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In the intelligent transportation field, the Internet of Things (IoT) is commonly applied using 3D object detection as a crucial part of Vehicle-to-Everything (V2X) cooperative perception. However, challenges arise from discrepancies in sensor configurations between vehicles and infrastructure, leading to variations in the scale and heterogeneity of point clouds. To address the performance differences caused by the generalization problem of 3D object detection models with heterogeneous LiDAR point clouds, we propose the Dual-Channel Generalization Neural Network (DCGNN), which incorporates a novel data-level downsampling and calibration module along with a cross-perspective Squeeze-and-Excitation attention mechanism for improved feature fusion. Experimental results using the DAIR-V2X dataset indicate that DCGNN outperforms detectors trained on single datasets, demonstrating significant improvements over selected baseline models.

Anterior shoulder dislocation is a common orthopedic emergency. While many reduction methods require sedation, the FARES (FAst, REliable, and Safe) and Spaso methods allow reduction without anesthesia. We conducted a single-center, prospective, randomized controlled trial comparing the FARES and Spaso methods for anterior shoulder dislocation reduction. Patients aged 20 to 90 years were enrolled. The assigned closed reduction procedures were performed without patient sedation by trained orthopedic residents. If two attempts with the assigned method failed, the alternative method was used. The primary outcome was the first-attempt success rate, while secondary outcomes included overall success rate with both methods, reduction time, and pain scores. During November 2013 and December 2015, a total of 32 patients were randomized to the FARES (n = 17) or Spaso (n = 15) method. The first-attempt success rates were 71.6% for the FARES group and 80.0% for the Spaso group ( p  = 0.691). Among patients with failed closed reduction using the first technique, all patients in the Spaso-following-FARES group achieved successful reduction, whereas none in the FARES-following-Spaso group achieved successful reduction ( p  = 0.092). Pain scores during reduction were comparable between the FARES (4.29 ± 1.69) and Spaso (3.80 ± 2.65) techniques, with no statistically significant difference ( p  = 0.542). Follow-up data were available for 28/32 patients (87.5%; mean 5.3 ± 2.2 years). Four patients were lost (3 FARES, 1 Spaso; p  = 0.726). Recurrent dislocation occurred in 3 patients (10.7%; 1 FARES, 2 Spaso; p  = 0.947), and 2 patients (1 per group; p  = 0.876) underwent surgery (arthroscopic stabilization and rotator cuff repair). Both the FARES and Spaso methods were effective for reducing anterior shoulder dislocations. Combining these methods may improve overall reduction rates. Clinical trial registration: This trial was registered at ClinicalTrials.gov (Registration number: NCT01979237) on 08/11/2013.

Asparaginyl endopeptidase （AEP） is an endo/lysosomal cysteine endopeptidase with a preference for an asparagine residue at the P1 site and plays an important role in the maturation of toll-like receptors 3/7/9. AEP is known to undergo autoproteolytic maturation at acidic pH for catalytic activation. Here, we describe crystal structures of the AEP proenzyme and the mature forms of AEP. Structural comparisons between AEP and caspases revealed similarities in the composition of key residues and in the catalytic mechanism. Mutagenesis studies identified N44, R46, H150, E189, C191, S217/S218 and D233 as residues that are essential for the cleavage of the peptide substrate. During maturation, autoproteolytic cleavage of AEP＇s cap domain opens up access to the active site on the core domain. Unexpectedly, an intermediate autoproteolytic maturation stage was discovered at approximately pH 4.5 in which the partially activated AEP could be reversed back to its proenzyme form. This unique feature was confirmed by the crystal structure of AEPpH4.s （AEP was matured at pH 4.5 and crystallized at pH 8.5）, in which the broken peptide bonds were religated and the structure was transformed back to its proenzyme form. Additionally, the AEP inhibitor cystatin C could be digested by the fully activated AEP, but could not be digested by activated cathepsins. Thus, we demonstrate for the first time that cystatins may regulate the activity of AEP through substrate competition for the active site.

Based on recent works, the most desirable high-temperature thermoelectric material would be highly-doped Si 1−x Ge x crystals or films with sufficiently high Ge concentrations so that simultaneous enhancing the power factor and wave-engineering of phonons could be possible on the ballistic thermal conductor. However, available thin film deposition methods such as metal organic chemical vapor deposition, electron-beam evaporation, or sputtering are unable to produce highly-doped SiGe single crystals or thick films of high quality. To fabricate the desired material, we here employ liquid phase epitaxy to make highly-doped (up to 2% GaP doping) SiGe crystals with minimized concentration variations on Si (111) and (100) substrates. We find that growing Si 1−x Ge x (x = 0.05~0.25) crystals from Ga solvents at relatively high vacuum pressure (0.1 torr) displays significant deviations from previous calculated phase diagram. Moreover, doping GaP into SiGe is found to affect the solubility of the system but not the resulting Ge concentration. We thus plot a new pressure-dependent phase diagram. We further demonstrate that the new pressure-induced liquid phase epitaxy technique can yield Si 1−x Ge x crystals of much higher Ge concentrations (x > 0.8) than those grown by the conventional method.

STAT6 participates in classical IL-4/IL-13 signaling and stimulator of interferon genes-mediated antiviral innate immune responses. Aberrations in STAT6-mediated signaling are linked to development of asthma and diseases of the immune system. In addition, STAT6 remains constitutively active in multiple types of cancer. Therefore, targeting STAT6 is an attractive proposition for treating related diseases. Although a lot is known about the role of STAT6 in transcriptional regulation, molecular details on how STAT6 recognizes and binds specific segments of DNA to exert its function are not clearly understood. Here, we report the crystal structures of a homodimer of phosphorylated STAT6 core fragment (STAT6CF) alone and bound with the N3 and N4 DNA binding site. Analysis of the structures reveals that STAT6 undergoes a dramatic conformational change on DNA binding, which was further validated by performing molecular dynamics simulation studies and small angle X-ray scattering analysis. Our data show that a larger angle at the intersection where the two protomers of STAT meet and the presence of a unique residue, H415, in the DNA-binding domain play important roles in discrimination of the N4 site DNA from the N3 site by STAT6. H415N mutation of STAT6CF decreased affinity of the protein for the N4 site DNA, but increased its affinity for N3 site DNA, both in vitro and in vivo. Results of our structure–function studies on STAT6 shed light on mechanism of DNA recognition by STATs in general and explain the reasons underlying STAT6’s preference for N4 site DNA over N3.

The ability of Mycobacterium tuberculosis ( Mtb ) to persist in its host may enable an evolutionary advantage for drug resistant variants to emerge. A potential strategy to prevent persistence and gain drug efficacy is to directly target the activity of enzymes that are crucial for persistence. We present a method for expedited discovery and structure-based design of lead compounds by targeting the hypoxia-associated enzyme L-alanine dehydrogenase (AlaDH). Biochemical and structural analyses of AlaDH confirmed binding of nucleoside derivatives and showed a site adjacent to the nucleoside binding pocket that can confer specificity to putative inhibitors. Using a combination of dye-ligand affinity chromatography, enzyme kinetics and protein crystallographic studies, we show the development and validation of drug prototypes. Crystal structures of AlaDH-inhibitor complexes with variations at the N6 position of the adenyl-moiety of the inhibitor provide insight into the molecular basis for the specificity of these compounds. We describe a drug-designing pipeline that aims to block Mtb to proliferate upon re-oxygenation by specifically blocking NAD accessibility to AlaDH. The collective approach to drug discovery was further evaluated through in silico analyses providing additional insight into an efficient drug development strategy that can be further assessed with the incorporation of in vivo studies.

Biomechanical deviations at individual joints are often identified by gait analysis of patients with cerebral palsy (CP). Analysis of the control of joint and leg stiffness of the locomotor system during gait in children with spastic diplegic CP has been used to reveal their control strategy, but the differences between before and after surgery remain unknown. The current study aimed to bridge the gap by comparing the leg stiffness—both skeletal and muscular components—and associated joint stiffness during gait in 12 healthy controls and 12 children with spastic diplegic CP before and after tendon release surgery (TRS). Each subject walked at a self-selected pace on a 10-meter walkway while their kinematic and forceplate data were measured to calculate the stiffness-related variables during loading response, mid-stance, terminal stance, and pre-swing. The CP group altered the stiffness of the lower limb joints and decreased the demand on the muscular components while maintaining an unaltered leg stiffness during stance phase after the TRS. The TRS surgery improved the joint and leg stiffness control during gait, although residual deficits and associated deviations still remained. It is suggested that the stiffness-related variables be included in future clinical gait analysis for a more complete assessment of gait in children with CP.

Aorto-right-atrial fistula is an uncommon condition with an unclear pathogenesis. We present the case of a 3-year-old girl with a giant omphalocele repaired days after birth and incidentally discovered with a celiacomesenteric trunk-to-right atrium fistula. Three-dimensional reconstruction CT unveiled its anatomical pattern, and the fistula was successfully closed using a Amplatzer vascular plug II percutaneously.

Sighting and binding of double-stranded DNA （ds- DNA） by a sensor in the cytoplasm trigger the activation of the immune-surveillance pathways [1]. The crystal structure of absent in melanoma 2 （AIM2） bound with DNA conclusively defines the role of AIM2 as a sensor in the innate immune system [2]. AIM2 belongs to the PYHIN family of proteins and contains a pyrin domain （PYD） followed by a hematopoietic interferon-inducible nuclear protein （HIN） domain （Figure 1A）. AIM2 binds DNA via the HIN domain and recruits the adaptor pro- tein apoptosis-associated speck-like protein containing a caspase recruitment domain （ASC） via the PYD. ASC in turn recruits caspase-1 via CARD-CARD interaction, resulting in the formation of inflammasomes comprised of AIM2, ASC and caspase-1. The molecular crowding of the AIM2 inflammasome ensures the proteolysis and transactivation of caspase-1. Activated caspase-1 cleaves pro-IL-1 ]3 and pro-IL-18 into their mature proinflamma- tory forms [3, 4]. The termination of inflammatory responses originated from inflammasomes can be accomplished by employing naturally occurring dominant-negative antagonists [4]. Dominant-negative proteins are similar to their canoni- cal counterparts except for a missing effector domain, so that they cannot relay the signals any further. They out- compete their canonical counterparts for ligands or bind- ing sites and thus block the downstream signal transduc- tion. Such regulation is essential for maintaining cellular homeostasis. To regulate inflammasome activation, mice have evolved a strategy that has so far not been discov- ered in humans. Mice use the H1N-only protein, p202, to sequester cytoplasmic dsDNA and render it unavailable for its canonical sensor, AIM2 [4]. p202 contains two HIN domains （HINa and H1Nb）, but lacks the PYD （Fig- ure 1A）. Therefore, p202 is unable to recruit the adaptor ASC, and its binding to DNA results in the termination of inflammasome signaling. The significance of p202 in the regulation of the innate immune responses is exem- plified by the fact that dysregulation of p202 function hasbeen linked to increased susceptibility to systemic lupus erythematosus [5]. To more clearly understand the mechanism of inhibi- tion of AIM2-mediated signaling by p202, it is essential to solve the structure of p202 in complex with DNA and compare it with that of AIM2 complexed with DNA. p202 has so far only been detected in mice. To compare the structure of AIM2 and p202 from the same species, we first solved the structure of the H1N domain of mu- rine AIM2 （mAIM2） in complex with dsDNA to 2.23 A resolution （Supplementary information, Table S1）. Although a 12-base pair （bp） long dsDNA was used for the crystallization, the HIN domain of mAIM2 seems to have lined up the DNA oligonucleotides end to end, gen- erating an appearance of a long and contiguous stretch of B-form DNA with putative major and minor grooves. As expected, the overall structure of the H1N domain of mAIM2 （Figure 1B） closely mirrors the structure of its human counterpart [2] （Supplementary information, Fig- ure S 1）. Minor deviations are observed at the N-terminus and in the loop regions. The surface electrostatic poten- tial distribution is similar, implying that the mechanism of tethering dsDNA is similar between human and mouse AIM2. The HIN domain of AIM2 consists of two oligonucle- otide/oligosaccharide （OB） folds [6] linked via a flexible linker （Figure 1B）. The proximal and distal OB folds are referred to as OB1 and OB2, respectively. Similar to the human ortholog, mAIM2 uses the helix-loop-helix motif located in the linker to engage DNA （Figure 1C）. Specifically, a short helix containing two turns is inserted horizontally to the vertical axis of the DNA spiral （Figure 1C）. Amino acids from the loop connecting helices ul and a2, and from helix ct2 interact with the major groove （Figure 1C）. A couple of interactions between OB2 and the DNA backbone are also observed. Residues N244, N245, K248, R249, R251, R255, K258, 0262 K273,

Consider material machinability and lattice mismatch sapphire as substrates for the ultraviolet-C light-emitting diodes (UV-C LEDs) are commonly used, but their high refractive index can result in the total internal reflection (TIR) of light whereby some light is absorbed, therefore caused reducing light extraction efficiency (LEE). In this study, we propose a method to optimize the thickness of a sapphire substrate light guide layer through first-order optical design which used the optical simulation software Ansys SPEOS to simulate and evaluate the light extraction efficiency. AlGaN UV-C LEDs wafers with a light guide layer thickness of 150–700 μm were used. The simulation proceeded under a center wavelength of 275 nm to determine the optimal thickness design of the light guide layer. Finally, the experimental results demonstrated that the initial light guide layer thickness of 150 μm the reference output power of 13.53 mW, and an increased thickness of 600 um resulted in output power of 20.58 mW. The LEE can be increased by 1.52 times through light guide layer thickness optimization. We propose a method to optimize the thickness of a sapphire substrate light guide layer through first-order optical design. AlGaN UV-C LEDs wafers with a light guide layer thickness of 150–700 μm were used. Finally, the experimental results demonstrated that the LEE can be increased by 1.52 times through light guide layer thickness optimization.