Proposal and preliminary design for a high speed civil transport aircraft. Swift: A high speed civil transport for the year 2000

To meet the needs of the growing passenger traffic market in light of an aging subsonic fleet, a new breed of aircraft must be developed. The Swift is an aircraft that will economically meet these needs by the year 2000. Swift is a 246 passenger, Mach 2.5, luxury airliner. It has been designed to provide the benefit of comfortable, high speed transportation in a safe manner with minimal environmental impact. This report will discuss the features of the Swift aircraft and establish a solid, foundation for this supersonic transport of tomorrow

Técnicas de biopsia para el diagnóstico de lesiones mamarias no palpables

Facing a non-palpable mammary lesion requiring a diagnostic biopsy, consideration must be given to the most suitable guiding method for obtaining the latter. Three methods are employed at present: stereotaxy (basically in cases of microcalcifications), echography (above all in the nodules), and magnetic resonance (for lesions not made visible through the previous systems). The next step is to select the most suitable biopsy technique. The most classical and reliable technique is the surgical biopsy with prior marking using a metallic harpoon, but, besides its high cost, it has the drawback of being an aggressive technique for the diagnosis of a benign pathology. Numerous systems of puncture have been developed as alternatives. Puncture with a fine needle is technically simple to carry out and can provide good results in the mammary nodules, but the existence of positive and negative false results has progressively limited its use. As an alternative, the systems of biopsy with a broad needle have made it possible to obtain multiple cylinders with a high diagnostic reliability, above all in the case of mammary nodules. However, their use in microcalcifications continues to show negative false results. The arrival of systems of vacuum-assisted biopsy has made it possible to obtain cylinders of greater quality, above all in cases of microcalcifications. Finally, the systems of percutaneous resection biopsy by means of cannulas with a diameter of 22 mm make it possible to completely extract lesions of a size below that of the cannula, with a reliability similar to that of the surgical biopsy

Temperature Effects in the Composition of Metal Halide Perovskite thin Films

Metal halide perovskites have shown to be a structure with great promise as an efficient photovoltaic, but at the same time it is affected by instability problems that degrade their performance. Degradation mechanisms vary with temperature, moisture, oxidation, and energy conversion during light exposure. We study performance loss due to temperature by probing diffusion of elemental composition across the thickness of films produced by spin coating and for temperatures ranging from 20 to 200°C. X-ray reflectivity was used to identify the electron density, composition, and quality of the films, aided with X-ray fluorescence and X-ray photoelectron spectroscopy studies to obtain information about degradation of the organic phase of the films

Pathways to paediatric urology subspecialisation:a study of casemix, incumbent attitudes and opinions

Objective: To identify any self-reported differences or attitudes towards certification, publication, or practice patterns between adult urology and paediatric general surgery-trained paediatric urology providers. There are no known published differences in clinical/operative/research outcomes in either group. Methods: An 18-item cross-sectional survey was compiled through the EAU Young Academic Urologists (YAU) office and disseminated to a trans-Atlantic convenience sample of current practising paediatric urologists. This was created using a mini-Delphi method to provide current semi-quantitative data relating to current opinions and attitudes of this cohort. Results: A total of 228 respondents completed the survey, with female respondents representing 37% and 34% for urology and paediatric general surgery, respectively. Nearly 90% overall respondents felt that a full 2-year paediatric fellowship program was very important and 94% endorsed a collaborative dedicated paediatric urology on call service, with 92% supporting the joint development of transitional care. Urology managed higher numbers of bedwetting (p = 0.04), bladder bowel dysfunction (p = 0.02), endourological procedures (p = 0.04), and robotics (p = 0.04). Paediatric general surgery managed higher numbers of laparoscopic reconstruction (p = 0.03), and posterior urethral valve ablation (p = 0.002). Conclusion: This study represents the first time that a cross-sectional cohort of paediatric urologists from different training backgrounds were compared to assess their productivity, practice patterns and attitudes. Paediatric urology is in a unique position to have two contributing specialities, with the ability to provide optimal transitional and lifelong care. We believe that there should be a strong emphasis on collaboration and to remove any historically-created barriers under policies of equity, diversity and inclusivity.</p

Residual γH2AX foci as an indication of lethal DNA lesions

<p>Abstract</p> <p>Background</p> <p>Evidence suggests that tumor cells exposed to some DNA damaging agents are more likely to die if they retain microscopically visible γH2AX foci that are known to mark sites of double-strand breaks. This appears to be true even after exposure to the alkylating agent MNNG that does not cause direct double-strand breaks but does produce γH2AX foci when damaged DNA undergoes replication.</p> <p>Methods</p> <p>To examine this predictive ability further, SiHa human cervical carcinoma cells were exposed to 8 DNA damaging drugs (camptothecin, cisplatin, doxorubicin, etoposide, hydrogen peroxide, MNNG, temozolomide, and tirapazamine) and the fraction of cells that retained γH2AX foci 24 hours after a 30 or 60 min treatment was compared with the fraction of cells that lost clonogenicity. To determine if cells with residual repair foci are the cells that die, SiHa cervical cancer cells were stably transfected with a RAD51-GFP construct and live cell analysis was used to follow the fate of irradiated cells with RAD51-GFP foci.</p> <p>Results</p> <p>For all drugs regardless of their mechanism of interaction with DNA, close to a 1:1 correlation was observed between clonogenic surviving fraction and the fraction of cells that retained γH2AX foci 24 hours after treatment. Initial studies established that the fraction of cells that retained RAD51 foci after irradiation was similar to the fraction of cells that retained γH2AX foci and subsequently lost clonogenicity. Tracking individual irradiated live cells confirmed that SiHa cells with RAD51-GFP foci 24 hours after irradiation were more likely to die.</p> <p>Conclusion</p> <p>Retention of DNA damage-induced γH2AX foci appears to be indicative of lethal DNA damage so that it may be possible to predict tumor cell killing by a wide variety of DNA damaging agents simply by scoring the fraction of cells that retain γH2AX foci.</p

Effect of molecular and electronic structure on the light harvesting properties of dye sensitizers

The systematic trends in structural and electronic properties of perylene diimide (PDI) derived dye molecules have been investigated by DFT calculations based on projector augmented wave (PAW) method including gradient corrected exchange-correlation effects. TDDFT calculations have been performed to study the visible absorbance activity of these complexes. The effect of different ligands and halogen atoms attached to PDI were studied to characterize the light harvesting properties. The atomic size and electronegativity of the halogen were observed to alter the relaxed molecular geometries which in turn influenced the electronic behavior of the dye molecules. Ground state molecular structure of isolated dye molecules studied in this work depends on both the halogen atom and the carboxylic acid groups. DFT calculations revealed that the carboxylic acid ligands did not play an important role in changing the HOMO-LUMO gap of the sensitizer. However, they serve as anchor between the PDI and substrate titania surface of the solar cell or photocatalyst. A commercially available dye-sensitizer, ruthenium bipyridine (RuBpy), was also studied for electronic and structural properties in order to make a comparison with PDI derivatives for light harvesting properties. Results of this work suggest that fluorinated, chlorinated, brominated, and iyodinated PDI compounds can be useful as sensitizers in solar cells and in artificial photosynthesis.Comment: Single pdf file, 14 pages with 7 figures and 4 table

DNA Damage Responses in Human Induced Pluripotent Stem Cells and Embryonic Stem Cells

BACKGROUND: Induced pluripotent stem (iPS) cells have the capability to undergo self-renewal and differentiation into all somatic cell types. Since they can be produced through somatic cell reprogramming, which uses a defined set of transcription factors, iPS cells represent important sources of patient-specific cells for clinical applications. However, before these cells can be used in therapeutic designs, it is essential to understand their genetic stability.\ud \ud METHODOLOGY/PRINCIPAL FINDINGS: Here, we describe DNA damage responses in human iPS cells. We observe hypersensitivity to DNA damaging agents resulting in rapid induction of apoptosis after γ-irradiation. Expression of pluripotency factors does not appear to be diminished after irradiation in iPS cells. Following irradiation, iPS cells activate checkpoint signaling, evidenced by phosphorylation of ATM, NBS1, CHEK2, and TP53, localization of ATM to the double strand breaks (DSB), and localization of TP53 to the nucleus of NANOG-positive cells. We demonstrate that iPS cells temporary arrest cell cycle progression in the G(2) phase of the cell cycle, displaying a lack of the G(1)/S cell cycle arrest similar to human embryonic stem (ES) cells. Furthermore, both cell types remove DSB within six hours of γ-irradiation, form RAD51 foci and exhibit sister chromatid exchanges suggesting homologous recombination repair. Finally, we report elevated expression of genes involved in DNA damage signaling, checkpoint function, and repair of various types of DNA lesions in ES and iPS cells relative to their differentiated counterparts.\ud \ud CONCLUSIONS/SIGNIFICANCE: High degrees of similarity in DNA damage responses between ES and iPS cells were found. Even though reprogramming did not alter checkpoint signaling following DNA damage, dramatic changes in cell cycle structure, including a high percentage of cells in the S phase, increased radiosensitivity and loss of DNA damage-induced G(1)/S cell cycle arrest, were observed in stem cells generated by induced pluripotency.\ud \u

Targeting the epigenome: effects of epigenetic treatment strategies on genomic stability in healthy human cells

Epigenetic treatment concepts have long been ascribed as being tumour-selective. Over the last decade, it has become evident that epigenetic mechanisms are essential for a wide range of intracellular functions in healthy cells as well. Evaluation of possible side-effects and their underlying mechanisms in healthy human cells is necessary in order to improve not only patient safety, but also to support future drug development. Since epigenetic regulation directly interacts with genomic and chromosomal packaging density, increasing genomic instability may be a result subsequent to drug-induced epigenetic modifications. This review highlights past and current research efforts on the influence of epigenetic modification on genomic stability in healthy human cells

Repair at Single Targeted DNA Double-Strand Breaks in Pluripotent and Differentiated Human Cells

Differences in ex vivo cell culture conditions can drastically affect stem cell physiology. We sought to establish an assay for measuring the effects of chemical, environmental, and genetic manipulations on the precision of repair at a single DNA double-strand break (DSB) in pluripotent and somatic human cells. DSBs in mammalian cells are primarily repaired by either homologous recombination (HR) or nonhomologous end-joining (NHEJ). For the most part, previous studies of DSB repair in human cells have utilized nonspecific clastogens like ionizing radiation, which are highly nonphysiologic, or assayed repair at randomly integrated reporters. Measuring repair after random integration is potentially confounded by locus-specific effects on the efficiency and precision of repair. We show that the frequency of HR at a single DSB differs up to 20-fold between otherwise isogenic human embryonic stem cells (hESCs) based on the site of the DSB within the genome. To overcome locus-specific effects on DSB repair, we used zinc finger nucleases to efficiently target a DSB repair reporter to a safe-harbor locus in hESCs and a panel of somatic human cell lines. We demonstrate that repair at a targeted DSB is highly precise in hESCs, compared to either the somatic human cells or murine embryonic stem cells. Differentiation of hESCs harboring the targeted reporter into astrocytes reduces both the efficiency and precision of repair. Thus, the phenotype of repair at a single DSB can differ based on either the site of damage within the genome or the stage of cellular differentiation. Our approach to single DSB analysis has broad utility for defining the effects of genetic and environmental modifications on repair precision in pluripotent cells and their differentiated progeny