478 research outputs found
Search for electric dipole moments at storage rings
Permanent electric dipole moments (EDMs) violate parity and time reversal
symmetry. Within the Standard Model (SM) they are many orders of magnitude
below present experimental sensitivity. Many extensions of the SM predict much
larger EDMs, which are therefore an excellent probe for the existence of "new
physics". Until recently it was believed that only electrically neutral systems
could be used for sensitive searches of EDMs. With the introduction of a novel
experimental method, high precision for charged systems will be within reach as
well. The features of this method and its possibilities are discussed.Comment: Proc. EXA2011, 6 pages;
http://www.springerlink.com/content/45l35376832vhrg0
Measurement of Permanent Electric Dipole Moments of Charged Hadrons in Storage Rings
Permanent Electric Dipole Moments (EDMs) of elementary particles violate two
fundamental symmetries: time reversal invariance (T) and parity (P). Assuming
the CPT theorem this implies CP-violation. The CP-violation of the Standard
Model is orders of magnitude too small to be observed experimentally in EDMs in
the foreseeable future. It is also way too small to explain the asymmetry in
abundance of matter and anti-matter in our universe. Hence, other mechanisms of
CP violation outside the realm of the Standard Model are searched for and could
result in measurable EDMs.
Up to now most of the EDM measurements were done with neutral particles. With
new techniques it is now possible to perform dedicated EDM experiments with
charged hadrons at storage rings where polarized particles are exposed to an
electric field. If an EDM exists the spin vector will experience a torque
resulting in change of the original spin direction which can be determined with
the help of a polarimeter. Although the principle of the measurement is simple,
the smallness of the expected effect makes this a challenging experiment
requiring new developments in various experimental areas.
Complementary efforts to measure EDMs of proton, deuteron and light nuclei
are pursued at Brookhaven National Laboratory and at Forschungszentrum Juelich
with an ultimate goal to reach a sensitivity of 10^{-29} e cm.Comment: 8 pages, 2 figure
Controlled release from zein matrices: Interplay of drug hydrophobicity and pH
Purpose: In earlier studies, the corn protein zein is found to be suitable as a sustained release agent, yet the range of drugs for which zein has been studied remains small. Here, zein is used as a sole excipient for drugs differing in hydrophobicity and isoelectric point: indomethacin, paracetamol and ranitidine. Methods: Caplets were prepared by hot-melt extrusion (HME) and injection moulding (IM). Each of the three model drugs were tested on two drug loadings in various dissolution media. The physical state of the drug, microstructure and hydration behaviour were investigated to build up understanding for the release behaviour from zein based matrix for drug delivery. Results: Drug crystallinity of the caplets increases with drug hydrophobicity. For ranitidine and indomethacin, swelling rates, swelling capacity and release rates were pH dependent as a consequence of the presence of charged groups on the drug molecules. Both hydration rates and release rates could be approached by existing models. Conclusion: Both the drug state as pH dependant electrostatic interactions are hypothesised to influence release kinetics. Both factors can potentially be used factors influencing release kinetics release, thereby broadening the horizon for zein as a tuneable release agent
Entry of the bat influenza H17N10 virus into mammalian cells is enabled by the MHC class II HLA-DR receptor
Haemagglutinin and neuraminidase surface glycoproteins of the bat influenza H17N10 virus neither bind to nor cleave sialic acid receptors, indicating that this virus employs cell entry mechanisms distinct from those of classical influenza A viruses. We observed that certain human haematopoietic cancer cell lines and canine MDCK II cells are susceptible to H17-pseudotyped viruses. We identified the human HLA-DR receptor as an entry mediator for H17 pseudotypes, suggesting that H17N10 possesses zoonotic potential
Dopaminergic drugs and the risk of hip or femur fracture: a population-based case–control study
SUMMARY: The effect of dopaminergic medication on the risk of hip/femur fractures is not clear. Our results showed a nearly twofold increased risk of hip/femur fractures in current dopaminergic drug users. Concomitant use of antidepressants further increased this risk. Fracture risk assessment may be warranted in elderly users of dopaminergic drugs. INTRODUCTION: Dopaminergic drugs, often used in the treatment of Parkinson's disease, have several pharmacological effects that may increase or decrease the risk of falling and fractures. Thus, the effect of dopaminergic medication on the risk of hip/femur fractures is not clear. The objective of the study was to examine the effect of dopaminergic medication and concomitant use of psychotropics on the risk of hip/femur fractures taking into account the timing of dopaminergic drug use. METHODS: A population-based case-control study in the PHARMO database was conducted for the period 1991 to 2002. Cases were patients aged 18 years and older with a first hip or femur fracture and matched to four control patients by year of birth, sex and geographical region. RESULTS: The study population included 6,763 cases and 26,341 controls. Current use of dopaminergic drugs (1-30 days before the index date) was associated with an increased risk of hip/femur fractures compared to never use (OR(adj) 1.76, 95% CI = 1.39-2.22), but this excess risk rapidly dropped to baseline levels when treatment had been discontinued >1 year ago. Concomitant use of antidepressants among current dopaminergic drug users further increased the risk of hip/femur fractures (OR(adj) 3.51, 95% CI = 2.10-5.87) while there was no additional risk with concomitant use of other psychotropics. CONCLUSIONS: Although the observed association between dopaminergic drugs and fracture risk may not be entirely causal, due to absence of information on the (severity of the) underlying disease, fracture risk assessment may be warranted in elderly users of dopaminergic drugs
The development of direct extrusion-injection moulded zein matrices as novel oral controlled drug delivery systems
Purpose: To evaluate the potential of zein as a sole excipient for controlled release formulations prepared by hot melt extrusion. Methods: Physical mixtures of zein, water and crystalline paracetamol were hot melt extruded (HME) at 80°C and injection moulded (IM) into caplet forms. HME-IM Caplets were characterised using differential scanning calorimetry, ATR-FTIR spectroscopy, scanning electron microscopy and powder X-ray diffraction. Hydration and drug release kinetics of the caplets were investigated and fitted to a diffusion model. Results: For the formulations with lower drug loadings, the drug was found to be in the non-crystalline state, while for the ones with higher drug loadings paracetamol is mostly crystalline. Release was found to be largely independent of drug loading but strongly dependent upon device dimensions, and predominately governed by a Fickian diffusion mechanism, while the hydration kinetics shows the features of Case II diffusion. Conclusions: In this study a prototype controlled release caplet formulation using zein as the sole excipient was successfully prepared using direct HME-IM processing. The results demonstrated the unique advantage of the hot melt extruded zein formulations on the tuneability of drug release rate by alternating the device dimensions
Differential regulation of neurotrophin expression in human bronchial smooth muscle cells
BACKGROUND: Human bronchial smooth muscle cells (HBSMC) may regulate airway inflammation by secreting cytokines, chemokines and growth factors. The neurotrophins, including nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF) and neurotrophin-3 (NT-3), have been shown to be elevated during airway inflammation and evoke airway hyperresponsiveness. We studied if HBSMC may be a source of NGF, BDNF and NT-3, and if so, how inflammatory cytokines may influence their production. METHODS: Basal and cytokine (IL-1β, IFN-γ, IL-4)-stimulated neurotrophin expression in HBSMC cultured in vitro was quantified. The mRNA expression was quantified by real-time RT-PCR and the protein secretion into the cell culture medium by ELISA. RESULTS: We observed a constitutive NGF, BDNF and NT-3 expression. IL-1β stimulated a transient increase of NGF, while the increase of BDNF had a later onset and was more sustained. COX-inhibitors (indomethacin and NS-398) markedly decreased IL-1β-stimulated secretion of BDNF, but not IL-1β-stimulated NGF secretion. IFN-γ increased NGF expression, down-regulated BDNF expression and synergistically enhanced IL-1β-stimulated NGF expression. In contrast, IL-4 had no effect on basal NGF and BDNF expression, but decreased IL-1β-stimulated NGF expression. NT-3 was not altered by the tested cytokines. CONCLUSION: Taken together, our data indicate that, in addition to the contractile capacity, HBSMC can express NGF, BDNF and NT-3. The expression of these neurotrophins may be differently regulated by inflammatory cytokines, suggesting a dynamic interplay that might have a potential role in airway inflammation
Reproductive performance of Norwegian cattle from 1985 to 2005: trends and seasonality
Declining reproductive performance is a serious breeding concern in many countries. To reveal the situation in Norwegian cattle, trends in reproductive performance were studied using insemination reports from 1985 to 2005 and data based on herd recording files from 1989 to 2005. The total number of first services was 469.765 in 1985 declining to 335.712 in 2005. The number of recorded herds and animals declined from 21.588 to 14.718 and 360.289 to 309.452 from 1989 to 2005, respectively. Sixty days non-return rate after single inseminations (NR60) increased from 68.1 in 1985 to 72.7% in 2005 (p < 0.001) and the number of services per inseminated animal (NIA) decreased from 1.8 to 1.6 (p < 0.001) from 1985 to 2005. However, return rates 0–3 days post insemination (RR0-3) increased from 6 to 12% in the same period (p < 0.001). NR60 was higher and the RR0-3 was lower in the summer season compared to the winter season during the whole period. A fertility index (FS), has been calculated from the herd recording files each year from 1989 to 2005. The average FS-index did not show a significant trend and the calving interval was also fairly constant between 12.4 and 12.6 months during this period. The average interval from calving to first and last insemination, respectively, increased from a low of 79 and 102 days in 1990 to a high of 86 and 108 days in 2005. Both intervals were consistently longer for cows in first lactation than for cows in later lactations. The percentage of inseminated animals reported culled because of poor fertility decreased from 6.0% in 1989 to 4.6% in 1996 and thereafter again increased to 6% in 2005. In conclusion, most fertility measures, mainly comprising the Norwegian Red (NRF) breed, show a relatively high level of reproductive performance with a positive or a relatively constant trend during the last two decades
Regulation of MYCN expression in human neuroblastoma cells
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81722.pdf (publisher's version ) (Open Access)BACKGROUND: Amplification of the MYCN gene in neuroblastoma (NB) is associated with a poor prognosis. However, MYCN-amplification does not automatically result in higher expression of MYCN in children with NB. We hypothesized that the discrepancy between MYCN gene expression and prognosis in these children might be explained by the expression of either MYCN-opposite strand (MYCNOS) or the shortened MYCN-isoform (DeltaMYCN) that was recently identified in fetal tissues. Both MYCNOS and DeltaMYCN are potential inhibitors of MYCN either at the mRNA or at the protein level. METHODS: Expression of MYCN, MYCNOS and DeltaMYCN was measured in human NB tissues of different stages. Transcript levels were quantified using a real-time reverse transcriptase polymerase chain reaction assay (QPCR). In addition, relative expression of these three transcripts was compared to the number of MYCN copies, which was determined by genomic real-time PCR (gQPCR). RESULTS: Both DeltaMYCN and MYCNOS are expressed in all NBs examined. In NBs with MYCN-amplification, these transcripts are significantly higher expressed. The ratio of MYCN:DeltaMYCN expression was identical in all tested NBs. This indicates that DeltaMYCN and MYCN are co-regulated, which suggests that DeltaMYCN is not a regulator of MYCN in NB. However, the ratio of MYCNOS:MYCN expression is directly correlated with NB disease stage (p = 0.007). In the more advanced NB stages and NBs with MYCN-amplification, relatively more MYCNOS is present as compared to MYCN. Expression of the antisense gene MYCNOS might be relevant to the progression of NB, potentially by directly inhibiting MYCN transcription by transcriptional interference at the DNA level. CONCLUSION: The MYCNOS:MYCN-ratio in NBs is significantly correlated with both MYCN-amplification and NB-stage. Our data indicate that in NB, MYCN expression levels might be influenced by MYCNOS but not by DeltaMYCN
Complications after hip arthroplasty and the association with hospital procedure volume: A nationwide retrospective cohort study on 50,080 total hip replacements with a follow-up of 3 months after surgery
Background and purpose: It has been suggested that a higher procedure volume is associated with less complications af
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