92 research outputs found
The thermal structure at the topside and above of polar mesosphere summer echoes over Spitsbergen 78° N
Simultaneous measurements of temperature and polar mesosphere summer echoes (PMSE) were performed at the polar cap (78° N) during summer 2001 and 2003. In summer time the mesopause region is characterized by extremely low temperatures around 120 K. It is remarkable that PMSE are practically never observed above 92 km although temperatures are low enough to allow the existence of ice particles. In this case study we compare the PMSE topside with temperatures measured by the potassium lidar and with frost point temperatures using water-vapor mixing ratios from models. We find striking discrepancies with our current understanding of ice particles and temperature in this region. In this case study we find that the temperature can be more than 20 K lower than the frost point temperature but no PMSE is observed above 92 km altitude. We show that the lack of PMSE does not necessarily imply that the temperature is too high
Functional expression of electrogenic sodium bicarbonate cotransporter 1 (NBCe1) in mouse cortical astrocytes is dependent on S255-257 and regulated by mTOR
The electrogenic sodium bicarbonate cotransporter 1, NBCe1 (SLC4A4), is the major bicarbonate transporter expressed in astrocytes. It is highly sensitive for bicarbonate and the main regulator of intracellular, extracellular, and synaptic pH, thereby modulating neuronal excitability. However, despite these essential functions, the molecular mechanisms underlying NBCe1-mediated astrocytic response to extracellular pH changes are mostly unknown. Using primary mouse cortical astrocyte cultures, we investigated the effect of long-term extracellular metabolic alkalosis on regulation of NBCe1 and elucidated the underlying molecular mechanisms by immunoblotting, biotinylation of surface proteins, intracellular H+ recording using the H+ -sensitive dye 2',7'-bis-(carboxyethyl)-5-(and-6)-carboxyfluorescein, and phosphoproteomic analysis. The results showed significant downregulation of NBCe1 activity following metabolic alkalosis without influencing protein abundance or surface expression of NBCe1. During alkalosis, the rate of intracellular H+ changes upon challenging NBCe1 was decreased in wild-type astrocytes, but not in cortical astrocytes from NBCe1-deficient mice. Alkalosis-induced decrease of NBCe1 activity was rescued after activation of mTOR signaling. Moreover, mass spectrometry revealed constitutively phosphorylated S255-257 and mutational analysis uncovered these residues being crucial for NBCe1 transport activity. Our results demonstrate a novel mTOR-regulated mechanism by which NBCe1 functional expression is regulated. Such mechanism likely applies not only for NBCe1 in astrocytes, but in epithelial cells as well
Simultaneous observations of Polar Mesosphere Summer Echoes at two different latitudes in Antarctica
Simultaneous observations of Polar Mesosphere Summer Echoes (PMSE) at Wasa and Davis in Antarctica have been compared. Data with simultaneous observations were obtained for 16 days between 18 January and 5 February 2007. Wasa is at a higher geographic latitude than Davis, but at lower geomagnetic latitude. PMSE strength and occurrence frequency were significantly higher at Wasa. The variation of daily PMSE occurrence over the measurement period was in agreement with temperature and frost-point estimates from the Microwave Limb Sounder on the Aura spacecraft for both Wasa and Davis. The diurnal variation of PMSE strength and occurrence frequency as well as the shape of the altitude profiles of average PMSE strength and occurrence frequency were similar for the two sites. The deepest part of the evening minimum in PMSE occurrence frequency occurred for the same magnetic local time at the two sites rather than for the same local solar time. The study indicates that PMSE strength and occurrence increase between 68.6° and 73° geographic latitude, consistent with observed differences in mesospheric temperatures and water vapor content. The average altitude distribution of PMSE varies relatively little with latitude in the same hemisphere
Simultaneous observations of NLCs and MSEs at midlatitudes: implications for formation and advection of ice particles
We combined ground-based lidar observations of noctilucent clouds (NLCs) with
collocated, simultaneous radar observations of mesospheric summer echoes
(MSEs) in order to compare ice cloud altitudes at a midlatitude site
(Kühlungsborn, Germany, 54° N, 12° E). Lidar
observations are limited to larger particles ( > 10 nm), while radars are
also sensitive to small particles ( < 10 nm), but require sufficient
ionization and turbulence at the ice cloud altitudes. The combined lidar and
radar data set thus includes some information on the size distribution within
the cloud and through this on the history of the cloud. The soundings for this
study are carried out by the IAP Rayleigh–Mie–Raman (RMR) lidar and the OSWIN VHF radar. On
average, there is no difference between the lower edges
(zlowNLC and zlowMSE). The mean
difference of the upper edges zupNLC and
zupMSE is  ∼ 500 m, which is much less than
expected from observations at higher latitudes. In contrast to high
latitudes, the MSEs above our location typically do not reach much higher than
the NLCs. In addition to earlier studies from our site, this gives additional
evidence for the supposition that clouds containing large enough particles to
be observed by lidar are not formed locally but are advected from higher
latitudes. During the advection process, the smaller particles in the upper
part of the cloud either grow and sediment, or they sublimate. Both processes
result in a thinning of the layer. High-altitude MSEs, usually indicating
nucleation of ice particles, are rarely observed in conjunction with lidar
observations of NLCs at Kühlungsborn.</p
Low-level laser therapy/photobiomodulation in the management of side effects of chemoradiation therapy in head and neck cancer: part 2: proposed applications and treatment protocols
Purpose: There is a large body of evidence supporting the efficacy of low-level laser therapy (LLLT), more recently termed photobiomodulation (PBM) for the management of oral mucositis (OM) in patients undergoing radiotherapy for head and neck cancer (HNC). Recent advances in PBM technology, together with a better understanding of mechanisms involved and dosimetric parameters may lead to the management of a broader range of complications associated with HNC treatment. This could enhance patient adherence to cancer therapy, and improve quality of life and treatment outcomes. The mechanisms of action, dosimetric, and safety considerations for PBM have been reviewed in part 1. Part 2 discusses the head and neck treatment side effects for which PBM may prove to be effective. In addition, PBM parameters for each of these complications are suggested and future research directions are discussed.
Methods: Narrative review and presentation of PBM parameters are based on current evidence and expert opinion.
Results: PBM may have potential applications in the management of a broad range of side effects of (chemo)radiation therapy (CRT) in patients being treated for HNC. For OM management, optimal PBM parameters identified were as follows: wavelength, typically between 633 and 685 nm or 780–830 nm; energy density, laser or light-emitting diode (LED) output between 10 and 150 mW; dose, 2–3 J (J/cm2), and no more than 6 J/cm2 on the tissue surface treated; treatment schedule, two to three times a week up to daily; emission type, pulsed (<100 Hz); and route of delivery, intraorally and/or transcutaneously. To facilitate further studies, we propose potentially effective PBM parameters for prophylactic and therapeutic use in supportive care for dermatitis, dysphagia, dry mouth, dysgeusia, trismus, necrosis, lymphedema, and voice/speech alterations.
Conclusion: PBM may have a role in supportive care for a broad range of complications associated with the treatment of HNC with CRT. The suggested PBM irradiation and dosimetric parameters, which are potentially effective for these complications, are intended to provide guidance for well-designed future studies. It is imperative that such studies include elucidating the effects of PBM on oncology treatment outcomes.National Institutes of Health (U.S.) (NIH grant R01AI050875
Low level laser therapy/photobiomodulation in the management of side effects of chemoradiation therapy in head and neck cancer: part 1: mechanisms of action, dosimetric, and safety considerations
Purpose:
There is a large body of evidence supporting the efficacy of low level laser therapy (LLLT), more recently termed photobiomodulation (PBM), for the management of oral mucositis (OM) in patients undergoing radiotherapy for head and neck cancer (HNC). Recent advances in PBM technology, together with a better understanding of mechanisms involved, may expand the applications for PBM in the management of other complications associated with HNC treatment. This article (part 1) describes PBM mechanisms of action, dosimetry, and safety aspects and, in doing so, provides a basis for a companion paper (part 2) which describes the potential breadth of potential applications of PBM in the management of side-effects of (chemo)radiation therapy in patients being treated for HNC and proposes PBM parameters.
Methods:
This study is a narrative non-systematic review.
Results:
We review PBM mechanisms of action and dosimetric considerations. Virtually, all conditions modulated by PBM (e.g., ulceration, inflammation, lymphedema, pain, fibrosis, neurological and muscular injury) are thought to be involved in the pathogenesis of (chemo)radiation therapy-induced complications in patients treated for HNC. The impact of PBM on tumor behavior and tumor response to treatment has been insufficiently studied. In vitro studies assessing the effect of PBM on tumor cells report conflicting results, perhaps attributable to inconsistencies of PBM power and dose. Nonetheless, the biological bases for the broad clinical activities ascribed to PBM have also been noted to be similar to those activities and pathways associated with negative tumor behaviors and impeded response to treatment. While there are no anecdotal descriptions of poor tumor outcomes in patients treated with PBM, confirming its neutrality with respect to cancer responsiveness is a critical priority.
Conclusion:
Based on its therapeutic effects, PBM may have utility in a broad range of oral, oropharyngeal, facial, and neck complications of HNC treatment. Although evidence suggests that PBM using LLLT is safe in HNC patients, more research is imperative and vigilance remains warranted to detect any potential adverse effects of PBM on cancer treatment outcomes and survival.National Institutes of Health (U.S.) (grant R01AI050875
The OTUD6B-LIN28B-MYC axis determines the proliferative state in multiple myeloma
Deubiquitylases (DUBs) are therapeutically amenable components of the ubiquitin machinery that stabilize substrate proteins. Their inhibition can destabilize oncoproteins that may otherwise be undruggable. Here, we screened for DUB vulnerabilities in multiple myeloma, an incurable malignancy with dependency on the ubiquitin proteasome system and identified OTUD6B as an oncogene that drives the G1/S-transition. LIN28B, a suppressor of microRNA biogenesis, is specified as a bona fide cell cycle-specific substrate of OTUD6B. Stabilization of LIN28B drives MYC expression at G1/S, which in turn allows for rapid S-phase entry. Silencing OTUD6B or LIN28B inhibits multiple myeloma outgrowth in vivo and high OTUD6B expression evolves in patients that progress to symptomatic multiple myeloma and results in an adverse outcome of the disease. Thus, we link proteolytic ubiquitylation with post-transcriptional regulation and nominate OTUD6B as a potential mediator of the MGUS-multiple myeloma transition, a central regulator of MYC, and an actionable vulnerability in multiple myeloma and other tumors with an activated OTUD6B-LIN28B axis
Occurrence of polar mesosphere summer echoes at very high latitudes
Observations of polar mesosphere summer echoes (PMSE) have been carried out
during the summer periodes 1999–2001 and 2003–2004 at the very high latitude of
78° N using the SOUSY Svalbard Radar (53.5 MHz) at Longyearbyen.
Although the measurements could not be done continuously in these seasons,
PMSE have been detected over more than 6600 h of 9300 h of observation
time overall. Using this data base, particular PMSE occurrence characteristics
have been determined. PMSE at Svalbard appear from the middle of May to the end of
August with an almost permanent total occurrence in June and July. Diurnal
variations are observable in the height-depend occurrence rates and in PMSE
thickness, they show a maximum around 09:00–10:00 UTC and a minimum around
21:00–22:00 UTC. PMSE occur nearly exclusively between a height of 80 km and 92 km with
a maximum near 85 km. However, PMSE appear not simultaneously over the entire
height range, the mean vertical PMSE extension is around 4–6 km in June and
July. Furthermore, typically PMSE are separated into several layers, and only
30% of all PMSE are single layers. The probability of multiple layers is
greater in June and July than at the beginning and the end of the PMSE season
and shows a marked 5-day-variation. The same variation is noticeable in the
seasonal dependence of the PMSE occurrence and the PMSE thickness. We finally
discuss potential geophysical processes to explain our observational results
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