underlying event; (iii) an equilibrium that reveals no information may obtain. Thus, feedback from an intervening agent materially alters the way in which price responds to information, and potentially undermines the viability of the market itself.
Early Prediction of Prognosis in Elderly Acute Stroke Patients
Authors: Bautista Alexander F. , Lenhardt Rainer , Yang Dongsheng , Yu Changhong , Heine Michael F. , Mascha Edward J. , Heine Cate , Neyer Thomas M. , Remmel Kerri , Akca Ozan
Published: April 2019

Objectives:

Acute stroke has a high morbidity and mortality in elderly population. Baseline confounding illnesses, initial clinical examination, and basic laboratory tests may impact prognostics. In this study, we aimed to establish a model for predicting in-hospital mortality based on clinical data available within 12 hours of hospital admission in elderly (≥ 65 age) patients who experienced stroke.

Design:

Retrospective observational cohort study.

Setting:

Academic comprehensive stroke center.

Patients:

Elderly acute stroke patients—2005–2009 (n = 462), 2010–2012 (n = 122), and 2016–2017 (n = 123).

Interventions:

None.

Measurements and Main Results:

After institutional review board approval, we retrospectively queried elderly stroke patients’ data from 2005 to 2009 (training dataset) to build a model to predict mortality. We designed a multivariable logistic regression model as a function of baseline severity of illness and laboratory tests, developed a nomogram, and applied it to patients from 2010 to 2012. Due to updated guidelines in 2013, we revalidated our model (2016–2017). The final model included stroke type (intracerebral hemorrhage vs ischemic stroke: odds ratio [95% CI] of 0.92 [0.50–1.68] and subarachnoid hemorrhage vs ischemic stroke: 1.0 [0.40–2.49]), year (1.01 [0.66–1.53]), age (1.78 [1.20–2.65] per 10 yr), smoking (8.0 [2.4–26.7]), mean arterial pressure less than 60 mm Hg (3.08 [1.67–5.67]), Glasgow Coma Scale (0.73 [0.66–0.80] per 1 point increment), WBC less than 11 K (0.31 [0.16–0.60]), creatinine (1.76 [1.17–2.64] for 2 vs 1), congestive heart failure (2.49 [1.06–5.82]), and warfarin (2.29 [1.17–4.47]). In summary, age, smoking, congestive heart failure, warfarin use, Glasgow Coma Scale, mean arterial pressure less than 60 mm Hg, admission WBC, and creatinine levels were independently associated with mortality in our training cohort. The model had internal area under the curve of 0.83 (0.79–0.89) after adjustment for over-fitting, indicating excellent discrimination. When applied to the test data from 2010 to 2012, the nomogram accurately predicted mortality with area under the curve of 0.79 (0.71–0.87) and scaled Brier’s score of 0.17. Revalidation of the same model in the recent dataset from 2016 to 2017 confirmed accurate prediction with area under the curve of 0.83 (0.75–0.91) and scaled Brier’s score of 0.27.

Conclusions:

Baseline medical problems, clinical severity, and basic laboratory tests available within the first 12 hours of admission provided strong independent predictors of in-hospital mortality in elderly acute stroke patients. Our nomogram may guide interventions to improve acute care of stroke.
Bounding Bias Due to Selection
Authors: Smith Louisa H. , VanderWeele Tyler J.
Published: April 2019

When epidemiologic studies are conducted in a subset of the population, selection bias can threaten the validity of causal inference. This bias can occur whether or not that selected population is the target population and can occur even in the absence of exposure–outcome confounding. However, it is often difficult to quantify the extent of selection bias, and sensitivity analysis can be challenging to undertake and to understand. In this article, we demonstrate that the magnitude of the bias due to selection can be bounded by simple expressions defined by parameters characterizing the relationships between unmeasured factor(s) responsible for the bias and the measured variables. No functional form assumptions are necessary about those unmeasured factors. Using knowledge about the selection mechanism, researchers can account for the possible extent of selection bias by specifying the size of the parameters in the bounds. We also show that the bounds, which differ depending on the target population, result in summary measures that can be used to calculate the minimum magnitude of the parameters required to shift a risk ratio to the null. The summary measure can be used to determine the overall strength of selection that would be necessary to explain away a result. We then show that the bounds and summary measures can be simplified in certain contexts or with certain assumptions. Using examples with varying selection mechanisms, we also demonstrate how researchers can implement these simple sensitivity analyses. See video abstract at, http://links.lww.com/EDE/B535.
Glomerular Filtration Rate Is a Major Predictor of Clearance of Oxcarbazepine Active Metabolite in Adult Chinese Epileptic Patients: A Population Pharmacokinetic Analysis
Authors: Lin Wei-Wei , Wang Chang-Lian , Jiao Zheng , Yu Xiao-Li , Zhang Jin , Zhang Wen-Bin , Lin Rong-Fang , Lin Shen , Lin Xin-Hua
Published: April 2019

Background:

Oxcarbazepine (OXC) is almost completely metabolized to its10-monohydroxy derivative (MHD), which is responsible for the pharmacological effects of the drug. Several studies have described the population pharmacokinetics (PPK) of MHD in pediatric patients, but little is known about its pharmacokinetics in adult patients. In addition, no study to date has proposed a model to investigate the influence of genetic polymorphisms on MHD pharmacokinetics. The aim of this study was to establish a PPK model of MHD to investigate the effects of genetic polymorphisms in UGT2B7, UGT1A9, ABCB1, and ABCB2 in adult Chinese patients with epilepsy and to develop a new dosage guideline for OXC.

Methods:

Data were prospectively collected from 187 adult patients with epilepsy who were taking OXC. MHD trough concentrations were detected by enzyme-multiplied immunoassay. Patients were genotyped for 4 single nucleotide polymorphisms (UGT2B7 802T>C, UGT1A9 I399C>T, ABCB1 3435C>T, and ABCB2 1249G>A). Other covariates included sex, age, body weight (BW), hepato-renal function, and concomitant medications. Data were analyzed using the nonlinear mixed effects modelling software.

Results:

The apparent clearance (CL) of MHD was significantly influenced by glomerular filtration rate and BW, and was unrelated to other covariates such as genetic polymorphisms and coadministration with levetiracetam, lamotrigine, and topiramate. Moreover, a new dosage guideline was proposed based on the final model to individualize OXC regimens for adult patients with varying BW and renal function.

Conclusions:

Glomerular filtration rate was first found as an important covariate influencing MHD CL. A PPK model was established to estimate the individual MHD CL for adult patients taking OXC and may be applied for individualizing doses in the target population.
Changes in Physical Performance and Their Association With Health-Related Quality of Life in a Mixed Nonischemic Cardiac Population That Participates in Rehabilitation
Authors: Tang Lars Hermann , Zwisler Ann-Dorthe , Doherty Patrick , Oldridge Neil , Berg Selina Kikkenborg , Christensen Jan
Published: April 2019

Purpose:

Exercise-based cardiac rehabilitation improves physical performance and health-related quality of life (HRQoL). However, whether improvements in physical performance are associated with changes in HRQoL has not been adequately investigated in a nonischemic cardiac population.

Methods:

Patients who were ablated for atrial fibrillation, who underwent heart valve surgery or who were treated for infective endocarditis, and who participated in 1 of 3 randomized controlled rehabilitation trials were eligible for the current study. Change in physical performance and HRQoL were measured before and after a 12-wk exercise intervention. Physical performance was assessed using a cardiopulmonary exercise test, a 6-min walk test, and a sit-to-stand test. Health-related quality of life was assessed using the generic 36-Item Short Form Health Survey and the disease-specific HeartQoL questionnaire. Spearman correlation coefficient (ρ) and linear regressions quantified the association between changes in physical outcome measures and changes in HRQoL.

Results:

A total of 344 patients were included (mean age: 60.8 ± 11.6 yr and 77% males). Associations between changes in physical outcome measures and HRQoL ranged from very weak to weak (ρ = −0.056 to 0.228). The observed associations were more dominant within physical dimensions of the HRQoL compared with mental or emotional dimensions. After adjusting for sex, age, and diagnosis, changes in physical performance explained no more than 20% of the variation in the HRQoL.

Conclusion:

The findings show that the positive improvement in HRQoL from exercise-based cardiac rehabilitation cannot simply be explained by an improvement in physical performance.
Does toe clipping for genotyping interfere with later-in-life nociception in mice?
Authors: Frezel Noémie , Kratzer Gilles , Verzar Philipp , Bürki Jérôme , Weber Fabienne A. , Zeilhofer Hanns Ulrich
Published: April 2019

Introduction:

Genetically modified mice are widely used in studies on human and animal physiology and pharmacology, including pain research. The experimental design usually includes comparisons of genetically modified mice with wild-type littermates, requiring biopsy material for genotyping and methods for unequivocal identification of individual mice. Ethical standards and, in some countries, legislation require that both needs are reached with a single procedure. Clipping of the most distal phalanx of up to two toes per paw (toe clipping) is the favored procedure in most research fields, but it may be problematic in sensory physiology and pain research.

Objectives:

To systematically investigate whether toe-clipping influences later-in-life nociceptive sensitivity or the susceptibility to neuropathic or inflammatory hyperalgesia.

Methods:

We tested in male mice whether the clipping of 2 toes of a hind paw influences nociceptive sensitivities to noxious heat or cold, or to mechanical stimulation under baseline conditions, after peripheral nerve injury (chronic constriction of the sciatic nerve) or during peripheral inflammation induced by subcutaneous zymosan A injection. We tested not only for the presence of significant differences but also specifically addressed bioequivalence using the 2 one-sided t test procedure. We chose a threshold of 25% variation of the control value for nonequivalence, which is usually taken as a threshold for biological relevance in pain tests.

Results:

Using this value, we found that for all conditions (non-neuropathic and non-inflamed, neuropathic and inflamed), nociceptive sensitivities significantly fell within the equivalence bounds of the non–toe-clipped control mice.

Conclusions:

These results suggest that toe clipping does not have long-term effects on nociceptive sensitivities and does not alter the susceptibility of male mice to neuropathic or inflammatory hyperalgesia.
Perfusion Zones of Extended Transverse Skin Paddles in Muscle-Sparing Latissimus Dorsi Myocutaneous Flaps for Breast Reconstruction
Authors: Koonce Stephanie L. , Barnavon Yoav , Newman Martin I. , Hwee Yin Kan
Published: April 2019

Background:

The authors report their experience using extended transversely oriented skin paddles in muscle-sparing latissimus dorsi pedicled flaps for breast reconstruction as an alternative to thoracodorsal artery perforator flaps.

Methods:

A retrospective review was conducted of patients who underwent muscle-sparing latissimus dorsi flap pedicled breast reconstruction from January of 2009 to July of 2014 with at least 3-month follow-up. Surgical outcomes and complications were analyzed.

Results:

Fifty-three patients underwent a total of 81 muscle-sparing latissimus dorsi pedicled flaps for breast reconstruction. Extended transversely oriented skin paddles ranged from 7 to 9 cm vertically by 25 to 35 cm horizontally and were perfused by a strip of latissimus dorsi muscle that was approximately 25 percent of the total muscular volume. Twenty patients had indocyanine green angiography revealing three distinct zones of perfusion in the extended transversely oriented skin paddles. The area of earliest perfusion (designated zone 1) was directly over the muscle containing the perforators. The second best area of perfusion (zone 2) was lateral to the muscle (toward the axilla). The last and relatively least well-perfused area (zone 3) was medial to the muscle (toward the spine). Zone 3 still had adequate viability. There were no flap losses. Minor complications included wound infection [six of 81 (7.4 percent)], fat necrosis [three of 81 (3.7 percent)], and seroma [four of 81 (4.9 percent)].

Conclusions:

Muscle-sparing latissimus dorsi pedicled flaps with extended transversely oriented skin paddles are reliable alternatives to thoracodorsal artery perforator flaps for breast reconstruction. Three zones of perfusion were delineated in the extended transversely oriented skin paddles on indocyanine green imaging, and all three zones were viable.

CLINICAL QUESTION/LEVEL OF EVIDENCE:

Therapeutic, IV.
The Latissimus Dorsi Myocutaneous Flap Is a Safe and Effective Method of Partial Breast Reconstruction in the Setting of Breast-Conserving Therapy
Authors: Mericli Alexander F. , Szpalski Caroline , Schaverien Mark V. , Selber Jesse C. , Adelman David M. , Garvey Patrick B. , Villa Mark T. , Robb Geoffrey , Baumann Donald P.
Published: April 2019

Background:

Reconstruction of partial breast defects in low-volume, nonptotic breasts can be challenging. The authors hypothesized that use of the latissimus dorsi flap in partial breast reconstruction is safe and associated with low complication and high patient satisfaction rates.

Methods:

All patients who underwent breast-conserving therapy and latissimus dorsi flap reconstruction from January 1, 2006, to December 31, 2016, were identified in a prospectively maintained database. Patient demographics, tumor characteristics, and complications were recorded. Patient-reported outcomes were assessed with the BREAST-Q breast-conserving therapy module. A group of plastic surgeons and laypersons used a five-point Likert scale to evaluate aesthetic outcomes in representative patients.

Results:

Forty-seven patients met the inclusion criteria. Median follow-up was 5.4 years. Most patients (93.6 percent) underwent immediate reconstruction. The mean resection volume was 219.5 cc (range, 70 to 877 cc). The overall complication rate was 8.5 percent. Grade 2 or 3 ptosis (OR, 1.21; 95 percent CI, 1.0 to 1.46; p = 0.03), smoking (OR, 13.1; 95 percent CI, 1.2 to 143.2; p = 0.03), and multicentric tumor (OR, 1.23; 95 percent CI, 1.04 to 1.64; p = 0.02) were associated with a higher complication rate. Ductal carcinoma in situ was associated with reoperation for positive margins (OR, 14.4; 95 percent CI, 2.1 to 100; p = 0.009). Of particular interest, patient-reported outcomes were favorable, with the highest rated domains being Satisfaction with Breasts (61; interquartile range, 37 to 77), Psychosocial Well-being (87; interquartile range, 63 to 100), and Physical Well-being (87; interquartile range, 81 to 100). The median aesthetic score was 4 (of 5).

Conclusions:

This is the first study to date using the BREAST-Q to assess patient-reported outcomes associated with the latissimus dorsi flap for partial breast reconstruction. The flap is safe and effective for reconstruction in the setting of breast-conserving therapy, providing aesthetically pleasing results with high patient satisfaction.

CLINICAL QUESTION/LEVEL OF EVIDENCE:

Therapeutic, IV.
Laue diffraction and time-resolved crystallography: a personal history
Authors: Moffat Keith
Published: April 2019

A personal, historical view is presented of Laue X-ray diffraction and its application to time-resolved studies of dynamic processes, largely in light-sensitive biological systems. In Laue diffraction, a stationary crystal is illuminated by a polychromatic X-ray source. Laue diffraction has inherent complications largely absent in monochromatic diffraction, and consequently fell into disuse for quantitative structure determination. However, the advent of naturally polychromatic, intense, pulsed storage ring X-ray sources in the 1970s led to re-examination at Daresbury and elsewhere of its underlying principles. Laue diffraction has been successfully applied at storage ring sources to time-resolved, pump–probe crystallographic studies, whose exposure time and time resolution were progressively reduced from minutes to seconds, milliseconds, nanoseconds and 100 ps. Most recently, hard X-ray free electron laser sources have been used to generate narrow bandpass Laue diffraction patterns. The femtosecond X-ray pulses from such sources are completely destructive, generate only one diffraction pattern per tiny crystal and have unusual properties. However, they too are being applied to time-resolved crystallography to explore, for example, isomerization and rapid tertiary structural changes on the chemical, femtosecond timescale.

This article is part of the theme issue ‘Fifty years of synchrotron science: achievements and opportunities’.
New nitrides: from high pressure–high temperature synthesis to layered nanomaterials and energy applications
Authors: McMillan Paul F.
Published: April 2019

We describe work carried out within our group to explore new transition metal and main group nitride phases synthesized using high pressure–high temperature techniques using X-ray diffraction and spectroscopy at synchrotron sources in the USA, UK and France to establish their structures and physical properties. Along with previously published data, we also highlight additional results that have not been presented elsewhere and that represent new areas for further exploration. We also describe new work being carried out to explore the properties of carbon nitride materials being developed for energy applications and the nature of few-layered carbon nitride nanomaterials with atomically ordered structures that form solutions in polar liquids via thermodynamically driven exfoliation.

This article is part of the theme issue ‘Fifty years of synchrotron science: achievements and opportunities’.
CoolBox: a interactive genomic data explorer for Jupyter Notebook
Authors: Xu Weize , Lin Da , Hong Ping , Yi Liang , Tyagi Rohit , Li Guoliang , Cao Gang
Published: April 2019

CoolBox is a Python package for interactive genomic data exploration based on Jupyter notebook. It provides a ggplot2-like Application Programming Interface (API) for genomic data visualization, and a Jupyter/ipywidgets based Graphical User Interface (GUI) for interactive data exploration. CoolBox is a versatile multi-omics explorer supporting most types of data formats generated by various sequencing technologies like RNA-Seq, ChIP-Seq, ChIA-PET and Hi-C.

Availability and implementation

CoolBox is purely implemented with Python, and the GUI widget in Jupyter notebook is based on the ipywidgets package. It is open-source and available under GPLv3 license at https://github.com/GangCaoLab/CoolBox.
FIREcaller: Detecting Frequently Interacting Regions from Hi-C Data
Authors: Crowley Cheynna , Yang Yuchen , Qiu Yunjiang , Hu Benxia , Abnousi Armen , Lipiński Jakub , Plewczyński Dariusz , Wu Di , Won Hyejung , Ren Bing , Hu Ming , Li Yun
Published: April 2019

Hi-C experiments have been widely adopted to study chromatin spatial organization, which plays an essential role in genome function. We have recently identified frequently interacting regions (FIREs) and found that they are closely associated with cell-type-specific gene regulation. However, computational tools for detecting FIREs from Hi-C data are still lacking. In this work, we present FIREcaller, a stand-alone, user-friendly R package for detecting FIREs from Hi-C data. FIREcaller takes raw Hi-C contact matrices as input, performs within-sample and cross-sample normalization, and outputs continuous FIRE scores, dichotomous FIREs, and super-FIREs. Applying FIREcaller to Hi-C data from various human tissues, we demonstrate that FIREs and super-FIREs identified, in a tissue-specific manner, are closely related to gene regulation, are enriched for enhancer-promoter (E-P) interactions, tend to overlap with regions exhibiting epigenomic signatures of cis-regulatory roles, and aid the interpretation or GWAS variants. The FIREcaller package is implemented in R and freely available at https://yunliweb.its.unc.edu/FIREcaller.

Highlights

– Frequently Interacting Regions (FIREs) can be used to identify tissue and cell-type-specific cis-regulatory regions.

– An R software, FIREcaller, has been developed to identify FIREs and clustered FIREs into super-FIREs.
The guanine nucleotide exchange factor GBF1 participates in rotavirus replication
Authors: Martínez José L. , Arnoldi Francesca , Schraner Elisabeth M. , Eichwald Catherine , Silva-Ayala Daniela , Lee Eunjoo , Sztul Elizabeth , Burrone Óscar R. , López Susana , Arias Carlos F.
Published: April 2019

Cellular and viral factors participate in the replication cycle of rotavirus. We report that the guanine nucleotide exchange factor GBF1, which activates the small GTPase Arf1 to induce COPI transport processes, is required for rotavirus replication since knocking down GBF1 expression by RNA interference, or inhibiting its activity by treatment with Brefeldin A (BFA) or Golgicide A (GCA) significantly reduce the yield of infectious viral progeny. This reduction in virus yield was related to a block in virus assembly since in the presence of either BFA or GCA the assembly of infectious mature triple-layered virions was significantly prevented and only doubled layered-particles were detected. We report that the catalytic activity of GBF1, but not the activation of Arf1, is essential for the assembly of the outer capsid of rotavirus. We show that both BFA and GCA, as well as interfering with the synthesis of GBF1, alter the electrophoretic mobility of glycoproteins VP7 and NSP4 and block the trimerization of the virus surface VP7, a step required for its incorporation into virus particles. Although a post-translational modification of VP7 (other than glycosylation) could be related to the lack of trimerization, we found that NSP4 might also be involved in this process, since knocking-down its expression reduces VP7 trimerizarion. In support, recombinant VP7 protein overexpressed in transfected cells formed trimers only when co-transfected with NSP4.

IMPORTANCE

Rotavirus, a member of the family Reoviridae, is the major cause of severe diarrhea in children and young animals worldwide. Despite the significant advances in the characterization of the biology of this virus, the mechanisms involved in morphogenesis of the virus particle are still poorly understood. In this work, we show that the guanine nucleotide exchange factor GBF1, relevant for the COPI/Arf1-mediated cellular vesicular transport, participates in the replication cycle of the virus, influencing the correct processing of viral glycoproteins VP7 and NSP4, and the assembly of the virus surface proteins VP7 and VP4.
Functional effects of variation in transcription factor binding highlight long-range gene regulation by epromoters
Authors: Mitchelmore Joanna , Grinberg Nastasiya , Wallace Chris , Spivakov Mikhail
Published: April 2019

Identifying DNA cis-regulatory modules (CRMs) that control the expression of specific genes is crucial for deciphering the logic of transcriptional control. Natural genetic variation can point to the possible gene regulatory function of specific sequences through their allelic associations with gene expression. However, comprehensive identification of causal regulatory sequences in brute-force association testing without incorporating prior knowledge is challenging due to limited statistical power and effects of linkage disequilibrium. Sequence variants affecting transcription factor (TF) binding at CRMs have a strong potential to influence gene regulatory function, which provides a motivation for prioritising such variants in association testing. Here, we generate an atlas of CRMs showing predicted allelic variation in TF binding affinity in human lymphoblastoid cell lines (LCLs) and test their association with the expression of their putative target genes inferred from Promoter Capture Hi-C and immediate linear proximity. We reveal over 1300 CRM TF-binding variants associated with target gene expression, the majority of them undetected with standard association testing. A large proportion of CRMs showing associations with the expression of genes they contact in 3D localise to the promoter regions of other genes, supporting the notion of ‘epromoters’: dual-action CRMs with promoter and distal enhancer activity.
Fungi form interkingdom microbial communities in the primordial human gut that develop with gestational age
Authors: Willis Kent A. , Purvis John H. , Myers Erin D. , Aziz Michael M. , Karabayir Ibrahim , Gomes Charles K. , Peters Brian M. , Akbilgic Oguz , Talati Ajay J. , Pierre Joseph F.
Published: April 2019

Fungal and bacterial commensal organisms play a complex role in the health of the human host. Expansion of commensal ecology after birth is a critical period in human immune development. However, the initial fungal colonization of the primordial gut remains undescribed. To investigate primordial fungal ecology, we performed amplicon sequencing and culture-based techniques of first-pass meconium, which forms in the fetal intestine prior to birth, from a prospective observational cohort of term-born and preterm newborns. Here, we describe fungal ecologies in the primordial gut that develop complexity with advancing gestational age at birth. Our findings suggest homeostasis of fungal commensals may represent an important aspect of human biology present even before birth. Unlike bacterial communities which gradually develop complexity, the domination of the fungal communities of some preterm infants by Saccromycetes, specificallyCandida, may suggest a pathologic association with preterm birth.
Hairless as a novel component of the Notch signaling pathway
Authors: Miller Steven W , Movsesyan Artem , Zhang Sui , Fernández Rosa , Posakony James W
Published: April 2019

Suppressor of Hairless [Su(H)], the transcription factor at the end of the Notch pathway in Drosophila, utilizes the Hairless protein to recruit two co-repressors, Groucho (Gro) and C-terminal Binding Protein (CtBP), indirectly. Hairless is present only in the Pancrustacea, raising the question of how Su(H) in other protostomes gains repressive function. We show that Su(H) from a wide array of arthropods, molluscs, and annelids includes motifs that directly bind Gro and CtBP; thus, direct co-repressor recruitment is ancestral in the protostomes. How did Hairless come to replace this ancestral paradigm? Our discovery of a protein (S-CAP) in Myriapods and Chelicerates that contains a motif similar to the Su(H)-binding domain in Hairless has revealed a likely evolutionary connection between Hairless and Metastasis-associated (MTA) protein, a component of the NuRD complex. Sequence comparison and widely conserved microsynteny suggest that S–CAP and Hairless arose from a tandem duplication of an ancestral MTA gene.
Pollen tube-triggered accumulation of NORTIA at the filiform apparatus facilitates fertilization inArabidopsis thaliana
Authors: Yuan Jing , Ju Yan , Jones Daniel S. , Zhang Weiwei , Lucca Noel , Staiger Christopher J. , Kessler Sharon A.
Published: April 2019

During gamete delivery inArabidopsis thaliana, intercellular communication between the attracted pollen tube and the receptive synergid cell leads to subcellular events in both cells culminating in the rupture of the tip-growing pollen tube and release of the sperm cells to achieve double fertilization. Live imaging of pollen tube reception revealed dynamic subcellular changes that occur in the female synergid cells. Pollen tube arrival triggers the trafficking of NORTIA (NTA) MLO protein from Golgi-associated compartments and the accumulation of endosomes at or near the synergid filiform apparatus, a membrane-rich region that acts as the site of communication between the pollen tube and synergids. Domain swaps and site-directed mutagenesis reveal that NTA’s C-terminal cytoplasmic tail with its calmodulin-binding domain influences the subcellular localization and function of NTA in pollen tube reception and that accumulation of NTA at the filiform apparatus is necessary and sufficient for MLO function in pollen tube reception.