Activity of the EBNA1 promoter associated with lytic replication (Fp) in Epstein-Barr virus associated disorders

Background/Aims - In Epstein-Barr virus (EBV) positive cell lines that are stably infected, three different promoters are known to direct the transcription of EBV nuclear antigen 1 (EBNA1). These are located in the BamHI-C, BamHI-Q, and BamHI-F regions of the viral genome (Cp, Qp, and Fp, respectively). Fp is activated upon induction of the viral lytic cycle. The aim of this study was to investigate the activity of Fp in EBV associated diseases. Methods - Using reverse transcriptase polymerase chain reaction, a qualitative analysis of EBNA1 promoter usage in various EBV associated diseases was performed. Results - Fp driven transcription was detected in the context of primary infection and/or lytic replication; at least a portion of the Fp driven transcripts encoded EBNA1. Qp driven EBNA1 transcripts were detected in most samples across the range of disorders tested. Cp driven EBNA1 transcripts were detected in the context of immune suppression and in samples containing EBV positive (nonneoplastic) lymphoid cells. Conclusions - These results confirm the previously proposed housekeeping function of the Qp promoter.published_or_final_versio

The Structural Colors of Photonic Glasses

The color of materials usually originates from a combination of wavelength-dependent absorption and scattering. Controlling the color without the use of absorbing dyes is of practical interest, not only because of undesired bleaching properties of dyes but also regarding minimization of environmental and health issues. Color control without dyes can be achieved by tuning the material's scattering properties in controlling size and spatial arrangement of scatterers. Herein, calibrated photonic glasses (PGs), which are isotropic materials made by random aggregation of nonabsorbing, monodisperse colloidal polystyrene spheres, are used to generate a wide spectral range of purely structural, angular-independent colors. Experimental reflectance spectra for different sized spheres compare well with a recent theoretical model, which establishes the latter as a tool for color mapping in PGs. It allows to determine the range of visible colors accessible in PGs as function of size, packing fraction, and refractive index of scatterers. It also predicts color saturation on top of the white reflectance as function of the sample's optical thickness. Blue, green, and red are obtained even with low index, while saturated green, cyan, yellow, and magenta can be reached in higher index PGs over several orders of magnitude of sample thickness.Deutsche Forschungsgemeinschaft. Grant Number: SFB1214 Swiss National Science Foundation. Grant Number: 200020M_162846 Alexander von Humboldt Foundatio

Highly Stable Perovskite Supercrystals via Oil-in-Oil Templating

Inorganic perovskites display an enticing foreground for their wide range of optoelectronic applications. Recently, supercrystals (SCs) of inorganic perovskite nanocrystals (NCs) have been reported to possess highly ordered structure as well as novel collective optical properties, opening new opportunities for efficient films. Here, we report the large-scale assembly control of spherical, cubic, and hexagonal SCs of inorganic perovskite NCs through templating by oil-in-oil emulsions. We show that an interplay between the roundness of the cubic NCs and the tension of the confining droplet surface sets the superstructure morphology, and we exploit this interplay to design dense hyperlattices of SCs. The SC films show strongly enhanced stability for at least two months without obvious structural degradation and minor optical changes. Our results on the controlled large-scale assembly of perovskite NC superstructures provide new prospects for the bottom-up production of optoelectronic devices based on the microfluidic production of mesoscopic building blocks

Sensing electric fields using single diamond spins

The ability to sensitively detect charges under ambient conditions would be a fascinating new tool benefitting a wide range of researchers across disciplines. However, most current techniques are limited to low-temperature methods like single-electron transistors (SET), single-electron electrostatic force microscopy and scanning tunnelling microscopy. Here we open up a new quantum metrology technique demonstrating precision electric field measurement using a single nitrogen-vacancy defect centre(NV) spin in diamond. An AC electric field sensitivity reaching ~ 140V/cm/\surd Hz has been achieved. This corresponds to the electric field produced by a single elementary charge located at a distance of ~ 150 nm from our spin sensor with averaging for one second. By careful analysis of the electronic structure of the defect centre, we show how an applied magnetic field influences the electric field sensing properties. By this we demonstrate that diamond defect centre spins can be switched between electric and magnetic field sensing modes and identify suitable parameter ranges for both detector schemes. By combining magnetic and electric field sensitivity, nanoscale detection and ambient operation our study opens up new frontiers in imaging and sensing applications ranging from material science to bioimaging

The Glasgow-Maastricht foot model, evaluation of a 26 segment kinematic model of the foot

BACKGROUND: Accurately measuring of intrinsic foot kinematics using skin mounted markers is difficult, limited in part by the physical dimensions of the foot. Existing kinematic foot models solve this problem by combining multiple bones into idealized rigid segments. This study presents a novel foot model that allows the motion of the 26 bones to be individually estimated via a combination of partial joint constraints and coupling the motion of separate joints using kinematic rhythms. METHODS: Segmented CT data from one healthy subject was used to create a template Glasgow-Maastricht foot model (GM-model). Following this, the template was scaled to produce subject-specific models for five additional healthy participants using a surface scan of the foot and ankle. Forty-three skin mounted markers, mainly positioned around the foot and ankle, were used to capture the stance phase of the right foot of the six healthy participants during walking. The GM-model was then applied to calculate the intrinsic foot kinematics. RESULTS: Distinct motion patterns where found for all joints. The variability in outcome depended on the location of the joint, with reasonable results for sagittal plane motions and poor results for transverse plane motions. CONCLUSIONS: The results of the GM-model were comparable with existing literature, including bone pin studies, with respect to the range of motion, motion pattern and timing of the motion in the studied joints. This novel model is the most complete kinematic model to date. Further evaluation of the model is warranted

Sex differences in the association between plasma copeptin and incident type 2 diabetes: the Prevention of Renal and Vascular Endstage Disease (PREVEND) study

AIMS/HYPOTHESIS: Vasopressin plays a role in osmoregulation, glucose homeostasis and inflammation. Therefore, plasma copeptin, the stable C-terminal portion of the precursor of vasopressin, has strong potential as a biomarker for the cardiometabolic syndrome and diabetes. Previous results were contradictory, which may be explained by differences between men and women in responsiveness of the vasopressin system. The aim of this study was to evaluate the usefulness of copeptin for prediction of future type 2 diabetes in men and women separately. METHODS: From the Prevention of Renal and Vascular Endstage Disease (PREVEND) study, 4,063 women and 3,909 men without diabetes at baseline were included. A total of 208 women and 288 men developed diabetes during a median follow-up of 7.7 years. RESULTS: In multivariable-adjusted models, we observed a stronger association of copeptin with risk of future diabetes in women (OR 1.49 [95% CI 1.24, 1.79]) than in men (OR 1.01 [95% CI 0.85, 1.19]) (p (interaction) < 0.01). The addition of copeptin to the Data from the Epidemiological Study on the Insulin Resistance Syndrome (DESIR) clinical model improved the discriminative value (C-statistic,+0.007, p = 0.02) and reclassification (integrated discrimination improvement [IDI] = 0.004, p < 0.01) in women. However, we observed no improvement in men. The additive value of copeptin in women was maintained when other independent predictors, such as glucose, high sensitivity C-reactive protein (hs-CRP) and 24 h urinary albumin excretion (UAE), were included in the model. CONCLUSIONS/INTERPRETATION: The association of plasma copeptin with the risk of developing diabetes was stronger in women than in men. Plasma copeptin alone, and along with existing biomarkers (glucose, hs-CRP and UAE), significantly improved the risk prediction for diabetes in women

Oxaliplatin-induced loss of phosphorylated heavy neurofilament subunit neuronal immunoreactivity in rat DRG tissue

<p>Abstract</p> <p>Background</p> <p>Oxaliplatin and related chemotherapeutic drugs cause painful chronic peripheral neuropathies in cancer patients. We investigated changes in neuronal size profiles and neurofilament immunoreactivity in L5 dorsal root ganglion (DRG) tissue of adult female Wistar rats after multiple-dose treatment with oxaliplatin, cisplatin, carboplatin or paclitaxel.</p> <p>Results</p> <p>After treatment with oxaliplatin, phosphorylated neurofilament heavy subunit (pNF-H) immunoreactivity was reduced in neuronal cell bodies, but unchanged in nerve fibres, of the L5 DRG. Morphometric analysis confirmed significant changes in the number (-75%; <it>P </it>< 0.0002) and size (-45%; <it>P </it>< 0.0001) of pNF-H-immunoreactive neurons after oxaliplatin treatment. pNF-H-immunoreactive neurons had overlapping size profiles and co-localisation with neurons displaying cell body immunoreactivity for parvalbumin, non-phospho-specific neurofilament medium subunit (NF-M) and non-phospho-specific neurofilament heavy subunit (NF-H), in control DRG. However, there were no significant changes in the numbers of neurons with immunoreactivity for parvalbumin (4.6%, <it>P </it>= 0.82), NF-M (-1%, <it>P </it>= 0.96) or NF-H (0%; <it>P </it>= 0.93) after oxaliplatin treatment, although the sizes of parvalbumin (-29%, <it>P </it>= 0.047), NF-M (-11%, <it>P </it>= 0.038) and NF-H (-28%; <it>P </it>= 0.0033) immunoreactive neurons were reduced. In an independent comparison of different chemotherapeutic agents, the number of pNF-H-immunoreactive neurons was significantly altered by oxaliplatin (-77.2%; <it>P </it>< 0.0001) and cisplatin (-35.2%; <it>P </it>= 0.03) but not by carboplatin or paclitaxel, and their mean cell body area was significantly changed by oxaliplatin (-31.1%; <it>P </it>= 0.008) but not by cisplatin, carboplatin or paclitaxel.</p> <p>Conclusion</p> <p>This study has demonstrated a specific pattern of loss of pNF-H immunoreactivity in rat DRG tissue that corresponds with the relative neurotoxicity of oxaliplatin, cisplatin and carboplatin. Loss of pNF-H may be mechanistically linked to oxaliplatin-induced neuronal atrophy, and serves as a readily measureable endpoint of its neurotoxicity in the rat model.</p

How functional programming mattered

In 1989 when functional programming was still considered a niche topic, Hughes wrote a visionary paper arguing convincingly ‘why functional programming matters’. More than two decades have passed. Has functional programming really mattered? Our answer is a resounding ‘Yes!’. Functional programming is now at the forefront of a new generation of programming technologies, and enjoying increasing popularity and influence. In this paper, we review the impact of functional programming, focusing on how it has changed the way we may construct programs, the way we may verify programs, and fundamentally the way we may think about programs