A single-particle soot photometer (SP2) was flown on a NASA WB-57F high-altitude research aircraft in November 2004 from Houston, Texas. The SP2 uses laser-induced incandescence to detect individual ...black carbon (BC) particles in an air sample in the mass range of approx.3-300 fg (approx.0.15-0.7 microns volume equivalent diameter). Scattered light is used to size the remaining non-BC aerosols in the range of approx.0.17-0.7 microns diameter. We present profiles of both aerosol types from the boundary layer to the lower stratosphere from two midlatitude flights. Results for total aerosol amounts in the size range detected by the SP2 are in good agreement with typical particle spectrometer measurements in the same region. All ambient incandescing particles were identified as BC because their incandescence properties matched those of laboratory-generated BC aerosol. Approximately 40% of these BC particles showed evidence of internal mixing (e.g., coating). Throughout profiles between 5 and 18.7 km, BC particles were less than a few percent of total aerosol number, and black carbon aerosol (BCA) mass mixing ratio showed a constant gradient with altitude above 5 km. SP2 data was compared to results from the ECHAM4/MADE and LmDzT-INCA global aerosol models. The comparison will help resolve the important systematic differences in model aerosol processes that determine BCA loadings. Further intercomparisons of models and measurements as presented here will improve the accuracy of the radiative forcing contribution from BCA.
Deletions involving regions of chromosome 10 occur in the vast majority (> 90%) of human glioblastoma multiformes. A region at chromosome 10q23-24 was implicated to contain a tumour suppressor gene ...and the identification of homozygous deletions in four glioma cell lines further refined the location. We have identified a gene, designated MMAC1, that spans these deletions and encodes a widely expressed 5.5-kb mRNA. The predicted MMAC1 protein contains sequence motifs with significant homology to the catalytic domain of protein phosphatases and to the cytoskeletal proteins, tensin and auxilin. MMAC1 coding-region mutations were observed in a number of glioma, prostate, kidney and breast carcinoma cell lines or tumour specimens. Our results identify a strong candidate tumour suppressor gene at chromosome 10q23.3, whose loss of function appears to be associated with the oncogenesis of multiple human cancers.
Purpose
Chronic hepatitis C infection and its treatment can considerably affect patients’ health-related quality-of-life (HRQoL). This study aimed to identify and summarise the current evidence base ...for health state utility values (HSUVs) in patients with chronic hepatitis C infection, generated using the EuroQol 5-dimensions (EQ-5D) questionnaire.
Methods
MEDLINE, Embase, the Cochrane Library and EconLit were searched from database inception through 31 August 2017. Eligible studies reported HSUVs elicited using the EQ-5D questionnaire in adults with chronic hepatitis C infection. Study quality and risk of bias were assessed.
Results
Of 1480 records identified, 26 studies were included. The most commonly defined health states described different stages of chronic hepatitis C infection and specific liver-related disease states, including METAVIR score, compensated and decompensated cirrhosis, hepatocellular carcinoma and liver transplantation. Patients with higher METAVIR scores tended to have lower EQ-5D scores compared to patients with lower METAVIR scores. Patients that achieved sustained virologic responses tended to have higher EQ-5D scores compared to those that did not. A meta-analysis conducted on three studies confirmed that patients with decompensated cirrhosis have significantly lower HSUVs than patients with compensated cirrhosis mean difference − 0.11 (95% CI − 0.19 to − 0.04), implying worse HRQoL. However, there was not sufficient evidence to compare how different treatments for chronic hepatitis C infection affect EQ-5D scores.
Conclusions
This study provides a summary of EQ-5D HSUVs for patients with chronic hepatitis C infection, and demonstrates that clinically important disease stages associated with treatment decisions are associated with differences in HRQoL.
A candidate tumor suppressor gene, MMAC1/PTEN, located in human chromosome band 10q23, was recently identified based on sequence alterations observed in several glioma, breast, prostate, and kidney ...tumor specimens or cell lines. To further investigate the mutational profile of this gene in human cancers, we examined a large set of human tumor specimens and cancer cell lines of many types for 10q23 allelic losses and MMAC1 sequence alterations. Loss of heterozygosity (LOH) at the MMAC1 locus was observed in approximately one-half of the samples examined, consistent with the high frequency of 10q allelic loss reported for many cancers. Of 124 tumor specimens exhibiting LOH that have been screened for MMAC1 alterations to date, we have detected variants in 13 (approximately 10%) of these primary tumors; the highest frequency of variants was found in glioblastoma specimens (approximately 23%). Novel alterations identified in this gene include a missense variant in a melanoma sample and a splicing variant and a nonsense mutation in pediatric glioblastomas. Of 76 tumor cell lines prescreened for probable LOH, microsequence alterations of MMAC1 were detected in 12 (approximately 16%) of the lines, including those derived from astrocytoma, leukemia, and melanoma tumors, as well as bladder, breast, lung, prostate, submaxillary gland, and testis carcinomas. In addition, in this set of tumor cell lines, we detected 11 (approximately 14%) homozygous deletions that eliminated coding portions of MMAC1, a class of abnormality not detected by our methods in primary tumors. These data support the occurrence of inactivating MMAC1 alterations in multiple human cancer types. In addition, we report the discovery of a putative pseudogene of MMAC1 localized on chromosome 9.
Prenatal alcohol exposure is recognized for altering DNA methylation profiles of brain cells during development, and to be part of the molecular basis underpinning Fetal Alcohol Spectrum Disorder ...(FASD) etiology. However, we have negligible information on the effects of alcohol exposure during pre-implantation, the early embryonic window marked with dynamic DNA methylation reprogramming, and on how this may rewire the brain developmental program.
Using a pre-clinical in vivo mouse model, we show that a binge-like alcohol exposure during pre-implantation at the 8-cell stage leads to surge in morphological brain defects and adverse developmental outcomes during fetal life. Genome-wide DNA methylation analyses of fetal forebrains uncovered sex-specific alterations, including partial loss of DNA methylation maintenance at imprinting control regions, and abnormal de novo DNA methylation profiles in various biological pathways (e.g., neural/brain development).
These findings support that alcohol-induced DNA methylation programming deviations during pre-implantation could contribute to the manifestation of neurodevelopmental phenotypes associated with FASD.
Crown ethers are effective at binding cations and through substitution onto the core of photoactive naphthalene diimide molecules (NDIs), cation binding can be detected via changes in UV-visible ...absorption and/or fluorescence emission. In this work, two new NDI-crown ether cation sensors (aza-15-crown-5 ether NDI, 5 , and aza-18-crown-6 ether NDI, 6 ) have been synthesised and changes in UV-visible and fluorescence spectra upon addition of various cations investigated. A substantial blue shift in the UV-visible absorption of 75 nm was observed for 6 with a 1 : 1 addition of Na + or K + , providing a clear colourimetric readout, however, no significant spectral changes were observed for 5 with the cations trialled at this level of analyte. Calcium cations do, however, elicit a response from 5 at substantially higher molar ratios, with some perturbation of the absorption spectrum observable, and an approximately six-fold increase in fluorescence emission. Theoretical calculations indicate that for 6 , K + and Na + bind to the ether oxygens resulting in a blue shift similar to that observed experimentally. Ca 2+ however, was found to bind quite differently with 5 via both the ether oxygens and the carbonyl group on the NDI. This observation highlights how small structural changes can lead to different and unexpected behaviour and that investigation of underlying binding mechanisms is important to inform the rational design of future systems.
MMAC/PTEN, a tumor suppressor gene located on chromosome 10q, has recently been shown to act as a phosphatidylinositol 3,4,5-triphosphate phosphatase and to modulate cell growth and apoptosis. ...Somatic mutations of MMAC/PTEN have been reported in a number of human cancers, especially in glioblastoma multiforme (GBM), although the number of identified mutations (approximately 10-35%) is significantly lower than the frequency of LOH affecting the MMAC/PTEN locus in the specimens (approximately 75-95%). To further investigate the possible alterations that may affect MMAC/PTEN, we examined the expression of the gene by reverse transcription-PCR in a series of gliomas. A significant difference (P < 0.001) was observed between the expression of MMAC/PTEN in GBMs versus lower grades of gliomas, thus mimicking the difference in allelic deletion associated with the locus in these tumors. Furthermore, Kaplan-Meier survival plots, adjusted for age and tumor grade, showed a significantly better prognosis for patients whose tumors expressed high levels of MMAC/PTEN. Additionally, immunostaining of GBMs revealed little or no MMAC/PTEN expression in about two-thirds of the tumors, whereas the other approximately one-third of tumors had significantly higher levels of expression. However, in about two-thirds of the high-expressing specimens, a heterogeneous pattern of expression was observed, indicating that certain cells within the tumor failed to express MMAC/PTEN. The combination of these results suggest that, in addition to molecular alterations affecting the gene, altered expression of MMAC/PTEN may play a significant role in the progression of GBM and patient outcome.
CD81 exerts a range of interesting effects on T cells including early thymocyte differentiation, LFA-1 activation, and provision of costimulation. To better understand the mechanisms by which CD81 ...influences T cell function we evaluated CD81 molecular complexes on T cells. The most prominent CD81-associated cell surface protein on thymocytes as well as a number of T cell and B cell lines has an apparent molecular mass of 75 kDa. The 75-kDa protein was purified and analyzed by matrix-assisted laser desorption ionization time-of-flight mass spectrometry followed by postsource-decay profiling. p75 is a novel type I transmembrane protein of the Ig superfamily which is most similar to FPRP. We cloned and sequenced both human and mouse PG regulatory-like protein (PGRL) and characterized mouse PGRL expression in both lymphocytes and nonlymphoid tissues. The discovery of PGRL allows for the clustering of a small family of related proteins including PGRL, FPRP, V7/CD101, and IGSF3. Expression constructs containing various domains of PGRL with an epitope tag were coexpressed with CD81 and used to determine that the interaction of CD81 with PGRL requires the membrane distal Ig3-Ig4 domains of PGRL. Although it remains to be determined whether PGRL possesses PG regulatory functions, transwell chamber experiments show that PGs and CD81 coordinately regulate T cell motility.
Optimization of the first CUPID detector module Augier, C.; Balata, M.; Barabash, A. S. ...
The European physical journal. C, Particles and fields,
09/2022, Letnik:
82, Številka:
9
Journal Article
Recenzirano
Odprti dostop
CUPID will be a next generation experiment searching for the neutrinoless double
β
decay, whose discovery would establish the Majorana nature of the neutrino. Based on the experience achieved with ...the CUORE experiment, presently taking data at LNGS, CUPID aims to reach a background free environment by means of scintillating Li
2
100
MoO
4
crystals coupled to light detectors. Indeed, the simultaneous heat and light detection allows us to reject the dominant background of
α
particles, as proven by the CUPID-0 and CUPID-Mo demonstrators. In this work we present the results of the first test of the CUPID baseline module. In particular, we propose a new optimized detector structure and light sensors design to enhance the engineering and the light collection, respectively. We characterized the heat detectors, achieving an energy resolution of (5.9 ± 0.2) keV FWHM at the
Q
-value of
100
Mo (about 3034 keV). We studied the light collection of the baseline CUPID design with respect to an alternative configuration which features gravity-assisted light detectors’ mounting. In both cases we obtained an improvement in the light collection with respect to past measures and we validated the particle identification capability of the detector, which ensures an
α
particle rejection higher than 99.9%, fully satisfying the requirements for CUPID.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
10.
Telomerase activity in human brain tumours Langford, L.A; Piatyszek, M.A; Shay, J.W ...
The Lancet (British edition),
11/1995, Letnik:
346, Številka:
8985
Journal Article
Recenzirano
Malignant gliomas are invasive into surrounding brain and are refractory to therapy. Telomerase stabilises telomere length and may immortalise cells to allow unlimited proliferation. Our analysis of ...telomerase activity in 90 human gliomas showed that 19 of 19 oligodendrogliomas and 38 of 51 glioblastoma multiformes have detectable telomerase activity. The absence of telomerase activity in anaplastic astrocytomas (2/20 positive) and in one-quarter (13/51) of the glioblastomas suggests that these tumours follow different pathways of neoplastic progression. Thus we have found that a distinct subgroup of brain tumour consists of transformed yet pre-immortal cells.
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