1,202 research outputs found
On the geometric-arithmetic mean inequality for matrices
In this paper refinements and converses of matrix forms of the geometric-arithmetic mean inequality are given
Deletion of the Notch ligand Jagged1 during cochlear maturation leads to inner hair cell defects and hearing loss
The mammalian cochlea is an exceptionally well-organized epithelium composed of hair cells, supporting cells, and innervating neurons. Loss or defects in any of these cell types, particularly the specialized sensory hair cells, leads to deafness. The Notch pathway is known to play a critical role in the decision to become either a hair cell or a supporting cell during embryogenesis; however, little is known about how Notch functions later during cochlear maturation. Uniquely amongst Notch ligands, Jagged1 (JAG1) is localized to supporting cells during cell fate acquisition and continues to be expressed into adulthood. Here, we demonstrate that JAG1 in maturing cochlear supporting cells is essential for normal cochlear function. Specifically, we show that deletion of JAG1 during cochlear maturation disrupts the inner hair cell pathway and leads to a type of deafness clinically similar to auditory neuropathy. Common pathologies associated with disruptions in inner hair cell function, including loss of hair cells, synapses, or auditory neurons, were not observed in JAG1 mutant cochleae. Instead, RNA-seq analysis of JAG1-deficient cochleae identified dysregulation of the Rho GTPase pathway, known to be involved in stereocilia development and maintenance. Interestingly, the overexpression of one of the altered genes, Diaph3, is responsible for autosomal dominant auditory neuropathy-1 (AUNA1) in humans and mice, and is associated with defects in the inner hair cell stereocilia. Strikingly, ultrastructural analyses of JAG1-deleted cochleae revealed stereocilia defects in inner hair cells, including fused and elongated bundles, that were similar to those stereocilia defects reported in AUNA1 mice. Taken together, these data indicate a novel role for Notch signaling in normal hearing development through maintaining stereocilia integrity of the inner hair cells during cochlear maturation
Absence of plastin 1 causes abnormal maintenance of hair cell stereocilia and a moderate form of hearing loss in mice
Hearing relies on the mechanosensory inner and outer hair cells (OHCs) of the organ of Corti, which convert mechanical deflections of their actin-rich stereociliary bundles into electrochemical signals. Several actin-associated proteins are essential for stereocilia formation and maintenance, and their absence leads to deafness. One of the most abundant actin-bundling proteins of stereocilia is plastin 1, but its function has never been directly assessed. Here, we found that plastin 1 knock-out (Pls1 KO) mice have a moderate and progressive form of hearing loss across all frequencies. Auditory hair cells developed normally in Pls1 KO, but in young adult animals, the stereocilia of inner hair cells were reduced in width and length. The stereocilia of OHCs were comparatively less affected; however, they also showed signs of degeneration in ageing mice. The hair bundle stiffness and the acquisition of the electrophysiological properties of hair cells were unaffected by the absence of plastin 1, except for a significant change in the adaptation properties, but not the size of the mechanoelectrical transducer currents. These results show that in contrast to other actin-bundling proteins such as espin, harmonin or Eps8, plastin 1 is dispensable for the initial formation of stereocilia. However, the progressive hearing loss and morphological defects of hair cells in adult Pls1 KO mice point at a specific role for plastin 1 in the preservation of adult stereocilia and optimal hearing. Hence, mutations in the human PLS1 gene may be associated with relatively mild and progressive forms of hearing loss
Cytisine versus varenicline for smoking cessation for MÄori (the indigenous people of New Zealand) and their extended family:Protocol for a randomized nonâinferiority trial
Background and aims Cytisine, a nicotinic acetylcholine receptor partial agonist (like varenicline) found in some plants, is a low-cost, effective smoking cessation medication that may appeal to MÄori [the indigenous people of New Zealand (NZ)]. The RAUORA trial aims to determine the effectiveness, safety and cost-effectiveness of cytisine (TabexÂź) versus varenicline (ChampixÂź) for smoking cessation in MÄori and the whÄnau (extended family) of MÄori. Design Pragmatic, community-based, open-label randomized non-inferiority trial. Setting Lakes District Health Board region, NZ. Participants Daily smokers (n = 2140) who self-identify as MÄori or whÄnau of MÄori, and are: aged â„ 18 years, motivated to quit smoking in the next 2 weeks, eligible for subsidized varenicline, able to provide verbal consent and have daily access to a mobile phone/internet. Recruitment uses multi-media advertising. Intervention and comparator Participants are randomized (1 : 1 ratio) to receive a prescription for 12 weeks of cytisine tablets [following the manufacturerâs dosing regimen for 25 days, then one 1.5-mg tablet every 6 hours (two per day) until 12 weeks] or varenicline tablets (following the manufacturerâs dosing regimen). Both groups receive brief stop-smoking advice from the prescribing doctor and withdrawal-orientated behavioural support via community-based stop-smoking counselling services (frequency, duration and mode of delivery tailored for participants) or a research assistant (six weekly 10â15- minute calls). Participants are advised to reduce their smoking over the first 4 days of treatment, with day 5 as their designated quit-date. Measurements The primary outcome is carbon monoxide-verified continuous abstinence at 6 months post-quit date. Secondary outcomes at 1, 3, 6 and 12 months post-quit date include: self-reported continuous abstinence, 7-day point prevalence abstinence, cigarettes per day, time to (re)lapse, adverse events, treatment adherence/compliance, treatment acceptability, nicotine withdrawal/urge to smoke and health-care utilization/health- related quality of life. Comments This trial compares cytisine and varenicline when used by the indigenous people of NZ and their extended family for smoking cessation
Candida species exhibit differential in vitro hemolytic activities
A total of 80 Candida isolates representing 14 species were examined for their respective responses to an in vitro hemolytic test. A modification of a previously described plate assay system where the yeasts are incubated on glucose (3%)-enriched sheep blood agar in a carbon dioxide (5%)-rich environment for 48 h was used to evaluate the hemolytic activity. A group of eight Candida species which included Candida albicans (15 isolates), C. dubliniensis (2), C. kefyr (2), C. krusei (4), C. zeylanoides (1), C. glabrata (34), C. tropicalis (5), and C. lusitaniae (2) demonstrated both alpha and beta hemolysis at 48 h postinoculation. Only alpha hemolysis was detectable in four Candida species, viz., C. famata (3), C. guilliermondii (4), C. rugosa (1), and C. utilis (1), while C. parapsilosis (5) and C. pelliculosa (1) failed to demonstrate any hemolytic activity after incubation for 48 h or longer. This is the first study to demonstrate the variable expression profiles of hemolysins by different Candida species.published_or_final_versio
UK Large-scale Wind Power Programme from 1970 to 1990: the Carmarthen Bay experiments and the Musgrove Vertical-Axis Turbines
This article describes the development of the Musgrove Vertical Axis Wind Turbine (VAWT)
concept, the UK âCarmarthen Bayâ wind turbine test programme, and UK governmentâs wind
power programme to 1990. One of the most significant developments in the story of British
wind power occurred during the 1970s, 1980s, and 1990s, with the development of the
Musgrove vertical axis wind turbine and its inclusion within the UK Governmentâs wind
turbine test programme. Evolving from a supervisorâs idea for an undergraduate project at
Reading University, the Musgrove VAWT was once seen as an able competitor to the
horizontal axis wind systems that were also being encouraged at the time by both the UK
government and the Central Electricity Generating Board, the then nationalised electricity
utility for England and Wales. During the 1980s and 1990s the most developed Musgrove
VAWT system, along with three other commercial turbine designs was tested at
Carmarthen Bay, South Wales as part of a national wind power test programme. From these
developmental tests, operational data was collected and lessons learnt, which were
incorporated into subsequent wind power operations.http://dx.doi.org/10.1260/03095240677860621
Geophysical studies with laser-beam detectors of gravitational waves
The existing high technology laser-beam detectors of gravitational waves may
find very useful applications in an unexpected area - geophysics. To make
possible the detection of weak gravitational waves in the region of high
frequencies of astrophysical interest, ~ 30 - 10^3 Hz, control systems of laser
interferometers must permanently monitor, record and compensate much larger
external interventions that take place in the region of low frequencies of
geophysical interest, ~ 10^{-5} - 3 X 10^{-3} Hz. Such phenomena as tidal
perturbations of land and gravity, normal mode oscillations of Earth,
oscillations of the inner core of Earth, etc. will inevitably affect the
performance of the interferometers and, therefore, the information about them
will be stored in the data of control systems. We specifically identify the
low-frequency information contained in distances between the interferometer
mirrors (deformation of Earth) and angles between the mirrors' suspensions
(deviations of local gravity vectors and plumb lines). We show that the access
to the angular information may require some modest amendments to the optical
scheme of the interferometers, and we suggest the ways of doing that. The
detailed evaluation of environmental and instrumental noises indicates that
they will not prevent, even if only marginally, the detection of interesting
geophysical phenomena. Gravitational-wave instruments seem to be capable of
reaching, as a by-product of their continuous operation, very ambitious
geophysical goals, such as observation of the Earth's inner core oscillations.Comment: 29 pages including 8 figures, modifications and clarifications in
response to referees' comments, to be published in Class. Quant. Gra
Solar System Processes Underlying Planetary Formation, Geodynamics, and the Georeactor
Only three processes, operant during the formation of the Solar System, are
responsible for the diversity of matter in the Solar System and are directly
responsible for planetary internal-structures, including planetocentric nuclear
fission reactors, and for dynamical processes, including and especially,
geodynamics. These processes are: (i) Low-pressure, low-temperature
condensation from solar matter in the remote reaches of the Solar System or in
the interstellar medium; (ii) High-pressure, high-temperature condensation from
solar matter associated with planetary-formation by raining out from the
interiors of giant-gaseous protoplanets, and; (iii) Stripping of the primordial
volatile components from the inner portion of the Solar System by super-intense
solar wind associated with T-Tauri phase mass-ejections, presumably during the
thermonuclear ignition of the Sun. As described herein, these processes lead
logically, in a causally related manner, to a coherent vision of planetary
formation with profound implications including, but not limited to, (a) Earth
formation as a giant gaseous Jupiter-like planet with vast amounts of stored
energy of protoplanetary compression in its rock-plus-alloy kernel; (b) Removal
of approximately 300 Earth-masses of primordial gases from the Earth, which
began Earth's decompression process, making available the stored energy of
protoplanetary compression for driving geodynamic processes, which I have
described by the new whole-Earth decompression dynamics and which is
responsible for emplacing heat at the mantle-crust-interface at the base of the
crust through the process I have described, called mantle decompression
thermal-tsunami; and, (c)Uranium accumulations at the planetary centers capable
of self-sustained nuclear fission chain reactions.Comment: Invited paper for the Special Issue of Earth, Moon and Planets
entitled Neutrino Geophysics Added final corrections for publicatio
Reaction Between Nitrogen and Spinel in Chromium
Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/66029/1/j.1151-2916.1968.tb15671.x.pd
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