bluuebunny/crossref_metadata_2025 huggingface dataset:
Kompositionspräparate für die Wirbelsäule
Authors: Roemer Franziska
Published: June 2018

Die Firma Wala Heilmittel GmbH hat eine Gruppe von anthroposophischen Präparaten entwickelt, die bei verschiedenen Wirbelsäulenbeschwerden indiziert sind.
Von der Funktion zur Konstitution
Authors: Schünemann Michael
Published: June 2018

Synergone der Firma Kattwiga zielen auf die Behandlung von Funktionsstörungen ab – und berücksichtigen dabei auch konstitutionelle Aspekte.
Isolierte Extremitätenperfusion zur lokalen Therapie: Echtzeit-Leckkontrolle mittels radioaktiv markierter Blutbestandteile
Authors: Schnorr Jürgen , Dresel Stefan
Published: June 2018

Die quantitative Leckkontrolle in Echtzeit ist während der isolierten Extremitätenperfusion mit hochdosierten Zytokinen und Chemotherapeutika bei lokal fortgeschrittenen Weichteilsarkomen und metastasierten malignen Melanomen notwendig, um unerwünschte systemische Nebenwirkungen zu vermeiden. Hierzu messen über dem Herzen und dem extrakoporalen Kreislauf positionierte Szintillationssonden die Verteilung der 111In-markierten Erythrozyten. Aus diesen zyklischen Messungen wird die Leckrate ermittelt. Die Anzeige des quantitativen Volumenübertritts ab Zytostatikagabe ist die Basis für alle weiteren eventuell notwendigen Eingriffe während der Perfusion.
A Novel c.125 T>G (p.Val42Gly) Mutation in The Human
INS Gene Leads to Neonatal Diabetes Mellitus via a Decrease in Insulin
Synthesis
Authors: Sun Fei , Du Wenhua , Ma Junhua , Gu Mingjun , Wang Jingnan , Zhu Hongling , Song Huaidong , Gao Guanqi
Published: June 2018

Background Neonatal diabetes mellitus is likely caused by monogenic
mutations, several of which have been identified. INS mutations have a broad
spectrum of clinical presentations, ranging from severe neonatal onset to
mild adult onset, which suggests that the products of different mutant INS
alleles behave differently and utilize distinct mechanisms to induce
diabetes. In this study, a neonatal diabetes mellitus patient’s INS
gene was sequenced, and functional experiments were conducted.

Methods The neonatal diabetes mellitus patient’s genomic DNA
was extracted, and the patient’s KCNJ11, ABCC8, and INS genes were
sequenced. A novel mutation was identified in INS, and the open reading
frame of this human mutant INS gene was inserted into the pMSCV-PIG plasmid.
The constructed pMSCV-PIG plasmid was combined with VSV-g and Gag-pol and
transfected into 293T cells to package the lentivirus. To stably overexpress
the mutant gene, INS-1 cells were infected with the virus. The levels of
insulin in the cell culture medium and cytoplasm were determined by ELISA
and immunocytochemistry, respectively.

Results A heterozygous mutation, c.125T>G (p. Val42Gly), was
identified in a neonatal diabetes mellitus patient’s INS gene. The
human mutant INS open reading frame was overexpressed in INS-1 cells, and
the mutant insulin was undetectable in the cell culture medium and
cytoplasm.

Conclusions The novel heterozygous activating mutation
c.125 T>G (p.Val42Gly) impairs the synthesis of insulin by
pancreatic beta cells, resulting in diabetes.
Pulmonary co-infection with nocardia species and nontuberculous mycobacteria mimicking miliary tuberculosis in a patient with Crohn’s disease under combined immunosuppressive therapy
Authors: Weber Marko , Rüddel Jessica , Bruns Tony , Pletz Mathias , Stallmach Andreas
Published: June 2018

Nocardiosis is a rare infection caused by ubiquitous soil-born, acid-resistant, Gram-positive bacteria that can be life-threatening in immunocompromised patients. Originally usually diagnosed in HIV-positive patients, only few cases have been reported in patients on immunosuppressive therapy for inflammatory bowel disease or rheumatologic disorders. We present a case of a 32-year-old man who was treated with infliximab, prednisolone, and azathioprine for severe terminal ileitis. Although the clinical status improved under triple immunosuppressive therapy, weight loss, weakness, and fatigue persisted. Laboratory studies revealed iron deficiency anemia, hypalbuminemia and raised inflammatory markers. Chest computed tomography scan showed multiple pulmonary nodules and a large cavity in the left upper lobe (segment 3a). Empiric tuberculostatic therapy was introduced for suspected miliary tuberculosis but stopped for lack of clinical improvement and negative tuberculosis tests (interferon-gamma release assay, microscopy, polymerase chain reaction). Finally, the diagnosis of pulmonary nocardiosis with concomitant pulmonary Mycobacterium avium infection was confirmed microbiologically, and the patient was treated with high-dose co-trimoxazole, clarithromycin, ethambutol, and rifampicin for 12 months.

This case report underlines the increased risk of severe and rare infections like nocardiosis with combination immunosuppressive therapy and the necessity for thorough diagnostic screening for opportunistic infection. Although long-term antibiotic treatment for nocardiosis is mandatory, the optimal timing to restart immunosuppressive therapy remains ambiguous.
Chronisch entzündliche Gelenkerkrankungen – ergotherapeutische Grundlagen für die Behandlung
Authors: Bitzer Susanne
Published: June 2018

Die Therapie entzündlicher rheumatischer Erkrankungen hat in den letzten Jahrzehnten enorme Fortschritte gemacht, auch das ergotherapeutische Konzept wurde verändert und angepasst. Im Vordergrund der Ergotherapie stehen ein aktives Übungsprogramm, passive Techniken, physikalische und thermische Anwendungen, Gelenkschule sowie die Beratung und Erprobung von Hilfsmitteln.

Die Autorin stellt das ergotherapeutische Vorgehen von der Befunderhebung über die Festlegung der Behandlungsziele bis zur therapeutischen Praxis am Beispiel der Hand vor.
Synthesis of Novel tricyclic pyrazolo(1,4)oxathiinopyrazines and Evaluation of Their Competency Towards the Inhibition of Lactate Dehydrogenase Activity-Inhibition of LDH Activity
Authors: Mukherjee Prasun , Das Asish , Mishra Raghwendra , Bhowmick Shovonlal , Saha Achintya
Published: June 2018

We have evaluated the LDH inhibitory property of novel pyrazolo[4′,3′:5,6][1,4]oxathiino[2,3-b]pyrazine derivatives which have been synthesized from easily available starting materials through a one-pot protocol that offers the use of elemental sulfur as the sulfur source. These newly synthesized compounds may aid to drug development for neoplastic and non-neoplastic diseases characterized by increased glucose metabolism. Additionally, they may act as suitable starting materials which can be further structurally modified for the development of new LDH inhibitors with higher efficacy and specificity.
Entzündliche Gelenkerkrankungen neuraltherapeutisch behandeln
Authors: Günter Uwe
Published: June 2018

Die Synovialitis ist sonographisch und histologisch als vermehrte Infiltration von Fibroblasten-ähnlichen Synoviozyten erkennbar, mit fakultativem Erguss. Am häufigsten findet man neben rheumatischen Erkrankungen an kleinen Gelenken eine Gonitis bzw. Gonarthritis reaktiver bzw. infektassoziierter Genese. Diverse Risiken werden diskutiert und weisen auf unterschiedliche Pathogenesen innerhalb des Neuro-Endokrino-Immunsystems hin.

Neben der Sympathikus-induzierten Arthritis unterhalten Antigen-Antikörper-Reaktionen bei teilweiser nachgewiesener Individualität der präsentierten Oberflächenstrukturen des Immunzellsystems die synovialen Befunde. Degenerativ induzierte Matrix-Metalloproteinasen provozieren auch proinflammatorische Zytokine sowie deren Gegenregulatoren.

Die neuraltherapeutische Behandlung kann mit immunmodulativ wirkenden Lokalanästhetika in vielen Fällen die Beschwerden lindern. Im Artikel wird ein Ausblick auf wichtige Injektionstechniken gegeben.
Klotho Restraining Egr1/TLR4/mTOR Axis to Reducing the Expression of Fibrosis and Inflammatory Cytokines in High Glucose Cultured Rat Mesangial Cells
Authors: Wu Can , Ma Xiaoyu , Zhou Yang , Liu Yv , Shao Ying , Wang Qiuyue
Published: June 2018

Anti-aging protein Klotho is closely associated with a variety of chronic diseases and age-related diseases. And Klotho gene deficiency enhances the phosphorylation of mammalian target of rapamycin (mTOR), resulting in exacerbating streptozotocin-stimulated diabetic glomerular injury and promoting the progression of early diabetic kidney disease (DKD). However, it has not yet been elucidated that the mechanism of Klotho function on the pathogenesis of diabetic glomerular injury. What’s more, insulin represents the antilipolytic effect via the mTOR-early growth response factor 1 (Egr1) regulatory axis in mammalian organism. Valsartan reduced the high glucose-activated toll like report 4 (TLR4) expression and inflammatory cytokines via inhibiting Egr1 expression. In this study, we aim to explore the effects of Klotho on Egr1 expression and TLR4/mTOR pathways activity in high glucose cultured rat mesangial cells (RMCs) in vitro. Our study revealed that high glucose upregulated Egr1 to aggravate the inflammation and fibrosis in RMCs. And high glucose activates Egr1/TLR4/mTOR regulatory axis in MCs, indicating that one coherent feedforward loop is formed. Anti-aging protein Klotho may attenuate glomerular inflammation and fibrosis to provide protection against diabetic kidney injury via inhibiting the activity of Egr1/TLR4/mTOR regulatory axis in high glucose conditions. This study complements the function mechanism of Egr1/TLR4/mTOR regulatory axis playing in the pathogenesis of DKD, and provides a new direction and theoretical basis for anti-aging protein Klotho in DKD treatment.
Seltene nuklearmedizinische Untersuchungen: Die Magenfunktionsszintigrafie
Authors: Linke Rainer
Published: June 2018

Nuklearmedizinische Verfahren erlauben die nicht invasive Erfassung von Organfunktionen des Verdauungstraktes, allerdings wird aufgrund des immer umfangreicher werdenden diagnostischen Spektrums (Atemtest, Ultraschall, Endoskopie, Manometrie, MRT) zunehmend seltener an diese Untersuchungsmethoden gedacht. Dennoch können nuklearmedizinische Verfahren weiterhin einen wichtigen Beitrag in der Diagnostik von Erkrankungen des oberen Gastrointestinaltraktes leisten. So kann szintigrafisch die Magenfunktion visuell und quantitativ erfasst werden.

Der Magen hat die Aufgabe, die Nahrung nach der Ösophaguspassage vorübergehend zu speichern und fraktioniert in den Dünndarm zu entleeren. Eine phasische Peristaltik des Magens dient der Durchmischung und Zerkleinerung des Speisebreis.

Störungen der Magenfunktion können Beschwerden wie Völlegefühl, Blähungen, epigastrische Schmerzen, Übelkeit und Erbrechen verursachen. Ursächlich für eine Magenfunktionsstörung sind operative Eingriffe (Fundoplikatio, Magenteilresektion), aber auch Stoffwechselerkrankungen (z. B. Diabetes mellitus), Kollagenosen, Gastritiden oder selten auch Tumoren. Zudem müssen auch funktionelle Krankheitsbilder oder Nebenwirkungen von Medikamenten in Betracht gezogen werden.

Mit der Magenfunktionsszintigrafie kann das Ausmaß einer Funktionsstörung einfach und schnell erfasst und können Kenntnisse über die Magenentleerung und die peristaltische Aktivität des Magens gewonnen werden. Untersuchungen mit radioaktiv markierten Testspeisen sind physiologisch und nicht invasiv. Je nach zugrundeliegender Erkrankung bzw. Störung finden sich typische Befundkombinationen, die eine differenzial- und artdiagnostische Einordnung ermöglichen.
Crystallization of hard spheres revisited. II. Thermodynamic modeling, nucleation work, and the surface of tension
Authors: Richard David , Speck Thomas
Published: June 2018

Combining three numerical methods (forward flux sampling, seeding of droplets, and finite-size droplets), we probe the crystallization of hard spheres over the full range from close to coexistence to the spinodal regime. We show that all three methods allow us to sample different regimes and agree perfectly in the ranges where they overlap. By combining the nucleation work calculated from forward flux sampling of small droplets and the nucleation theorem, we show how to compute the nucleation work spanning three orders of magnitude. Using a variation of the nucleation theorem, we show how to extract the pressure difference between the solid droplet and ambient liquid. Moreover, combining the nucleation work with the pressure difference allows us to calculate the interfacial tension of small droplets. Our results demonstrate that employing bulk quantities yields inaccurate results for the nucleation rate.
Growth, stress, and defects of heteroepitaxial diamond on Ir/YSZ/Si(111)
Authors: Gallheber B.-C. , Fischer M. , Mayr M. , Straub J. , Schreck M.
Published: June 2018

Basic understanding of the fundamental processes in crystal growth as well as the structural quality of diamond synthesized by chemical vapour deposition on iridium surfaces has reached a high level for samples with (001) orientation. Diamond deposition on the alternative (111) surface is generally more challenging but of appreciable technological interest, too. In the present work, heteroepitaxy of diamond on Ir/YSZ/Si(111) with different off-axis angles and directions has been studied. During the growth of the first microns, strong and complex intrinsic stress states were rapidly formed. They restricted the range of suitable temperatures in this study to values between 830 °C and 970 °C. At low-stress conditions, the maximum growth rates were about 1 μm/h. They facilitated long-time processes which yielded pronounced structural improvements with minimum values of 0.08° for the azimuthal mosaic spread, 4 × 107 cm−2 for the dislocation density and 1.8 cm−1 for the Raman line width. This refinement is even faster than on (001) growth surfaces. It indicates substantial differences between the two crystal directions in terms of merging of mosaic blocks and annihilation of dislocations. Crystals with a thickness of up to 330 μm have been grown. The correlation of photoluminescence and μ-Raman tomograms with topography data also revealed fundamental differences in the off-axis growth between (001) and (111) orientation. Finally, the analysis of the microscopic structures at the growth surface provided the base for a model that can conclusively explain the intriguing reversal of stress tensor anisotropy caused by a simple inversion in sign of the off-axis angle.
A sandwich-like differential B-dot based on EACVD polycrystalline diamond slice
Authors: Xu P. , Yu Y. , Xu L. , Zhou H. Y. , Qiu C. J.
Published: June 2018

In this article, we present a method of mass production of a standardized high-performance differential B-dot magnetic probe together with the magnetic field measurement in a pulsed current device with the current up to hundreds of kilo-Amperes. A polycrystalline diamond slice produced in an Electron Assisted Chemical Vapor Deposition device is used as the base and insulating material to imprint two symmetric differential loops for the magnetic field measurement. The SP3 carbon bond in the cubic lattice structure of diamond is confirmed by Raman spectra. The thickness of this slice is 20 μm. A gold loop is imprinted onto each surface of the slice by using the photolithography technique. The inner diameter, width, and thickness of each loop are 0.8 mm, 50 μm, and 1 μm, respectively. It provides a way of measuring the pulsed magnetic field with a high spatial and temporal resolution, especially in limited space. This differential magnetic probe has demonstrated a very good common-mode rejection rate through the pulsed magnetic field measurement.
The Heidelberg compact electron beam ion traps
Authors: Micke P. , Kühn S. , Buchauer L. , Harries J. R. , Bücking T. M. , Blaum K. , Cieluch A. , Egl A. , Hollain D. , Kraemer S. , Pfeifer T. , Schmidt P. O. , Schüssler R. X. , Schweiger Ch. , Stöhlker T. , Sturm S. , Wolf R. N. , Bernitt S. , Crespo López-Urrutia J. R.
Published: June 2018

Electron beam ion traps (EBITs) are ideal tools for both production and study of highly charged ions (HCIs). In order to reduce their construction, maintenance, and operation costs, we have developed a novel, compact, room-temperature design, the Heidelberg Compact EBIT (HC-EBIT). Four already commissioned devices operate at the strongest fields (up to 0.86 T) reported for such EBITs using permanent magnets, run electron beam currents up to 80 mA, and energies up to 10 keV. They demonstrate HCI production, trapping, and extraction of pulsed Ar16+ bunches and continuous 100 pA ion beams of highly charged Xe up to charge state 29+, already with a 4 mA, 2 keV electron beam. Moreover, HC-EBITs offer large solid-angle ports and thus high photon count rates, e.g., in x-ray spectroscopy of dielectronic recombination in HCIs up to Fe24+, achieving an electron-energy resolving power of E/ΔE > 1500 at 5 keV. Besides traditional on-axis electron guns, we have also implemented a novel off-axis gun for laser, synchrotron, and free-electron laser applications, offering clear optical access along the trap axis. We report on its first operation at a synchrotron radiation facility demonstrating the resonant photoexcitation of highly charged oxygen.
Anisotropic thermal transport in van der Waals layered alloys WSe2(1-x)Te2x
Authors: Qian Xin , Jiang Puqing , Yu Peng , Gu Xiaokun , Liu Zheng , Yang Ronggui
Published: June 2018

Transition metal dichalcogenide (TMD) alloys have attracted great interest in recent years due to their tunable electronic properties and the semiconductor-metal phase transition along with their potential applications in solid-state memories and thermoelectrics among others. However, the thermal conductivity of layered TMD alloys remains largely unexplored despite that it plays a critical role in the reliability and functionality of TMD-enabled devices. In this work, we study the composition- and temperature-dependent anisotropic thermal conductivity of the van der Waals layered TMD alloys WSe2(1-x)Te2x in both the in-plane direction (parallel to the basal planes) and the cross-plane direction (along the c-axis) using time-domain thermoreflectance measurements. In the WSe2(1-x)Te2x alloys, the cross-plane thermal conductivity is observed to be dependent on the heating frequency (modulation frequency of the pump laser) due to the non-equilibrium transport between different phonon modes. Using a two-channel heat conduction model, we extracted the anisotropic thermal conductivity at the equilibrium limit. A clear discontinuity in both the cross-plane and the in-plane thermal conductivity is observed as x increases from 0.4 to 0.6 due to the phase transition from the 2H to the Td phase in the layered alloys. The temperature dependence of thermal conductivity for the TMD alloys was found to become weaker compared with the pristine 2H WSe2 and Td WTe2 due to the atomic disorder. This work serves as an important starting point for exploring phonon transport in layered alloys.
Structural and electronic properties of Ga2O3-Al2O3 alloys
Authors: Peelaers Hartwin , Varley Joel B. , Speck James S. , Van de Walle Chris G.
Published: June 2018

Ga2O3 is emerging as an important electronic material. Alloying with Al2O3 is a viable method to achieve carrier confinement, to increase the bandgap, or to modify the lattice parameters. However, the two materials have very different ground-state crystal structures (monoclinic β-gallia for Ga2O3 and corundum for Al2O3). Here, we use hybrid density functional theory calculations to assess the alloy stabilities and electronic properties of the alloys. We find that the monoclinic phase is the preferred structure for up to 71% Al incorporation, in close agreement with experimental phase diagrams, and that the ordered monoclinic AlGaO3 alloy is exceptionally stable. We also discuss bandgap bowing, lattice constants, and band offsets that can guide future synthesis and device design efforts.
Unconditionally marginal stability of harmonic electron hole equilibria in current-driven plasmas
Authors: Schamel Hans
Published: June 2018

Two forms of the linearized eigenvalue problem with respect to linear perturbations of a privileged cnoidal electron hole as a structural nonlinear equilibrium element are established. Whereas its integral form involves integrations along the characteristics or unperturbed particle orbits, the differential form has to cope with a differential operator of infinite order. Both are hence faced with difficulties to obtain a solution. A first successful attempt is, however, made by addressing a single harmonic wave as a nonlinear equilibrium structure. By this microscopic nonlinear approach, its marginal stability against linear perturbations in both linear stability regimes, the sub- and super-critical one, is shown independent of the mobility of ions and in favor with recent observations. Responsible for vanishing damping (growth) is the microscopic distortion of the resonant distribution function. The macroscopic form of the trapping nonlinearity—the 3/2 power term of the electrostatic potential in the density—which disappears in the monochromatic harmonic wave limit is consequently necessary for the occurrence of a nonlinear plasma instability in the sub-critical regime.
Stability enhancement of yttrium substituted nickel zinc ferrite/PZT magnetoelectric gyrators under high power conditions
Authors: Leung Chung Ming , Sreenivasulu G. , Zhuang Xin , Gao Min , Tang Xiao , Xu Junran , Li Jiefang , Srinivasan G. , Viehland D.
Published: June 2018

The influence of yttrium (Y) ion substitution on the magneto-mechanical properties of nickel-zinc ferrite (Ni0.7Zn0.3YxFe2-xO4) or NZFO-Y and the power efficiency (η) of magnetoelectric (ME) gyrators consisting of NZFO-Y/Pb(Zr, Ti)O3 layers were studied. X-ray diffraction (XRD) of polycrystalline samples of NZFO-Y indicated that yttrium incorporated into the crystal lattice resulted in an enlargement of the lattice parameter. Also, the density and ionic hopping length were increased, and the porosity was decreased. Together, these resulted in significant changes in the magneto-mechanical coupling (k33,m) and mechanical quality (Qm) factors. It was found that k33,m decreased with the increasing Y content for 0 ≤ x ≤ 0.08, whereas Qm was increased. For x > 0.05, the values of k33,m and Qm were found to be nearly stable with increasing input power density (PD-Ms) up to 47 W/in3. Under this high power driving condition for 20 min, we found that the power conversion stability of ME gyrators was increased with the increasing Y content in the ferrite and that a maximum power conversion efficiency occurred near 77%. These findings offer the potential for ferrite-based ME gyrator applications in power electronic conversion devices.
Antimony in the Lot–Garonne river system: a 14-year record of solid–liquid partitioning and fluxes
Authors: Gil-Díaz Teba , Schäfer Jörg , Coynel Alexandra , Bossy Cécile , Dutruch Lionel , Blanc Gérard
Published: June 2018

Environmental contextAntimony is a trace element ubiquitously present in the environment, but data are lacking on its spatio-temporal distribution in aquatic environments. Long-term records serve as essential tools to decipher temporal patterns, historical sources and sinks and background concentrations in an area. We characterise the temporal concentrations, transport and behaviour of antimony in the Garonne River watershed, the main tributary to the Gironde Estuary, the largest estuary in south-west Europe.
AbstractKnowledge of the environmental chemistry of antimony (Sb) in aquatic systems is limited, and a better understanding of its geochemical behaviour is needed. Based on a fourteen-year survey (2003–2016) with monthly measurements of dissolved and particulate Sb at five sites in the Lot–Garonne river system, combined with daily measurements of water discharge and suspended particulate matter, this work characterises Sb behaviour in the upstream major river watershed of the Gironde Estuary. The survey provides a first regional geochemical Sb background in the Garonne River watershed for dissolved (~0.2 µg L−1) and Th-normalised particulate Sb (Sbp/Thp ~0.25) concentrations. Observed decreasing temporal trends (<1 ng L−1 in dissolved and <0.02 mg kg−1 in particulate concentrations per month) at sites representing natural concentrations probably reflect global atmospheric Sb dynamics at the watershed scale. Regular seasonal cycles of solid/liquid partitioning, with higher solubility in summer (matching high dissolved and low particulate concentrations), reflect water-discharge and suspended particulate matter transport dynamics and possibly seasonal (bio)geochemical processes. Furthermore, this coefficient decreases from the river to the estuarine reaches (from average log10Kd 4.3 to minimum 3.7 L kg−1), suggesting an increased solubility of Sb in estuarine systems. Flux estimates indicate the relevance of the dissolved fraction in Sb transport (with negligible influence of the colloidal fraction) and a total flux (dissolved + particulate) entering the Gironde Estuary of 5.66 ± 2.96 t year−1 (~50 % particulate). These results highlight the importance of timescales and environmental parameters for understanding and prediction of future Sb biogeochemistry.
Macrophage phenotype and bioenergetics are controlled by oxidized phospholipids identified in lean and obese adipose tissue
Authors: Serbulea Vlad , Upchurch Clint M. , Schappe Michael S. , Voigt Paxton , DeWeese Dory E. , Desai Bimal N. , Meher Akshaya K. , Leitinger Norbert
Published: June 2018

Significance

Adipose tissue macrophages (ATMs) maintain adipose tissue homeostasis. However, during obesity ATMs become inflammatory, resulting in impaired adipose tissue function. Oxidative stress increases during obesity, which is thought to contribute to adipose tissue inflammation. To date, the connection between oxidative stress and adipose tissue inflammation remain unclear. In this study, we identify two classes of phospholipid oxidation products in lean and obese adipose tissue, which polarize macrophages to an antioxidant or proinflammatory state, respectively. Furthermore, we show that these phospholipids differently affect macrophage cellular metabolism, reflecting the metabolisms of ATMs found in lean and obese adipose tissue. Identification of pathways controlling ATM metabolism will lead to novel therapies for insulin resistance.
Bacterial iron acquisition mediated by outer membrane translocation and cleavage of a host protein
Authors: Mosbahi Khedidja , Wojnowska Marta , Albalat Amaya , Walker Daniel
Published: June 2018

Significance

The outer membrane of Gram-negative bacteria is a highly impermeable barrier to a range of toxic chemicals and is responsible for the resistance of these bacteria to important classes of antibiotics. In this work, we show that plant pathogenic
Pectobacterium
spp. acquire iron from the small, stable, and abundant iron-containing plant protein ferredoxin by transporting ferredoxin across the outer membrane for intracellular processing by a highly specific protease, which induces iron release. The presence of homologous uptake and processing proteins in a range of important animal and plant pathogens suggests an exploitable route through which large molecules can penetrate the outer membrane of Gram-negative bacteria.
Evidence for mutual allocation of social attention through interactive signaling in a mormyrid weakly electric fish
Authors: Worm Martin , Landgraf Tim , Prume Julia , Nguyen Hai , Kirschbaum Frank , von der Emde Gerhard
Published: June 2018

Significance

Interactive electric signaling between mormyrid weakly electric fish by means of echoing a conspecific’s signals has been discussed both in the context of jamming avoidance during active electrolocation and as a strategy for electrocommunication. By confronting individuals of the weakly electric fish
Mormyrus rume proboscirostris
with a mobile robot that responds dynamically to the signaling activity of the fish, we show that interactive signaling, in turn, leads to increased synchronization of communication signals by the receiving animals. Synchronization of electric signaling occurred most frequently in approach configurations, suggesting that echoing may be employed specifically to address conspecific individuals and to initiate mutual allocation of social attention during electrocommunication.
Microscale optoelectronic infrared-to-visible upconversion devices and their use as injectable light sources
Authors: Ding He , Lu Lihui , Shi Zhao , Wang Dan , Li Lizhu , Li Xichen , Ren Yuqi , Liu Changbo , Cheng Dali , Kim Hoyeon , Giebink Noel C. , Wang Xiaohui , Yin Lan , Zhao Lingyun , Luo Minmin , Sheng Xing
Published: June 2018

Significance

Materials and devices that upconvert photons from low to high frequencies are of tremendous interest for broad applications in bio- and chemical sensing, infrared imaging, display, and photovoltaics. Here we develop self-powered, micrometer-scale optoelectronic upconversion devices for infrared-to-visible photon upconversion. The realized microscale optoelectronic device exhibits a practical efficiency of 1.5% under incoherent low-power illumination, with emission intensity linearly dependent on excitation. Other remarkable advances over conventional approaches include broadband absorption, wide-emission spectral tunability (red, yellow, and blue), and fast dynamics. Encapsulated ultraminiaturized devices can be implanted into subdermal tissues and provide stable operation in behaving animals. Demonstrations of optogenetic stimulation in living animals present their potential for biomedical uses.
Isotropic, nematic, and lamellar phases in colloidal suspensions of nanosheets
Authors: Davidson Patrick , Penisson Christophe , Constantin Doru , Gabriel Jean-Christophe P.
Published: June 2018

Significance

Colloidal suspensions of electrically charged nanometric sheets (nanosheets), like graphene oxide or clays, which are widely used in industry, form liquid-crystalline phases. These include the nematic phase, where all nanosheets are approximately parallel, and the lamellar phase, where they also form equidistant layers. When the particle diameter is large (100 nm to 1 µm), distinguishing these phases is quite challenging. Using newly available synchrotron small-angle X-ray scattering setups, we unambiguously identified both phases, in H
3
Sb
3
P
2
O
14
nanosheet suspensions, by analyzing their X-ray scattering patterns. The lamellar domain size reaches 20 µm, which means each layer is made of ∼1,000 nanosheets. Because the lamellar phase was rarely predicted in suspensions of charged disks, these systems should be revisited by theory or simulations.
Primary productivity below the seafloor at deep-sea hot springs
Authors: McNichol Jesse , Stryhanyuk Hryhoriy , Sylva Sean P. , Thomas François , Musat Niculina , Seewald Jeffrey S. , Sievert Stefan M.
Published: June 2018

Significance

The existence of a chemosynthetic subseafloor biosphere was immediately recognized when deep-sea hot springs were discovered in 1977. However, quantifying how much new carbon is fixed in this environment has remained elusive. In this study, we incubated natural subseafloor communities under in situ pressure/temperature and measured their chemosynthetic growth efficiency and metabolic rates. Combining these data with fluid flux and in situ chemical measurements, we derived empirical constraints on chemosynthetic activity in the natural environment. Our study shows subseafloor microorganisms are highly productive (up to 1.4 Tg C produced yearly), fast-growing (turning over every 17–41 hours), and physiologically diverse. These estimates place deep-sea hot springs in a quantitative framework and allow us to assess their importance for global biogeochemical cycles.
Monitoring molecular nonadiabatic dynamics with femtosecond X-ray diffraction
Authors: Bennett Kochise , Kowalewski Markus , Rouxel Jérémy R. , Mukamel Shaul
Published: June 2018

Significance

X-ray crystallography has long been used to determine the structure of crystals and molecular samples. More recent advancements in light sources and computational methods made it possible to routinely determine the structure of large proteins. The introduction of X-ray free-electron lasers opens up the possibility to track the dynamics of molecular structures on a femtosecond time scale and to create molecular movies of chemical reactions. The theory of time-independent diffraction is well known. However, time-resolved diffraction techniques pose not only new challenges to experiments but also to their interpretation. In this work, we present a unified theoretical framework that will aid experimental interpretations as well as predictions of types of X-ray diffraction experiments.
Enhanced mRNA delivery into lymphocytes enabled by lipid-varied libraries of charge-altering releasable transporters
Authors: McKinlay Colin J. , Benner Nancy L. , Haabeth Ole A. , Waymouth Robert M. , Wender Paul A.
Published: June 2018

Significance

The transfection of lymphocytes with genetic material is a significant unmet need in immunotherapy and the treatment of many diseases. Current transfection strategies primarily rely on physical methods that must be conducted ex vivo and are often inefficient. We identified mixtures of lipid-varied mRNA delivery vehicles (charge-altering releasable transporters, CARTs) that show enhanced uptake into multiple lymphocyte cell types. The top performing lipid mixtures were rapidly identified using a combinatorial strategy and the resulting information was used to design single-delivery agents incorporating both lipid domains using our two-step organocatalytic ring-opening polymerization. Hybrid-lipid CARTs show >80% mRNA transfection efficiency in vitro and >1.5% lymphocyte transfection efficiency in mice, which is higher than previously reported systems. These materials should enable new immunotherapy strategies and applications.
Staphylococcus aureus
targets the purine salvage pathway to kill phagocytes
Authors: Winstel Volker , Missiakas Dominique , Schneewind Olaf
Published: June 2018

Significance

Immune evasion by the human pathogen
Staphylococcus aureus
includes the synthesis of cytotoxic deoxyadenosine (dAdo) from neutrophil extracellular traps to eliminate macrophages. The signaling pathway that triggers dAdo-mediated apoptosis in macrophages is not known. By using a genome-wide CRISPR-Cas9 knockout screen, we demonstrate that
S. aureus
-derived dAdo targets the purine salvage pathway to provoke caspase-3–dependent cell death in human macrophages, thereby antagonizing host immune responses and promoting the establishment of invasive disease. Interference with the staphylococcal dAdo signaling pathway may boost macrophage survival and phagocytic clearance of bacteria, providing new strategies for the treatment of
S. aureus
infections.
Bright quantum dots emitting at ∼1,600 nm in the NIR-IIb window for deep tissue fluorescence imaging
Authors: Zhang Mingxi , Yue Jingying , Cui Ran , Ma Zhuoran , Wan Hao , Wang Feifei , Zhu Shoujun , Zhou Ying , Kuang Yun , Zhong Yeteng , Pang Dai-Wen , Dai Hongjie
Published: June 2018

Significance

In vivo fluorescence imaging in near IR-IIb window (1,500–1,700 nm) can provide high spatial and temporal resolution and deep tissue penetration for fundamental research and potential translations. Herein, a bright fluorescent probe emitting at ∼1,600 nm based on lead sulfide (PbS)/CdS quantum dots was developed. The CdS shell helped to chemically passivate and retain the high fluorescence of the PbS core after phase transfer to aqueous solutions for biocompatibility. The 1,600-nm emitting probe allowed noninvasive, millimeter-deep fluorescence imaging at high speeds up to 60 frames per second with micrometer-scale spatial resolution in 2D wide-field and 3D confocal modes. The probes were nontoxic and largely excreted over 1 month, providing a tool for in vivo research of preclinical animal models.
Specific binding of PCBP1 to heavily oxidized RNA to induce cell death
Authors: Ishii Takashi , Hayakawa Hiroshi , Igawa Tatsuhiro , Sekiguchi Takeshi , Sekiguchi Mutsuo
Published: June 2018

Significance

The binding of human PCBP1 protein to heavily oxidized RNA triggers the induction of apoptosis-related reactions, including the activation of caspase-3 and the cleavage of PARP-1. The introduction of amino acid substitutions in the PCBP1 abolishes this, resulting in the failure of PARP-1 cleavage. Human cells appear to possess a mechanism to induce cell death when their messenger RNAs are severely damaged. This mechanism might be related to the accumulation of abnormal proteins in long-lived cells, such as those in the nervous system.
HRS–WASH axis governs actin-mediated endosomal recycling and cell invasion
Authors: MacDonald Ewan , Brown Louise , Selvais Arnaud , Liu Han , Waring Thomas , Newman Daniel , Bithell Jessica , Grimes Douglas , Urbé Sylvie , Clague Michael J. , Zech Tobias
Published: June 2018

Transmembrane proteins in the sorting endosome are either recycled to their point of origin or destined for lysosomal degradation. Lysosomal sorting is mediated by interaction of ubiquitylated transmembrane proteins with the endosomal sorting complex required for transport (ESCRT) machinery. In this study, we uncover an alternative role for the ESCRT-0 component hepatocyte growth factor–regulated tyrosine kinase substrate (HRS) in promoting the constitutive recycling of transmembrane proteins. We find that endosomal localization of the actin nucleating factor Wiscott-Aldrich syndrome protein and SCAR homologue (WASH) requires HRS, which occupies adjacent endosomal subdomains. Depletion of HRS results in defective constitutive recycling of epidermal growth factor receptor and the matrix metalloproteinase MT1–MMP, leading to their accumulation in internal compartments. We show that direct interactions with endosomal actin are required for efficient recycling and use a model system of chimeric transferrin receptor trafficking to show that an actin-binding motif can counteract an ubiquitin signal for lysosomal sorting. Directed receptor recycling is used by cancer cells to achieve invasive migration. Accordingly, abrogating HRS- and actin-dependent MT1-MMP recycling results in defective matrix degradation and invasion of triple-negative breast cancer cells.
Exorcism and Religious Politics in Fifteenth-Century Florence
Authors: Walden Justine
Published: June 2018

This article examines a series of messages concerning politics and geography that the religious order of the Vallombrosans embedded within a series of exorcism manuscripts and addressed to Lorenzo de’ Medici in the late fifteenth century. The Vallombrosans crafted their manuscripts to negotiate a host of troubles: schism over reform, friction with Lorenzo, diminishing social status, increased marginality, competition with rival religious orders, new definitions of orthodoxy, and alternate forms of religious devotion. I frame Vallombrosan troubles and their turn to exorcism as symptomatic of the increased predominance of Mendicant Observants over older orders, and link this shift to a newly active and politicized demonology.
The Renaissance Footprint: The Material Trace in Print Culture from Dürer to Spenser
Authors: Gordon Andrew
Published: June 2018

This article argues that Renaissance print culture appropriated the cultural meanings of the footprint. The potent analogy between the printing press and printing foot informed Reformation debates over Christ’s footprints as objects of devotion and subjects of representation. In sixteenth-century England a model for investigative reading informed by Erasmian humanism was developed in the print projects of George Gascoigne and Edmund Spenser. Experimentation with effects of the press and the material environment of the page culminated in extensive play upon the material and metaphorical sign of the printing foot in Spenser’s “Amoretti.”
Systematic review and meta-regressions: management of eosinophilic esophagitis requires histologic assessment
Authors: Chang J W , Yeow R Y , Waljee A K , Rubenstein J H
Published: June 2018

Treatment endpoints in eosinophilic esophagitis (EoE) are response of eosinophilic inflammation and of symptoms. Steroids and diet therapy are effective in inducing histologic response in EoE, but there may be poor correlation between histologic and symptomatic response. Despite this, we find that in clinical practice symptoms are commonly used to guide management without assessing histologic response. We hypothesized that symptom response alone is not reliable in assessing response to therapy and is confounded by endoscopic dilation. We conducted a systematic review and meta-regressions to estimate the association of histologic and symptomatic response, stratified by whether concurrent dilation was permitted. We performed a systematic search of PubMed, EMBASE, and Web of Science for studies describing both histologic and symptomatic responses to dilation, steroid, and diet therapies. We abstracted the proportion of histologic response and symptom response. Studies were stratified by whether dilation was permitted. We performed meta-regressions of the association between the proportions with histologic and symptomatic response, stratified by whether dilation was permitted. We identified 1359 articles, of which 62 articles were assessed for eligibility, and 23 were included providing data on 1202 patients with EoE. Unstratified meta-regression of histologic versus symptomatic response showed moderate association and large heterogeneity (inconsistency index [I2] = 89%). In adult studies in which dilation was allowed, there was weak association between symptomatic and histologic response (β1 = 0.21), minimal symptomatic response of 67% and the heterogeneity persisted, I2 = 77%. In studies that prohibited dilation, maximal symptomatic response was 72% and was moderately associated with histologic response (β1 = 0.39) with less heterogeneity, I2 = 59%. Studies of EoE that permit dilation obscure the relation between histologic and symptomatic response and have a high floor effect for symptomatic response. Studies that prohibit dilation demonstrate moderate association between histologic and symptomatic response, but have a ceiling effect for symptomatic response. Our results demonstrate that success of dietary or medical management for EoE cannot be judged by symptoms alone, and require histologic assessment, particularly if dilation has been performed.
A usability and safety analysis of electronic health records: a multi-center study
Authors: Ratwani Raj M , Savage Erica , Will Amy , Arnold Ryan , Khairat Saif , Miller Kristen , Fairbanks Rollin J , Hodgkins Michael , Hettinger A Zachary
Published: June 2018

To characterize the variability in usability and safety of EHRs from two vendors across four healthcare systems (2 Epic and 2 Cerner). Twelve to 15 emergency medicine physicians participated from each site and completed six clinical scenarios. Keystroke, mouse click, and video data were collected. From the six scenarios, two diagnostic imaging, laboratory, and medication tasks were analyzed. There was wide variability in task completion time, clicks, and error rates. For certain tasks, there were an average of a nine-fold difference in time and eight-fold difference in clicks. Error rates varied by task (X-ray 16.7% to 25%, MRI: 0 to 10%, Lactate: 0% to 14.3%, Tylenol: 0 to 30%; Taper: 16.7% to 50%). The variability in time, clicks, and error rates highlights the need for improved implementation optimization. EHR implementation, in addition to vendor design and development, is critical to usable and safe products.
The electronic elephant in the room: Physicians and the electronic health record
Authors: Kroth Philip J , Morioka-Douglas Nancy , Veres Sharry , Pollock Katherine , Babbott Stewart , Poplau Sara , Corrigan Katherine , Linzer Mark
Published: June 2018

Objectives

Determine the specific aspects of health information and communications technologies (HICT), including electronic health records (EHRs), most associated with physician burnout, and identify effective coping strategies.

Materials and methods

We performed a qualitative analysis of transcripts from 2 focus groups and a burnout assessment of ambulatory physicians—each at 3 different health care institutions with 3 different EHRs.

Results

Of the 41 clinicians, 71% were women, 98% were physicians, and 73% worked in primary care for an average of 11 years. Only 22% indicated sufficient time for documentation. Fifty-six percent noted “a great deal of stress” because of their job. Forty-two percent reported “poor” or “marginal” control over workload. Even though 90% reported EHR proficiency, 56% indicated EHR time at home was “excessive” or “moderately high.” Focus group themes included HICT “successes” where all patients’ information is accessible from multiple locations. HICT “stressors” included inefficient user interfaces, unpredictable system response times, poor interoperability between systems and excessive data entry. “Adverse outcomes” included ergonomic problems (eg, eye strain and hand, wrist, and back pain) and decreased attractiveness of primary care. Suggested “organizational changes” included EHR training, improved HICT usability, and scribes. “Personal/resilience” strategies focused on self-care (eg, exercise, maintaining work-life boundaries, and positive thinking).

Discussion and conclusion

HICT use, while beneficial in many ways for patients and providers, has also increased the burden of ambulatory practice with personal and professional consequences. HICT and clinic architectural and process redesign are likely necessary to make significant overall improvements.
Human Exposure to Radioactivity From Tobacco Smoke: Systematic Review
Authors: Laking George Robert
Published: June 2018

Introduction

Tobacco has been known to contain radioactive polonium and lead for 50 years but the literature is divided as to the public health significance. I review the data on tobacco radioactivity and its internalization by smokers.

Methods

Data sources: Reports of lead-210 and polonium-210 content of tobacco leaf, cigarettes, cigarette smoke, and human respiratory tissues, published between 1964 and September 2017. Study selection: Any identified study that reported values for lead-210 and polonium-210 content. Data extraction: Data quality was addressed by comparative review of analytic methods.

Results

The data about radiation content of tobacco and smoke are robust. Early reports suggesting microsievert lifetime doses of inhaled radioactivity to smokers were not borne out. The results remain sensitive to pharmacological assumptions around absorption and redistribution of inhaled radionuclides, and radiobiological assumptions about interaction with human tissues.

Conclusions

Literature on tobacco radioactivity has not fully contended with pharmacological and radiobiological uncertainty, and is therefore divided as to health significance. This does much to explain regulatory inaction over the last half century. Before radiation safety law can offer a vehicle for tobacco control, more must be learnt about the pharmacology and radiobiology of inhaled radionuclides in tobacco smoke.

Implications

This work makes it apparent that the study of tobacco smoke radioactivity has been scientifically stagnant for the last 40 years. The field cannot advance until we improve understanding of the pharmacology and radiobiology of inhaled radionuclides in tobacco smoke. Despite this, a subset of contemporary authors is still suggesting individual health risks about 1000 times higher than can be supported by internationally accepted models.
Infectious Scleritis: What the ID Clinician Should Know
Authors: Guerrero-Wooley Richelle L , Peacock James E
Published: June 2018

Scleritis is an inflammatory process involving the outer coating of the globe which is characterized by focal or diffuse hyperemia, moderate to severe pain, and frequent impairment of vision. Most cases of scleritis are autoimmune in nature and are managed with topical and/or systemic corticosteroids. Infectious scleritis is a less common entity, occurring in 5%–10% of cases, and requiring directed antimicrobial therapy. We present a case of Nocardia farcinica anterior nodular scleritis diagnosed via positive culture of an excisional biopsy of a scleral nodule. The patient improved after combined surgical and medical therapy with amoxicillin-clavulanate and moxifloxacin for 12 months. Based on a literature review, a summary of reported cases of infectious scleritis is provided, and guidelines pertaining to diagnosis and management are offered.