Myeloid immune checkpoint ILT3/LILRB4/gp49B can co-tether fibronectin with integrin on macrophages.

LILRB4 (B4, also known as ILT3/CD85k) is an immune checkpoint of myeloid lineage cells, albeit its mode of function remains obscure. Our recent identification of a common ligand for both human B4 and its murine ortholog gp49B as the fibronectin (FN) N-terminal 30 kDa domain poses the question of how B4/gp49B regulate cellular activity upon recognition of FN in the plasma and/or the extracellular matrix. Since FN in the extracellular matrix is tethered by FN-binding integrins, we hypothesized that B4/gp49B would tether FN in cooperation with integrins on the cell surface, thus they should be in close vicinity to integrins spatially. This scenario suggests a mode of function of B4/gp49B by which the FN-induced signal is regulated. The FN pull-down complex was found to contain gp49B and integrin ß 1 in bone marrow-derived macrophages. The confocal fluorescent signals of the three molecules on the intrinsically FN-tethering macrophages were correlated to each other. When FN-poor macrophages adhered to culture plates, the gp49-integrin ß 1 signal correlation increased at the focal adhesion, supporting the notion that gp49B and integrin ß 1 become spatially closer to each other there. Adherence of RAW264.7 and THP-1 cells to immobilized FN induced phosphorylation of spleen tyrosine kinase, whose level was augmented under B4/gp49B deficiency. Thus, we concluded that B4/gp49B can co-tether FN in cooperation with integrin in the cis configuration on the same cell, forming a B4/gp49B-FN-integrin triplet as a regulatory unit of a focal adhesion-dependent pro-inflammatory signal in macrophages.

Quantifying Carbon Active Sites Chemisorbing Hydrogen on Oxygen Containing Activated Carbons during Heat Treatment in Hydrogen Atmosphere.

Carbon edge sites have been widely studied because of their importance in surface reactivity and electronic properties. The surface chemistry of the carbon edge sites is relevant to various reactions, and carbon active sites are key topics in many applications. Temperature-programmed desorption (TPD) and temperature-programmed reaction (TPR) techniques are used to clarify the fate of oxygen atoms present as CO-yielding functional groups on the activated carbon during heat treatment in hydrogen with an argon balance atmosphere. It has been elucidated that CO is decomposed, H2O is released by a reduction reaction with atmospheric H2, and CO2 is evolved by secondary reactions from the CO-yielding functional groups during TPR. Atmospheric H2 consumption during TPR is observed and its rate is characterized. The amounts of carbon active sites are quantified by determining the amount of H2 chemisorbed onto the carbon surfaces. Finally, it is quantitatively determined that the active sites that chemisorb hydrogen are generated after the decomposition of CO and CO2 caused by secondary reactions between ca. 700 and 1100 K from the CO-yielding functional groups. The origin of these CO-yielding functional groups is generally attributed to phenol/ether groups. In addition to these oxygen-containing functional group decompositions, some free sites on the edge sites are activated for H2 chemisorption by heat treatment between ca. 700 and 1100 K.

Design and fabrication of a supermirror with smooth and broad response for hard x-ray telescopes.

We present our design and fabrication scheme of a supermirror for hard x-ray telescopes to improve the performance of reflection. Supermirrors are designed to achieve target reflectivity profiles with small ripples in the interesting energy range with a limited number of layer pairs. Starting from conventional design methods, we optimized the thickness distribution of the structure using a numerical approach with the merit function established for this application. As an example, a platinum-carbon supermirror structure of 123 layer pairs with a varying d-space of 2-6 nm was designed to enhance the reflectivity in the energy range from 11 to 55 keV with a flat top at a grazing angle of 0.28 deg. The multilayer thus designed was deposited on a float glass by our DC magnetron sputtering system. The reflectivity profile was successfully measured to be ~20% with little oscillation in all energy band of interest.

Case report: Backward gait training combined with gait-synchronized cerebellar transcranial alternating current stimulation in progressive supranuclear palsy.

Progressive supranuclear palsy (PSP) is characterized by recurrent falls caused by postural instability, and a backward gait is considered beneficial for postural instability. Furthermore, a recent approach for rehabilitation combined with gait-oriented synchronized stimulation using non-invasive transcranial patterned stimulation could be promising for balance function. Here, we present a case of PSP with backward gait training combined with gait-synchronized transcranial alternating current stimulation (tACS). A 70-year-old woman with PSP-Richardson's syndrome underwent backward gait training combined with synchronized cerebellar tACS. Initially, she underwent short-term intervention with combined training of backward gait with synchronized cerebellar tACS, asynchronized, or sham stimulation according to the N-of-1 study design. Synchronized tACS training demonstrated a decrease in postural instability, whereas asynchronized or sham stimulation did not. The additional long-term interventions of combined backward gait training with synchronized cerebellar tACS demonstrated further decrease in postural instability with improvements in gait speed, balance function, and fall-related self-efficacy in daily life. The present case describes a novel approach for motor symptoms in a patient with PSP. Backward gait training with synchronized cerebellar tACS may be a promising therapeutic approach.

Case report: A novel approach of closed-loop brain stimulation combined with robot gait training in post-stroke gait disturbance.

Most post-stroke patients have long-lasting gait disturbances that reduce their daily activities. They often show impaired hip and knee joint flexion and ankle dorsiflexion of the lower limbs during the swing phase of gait, which is controlled by the corticospinal tract from the primary motor cortex (M1). Recently, we reported that gait-synchronized closed-loop brain stimulation targeting swing phase-related activity in the affected M1 can improve gait function in post-stroke patients. Subsequently, a gait-training robot (Orthobot®) was developed that could assist lower-limb joint movements during the swing phase of gait. Therefore, we investigated whether gait-synchronized closed-loop brain stimulation combined with robot-assisted training targeting the swing phase could enhance the recovery of post-stroke gait disturbance. A 57-year-old female patient with chronic post-stroke hemiparesis underwent closed-loop brain stimulation combined with robot-assisted training for 10 min 2 years after left pons infarction. For closed-loop brain stimulation, we used transcranial oscillatory electrical current stimulation over the lesioned M1 foot area with 1.5 mA of DC offset and 0-3 mA of sine-wave formed currents triggered by the paretic heel contact to set the maximum current just before the swing phase (intervention A; two times repeated, A1 and A2). According to the N-of-1 study design, we also performed sham stimulation (intervention B) and control stimulation not targeting the swing phase (intervention C) combined with robot-assisted training in the order of A1-B-A2-C interventions. As a result, we found larger improvements in gait speed, the Timed Up and Go test result, and muscle strength after the A1 and A2 interventions than after the B and C interventions. After confirming the short-term effects, we performed an additional long-term intervention twice a week for 5 weeks, for a total of 10 sessions. Gait parameters also largely improved after long-term intervention. Gait-synchronized closed-loop brain stimulation combined with robot-assisted training targeting the swing phase of gait may promote the recovery of gait function in post-stroke patients. Further studies with a larger number of patients are necessary.

Sustainable, affordable and functional: reimagining prosthetic liners in resource limited environments.

PURPOSE: The purpose of this study was to evaluate function and performance of unilateral trans-tibial prosthesis users wearing an affordable liner in three types of socket designs. METHODS: Five unilateral trans-tibial amputees participated, were provided an Affordable Ethyl-Vinyl-Acetate Roll-On liner (AERO) roll-on liner with patella tendon bearing (PTB) prosthesis, PE-Lite liner with PTB prosthesis, and an (AERO) liner with total-surface bearing (TSB) prosthesis. A battery of outcome measures; step-counts, socket comfort score (SCS), orthotics prosthetics user survey (OPUS) and socket pressure measurement during walking were administered. RESULTS: Comparisons of step-counts indicated that PTB-AERO (3604 ± 815) was not significantly different than PTB-PE-Lite (3386 ± 942). Mean SCS was 9.2 ± .83 and 7.2 ± 2.1 for PTB-AERO and PTB-PE-Lite. A 6.6% decrease in mean peak pressure was observed between PTB-PE-Lite and TSB-AERO, and 3.2% difference between PTB-PE-Lite and PTB-AERO. CONCLUSION: An affordable ($20 USD) and sustainably fabricated prosthesis liner was created and evaluated in trans-tibial prosthesis users. These initial results garner preliminary support for use of the AERO prosthetic liner and continued research.Implications for rehabilitationLower limb prosthetics in less-resourced settings can leverage locally sourced and affordable materials to fabricate roll-on liners for use in modern prosthetic sockets.The cost of the AERO liner is markedly lower than current standard of care gel liners, yet still facilitates use of current prosthetic sockets.

Strain Dependent Electronic Structure and Band Offset Tuning at Heterointerfaces of ASnO3 (A=Ca, Sr, and Ba) and SrTiO3.

The valence band (VB) electronic structure and VB alignments at heterointerfaces of strained epitaxial stannate ASnO3 (A=Ca, Sr, and Ba) thin films are characterized using in situ X-ray and ultraviolet photoelectron spectroscopies, with band gaps evaluated using spectroscopic ellipsometry. Scanning transmission electron microscopy with geometric phase analysis is used to resolve strain at atomic resolution. The VB electronic structure is strain state dependent in a manner that correlated with a directional change in Sn-O bond lengths with strain. However, VB offsets are found not to vary significantly with strain, which resulted in ascribing most of the difference in band alignment, due to a change in the band gaps with strain, to the conduction band edge. Our results reveal significant strain tuning of conduction band offsets using epitaxial buffer layers, with strain-induced offset differences as large as 0.6 eV possible for SrSnO3. Such large conduction band offset tunability through elastic strain control may provide a pathway to minimize the loss of charge confinement in 2-dimensional electron gases and enhance the performance of photoelectrochemical stannate-based devices.

Mid-facial deformity secondary to a traumatic haemorrhage in a maxillary cyst.

Serious symptoms caused by intra-cystic bleeding are very rare. We describe a case of a maxillary cyst presenting with mid-facial deformity in a Japanese woman. She underwent bilateral Caldwell-Luc procedure 21 years earlier and suffered left cheek trauma 4 years earlier. She presented soon after the trauma complaining of left mid-facial deformity, and computed tomography showed a trilocular cystic lesion in the left maxilla. We performed facial osteotomy concurrent with cyst enucleation with lateral rhinotomy. Serosanguineous fluid filled the cyst cavity just below the face; however, additional cyst cavities contained straw-coloured fluid. She showed no signs of recurrence at the end of a 20-month follow-up, and her postoperative appearance was excellent. Histopathological examination showed that all cyst walls were lined by ciliated columnar epithelium, which was consistent with surgical ciliated cyst. We consider that the increased intra-cystic pressure caused by traumatic haemorrhage induced expansion of the pre-existing surgical ciliated cyst.

Structure and molecular dynamics simulation of archaeal prefoldin: the molecular mechanism for binding and recognition of nonnative substrate proteins.

Prefoldin (PFD) is a heterohexameric molecular chaperone complex in the eukaryotic cytosol and archaea with a jellyfish-like structure containing six long coiled-coil tentacles. PFDs capture protein folding intermediates or unfolded polypeptides and transfer them to group II chaperonins for facilitated folding. Although detailed studies on the mechanisms for interaction with unfolded proteins or cooperation with chaperonins of archaeal PFD have been performed, it is still unclear how PFD captures the unfolded protein. In this study, we determined the X-ray structure of Pyrococcus horikoshii OT3 PFD (PhPFD) at 3.0 A resolution and examined the molecular mechanism for binding and recognition of nonnative substrate proteins by molecular dynamics (MD) simulation and mutation analyses. PhPFD has a jellyfish-like structure with six long coiled-coil tentacles and a large central cavity. Each subunit has a hydrophobic groove at the distal region where an unfolded substrate protein is bound. During MD simulation at 330 K, each coiled coil was highly flexible, enabling it to widen its central cavity and capture various nonnative proteins. Docking MD simulation of PhPFD with unfolded insulin showed that the beta subunit is essentially involved in substrate binding and that the alpha subunit modulates the shape and width of the central cavity. Analyses of mutant PhPFDs with amino acid replacement of the hydrophobic residues of the beta subunit in the hydrophobic groove have shown that beta Ile107 has a critical role in forming the hydrophobic groove.