Summary
Sialic acids are nine‐carbon‐backbone sugars that occupy outermost positions on vertebrate cells and secreted sialoglycoproteins. These negatively charged hydrophilic carbohydrates have a ...variety of biological, biophysical and immunological functions. Mucosal surfaces and secretions of the mouth, airway, gut and vagina are especially sialoglycan‐rich. Given their prominent positions and important functions, a variety of microbial strategies have targeted host sialic acids for adherence, mimicry and/or degradation. Here we review the roles of bacterial sialidases (neuraminidases) during colonization and pathogenesis of mammalian mucosal surfaces. Evidence is presented to support the myriad roles of mucosal sialoglycans in protecting the host from bacterial infection. In opposition, many bacteria hydrolyse sialic acids during associations with the gastrointestinal, oral, respiratory and reproductive tracts. Sialidases promote bacterial survival in mucosal niche environments in several ways, including: (i) nutritional benefits of sialic acid catabolism, (ii) unmasking of cryptic host ligands used for adherence, (iii) participation in biofilm formation and (iv) modulation of immune function. Bacterial sialidases are among the best‐studied enzymes involved in pathogenesis and may also drive commensal and/or symbiotic host associations. Future studies should continue to define host substrates of bacterial sialidases and the mechanisms of theirpathologic, commensal and symbiotic interactions with the mammalian host.
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BFBNIB, DOBA, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, UILJ, UKNU, UL, UM, UPUK
•Carbon black (CB) is an efficient optical sensitizer compatible with 1,1-diamino-2,2-dinitroethene (FOX-7).•A CB doped insensitive explosive FOX-7 can be ignited by a low-power diode laser.•Laser ...ignitibility of the optically sensitized FOX-7 is mainly affected by laser power among the other parameters.•Inhomogeneities in the explosive affect laser ignition reliability.
An experimental investigation into laser ignitibility of insensitive secondary explosives, 1,1-diamino-2,2-dinitroethene (FOX-7) has been carried out, using a diode laser of continuous wave at the laser wavelength of 974nm. The direct optical ignition of an insensitive explosive will add more safety features to insensitive munitions (IM) or explosive devices. In this study, effects of laser parameters on the ignitibility were analysed in terms of laser ignition threshold, the times to initiate the ignition and full combustion, and burning sustainability. The results have shown that carbon black (CB) as an optical sensitizer is compatible with FOX-7, and significantly enhances laser ignitibility of the explosive when a small amount of CB is uniformly doped in FOX-7. The delay times for ignition and subsequent development of sustainable burning of the material are mainly determined by ignition laser power, although the other laser parameters have effects. The minimum laser power required to ignite the optically sensitized FOX-7 was found below 10W and a fast ignition was initiated in as short as 70μs by a laser power of 40W. Also the effect of the mixture uniformity of FOX-7/CB on laser ignition performance was evaluated in this study.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Control of urinary drainage and voiding Hill, Warren G
Clinical journal of the American Society of Nephrology,
2015-Mar-06, Volume:
10, Issue:
3
Journal Article
Peer reviewed
Open access
Urine differs greatly in ion and solute composition from plasma and contains harmful and noxious substances that must be stored for hours and then eliminated when it is socially convenient to do so. ...The urinary tract that handles this output is composed of a series of pressurizable muscular compartments separated by sphincteric structures. With neural input, these structures coordinate the delivery, collection, and, ultimately, expulsion of urine. Despite large osmotic and chemical gradients in this waste fluid, the bladder maintains a highly impermeable surface in the face of a physically demanding biomechanical environment, which mandates recurring cycles of surface area expansion and increased wall tension during filling, followed by rapid wall compression during voiding. Afferent neuronal inflow from mucosa and submucosa communicates sensory information about bladder fullness, and voiding is initiated consciously through coordinated central and spinal efferent outflow to the detrusor, trigonal internal sphincter, and external urethral sphincter after periods of relative quiescence. Provocative new findings suggest that in some cases, lower urinary tract symptoms, such as incontinence, urgency, frequency, overactivity, and pain may be viewed as a consequence of urothelial defects (either urothelial barrier breakdown or inappropriate signaling from urothelial cells to underlying sensory afferents and potentially interstitial cells). This review describes the physiologic and anatomic mechanisms by which urine is moved from the kidney to the bladder, stored, and then released. Relevant clinical examples of urinary tract dysfunction are also discussed.
An archive of land-based, surface-observed cloud reports has been updated and now spans 39 years from 1971 through 2009. Cloud-type information at weather stations is available in individual reports ...or in long-term, seasonal, and monthly averages. A shift to a new data source and the automation of cloud reporting in some countries has reduced the number of available stations; however, this dataset still represents most of the global land area.
Global-average trends of cloud cover suggest a small decline in total cloud cover, on the order of 0.4% per decade. Declining clouds in middle latitudes at high and middle levels appear responsible for this trend. An analysis of zonal cloud cover changes suggests poleward shifts of the jet streams in both hemispheres. The observed displacement agrees with other studies.
Changes seen in cloud types associated with the Indian monsoon are consistent with previous work suggesting that increased pollution (black carbon) may be affecting monsoonal precipitation, causing drought in northern India. A similar analysis over northern China does not show an obvious aerosol connection.
Past reports claiming a shift from stratiform to cumuliform cloud types over Russia were apparently partially based on spurious data. When the faulty stations are removed, a trade-off of stratiform and cumuliform cloud cover is still observed, but muted, over much of northern Eurasia.
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BFBNIB, DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Tall, spiky snow structures (penitentes) occur high in subtropical mountains, in the form of blades oriented east-west and tilted toward the noontime sun. By trapping sunlight, they cause a reduction ...of albedo by ~0.3 relative to flat snow. The formation of penitentes, explained by Lliboutry in 1954, requires weather conditions allowing the troughs to deepen rapidly by melting while the peaks remain dry and cold by sublimation, losing little mass, because of the 8.5-fold difference in latent heats. Lliboutry's explanation has been misrepresented in some recent publications. A concern has been raised that in the low latitudes of Jupiter's moon Europa, the ice surface may have developed penitentes, which would pose a hazard to a lander. They would require a different mechanism of formation, because Europa is too cold for melting to occur. If penitentes are present on Europa, they cannot be resolved by the coarse-resolution satellite images available now, but the high albedo of Europa (~0.7 at visible wavelengths) argues against the existence of such extreme roughness.
The Canadian Earth System Model version 5 (CanESM5) is a global
model developed to simulate historical climate change and variability, to
make centennial-scale projections of future climate, and to ...produce
initialized seasonal and decadal predictions. This paper describes the model
components and their coupling, as well as various aspects of model
development, including tuning, optimization, and a reproducibility strategy.
We also document the stability of the model using a long control simulation,
quantify the model's ability to reproduce large-scale features of the
historical climate, and evaluate the response of the model to external
forcing. CanESM5 is comprised of three-dimensional atmosphere (T63 spectral
resolution equivalent roughly to 2.8∘) and ocean (nominally 1∘) general
circulation models, a sea-ice model, a land surface scheme, and explicit
land and ocean carbon cycle models. The model features relatively coarse
resolution and high throughput, which facilitates the production of large
ensembles. CanESM5 has a notably higher equilibrium climate sensitivity
(5.6 K) than its predecessor, CanESM2 (3.7 K), which we briefly discuss, along
with simulated changes over the historical period. CanESM5 simulations
contribute to the Coupled Model Intercomparison Project phase 6 (CMIP6)
and will be employed for climate science and service applications in Canada.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Peripheral neuropathies are highly prevalent and are most often associated with chronic disease, side effects from chemotherapy, or toxic-metabolic abnormalities. Neuropathies are less commonly ...caused by genetic mutations, but studies of the normal function of mutated proteins have identified particular vulnerabilities that often implicate mitochondrial dynamics and axon transport mechanisms. Hereditary sensory and autonomic neuropathies are a group of phenotypically related diseases caused by monogenic mutations that primarily affect sympathetic and sensory neurons. Here, I review evidence to indicate that many genetic neuropathies are caused by abnormalities in axon transport. Moreover, in hereditary sensory and autonomic neuropathies. There may be specific convergence on gene mutations that disrupt nerve growth factor signaling, upon which sympathetic and sensory neurons critically depend.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Brain glioma treatment with checkpoint inhibitor antibodies to cytotoxic T-lymphocyte-associated antigen 4 (a-CTLA-4) and programmed cell death-1 (a-PD-1) was largely unsuccessful due to their ...inability to cross blood-brain barrier (BBB). Here we describe targeted nanoscale immunoconjugates (NICs) on natural biopolymer scaffold, poly(β-L-malic acid), with covalently attached a-CTLA-4 or a-PD-1 for systemic delivery across the BBB and activation of local brain anti-tumor immune response. NIC treatment of mice bearing intracranial GL261 glioblastoma (GBM) results in an increase of CD8+ T cells, NK cells and macrophages with a decrease of regulatory T cells (Tregs) in the brain tumor area. Survival of GBM-bearing mice treated with NIC combination is significantly longer compared to animals treated with single checkpoint inhibitor-bearing NICs or free a-CTLA-4 and a-PD-1. Our study demonstrates trans-BBB delivery of tumor-targeted polymer-conjugated checkpoint inhibitors as an effective GBM treatment via activation of both systemic and local privileged brain tumor immune response.
Results are presented from experiments performed with the Community Climate System Model, version 4 (CCSM4) for the Coupled Model Intercomparison Project phase 5 (CMIP5). These include multiple ...ensemble members of twentieth-century climate with anthropogenic and natural forcings as well as single-forcing runs, sensitivity experiments with sulfate aerosol forcing, twenty-first-century representative concentration pathway (RCP) mitigation scenarios, and extensions for those scenarios beyond 2100–2300. Equilibrium climate sensitivity of CCSM4 is 3.20°C, and the transient climate response is 1.73°C. Global surface temperatures averaged for the last 20 years of the twenty-first century compared to the 1986–2005 reference period for six-member ensembles from CCSM4 are +0.85°, +1.64°, +2.09°, and +3.53°C for RCP2.6, RCP4.5, RCP6.0, and RCP8.5, respectively. The ocean meridional overturning circulation (MOC) in the Atlantic, which weakens during the twentieth century in the model, nearly recovers to early twentieth-century values in RCP2.6, partially recovers in RCP4.5 and RCP6, and does not recover by 2100 in RCP8.5. Heat wave intensity is projected to increase almost everywhere in CCSM4 in a future warmer climate, with the magnitude of the increase proportional to the forcing. Precipitation intensity is also projected to increase, with dry days increasing in most subtropical areas. For future climate, there is almost no summer sea ice left in the Arctic in the high RCP8.5 scenario by 2100, but in the low RCP2.6 scenario there is substantial sea ice remaining in summer at the end of the century.
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BFBNIB, DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Abstract
Phthalate diesters, widely used in flexible plastics and consumer products, have become prevalent contaminants in the environment. Human exposure is ubiquitous and higher phthalate ...metabolite concentrations documented in patients using medications with phthalate-containing slow release capsules raises concerns for potential health effects. Furthermore, animal studies suggest that phthalate exposure can modulate circulating hormone concentrations and thus may be able to adversely affect reproductive physiology and the development of estrogen sensitive target tissues. Therefore, we conducted a systematic review of the epidemiological and experimental animal literature examining the relationship between phthalate exposure and adverse female reproductive health outcomes. The epidemiological literature is sparse for most outcomes studied and plagued by small sample size, methodological weaknesses, and thus fails to support a conclusion of an adverse effect of phthalate exposure. Despite a paucity of experimental animal studies for several phthalates, we conclude that there is sufficient evidence to suggest that phthalates are reproductive toxicants. However, we note that the concentrations needed to induce adverse health effects are high compared to the concentrations measured in contemporary human biomonitoring studies. We propose that the current patchwork of studies, potential for additive effects and evidence of adverse effects of phthalate exposure in subsequent generations and at lower concentrations than in the parental generation support the need for further study.
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DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
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