bluuebunny/crossref_metadata_2025 huggingface dataset:
Feasibility of transabdominal Doppler ultrasonography for
studying ovarian blood flow characteristics in cycling gilts
Authors: Stark Rosa , Herlt Catherine , Sigmarsson Haukur L. , Kauffold Johannes
Published: April 2019

Objective The aim of this study was to assess ovarian blood flow
characteristics by applying transabdominal color Doppler ultrasonography during
the course of the estrous cycle in gilts.

Materials and methods Estrus and ovulation were synchronized in 15
pubertal gilts. During their consecutive spontaneous estrous cycle the gilts
were sonographically scanned daily and ovarian blood flow was determined by
imaging perfused areas of the ovarian hilus and the ovarian tissue. Recorded
video clips were then analyzed for the parameters perfused area (Amix), blood
flow velocity (vmix) as well as resistance (RIvmix) and pulsatility index
(PIvmix) using the software PixelFlux®.

Results All blood flow parameters showed an estrous cycle dependent
course, with Amix and vmix being highest in diestrus, followed by proestrus,
while RIvmix and PIvmix patterns were inversely proportional.

Conclusion and clinical relevance Transabdominal color Doppler
ultrasonography proved feasible to study ovarian perfusion characteristics in
pubertal gilts. The ovarian blood flow was dependent on the stage of estrous
cycle and highest in diestrus. The results of this study encourage the use of
color Doppler ultrasonography to also investigate reasons of ovary-caused
infertility including corpus luteum insufficiency or seasonal effects on ovary
function.
Schmerz- und Stressbestimmung bei der Injektion und
Kastration von Saugferkeln unter Lokalanästhesie mit Procain und
Lidocain
Authors: Hofmann Katharina , Rauh Anna , Harlizius Jürgen , Weiß Christine , Scholz Tobias , Schulze-Horsel Theodor , Escribano Damián , Ritzmann Mathias , Zöls Susanne
Published: April 2019

Ziel Vergleich der Wirksamkeit der Lokalanästhesie (LA) mit Procain 2 %
und Lidocain 5 % bei skrotaler kombiniert mit inguinaler Applikation mit der
testikulären Applikation von Lidocain 1 % zur Beurteilung der schmerzbedingten
Stressreaktion auf Injektion und Kastration.

Material und Methoden In 2 Teilversuchen (TV) wurden 232 männliche
Saugferkel eingeschlossen und verschiedenen Gruppen zugeordnet. TV1 (n = 112):
Gruppe H: Fixation der Ferkel wie bei der Injektion, keine Applikation; Gruppe
L5: Applikation von Lidocain 5 % inguinal und skrotal; Gruppe P2: Applikation
von Procain 2 % inguinal und skrotal; Gruppe L1: intratestikuläre Injektion von
Lidocain 1 %. Eine Blutentnahme erfolgte jeweils 45 Minuten vor sowie 30 Minuten
nach der Injektion (p. i.). TV2 (n = 120): Gruppe H: nur Handling wie bei der
Injektion und Kastration; Gruppe K: Fixation wie bei der Injektion und
betäubungslose Kastration nach 30 Minuten; Gruppen L5, P2 und L1: Verfahren wie
in TV1 mit Kastration 30 Minuten nach Injektion. Jedem Ferkel wurde 75 Minuten
vor sowie 30, 60 und 240 Minuten nach der Kastration (p. c.) Blut entnommen.
Untersuchte Parameter waren Serumkonzentration von Kortisol und Chromogranin A
(CgA) sowie Wundheilung, Gewichtsentwicklung und Verluste bis zum Absetzen.

Ergebnisse TV1: In Gruppe P2 ergab sich p. i. ein signifikant höherer
Anstieg der Kortisol- und CgA-Konzentration als in den anderen Gruppen. Die
mittlere Kortisolkonzentration der Gruppe P2 war p. i. im Vergleich zu denen der
übrigen Gruppen signifikant höher. TV2: Alle Gruppen wiesen im Vergleich zu
Gruppe H 30 Minuten p. c. einen signifikanten Anstieg der Kortisolkonzentration
auf. In Gruppe P2 wurde die höchste Kortisolkonzentration 60 Minuten p. c.
gemessen und der Anstieg der Kortisolkonzentration fiel im Vergleich zu den
restlichen Gruppen signifikant höher aus. In Gruppe L1 zeigte sich 60 Minuten p.
c. ein signifikant höherer Anstieg der CgA-Konzentration als in den anderen
Gruppen. Wundheilung, Körpergewicht und Verluste ließen keine signifikanten
Unterschiede zwischen den Gruppen erkennen.

Schlussfolgerung Die inguinale und skrotale Injektion von Procain 2 %
erzeugte eine höhere neuroendokrine Stressreaktion als die inguinale und
skrotale Applikation von Lidocain 5 % sowie die intratestikuläre Injektion von
Lidocain 1 %. Die LA mit Procain 2 % sowie Lidocain 1 % und 5 % führte zu keiner
vollständigen Schmerzausschaltung. Die Kastration unter LA mit Procain 2 %
verursachte eine höhere Schmerzreaktion als die betäubungslose Kastration. In
beiden Lidocaingruppen (L1, L5) traten nach Kastration tendenziell geringere
Schmerzreaktionen auf als in Gruppe K. Diese Ergebnisse bieten eine Grundlage
für weitere Untersuchungen und können Ansätze bieten, um Lokalanästhetika mit
höherer analgetischer Potenz längerer Wirksamkeit auf geeignete Weise zu
applizieren.
Therapeutische Möglichkeiten bei obstruktiver Urolithiasis
des kleinen Wiederkäuers
Authors: Sickinger Marlene
Published: April 2019

Die Diagnose der obstruktiven Urolithiasis beim kleinen Wiederkäuer stellt
behandelnde Tierärzte mitunter vor eine Vielzahl an Entscheidungen. Bei der Wahl
der bestmöglichen Therapie müssen sowohl die Nutzungsrichtung, ökonomische
Aspekte, die Möglichkeiten in der einzelnen Praxis als auch emotionale Aspekte
der Besitzer von Hobbytieren in die Entscheidung zur Therapie (oder Euthanasie)
einbezogen werden. Ziel dieses Artikels ist es, die prinzipiell vorhandenen
Therapieoptionen aufzuzeigen, um eine Behandlungsentscheidung auf Grundlage der
aktuellen Forschung zu ermöglichen. Die für den Einzelfall gewählte Methode kann
dabei selbstverständlich von der wissenschaftlich betrachteten bestmöglichen
Auswahl abweichen.
Melanose von Fettgewebe bei einem 17 Monate alten Stier der
Rasse Deutsches Fleckvieh (Bos taurus)
Authors: Breuer Wolfram , Hafner-Marx Angela , Sticklat Rebecca
Published: April 2019

Bei der fleischhygienischen Untersuchung eines 17 Monate alten Stiers (Deutsches
Fleckvieh) fiel eine ungleichmäßige Schwarzfärbung verschiedener Gewebe auf.
Besonders auffällig war das perirenale Fettgewebe. Die histopathologische
Untersuchung ermöglichte die Diagnose einer Melanose im Sinn einer kongenitalen
melanozytären Dystopie. Nach Kenntnis der Autoren ist die Melanose von
Fettgewebe beim Rind bislang nicht beschrieben worden. Ein Zusammenhang zwischen
Adipositas und Pigmentanomalie wird diskutiert.
Auswirkungen von Chlamydien auf
Rinderspermien
Authors: Schneider Florian
Published: April 2019

Eckert T, Goericke-Pesch S, Heydel C et al. Interaction of different Chlamydiae
species with bovine spermatozoa. BMC Microbiol 2019; 19: 23

Bei der Frau spielt die Chlamydieninfektion im Rahmen von
Fruchtbarkeitsstörungen eine wichtige Rolle. Auch beim weiblichen Nutztier
werden Reproduktionsstörungen mit Chlamydieninfektionen in Zusammenhang
gebracht. Erkenntnisse über die Beeinflussung der Fortpflanzung durch diese
Erreger beim männlichen Tier gibt es kaum. Die Studie untersuchte daher die
Auswirkung einer Chlamydieninfektion auf Rindersperma in vitro.
PRRSV: Risikofaktoren und Herdenprävalenz in
Deutschland
Authors: Ganz Sebastian
Published: April 2019

Nathues C, Janssen E, Duengelhoef A et al. Cross-sectional study on risk factors
for Porcine Reproductive and Respiratory Syndrome virus sow herd instability in
German breeding herds. Acta Vet Scand 2018; 60 (1): 1–8

In mit PRRSV (Porcine Reproductive and Respiratory Syndrom Virus) infizierten
Schweinebeständen zeigen die Tiere oftmals ernsthafte klinische Symptome.
Die Schwere der Symptomatik hängt von der Virulenz der jeweiligen
Virusstämme ab. Deshalb ist die Impfung gegen diesen Erreger sinnvoll und
wird empfohlen, auch wenn sie nicht immer klinische Fälle verhindert bzw.
das Virus vollends eliminiert. Aufgrund dessen rückt die Prävention durch
Verbesserung der innerbetrieblichen Abläufe zunehmend in den Fokus. Um
solche Maßnahmen erfolgreich etablieren zu können, ist es wichtig, den
epidemiologischen Status der Herde und mögliche Risikofaktoren zu kennen.
Ziel der Studie war deshalb, die Prävalenz der Infektion in Sauenbetrieben
in Norddeutschland zu eruieren und verschiedene Arbeitsabläufe hinsichtlich
des Risikos der Erregerverbreitung zu untersuchen.
Optimization of Whole-Body CT Examinations of Polytrauma Patients in Comparison with the Current Diagnostic Reference Levels
Authors: Schäfer Stefan B. , Rudolph Claudia , Kolodziej Martin , Mauermann Frank , Roller Fritz Christian , Krombach Gabriele Anja
Published: April 2019

Purpose Evaluation of the dose values of a polytrauma whole-body CT examination used in clinical practice with regard to the 2016 updated diagnostic reference levels and reduction of the mean exposure levels using simple optimization steps.

Materials and Methods In each case, 100 exposure values before and after dose optimization were compared with the old and new diagnostic reference levels. The grayscale values and the signal-to-noise ratio (SNR) were determined for the lung, the aortic arch and the liver. A visual assessment of the image quality was performed by two radiologists on the basis of a Likert scale (0 – non-diagnostic, 1 – poor visualization, 2 – moderate visualization, 3 – good visualization, 4 – excellent visualization) for CT examinations both before and after optimization.

Results The acquired exposure values after dose optimization were below the old and new diagnostic reference levels (1319.98 ± 463.16 mGy · cm) while the mean value of the exposure values before optimization (1774.96 ± 608.78 mGy · cm) exceeded the current diagnostic reference levels. The measured grayscale values (HU) were (before versus after optimization): lung – 833 HU vs. – 827 HU (p = 0.43), aortic arch 341 HU vs. 343 HU (p = 0.70) and liver 68 HU vs. 67 HU (p = 0.35). After dose optimization the SNR in the lung was minimally higher, while it was minimally lower in the two other regions than before the optimization. Visual assessment of the image quality showed almost identical values with 3.85 evaluation points before and 3.82 evaluation points after dose optimization (p = 0.57).

Conclusion Due to the updating of the diagnostic reference levels, an analysis of the own exposure values is necessary in order to be able to detect high values promptly and to initiate appropriate measures for dose reduction. Appropriate adaptation of the examination parameters with consideration of the necessary image quality allows a significant reduction of the radiation exposure in most cases, also on CT devices of older generations.

Key Points:

Citation Format
DBU-Catalyzed Michael Reaction of Enones with 1,3-Diketones and the Subsequent Iodine-Mediated Transformation of the Adducts to Polysubstituted Phenols
Authors: Miao Chun-Bao , Chen Mei-Ling , Sun Xiao-Qiang , Yang Hai-Tao
Published: April 2019

An efficient DBU-catalyzed Michael reaction of enones with 1,3-diketones has been developed for the gram-scale preparation of the Michael adducts. It is attractive that most of the adducts can be obtained with high purity through simple filtration. A convenient I2-mediated transformation of the adducts to polysubstituted phenols has also been exploited. This conversion is remarkable with the cyclization and aromatization processes by using DBU as the base and I2 as the oxidant. Furthermore, hydroxylated (E)-stilbene derivatives can be easily prepared by using this method. The readily available starting materials, metal-free and mild conditions make this approach simple and practical.
Fe-Catalyzed Bisphosphorylation of Amino-2-en-1-ones with Trialkyl Phosphites
Authors: Guo Shengmei , Jie Kun , Huang Ling , Zhang Zhebin , Wang Yufeng , Fu Zhengjiang , Cai Hu
Published: April 2019

A facile bisphosphorylation of amino-2-en-1-ones with trialkyl phosphites mediated by iron is developed. The reaction is considered to go through two Michael addition progresses. A variety of amino-2-en-1-ones are bisphosphorylated in high yields with functional group tolerance. In addition, the protocol of introduction of two different phosphates into one molecule is successful through a cascade reaction.
Oligodendroglioma with Sarcomatous Transformation: Case Report and Literature Review
Authors: Figueiredo Gonçalo Cerdeira , Pinheiro Célia Maria , Calheiros Alfredo Luís
Published: April 2019

Oligodendrogliomas are infiltrative tumors of the central nervous system considered to be morphologically stable and to offer a better prognosis. Here, we describe the case of a 36-year-old man with an initial diagnosis of oligodendroglioma, World Health Organization (WHO) grade II, who presented transformation to a sarcomatous form, while maintaining the oligodendroglial component as well as the genetic characteristics of the initial tumor without having undergone any complementary treatments previously. Despite the favorable genetic characteristics, the tumor presented poor response to complementary treatments, and rapid progression, including spinal metastasis.
The Lowering of Bilirubin Levels in Full-Term Newborns by the Effect of Combined Massage Therapy and Phototherapy Practice
Authors: Ahmadipour Shokoufeh , Mardani Mahnaz , Mohsenzadeh Azam , Baharvand Parastoo , Nazeri Mohammad Ghaed
Published: April 2019

Objective Various therapeutic treatments have been prescribed for decreasing the bilirubin level. Massage therapy is one of the neonate treatments for jaundice. The aim of this study is to investigate the effects of combined massage therapy and phototherapy on neonatal jaundice.

Study Design This study was performed at Shahid Madani Hospital in the city of Khorramabad in 2016, where 83 healthy full-term infants were enrolled. They were selected through convenience sampling and then were randomly assigned to the intervention and control groups. The control group (n = 43) received phototherapy, whereas infants in the intervention group (n = 40) received 4 days of massage and phototherapy. The serum bilirubin level, frequency of stooling and amount of urination, duration of hospitalization, and feeding frequency were analyzed using SPSS by descriptive and analytical statistics (mixed regression models).

Results Baseline levels of bilirubin were similar between the two groups (p > 0.05). The bilirubin level was measured as 13.4 ± 0.7 mg/dL in the intervention group on day 1. It stood at 14.4 ± 1.5 mg/dL in the control group, which was not statistically significantly different. However, the mean bilirubin level was decreased on day 4 of hospitalization to 7.4 ± 0.56 mg/dL and 9.0 ± 2.3 mg/dL, showing a significant difference decrease in the intervention and control group (p < 0.05), respectively.

Conclusion Intervention had a significant role in decreasing the bilirubin level, amount of urination, and duration of hospitalization of full-term infants suffering from hyperbilirubinemia.
Terahertz monolithic integrated waveguide transmission lines based on wide bandgap semiconductor materials
Authors: Li Yang , Ma Xiao-Hua , Yang Lin-An , Ao Jin-Ping , Hao Yue
Published: April 2019

In this paper, terahertz monolithic integrated waveguide (TMIW) transmission lines (TLs) are analyzed and fabricated based on wide bandgap semiconductor materials. The ignored parameters of TLs at low frequencies, such as the via-hole shape, the titanium/gold thickness and roughness, and the micropipe effect of material, are especially investigated based on the semiconductor fabrication technique and the terahertz-wave theory. Subsequently, the fine optimized TMIW-TL and the transition to grounded coplanar waveguide are fabricated. The measurement shows that the attenuation constant of a TL is as low as 0.19 dB/λg at 220 GHz. The proposed TMIW can provide electrical performance similar to the conventional air-filled waveguide, while it has only 10% of the volume, which indicates a great potential for future terahertz integrated systems.
Monolithic integration of transition metal oxide multiple quantum wells on silicon (001)
Authors: Ortmann J. Elliott , Kwon Sunah , Posadas Agham B. , Kim Moon J. , Demkov Alexander A.
Published: April 2019

The SrTiO3/LaAlO3 (STO/LAO) system has been the subject of intense research efforts since the discovery of a two-dimensional electron gas at the interface of these two band insulators. However, recent reports have focused on the system's optical properties arising from the huge 2.4 eV conduction band offset between STO and LAO and the ability to confine charge carriers in STO quantum wells. While the STO/LAO system shows promise for use in a variety of next-generation optical and electro-optical devices, the technological compatibility of such devices relies in large part on the successful integration of high-quality STO/LAO quantum structures on silicon. In this report, we demonstrate the monolithic integration of STO/LAO multiple quantum wells on silicon (001) with molecular beam epitaxy. Our electron diffraction, X-ray diffraction, and electron microscopy results indicate the excellent crystalline quality with which these heterostructures can be fabricated. We consider the correlated strain and thermal mechanisms at play in our heterostructures and how they contribute to heterostructure growth. Furthermore, we discuss general considerations for the deposition of other complex transition metal oxide heterostructures on silicon. Our results support the potential for STO/LAO quantum structures to find use in next-generation optical devices, including integrated sensors, light sources, and photonics.
Poly-Si/SiOx/c-Si passivating contact with 738 mV implied open circuit voltage fabricated by hot-wire chemical vapor deposition
Authors: Li Shenghao , Pomaska Manuel , Hoß Jan , Lossen Jan , Pennartz Frank , Nuys Maurice , Hong Ruijiang , Schmalen Andreas , Wolff Johannes , Finger Friedhelm , Rau Uwe , Ding Kaining
Published: April 2019

Hot-wire chemical vapor deposition (HWCVD) was utilized to develop a fast and high quality a-Si:H thin film fabrication method for poly-Si/SiOx carrier selective passivating contacts targeting at n-type passivated emitter rear totally diffused crystalline silicon solar cells. The microstructure and hydrogen content of the a-Si:H thin films were analyzed by Fourier-transform infrared spectroscopy in order to understand the influence of film properties on passivation and conductivity. Dense layers were found to be beneficial for good passivation. On the other hand, blistering appeared as a-Si:H layers became more and more dense. However, by adjusting the SiH4 flow rate and the substrate heater temperature, blistering of a-Si:H could be avoided. A suitable process window was found and firing-stable implied open circuit voltage (iVoc) of up to 738 mV was achieved. In addition to high iVoc, a low contact resistivity of 0.034 Ω cm2 was also achieved. The deposition rate of the a-Si:H layers was 7 Å/s by using HWCVD, which is one order of magnitude higher than the deposition rate reported using other deposition methods.
MIS-TSC: A combination of the thermally stimulated current method and a metal-insulator-semiconductor device for unipolar trap spectroscopy
Authors: Rojek Karsten , Schmechel Roland , Benson Niels
Published: April 2019

To determine the density of states distribution of traps within a semiconductor, the thermally stimulated current (TSC) method is often applied. However, the bipolar nature of the typical device structure does not allow for strict unipolar operation, and therefore the method does not allow for the separate evaluation of electron and hole traps. The recombination between electrons and holes makes the interpretation of the data difficult, which becomes an essential drawback of this method. To address these issues, we propose the use of a metal insulator semiconductor (MIS) device structure for TSC measurements, which can be operated strictly unipolar by the sign of the applied voltage during the charging process. Thus, the problem of recombination and bipolar contribution to the measurement signal is avoided. As an additional benefit, the MIS device structure typically results in very low leakage currents, and thus a low noise level for the measurement. This permits precise measurements even below 1 pA, and consequently increases the resolution of the method. This aspect is especially important for fractional TSC, as the measurement time is long and the current low when compared to the envelope measurement. Here, we demonstrate the basic principle of this TSC approach, which we name MIS-TSC, using the well-studied organic semiconductor P3HT as a benchmark.
Non-empirical, low-cost recovery of exact conditions with model-Hamiltonian inspired expressions in jmDFT
Authors: Bajaj Akash , Liu Fang , Kulik Heather J.
Published: April 2019

Density functional theory (DFT) is widely applied to both molecules and materials, but well known energetic delocalization and static correlation errors in practical exchange-correlation approximations limit quantitative accuracy. Common methods that correct energetic delocalization errors, such as the Hubbard U correction in DFT+U or Hartree-Fock exchange in global hybrids, do so at the cost of worsening static correlation errors. We recently introduced an alternate approach [Bajaj et al., J. Chem. Phys. 147, 191101 (2017)] known as judiciously modified DFT (jmDFT), wherein the deviation from exact behavior of semilocal functionals over both fractional spin and charge, i.e., the so-called flat plane, was used to motivate functional forms of second order analytic corrections. In this work, we introduce fully nonempirical expressions for all four coefficients in a DFT+U+J-inspired form of jmDFT, where all coefficients are obtained only from energies and eigenvalues of the integer-electron systems. We show good agreement for U and J coefficients obtained nonempirically as compared with the results of numerical fitting in a jmDFT U+J/J′ correction. Incorporating the fully nonempirical jmDFT correction reduces and even eliminates the fractional spin error at the same time as eliminating the energetic delocalization error. We show that this approach extends beyond s-electron systems to higher angular momentum cases including p- and d-electrons. Finally, we diagnose some shortcomings of the current jmDFT approach that limit its ability to improve upon DFT results for cases such as weakly bound anions due to poor underlying semilocal functional behavior.
Theoretical design of coupled high contrast grating (CHCG) waveguides to enhance CO2 light-absorption for gas sensing applications
Authors: Hemati Tahere , Weng Binbin
Published: April 2019

In this work, we present a theoretical study on using high contrast grating (HCG) designs to enhance light–gas interaction in the mid-infrared range. The optical behavior of a single layer HCG was studied under the presence of CO2 gas. Through optimizing the structure parameters, we could confine an intense electric field over the grating layer. Consequently, about 200 times of light-absorption enhancement was observed. To further improve the performance, a coupled HCG (CHCG) was proposed to introduce another vertical photonic confinement mechanism. We found that CHCG can restrict much intense light energy in the structure leading to over 600 times of light-absorption enhancement. However, it is noticed that a significant part of the concentrated electric field was still trapped in the high index areas, where the gas cannot interact. To address this issue, a modified CHCG with a thin substrate thickness was proposed. Through the optimization (T=1.149μm), we were able to redistribute most of the light energy into the void space of the CHCG layer which resulted in close to 1400 times of improvement. This work clearly demonstrates that using HCG for enhancing light–gas interaction is a promising approach to make on-chip gas sensing devices. Furthermore, it can also be integrated into other photonic components, e.g., fibers for advanced sensing system development.
Distribution patterns of east Australian humpback whales (Megaptera novaeangliae) in Hervey Bay, Queensland: a historical perspective
Authors: Stack S. H. , Currie J. J. , McCordic J. A. , Machernis A. F. , Olson G. L.
Published: April 2019

Tourism activities are expanding in both terrestrial and marine environments, which can have detrimental effects on the target species. Balancing the amount of disturbance a population of animals receives against the educational value of tourism requires localised research and adaptive management. This study examined the distribution of humpback whales within Hervey Bay, Queensland, using data spanning 2004–16, just before the implementation of a commercial ‘swim-with-whales’ program. Spatial and temporal patterns of humpback whale calves were of particular interest given that they are more vulnerable to human-related disturbances than other group types. We found that humpback whales displayed a distinct spatial segregation in Hervey Bay based on pod composition. Most whales displayed a residency time of two to three days, with females having a somewhat shorter residency time than males. These findings suggest that humpback whales in Hervey Bay not only display temporal segregation dependent on maturation and reproductive status, but fine-scale spatial distribution based on pod composition. Understanding habitat preference and patterns of habitat use of humpback whales in Hervey Bay is critical for effective management of the newly sanctioned swim-with-whale tourism in Hervey Bay and the sustained recovery of humpback whales in this region.
Insights into the global emergence of antifungal drug resistance
Authors: Boyce Kylie , Morrissey Orla , Idnurm Alexander , Macreadie Ian
Published: April 2019

The global prevalence of fungal diseases has escalated in the last several decades. Currently, it is estimated that fungi infect 1.7 billion people annually and result in 1.5 million deaths every year1. Deaths due to fungal infections are increasing, with mortality often exceeding 50%, further increasing to 100% if treatment is delayed1. Despite these staggering figures, the contribution of fungal infections to the global burden of disease remains under-recognised. In Australia, over a 5-year period fungal infections cost Australia an estimated $583 million2. The median cost for one invasive fungal disease (IFD) is AU$30957, increasing to AU$80291 if the patient is admitted to an intensive care unit3. Treatment of fungal infections poses significant challenges due to the small number of safe and effective antifungal drugs available and emerging antifungal drug resistance. Resistance to every class of antifungal drugs has been described and for some drug classes is extremely common4,5.
Laser ablation–accelerator mass spectrometry reveals complete bomb 14C signal in an otolith with confirmation of 60-year longevity for red snapper (Lutjanus campechanus)
Authors: Andrews Allen H. , Yeman Christiane , Welte Caroline , Hattendorf Bodo , Wacker Lukas , Christl Marcus
Published: April 2019

Bomb-produced 14C has been used to make valid estimates of age for various marine organisms for 25 years, but fish ages that lead to birth years earlier than the period of increase in 14C lose their time specificity. As a result, bomb 14C dating is limited to a minimum age from the last year of prebomb levels because the temporal variation in 14C in the marine surface layer is negligible for decades before c. 1958. The longevity of red snapper (Lutjanus campechanus) in the Gulf of Mexico remains unresolved despite various forms of support for ages near 50–60 years. Although the age and growth of red snapper have been verified or validated to a limited extent, some scepticism remains about longevity estimates that exceed 30 years. In this study, red snapper otoliths were analysed for 14C using a novel laser ablation–accelerator mass spectrometry technique to provide a continuous record of 14C uptake. This approach provided a basis for age validation that extends beyond the normal limits of bomb 14C dating with confirmation of a 60-year longevity for red snapper in the Gulf of Mexico.
Phase-conjugate mirror for water waves driven by the Faraday instability
Authors: Bacot Vincent , Durey Guillaume , Eddi Antonin , Fink Mathias , Fort Emmanuel
Published: April 2019

Significance

Nonlinear and parametric processes are central in mastering wave propagation. They are at the core of numerous applications in optics and acoustics. In the case of water waves, the Faraday instability is the archetype of a parametric excitation. A periodic vertical excitation results in the destabilization of a liquid interface. However, it has always been interpreted as an instability, completely overshadowing its potential to control water-wave propagation. In this paper, we unveil the ability of this temporal modulation to act as a phase-conjugate mirror. We show that waves refocus to any initial emitting source position, whatever the shape of the mirror. This paper thus revisits this historical instability and opens up exciting perspectives in water-wave manipulation.
Structural insights into RNA recognition by the Chikungunya virus nsP2 helicase
Authors: Law Yee-Song , Utt Age , Tan Yaw Bia , Zheng Jie , Wang Sainan , Chen Ming Wei , Griffin Patrick R. , Merits Andres , Luo Dahai
Published: April 2019

Chikungunya virus (CHIKV) is transmitted to humans through mosquitoes and causes Chikungunya fever. Nonstructural protein 2 (nsP2) exhibits the protease and RNA helicase activities that are required for viral RNA replication and transcription. Unlike for the C-terminal protease, the structure of the N-terminal RNA helicase (nsP2h) has not been determined. Here, we report the crystal structure of the nsP2h bound to the conserved 3′-end 14 nucleotides of the CHIKV genome and the nonhydrolyzable transition-state nucleotide analog ADP-AlF
4
. Overall, the structural analysis revealed that nsP2h adopts a uniquely folded N-terminal domain followed by a superfamily 1 RNA helicase fold. The conserved helicase motifs establish polar contacts with the RNA backbone. There are three hydrophobic residues (Y161, F164, and F287) which form stacking interactions with RNA bases and thereby bend the RNA backbone. An F287A substitution that disrupted these stacking interactions increased the basal ATPase activity but decreased the RNA binding affinity. Furthermore, the F287A substitution reduced viral infectivity by attenuating subgenomic RNA synthesis. Replication of the mutant virus was restored by pseudoreversion (A287V) or adaptive mutations in the RecA2 helicase domain (T358S or V410I). Y161A and/or F164A substitutions, which were designed to disrupt the interactions with the RNA molecule, did not affect the ATPase activity but completely abolished the replication and transcription of viral RNA and the infectivity of CHIKV. Our study sheds light on the roles of the RNA helicase region in viral replication and provides insights that might be applicable to alphaviruses and other RNA viruses in general.
Exaggeration and cooption of innate immunity for social defense
Authors: Kutsukake Mayako , Moriyama Minoru , Shigenobu Shuji , Meng Xian-Ying , Nikoh Naruo , Noda Chiyo , Kobayashi Satoru , Fukatsu Takema
Published: April 2019

Social insects often exhibit striking altruistic behaviors, of which the most spectacular ones may be self-destructive defensive behaviors called autothysis, “self-explosion,” or “suicidal bombing.” In the social aphid
Nipponaphis monzeni
, when enemies damage their plant-made nest called the gall, soldier nymphs erupt to discharge a large amount of body fluid, mix the secretion with their legs, and skillfully plaster it over the plant injury. Dozens of soldiers come out, erupt, mix, and plaster, and the gall breach is promptly sealed with the coagulated body fluid. What molecular and cellular mechanisms underlie the self-sacrificing nest repair with body fluid for the insect society? Here we demonstrate that the body cavity of soldier nymphs is full of highly differentiated large hemocytes that contain huge amounts of lipid droplets and phenoloxidase (PO), whereas their hemolymph accumulates huge amounts of tyrosine and a unique repeat-containing protein (RCP). Upon breakage of the gall, soldiers gather around the breach and massively discharge the body fluid. The large hemocytes rupture and release lipid droplets, which promptly form a lipidic clot, and, concurrently, activated PO converts tyrosine to reactive quinones, which cross-link RCP and other macromolecules to physically reinforce the clot to seal the gall breach. Here, soldiers’ humoral and cellular immune mechanisms for wound sealing are extremely up-regulated and utilized for colony defense, which provides a striking case of direct evolutionary connection between individual immunity and social immunity and highlights the importance of exaggeration and cooption of preexisting traits to create evolutionary novelties.
Phase 1 repolarization rate defines Ca2+ dynamics and contractility on intact mouse hearts
Authors: López Alarcón María Micaela , Rodríguez de Yurre Ainhoa , Felice Juan Ignacio , Medei Emiliano , Escobar Ariel L.
Published: April 2019

In the heart, Ca2+ influx through L-type Ca2+ channels triggers Ca2+ release from the sarcoplasmic reticulum. In most mammals, this influx occurs during the ventricular action potential (AP) plateau phase 2. However, in murine models, the influx through L-type Ca2+ channels happens in early repolarizing phase 1. The aim of this work is to assess if changes in the open probability of 4-aminopyridine (4-AP)–sensitive Kv channels defining the outward K+ current during phase 1 can modulate Ca2+ currents, Ca2+ transients, and systolic pressure during the cardiac cycle in intact perfused beating hearts. Pulsed local-field fluorescence microscopy and loose-patch photolysis were used to test the hypothesis that a decrease in a transient K+ current (Ito) will enhance Ca2+ influx and promote a larger Ca2+ transient. Simultaneous recordings of Ca2+ transients and APs by pulsed local-field fluorescence microscopy and loose-patch photolysis showed that a reduction in the phase 1 repolarization rate increases the amplitude of Ca2+ transients due to an increase in Ca2+ influx through L-type Ca2+ channels. Moreover, 4-AP induced an increase in the time required for AP to reach 30% repolarization, and the amplitude of Ca2+ transients was larger in epicardium than endocardium. On the other hand, the activation of Ito with NS5806 resulted in a reduction of Ca2+ current amplitude that led to a reduction of the amplitude of Ca2+ transients. Finally, the 4-AP effect on AP phase 1 was significantly smaller when the L-type Ca2+ current was partially blocked with nifedipine, indicating that the phase 1 rate of repolarization is defined by the competition between an outward K+ current and an inward Ca2+ current.
Cutaneous perfusion of the human lactating breast: a pilot study with laser Doppler perfusion monitoring
Authors: van der Hoek Miriam , den Haan Lya , Kaspers Ageeth , Steenbergen Wiendelt , Bosschaart Nienke
Published: April 2019

Objective: Knowledge on the hemodynamics of the human lactating breast contributes to our understanding of lactation physiology, as well as the development and management of breastfeeding problems. The objective of this pilot study was to investigate whether laser Doppler perfusion monitoring (LDPM) can be employed to measure physiological changes in mammary cutaneous perfusion during milk extraction. Approach: We evaluated mammary cutaneous perfusion with LDPM in nine lactating women during milk extraction in both the ipsilateral (‘milk extracting’) and contralateral (‘passive’) breast. Fourier domain filtering of the LDPM signal was applied to correct for the influence of the periodic tissue movement caused by the breast pump. Main results: Cutaneous perfusion increased temporary during 23.7  ±  18.9 s by 18%–74% for all women who sensed their milk ejection reflex (n  =  6) in both the ipsilateral and contralateral breast. For those women who did not sense a milk ejection reflex (n  =  3), the changes in cutaneous perfusion were less outspoken (maximally 26%). Significance: This pilot study provides new insights into mammary hemodynamics and demonstrates that LDPM is a promising method for the further investigation of physiological changes in mammary cutaneous perfusion during milk ejection. Objective feedback on the occurrence and progression of milk ejection can support lactation research in general, maternal breastfeeding confidence, and may be an early indicator for the development of breastfeeding problems.
Magnetism and magneto-optical effects in bulk and few-layer CrI3: a theoretical GGA + U study
Authors: Kumar Gudelli Vijay , Guo Guang-Yu
Published: April 2019

The latest discovery of ferromagnetism in atomically thin films of semiconductors Cr2Ge2Te6 and CrI3 has unleashed numerous opportunities for fundamental physics of magnetism in two-dimensional (2D) limit and also for technological applications based on 2D magnetic materials. To exploit these 2D magnetic materials, however, the mechanisms that control their physical properties should be thoroughly understood. In this paper, we present a comprehensive theoretical study of the magnetic, electronic, optical and magneto-optical (MO) properties of multilayers (monolayer (ML), bilayer (BL) and trilayer) as well as bulk CrI3, based on the density functional theory with the generalized gradient approximation plus on-site Coulomb repulsion scheme. Interestingly, all the structures except the BL, are found to be single-spin ferromagnetic semiconductors. They all have a large out-of-plane magnetic anisotropy energy (MAE) of ∼0.5 meV/Cr, in contrast to the significantly thickness-dependent MAE in multilayers of Cr2Ge2Te6. These large MAEs suppress transverse spin fluctuations and thus stabilize long-range magnetic orders at finite temperatures down to the ML limit. They also exhibit strong MO effects with their Kerr and Faraday rotation angles being comparable to that of best-known bulk MO materials. The shape and position of the main features in the optical and MO spectra are found to be nearly thickness-independent although the magnitude of Kerr rotation angles increases monotonically with the film thickness. Magnetic transition temperatures estimated based on calculated exchange coupling parameters, calculated optical conductivity spectra, MO Kerr and Faraday rotation angles agree quite well with available experimental data. The calculated MAE as well as optical and MO properties are analyzed in terms of the calculated orbital-decomposed densities of states, band state symmetries and dipole selection rules. Our findings of large out-of-plane MAEs and strong MO effects in these single-spin ferromagnetic semiconducting CrI3 ultrathin films suggest that they will find valuable applications in semiconductor MO and spintronic nanodevices.
Mechanistic and experimental models of cell migration reveal the importance of cell-to-cell pushing in cell invasion
Authors: Matsiaka Oleksii M , Baker Ruth E , Shah Esha T , Simpson Matthew J
Published: April 2019

Moving fronts of cells are essential for development, repair and disease progression. Therefore, understanding and quantifying the details of the mechanisms that drive the movement of cell fronts is of wide interest. Quantitatively identifying the role of intercellular interactions, and in particular the role of cell pushing, remains an open question. In this work, we report a combined experimental-modelling approach showing that intercellular interactions contribute significantly to the spatial spreading of a population of cells. We use a novel experimental data set with PC-3 prostate cancer cells that have been pretreated with Mitomycin-C to suppress proliferation. This allows us to experimentally separate the effects of cell migration from cell proliferation, thereby enabling us to focus on the migration process in detail as the population of cells recolonizes an initially-vacant region in a series of two-dimensional experiments. We quantitatively model the experiments using a stochastic modelling framework, based on Langevin dynamics, which explicitly incorporates random motility and various intercellular forces including: (i) long range attraction (adhesion); and (ii) finite size effects that drive short range repulsion (pushing). Quantitatively comparing the ability of this model to describe the experimentally observed population-level behaviour provides us with quantitative insight into the roles of random motility and intercellular interactions. To quantify the mechanisms at play, we calibrate the stochastic model to match experimental cell density profiles to obtain estimates of cell diffusivity, D, and the amplitude of intercellular forces, f
0. Our analysis shows that taking a standard modelling approach which ignores intercellular forces provides a poor match to the experimental data whereas incorporating intercellular forces, including short-range pushing and longer range attraction, leads to a faithful representation of the experimental observations. These results demonstrate a significant role of cell pushing during cell front movement and invasion.
Association Between Speed of Multimorbidity Accumulation in Old Age and Life Experiences: A Cohort Study
Authors: Dekhtyar Serhiy , Vetrano Davide Liborio , Marengoni Alessandra , Wang Hui-Xin , Pan Kuan-Yu , Fratiglioni Laura , Calderón-Larrañaga Amaia
Published: April 2019

Rapidly accumulating multiple chronic conditions (multimorbidity) during aging are associated with many adverse outcomes. We explored the association between 4 experiences throughout life—childhood socioeconomic circumstances, early-adulthood education, midlife occupational stress, and late-life social network—and the speed of chronic disease accumulation. We followed 2,589 individuals aged ≥60 years from the Swedish National Study on Aging and Care in Kungsholmen for 9 years (2001–2013). Information on life experiences was collected from detailed life-history interviews. Speed of disease accumulation was operationalized as the change in the count of chronic conditions obtained from clinical examinations, medical histories, laboratory data, drug use, and register linkages over 9 years. Linear mixed models were used to analyze the data. Speed of disease accumulation was lower in individuals with more than elementary education (for secondary, β × time = −0.065, 95% CI: −0.126, −0.004; for university, β × time = −0.118, 95% CI: −0.185, −0.050); for active occupations compared with high-strain jobs (β × time = −0.078, 95% CI: −0.138, −0.017); and for richer social networks (for moderate tertile, β × time = −0.102, 95% CI: −0.149, −0.055; for highest tertile, β × time = −0.135, 95% CI: −0.182, −0.088). The association between childhood circumstances and speed of disease accumulation was attenuated by later-life experiences. Diverse experiences throughout life might decelerate chronic disease accumulation during aging.
LAmbDA: label ambiguous domain adaptation dataset integration reduces batch effects and improves subtype detection
Authors: Johnson Travis S , Wang Tongxin , Huang Zhi , Yu Christina Y , Wu Yi , Han Yatong , Zhang Yan , Huang Kun , Zhang Jie
Published: April 2019

Motivation

Rapid advances in single cell RNA sequencing (scRNA-seq) have produced higher-resolution cellular subtypes in multiple tissues and species. Methods are increasingly needed across datasets and species to (i) remove systematic biases, (ii) model multiple datasets with ambiguous labels and (iii) classify cells and map cell type labels. However, most methods only address one of these problems on broad cell types or simulated data using a single model type. It is also important to address higher-resolution cellular subtypes, subtype labels from multiple datasets, models trained on multiple datasets simultaneously and generalizability beyond a single model type.

Results

We developed a species- and dataset-independent transfer learning framework (LAmbDA) to train models on multiple datasets (even from different species) and applied our framework on simulated, pancreas and brain scRNA-seq experiments. These models mapped corresponding cell types between datasets with inconsistent cell subtype labels while simultaneously reducing batch effects. We achieved high accuracy in labeling cellular subtypes (weighted accuracy simulated 1 datasets: 90%; simulated 2 datasets: 94%; pancreas datasets: 88% and brain datasets: 66%) using LAmbDA Feedforward 1 Layer Neural Network with bagging. This method achieved higher weighted accuracy in labeling cellular subtypes than two other state-of-the-art methods, scmap and CaSTLe in brain (66% versus 60% and 32%). Furthermore, it achieved better performance in correctly predicting ambiguous cellular subtype labels across datasets in 88% of test cases compared with CaSTLe (63%), scmap (50%) and MetaNeighbor (50%). LAmbDA is model- and dataset-independent and generalizable to diverse data types representing an advance in biocomputing.

Availability and implementation

github.com/tsteelejohnson91/LAmbDA

Supplementary information

Supplementary data are available at Bioinformatics online.
The incorporation of cystine by the soluble carrier family 7 member 11 (SLC7A11) is a component of the redox regulatory mechanism in stallion spermatozoa†
Authors: Ortiz-Rodriguez José Manuel , Martín-Cano Francisco E , Ortega-Ferrusola Cristina , Masot Javier , Redondo Eloy , Gázquez Antonio , Gil María C , Aparicio Inés M , Rojo-Domínguez Patricia , Tapia José A , Rodriguez-Martínez Heriberto , Peña Fernando J
Published: April 2019

Oxidative stress is considered a major mechanism causing sperm damage during cryopreservation and storage, and underlies male factor infertility. Currently, oxidative stress is no longer believed to be caused only by the overproduction of reactive oxygen species, but rather by the deregulation of redox signaling and control mechanisms. With this concept in mind, here, we describe for the first time the presence of the soluble carrier family 7 member 11 (SLC7A11) antiporter, which exchanges extracellular cystine (Cyss) for intracellular glutamate, in stallion spermatozoa, as well as its impact on sperm function using the specific inhibitor sulfasalazine. Spermatozoa incubated with Cyss exhibited an increased intracellular GSH content compared with controls (P < 0.01): 50% in fresh extended stallion spermatozoa and 30% in frozen-thawed spermatozoa. This effect was prevented by the addition of sulfasalazine to the media. Cystine supplementation also reduced the oxidation–reduction potential of spermatozoa, with sulfasalazine only preventing this effect on fresh spermatozoa that were incubated for 3 h at 37°C, but not in frozen-thawed spermatozoa. While sulfasalazine reduced the motility of frozen-thawed spermatozoa, it increased motility in fresh samples. The present findings provide new and relevant data on the mechanism regulating the redox status of spermatozoa and suggest that a different redox regulatory mechanism exists in cryopreserved spermatozoa, thus providing new clues to improve current cryopreservation technologies and treat male factor infertility.