Gamma evaluation with Octavius 4D phantom for pretreatment of modern radiotherapy treatment techniques

Purpose: In modern radiotherapy techniques such as intensity-modulated radiation therapy (IMRT) and volume modulated arc therapy (VMAT), the quality assurance (QA) process is vital. The goal of the study was to verify the treatment planning dose delivered during delivery of complex treatment plans. The QA standard is to perform patient-specific comparisons between planned doses and doses measured in a phantom. Materials and Methods: Ninety-five complex IMRT and VMAT plans for different pathologies planned using Eclipse treatment planning system (TPS). The Octavius 4D phantom has been used to verify patient specific quality assurance of all VMAT plans calculating with different algorithms. Conclusion: Overall, good agreement was observed between measured and calculated doses in most cases with gamma values above 1 in >95% of measured points in volumetric 3D analysis and 1 in >90% in 2D analysis. The Octavius 4D phantom is an effective and efficient method for patient specific QA

Structure-Activity Determinants in Antifungal Plant Defensins MsDef1 and MtDef4 with Different Modes of Action against Fusarium graminearum

Plant defensins are small cysteine-rich antimicrobial proteins. Their three-dimensional structures are similar in that they consist of an α-helix and three anti-parallel β-strands stabilized by four disulfide bonds. Plant defensins MsDef1 and MtDef4 are potent inhibitors of the growth of several filamentous fungi including Fusarium graminearum. However, they differ markedly in their antifungal properties as well as modes of antifungal action. MsDef1 induces prolific hyperbranching of fungal hyphae, whereas MtDef4 does not. Both defensins contain a highly conserved γ-core motif (GXCX3–9C), a hallmark signature present in the disulfide-stabilized antimicrobial peptides, composed of β2 and β3 strands and the interposed loop. The γ-core motifs of these two defensins differ significantly in their primary amino acid sequences and in their net charge. In this study, we have found that the major determinants of the antifungal activity and morphogenicity of these defensins reside in their γ-core motifs. The MsDef1-γ4 variant in which the γ-core motif of MsDef1 was replaced by that of MtDef4 was almost as potent as MtDef4 and also failed to induce hyperbranching of fungal hyphae. Importantly, the γ-core motif of MtDef4 alone was capable of inhibiting fungal growth, but that of MsDef1 was not. The analysis of synthetic γ-core variants of MtDef4 indicated that the cationic and hydrophobic amino acids were important for antifungal activity. Both MsDef1 and MtDef4 induced plasma membrane permeabilization; however, kinetic studies revealed that MtDef4 was more efficient in permeabilizing fungal plasma membrane than MsDef1. Furthermore, the in vitro antifungal activity of MsDef1, MsDef1-γ4, MtDef4 and peptides derived from the γ-core motif of each defensin was not solely dependent on their ability to permeabilize the fungal plasma membrane. The data reported here indicate that the γ-core motif defines the unique antifungal properties of each defensin and may facilitate de novo design of more potent antifungal peptides

Incorporation of Radio Frequency Identification Tag in Dentures to Facilitate Recognition and Forensic Human Identification

Forensic identification using odontology is based on the comparison of ante-mortem and post mortem dental records. The insertion of a radio frequency identification (RFId) tag into dentures could be used as an aid to identify decomposed bodies, by storing personal identification data in a small transponder that can be radio-transmitted to a reader connected to a computer. A small passive, 12 x 2,1 mm, read-only RFId-tag was incorporated into the manufacture of three trial complete upper dentures and tested for a signal. The aim of this article is to demonstrate the feasibility of manufacturing such a dental prosthesis, the technical protocols for its implantation in the denture resin and its working principles. Future research and tests are required in order to verify human compatibility of the tagged denture and also to evaluate any potential deterioration in strength when subjected to high temperatures, or for damage resulting from everyday wear and tear. It should also be able to withstand the extreme conditions resulting from major accidents or mass disasters and procedures used to perform a forensic identification

A linear 19-Mer plant defensin-derived peptide acts synergistically with caspofungin against Candida albicans biofilms.

Transplantation and autoimmunit

Determinants of the prevalence of gout in the general population: a systematic review and meta-regression

Studies on the occurrence of gout show a large range in estimates. However, a clear insight into the factors responsible for this variation in estimates is lacking. Therefore, our aim was to review the literature on the prevalence and incidence of gout systematically and to obtain insight into the degree of and factors contributing to the heterogeneity. We searched MEDLINE, EMBASE, and Web of Science (January 1962 to July 2012) to identify primary studies on the prevalence and incidence of gout in the general population. Data were extracted by two persons on sources of clinical heterogeneity, methodological heterogeneity, and variation in outcome reporting. Meta-analysis and meta-regression analysis were performed for the prevalence of gout. Of 1,466 articles screened, 77 articles were included, of which 71 reported the prevalence and 12 the incidence of gout. The pooled prevalence (67 studies; N = 12,226,425) based on a random effects model was 0.6 % (95 % CI 0.4; 0.7), however there was a high level of heterogeneity (I2 = 99.9 %). Results from a mixed-effects meta-regression model indicated that age (p = 0.019), sex (p < 0.001), continent (p < 0.001), response rate (p = 0.016), consistency in data collection (p = 0.002), and case definition (p < 0.001) were significantly associated with gout prevalence and jointly accounted for 88.7 % of the heterogeneity. The incidence in the total population ranged from 0.06 to 2.68 per 1,000 person-years. In conclusion, gout is a common disease and the large variation in the prevalence data on gout is explained by sex, continent on which the study was performed, and the case definition of gout

Measurement of the Bottom-Strange Meson Mixing Phase in the Full CDF Data Set

We report a measurement of the bottom-strange meson mixing phase \beta_s using the time evolution of B0_s -> J/\psi (->\mu+\mu-) \phi (-> K+ K-) decays in which the quark-flavor content of the bottom-strange meson is identified at production. This measurement uses the full data set of proton-antiproton collisions at sqrt(s)= 1.96 TeV collected by the Collider Detector experiment at the Fermilab Tevatron, corresponding to 9.6 fb-1 of integrated luminosity. We report confidence regions in the two-dimensional space of \beta_s and the B0_s decay-width difference \Delta\Gamma_s, and measure \beta_s in [-\pi/2, -1.51] U [-0.06, 0.30] U [1.26, \pi/2] at the 68% confidence level, in agreement with the standard model expectation. Assuming the standard model value of \beta_s, we also determine \Delta\Gamma_s = 0.068 +- 0.026 (stat) +- 0.009 (syst) ps-1 and the mean B0_s lifetime, \tau_s = 1.528 +- 0.019 (stat) +- 0.009 (syst) ps, which are consistent and competitive with determinations by other experiments.Comment: 8 pages, 2 figures, Phys. Rev. Lett 109, 171802 (2012

Surface Localization of Glucosylceramide during Cryptococcus neoformans Infection Allows Targeting as a Potential Antifungal

Cryptococcus neoformans (Cn) is a significant human pathogen that, despite current treatments, continues to have a high morbidity rate especially in sub-Saharan Africa. The need for more tolerable and specific therapies has been clearly shown. In the search for novel drug targets, the gene for glucosylceramide synthase (GCS1) was deleted in Cn, resulting in a strain (Δgcs1) that does not produce glucosylceramide (GlcCer) and is avirulent in mouse models of infection. To understand the biology behind the connection between virulence and GlcCer, the production and localization of GlcCer must be characterized in conditions that are prohibitive to the growth of Δgcs1 (neutral pH and high CO2). These prohibitive conditions are physiologically similar to those found in the extracellular spaces of the lung during infection. Here, using immunofluorescence, we have shown that GlcCer localization to the cell surface is significantly increased during growth in these conditions and during infection. We further seek to exploit this localization by treatment with Cerezyme (Cz), a recombinant enzyme that metabolizes GlcCer, as a potential treatment for Cn. Cz treatment was found to reduce the amount of GlcCer in vitro, in cultures, and in Cn cells inhabiting the mouse lung. Treatment with Cz induced a membrane integrity defect in wild type Cn cells similar to Δgcs1. Cz treatment also reduced the in vitro growth of Cn in a dose and condition dependent manner. Finally, Cz treatment was shown to have a protective effect on survival in mice infected with Cn. Taken together, these studies have established the legitimacy of targeting the GlcCer and other related sphingolipid systems in the development of novel therapeutics

Petunia Floral Defensins with Unique Prodomains as Novel Candidates for Development of Fusarium Wilt Resistance in Transgenic Banana Plants

Antimicrobial peptides are a potent group of defense active molecules that have been utilized in developing resistance against a multitude of plant pathogens. Floral defensins constitute a group of cysteine-rich peptides showing potent growth inhibition of pathogenic filamentous fungi especially Fusarium oxysporum in vitro. Full length genes coding for two Petunia floral defensins, PhDef1 and PhDef2 having unique C- terminal 31 and 27 amino acid long predicted prodomains, were overexpressed in transgenic banana plants using embryogenic cells as explants for Agrobacterium–mediated genetic transformation. High level constitutive expression of these defensins in elite banana cv. Rasthali led to significant resistance against infection of Fusarium oxysporum f. sp. cubense as shown by in vitro and ex vivo bioassay studies. Transgenic banana lines expressing either of the two defensins were clearly less chlorotic and had significantly less infestation and discoloration in the vital corm region of the plant as compared to untransformed controls. Transgenic banana plants expressing high level of full-length PhDef1 and PhDef2 were phenotypically normal and no stunting was observed. In conclusion, our results suggest that high-level constitutive expression of floral defensins having distinctive prodomains is an efficient strategy for development of fungal resistance in economically important fruit crops like banana