Temporin A and Bombinin H2 antimicrobial peptides exhibit selective cytotoxicity to lung cancer cells

Background. Recently, antimicrobial peptides (AMPs) have been investigated for their use in cancer therapy. They have been reported to selectively target and kill cancer cells whilst leaving normal healthy cells unaffected. Certain Anura AMPs have expressed selective cytotoxicity against tumour cells. Aim. To test the potential of Anura AMPs bombinin H2, bombinin H4, temporin A, and temporin L for use as therapeutic agents for non-small cell lung carcinoma (NSCLC). Methods. Cytotoxic effects on NSCLC cell lines A549 and Calu-3 and normal epithelial cell line Beas-2B were tested using the CellTox Green Cytotoxicity Assay. Their haemolytic effects on human erythrocytes were also tested for their clinical relevance. Cell membrane profiling, using MALDI-TOF, was performed to ascertain if membrane characteristics of the NSCLC and Beas-2B cell lines may contribute to the AMPs mode of action. Results. Bombinin H4 (100-1.5 μM, p<0.05) and temporin A (100-50 μM, p<0.05) showed selective cytotoxicity towards the NSCLC cell lines. Furthermore, they exhibited low levels of haemolytic activity (bombinin H4, 0.061%; temporin A, 0.874%) comparable to untreated cells. Cell membrane profiling showed the phospholipid composition of normal epithelial cell line Beas-2B to be divergent from the cancerous cell lines. However, there was an overlap in the phospholipid profiles of the NSCLC cell lines supporting the hypothesis that the AMPs may have a selective affinity via the membrane composition of cancerous cell lines. Conclusion. These results suggest that bombinin H4 and temporin A show potential for application in lung cancer therapies. Further in vitro and in vivo studies are required to develop a greater understanding of their use as anticancer agents

Song Crown: A New Compilation of Sweet Gospel Songs

https://digitalcommons.acu.edu/crs_books/1255/thumbnail.jp

Superconductors with Magnetic Impurities: Instantons and Sub-gap States

When subject to a weak magnetic impurity potential, the order parameter and quasi-particle energy gap of a bulk singlet superconductor are suppressed. According to the conventional mean-field theory of Abrikosov and Gor'kov, the integrity of the energy gap is maintained up to a critical concentration of magnetic impurities. In this paper, a field theoretic approach is developed to critically analyze the validity of the mean field theory. Using the supersymmetry technique we find a spatially homogeneous saddle-point that reproduces the Abrikosov-Gor'kov theory, and identify instanton contributions to the density of states that render the quasi-particle energy gap soft at any non-zero magnetic impurity concentration. The sub-gap states are associated with supersymmetry broken field configurations of the action. An analysis of fluctuations around these configurations shows how the underlying supersymmetry of the action is restored by zero modes. An estimate of the density of states is given for all dimensionalities. To illustrate the universality of the present scheme we apply the same method to study `gap fluctuations' in a normal quantum dot coupled to a superconducting terminal. Using the same instanton approach, we recover the universal result recently proposed by Vavilov et al. Finally, we emphasize the universality of the present scheme for the description of gap fluctuations in d-dimensional superconducting/normal structures.Comment: 18 pages, 9 eps figure

First detection of [CII]158um at high redshift: vigorous star formation in the early universe

We report the detection of the 2P_3/2 -> 2P_1/2 fine-structure line of C+ at 157.74 micron in SDSSJ114816.64+525150.3 (hereafter J1148+5251), the most distant known quasar, at z=6.42, using the IRAM 30-meter telescope. This is the first detection of the [CII] line at high redshift, and also the first detection in a Hyperluminous Infrared Galaxy (L_FIR > 10^13 Lsun). The [CII] line is detected at a significance level of 8 sigma and has a luminosity of 4.4 x 10^9 Lsun. The L_[CII]/L_FIR ratio is 2 x 10^-4, about an order of magnitude smaller than observed in local normal galaxies and similar to the ratio observed in local Ultraluminous Infrared Galaxies. The [CII] line luminosity indicates that the host galaxy of this quasar is undergoing an intense burst of star formation with an estimated rate of ~3000 Msun/yr. The detection of C+ in SDSS J1148+5251 suggests a significant enrichment of metals at z ~ 6 (age of the universe ~870 Myr), although the data are consistent with a reduced carbon to oxygen ratio as expected from chemical evolutionary models of the early phases of galaxy formation.Comment: 5 pages, 2 figures, accepted by A&A Letter

The Number and Transmission of [PSI+] Prion Seeds (Propagons) in the Yeast Saccharomyces cerevisiae

Yeast (Saccharomyces cerevisiae) prions are efficiently propagated and the on-going generation and transmission of prion seeds (propagons) to daughter cells during cell division ensures a high degree of mitotic stability. The reversible inhibition of the molecular chaperone Hsp104p by guanidine hydrochloride (GdnHCl) results in cell division-dependent elimination of yeast prions due to a block in propagon generation and the subsequent dilution out of propagons by cell division.Analysing the kinetics of the GdnHCl-induced elimination of the yeast [PSI+] prion has allowed us to develop novel statistical models that aid our understanding of prion propagation in yeast cells. Here we describe the application of a new stochastic model that allows us to estimate more accurately the mean number of propagons in a [PSI+] cell. To achieve this accuracy we also experimentally determine key cell reproduction parameters and show that the presence of the [PSI+] prion has no impact on these key processes. Additionally, we experimentally determine the proportion of propagons transmitted to a daughter cell and show this reflects the relative cell volume of mother and daughter cells at cell division.While propagon generation is an ATP-driven process, the partition of propagons to daughter cells occurs by passive transfer via the distribution of cytoplasm. Furthermore, our new estimates of n(0), the number of propagons per cell (500-1000), are some five times higher than our previous estimates and this has important implications for our understanding of the inheritance of the [PSI+] and the spontaneous formation of prion-free cells

Two Decades Using Stentless Porcine Aortic Root in Right Ventricular Outflow Tract Reconstruction

Background The stentless porcine aortic root prosthesis (SPAR) has been described as a suitable valve for right ventricular outflow tract reconstruction (RVOTR). Indiana University Methodist Hospital in Indianapolis, Indiana began using this valve for RVOTR in 1998. This study reports medium-term to late- term outcomes of the valve in the pulmonary position. Methods A retrospective chart review was conducted of patients older than 18 years of age who underwent RVOTR with a SPAR between April 2000 and October 2019. Primary outcomes included survival and freedom from any valvular reintervention. Secondary outcomes included endocarditis and conduit dysfunction detected by routine echocardiography or cardiac magnetic resonance imaging. Results A total of 135 patients underwent RVOTR with a SPAR at a median age of 32.4 years (range, 18 to 71 years). Of these patients, 129 had previous surgery. Indications included pulmonary insufficiency (90.4%), stenosis (34.8%), endocarditis (7.4%), and carcinoid (4.4%). Median follow-up was 2.97 years (interquartile range, 0.6 to 8.0 years). Overall survival was 93.3%, with 3 perioperative death and 6 late deaths. Endocarditis developed in 4 patients (2.9%), 2 of whom required reoperation. Progressive conduit degradation was evident at 10 years, with 22.2% and 7.7% having moderate stenosis and insufficiency, respectively. Eight (5.9%) reinterventions included 2 surgical replacements, 3 percutaneous replacements, and 3 balloon valvuloplasties at means of 8.5, 7.4, and 2.2 years, respectively. Overall freedom from reintervention at 1, 5, and 10 years was 99.1%, 94.7% and 90.7%, respectively. Conclusions In this large, single-institution experience with a long follow-up period, use of the SPAR demonstrated excellent midterm to long-term durability, low rates of endocarditis, and high freedom from reintervention

Influenza Surveillance among Outpatients and Inpatients in Morocco, 1996–2009

There is limited information about the epidemiology of influenza in Africa. We describe the epidemiology and seasonality of influenza in Morocco from 1996 to 2009 with particular emphasis on the 2007-2008 and 2008-2009 influenza seasons. Successes and challenges of the enhanced surveillance system introduced in 2007 are also discussed.Virologic sentinel surveillance for influenza virus was initiated in Morocco in 1996 using a network of private practitioners that collected oro-pharyngeal and naso-pharyngeal swabs from outpatients presenting with influenza-like-illness (ILI). The surveillance network expanded over the years to include inpatients presenting with severe acute respiratory illness (SARI) at hospitals and syndromic surveillance for ILI and acute respiratory infection (ARI). Respiratory samples and structured questionnaires were collected from eligible patients, and samples were tested by immunofluorescence assays and by viral isolation for influenza viruses.We obtained a total of 6465 respiratory specimens during 1996 to 2009, of which, 3102 were collected during 2007-2009. Of those, 2249 (72%) were from patients with ILI, and 853 (27%) were from patients with SARI. Among the 3,102 patients, 98 (3%) had laboratory-confirmed influenza, of whom, 85 (87%) had ILI and 13 (13%) had SARI. Among ILI patients, the highest proportion of laboratory-confirmed influenza occurred in children less than 5 years of age (3/169; 2% during 2007-2008 and 23/271; 9% during 2008-2009) and patients 25-59 years of age (8/440; 2% during 2007-2009 and 21/483; 4% during 2008-2009). All SARI patients with influenza were less than 14 years of age. During all surveillance years, influenza virus circulation was seasonal with peak circulation during the winter months of October through April.Influenza results in both mild and severe respiratory infections in Morocco, and accounted for a large proportion of all hospitalizations for severe respiratory illness among children 5 years of age and younger

Numerical Algebraic Geometry: A New Perspective on String and Gauge Theories

The interplay rich between algebraic geometry and string and gauge theories has recently been immensely aided by advances in computational algebra. However, these symbolic (Gr\"{o}bner) methods are severely limited by algorithmic issues such as exponential space complexity and being highly sequential. In this paper, we introduce a novel paradigm of numerical algebraic geometry which in a plethora of situations overcomes these short-comings. Its so-called 'embarrassing parallelizability' allows us to solve many problems and extract physical information which elude the symbolic methods. We describe the method and then use it to solve various problems arising from physics which could not be otherwise solved.Comment: 36 page