Abstract
Asteroids (24) Themis and (65) Cybele have an absorption feature at 3.1
μ
m reported to be directly linked to surface water ice. We searched for water vapor escaping from these asteroids ...with the Herschel Space Observatory Heterodyne Instrument for the Far Infrared. While no H
2
O line emission was detected, we obtain sensitive 3
σ
water production rate upper limits of
Q
(H
2
O) < 4.1 × 10
26
molecules s
−1
for Themis and
Q
(H
2
O) < 7.6 × 10
26
molecules s
−1
for Cybele. Using a thermophysical model, we merge data from the Subaru/Cooled Mid-Infrared Camera and Spectrometer and the Herschel/Spectral and Photometric Imaging Receiver with the contents of a multi-observatory database to derive new radiometric properties for these two asteroids. For Themis, we find a thermal inertia
J m
−2
s
−1/2
K
−1
, a diameter
km, and a geometric
V
-band albedo
p
V
= 0.07 ± 0.01. For Cybele, we obtain a thermal inertia
J m
−2
s
−1/2
K
−1
, a diameter 282 ± 9 km, and an albedo
p
V
= 0.042 ± 0.005. Using all inputs, we estimate that water ice intimately mixed with the asteroids’ dark surface material would cover <0.0017% (for Themis) and <0.0033% (for Cybele) of their surfaces, while an areal mixture with very clean ice (Bond albedo 0.8 for Themis and 0.7 for Cybele) would cover <2.2% (for Themis) and <1.5% (for Cybele) of their surfaces. While surface (and subsurface) water ice may exist in small localized amounts on both asteroids, it is not the reason for the observed 3.1
μ
m absorption feature.
We recently reported a truncating deletion in the NFKBIE gene, which encodes IκBε, a negative feedback regulator of NF-κB, in clinically aggressive chronic lymphocytic leukemia (CLL). Because ...preliminary data indicate enrichment of NFKBIE aberrations in other lymphoid malignancies, we screened a large patient cohort (n = 1460) diagnosed with different lymphoid neoplasms. While NFKBIE deletions were infrequent in follicular lymphoma, splenic marginal zone lymphoma, and T-cell acute lymphoblastic leukemia (<2%), slightly higher frequencies were seen in diffuse large B-cell lymphoma, mantle cell lymphoma, and primary central nervous system lymphoma (3% to 4%). In contrast, a remarkably high frequency of NFKBIE aberrations (46/203 cases 22.7%) was observed in primary mediastinal B-cell lymphoma (PMBL) and Hodgkin lymphoma (3/11 cases 27.3%). NFKBIE-deleted PMBL patients were more often therapy refractory (P = .022) and displayed inferior outcome compared with wild-type patients (5-year survival, 59% vs 78%; P = .034); however, they appeared to benefit from radiotherapy (P = .022) and rituximab-containing regimens (P = .074). NFKBIE aberrations remained an independent factor in multivariate analysis (P = .003) and when restricting the analysis to immunochemotherapy-treated patients (P = .008). Whole-exome sequencing and gene expression profiling verified the importance of NF-κB deregulation in PMBL. In summary, we identify NFKBIE aberrations as a common genetic event across B-cell malignancies and highlight NFKBIE deletions as a novel poor-prognostic marker in PMBL.
•A recurrent 4-bp deletion in the NFKBIE gene is a common event during lymphomagenesis in various lymphoid malignancies.•The deletion occurs in 22.7% of PMBL cases and is associated with a particularly aggressive clinical disease course.
Clinical trials of high-dose androgen (HDA) therapy for prostate cancer (PC) have shown promising efficacy but are limited by lack of criteria to identify likely responders. To elucidate factors that ...govern the growth-repressive effects of HDAs, we applied an unbiased integrative approach using genetic screens and transcriptional profiling of PC cells with or without demonstrated phenotypic sensitivity to androgen-mediated growth repression. Through this comprehensive analysis, we identified genetic events and related signaling networks that determine the response to both HDA and androgen withdrawal. We applied these findings to develop a gene signature that may serve as an early indicator of treatment response and identify men with tumors that are amenable to HDA therapy.
We directly measured twenty overhanging cliffs on the surface of comet 67P/Churyumov–Gerasimenko extracted from the latest shape model and estimated the minimum tensile strengths needed to support ...them against collapse under the comet’s gravity. We find extremely low strengths of around 1 Pa or less (1 to 5 Pa, when scaled to a metre length). The presence of eroded material at the base of most overhangs, as well as the observed collapse of two features andthe implied previous collapse of another, suggests that they are prone to failure and that the true material strengths are close to these lower limits (although we only consider static stresses and not dynamic stress from, for example, cometary activity). Thus, a tensile strength of a few pascals is a good approximation for the tensile strength of the 67P nucleus material, which is in agreement with previous work. We find no particular trends in overhang properties either with size over the ~10–100 m range studied here or location on the nucleus. There are no obvious differences, in terms of strength, height or evidence of collapse, between the populations of overhangs on the two cometary lobes, suggesting that 67P is relatively homogenous in terms of tensile strength. Low material strengths are supportive of cometary formation as a primordial rubble pile or by collisional fragmentation of a small body (tens of km).
Neonatal and infant immune responses are characterized by a limited capability to generate protective Ab titers and memory B cells as seen in adults. Multiple studies support an immature or even ...impaired character of umbilical cord blood (UCB) B cells themselves. In this study, we provide a comprehensive molecular and functional comparison of B cell subsets from UCB and adult peripheral blood. Most UCB B cells have a mature, naive B cell phenotype as seen in adults. The UCB Ig repertoire is highly variable but interindividually conserved, as BCR clonotypes are frequently shared between neonates. Furthermore, UCB B cells show a distinct transcriptional program that confers accelerated responsiveness to stimulation and facilitated IgA class switching. Stimulation drives extensive differentiation into Ab-secreting cells, presumably limiting memory B cell formation. Humanized mice suggest that the distinctness of UCB versus adult B cells is already reflected by the developmental program of hematopoietic precursors, arguing for a layered B-1/B-2 lineage system as in mice, albeit our findings suggest only partial comparability to murine B-1 cells. Our study shows that UCB B cells are not immature or impaired but differ from their adult mature counterpart in a conserved BCR repertoire, efficient IgA class switching, and accelerated, likely transient response dynamics.
Human hepatocytes display substantial functional inter-individual variation regarding drug metabolizing functions. In order to investigate if this diversity is mirrored in hepatocytes derived from ...different human pluripotent stem cell (hPSC) lines, we evaluated 25 hPSC lines originating from 24 different donors for hepatic differentiation and functionality. Homogenous hepatocyte cultures could be derived from all hPSC lines using one standardized differentiation procedure. To the best of our knowledge this is the first report of a standardized hepatic differentiation procedure that is generally applicable across a large panel of hPSC lines without any adaptations to individual lines. Importantly, with regard to functional aspects, such as Cytochrome P450 activities, we observed that hepatocytes derived from different hPSC lines displayed inter-individual variation characteristic for primary hepatocytes obtained from different donors, while these activities were highly reproducible between repeated experiments using the same line. Taken together, these data demonstrate the emerging possibility to compile panels of hPSC-derived hepatocytes of particular phenotypes/genotypes relevant for drug metabolism and toxicity studies. Moreover, these findings are of significance for applications within the regenerative medicine field, since our stringent differentiation procedure allows the derivation of homogenous hepatocyte cultures from multiple donors which is a prerequisite for the realization of future personalized stem cell based therapies.
Aims.
We provide a measurement of the seasonal evolution of the dust deposit erosion and accretion in the Hapi region of comet 67P/Churyumov-Gerasimenko with a vertical accuracy of 0.2–0.9 m.
...Methods.
We used OSIRIS Narrow Angle Camera images with a spatial scale of lower than 1.30 m px
−1
and developed a tool to monitor the time evolution of 22 boulder heights with respect to the surrounding dust deposit. The tool is based on the measurement of the shadow length projected by the boulder on the surrounding pebble deposit. Assuming the position of the boulders does not change during the observational period, boulder height variations provide an indication of how the thickness of the surrounding dust layer varies over time through erosion and accretion phenomena.
Results.
We measured an erosion of the dust deposit of 1.7 ± 0.2 m during the inbound orbit until 12 December, 2014. This value nearly balances the fallout from the southern hemisphere during perihelion cometary activity. During the perihelion phase, the dust deposit then increased by 1.4 ± 0.8 m. This is interpreted as a direct measurement of the fallout thickness. By comparing the erosion rate and dust volume loss rate at the Hapi region measured in the coma, the fallout represents ~96% in volume of the ejecta. The amount of the eroded pristine material from the southern hemisphere, together with its subsequent transport and fallout on the nucleus, led us to discuss the pristine water ice abundance in comet 67P. We determine that the refractory-to-ice mass ratio ranges from 6 to 110 in the perihelion-eroded pristine nucleus, providing a pristine ice mass fraction of (8 ± 7)% in mass.
Electrochemistry (EC) coupled to mass spectrometry (MS) has already been successfully applied to metabolism research for pharmaceutical applications, especially for the oxidation behaviour of drug ...substances. Xenobiotics (chemicals in the environment) also undergo various conversions; some of which are oxidative reactions. Therefore, EC-MS might be a suitable tool for the investigation of oxidative behaviour of xenobiotics. A further evaluation of this approach to environmental research is presented in the present paper using sulfonamide antibiotics. The results with sulfadiazine showed that EC-MS is a powerful tool for the elucidation of the oxidative degradation mechanism within a short time period. In addition, it was demonstrated that EC-MS can be used as a fast and easy method to model the chemical binding of xenobiotics to soil. The reaction of sulfadiazine with catechol, as a model substance for organic matter in soil, led to the expected chemical structure. Finally, by using EC-MS a first indication was obtained of the persistence of a component under chemical oxidation conditions for the comparison of the oxidative stability of different classes of xenobiotics. Overall, using just a few examples, the study demonstrates that EC-MS can be applied as a versatile tool for mechanistic studies of oxidative degradation pathways of xenobiotics and their possible interaction with soil organic matter as well as their oxidative stability in the environment. Further studies are needed to evaluate the full range of possibilities of the application of EC-MS in environmental research.
Today, even in access networks, data traffic is enormously increasing, a trend that causes existing passive optical network (PON) infrastructures to become bottlenecks in a tele- and ...data-communication infrastructure, which is aimed to be both broadband and seamless. Thus, two major objectives are considered for next-generation PONs (NG-PONs), i.e., first, bandwidth increase, and second, reach extension to reduce deployment costs. Here, we describe a new reach extension scheme that at the same time allows increasing the number of subscribers in the network. The amplification technique is based on a bidirectional semiconductor optical amplifier (SOA). It is shown that the extender configuration not only meets the bandwidth and budget requirements for NG-PONs but also remarkably improves them. Differential (quadrature) phase-shift keying (D(Q)PSK) signals are investigated in this paper. Hybrid wavelength-division multiplexing/time-division multiplexing (WDM/TDM) transmission up to 120-Gb/s downstream and 40-Gb/s upstream are experimentally demonstrated. The access budget of 33.4 dB is achieved at 10 Gb/s on every WDM channel in case of DPSK enabling a splitting ratio of 1:512 per wavelength. Furthermore, optical power budget of 40 dB is obtained when DQPSK is used, where a splitting ratio of 1024 per wavelength can be supported. Additionally, a cost-efficient chirped managed directly modulated laser scheme is proposed for DPSK signal generation in U.S. scenario enabling a high-power budget performance low-cost transmitter configuration, which appears suitable for NG-PON application. The proposed technique also alleviates nonlinear impairments specifically, cross-phase modulation (XPM), which appear in dense WDM transmission.
European consensus statement on expert colposcopy McGee, A.E.; Alibegashvili, T.; Elfgren, K. ...
European journal of obstetrics & gynecology and reproductive biology,
11/2023, Letnik:
290
Journal Article
Recenzirano
Odprti dostop
Following the publication of the European consensus statement on standards for essential colposcopy in 2020, the need for standards relating to more complex and challenging colposcopy practice was ...recognised. These standards relate to colposcopy undertaken in patients identified through cervical screening and tertiary referrals from colposcopists who undertake standard colposcopy only.
This set of recommendations provides a review of the current literature and agreement on care for recognised complex cases. With good uptake of human papillomavirus (HPV) immunisation, we anticipate a marked reduction in cervical disease over the next decade. Still, the expert colposcopist will continue to be vital in managing complex cases, including previous cervical intraepithelial neoplasia (CIN)/complex screening histories and multi-zonal disease.
To provide expert guidance on complex colposcopy cases through published evidence and expert consensus.
Members of the EFC and ESGO formed a working group to identify topics considered to be the remit of the expert rather than the standard colposcopy service. These were presented at the EFC satellite meeting, Helsinki 2021, for broader discussion and finalisation of the topics.
The agreed standards included colposcopy in pregnancy and post-menopause, investigation and management of glandular abnormalities, persistent high-risk HPV+ with normal/low-grade cytology, colposcopy management of type 3 transformation zones (TZ), high-grade cytology and normal colposcopy, colposcopy adjuncts, follow-up after treatment with CIN next to TZ margins and follow-up after treatment with CIN with persistent HPV+, and more. These standards are under review to create a final paper of consensus standards for dissemination to all EFC and ESGO members.
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