Proximity effecs and curie temperature enhancement in Co/EuS and Fe/EuS multilayers

Two identical Co/EuS and Fe/EuS multilayers of six periods each and with individual layers of about 4 nm thick are grown by e-beam evaporation under ultrahigh vacuum conditions. The films show polycrystalline structure with a grain size limited by the individual layer thickness. Both multilayers consist of almost continuous layers with some roughness. The surface peak-to-peak roughness is about 4–5 nm. Magnetization measurements and calculations of the loops based on a Stoner–Wohlfarth-like model allow us to determine the direct antiferromagnetic exchange coupling constant between the 3d metal and EuS at 5 K. Both samples show strong enhancement of the Curie temperature of EuS up to at least 50 K with a EuS magnetization tail, which persists up to about 100 K. The J = 7/2 character of the EuS layers is shown to be responsible for the large Curie temperature enhancement

Band-gap tuning at the strong quantum confinement regime in magnetic semiconductor EuS thin films

Ultraviolet-visible absorption spectra of nanoscaled EuS thin films reveal a blue shift of the energy between the top-valence and bottom-conduction bands. This band-gap tuning changes smoothly with decreasing film thickness and becomes significant below the exciton Bohr diameter ~3.5nm indicating strong quantum confinement effects. The results are reproduced in the framework of the potential morphing method in Hartree Fock approximation. The large values of the effective mass of the holes, due to localization of the EuS ƒ-states, limit the blue shift to about 0.35eV. This controllable band-gap tuning of magnetic semiconductor EuS renders it useful for merging spintronics and optoelectronics

Layering and temperature-dependent magnetization and anisotropy of naturally produced Ni/NiO multilayers

Ni/NiO multilayers were grown by magnetron sputtering at room temperature, with the aid of the natural oxidation procedure. That is, at the end of the deposition of each single Ni layer, air is let to flow into the vacuum chamber through a leak valve. Then, a very thin NiO layer (~1.2nm) is formed. Simulated x-ray reflectivity patterns reveal that layering is excellent for individual Ni-layer thickness larger than 2.5nm, which is attributed to the intercalation of amorphous NiO between the polycrystalline Ni layers. The magnetization of the films, measured at temperatures 5–300K, has almost bulk- like value, whereas the films exhibit a trend to perpendicular magnetic anisotropy (PMA) with an unusual significant positive interface anisotropy contribution, which presents a weak temperature dependence. The power-law behavior of the multilayers indicates a non-negligible contribution of higher order anisotropies in the uniaxial anisotropy. Bloch-law fittings for the temperature dependence of the magnetization in the spin-wave regime show that the magnetization in the multilayers decreases faster as a function of temperature than the one of bulk Ni. Finally, when the individual Ni-layer thickness decreases below 2nm, the multilayer stacking vanishes, resulting in a dramatic decrease of the interface magnetic anisotropy and consequently in a decrease of the perpendicular magnetic anisotropy

The Killing of African Trypanosomes by Ethidium Bromide

Introduced in the 1950s, ethidium bromide (EB) is still used as an anti-trypanosomal drug for African cattle although its mechanism of killing has been unclear and controversial. EB has long been known to cause loss of the mitochondrial genome, named kinetoplast DNA (kDNA), a giant network of interlocked minicircles and maxicircles. However, the existence of viable parasites lacking kDNA (dyskinetoplastic) led many to think that kDNA loss could not be the mechanism of killing. When recent studies indicated that kDNA is indeed essential in bloodstream trypanosomes and that dyskinetoplastic cells survive only if they have a compensating mutation in the nuclear genome, we investigated the effect of EB on kDNA and its replication. We here report some remarkable effects of EB. Using EM and other techniques, we found that binding of EB to network minicircles is low, probably because of their association with proteins that prevent helix unwinding. In contrast, covalently-closed minicircles that had been released from the network for replication bind EB extensively, causing them, after isolation, to become highly supertwisted and to develop regions of left-handed Z-DNA (without EB, these circles are fully relaxed). In vivo, EB causes helix distortion of free minicircles, preventing replication initiation and resulting in kDNA loss and cell death. Unexpectedly, EB also kills dyskinetoplastic trypanosomes, lacking kDNA, by inhibiting nuclear replication. Since the effect on kDNA occurs at a >10-fold lower EB concentration than that on nuclear DNA, we conclude that minicircle replication initiation is likely EB's most vulnerable target, but the effect on nuclear replication may also contribute to cell killing

Electronic sculpting of ligand-GPCR subtype selectivity:the case of angiotensin II

GPCR subtypes possess distinct functional and pharmacological profiles, and thus development of subtype-selective ligands has immense therapeutic potential. This is especially the case for the angiotensin receptor subtypes AT1R and AT2R, where a functional negative control has been described and AT2R activation highlighted as an important cancer drug target. We describe a strategy to fine-tune ligand selectivity for the AT2R/AT1R subtypes through electronic control of ligand aromatic-prolyl interactions. Through this strategy an AT2R high affinity (<i>K</i>_i = 3 nM) agonist analogue that exerted 18,000-fold higher selectivity for AT2R versus AT1R was obtained. We show that this compound is a negative regulator of AT1R signaling since it is able to inhibit MCF-7 breast carcinoma cellular proliferation in the low nanomolar range

Kinetics and Determining Factors of the Virologic Response to Antiretrovirals during Pregnancy

HIV-infected pregnant women with undetectable plasma HIV RNA concentrations at delivery pose a minimal risk of vertical transmission. We studied the kinetics and the determinants of the virologic response to antiretroviral therapy in 117 consecutive pregnancies. Patients who initiated therapy during pregnancy had a VL decrease of 2 and 2.5 log10 after 4 and 24 weeks, respectively. Therapeutic drug monitoring (TDM) of the protease inhibitors administered in doses recommended for nonpregnant adults resulted in below-target concentrations in 29%, 35%, and 44% of 1st, 2nd, and 3rd trimester measurements, respectively, but low drug concentrations did not correlate with virologic failure. Demographic characteristics, antiretroviral experience prior to pregnancy, baseline VL, or use of specific antiretrovirals did not affect the virologic response. Adherence to ≥95% of prescribed doses and utilization of psychosocial services were associated with undetectable plasma HIV RNA at delivery. In conclusion, the virologic responses of pregnant and nonpregnant adults share similar charactersitics

Inhaled corticosteroid use is associated with increased circulating tregulatory cells in children with asthma

BACKGROUND: T regulatory (Treg) cells are important in balancing immune responses and dysregulation of Treg cells has been implicated in the pathogenesis of multiple disease states including asthma. In this study, our primary aim was to determine Treg cell frequency in the peripheral blood of children with and without asthma. The secondary aim was to explore the association between Treg cell frequency with allergen sensitization, disease severity and medication use. METHODS: Peripheral blood mononuclear cells from healthy control subjects (N = 93) and asthmatic children of varying disease severity (N = 66) were characterized by multi-parameter flow cytometry. RESULTS: Our findings demonstrate that children with asthma had a significantly increased frequency of Treg cells compared to children without asthma. Using a multivariate model, increased Treg cell frequency in children with asthma was most directly associated with inhaled corticosteroid use, and not asthma severity, allergic sensitization, or atopic status of the asthma. CONCLUSION: We conclude that low dose, local airway administration of corticosteroids is sufficient to impact the frequency of Treg cells in the peripheral blood. These data highlight the importance of considering medication exposure when studying Treg cells and suggest inhaled corticosteroid use in asthmatics may improve disease control through increased Treg cell frequency

Chromosome 10q26-driven age-related macular degeneration is associated with reduced levels of HTRA1 in human retinal pigment epithelium

Genome-wide association studies have identified the chromosome 10q26 (Chr10) locus, which contains the age-related maculopathy susceptibility 2 (ARMS2) and high temperature requirement A serine peptidase 1 (HTRA1) genes, as the strongest genetic risk factor for age-related macular degeneration (AMD) [L.G. Fritsche et al., Annu. Rev. Genomics Hum. Genet. 15, 151–171, (2014)]. To date, it has been difficult to assign causality to any specific single nucleotide polymorphism (SNP), haplotype, or gene within this region because of high linkage disequilibrium among the disease-associated variants [J. Jakobsdottir et al. Am. J. Hum. Genet. 77, 389–407 (2005); A. Rivera et al. Hum. Mol. Genet. 14, 3227–3236 (2005)]. Here, we show that HTRA1 messenger RNA (mRNA) is reduced in retinal pigment epithelium (RPE) but not in neural retina or choroid tissues derived from human donors with homozygous risk at the 10q26 locus. This tissue-specific decrease is mediated by the presence of a noncoding, cis-regulatory element overlapping the ARMS2 intron, which contains a potential Lhx2 transcription factor binding site that is disrupted by risk variant rs36212733. HtrA1 protein increases with age in the RPE–Bruch’s membrane (BM) interface in Chr10 nonrisk donors but fails to increase in donors with homozygous risk at the 10q26 locus. We propose that HtrA1, an extracellular chaperone and serine protease, functions to maintain the optimal integrity of the RPE–BM interface during the aging process and that reduced expression of HTRA1 mRNA and protein in Chr10 risk donors impairs this protective function, leading to increased risk of AMD pathogenesis. HtrA1 augmentation, not inhibition, in high-risk patients should be considered as a potential therapy for AMD

Toward Predicting Success and Failure in CS2: A Mixed-Method Analysis

Factors driving success and failure in CS1 are the subject of much study but less so for CS2. This paper investigates the transition from CS1 to CS2 in search of leading indicators of success in CS2. Both CS1 and CS2 at the University of North Carolina Wilmington (UNCW) are taught in Python with annual enrollments of 300 and 150 respectively. In this paper, we report on the following research questions: 1) Are CS1 grades indicators of CS2 grades? 2) Does a quantitative relationship exist between CS2 course grade and a modified version of the SCS1 concept inventory? 3) What are the most challenging aspects of CS2, and how well does CS1 prepare students for CS2 from the student's perspective? We provide a quantitative analysis of 2300 CS1 and CS2 course grades from 2013--2019. In Spring 2019, we administered a modified version of the SCS1 concept inventory to 44 students in the first week of CS2. Further, 69 students completed an exit questionnaire at the conclusion of CS2 to gain qualitative student feedback on their challenges in CS2 and on how well CS1 prepared them for CS2. We find that 56% of students' grades were lower in CS2 than CS1, 18% improved their grades, and 26% earned the same grade. Of the changes, 62% were within one grade point. We find a statistically significant correlation between the modified SCS1 score and CS2 grade points. Students identify linked lists and class/object concepts among the most challenging. Student feedback on CS2 challenges and the adequacy of their CS1 preparations identify possible avenues for improving the CS1-CS2 transition.Comment: The definitive Version of Record was published in 2020 ACM Southeast Conference (ACMSE 2020), April 2-4, 2020, Tampa, FL, USA. 8 page