Endothelial progenitor cells in diabetic retinopathy

Diabetic retinopathy (DR) is a leading cause of visual impairment worldwide. Patients with DR may irreversibly lose sight as a result of the development of diabetic macular edema (DME) and/or proliferative diabetic retinopathy (PDR); retinal blood vessel dysfunction and degeneration plays an essential role in their pathogenesis. Although new treatments have been recently introduced for DME, including intravitreal vascular endothelial growth factor inhibitors (anti-VEGFs) and steroids, a high proportion of patients (~40-50%) do not respond to these therapies. Furthermore, for people with PDR, laser photocoagulation remains a mainstay therapy despite this being an inherently destructive procedure. Endothelial progenitor cells (EPCs) are a low-frequency population of circulating cells known to be recruited to sites of vessel damage and tissue ischemia where they promote vascular healing and re-perfusion. A growing body of evidence suggests that the number and function of EPCs are altered in patients with varying degrees of diabetes duration, metabolic control, and in the presence or absence of DR. Although there are no clear-cut outcomes from these clinical studies, there is mounting evidence that some EPC sub-types may be involved in the pathogenesis of DR and may also serve as biomarkers for disease progression and stratification. Moreover, some EPC sub-types have considerable potential as therapeutic modalities for DME and PDR in the context of cell therapy. This study presents basic clinical concepts of DR and combines this with a general insight on EPCs and their relation to future directions in understanding and treating this important diabetic complication.

High-impedance metasurfaces with interwoven conductor patterns

High impedance metasurfaces (HIMSs) formed by interwoven conductor arrays are proposed. Bandwidth comparable with that of the basic square patches is achieved at an order of magnitude smaller unit cells. The presented structures are apt for small mobile terminals and low frequency applications.

Prenatal hypoxia leads to increased muscle sympathetic nerve activity, sympathetic hyperinnervation, premature blunting of NPY signalling and hypertension in adult life

Adverse conditions prenatally increase the risk of cardiovascular disease, including hypertension. Chronic hypoxia in utero (CHU) causes endothelial dysfunction, but whether sympathetic vasoconstrictor nerve functioning is altered is unknown. We, therefore, compared in male CHU and control (N) rats muscle sympathetic nerve activity, vascular sympathetic innervation density, and mechanisms of sympathetic vasoconstriction. In young (Y)-CHU and Y-N rats (≈3 months), baseline arterial blood pressure was similar. However, tonic muscle sympathetic nerve activity recorded focally from arterial vessels of spinotrapezius muscle had higher mean frequency in Y-CHU than in Y-N rats (0.56±0.075 versus 0.33±0.036 Hz), and the proportions of single units with high instantaneous frequencies (1–5 and 6–10 Hz) being greater in Y-CHU rats. Sympathetic innervation density of tibial arteries was ≈50% greater in Y-CHU than in Y-N rats. Increases in femoral vascular resistance evoked by sympathetic stimulation at low frequency (2 Hz for 2 minutes) and bursts at 20 Hz were substantially smaller in Y-CHU than in Y-N rats. In Y-N only, the neuropeptide Y Y1-receptor antagonist BIBP3226 attenuated these responses. By contrast, baseline arterial blood pressure was higher in middle-aged (M)-CHU than in M-N rats (≈9 months; 139±3 versus 126±3 mmHg, respectively). BIBP3226 had no effect on femoral vascular resistance increases evoked by 2 Hz or 20 Hz bursts in M-N or M-CHU rats. These results indicate that fetal programming induced by prenatal hypoxia causes an increase in centrally generated muscle sympathetic nerve activity in youth and hypertension by middle age. This is associated with blunting of sympathetically evoked vasoconstriction and its neuropeptide Y component that may reflect premature vascular aging and contribute to increased risk of cardiovascular disease

Amplitude modulation of quantum-ion-acoustic wavepackets in electron-positron-ion plasmas: Modulational instability, envelope modes, extreme waves

A semirelativistic fluid model is employed to describe the nonlinear amplitude modulation of low-frequency (ionic scale) electrostatic waves in an unmagnetized electron-positron-ion plasma. Electrons and positrons are assumed to be degenerated and inertialess, whereas ions are warm and classical. A multiscale perturbation method is used to derive a nonlinear Schrödinger equation for the envelope amplitude, based on which the occurrence of modulational instability is investigated in detail. Various types of localized ion acoustic excitations are shown to exist, in the form of either bright type envelope solitons (envelope pulses) or dark-type envelope solitons (voids, holes). The plasma configurational parameters (namely, the relativistic degeneracy parameter, the positron concentration, and the ionic temperature) are shown to affect the conditions for modulational instability significantly, in fact modifying the associated threshold as well as the instability growth rate. In particular, the relativistic degeneracy parameter leads to an enhancement of the modulational instability mechanism. Furthermore, the effect of different relevant plasma parameters on the characteristics (amplitude, width) of these envelope solitary structures is also presented in detail. Finally, the occurrence of extreme amplitude excitation (rogue waves) is also discussed briefly. Our results aim at elucidating the formation and dynamics of nonlinear electrostatic excitations in superdense astrophysical regimes.

Tephra from andesitic Shiveluch volcano, Kamchatka, NW Pacific: chronology of explosive eruptions and geochemical fingerprinting of volcanic glass

The ~16-ka-long record of explosive eruptions from Shiveluch volcano (Kamchatka, NW Pacific) is refined using geochemical fingerprinting of tephra and radiocarbon ages. Volcanic glass from 77 prominent Holocene tephras and four Late Glacial tephra packages was analyzed by electron microprobe. Eruption ages were estimated using 113 radiocarbon dates for proximal tephra sequence. These radiocarbon dates were combined with 76 dates for regional Kamchatka marker tephra layers into a single Bayesian framework taking into account the stratigraphic ordering within and between the sites. As a result, we report ~1,700 high-quality glass analyses from Late Glacial–Holocene Shiveluch eruptions of known ages. These define the magmatic evolution of the volcano and provide a reference for correlations with distal fall deposits. Shiveluch tephras represent two major types of magmas, which have been feeding the volcano during the Late Glacial–Holocene time: Baidarny basaltic andesites and Young Shiveluch andesites. Baidarny tephras erupted mostly during the Late Glacial time (~16–12.8 ka BP) but persisted into the Holocene as subordinate admixture to the prevailing Young Shiveluch andesitic tephras (~12.7 ka BP–present). Baidarny basaltic andesite tephras have trachyandesite and trachydacite (SiO₂ < 71.5 wt%) glasses. The Young Shiveluch andesite tephras have rhyolitic glasses (SiO₂ > 71.5 wt%). Strongly calc-alkaline medium-K characteristics of Shiveluch volcanic glasses along with moderate Cl, CaO and low P₂O₅ contents permit reliable discrimination of Shiveluch tephras from the majority of other large Holocene tephras of Kamchatka. The Young Shiveluch glasses exhibit wave-like variations in SiO₂ contents through time that may reflect alternating periods of high and low frequency/volume of magma supply to deep magma reservoirs beneath the volcano. The compositional variability of Shiveluch glass allows geochemical fingerprinting of individual Shiveluch tephra layers which along with age estimates facilitates their use as a dating tool in paleovolcanological, paleoseismological, paleoenvironmental and archeological studies. Electronic tables accompanying this work offer a tool for statistical correlation of unknown tephras with proximal Shiveluch units taking into account sectors of actual tephra dispersal, eruption size and expected age. Several examples illustrate the effectiveness of the new database. The data are used to assign a few previously enigmatic wide-spread tephras to particular Shiveluch eruptions. Our finding of Shiveluch tephras in sediment cores in the Bering Sea at a distance of ~600 km from the source permits re-assessment of the maximum dispersal distances for Shiveluch tephras and provides links between terrestrial and marine paleoenvironmental records.

Heating Mechanisms for Intermittent Loops in Active Region Cores from AIA/SDO EUV Observations

We investigate intensity variations and energy deposition in five coronal loops in active region cores. These were selected for their strong variability in the AIA/SDO 94 Å intensity channel. We isolate the hot Fe XVIII and Fe XXI components of the 94 Å and 131 Å by modeling and subtracting the "warm" contributions to the emission. HMI/SDO data allow us to focus on "inter-moss" regions in the loops. The detailed evolution of the inter-moss intensity time series reveals loops that are impulsively heated in a mode compatible with a nanoflare storm, with a spike in the hot 131 Å signals leading and the other five EUV emission channels following in progressive cooling order. A sharp increase in electron temperature tends to follow closely after the hot 131 Å signal confirming the impulsive nature of the process. A cooler process of growing emission measure follows more slowly. The Fourier power spectra of the hot 131 Å signals, when averaged over the five loops, present three scaling regimes with break frequencies near 0.1 min–1 and 0.7 min–1. The low frequency regime corresponds to 1/f noise; the intermediate indicates a persistent scaling process and the high frequencies show white noise. Very similar results are found for the energy dissipation in a 2D "hybrid" shell model of loop magneto-turbulence, based on reduced magnetohydrodynamics, that is compatible with nanoflare statistics. We suggest that such turbulent dissipation is the energy source for our loops

An Informant Report Behavior Diary for Measuring Temper Outbursts in an Intervention Setting

Temper outbursts are associated with several psychological disorders and comprise a high priority for intervention. However, the low frequency of outbursts presents a challenge for valid measurement. In the present study an informant report behavior diary for measuring temper outbursts was developed and its validity assessed in a case series. Caregivers of 12 individuals with the neurodevelopmental disorder Prader-Willi syndrome (PWS, in which temper outbursts are common) completed a behavior diary over 4 weeks, and a structured interview. Heart rate and movement data were recorded during a sample of the days subject to diary reporting. Individuals with PWS completed self-report ratings of negative emotion experience. Behavior diaries showed high concordance with the component behaviors and duration of temper outbursts reported in structured interviews; but tended to report a lower frequency. For outbursts reported in diaries during physiological recording, heart rate was consistently elevated above a resting state baseline; and was comparable to that recorded during high physical activity. Available self-report data demonstrated correspondence with the diaries but few self-report data were produced. The present results provide critical proof of principle data supporting the concurrent validity of the ecologically valid, resource efficient diaries, which can be exploited in future research.

MHD wave modes resolved in fine-scale chromospheric magnetic structures

Within the last decade, due to significant improvements in the spatial and temporal resolution of chromospheric data, magneto hydrodynamic (MHD)wave studies in this fascinating region of the Sun's atmosphere have risen to the forefront of solar physics research. In this review we begin by reviewing the challenges and debates that have manifested in relation to MHD wave mode identification in fine-scale chromosphericmagnetic structures, including spicules, fibrils and mottles. Next we goon to discuss how the process of accurately identifying MHD wave modes also has a crucial role to play in estimating their wave energy flux.This is of cardinal importance for estimating what the possible contribution of MHD waves is to solar atmospheric heating. Finally, we detail how such advances in chromospheric MHD wave studies have also allowed us, for the first time, to implement cutting-edge magneto seismological techniques that provide new insight into the sub-resolution plasma structuring of the lower solar atmosphere.

The paradox of invasion: Reeves’ muntjac deer invade the British Isles from a limited number of founding females

High levels of genetic diversity and high propagule pressure are favoured by conservation biologists as the basis for successful reintroductions and ensuring the persistence of populations. However, invasion ecologists recognize the ‘paradox of invasion’, as successful species introductions may often be characterized by limited numbers of individuals and associated genetic bottlenecks. In the present study, we used a combination of high-resolution nuclear and mitochondrial genetic markers to investigate the invasion history of Reeves' muntjac deer in the British Isles. This invasion has caused severe economic and ecological damage, with secondary spread currently a concern throughout Europe and potentially globally. Microsatellite analysis based on eight loci grouped all 176 introduced individuals studied from across the species' range in the UK into one genetic cluster, and seven mitochondrial D-loop haplotypes were recovered, two of which were present at very low frequency and were related to more common haplotypes. Our results indicate that the entire invasion can be traced to a single founding event involving a low number of females. These findings highlight the fact that even small releases of species may, if ignored, result in irreversible and costly invasion, regardless of initial genetic diversity or continual genetic influx.

Injection locked oscillator lock detector

A simple circuit that is able to indicate if an injection-locked oscillator is in the locked condition by providing a ‘high’ or ‘low’ output is presented. The detector is compatible with most injection-locked oscillators as all that is required is access to the low-frequency bias circuit, with no direct access needed to the RF/microwave signals. To prove the universal nature of the lock detector it is successfully demonstrated practically for two scenarios: (i) a 1 GHz injection-locked VCO and (ii) a 60 GHz SiGe VCO MMIC.

Diagnostic value of increased sensitivity by massively parallel sequencing

Routine molecular diagnostics modalities are unable to confidently detect low frequency mutations (<5-15%) that may indicate response to targeted therapies. We confirm the presence of a low frequency NRAS mutation in a rectal cancer patient using massively parallel sequencing when previous Sanger sequencing results proved negative and Q-PCR testing inconclusive. There is increasing evidence that these low frequency mutations may confer resistance to anti-EGFR therapy. In view of negative/inconclusive Sanger sequencing and Q-PCR results for NRAS mutations in a KRAS wt rectal case, the diagnostic biopsy and 4 distinct subpopulations of cells in the resection specimen after conventional chemo/radiotherapy were massively parallel sequenced using the Ion Torrent PGM. DNA was derived from FFPE rectal cancer tissue and amplicons produced using the Cancer Hotspot Panel V2 and sequenced using semiconductor technology. NRAS mutations were observed at varying frequencies in the patient biopsy (12.2%) and all four subpopulations of cells in the resection with an average frequency of 7.3% (lowest 2.6%). The results of the NGS also provided the mutational status of 49 other genes that may have prognostic or predictive value, including KRAS and PIK3CA. NGS technology has been postulated in diagnostics because of its capability to generate results in large panels of clinically meaningful genes in a cost-effective manner. This case illustrates another potential advantage of this technology: its use for detecting low frequency mutations that may influence therapeutic decisions in cancer treatment.

An Ultrasonic Relaxation Study of 1-Alkyl-3-Methylmidazolium-Based Room Temperature Ionic Liquids: Probing the Role of Alkyl Chain Length in the Cation

Ultrasound absorption spectra of four 1-alkyl-3-methylimidazolium bis(trifluoromethylsulfonyl)imide were determined as a function of the alkyl chain length on the cation from 1-propyl- to 1-hexyl- from 293.15 to 323.15 K at ambient pressure. Herein, the ultrasound absorption measurements were carried out using a standard pulse technique within a frequency range from 10 to 300 MHz. Additionally the speed of sound, density and viscosity have been measured. The presence of strong dissipative processes during the ultrasound wave propagation was found experimentally, i.e. relaxation processes in the megahertz range were observed for all compounds over the whole temperature range. The relaxation spectra (both relaxation amplitude and relaxation frequency) were shown to be dependent on the alkyl side chain length of the 1-alkyl-3-methylimidazolium ring. In most cases, a single Debye model described the absorption spectra very well. However, a comparison of the determined spectra with the spectra of a few other imidazolium-based ionic liquids reported in the literature (in part recalculated in this work) shows that the complexity of the spectra increases rapidly with the elongation of the alkyl chain length on the cation. This complexity indicates that both the volume viscosity and the shear viscosity are involved in relaxation processes even in relatively low frequency ranges. As a consequence, the sound velocity dispersion is present at relatively low megahertz frequencies.

MHD Wave Modes Resolved in Fine-Scale Chromospheric Magnetic Structures

Due to its complex and dynamic fine-scale structure, the chromosphere is a particularly challenging region of the Sun's atmosphere to understand. It is now widely accepted that to model chromospheric dynamics, even on a magnetohydrodynamic (MHD) scale, while also calculating spectral line emission, one must realistically include the effects of partial ionization and radiative transfer in a multi-fluid plasma under non-LTE conditions. Accurate quantification of MHD wave energetics must befounded on a precise identification of the actual wave mode being observed. This chapter focuses on MHD kink-mode identification, MHD sausage mode identification, and MHD torsional Alfvén wave identification. It then reviews progress in determining more accurate energy flux estimations of specific MHD wave modes observed in the chromosphere. The chapter finally examines how the discovery of these MHD wave modes has helped us advance the field of chromosphericmagnetoseismology.

Ultra-High-Resolution Observations of MHD Waves in Photospheric Magnetic Structures

This chapter reviews the recent observations of waves and oscillations manifesting in fine-scale magnetic structures in the solar photosphere, which are often interpreted as the "building blocks' of the magnetic Sun. The authors found, through phase relationships between the various waveforms, that small-scale magnetic bright points (MBPs) in the photosphere demonstrated signatures of specific magnetoacoustic waves, in particular the sausage and kink modes. Modern magnetohydrodynamic (MHD) simulations of the lower solar atmosphere clearly show how torsional motions can easily be induced in magnetic elements in the photosphere through the processes of vortical motions and/or buffeting by neighboring granules. The authors detected significant power associated with high-frequency horizontal motions, and suggested that these cases may be especially important in the creation of a turbulent environment that efficiently promotes Alfvén wave dissipation.

Real-Time Multiple Event Detection and Classification Using Moving Window PCA

This paper proposes a method for the detection and classification of multiple events in an electrical power system in real-time, namely; islanding, high frequency events (loss of load) and low frequency events (loss of generation). This method is based on principal component analysis of frequency measurements and employs a moving window approach to combat the time-varying nature of power systems, thereby increasing overall situational awareness of the power system. Numerical case studies using both real data, collected from the UK power system, and simulated case studies, constructed using DigSilent PowerFactory, for islanding events, as well as both loss of load and generation dip events, are used to demonstrate the reliability of the proposed method.