Re-analysis of published data from the UKDMC NaI(Tl) dark matter experiment is presented using latest spin factors and comparison is made with the sensitivity predicted for NAIAD, a 100 kg NaI ...detector concept based on unencapsulated NaI(Tl). We present experimental results and Monte Carlo simulations for NAIAD and show that a factor of 1.5–2 improvement in energy threshold is achievable over conventional NaI dark matter detectors with consequent ∼50% improvement in nuclear recoil discrimination at 10 keV. An overall improvement in sensitivity to spin dependent WIMP interactions of factor 50, based on 100 kg×yrs of data, is predicted relative to previous UKDMC limits.
Abstract This study examined the gene transfer efficiency and toxicity of 2-kDa polyethylenimine conjugated to gold nanoparticles (PEI2-GNPs) in the human cornea in vitro and rabbit cornea in vivo. ...PEI2-GNPs with nitrogen-to-phosphorus ratios of up to 180 exhibited significant transgene delivery in the human cornea without altering the viability or phenotype of these cells. Similarly, PEI2-GNPs applied to corneal tissues collected after 12 hours, 72 hours, or 7 days exhibited appreciable gold uptake throughout the rabbit stroma with gradual clearance of GNPs over time. Transmission electron microscopy detected GNPs in the keratocytes and the extracellular matrix of the rabbit corneas. Additionally, slit-lamp biomicroscopy in live animals even 7 days after topical PEI2-GNP application to the cornea detected no inflammation, redness, or edema in rabbit eyes in vivo, with only moderate cell death and immune reactions. These results suggest that PEI2-GNPs are safe for the cornea and can potentially be useful for corneal gene therapy in vivo. From the Clinical Editor This study examined the gene transfer efficiency and toxicity of 2-kDa polyethylenimine conjugated to gold nanoparticles in the human cornea in vitro and rabbit cornea in vivo. The results suggest that PEI2-GNPs are safe for the cornea and can potentially be useful for corneal gene therapy in vivo.
Dark matter candidates such as the weakly interacting massive particles can be detected through elastic scatterings with a nucleus. The scintillation efficiency of carbon and hydrogen nuclear recoils ...in an organic liquid scintillator was measured for such a possible dark matter detector. The recoil energies from 50 keV to ∼1 MeV were explored for both nuclei. The carbon recoil efficiency, of particular interest for a dark matter detector, was observed to increase from 0.8
+0.09
−0.11% of the electron recoil efficiency at 500 keV to 4.8
+0.85
−2.99% at 46 keV. Such an enhancement is very encouraging for the purpose of dark matter searches as well as other similar low-energy experiments, and the results are well described by a modified Birks' light yield formula.
Background There is uncertainty about the nature of the relationship between mite allergen exposure during infancy and the expression of allergic diseases in childhood. Objective We sought to explore ...the relationships between repeated measurements of mite allergen exposure during the first 5 years of life and clinical allergic disease outcomes at age 5 years. Methods In a birth cohort of 516 at-risk children, 13 bed dust samples were collected between birth and 5 years of age and analyzed for mite allergen. At age 5 years, the presence of mite atopy was assessed based on skin prick test results, and clinical assessments for asthma, eczema, and wheeze were conducted. The association of allergen exposure with each clinical outcome was examined by means of logistic regression, with adjustments for potential confounders. Results The lowest and highest mite exposure quintiles, expressed as mean allergen concentration averaged over 0 to 5 years, were associated with a lower prevalence of mite atopy and of asthma compared with intermediate levels of exposure. These relationships, when determined by using average allergen concentration over 0 to 18 months, were weaker. Conclusions This study demonstrates a nonlinear relationship between mite allergen exposure and clinical outcomes in this generally high mite allergen environment.
The first underground data run of the ZEPLIN-II experiment has set a limit on the nuclear recoil rate in the two-phase xenon detector for direct dark matter searches. In this Letter the results from ...this run are converted into the limits on spin-dependent WIMP-proton and WIMP-neutron cross-sections. The minimum of the curve for WIMP-neutron cross-section corresponds to
7
×
10
−2
pb
at a WIMP mass of around 65 GeV.
Activation of the PI3K/AKT/mTOR pathway through loss of phosphatase and tensin homolog (PTEN) occurs in approximately 50% of patients with metastatic castration-resistant prostate cancer (mCRPC). ...Recent evidence suggests that combined inhibition of the androgen receptor (AR) and AKT may be beneficial in mCRPC with PTEN loss.
mCRPC patients who previously failed abiraterone and/or enzalutamide, received escalating doses of AZD5363 (capivasertib) starting at 320 mg twice daily (b.i.d.) given 4 days on and 3 days off, in combination with enzalutamide 160 mg daily. The co-primary endpoints were safety/tolerability and determining the maximum tolerated dose and recommended phase II dose; pharmacokinetics, antitumour activity, and exploratory biomarker analysis were also evaluated.
Sixteen patients were enrolled, 15 received study treatment and 13 were assessable for dose-limiting toxicities (DLTs). Patients were treated at 320, 400, and 480 mg b.i.d. dose levels of capivasertib. The recommended phase II dose identified for capivasertib was 400 mg b.i.d. with 1/6 patients experiencing a DLT (maculopapular rash) at this level. The most common grade ≥3 adverse events were hyperglycemia (26.7%) and rash (20%). Concomitant administration of enzalutamide significantly decreased plasma exposure of capivasertib, though this did not appear to impact pharmacodynamics. Three patients met the criteria for response (defined as prostate-specific antigen decline ≥50%, circulating tumour cell conversion, and/or radiological response). Responses were seen in patients with PTEN loss or activating mutations in AKT, low or absent AR-V7 expression, as well as those with an increase in phosphorylated extracellular signal-regulated kinase (pERK) in post-exposure samples.
The combination of capivasertib and enzalutamide is tolerable and has antitumour activity, with all responding patients harbouring aberrations in the PI3K/AKT/mTOR pathway.
NCT02525068
•Preclinical data suggest that inhibition of both the AR and PI3K/AKT/mTOR signalling has synergistic activity in PTEN loss prostate cancer models.•Here we present a phase I clinical trial of enzalutamide combined with the AKT inhibitor capivasertib in patients with mCRPC and show that this regimen is safe and tolerable.•This combination has antitumour activity with all responding patients harbouring aberrations in the PI3K/AKT/mTOR pathway.
We present results from a GEANT4-based Monte Carlo tool for end-to-end simulations of the ZEPLIN-III dark matter experiment. ZEPLIN-III is a two-phase detector which measures both the scintillation ...light and the ionisation charge generated in liquid xenon by interacting particles and radiation. The software models the instrument response to radioactive backgrounds and calibration sources, including the generation, ray-tracing and detection of the primary and secondary scintillations in liquid and gaseous xenon, and subsequent processing by data acquisition electronics. A flexible user interface allows easy modification of detector parameters at run time. Realistic datasets can be produced to help with data analysis, an example of which is the position reconstruction algorithm developed from simulated data. We present a range of simulation results confirming the original design sensitivity of a few times 10
−8
pb to the WIMP-nucleon cross-section.
CsI(Tl) for WIMP dark matter searches Kudryavtsev, V.A; Spooner, N.J.C; Tovey, D.R ...
Nuclear instruments & methods in physics research. Section A, Accelerators, spectrometers, detectors and associated equipment,
2001, 2001-1-00, Letnik:
456, Številka:
3
Journal Article
Recenzirano
Odprti dostop
We report a study of CsI(Tl) scintillator to assess its applicability in experiments to search for dark matter particles. Measurements of the mean scintillation pulse shapes due to nuclear and ...electron recoils have been performed. We find that, as with NaI(Tl), pulse shape analysis can be used to discriminate between electron and nuclear recoils down to 4 keV. However, the discrimination factor is typically 10–15% better than in NaI(Tl) above 4 keV. The quenching factor for caesium and iodine recoils was measured and found to increase from 11% to ∼17% with decreasing recoil energy from 60 to 12 keV. Based on these results, the potential sensitivity of CsI(Tl) to dark matter particles in the form of neutralinos was calculated. We find an improvement over NaI(Tl) for the spin-independent WIMP–nucleon interactions up to a factor of 5 assuming comparable electron background levels in the two scintillators.
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