A chemical survey of exoplanets with ARIEL

Thousands of exoplanets have now been discovered with a huge range of masses, sizes and orbits: from rocky Earth-like planets to large gas giants grazing the surface of their host star. However, the essential nature of these exoplanets remains largely mysterious: there is no known, discernible pattern linking the presence, size, or orbital parameters of a planet to the nature of its parent star. We have little idea whether the chemistry of a planet is linked to its formation environment, or whether the type of host star drives the physics and chemistry of the planet’s birth, and evolution. ARIEL was conceived to observe a large number (~1000) of transiting planets for statistical understanding, including gas giants, Neptunes, super-Earths and Earth-size planets around a range of host star types using transit spectroscopy in the 1.25–7.8 μm spectral range and multiple narrow-band photometry in the optical. ARIEL will focus on warm and hot planets to take advantage of their well-mixed atmospheres which should show minimal condensation and sequestration of high-Z materials compared to their colder Solar System siblings. Said warm and hot atmospheres are expected to be more representative of the planetary bulk composition. Observations of these warm/hot exoplanets, and in particular of their elemental composition (especially C, O, N, S, Si), will allow the understanding of the early stages of planetary and atmospheric formation during the nebular phase and the following few million years. ARIEL will thus provide a representative picture of the chemical nature of the exoplanets and relate this directly to the type and chemical environment of the host star. ARIEL is designed as a dedicated survey mission for combined-light spectroscopy, capable of observing a large and well-defined planet sample within its 4-year mission lifetime. Transit, eclipse and phase-curve spectroscopy methods, whereby the signal from the star and planet are differentiated using knowledge of the planetary ephemerides, allow us to measure atmospheric signals from the planet at levels of 10–100 part per million (ppm) relative to the star and, given the bright nature of targets, also allows more sophisticated techniques, such as eclipse mapping, to give a deeper insight into the nature of the atmosphere. These types of observations require a stable payload and satellite platform with broad, instantaneous wavelength coverage to detect many molecular species, probe the thermal structure, identify clouds and monitor the stellar activity. The wavelength range proposed covers all the expected major atmospheric gases from e.g. H2O, CO2, CH4 NH3, HCN, H2S through to the more exotic metallic compounds, such as TiO, VO, and condensed species. Simulations of ARIEL performance in conducting exoplanet surveys have been performed – using conservative estimates of mission performance and a full model of all significant noise sources in the measurement – using a list of potential ARIEL targets that incorporates the latest available exoplanet statistics. The conclusion at the end of the Phase A study, is that ARIEL – in line with the stated mission objectives – will be able to observe about 1000 exoplanets depending on the details of the adopted survey strategy, thus confirming the feasibility of the main science objectives.Peer reviewedFinal Published versio

Derivation of a Triple Mosaic Adenovirus for Cancer Gene Therapy

A safe and efficacious cancer medicine is necessary due to the increasing population of cancer patients whose particular diseases cannot be cured by the currently available treatment. Adenoviral (Ad) vectors represent a promising therapeutic medicine for human cancer therapy. However, several improvements are needed in order for Ad vectors to be effective cancer therapeutics, which include, but are not limited to, improvement of cellular uptake, enhanced cancer cell killing activity, and the capability of vector visualization and tracking once injected into the patients. To this end, we attempted to develop an Ad as a multifunctional platform incorporating targeting, imaging, and therapeutic motifs. In this study, we explored the utility of this proposed platform by generating an Ad vector containing the poly-lysine (pK), the herpes simplex virus type 1 (HSV-1) thymidine kinase (TK), and the monomeric red fluorescent protein (mRFP1) as targeting, tumor cell killing, and imaging motifs, respectively. Our study herein demonstrates the generation of the triple mosaic Ad vector with pK, HSV-1 TK, and mRFP1 at the carboxyl termini of Ad minor capsid protein IX (pIX). In addition, the functionalities of pK, HSV-1 TK, and mRFP1 proteins on the Ad vector were retained as confirmed by corresponding functional assays, indicating the potential multifunctional application of this new Ad vector for cancer gene therapy. The validation of the triple mosaic Ad vectors also argues for the ability of pIX modification as a base for the development of multifunctional Ad vectors

Vertebroplasty and kyphoplasty: a comparative review of efficacy and adverse events

Vertebroplasty and kyphoplasty have become common surgical techniques for the treatment of vertebral compression fractures. Vertebroplasty involves the percutaneous injection of bone cement into the cancellous bone of a vertebral body with the goals of pain alleviation and preventing further loss of vertebral body height. Kyphoplasty utilizes an inflatable balloon to create a cavity for the cement with the additional potential goals of restoring height and reducing kyphosis. Vertebroplasty and kyphoplasty are effective treatment options for the reduction of pain associated with vertebral body compression fractures. Biomechanical studies demonstrate that kyphoplasty is initially superior for increasing vertebral body height and reducing kyphosis, but these gains are lost with repetitive loading. Complications secondary to extravasation of cement include compression of neural elements and venous embolism. These complications are rare but more common with vertebroplasty. Vertebroplasty and kyphoplasty are both safe and effective procedures for the treatment of vertebral body compression fractures

Aggressive mammary carcinoma progression in Nrf2 knockout mice treated with 7,12-dimethylbenz[a]anthracene

<p>Abstract</p> <p>Background</p> <p>Activation of nuclear factor erythroid 2-related factor (Nrf2), which belongs to the basic leucine zipper transcription factor family, is a strategy for cancer chemopreventive phytochemicals. It is an important regulator of genes induced by oxidative stress, such as glutathione S-transferases, heme oxygenase-1 and peroxiredoxin 1, by activating the antioxidant response element (ARE). We <it>hypothesized </it>that (1) the citrus coumarin auraptene may suppress premalignant mammary lesions via activation of Nrf2/ARE, and (2) that Nrf2 knockout (KO) mice would be more susceptible to mammary carcinogenesis.</p> <p>Methods</p> <p>Premalignant lesions and mammary carcinomas were induced by medroxyprogesterone acetate and 7,12-dimethylbenz[a]anthracene treatment. The 10-week pre-malignant study was performed in which 8 groups of 10 each female wild-type (WT) and KO mice were fed either control diet or diets containing auraptene (500 ppm). A carcinogenesis study was also conducted in KO vs. WT mice (n = 30-34). Comparisons between groups were evaluated using ANOVA and Kaplan-Meier Survival statistics, and the Mann-Whitney U-test.</p> <p>Results</p> <p>All mice treated with carcinogen exhibited premalignant lesions but there were no differences by genotype or diet. In the KO mice, there was a dramatic increase in mammary carcinoma growth rate, size, and weight. Although there was no difference in overall survival, the KO mice had significantly lower mammary tumor-free survival. Also, in the KO mammary carcinomas, the active forms of NF-κB and β-catenin were increased ~2-fold whereas no differences in oxidized proteins were observed. Many other tumors were observed, including lymphomas. Interestingly, the incidences of lung adenomas in the KO mice were significantly higher than in the WT mice.</p> <p>Conclusions</p> <p>We report, for the first time, that there was no apparent difference in the formation of premalignant lesions, but rather, the KO mice exhibited rapid, aggressive mammary carcinoma progression.</p

African-American inflammatory bowel disease in a Southern U.S. health center

<p>Abstract</p> <p>Background</p> <p>Inflammatory Bowel Diseases (IBD) remain significant health problems in the US and worldwide. IBD is most often associated with eastern European ancestry, and is less frequently reported in other populations of African origin e.g. African Americans ('AAs'). Whether AAs represent an important population with IBD in the US remains unclear since few studies have investigated IBD in communities with a majority representation of AA patients. The Louisiana State University Health Sciences Center in Shreveport (LSUHSC-S) is a tertiary care medical center, with a patient base composed of 58% AA and 39% Caucasian (W), ideal for evaluating racial (AA vs. W) as well and gender (M vs. F) influences on IBD.</p> <p>Methods</p> <p>In this retrospective study, we evaluated 951 visits to LSUHSC-S for IBD (between 2000 to 2008) using non-identified patient information based on ICD-9 medical record coding (Crohn's disease 'CD'-555.0- 555.9 and ulcerative colitis 'UC'-556.0-556.9).</p> <p>Results</p> <p>Overall, there were more cases of CD seen than UC. UC and CD affected similar ratios of AA and Caucasian males (M) and females (F) with a rank order of WF > WM > AAF > AAM. Interestingly, in CD, we found that annual visits per person was the highest in AA M (10.7 ± 1.7); significantly higher (* -p < 0.05) than in WM (6.3 ± 1.0). Further, in CD, the female to male (F: M) ratio in AA was significantly higher (*- p < 0.05) (1.9 ± 0.2) than in Caucasians (F:M = 1.3 ± 0.1) suggesting a female dominance in AACD; no differences were seen in UC F: M ratios.</p> <p>Conclusion</p> <p>Although Caucasians still represent the greatest fraction of IBD (~64%), AAs with IBD made up >1/3 (36.4%) of annual IBD cases from 2000-2008 at LSUHSC-S. Further studies on genetic and environments risks for IBD risk in AAs are needed to understand differences in presentation and progression in AAs and other 'non-traditional' populations.</p

Genomic survey of the non-cultivatable opportunistic human pathogen, Enterocytozoon bieneusi

© 2009 The Authors. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in PLoS Pathogens 5 (2009): e1000261, doi:10.1371/journal.ppat.1000261.Enterocytozoon bieneusi is the most common microsporidian associated with human disease, particularly in the immunocompromised population. In the setting of HIV infection, it is associated with diarrhea and wasting syndrome. Like all microsporidia, E. bieneusi is an obligate, intracellular parasite, but unlike others, it is in direct contact with the host cell cytoplasm. Studies of E. bieneusi have been greatly limited due to the absence of genomic data and lack of a robust cultivation system. Here, we present the first large-scale genomic dataset for E. bieneusi. Approximately 3.86 Mb of unique sequence was generated by paired end Sanger sequencing, representing about 64% of the estimated 6 Mb genome. A total of 3,804 genes were identified in E. bieneusi, of which 1,702 encode proteins with assigned functions. Of these, 653 are homologs of Encephalitozoon cuniculi proteins. Only one E. bieneusi protein with assigned function had no E. cuniculi homolog. The shared proteins were, in general, evenly distributed among the functional categories, with the exception of a dearth of genes encoding proteins associated with pathways for fatty acid and core carbon metabolism. Short intergenic regions, high gene density, and shortened protein-coding sequences were observed in the E. bieneusi genome, all traits consistent with genomic compaction. Our findings suggest that E. bieneusi is a likely model for extreme genome reduction and host dependence.This research was supported by National Institutes of Health (NIH) grants R21 AI064118 (DEA) and R21 AI52792 (ST). HGM was supported in part by NIH contracts HHSN266200400041C and HHSN2662004037C (Bioinformatics Resource Centers) and by the G. Unger Vetlesen Foundation

Besides Purkinje cells and granule neurons: an appraisal of the cell biology of the interneurons of the cerebellar cortex

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Targeting poly(ADP-ribose) polymerase activity for cancer therapy

Poly(ADP-ribosyl)ation is a ubiquitous protein modification found in mammalian cells that modulates many cellular responses, including DNA repair. The poly(ADP-ribose) polymerase (PARP) family catalyze the formation and addition onto proteins of negatively charged ADP-ribose polymers synthesized from NAD+. The absence of PARP-1 and PARP-2, both of which are activated by DNA damage, results in hypersensitivity to ionizing radiation and alkylating agents. PARP inhibitors that compete with NAD+ at the enzyme’s activity site are effective chemo- and radiopotentiation agents and, in BRCA-deficient tumors, can be used as single-agent therapies acting through the principle of synthetic lethality. Through extensive drug-development programs, third-generation inhibitors have now entered clinical trials and are showing great promise. However, both PARP-1 and PARP-2 are not only involved in DNA repair but also in transcription regulation, chromatin modification, and cellular homeostasis. The impact on these processes of PARP inhibition on long-term therapeutic responses needs to be investigated

Manufacture Techniques of Chitosan-Based Microcapsules to Enhance Functional Properties of Textiles

In recent years, the textile industry has been moving to novel concepts of products, which could deliver to the user, improved performances. Such smart textiles have been proven to have the potential to integrate within a commodity garment advanced feature and functional properties of different kinds. Among those functionalities, considerable interest has been played in functionalizing commodity garments in order to make them positively interact with the human body and therefore being beneficial to the user health. This kind of functionalization generally exploits biopolymers, a class of materials that possess peculiar properties such as biocompatibility and biodegradability that make them suitable for bio-functional textile production. In the context of biopolymer chitosan has been proved to be an excellent potential candidate for this kind of application given its abundant availability and its chemical properties that it positively interacts with biological tissue. Notwithstanding the high potential of chitosan-based technologies in the textile sectors, several issues limit the large-scale production of such innovative garments. In facts the morphologies of chitosan structures should be optimized in order to make them better exploit the biological activity; moreover a suitable process for the application of chitosan structures to the textile must be designed. The application process should indeed not only allow an effective and durable fixation of chitosan to textile but also comply with environmental rules concerning pollution emission and utilization of harmful substances. This chapter reviews the use of microencapsulation technique as an approach to effectively apply chitosan to the textile material while overcoming the significant limitations of finishing processes. The assembly of chitosan macromolecules into microcapsules was proved to boost the biological properties of the polymer thanks to a considerable increase in the surface area available for interactions with the living tissues. Moreover, the incorporation of different active substances into chitosan shells allows the design of multifunctional materials that effectively combine core and shell properties. Based on the kind of substances to be incorporated, several encapsulation processes have been developed. The literature evidences how the proper choices concerning encapsulation technology, chemical formulations, and process parameter allow tuning the properties and the performances of the obtained microcapsules. Furthermore, the microcapsules based finishing process have been reviewed evidencing how the microcapsules morphology can positively interact with textile substrate allowing an improvement in the durability of the treatment. The application of the chitosan shelled microcapsules was proved to be capable of imparting different functionalities to textile substrates opening possibilities for a new generation of garments with improved performances and with the potential of protecting the user from multiple harms. Lastly, a continuous interest was observed in improving the process and formulation design in order to avoid the usage of toxic substances, therefore, complying with an environmentally friendly approach