Perspectives on weak interactions in complex materials at different length scales.

Nanocomposite materials consist of nanometer-sized quantum objects such as atoms, molecules, voids or nanoparticles embedded in a host material. These quantum objects can be exploited as a super-structure, which can be designed to create material properties targeted for specific applications. For electromagnetism, such targeted properties include field enhancements around the bandgap of a semiconductor used for solar cells, directional decay in topological insulators, high kinetic inductance in superconducting circuits, and many more. Despite very different application areas, all of these properties are united by the common aim of exploiting collective interaction effects between quantum objects. The literature on the topic spreads over very many different disciplines and scientific communities. In this review, we present a cross-disciplinary overview of different approaches for the creation, analysis and theoretical description of nanocomposites with applications related to electromagnetic properties.

Low-energy electron ionization mass spectrometer for efficient detection of low mass species.

The design of a high-efficiency mass spectrometer is described, aimed at residual gas detection of low mass species using low-energy electron impact, with particular applications in helium atom microscopy and atomic or molecular scattering. The instrument consists of an extended ionization volume, where electrons emitted from a hot filament are confined using a solenoidal magnetic field to give a high ionization probability. Electron space charge is used to confine and extract the gas ions formed, which are then passed through a magnetic sector mass filter before reaching an ion counter. The design and implementation of each of the major components are described in turn, followed by the overall performance of the detector in terms of mass separation, detection efficiency, time response, and background count rates. The linearity of response with emission current and magnetic field is discussed. The detection efficiency for helium is very high, reaching as much as 0.5%, with a time constant of (198 ± 6) ms and a background signal equivalent to an incoming helium flux of (8.7 ± 0.2) × 106 s-1.

Erratum: Bending Rigidity of 2D Silica [Phys. Rev. Lett. 120, 226101 (2018)].

This corrects the article DOI: 10.1103/PhysRevLett.120.226101.

Temperature-Dependent Bending Rigidity of AB-Stacked Bilayer Graphene.

The change in bending rigidity with temperature κ(T) for 2D materials is highly debated: theoretical works predict both increase and decrease. Here we present measurements of κ(T), for a 2D material: AB-stacked bilayer graphene. We obtain κ(T) from phonon dispersion curves measured with helium atom scattering in the temperature range 320-400 K. We find that the bending rigidity increases with temperature. Assuming a linear dependence over the measured temperature region we obtain κ(T)=[(1.3±0.1)+(0.006±0.001)T/K] eV by fitting the data. We discuss this result in the context of existing predictions and room temperature measurements.

Serum concentration of mineralocorticoids, glucocorticoids, and sex steroids in peripartum bitches.

The aim of the work was to describe the profile of steroid hormones in the peripartum period of the bitch. Twenty-five healthy pregnant bitches presented for pregnancy monitoring and parturition assistance were included in the study. A blood sample was collected for routine progesterone assay, and serum was stored at -20°C. The day of parturition and the number of delivered puppies were registered. Concentrations of corticosteroids, androgens, progestogens, estrogens, for a total number of 17 different hormones, were measured using ultra-performance supercritical fluid chromatography-tandem mass spectrometry. Data were analyzed using a repeated measure, mixed-model approach, taking into account day (from day -4 to day +2 from parturition), age, parity (primiparous vs pluriparous), number of delivered puppies (<4 vs 4-8 vs > 8), and interactions between factors. Day related to parturition significantly affected the concentration of progesterone (P < 0.001), testosterone (P < 0.001), 17α-hydroxyprogesterone (P = 0.0002), and cortisone (P = 0.006). Estrogen concentration did not show any significant variation over time. Testosterone and androstenedione showed an abrupt decline on the day of parturition. The concentration of all glucocorticoids increased the day before parturition. Age or parity was not significantly associated with any of the steroids. Litter size significantly affected concentrations of aldosterone (P = 0.02) and etiocholanolone (P = 0.01). Aldosterone concentrations were higher in litters with 4 to 8 pups than in litters with more than 8 pups (P = 0.02). None of the steroids measured in our study, with the already known exception of progesterone, shows potential to be clinically useful in predicting the onset of parturition in the bitch.

Human induced pluripotent stem cells (BIONi010-C) generate tight cell monolayers with blood-brain barrier traits and functional expression of large neutral amino acid transporter 1 (SLC7A5).

The barrier properties of the brain capillary endothelium, the blood-brain barrier (BBB) restricts uptake of most small and all large molecule drug compounds to the CNS. There is a need for predictive human in vitro models of the BBB to enable studies of brain drug delivery. Here, we investigated whether human induced pluripotent stem cell (hiPSC) line (BIONi010-C) could be differentiated to brain capillary endothelial- like cells (BCEC) and evaluated their potential use in drug delivery studies. BIONi010-C hIPSCs were differentiated according to established protocols. BCEC monolayers displayed transendothelial electrical resistance (TEER) values of 5,829±354 Ω∙cm2, a Papp,mannitol of 1.09±0.15 ∙ 10-6 cm∙s-1 and a Papp,diazepam of 85.7 ± 5.9 ∙ 10-6 cm ∙s-1. The Pdiazepam/Pmannitol ratio of ~80, indicated a large dynamic passive permeability range. Monolayers maintained their integrity after medium exchange. Claudin-5, Occludin, Zonulae Occludens 1 and VE-Cadherin were expressed at the cell-cell contact zones. Efflux transporters were present at the mRNA level, but functional efflux of substrates was not detected. Transferrin-receptor (TFR), Low density lipoprotein receptor-related protein 1 (LRP1) and Basigin receptors were expressed at the mRNA-level. The presence and localization of TFR and LRP1 were verified at the protein level. A wide range of BBB-expressed solute carriers (SLC's) were detected at the mRNA level. The presence and localization of SLC transporters GLUT1 and LAT1 was verified at the protein level. Functional studies revealed transport of the LAT1 substrate [3H]-L-Leucine and the LRP1 substrate angiopep-2. In conclusion, we have demonstrated that BIONi010-C-derived BCEC monolayers exhibited, BBB properties including barrier tightness and integrity, a high dynamic range, expression of some of the BBB receptor and transporter expression, as well as functional transport of LAT1 and LRP1 substrates. This suggests that BIONi010-C-derived BCEC monolayers may be useful for studying the roles of LAT-1 and LRP1 in brain drug delivery.

Anti-Müllerian hormone (AMH) concentrations are maximal at puberty in male donkeys and secretion is redirected from the blood stream to seminal plasma.

Sertoli cells produce anti-Müllerian hormone (AMH) and number of these cells is associated with numbers of sperm produced. The study aim was to quantify AMH concentrations in serum and seminal plasma of donkeys during puberty, and to correlate the values with those for testicular width and semen quality of sexually mature males. Blood was collected from five donkeys every second month from 4 to 24 months of age, and then once at 40 months of age. Semen was collected once monthly, from 13 to 19 and 23-25 months of age. There was quantification of AMH concentrations in serum and seminal plasma. During puberty, there was a redirection of AMH secretion from the blood stream into seminal plasma. In serum, AMH concentrations increased during puberty with a maximal concentration at 16 months and the changes were similar for seminal plasma with a maximal concentration at 18 months of age. Serum AMH concentrations from 14-20 were greater than at 12 or 22 months of age. Maximal serum AMH concentrations were associated with testicular width at 24 months (r = 0.97, P = 0.005), but not with sperm count, sperm motility or percentage of sperm with normal morphology at 42 months of age. There were no significant correlations among values for AMH concentrations in seminal plasma during puberty and values for any of the seminal variables.

The use of surfactant-filled mesoporous silica as an immobilising medium for a fluorescence lifetime pH indicator, providing long-term calibration stability.

Surfactant filled mesoporous silica is applied as a matrix for immobilizing the fluorescence lifetime pH-indicator acridine. We demonstrate that this type of encapsulation provides a stable and uniform chemical environment for the indicator and has good proton transport properties leading to rapid pH response times. Furthermore, the immobilising medium effectively prevents leaching of the indicator, facilitates high long-term stability and does not influence the pH sensing-range of the indicator.

Velocity distributions in microskimmer supersonic expansion helium beams: High precision measurements and modeling.

Supersonic molecular beams are used in many applications ranging from spectroscopy and matter wave optics to surface science. The experimental setup typically includes a conically shaped, collimating aperture, the skimmer. It has been reported that microskimmers with diameters below 10 µm produce beams with significantly broader velocity distributions (smaller speed ratios) than larger skimmers. Various explanations for this phenomenon have been proposed, but up till now, only a limited amount of data has been available. Here we present a systematic study of the velocity distribution in microskimmer supersonic expansion helium beams. We compare a 4 µm diameter skimmer with a 390 µm diameter skimmer for room temperature and cooled beams in the pressure range 11-181 bars. Our measurements show that for properly aligned skimmers, the only difference is that the most probable velocity for a given pressure and temperature is slightly lower for a microskimmed beam. We ascribed this to the comparatively narrow and long geometry of the microskimmers which can lead to local pressure variations along the skimmer channel. We compare our measurements to a model for the supersonic expansion and obtain good agreement between the experiments and simulations.

Bending Rigidity of 2D Silica.

A chemically stable bilayers of SiO_{2} (2D silica) is a new, wide band gap 2D material. Up till now graphene has been the only 2D material where the bending rigidity has been measured. Here we present inelastic helium atom scattering data from 2D silica on Ru(0001) and extract the first bending rigidity, κ, measurements for a nonmonoatomic 2D material of definable thickness. We find a value of κ=8.8 eV±0.5 eV which is of the same order of magnitude as theoretical values in the literature for freestanding crystalline 2D silica.

Fast resolution change in neutral helium atom microscopy.

In neutral helium atom microscopy, a beam of atoms is scanned across a surface. Though still in its infancy, neutral helium microscopy has seen a rapid development over the last few years. The inertness and low energy of the helium atoms (less than 0.1 eV) combined with a very large depth of field and the fact that the helium atoms do not penetrate any solid material at low energies open the possibility for a non-destructive instrument that can measure topology on the nanoscale even on fragile and insulating surfaces. The resolution is determined by the beam spot size on the sample. Fast resolution change is an attractive property of a microscope because it allows different aspects of a sample to be investigated and makes it easier to identify specific features. However up till now it has not been possible to change the resolution of a helium microscope without breaking the vacuum and changing parts of the atom source. Here we present a modified source design, which allows fast, step wise resolution change. The basic design idea is to insert a moveable holder with a series of collimating apertures in front of the source, thus changing the effective source size of the beam and thereby the spot size on the surface and thus the microscope resolution. We demonstrate a design with 3 resolution steps. The number of resolution steps can easily be extended.

The association between the serum concentration of canine prostate specific esterase (CPSE) and the size of the canine prostate.

Benign prostatic hyperplasia (BPH) is an age-related disorder in the intact male dog that is associated with an increase in the prostatic size. Ultrasonography gives a reliable estimate of the prostatic size, but a method for screening the prostate size using a serum sample has advantages, such as requiring less expensive equipment. The primary aim of the study was to study the association between the concentration of the circulating biomarker canine prostate specific esterase (CPSE) and prostatic size. Seventy-nine dogs that were four years old or older were included in the study. Ultrasonography was used for calculating the volume of the prostate. The calculated volume was divided by an estimate of the normal prostatic volume in dogs aged one to four years, to determine the relative prostatic size: the size of the prostate in relation to the normal size in dogs 1-4 years old (Srel). CPSE was analyzed from serum samples. Multiple linear regression analysis was used for studying associations between variables. Prediction intervals for the relative prostatic size based on CPSE concentrations were calculated, as were receiver operating curves for CPSE concentrations predicting Srel. The concentration of CPSE was associated with the relative size and contour of the prostate (P < 0.001). All dogs with clinical signs of BPH had an Srel ≥ 2.5. A CPSE concentration of 200 ng/mL predicted Srel to 2.5 (95% P.I: 1.2-4.8). Based on ROC analysis, the optimal discrimination threshold for CPSE concentration for Srel ≥ 2.5 was estimated as 90 ng/mL (95% confidence interval: 50-140), with a sensitivity of 85% and a specificity of 72%. Screening for CPSE is of potential value in the aging intact male dogs. Although many dogs with an Srel ≥ 2.5 show no clinical signs, the insidious nature of BPH supports further investigations of the prostate in these dogs, corresponding to a CPSE concentration of approximately 90 ng/mL or higher.

T1 Recovery Is Predominantly Found in Black Holes and Is Associated with Clinical Improvement in Patients with Multiple Sclerosis.

BACKGROUND AND PURPOSE: Quantitative MR imaging parameters help to evaluate disease progression in multiple sclerosis and increase correlation with clinical disability. We therefore hypothesized that T1 values might be a marker for ongoing tissue damage or even remyelination and may help increase clinical correlation. MATERIALS AND METHODS: MR imaging was performed in 17 patients with relapsing-remitting MS at baseline and after 12 months of starting immunotherapy with dimethyl fumarate. On baseline images, lesion segmentation was performed for normal-appearing white matter, T2 hyperintense (FLAIR lesions), T1 hypointense (black holes), and contrast-enhancing lesions, and T1 relaxation times were obtained at baseline and after 12 months. Changes in clinical status were assessed by using the Expanded Disability Status Scale and Symbol Digit Modalities Test at both dates (Expanded Disability Status Scale-difference/Symbol Digit Modalities Test-diff). RESULTS: The highest T1 relaxation time at baseline was measured in black holes (1460.2 ± 209.46 ms) followed by FLAIR lesions (1400.38 ± 189.1 ms), pure FLAIR lesions (1327.5 ± 210.04 ms), contrast-enhancing lesions (1205.59 ± 199.95 ms), and normal-appearing white matter (851.34 ± 30.61 ms). After 12 months, T1 values had decreased significantly in black holes (1369.4 ± 267.81 ms), contrast-enhancing lesions (1079.57 ± 183.36 ms) (both P < .001), and normal-appearing white matter (841.98 ± 36.1 ms, P = .006). With the Jonckheere-Terpstra Test, better clinical scores were associated with decreasing T1 relaxation times in black holes (P < .05). CONCLUSIONS: T1 relaxation time is a useful quantitative MR imaging technique, which helps detect changes in MS lesions with time. We assume that these changes are associated with the degree of myelination within the lesions themselves and are pronounced in black holes. Additionally, decreasing T1 values in black holes were associated with clinical improvement.

Environmental Risk Factors for Diabetes Mellitus in Cats.

BACKGROUND: Diabetes in cats resembles type 2 diabetes in people. The etiology is not fully understood, but both genetic and environmental factors are believed to contribute. OBJECTIVES: To assess the associations of environmental risk factors with diabetes in cats. ANIMALS: Cats with a diagnosis of diabetes (n = 396) insured by a Swedish insurance company during years 2009-2013, and a control group (n = 1,670) matched on birth year. METHODS: A web-based questionnaire was used in a case-control study. An invitation to participate was sent to owners of 1,369 diabetic cats and 5,363 control cats. The survey contained questions related to the cat's breed, age, sex, neutering status, body condition, housing, access to the outdoors, activity level, diet, eating behavior, feeding routine, general health, stressful events, other pets in the household, medications, and vaccination status. Data were analyzed by multiple logistic regression. RESULTS: Response rate was 35% for the diabetic group and 32% for the control group. Indoor confinement, being a greedy eater, and being overweight were associated with an increased risk of diabetes. In cats assessed by owners as being normal weight, there was an association between eating predominantly dry food and an increased risk of diabetes (Odds ratio 3.8; 95% confidence intervals 1.3-11.2). CONCLUSIONS AND CLINICAL IMPORTANCE: Dry food is commonly fed to cats worldwide. The association found between dry food and an increased risk of diabetes in cats assessed as normal weight by owners warrants further attention.

Diagnostic possibilities from a serum sample-Clinical value of new methods within small animal reproduction, with focus on anti-Müllerian hormone.

During the last decade, analysis of anti-Müllerian hormone (AMH), highly conserved between mammalian species, has contributed to new information in reproductive endocrinology, due to clinically available diagnostic assays. AMH is produced solely in the gonads, in the Sertoli cells of testes and granulosa cells of the ovary, and thus offers possibilities to diagnose physiologic and pathologic conditions involving these organs. This article reviews indications for AMH analysis in cats and dogs, including diagnosing the presence of gonads, and granulosa or Sertoli cell tumours. Diagnostic challenges are addressed. One specific organ, the prostate, is commonly affected by pathologic changes in older dogs. A commercial assay for analysing canine prostatic specific esterase (CPSE) enables analysis of CPSE in clinical practice, of potential value in the workup of benign prostatic hyperplasia in male dogs. This is described in this review, as is a new method for analysis of steroids: liquid chromatography-tandem mass spectrometry LC-MS/MS. Steroids have since long been analysed in studies on reproduction, and LC-MS/MS has the advantage of allowing analysis of panels of multiple steroids from small sample volumes. Altogether, these available methods may give new insights into small animal reproduction and are valuable tools for the practicing veterinarian.

Atomic resolution imaging of beryl: an investigation of the nano-channel occupation.

Beryl in different varieties (emerald, aquamarine, heliodor etc.) displays a wide range of colours that have fascinated humans throughout history. Beryl is a hexagonal cyclo-silicate (ring-silicate) with channels going through the crystal along the c-axis. The channels are about 0.5 nm in diameter and can be occupied by water and alkali ions. Pure beryl (Be3 Al2 Si6 O18 ) is colourless (variety goshenite). The characteristic colours are believed to be mainly generated through substitutions with metal atoms in the lattice. Which atoms that are substituted is still debated it has been proposed that metal ions may also be enclosed in the channels and that this can also contribute to the crystal colouring. So far spectroscopy studies have not been able to fully answer this. Here we present the first experiments using atomic resolution scanning transmission electron microscope imaging (STEM) to investigate the channel occupation in beryl. We present images of a natural beryl crystal (variety heliodor) from the Bin Thuan Province in Vietnam. The channel occupation can be visualized. Based on the image contrast in combination with ex situ element analysis we suggest that some or all of the atoms that are visible in the channels are Fe ions.

High molecular weight PEGylation of human pancreatic polypeptide at position 22 improves stability and reduces food intake in mice.

BACKGROUND AND PURPOSE: Human pancreatic polypeptide (hPP) is known to suppress appetite and food intake, thereby representing a potential therapeutic approach against obesity and associated metabolic disorders. The aim of this study was to improve hPP stability by covalent PEGylation with diverse molecular weight polyethylene glycols (PEGs) at two positions using promising lead structures while maintaining target activity. EXPERIMENTAL APPROACH: Modified peptides were synthesized by combined solid-phase and solution-phase peptide synthesis. Their potency was investigated in constitutively expressing human epithelial cells and isolated human colonic mucosa as well as receptor-transfected artificial cell lines. Human blood plasma and porcine liver homogenates were used to examine the in vitro stability of the analogues. The most promising variants were injected s.c. in C57BL/6JRj mice to monitor fasting-induced food intake and bioavailability. KEY RESULTS: In human epithelia and colonic mucosal preparations, activity of the modified hPP peptides depended on the core sequence and latency of the peptides was related to PEG size. Peptides modified with a 22 kDa PEG (PEG22) remained intact in blood plasma and on incubation with liver homogenates for more than 96 h. Finally, hPP2-36 , [K22 (PEG22)]hPP2-36 and [K22 (PEG22),Q34 ]hPP significantly reduced cumulative food intake in mice over 16 h after s.c. administration. CONCLUSIONS AND IMPLICATIONS: Modification with PEG22 at position 22 stabilizes hPP significantly while extending its biological activities and could be used in drug development prospectively.

Immunolocalization of E-cadherin and ß-catenin in the cyclic and early pregnant canine endometrium.

Putative changes in E-cadherin and ß-catenin during implantation in dogs are of interest to study, as they are relevant proteins for epithelial integrity. E-cadherin and ß-catenin were immunolocalized in the canine endometrium during the estrous cycle and early pregnancy, using monoclonal antibodies. Both proteins were detected in all types of endometrial epithelia (surface epithelium [SE], superficial glandular, and deep glandular epithelia) at all stages of the estrous cycle and in early placental structures. E-cadherin depicted a gradient of intensity apparently being lowest in the SE to progressively increase toward the deepness of the endometrial glands, regardless of the stage of estrous cycle. The overall immunostaining was, however, weaker at diestrus. In pregnant samples, the trophoblast was conspicuously immunolabeled compared with the endometrial surface lining epithelium. In the latter, the cytoplasmic pattern predominated over the membrane-bound, as was also seen in the decidual cells of the placental labyrinth. In the early placenta, only trophoblast cells and lacunae retained membrane signals. ß-Catenin membrane labeling appeared relatively constant throughout the cycle, although a tendency toward a decrease in intensity was detected at the secretory stages. In addition, a dislocation of the immunoreaction from membrane to the cytoplasm was observed in both the SE and the glandular epithelia at particular stages of the cycle. In early pregnancy, a loss of the membranous pattern was observed in the SE and labyrinth, but neither on trophoblast nor in lacunae. The results show the existence of a softening of the adherens junctional complex in progestagen-dominated stages favoring embryo-maternal interactions and endometrial invasion during canine implantation.

X-ray scattering measurements of dissociation-induced metallization of dynamically compressed deuterium.

Hydrogen, the simplest element in the universe, has a surprisingly complex phase diagram. Because of applications to planetary science, inertial confinement fusion and fundamental physics, its high-pressure properties have been the subject of intense study over the past two decades. While sophisticated static experiments have probed hydrogen's structure at ever higher pressures, studies examining the higher-temperature regime using dynamic compression have mostly been limited to optical measurement techniques. Here we present spectrally resolved x-ray scattering measurements from plasmons in dynamically compressed deuterium. Combined with Compton scattering, and velocity interferometry to determine shock pressure and mass density, this allows us to extract ionization state as a function of compression. The onset of ionization occurs close in pressure to where density functional theory-molecular dynamics (DFT-MD) simulations show molecular dissociation, suggesting hydrogen transitions from a molecular and insulating fluid to a conducting state without passing through an intermediate atomic phase.

A modified time-of-flight method for precise determination of high speed ratios in molecular beams.

Time-of-flight (TOF) is a standard experimental technique for determining, among others, the speed ratio S (velocity spread) of a molecular beam. The speed ratio is a measure for the monochromaticity of the beam and an accurate determination of S is crucial for various applications, for example, for characterising chromatic aberrations in focussing experiments related to helium microscopy or for precise measurements of surface phonons and surface structures in molecular beam scattering experiments. For both of these applications, it is desirable to have as high a speed ratio as possible. Molecular beam TOF measurements are typically performed by chopping the beam using a rotating chopper with one or more slit openings. The TOF spectra are evaluated using a standard deconvolution method. However, for higher speed ratios, this method is very sensitive to errors related to the determination of the slit width and the beam diameter. The exact sensitivity depends on the beam diameter, the number of slits, the chopper radius, and the chopper rotation frequency. We present a modified method suitable for the evaluation of TOF measurements of high speed ratio beams. The modified method is based on a systematic variation of the chopper convolution parameters so that a set of independent measurements that can be fitted with an appropriate function are obtained. We show that with this modified method, it is possible to reduce the error by typically one order of magnitude compared to the standard method.