Ion-exchange is a popular method to strengthen alkali-containing glasses. However, the experimentally observed residual compressive stress profiles often deviate from the theoretical profiles: a ...subsurface compression maximum is often observed, while monotonically decreasing stress with depth is expected. It is suggested here that this discrepancy can be accounted for by considering a surface stress relaxation process that takes place at a faster rate than bulk stress relaxation in the presence of water. This suggestion is based upon experimental data indicating the presence of water impurity in the molten salt used for ion-exchange strengthening of glasses. Recent work characterizing surface stress relaxation in oxide glass fibers as a diffusion controlled process aided by molecular water diffusion was applied to better explain the development of a subsurface compressive maximum within an accelerated timeframe. By combining the new surface stress relaxation diffusion mechanism with the well-established ion-exchange mechanism, a mathematical model predicting a subsurface maximum stress is developed with a good agreement to published data.
•A surface relaxation mechanism is shown to cause subsurface compressive stress peak.•Hastened surface relaxation is due to trace water impurity in the molten salt.•Analytical models developed to predict ion-exchanged glass stress-depth profiles.
5
μm thick CrN–Ag composite layers, containing 22
at.% Ag solid lubricant, were deposited by reactive magnetron co-sputtering on 440C stainless-steel substrates at
T
s
=
300, 400, 500, and 600
°C. ...Vacuum annealing experiments at
T
a
=
425, 525, and 625
°C show that Ag diffuses to the coating surface to form lubricious surface aggregates and that the rate for Ag lubricant transport increases with
T
a
>
T
s, as determined by quantitative electron microscopy surface analyses. However, the Ag remains in the CrN matrix for
T
a
<
T
s. This is attributed to an increasing Ag aggregate size within the composite with increasing
T
s, leading to a decrease in the chemical potential and, in turn, negligible diffusion until
T
a exceeds
T
s. The tribological response during ball-on-disk sliding in ambient air against 6-mm-alumina balls was found to depend strongly on both
T
s and the testing temperature
T
t
=
450, 550, and 650
°C. The key parameter that determines lubricant transport and, in turn, tribological properties is the temperature difference Δ
T
=
T
t
−
T
s. For Δ
T
<
0, the lubricious Ag within the CrN matrix causes a moderate (25–35%) reduction in the friction coefficient from
μ
=
0.41–0.51 for pure CrN to
μ
=
0.31–0.34 for the composite. In contrast, at Δ
T
>
0, the Ag diffuses to the surface, partially transfers to the counterface, and forms a lubricious interface layer, reducing the friction by up to 60% to
μ
=
0.16–0.24. However, continuous wear at Δ
T
>
0 causes Ag depletion which results in an increasing friction and wear, and ultimately mechanical failure of the coating. The lubricant transport rate and, in turn, the lifetime before the Ag is depleted depend both strongly on Δ
T, and can therefore be optimized for a given application.
5
µm thick CrN–Ag composite layers with 22
at.% Ag were deposited by reactive magnetron co-sputtering on 440C stainless steel substrates. Increasing the growth temperature from
T
s
=
500 to 600 to ...700
°C leads to Ag segregation within the CrN matrix and the formation of embedded lamellar Ag aggregates with increasing size, <
10
5, 9
×
10
6, and 7
×
10
7
nm
3, respectively. Ball-on-disk tests against 100Cr6 steel, followed by optical profilometry and energy dispersive spectroscopy, indicate that the Ag grains for
T
s
=
500
°C are too small to facilitate an effective lubricious surface layer, resulting in a friction coefficient
μ
=
0.58 and a composite coating wear rate of 3.8
×
10
−
6
mm
3/Nm that are nearly identical to those measured for pure CrN with
μ
=
0.64 and 3.6
×
10
−
6
mm
3/Nm. The
T
s
=
600
°C coating exhibits a Ag concentration which is 15% higher within than outside the wear track, and acts as a lubricious layer that reduces
μ to 0.47 and yields a 16× and 2.4× lower wear rate for coating and counterface, respectively.
T
s
=
700
°C leads to a dramatic increase in surface roughness and an associated increase in friction,
μ
=
0.85, and wear, 9.9
×
10
−
6
mm
3/Nm. Replacing the steel counterface with an alumina ball results in the lowest
μ
=
0.50 for
T
s
=
500
°C, attributed to the presence of Ag and the relatively low hardness of 16.5
GPa for this particular coating. In contrast, friction and wear increase dramatically for
T
s
=
600
°C, which is attributed to a breakdown of the lubricious Ag layer by the harder counterface. The transient friction coefficient μ
t during experiments with continuously increasing testing temperature
T
t
=
25–700
°C initially decreases for all samples, attributed to drying of the environment and an effective softening of both coating and counterface. For the
T
s
=
500
°C coating, a temperature activated solid lubricant transport yields a lubricious Ag surface layer and a very low
μ
t
=
0.05 at
T
t
~
500
°C. All coatings exhibit an increasing
μ
t for
T
t
>
500
°C, which is attributed to oxidative degradation.
CrN–Ag composite coatings, 2 and 5
μm thick and containing 22
at.% Ag solid lubricant, were grown on Si(001) and 440C stainless steel substrates by reactive co-sputtering at T
s
=
500
°C, and were ...covered with 200
nm thick pure CrN diffusion barrier cap layers. Annealing experiments at T
a
=
625
°C, followed by quantitative scanning electron microscopy, energy dispersive x-ray spectroscopy, and Auger depth profile analyses indicate considerable Ag transport to the top surface for a barrier layer deposited at a substrate floating potential of −30
V, but negligible Ag diffusion when deposited with a substrate bias potential of −150
V. This is attributed to ion-irradiation induced densification which makes the cap layer an effective diffusion barrier. High temperature tribological sliding tests of this coating system against alumina balls at T
t
=
550
°C indicate an initial friction coefficient μ
=
0.43
±
0.04 which decreases monotonically to 0.23
±
0.03. This is attributed to the development of wear mediated openings in the barrier layer which allow Ag lubricant to diffuse to the sliding top surface. In contrast, pure CrN exhibits a constant μ
=
0.41
±
0.02 while CrN–Ag composite coatings without cap layer show a low transient μ
=
0.16
±
0.03, attributed to Ag transport to the surface, that however increases to μ
=
0.39
±
0.04 after ~
6000
cycles as the Ag reservoir in the coating is depleted. That is, the dense CrN cap layer reduces the Ag lubricant flow rate and therefore prolongs the time when the coating provides effective lubrication. This results in a cumulative wear rate over 10,000 cycles of 3.1
×
10
−6
mm
3/Nm, which is 3.3
×
lower than without diffusion barrier layer.
Pristine silica glass fiber is well known to become mechanically weaker when heat-treated in the presence of water vapor. However, the same fiber was found to become stronger if heat-treated while ...held under a sub-critical tensile stress at a temperature far below the glass transition temperature. The added strength of the stress-treated fiber was nearly equal to the applied tensile stress. This added strength was attributed to the formation of a compressive stress layer on the surface of the glass, created by a surface stress relaxation process that occurred while being held under the tensile stress. The presence of the surface compressive stress was confirmed by observing the bending of the fiber when 1) a tensile-stressed fiber was sliced and 2) a bending-stressed fiber was released from the stress. In the present paper we demonstrate that even though heat-treatment of a silica glass fiber in water vapor weakens the glass, a tensile stress application during the heat-treatment can increase the strength of silica glass fibers. Silica glass fibers with estimated strengths of ~7–8GPa were produced, exceeding that of other fibers previously reported to have a maximum strength of ~5.5GPa at room temperature in air. This new glass strengthening method does not require glass to be of a minimum thickness, as in tempering, or a glass containing alkali ions, as in ion-exchange.
•Silica glass fiber becomes stronger when heated while subjected to a tensile stress.•The fiber subjected to tensile stress acquires a surface residual compressive stress.•The residual stress is produced by surface stress relaxation promoted by water.
CrN–Ag composite layers, 5-µm-thick and containing 22 at.% Ag, were co-deposited by reactive magnetron sputtering on Si(001) substrates in a 0.4 Pa pure nitrogen atmosphere at growth temperatures
T
s
...=
500, 600, and 700 °C. A combination of X-ray diffraction and cross-sectional microscopy analyses show that Ag segregates to form precipitates with an average size that increases from <
25 nm to ~
300
×
300
×
100 nm
3 to ~
600
×
600
×
200 nm
3 for
T
s
=
500, 600, and 700 °C, respectively. At high
T
s, the precipitates extend along the surface plane to form horizontal lamellae that cause grain re-nucleation and, in turn, a disruption of the columnar microstructure and a transition from a strong 002 texture for pure CrN to a mixed preferred orientation for the composite coatings. In addition, Ag segregates to form mounds on the growing layer surface that result in the nucleation of nodules which exhibit an increased growth rate and extend up to 1 and 5 µm above the surface for
T
s
=
600 and 700 °C, respectively, but are absent for
T
s
=
500 °C. The cross-sectional microhardness increases with
T
s from 17 to 20 to 24 GPa for
T
s
=
500, 600, and 700 °C, respectively, which is attributed to a decrease in the effective Ag concentration associated with temperature-activated segregation. The measured hardness for pure CrN is 28 GPa.
MicroRNAs (miRNAs) are versatile regulators of gene expression with profound implications for human disease including atherosclerosis, but whether they can exert posttranslational functions to ...control cell adaptation and whether such noncanonical features harbor pathophysiological relevance is unknown. Here, we show that miR-126-5p sustains endothelial integrity in the context of high shear stress and autophagy. Bound to argonaute-2 (Ago2), miR-126-5p forms a complex with Mex3a, which occurs on the surface of autophagic vesicles and guides its transport into the nucleus. Mutational studies and biophysical measurements demonstrate that Mex3a binds to the central U- and G-rich regions of miR-126-5p with nanomolar affinity via its two K homology domains. In the nucleus, miR-126-5p dissociates from Ago2 and binds to caspase-3 in an aptamer-like fashion with its seed sequence, preventing dimerization of the caspase and inhibiting its activity to limit apoptosis. The antiapoptotic effect of miR-126-5p outside of the RNA-induced silencing complex is important for endothelial integrity under conditions of high shear stress promoting autophagy: ablation of Mex3a or ATG5 in vivo attenuates nuclear import of miR-126-5p, aggravates endothelial apoptosis, and exacerbates atherosclerosis. In human plaques, we found reduced nuclear miR-126-5p and active caspase-3 in areas of disturbed flow. The direct inhibition of caspase-3 by nuclear miR-126-5p reveals a noncanonical mechanism by which miRNAs can modulate protein function.
OBJECTIVE—Cardiovascular diseases and depression are the leading causes of disability in Western countries. Clinical data on potential cardiovascular effects of serotonin reuptake inhibitors (SSRIs), ...the most commonly used antidepressant drugs, are controversial. In addition to blocking serotonin reuptake transporter in the brain, SSRIs deplete the major peripheral serotonin (5-hydroxytryptamine 5-HT) storage by inhibiting serotonin reuptake transporter–mediated uptake in platelets. In this study, we aimed to investigate the effect of chronic SSRI intake on the development of atherosclerosis.
APPROACH AND RESULTS—Treatment of apolipoprotein E–deficient mice with the SSRI fluoxetine for 2, 4, or 16 weeks increased atherosclerotic lesion formation, with most pronounced effect during early plaque development. Intravital microscopy of carotid arteries revealed enhanced myeloid cell adhesion on fluoxetine treatment. Mechanistically, we found that fluoxetine augmented vascular permeability and increased chemokine-induced integrin-binding activity of circulating leukocytes. In vitro stimulation of murine blood demonstrated that fluoxetine, but not 5-HT, could directly promote β1 and β2 integrin activation provided C-C motif chemokine ligand 5 was also present. Similar effects were observed with the SSRI escitalopram. Enhanced C-C motif chemokine ligand 5–induced integrin activation by fluoxetine was also confirmed in a human neutrophil-like cell line. In contrast to the proatherogenic properties of fluoxetine, pharmacological inhibition of the peripheral 5-HT synthesizing enzyme tryptophan hydroxylase 1 did not promote atherosclerosis, suggesting that the proatherogenic effect of fluoxetine occurs independent of peripheral 5-HT depletion.
CONCLUSIONS—SSRI intake may promote atherosclerosis and therefore potentially increase the risk for acute cardiovascular events by a mechanism that is independent of 5-HT depletion.
Chemokines and galectins are simultaneously upregulated and mediate leukocyte recruitment during inflammation. Until now, these effector molecules have been considered to function independently. ...Here, we tested the hypothesis that they form molecular hybrids. By systematically screening chemokines for their ability to bind galectin‐1 and galectin‐3, we identified several interacting pairs, such as CXCL12 and galectin‐3. Based on NMR and MD studies of the CXCL12/galectin‐3 heterodimer, we identified contact sites between CXCL12 β‐strand 1 and Gal‐3 F‐face residues. Mutagenesis of galectin‐3 residues involved in heterodimer formation resulted in reduced binding to CXCL12, enabling testing of functional activity comparatively. Galectin‐3, but not its mutants, inhibited CXCL12‐induced chemotaxis of leukocytes and their recruitment into the mouse peritoneum. Moreover, galectin‐3 attenuated CXCL12‐stimulated signaling via its receptor CXCR4 in a ternary complex with the chemokine and receptor, consistent with our structural model. This first report of heterodimerization between chemokines and galectins reveals a new type of interaction between inflammatory mediators that can underlie a novel immunoregulatory mechanism in inflammation. Thus, further exploration of the chemokine/galectin interactome is warranted.
Synopsis
Chemokines and galectins are simultaneously upregulated during inflammation and mediate leukocyte recruitment. A systematic screen now demonstrates their physical interaction as heterodimers, identifying several novel interacting pairs.
Chemokines and galectins can engage in cross talk by pairing, as exemplified by galectin‐3 and CXCL12.
The association of CXCL12 with galectin‐3 appears to have potential for modulating chemokine activity.
Galectin‐3 inhibits CXCL12‐induced chemotaxis of leukocytes and their recruitment to inflammation sites.
Galectin‐3 attenuates CXCL12‐stimulated signaling via its receptor CXCR4 in a ternary complex.
Chemokines and galectins are simultaneously upregulated during inflammation and mediate leukocyte recruitment. A systematic screen now demonstrates their physical interaction as heterodimers, identifying several novel interacting pairs.
Chemokines orchestrate leukocyte trafficking and function in health and disease. Heterophilic interactions between chemokines in a given microenvironment may amplify, inhibit, or modulate their ...activity; however, a systematic evaluation of the chemokine interactome has not been performed. We used immunoligand blotting and surface plasmon resonance to obtain a comprehensive map of chemokine-chemokine interactions and to confirm their specificity. Structure-function analyses revealed that chemokine activity can be enhanced by CC-type heterodimers but inhibited by CXC-type heterodimers. Functional synergism was achieved through receptor heteromerization induced by CCL5-CCL17 or receptor retention at the cell surface via auxiliary proteoglycan binding of CCL5-CXCL4. In contrast, inhibitory activity relied on conformational changes (in CXCL12), affecting receptor signaling. Obligate CC-type heterodimers showed high efficacy and potency and drove acute lung injury and atherosclerosis, processes abrogated by specific CCL5-derived peptide inhibitors or knock-in of an interaction-deficient CXCL4 variant. Atheroprotective effects of CCL17 deficiency were phenocopied by a CCL5-derived peptide disrupting CCL5-CCL17 heterodimers, whereas a CCL5 α-helix peptide mimicked inhibitory effects on CXCL12-driven platelet aggregation. Thus, formation of specific chemokine heterodimers differentially dictates functional activity and can be exploited for therapeutic targeting.
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