350 Micron Dust Emission from High Redshift Objects

We report observations of a sample of high redshift sources (1.8<z<4.7), mainly radio-quiet quasars, at 350 microns using the SHARC bolometer camera at the Caltech Submillimeter Observatory. Nine sources were detected (>4-sigma) and upper limits were obtained for 11 with 350 micron flux density limits (3-sigma) in the range 30-125mJy. Combining published results at other far-infrared and millimeter wavelengths with the present data, we are able to estimate the temperature of the dust, finding relatively low values, averaging 50K. From the spectral energy distribution, we derive dust masses of a few 10^8 M_sun and luminosities of 4-33x10^{12} L_sun (uncorrected for any magnification) implying substantial star formation activity. Thus both the temperature and dust masses are not very different from those of local ultraluminous infrared galaxies. For this redshift range, the 350 micron observations trace the 60-100 micron rest frame emission and are thus directly comparable with IRAS studies of low redshift galaxies.Comment: 5 pages, 2 PS figures. Accepted for publication in Astrophysical Journal Letter

Phosphorescence-Fluorescence ratio imaging for monitoring the oxygen status during photodynamic therapy

The effectiveness of photodynamic therapy is strongly dependent on the availabilty of oxygen. In the present paper we show that the ratio between photosensitiser phosphorescence and fluorescence is a parameter that can be used to monitor the competition between singlet oxygen production and other processes quenching the photosensitiser triplet state. We present a theoretical basis for the validity of this approach and a series of in vitro imaging experiments

In situ light dosimetry during photodynamic therapy of Barrett's esophagus with 5-aminolevulinic acid

Background and Objectives: Previous studies with PhotoDynamic Therapy (PDT) in bladder and bronchi have shown that due to scattering and reflection, the actually delivered fluence rate on the surface in a hollow organ can be significantly higher than expected. In this pilot study, we investigated the differences between the primary calculated and the actual measured fluence rate during PDT of Barrett's Esophagus (BE) using 23 independent clinical measurements in 15 patients. Study Design/Materials and Methods: A KTP-dye module laser at 630 nm was used as light source. Light delivery was performed using a cylindrical light diffuser inserted in the center of an inflatable transparent balloon with a length corresponding to the length of the Barrett's epithelium. The total light output power of the cylindrical diffuser was calibrated using an integrating sphere to deliver a primary fluence rate of 100 mW cm-2. Two fiber-optic pseudo sphere isotropic detectors were placed on the balloon and were used to measure fluence rate at the surface of the esophageal wall during PDT. Results and Conclusions: The actual fluence rate measured was 1.5-3.9 times higher than the primary fluence rate for 630 nm. In general, the fluence rate amplification factor decreased with increasing redness of the tissue and was less for shorter diffusers. Fluence rate variations in time were observed which coincided with patients coughing, movement, and esophageal spasms. These factors combined with inter patient variability of the fluence rate measured appears to justify the routine application of this technique in PDT of BE

Somatostatin analogues for receptor targeted photodynamic therapy

Photodynamic therapy (PDT) is an established treatment modality, used mainly for anticancer therapy that relies on the interaction of photosensitizer, light and oxygen. For the treatment of pathologies in certain anatomical sites, improved targeting of the photosensitizer is necessary to prevent damage to healthy tissue. We report on a novel dual approach of targeted PDT (vascular and cellular targeting) utilizing the expression of neuropeptide somatostatin receptor (sst2) on tumor and neovascular-endothelial cells. We synthesized two conjugates containing the somatostatin analogue [Tyr3]-octreotate and Chlorin e6 (Ce6): Ce6-K3-[Tyr3]-octreotate (1) and Ce6-[Tyr3]-octreotate-K3-[Tyr3]-octreotate (2). Investigation of the uptake and photodynamic activity of conjugates in-vitro in human erythroleukemic K562 cells showed that conjugation of [Tyr3]-octreotate with Ce6 in conjugate 1 enhances uptake (by a factor 2) in cells over-expressing sst2 compared to wild-type cells. Co-treatment with excess free Octreotide abrogated the phototoxicity of conjugate 1 indicative of a specific sst2-mediated effect. In contrast conjugate 2 showed no receptor-mediated effect due to its high hydrophobicity. When compared with un-conjugated Ce6, the PDT activity of conjugate 1 was lower. However, it showed higher photostability which may compensate for its lower phototoxicity. Intra-vital fluorescence pharmacokinetic studies of conjugate 1 in rat skin-fold observation chambers transplanted with sst2+ AR42J acinar pancreas tumors showed significantly different uptake profiles compared to free Ce6. Co-treatment with free Octreotide significantly reduced conjugate uptake in tumor tissue (by a factor 4) as well as in the chamber neo-vasculature. These results show that conjugate 1 might have potential as an in-vivo sst2 targeting photosensitizer conjugate

Antarctic climate change and the environment: an update

We present an update of the ‘key points’ from the Antarctic Climate Change and the Environment (ACCE) report that was published by the Scientific Committee on Antarctic Research (SCAR) in 2009. We summarise subsequent advances in knowledge concerning how the climates of the Antarctic and Southern Ocean have changed in the past, how they might change in the future, and examine the associated impacts on the marine and terrestrial biota. We also incorporate relevant material presented by SCAR to the Antarctic Treaty Consultative Meetings, and make use of emerging results that will form part of the Intergovernmental Panel on Climate Change (IPCC) Fifth Assessment Repor

In vivo quantification of photosensitizer fluorescence in the skin-fold observation chamber using dual-wavelength excitation and NIR imaging

A major challenge in biomedical optics is the accurate quantification of in vivo fluorescence images. Fluorescence imaging is often used to determine the pharmacokinetics of photosensitizers used for photodynamic therapy. Often, however, this type of imaging does not take into account differences in and changes to tissue volume and optical properties of the tissue under interrogation. To address this problem, a ratiometric quantification method was developed and applied to monitor photosensitizer meso-tetra (hydroxyphenyl) chlorin (mTHPC) pharmacokinetics in the rat skin-fold observation chamber. The method employs a combination of dual-wavelength excitation and dualwavelength detection. Excitation and detection wavelengths were selected in the NIR region. One excitation wavelength was chosen to be at the Q band of mTHPC, whereas the second excitation wavelength was close to its absorption minimum. Two fluorescence emission bands were used; one at the secondary fluorescence maximum of mTHPC centered on 720 nm, and one in a region of tissue autofluorescence. The first excitation wavelength was used to excite the mTHPC and autofluorescence and the second to excite only autofluorescence, so that this could be subtracted. Subsequently, the autofluorescence-corrected mTHPC image was divided by the autofluorescence signal to correct for variations in tissue optical properties. This correction algorithm in principle results in a linear relation between the corrected fluorescence and photosensitizer concentration. The limitations of the presented method and comparison with previously published and validated techniques are discussed

Effects of antiplatelet therapy on stroke risk by brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases: subgroup analyses of the RESTART randomised, open-label trial

Background Findings from the RESTART trial suggest that starting antiplatelet therapy might reduce the risk of recurrent symptomatic intracerebral haemorrhage compared with avoiding antiplatelet therapy. Brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases (such as cerebral microbleeds) are associated with greater risks of recurrent intracerebral haemorrhage. We did subgroup analyses of the RESTART trial to explore whether these brain imaging features modify the effects of antiplatelet therapy

The IPD-IMGT/HLA Database

It is 24 years since the IPD-IMGT/HLA Database, http://www.ebi.ac.uk/ipd/imgt/hla/, was first released, providing the HLA community with a searchable repository of highly curated HLA sequences. The database now contains over 35 000 alleles of the human Major Histocompatibility Complex (MHC) named by the WHO Nomenclature Committee for Factors of the HLA System. This complex contains the most polymorphic genes in the human genome and is now considered hyperpolymorphic. The IPD-IMGT/HLA Database provides a stable and user-friendly repository for this information. Uptake of Next Generation Sequencing technology in recent years has driven an increase in the number of alleles and the length of sequences submitted. As the size of the database has grown the traditional methods of accessing and presenting this data have been challenged, in response, we have developed a suite of tools providing an enhanced user experience to our traditional web-based users while creating new programmatic access for our bioinformatics user base. This suite of tools is powered by the IPD-API, an Application Programming Interface (API), providing scalable and flexible access to the database. The IPD-API provides a stable platform for our future development allowing us to meet the future challenges of the HLA field and needs of the community

Potential red-flag identification of colorectal adenomas with wide-field fluorescence molecular endoscopy

Adenoma miss rates in colonoscopy are unacceptably high, especially for sessile serrated adenomas / polyps (SSA/Ps) and in high-risk populations, such as patients with Lynch syndrome. Detection rates may be improved by fluorescence molecular endoscopy (FME), which allows morphological visualization of lesions with high-definition white-light imaging as well as fluorescence-guided identification of lesions with a specific molecular marker. In a clinical proof-of-principal study, we investigated FME for colorectal adenoma detection, using a fluorescently labelled antibody (bevacizumab-800CW) against vascular endothelial growth factor A (VEGFA), which is highly upregulated in colorectal adenomas. Methods: Patients with familial adenomatous polyposis (n = 17), received an intravenous injection with 4.5, 10 or 25 mg of bevacizumab-800CW. Three days later, they received NIR-FME. Results: VEGFA-targeted NIR-FME detected colorectal adenomas at all doses. Best results were achieved in the highest (25 mg) cohort, which even detected small adenomas ( < 3 mm). Spectroscopy analyses of freshly excised specimen demonstrated the highest adenoma-to-normal ratio of 1.84 for the 25 mg cohort, with a calculated median tracer concentration in adenomas of 6.43 nmol/mL. Ex vivo signal analyses demonstrated NIR fluorescence within the dysplastic areas of the adenomas. Conclusion: These results suggest that NIR-FME is clinically feasible as a real-time, red-flag technique for detection of colorectal adenomas