The potent anti-cancer agent
cis-diamminedichloroplatinum (II) (cisplatin) is currently used for treating bladder cancer. However, clinical use of this drug for long periods is often limited because ...of the appearance of cisplatin-resistant bladder tumor cells. We employed the method of a differential display reverse transcriptase polymerase chain reaction to identify the differentially expressed genes in the parental human bladder cancer cell line, T24 and three cisplatin-resistant cell lines. We report here that cisplatin-resistant cell lines overexpress Bcl-2 family protein Bcl-2-related gene expressed in fetal liver (Bfl-1)/A1 as compared with their parental cell. Cisplatin and γ-irradiation induced expression of Bfl-1/A1 in T24R2 cells but not in T24 cells. Among Bcl-2 family members, Bfl-1/A1 showed the most significant alteration of the expression level in resistant cells. The nuclear translocation of nuclear factor-kappaB (NF-κB) by cisplatin and γ-irradiation selectively occurred in T24R2 cells. Mitochondrial depolarization and cell death by cisplatin were also prevented in T24R2 cells. Moreover, Bfl-1/A1 inhibited cisplatin- and TNF-α-induced apoptosis in BOSC23 cells. Our findings suggest that the induction of Bfl-1/A1 by NF-κB may be important in controlling resistance to cisplatin responses in bladder tumor cells.
We searched for the CP-violating rare decay of the neutral kaon, KL→π0νν¯, in data from the first 100 hours of physics running in 2013 of the J-PARC KOTO experiment. One candidate event was observed ...while 0.34±0.16 background events were expected. We set an upper limit of 5.1×10−8 for the branching fraction at the 90% confidence level (C.L.). An upper limit of 3.7×10−8 at the 90% C.L. for the KL→π0X0 decay was also set for the first time, where X0 is an invisible particle with a mass of 135 MeV/c2.
Abstract
Background
Paradoxical beneficial effects of obesity on all-cause and cardiovascular mortality have been reported in multiple cohort studies based on patients with cardiovascular disease as ...well as general populations. However, the association between the presence of obesity at baseline and the better survival rates could not be directly interpreted into the beneficial effect of gain in obesity or fatness on the mortality, which makes it difficult to provide any recommendation for the management of obesity. Therefore, we investigated the influence of the changes in body fat on all-cause and cardiovascular mortality in a general population.
Methods
A population-based cohort study has been conducted for 12 years (from 2001 to 2012). A total of 5,259 subjects in whom body compositions using a bio-impedance method were measured at least 2 times during the observational period were included. The causes of death was identified from the nation-wide database in KOSTAT. I20-I82 and R99 in the International Classification of Disease-10 codes were defined as a cardiovascular death. The subjects were evenly divided into 3 groups by the percentages of the changes in body fat (Δ%BF; decreased Δ%BF <0.0% vs. increased Δ%BF 0.0–13.7% vs. highly increased Δ%BF ≥13.7%). Inverse probability of treatment weighting was applied to balance the covariate differences among the groups.
Results
The age was 51.2±8.5 years and 51.6% was male. Median observation duration was 163 (the interquartile range: 157–168) months. The all-cause death and cardiovascular death occurred most frequently in the decreased Δ%BF group and least frequent in the highly increased Δ%BF group in both unweighted and weighted cohort. Multivariate Cox proportional hazard models showed that the risk of all-cause death was lower in the increased and highly increased Δ%BF groups (hazard ratio HR 0.61 0.47–0.80 and 0.24 0.17–0.34, respectively) and the risk of cardiovascular death was lower in the highly increased Δ%BF group (HR 0.20 0.08–0.48), compared to those in the decreased Δ%BF group after adjustment for all covariates including physical activities and the changes in muscle mass. The risk of all-cause death and cardiovascular death linearly decreased with increasing Δ%BF (HR 0.72 0.67–0.77 and 0.70 0.60–0.82, respectively).
Conclusion
The increase in body fat is associated with a lower risk of all-cause death and cardiovascular death in a middle-age general population, independently with physical activities and the changes in muscle mass.
The thermal stability of coupled trilayer synthetic antiferromagnets is investigated in the framework of the new model, taking into account of the magnetostatic fields. At magnetic and other ...parameters typical for magnetic random access memory applications, the thermal stability of magnetic cells becomes problematic as the lateral dimensions approach 150
nm. At these dimensions, the energy barrier at zero applied field is calculated to be 40
kT (at room temperature) and it decreases with increasing applied field. The effects related with the shape anisotropy, which are expected to be strong in this size range, are not properly described by the existing model. The present results show that this problem can be solved by accurately quantifying the magnetostatic fields.
The effects of the yttrium nitrate (YN) content on nitrogen doping and the electrical resistivity of SiC ceramics were investigated. The YN was found to be an effective sintering additive for the ...full densification of SiC ceramics by hot‐pressing. The hot‐pressed bulk samples were identified as polycrystalline zincblende β‐SiC with a small amount of α‐SiC and Y2O3 crystallites. The SiC grains contained nitrogen (N) as an impurity that contributed to the decrease in electrical resistivity of the samples. An optimum YN composition exists for which the N concentration is maximized to give the lowest resistivity. The SiC samples exhibited a resistivity as low as ~10−3 Ω·cm and a carrier density of ~1020 cm−3, which was excited from the N donor levels. The resistivity of the samples was maintained in the same order of magnitude over a wide temperature range (4–300 K).
Background This study tested the hypothesis that microstructural white matter abnormalities in frontostriatal-limbic tracts are associated with poor response inhibition on the Stroop task in ...depressed elders. Method Fifty-one elders with major depression participated in a 12-week escitalopram trial. Diffusion tensor imaging was used to determine fractional anisotropy (FA) in white matter regions. Executive function (response inhibition) was assessed with the Stroop task. Voxelwise correlational analysis was used to examine the relationship between Stroop performance and fractional anisotropy. Results Significant associations between FA and Stroop color word interference were evident in multiple frontostriatal-limbic regions, including white matter lateral to the anterior and posterior cingulate cortex and white matter in prefrontal, insular, and parahippocampal regions. Conclusions These findings suggest that microstructural white matter abnormalities of frontostriatal-limbic networks are associated with executive dysfunction of late-life depression. This observation provides the rationale for examination of specific frontostriatal-limbic pathways in the pathophysiology of geriatric depression.
Main text
The pilot study CCQM-P204 was aimed at evaluating the level of compatibility of laboratories' measurement capabilities to value assign isotope ratios in samples of pure CO
2
gas, expressed ...as isotope delta values relative to the relevant international scale: δ
13
C
VPDB
and δ
18
O
VPDB-CO2
.
Pure CO
2
gas samples were prepared by the BIPM in batches of 10 samples of the same gas and circulated to participants for measurement. Each participant received four samples of CO
2
with a different nominal δ
13
C
VPDB
value: −1 ‰; −9 ‰; −35 ‰; and −42 ‰. The BIPM was also responsible for evaluating the homogeneity and stability of the samples. The co-coordinator IAEA received one sample per batch to confirm the batch-to-batch homogeneity. Within-batch and between-batch inhomogeneity was assessed and found to be negligible in comparison to the spread of results reported by participants.
Participants used the analytical technique of their choice to measure the isotope delta values. They were requested to report the measurement results together with detailed information on their traceability, measurement methods and data treatment. Results of the comparison were to be compiled by the BIPM and evaluated jointly by the BIPM and the IAEA. The majority of participants reported results using DI-IRMS, and those that reported results based on laser spectroscopy techniques showed a very similar dispersion of results as for DI-IRMS, although generally with greater uncertainty.
A total of nineteen participants reported their measurements, with two of them reporting results with different reference materials to provide more insight into the traceability of the measurements. The results were reported with traceability to three different VPDB scale realizations, notably VPDB, VPDB-LSVEC and VPDB2020, with 8, 7 and 6 results reported respectively for each of these. Participants agreed that results based on VPDB and VPDB2020 scale realizations should, in principle, lead to consistent results, whereas those based on VPDB-LSVEC should show a bias that increased as samples became more depleted in
13
C, with the bias approaching 0.2 ‰ for the most depleted sample. This bias was demonstrated by the participant reporting the most precise measurements based on the VPDB-LSVEC realizations, whereas for 2 participants using VPDB-LSVEC scale realizations other issues dominated the consistency of their results. The 3 laboratories using the NIST (8562,8563, 8564) reference materials (reported as on the VPDB-LSVEC scale), were highly consistent with each other, but the reported bias for the VPDB-LSVEC realization was not evident, with the historical method used for value assignment of the NIST RMs, and their relatively large uncertainty, being identified as possible causes for this.
In general, for all results the dispersion was greater than expected based on the measurement uncertainties reported by participants. This dispersion increased as the samples became more depleted in
13
C, so that results that were traceable to realizations of the VPDB scale that could be considered equivalent (VPDB and VPDB2020) did not lead to ensembles that were fully consistent within their stated uncertainties. Either the reduced chi-squared or Birge Ratio provide easily calculated quantities to characterise lack of consistency in a data set, where consistent data would lead to values of unity for either of these, and discrepant data leading to increased values. This is most readily demonstrated by considering results based on DI-IRMS with traceability to the VPDB scale through either VPDB and VPDB 2020 realizations, where the standard deviation of 16 results was 0.043 ‰ and a Birge Ratio of 2.7 calculated for nominally −1‰ for δ
13
C, and the standard deviation was 0.12 ‰ and a Birge Ratio of 2.9 calculated at nominally −9 ‰ for δ
18
O. For the samples where the nominal δ
13
C value was −42 ‰, the standard deviation of 17 results was 0.085 ‰ and a Birge Ratio of 4.5 calculated for δ
13
C, and the standard deviation was 0.24 ‰ and a Birge Ratio of 3.4 calculated for δ
18
O at nominally −36 ‰. The observed magnitude of the standard deviation of results can also be compared to the standard uncertainty of the IAEA-603 materials certified values (0.01 ‰ for δ
13
C and 0.04 ‰ δ
18
O) and the smallest standard uncertainties reported by a participant (0.005 ‰ for δ
13
C, and 0.01 ‰ for δ
18
O). These results indicate an underestimation of uncertainty for reported results, especially for those with the smallest uncertainties. Components of uncertainty that should be reviewed before future comparisons include: the uncertainty contribution from reference materials; the uncertainty associated with the phosphoric acid reaction with carbonate reference materials; corrections and uncertainties related to cross-contamination effects in the IRMS; appropriate methods for combining uncertainties of multiple reference materials and accounting for their correlations. A retreatment of results, which normalizes results to the −1 ‰ and −42 ‰ δ
13
C samples, leads to improvement in the consistency of results as demonstrated for measurements on the nominally −35 ‰ δ
13
C, −30 ‰ δ18O samples for which the standard deviation is reduced to 0.034 ‰ and 0.057 ‰ for δ
13
C and δ
18
O respectively (from 0.072 ‰ and 0.198 ‰ without normalization). The results of the comparison indicate that once issues of non-ideal methods and use of LSVEC are removed, discrepancies in results arise from the challenges in accurately transferring delta values from carbonate reference materials to CO
2
gaseous samples, and that these issues can be reduced by having appropriate gaseous reference standards for calibration when measuring CO
2
gaseous samples. This is consistent with the identical treatment principle that is preferred in the isotope ratio measurement community.
An analysis of results is presented in this report, with further consideration of the impact of the measurement method, the scale, and the reference materials. Uncertainties reported by participants are detailed and analysed, highlighting important differences in the uncertainty sources considered. Although CCQM-P204 was a comparison organised within the CCQM/GAWG and IRWG, no reference value was calculated, mainly because not all results appeared to be strictly on the same scale. Instead, a list of recommendations is provided to encourage more harmonised measurement practices and reach better consistency in future comparisons on similar materials.
To reach the main text of this paper, click on
Final Report
. Note that this text is that which appears in Appendix B of the BIPM key comparison database
https://www.bipm.org/kcdb/
.
The final report has been peer-reviewed and approved for publication by the CCQM, according to the provisions of the CIPM Mutual Recognition Arrangement (CIPM MRA).
Squaric acid immunotherapy for warts in children Silverberg, Nanette B.; Lim, Joseph K.; Paller, Amy S. ...
Journal of the American Academy of Dermatology,
05/2000, Letnik:
42, Številka:
5
Journal Article
Recenzirano
Background: Warts are a common pediatric skin infection caused by human papillomavirus (HPV). Spontaneous clearance of warts involves anti-HPV immunity, which may be enhanced by contact sensitizers. ...Squaric acid dibutylester (SADBE) is a nonmutagenic sensitizing agent useful for immunotherapy of alopecia areata. Objective: We hypothesized that SADBE home application might be effective therapy for warts. Methods: An open-label, retrospective study of 61 children with warts was performed. Sensitization with 2% SADBE on the forearm was followed with home application of 0.2% SADBE to warts 3 to 7 nights per week for at least 3 months. Results: Complete clearing occurred in 34 patients (58%), with a mean duration of therapy of 7 weeks. Partial clearing occurred in 11 (18%), and no response in 14 (24%). Clearance correlated with plantar distribution, wart duration under 2 years (P <.05), and first-line therapy with SADBE. Mild side effects occurred in one third of patients, were limited most commonly to mild erythema at the site of sensitization, and necessitated discontinuation of therapy in only 2 patients. Conclusion: SADBE topical immunotherapy is a safe, effective option for home therapy of warts in children. (J Am Acad Dermatol 2000;42:803-8.)
The effect of the additive composition on the electrical resistivity of hot-pressed liquid-phase sintered (LPS)-SiC was investigated, using AlN-RE2O3 (RE = Sc, Nd, Eu, Gd, Ho, Er, Lu) mixtures at a ...molar ratio of 60:40. All specimens were sintered to densities >95% of the theoretical density by adding 5 wt% in-situ synthesised nano-sized SiC and 1 wt% AlN-RE2O3 additives. Six of the seven SiC ceramics showed very low electrical resistivity, of the order of 10 exp(-4) ohm.m, and this was attributed to the growth of nitrogen-doped SiC grains and the confinement of non-conducting RE-containing phases in the junction areas. The SiC ceramics sintered with AlN-Lu2O3 had a relatively high electrical resistivity (about 10 exp(-2) ohm.m) due to its lower carrier density (about 10 exp(17)/cm3), which was caused by the growth of faceted grains and the resulting weak interface between SiC grains.
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