Low Molecular Weight Opioid Peptide Esters Could be Developed as a New Class of Analgesics

Low molecular weight opioid peptide esters (OPE) could become a class of analgesics with different side effect profiles than current opiates. OPE may have sufficient plasma stability to cross the blood brain barrier (BBB), undergo ester hydrolysis and produce analgesia. OPE of dipeptides, tyr-pro and tyr-gly conjugated to ethanol have a structure similar to the anesthestic agent, etomidate. Based upon the analgesic activity of dipeptide opioids, Lipinski’s criteria, and permeability of select GABA esters to cross the BBB, opioid peptides (OP) conjugated to ethanol, cholesterol or 3-glucose are lead recommendations. Preliminary animal data suggests that tyr-pro-ethyl ester crosses the BBB and unexpectedly produces hyperalgesia. Currently, there are no approved OP analgesics available for clinical use. Clinical trials of good manufacturing practice OP administered to patients suffering from chronic pain with indwelling intrathecal pumps could resolve the issue that OP may be superior to opiates and may redirect research

Game Form Misconceptions Do Not Explain the Endowment Effect

We test the claim that game form misconception among subjects making choices through the Becker-DeGroot-Marschak (BDM) value elicitation procedure provides an explanation for the endowment effect, as suggested by Cason and Plott (forthcoming). We employ a design that allows us to clearly identify whether subjects comprehend the incentive properties of a price-list version of the BDM procedure. We find a robust endowment effect, even among those subjects whose elicited valuations for a known monetary value and whose ability to calculate the payoffs resulting from their choices indicate no misconception of the task. We conclude that game form misconceptions alone are unlikely to account for behavioral patterns like the endowment effect

Study of the accreting pulsar 4U 0115+634 with a bulk and thermal Comptonization model

Highly magnetized pulsars accreting matter in a binary system are bright sources in the X-ray band (0.1-100 keV). Despite the early comprehension of the basic emission mechanism, their spectral energy distribution is generally described by phenomenological or simplified models. We propose a study of the spectral emission from the high mass X-ray binary pulsar 4U 0115+634 by means of thermal and bulk Comptonization models based on the physical properties of such objects. For this purpose, we analyze the BeppoSAX data in the energy range 0.7-100 keV of the 1999 giant outburst, 12 days after the maximum. We model the spectral energy distribution of the system using a two-component continuum. At higher energy, above ~7 keV, the emission is due to thermal and bulk Comptonization of the seed photons produced by cyclotron cooling of the accretion column, and at lower energy, the emission is due to thermal Comptonization of a blackbody source in a diffuse halo close to the stellar surface. From the best fit parameters, we argue that the cyclotron emission is produced ~1.7 km above the stellar surface, and escapes from the column near its base, where the absorption features are generated by the interaction with the magnetic field in a surrounding halo. We find that in 4U 0115+634, the observed spectrum is dominated by reprocessed cyclotron radiation, whereas in other bright sources with stronger magnetic fields such as Her X-1, the spectrum is dominated by reprocessed bremsstrahlung.Comment: 12 pages, accepted for publication on Astronomy and Astrophysic

Bmi-1 is required for maintenance of adult self-renewing haematopoietic stem cells

A central issue in stem cell biology is to understand the mechanisms that regulate the self-renewal of haematopoietic stem cells (HSCs), which are required for haematopoiesis to persist for the lifetime of the animal(1). We found that adult and fetal mouse and adult human HSCs express the proto-oncogene Bmi-1. The number of HSCs in the fetal liver of Bmi-1(-/-) mice(2) was normal. In postnatal Bmi-1(-/-) mice, the number of HSCs was markedly reduced. Transplanted fetal liver and bone marrow cells obtained from Bmi-1(-/-) mice were able to contribute only transiently to haematopoiesis. There was no detectable self-renewal of adult HSCs, indicating a cell autonomous defect in Bmi-1(-/-) mice. A gene expression analysis revealed that the expression of stem cell associated genes(3), cell survival genes, transcription factors, and genes modulating proliferation including p16(Ink4a) and p19(Arf) was altered in bone marrow cells of the Bmi-1(-/-) mice. Expression of p16(Ink4a) and p19(Arf) in normal HSCs resulted in proliferative arrest and p53-dependent cell death, respectively. Our results indicate that Bmi-1 is essential for the generation of self-renewing adult HSCs.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/62508/1/nature01587.pd

EFSA Panel on Dietetic Products, Nutrition and Allergies (NDA); Scientific Opinion on the substantiation of a health claim related to monacolin K in SYLVAN BIO red yeast rice and maintenance of normal blood LDL - cholesterol concentrations pursuant to Article 13(5) of Regulation (EC) No 1924/2006

Following an application from Sylvan Bio Europe BV, submitted for authorisation of a health claim pursuant to Article 13(5) of Regulation (EC) No 1924/2006 via the Competent Authority of the Netherlands, the Panel on Dietetic Products, Nutrition and Allergies (NDA) was asked to deliver an opinion on the scientific substantiation of a health claim related to monacolin K in SYLVAN BIO red yeast rice and maintenance of normal blood LDL-cholesterol concentrations. The food, monacolin K in SYLVAN BIO red yeast rice, that is the subject of the health claim is sufficiently characterised. The claimed effect, maintenance of normal blood LDL cholesterol concentrations, is a beneficial physiological effect. A claim on monacolin K from red yeast rice and maintenance of normal blood LDL-cholesterol concentrations has already been assessed with a favourable outcome at daily intakes of 10 mg monacolin K from any red yeast rice preparation (which would include SYLVAN BIO red yeast rice). The evidence provided by the applicant for the present application does not establish that monacolin K in SYLVAN BIO red yeast rice is different from monacolin K in other red yeast rice preparations with respect to its effect on blood LDL-cholesterol concentrations

The Intermediate Scale Branch of the Landscape

Three branches of the string theory landscape have plausibly been identified. One of these branches is expected to exhibit a roughly logarithmic distribution of supersymmetry breaking scales. The original KKLT models are in this class. We argue that certain features of the KKLT model are generic to this branch, and that the resulting phenomenology depends on a small set of discrete choices. As in the MSSM, the weak scale in these theories is tuned; a possible explanation is selection for the dark matter density.Comment: 16 pages. More thorough analysis; additonal reference

A systematic review of methods to immobilise breast tissue during adjuvant breast irradiation

Greater use of 3D conformal, Intensity Modulated Radiotherapy (IMRT) and external beam partial breast irradiation following local excision (LE) for breast cancer has necessitated a review of the effectiveness of immobilisation methods to stabilise breast tissue. To identify the suitability of currently available breast (rather than thorax) immobilisation techniques an appraisal of the literature was undertaken. The aim was to identify and evaluate the benefit of additional or novel immobilisation approaches (beyond the standard supine, single arm abducted and angled breast board technique adopted in most radiotherapy departments). A database search was supplemented with an individual search of key radiotherapy peer-reviewed journals, author searching, and searching of the grey literature. A total of 27 articles met the inclusion criteria. The review identified good reproducibility of the thorax using the standard supine arm-pole technique. Reproducibility with the prone technique appears inferior to supine methods (based on data from existing randomised controlled trials). Assessing the effectiveness of additional breast support devices (such as rings or thermoplastic material) is hampered by small sample sizes and a lack of randomised data for comparison. Attention to breast immobilisation is recommended, as well as agreement on how breast stability should be measured using volumetric imaging. Keywords: Breast, immobilisation, positioning, reproducibility, review.</p

Unusual quasars from the Sloan Digital Sky Survey selected by means of Kohonen self-organising maps

We exploit the spectral archive of the Sloan Digital Sky Survey (SDSS) Data Release 7 to select unusual quasar spectra. The selection method is based on a combination of the power of self-organising maps and the visual inspection of a huge number of spectra. Self-organising maps were applied to nearly 10^5 spectra classified as quasars by the SDSS pipeline. Particular attention was paid to minimise possible contamination by rare peculiar stellar spectral types. We present a catalogue of 1005 quasars with unusual spectra. This large sample provides a useful resource for both studying properties and relations of/between different types of unusual quasars and selecting particularly interesting objects. The spectra are grouped into six types. All these types turn out to be on average more luminous than comparison samples of normal quasars after a statistical correction is made for intrinsic reddening. Both the unusual broad absorption line (BAL) quasars and the strong iron emitters have significantly lower radio luminosities than normal quasars. We also confirm that strong BALs avoid the most radio-luminous quasars. Finally, we create a sample of quasars similar to the two "mysterious" objects discovered by Hall et al. (2002) and briefly discuss the quasar properties and possible explanations of their highly peculiar spectra. (Abstract modified to match the arXiv format)Comment: Added reference to section 6; a few typos corrected; corrections according to the version published in Astronomy and Astrophysic