Optical amplification-free deep reservoir computing-assisted high-baudrate short-reach communication.

An optical amplification-free deep reservoir computing (RC)-assisted high-baudrate intensity modulation direct detection (IM/DD) system is experimentally demonstrated using a 100G externally modulated laser operated in C-band. We transmit 112 Gbaud 4-level pulse amplitude modulation (PAM4) and 100 Gbaud 6-level PAM (PAM6) signals over a 200-m single-mode fiber (SMF) link without any optical amplification. The decision feedback equalizer (DFE), shallow RC, and deep RC are adopted in the IM/DD system to mitigate impairment and improve transmission performance. Both PAM transmissions over a 200-m SMF with bit error rate (BER) performance below 6.25% overhead hard-decision forward error correction (HD-FEC) threshold are achieved. In addition, the BER of the PAM4 signal is below the KP4-FEC limit after 200-m SMF transmission enabled by the RC schemes. Thanks to the use of a multiple-layer structure, the number of weights in deep RC has been reduced by approximately 50% compared with the shallow RC, whereas the performance is comparable. We believe that the optical amplification-free deep RC-assisted high-baudrate link has a promising application in intra-data center communications.

Role of Mast-Cell-Derived RANKL in Ovariectomy-Induced Bone Loss in Mice.

Mast cells may contribute to osteoporosis development, because patients with age-related or post-menopausal osteoporosis exhibit more mast cells in the bone marrow, and mastocytosis patients frequently suffer from osteopenia. We previously showed that mast cells crucially regulated osteoclastogenesis and bone loss in ovariectomized, estrogen-depleted mice in a preclinical model for post-menopausal osteoporosis and found that granular mast cell mediators were responsible for these estrogen-dependent effects. However, the role of the key regulator of osteoclastogenesis, namely, receptor activator of NFκB ligand (RANKL), which is secreted by mast cells, in osteoporosis development has, to date, not been defined. Here, we investigated whether mast-cell-derived RANKL participates in ovariectomy (OVX)-induced bone loss by using female mice with a conditional Rankl deletion. We found that this deletion in mast cells did not influence physiological bone turnover and failed to protect against OVX-induced bone resorption in vivo, although we demonstrated that RANKL secretion was significantly reduced in estrogen-treated mast cell cultures. Furthermore, Rankl deletion in mast cells did not influence the immune phenotype in non-ovariectomized or ovariectomized mice. Therefore, other osteoclastogenic factors released by mast cells might be responsible for the onset of OVX-induced bone loss.

Phantom Stimulation for Cochlear Implant Users With Residual Low-Frequency Hearing.

OBJECTIVE: In cochlear implants (CIs), phantom stimulation can be used to extend the pitch range toward apical regions of the cochlea. Phantom stimulation consists of partial bipolar stimulation, in which current is distributed across two intracochlear electrodes and one extracochlear electrode as defined by the compensation coefficient σ. The aim of this study was, (1) to evaluate the benefit of conveying low-frequency information through phantom stimulation for cochlear implant (CI) subjects with low-frequency residual hearing using electric stimulation alone, (2) to compare the speech reception thresholds obtained from electric-acoustic stimulation (EAS) and electric stimulation in combination with phantom stimulation (EPS), and (3) to investigate the effect of spectrally overlapped bandwidth of speech conveyed via simultaneous acoustic and phantom stimulation on speech reception thresholds. DESIGN: Fourteen CI users with ipsilateral residual hearing participated in a repeated-measures design. Phantom stimulation was used to extend the frequency bandwidth of electric stimulation of EAS users towards lower frequencies without changing their accustomed electrode-frequency allocation. Three phantom stimulation configurations with different σ's were tested causing different degrees of electric field shaping towards apical regions of the cochlea that may affect the place of stimulation. A baseline configuration using a moderate value of σ () for all subjects, a configuration that was equivalent to monopolar stimulation by setting σ to 0 () and a configuration that used the largest value of σ for each individual subject (). Speech reception thresholds were measured for electric stimulation alone, EAS and EPS. Additionally, acoustic stimulation and phantom stimulation were presented simultaneously (EAS+PS) to investigate their mutual interaction. Besides the spectral overlap, the electrode insertion depth obtained from cone-beam computed-tomography scans was determined to assess the impact of spatial overlap between electric and acoustic stimulation on speech reception. RESULTS: Speech perception significantly improved by providing additional acoustic or phantom stimulation to electric stimulation. There was no significant difference between EAS and EPS. However, two of the tested subjects were able to perform the speech perception test using EAS but not using EPS. In comparison to the subject's familiar EAS listening mode, the speech perception deteriorated when acoustic stimulation and phantom stimulation conveyed spectrally overlapped information simultaneously and this deterioration increased with larger spectral overlap. CONCLUSIONS: (1) CI users with low-frequency acoustic residual hearing benefit from low-frequency information conveyed acoustically through combined EAS. (2) Improved speech reception thresholds through low-frequency information conveyed via phantom stimulation were observed for EAS subjects when acoustic stimulation was not used. (3) Speech perception was negatively affected by combining acoustic and phantom stimulation when both stimulation modalities overlapped spectrally in comparison to the familiar EAS.

Interaction Between Electric and Acoustic Stimulation Influences Speech Perception in Ipsilateral EAS Users.

OBJECTIVES: The aim of this study was to determine electric-acoustic masking in cochlear implant users with ipsilateral residual hearing and different electrode insertion depths and to investigate the influence on speech reception. The effects of different fitting strategies-meet, overlap, and a newly developed masking adjusted fitting (UNMASKfit)-on speech reception are compared. If electric-acoustic masking has a detrimental effect on speech reception, the individualized UNMASKfit map might be able to reduce masking and thereby enhance speech reception. DESIGN: Fifteen experienced MED-EL Flex electrode recipients with ipsilateral residual hearing participated in a crosssover design study using three fitting strategies for 4 weeks each. The following strategies were compared: (1) a meet fitting, dividing the frequency range between electric and acoustic stimulation, (2) an overlap fitting, delivering part of the frequency range both acoustically and electrically, and (3) the UNMASKfit, reducing the electric stimulation according to the individual electric-on-acoustic masking strength. A psychoacoustic masking procedure was used to measure the changes in acoustic thresholds due to the presence of electric maskers. Speech reception was measured in noise with the Oldenburg Matrix Sentence test. RESULTS: Behavioral thresholds of acoustic probe tones were significantly elevated in the presence of electric maskers. A maximum of masking was observed when the difference in location between the electric and acoustic stimulation was around one octave in place frequency. Speech reception scores and strength of masking showed a dependency on residual hearing, and speech reception was significantly reduced in the overlap fitting strategy. Electric- acoustic stimulation significantly improved speech reception over electric stimulation alone, with a tendency toward a larger benefit with the UNMASKfit map. In addition, masking was significantly inversely correlated to the speech reception performance difference between the overlap and the meet fitting. CONCLUSIONS: (1) This study confirmed the interaction between ipsilateral electric and acoustic stimulation in a psychoacoustic masking experiment. (2) The overlap fitting yielded poorer speech reception performance in stationary noise especially in subjects with strong masking. (3) The newly developed UNMASKfit strategy yielded similar speech reception thresholds with an enhanced acoustic benefit, while at the same time reducing the electric stimulation. This could be beneficial in the long-term if applied as a standard fitting, as hair cells are exposed to less possibly adverse electric stimulation. In this study, the UNMASKfit allowed the participants a better use of their natural hearing even after 1 month of adaptation. It might be feasible to transfer these results to the clinic, by fitting patients with the UNMASKfit upon their first fitting appointment, so that longer adaptation times can further improve speech reception.

Amplitude growth of intracochlear electrocochleography in cochlear implant users with residual hearing.

In cochlear implant (CI) users with residual hearing, the electrode-nerve interface can be investigated combining electric-acoustic stimulation (EAS) via electrocochleography (ECochG), a technique to record cochlear potentials evoked by acoustic stimulation. EAS interaction was shown in previous studies using psychoacoustic experiments. This work characterizes EAS interaction through psychophysical experiments and the amplitude growth of cochlear microphonics (CM) and auditory nerve neurophonics (ANN) derived from intracochlear ECochG recordings. Significant CM responses were recorded at psychoacoustic threshold levels. The mean difference between psychoacoustic and CM threshold was 17.5 dB. No significant ANN responses were recorded at the psychoacoustic threshold level. At the psychoacoustic most comfortable level, significant CM and ANN responses were recorded. In the presence of electrical stimulation, the psychoacoustic detection thresholds were elevated on average by 2.38 dB while the recorded CM amplitudes were attenuated on average by 1.15 dB. No significant differences in electrophysiological EAS interaction across acoustic stimulation levels were observed from CM recordings. The presence of psychophysical and electrophysiological EAS interaction demonstrates that some aspects of psychoacoustic EAS interaction can be measured via intracochlear ECochG.

Electric-acoustic interaction measurements in cochlear-implant users with ipsilateral residual hearing using electrocochleography.

Cochlear implantation is increasingly being used as a hearing-loss treatment for patients with residual hearing in the low acoustic frequencies. These patients obtain combined electric-acoustic stimulation (EAS). Substantial residual hearing and relatively long electrode arrays can lead to interactions between the electric and acoustic stimulation. This work investigated EAS interaction through psychophysical and electrophysiological measures. Moreover, cone-beam computed-tomography data was used to characterize the interaction along spatial cochlear locations. Psychophysical EAS interaction was estimated based on the threshold of audibility of an acoustic probe stimulus in the presence of a simultaneously presented electric masker stimulus. Intracochlear electrocochleography was used to estimate electrophysiological EAS interaction via the telemetry capability of the cochlear implant. EAS interaction was observed using psychophysical and electrophysiological measurements. While psychoacoustic EAS interaction was most pronounced close to the electrical stimulation site, electrophysiological EAS interaction was observed over a wider range of spatial cochlear locations. Psychophysical EAS interaction was significantly larger than electrophysiological EAS interaction for acoustic probes close to the electrode position.

Observation of room-temperature magnetic skyrmions and their current-driven dynamics in ultrathin metallic ferromagnets.

Magnetic skyrmions are topologically protected spin textures that exhibit fascinating physical behaviours and large potential in highly energy-efficient spintronic device applications. The main obstacles so far are that skyrmions have been observed in only a few exotic materials and at low temperatures, and fast current-driven motion of individual skyrmions has not yet been achieved. Here, we report the observation of stable magnetic skyrmions at room temperature in ultrathin transition metal ferromagnets with magnetic transmission soft X-ray microscopy. We demonstrate the ability to generate stable skyrmion lattices and drive trains of individual skyrmions by short current pulses along a magnetic racetrack at speeds exceeding 100 m s(-1) as required for applications. Our findings provide experimental evidence of recent predictions and open the door to room-temperature skyrmion spintronics in robust thin-film heterostructures.

Solution of the inhomogeneous Maxwell's equations using a Born series.

An algorithm for the numerical solution of the inhomogeneous Maxwell's equations is presented. The algorithm solves the inhomogeneous vector wave equation of the electric field by writing the solution as a convergent Born series. Compared to two dimensional finite difference time domain calculations, solutions showing the same accuracy can be calculated more than three orders of magnitude faster.

Improving bone defect healing using magnesium phosphate granules with tailored degradation characteristics.

OBJECTIVES: Dental implant placement frequently requires preceding bone augmentation, for example, with hydroxyapatite (HA) or ß-tricalcium phosphate (ß-TCP) granules. However, HA is degraded very slowly in vivo and for ß-TCP inconsistent degradation profiles from too rapid to rather slow are reported. To shorten the healing time before implant placement, rapidly resorbing synthetic materials are of great interest. In this study, we investigated the potential of magnesium phosphates in granular form as bone replacement materials. METHODS: Spherical granules of four different materials were prepared via an emulsion process and investigated in trabecular bone defects in sheep: struvite (MgNH4PO4·6H2O), K-struvite (MgKPO4·6H2O), farringtonite (Mg3(PO4)2) and ß-TCP. RESULTS: All materials except K-struvite exhibited promising support of bone regeneration, biomechanical properties and degradation. Struvite and ß-TCP granules degraded at a similar rate, with a relative granules area of 29% and 30% of the defect area 4 months after implantation, respectively, whereas 18% was found for farringtonite. Only the K-struvite granules degraded too rapidly, with a relative granules area of 2% remaining, resulting in initial fibrous tissue formation and intermediate impairment of biomechanical properties. SIGNIFICANCE: We demonstrated that the magnesium phosphates struvite and farringtonite have a comparable or even improved degradation behavior in vivo compared to ß-TCP. This emphasizes that magnesium phosphates may be a promising alternative to established calcium phosphate bone substitute materials.

Activation function 2 (AF2) domain of estrogen receptor-α regulates mechanotransduction during bone fracture healing in estrogen-competent mice.

External mechanostimulation applied by whole-body low-magnitude high-frequency vibration (LMHFV) was demonstrated to cause no or negative effects on fracture healing in estrogen-competent rodents, while in ovariectomized (OVX), estrogen-deficient rodents bone formation after fracture was improved. Using mice with an osteoblast-specific deletion of the estrogen receptor α (ERα), we demonstrated that ERα signaling in osteoblasts is required for both the anabolic and catabolic effects of LMHFV during bone fracture healing in OVX and non-OVX mice, respectively. Because the vibration effects mediated by ERα were strictly dependent on the estrogen status, we hypothesized different roles of ligand-dependent and -independent ERα signaling. To investigate this assumption in the present study, we used mice with a deletion of the C-terminal activation function (AF) domain-2 of the ERα receptor, which mediated ligand-dependent ERα signaling (ERαAF-20). OVX and non-OVX ERαAF-20 animals were subjected to femur osteotomy followed by vibration treatment. We revealed that estrogen-competent mice lacking the AF-2 domain were protected from LMHFV-induced impaired bone regeneration, while the anabolic effects of vibration in OVX mice were not affected by the AF-2 knockout. RNA sequencing further showed that genes involved in Hippo/Yap1-Taz and Wnt signaling were significantly downregulated upon LMHFV in the presence of estrogen in vitro. In conclusion, we demonstrated that the AF-2 domain is crucial for the negative effects of vibration during bone fracture healing in estrogen-competent mice suggesting that the osteoanabolic effects of vibration are rather mediated by ligand-independent ERα signaling.

Inertia and chiral edge modes of a Skyrmion magnetic bubble.

The dynamics of a vortex in a thin-film ferromagnet resembles the motion of a charged massless particle in a uniform magnetic field. Similar dynamics is expected for other magnetic textures with a nonzero Skyrmion number. However, recent numerical simulations reveal that Skyrmion magnetic bubbles show significant deviations from this model. We show that a Skyrmion bubble possesses inertia and derive its mass from the standard theory of a thin-film ferromagnet. In addition to center-of-mass motion, other low energy modes are waves on the edge of the bubble traveling with different speeds in opposite directions.

Accelerated bone regeneration through rational design of magnesium phosphate cements.

Results of several studies during past years suggested that magnesium phosphate cements (MPCs) not only show excellent biocompatibility and osteoconductivity, but they also provide improved regeneration capacity due to higher solubility compared to calcium phosphates. These findings also highlighted that chemical similarity of bone substitutes to the natural bone tissue is not a determinant factor in the success of regenerative strategies. The aim of this study was to further improve the degradation speed of MPCs for a fast bone ingrowth within a few months. We confirmed our hypothesis, that decreasing the powder-liquid ratio (PLR) of cement results in an increased content of highly soluble phases such as struvite (MgNH4PO4⋅6H2O) as well as K-struvite (MgKPO4⋅6H2O). Promising compositions with a low PLR of 1 g ml-1 were implanted in partially-loaded tibia defects in sheep. Both cements were partially degraded and replaced by bone tissue after 4 months. The degradation speed of the K-struvite cement was significantly higher compared to the struvite cement, initially resulting in the formation of a cell-rich resorption zone at the surface of some implants, as determined by histology. Overall, both MPCs investigated in this study seem to be promising as an alternative to the clinically well-established, but slowly degrading calcium phosphate cements, depending on defect size and desired degradation rate. Whereas the K-struvite cement might require further modification towards a slower resorption and reduced inflammatory response in vivo, the struvite cement appears promising for the treatment of bone defects due to its continuous degradation with simultaneous new bone formation. STATEMENT OF SIGNIFICANCE: Cold setting bone cements are used for the treatment of bone defects that exceed a critical size and cannot heal on their own. They are applied pasty into the bone defect and harden afterwards so that the shape adapts to the individual defect. Magnesium phosphates such as magnesium ammonium phosphate hexahydrate (struvite) belong to a new class of these cold setting bone cements. They degrade much faster than the clinically established calcium phosphates. In this study, a magnesium phosphate that has hardly been investigated so far was implanted into partially-loaded defects in sheeps: Potassium magnesium phosphate hexahydrate. This showed even faster resorption compared to the struvite cement: after 4 months, 63% of the cement was already degraded.

Inhibition of Cdk5 Ameliorates Skeletal Bone Loss in Glucocorticoid-Treated Mice.

Glucocorticoids (GCs) are widely used to treat inflammatory diseases. However, their long-term use leads to glucocorticoid-induced osteoporosis, increasing morbidity and mortality. Both anabolic and anti-resorptive drugs are used to counteract GC-induced bone loss, however, they are expensive and/or have major side effects. Therefore, identifying new targets for cost-effective, small-molecule inhibitors is essential. We recently identified cyclin-dependent kinase 5 (Cdk5) as a suppressor of osteoblast differentiation and showed that its inhibition with roscovitine promoted osteoblastogenesis, thus improving the skeletal bone mass and fracture healing. Here, we assessed whether Cdk5 knockdown or inhibition could also reverse the GC-mediated suppression of osteoblast differentiation, bone loss, and fracture healing. We first demonstrated that Cdk5 silencing abolished the dexamethasone (Dex)-induced downregulation of alkaline phosphatase (Alp) activity, osteoblast-specific marker gene expression (Runx2, Sp7, Alpl, and Bglap), and mineralization. Similarly, Cdk5 inhibition rescued Dex-induced suppression of Alp activity. We further demonstrated that Cdk5 inhibition reversed prednisolone (Pred)-induced bone loss in mice, due to reduced osteoclastogenesis rather than improved osteoblastogenesis. Moreover, we revealed that Cdk5 inhibition failed to improve Pred-mediated impaired fracture healing. Taken together, we demonstrated that Cdk5 inhibition with roscovitine ameliorated GC-mediated bone loss but did not reverse GC-induced compromised fracture healing in mice.

Inhibition of Cdk5 increases osteoblast differentiation and bone mass and improves fracture healing.

Identification of regulators of osteoblastogenesis that can be pharmacologically targeted is a major goal in combating osteoporosis, a common disease of the elderly population. Here, unbiased kinome RNAi screening in primary murine osteoblasts identified cyclin-dependent kinase 5 (Cdk5) as a suppressor of osteoblast differentiation in both murine and human preosteoblastic cells. Cdk5 knockdown by siRNA, genetic deletion using the Cre-loxP system, or inhibition with the small molecule roscovitine enhanced osteoblastogenesis in vitro. Roscovitine treatment significantly enhanced bone mass by increasing osteoblastogenesis and improved fracture healing in mice. Mechanistically, downregulation of Cdk5 expression increased Erk phosphorylation, resulting in enhanced osteoblast-specific gene expression. Notably, simultaneous Cdk5 and Erk depletion abrogated the osteoblastogenesis conferred by Cdk5 depletion alone, suggesting that Cdk5 regulates osteoblast differentiation through MAPK pathway modulation. We conclude that Cdk5 is a potential therapeutic target to treat osteoporosis and improve fracture healing.

Distinct Glucocorticoid Receptor Actions in Bone Homeostasis and Bone Diseases.

Glucocorticoids (GCs) are steroid hormones that respond to stress and the circadian rhythm. Pharmacological GCs are widely used to treat autoimmune and chronic inflammatory diseases despite their adverse effects on bone after long-term therapy. GCs regulate bone homeostasis in a cell-type specific manner, affecting osteoblasts, osteoclasts, and osteocytes. Endogenous physiological and exogenous/excessive GCs act via nuclear receptors, mainly via the GC receptor (GR). Endogenous GCs have anabolic effects on bone mass regulation, while excessive or exogenous GCs can cause detrimental effects on bone. GC-induced osteoporosis (GIO) is a common adverse effect after GC therapy, which increases the risk of fractures. Exogenous GC treatment impairs osteoblastogenesis, survival of the osteoblasts/osteocytes and prolongs the longevity of osteoclasts. Under normal physiological conditions, endogenous GCs are regulated by the circadian rhythm and circadian genes display oscillatory rhythmicity in bone cells. However, exogenous GCs treatment disturbs the circadian rhythm. Recent evidence suggests that the disturbed circadian rhythm by continuous exogenous GCs treatment can in itself hamper bone integrity. GC signaling is also important for fracture healing and rheumatoid arthritis, where crosstalk among several cell types including macrophages and stromal cells is indispensable. This review summarizes the complexity of GC actions via GR in bone cells at cellular and molecular levels, including the effect on circadian rhythmicity, and outlines new therapeutic possibilities for the treatment of their adverse effects.

Estrogen Receptor α Signaling in Osteoblasts is Required for Mechanotransduction in Bone Fracture Healing.

Biomechanical stimulation by whole-body low-magnitude high-frequency vibration (LMHFV) has demonstrated to provoke anabolic effects on bone metabolism in both non-osteoporotic and osteoporotic animals and humans. However, preclinical studies reported that vibration improved fracture healing and bone formation in osteoporotic, ovariectomized (OVX) mice representing an estrogen-deficient hormonal status, but impaired bone regeneration in skeletally healthy non-OVX mice. These effects were abolished in general estrogen receptor α (ERα)-knockout (KO) mice. However, it remains to be elucidated which cell types in the fracture callus are targeted by LMHFV during bone healing. To answer this question, we generated osteoblast lineage-specific ERα-KO mice that were subjected to ovariectomy, femur osteotomy and subsequent vibration. We found that the ERα specifically on osteoblastic lineage cells facilitated the vibration-induced effects on fracture healing, because in osteoblast lineage-specific ERα-KO (ERαfl/fl; Runx2Cre) mice the negative effects in non-OVX mice were abolished, whereas the positive effects of vibration in OVX mice were reversed. To gain greater mechanistic insights, the influence of vibration on murine and human osteogenic cells was investigated in vitro by whole genome array analysis and qPCR. The results suggested that particularly canonical WNT and Cox2/PGE2 signaling is involved in the mechanotransduction of LMHFV under estrogen-deficient conditions. In conclusion, our study demonstrates a critical role of the osteoblast lineage-specific ERα in LMHFV-induced effects on fracture healing and provides further insights into the molecular mechanism behind these effects.

Proposal of a robust measurement scheme for the nonadiabatic spin torque using the displacement of magnetic vortices.

A spin-polarized current traversing a ferromagnet with continuously varying magnetization exerts a torque on the magnetization. The nonadiabatic contribution to this spin-transfer torque is currently under strong debate, as its value differs by orders of magnitude in theoretical predictions and in measurements. Here, a measurement scheme is presented that allows us to determine the strength of the nonadiabatic spin torque accurately and directly. Analytical and numerical calculations show that the scheme is robust against the uncertainties of the exact current direction and Oersted fields.

The role of electroneural versus electrophonic stimulation on psychoacoustic electric-acoustic masking in cochlear implant users with residual hearing.

Cochlear implant (CI) candidates with residual low-frequency hearing are nowadays often implanted with CI electrode arrays that allow preserving their acoustic hearing in the implanted ear. These subjects receiving combined electric-acoustic stimulation (EAS) show enhanced speech perception scores when compared to traditional CI users without acoustic component. However, these benefits are limited by interaction effects such as masking between electric and acoustic stimulation. This study evaluates ipsilateral electric-acoustic masking in a psychophysical experiment conducted in 5 EAS subjects. The elevation of acoustic pure tone thresholds through simultaneous presentation of electric pulse trains and vice versa is measured for different acoustic frequencies and different settings of the electric stimuli. Electric-acoustic interaction could originate either from electroneural stimulation of auditory nerve fibers or from electrophonic stimulation of hair cells. The two fundamental goals of this study are to investigate the effects of stimulation rate and phase duration of the electric stimulus on electric-acoustic masking and to investigate the origin of electric-acoustic masking by assessing the contributions of electroneural versus electrophonic stimulation. The amount of electric-acoustic masking in the present study was independent of pulse rate and phase duration of the electric stimuli. Moreover, the results demonstrate that electric-acoustic masking depends on the spatial distance between the locations of electric or acoustic excitation in the cochlea, but not on the spectral content of the electric stimulus. We thereby conclude that psychoacoustic electric-acoustic masking in EAS users is dominated by electroneural-acoustic interaction, whereas the contribution of electrophonic stimulation is negligible.

Intact Glucocorticoid Receptor Dimerization Is Deleterious in Trauma-Induced Impaired Fracture Healing.

Following severe trauma, fracture healing is impaired because of overwhelming systemic and local inflammation. Glucocorticoids (GCs), acting via the glucocorticoid receptor (GR), influence fracture healing by modulating the trauma-induced immune response. GR dimerization-dependent gene regulation is essential for the anti-inflammatory effects of GCs. Therefore, we investigated in a murine trauma model of combined femur fracture and thoracic trauma, whether effective GR dimerization influences the pathomechanisms of trauma-induced compromised fracture healing. To this end, we used mice with decreased GR dimerization ability (GRdim). The healing process was analyzed by cytokine/chemokine multiplex analysis, flow cytometry, gene-expression analysis, histomorphometry, micro-computed tomography, and biomechanical testing. GRdim mice did not display a systemic or local hyper-inflammation upon combined fracture and thorax trauma. Strikingly, we discovered that GRdim mice were protected from fracture healing impairment induced by the additional thorax trauma. Collectively and in contrast to previous studies describing the beneficial effects of intact GR dimerization in inflammatory models, we report here an adverse role of intact GR dimerization in trauma-induced compromised fracture healing.

Dependence of magnetic domain-wall motion on a fast changing current.

A dependence of current-induced domain-wall motion in nanowires on the temporal shape of current pulses is observed. The results show that the motion of the wall is amplified for alterations of the current on a time scale smaller than the intrinsic time scale of the domain wall which is a few nanoseconds in permalloy. This effect arises from an additional force on the wall by the spin-transfer torque due to a fast changing current and improves the efficiency of domain-wall motion. The observations provide an understanding for the efficient domain-wall motion with nanosecond current pulses.