This paper proposed a multi-layered 3D NDT (normal distribution transform) scan-matching approach for robust localization even in the highly dynamic environment of warehouse logistics. Our approach ...partitioned a given 3D point-cloud map and the scan measurements into several layers regarding the degree of environmental changes in the height direction and computed the covariance estimates for each layer using 3D NDT scan-matching. Because the covariance determinant is the estimate's uncertainty, we can determine which layers are better to use in the localization in the warehouse. If the layer gets close to the warehouse's floor, the degree of environmental changes, such as the cluttered warehouse layout and position of boxes, would be significantly large, while it has many good features for scan-matching. If the observation at a specific layer is not explained well enough, then the layer for localization can be switched to other layers with lower uncertainties. Thus, the main novelty of this approach is that localization robustness can be improved even in very cluttered and dynamic environments. This study also provides the simulation-based validation using Nvidia's Omniverse Isaac sim and detailed mathematical descriptions for the proposed method. Moreover, the evaluated results of this study can be a good starting point for further mitigating the effects of occlusion in warehouse navigation of mobile robots.
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We report a novel negative photoconductivity (NPC) mechanism in n-type indium arsenide nanowires (NWs). Photoexcitation significantly suppresses the conductivity with a gain up to 105. The origin of ...NPC is attributed to the depletion of conduction channels by light assisted hot electron trapping, supported by gate voltage threshold shift and wavelength-dependent photoconductance measurements. Scanning photocurrent microscopy excludes the possibility that NPC originates from the NW/metal contacts and reveals a competing positive photoconductivity. The conductivity recovery after illumination substantially slows down at low temperature, indicating a thermally activated detrapping mechanism. At 78 K, the spontaneous recovery of the conductance is completely quenched, resulting in a reversible memory device, which can be switched by light and gate voltage pulses. The novel NPC based optoelectronics may find exciting applications in photodetection and nonvolatile memory with low power consumption.
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Magnetic, fluorescent core–shell nanoparticles consist of a single Fe3O4 nanocrystal core and a dye‐doped mesoporous silica shell with a poly(ethylene glycol) coating (see picture of TEM images and ...schematic depictions). These nanoparticles can be used as magnetic resonance and fluorescence imaging agents, and as drug delivery vehicles, thus making them novel candidates for simultaneous cancer diagnosis and therapy.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
The implementation of ultrahigh‐density cross‐point array structures has received considerable interest as emerging storage devices, and threshold switching devices are regarded to be promising as to ...the suppression of leakage current in cross‐point array structures. Threshold switching devices need to modulate the threshold voltage (Vth) depending on the various memory elements to achieve proper selector device in cross‐point array structures. However, only limited methods are available for controlling Vth. Therefore, the nitrogen (N) doping effects on trap states, density of localized states, and Vth of the amorphous Ga2Te3 (a‐Ga2Te3) selector devices are investigated herein. Furthermore, the electrical conduction behavior is fitted using a trap‐controlled space charge limited conduction mechanism with two transition voltages, i.e., the space charge limited voltage (VSCL) and trap‐filled limited voltage (VTFL). The optical bandgap energy and optical Urbach energy are affected by the N doping in a‐Ga2Te3. In addition, N doping in a‐Ga2Te3 increases the density of localized states. These effects increase both the transition voltages (VSCL and VTFL). Thus, doping a‐Ga2Te3 with N reduces Vth when the trap states are changed. Furthermore, N‐doped a‐Ga2Te3 selector devices exhibit highly reliable switching up to 109 cycles.
The threshold voltage of amorphous Ga2Te3 selector devices can be modulated by nitrogen doping with excellent stability over at least 109 switching cycles. Nitrogen‐induced changes of trap states reduce the threshold voltage and increase the transition voltages demarking the different regimes of current–voltage behavior in the high‐resistance state, as described by the trap‐controlled space charge limited conduction model.
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Missense mutations of leucine-rich repeat kinase 2 (LRRK2), including the G2019S mutant, are responsible for the pathogenesis of Parkinson’s disease. In this work, structure-based virtual screening ...of a large chemical library was carried out to identify a number of novel inhibitors of the G2019S mutant of LRRK2, the biochemical potencies of which ranged from the low micromolar to the submicromolar level. The discovery of these potent inhibitors was made possible due to the modification of the original protein–ligand binding energy function in order to include an accurate ligand dehydration energy term. The results of extensive molecular docking simulations indicated that the newly identified inhibitors were bound to the ATP-binding site of the G2019S mutant of LRRK2 through the multiple hydrogen bonds with backbone amide groups in the hinge region as well as the hydrophobic interactions with the nonpolar residues in the P-loop, hinge region, and interdomain region. Among 18 inhibitors derived from virtual screening, 4-(2-amino-5-phenylpyrimidin-4-yl)benzene-1,3-diol (Inhibitor 2) is most likely to serve as a new molecular scaffold to optimize the biochemical potency, because it revealed submicromolar inhibitory activity in spite of its low molecular weight (279.3 amu). Indeed, a highly potent inhibitor (Inhibitor 2n) of the G2019S mutant was derived via the structure-based de novo design using the structure of Inhibitor 2 as the molecular core. The biochemical potency of Inhibitor 2n surged to the nanomolar level due to the strengthening of hydrophobic interactions in the ATP-binding site, which were presumably caused by the substitutions of small nonpolar moieties. Due to the high biochemical potency against the G2019S mutant of LRRK2 and the putatively good physicochemical properties, Inhibitor 2n is anticipated to serve as a new lead compound for the discovery of antiparkinsonian medicines.
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Abstract
Superconductivity in the vicinity of a competing electronic order often manifests itself with a superconducting dome, centered at a presumed quantum critical point in the phase diagram. This ...common feature, found in many unconventional superconductors, has supported a prevalent scenario in which fluctuations or partial melting of a parent order are essential for inducing or enhancing superconductivity. Here we present a contrary example, found in IrTe
2
nanoflakes of which the superconducting dome is identified well inside the parent stripe charge ordering phase in the thickness-dependent phase diagram. The coexisting stripe charge order in IrTe
2
nanoflakes significantly increases the out-of-plane coherence length and the coupling strength of superconductivity, in contrast to the doped bulk IrTe
2
. These findings clarify that the inherent instabilities of the parent stripe phase are sufficient to induce superconductivity in IrTe
2
without its complete or partial melting. Our study highlights the thickness control as an effective means to unveil intrinsic phase diagrams of correlated van der Waals materials.
Chalcogenide materials of the amorphous phase with low band gaps were reported to show Ovonic threshold switching (OTS), making them suitable for selection devices in cross-point memory arrays. ...Herein, we report that ZnTe films with polycrystalline structures show OTS behavior. Nearly stoichiometric ZnTe thin films were deposited by an RF sputtering method. X-ray diffraction analysis indicated that the films were polycrystalline. The optical band gaps of the ZnTe films were estimated as 2.2 eV from UV-visible spectroscopy transmittance measurements. Photoluminescence measurements indicated the existence of deep-level defects in the ZnTe thin films. Although these ZnTe films have a polycrystalline structure with a relatively high band gap, I-V profiles show OTS characteristics, with a selectivity of over 104, fast threshold switching time in the sub-10 ns scale, and thermal stability up to 400 °C. ZnTe also shows switching endurance for more than 109 cycles without Vth drift, maintaining its selectivity of 104. Thus, we improved the threshold switching characteristics by using a wide band-gap and polycrystalline-structured ZnTe-based chalcogenide material. Post-annealing experiments indicated that the thermal budget of the ZnTe thin film was sufficient for stacked cross-point array structures, thereby overcoming a previous limitation of chalcogenide switching materials. This material is promising for application in high-density cross-point memory arrays as the selection device.
Exosomes are cell-derived vesicles containing heterogeneous active biomolecules such as proteins, lipids, mRNAs, receptors, immune regulatory molecules, and nucleic acids. They typically range in ...size from 30 to 150 nm in diameter. An exosome’s surfaces can be bioengineered with antibodies, fluorescent dye, peptides, and tailored for small molecule and large active biologics. Exosomes have enormous potential as a drug delivery vehicle due to enhanced biocompatibility, excellent payload capability, and reduced immunogenicity compared to alternative polymeric-based carriers. Because of active targeting and specificity, exosomes are capable of delivering their cargo to exosome-recipient cells. Additionally, exosomes can potentially act as early stage disease diagnostic tools as the exosome carries various protein biomarkers associated with a specific disease. In this review, we summarize recent progress on exosome composition, biological characterization, and isolation techniques. Finally, we outline the exosome’s clinical applications and preclinical advancement to provide an outlook on the importance of exosomes for use in targeted drug delivery, biomarker study, and vaccine development.
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The patella-patellar tendon angle (PPTA) assessing the sagittal patellar tilt was reported to be related with anterior knee pain. Herein, clinical effect of PPTA in patients with medial patellar ...plica (MPP) syndrome, chondromalacia patella, and infrapatellar fat pad (IPFP) syndrome, the most common causes of anterior knee pain, was evaluated. In this retrospective study, 156 patients with anterior knee pain who underwent magnetic resonance imaging (MRI) and arthroscopic surgery that confirmed isolated MPP syndrome, chondromalacia patella, or IPFP syndrome from June 2011 to January 2021 were included in the study group and 118 patients without knee pathology on MRI during the same period were included in the control group. The PPTA was measured on knee MRI and compared between the two groups. A receiver operating characteristic (ROC) analysis was used to evaluate the value of PPTA for predicting the risk of patellofemoral joint disorder. The mean PPTA was significantly smaller in study group (138.1 ± 4.2°) than control group (142.1 ± 4.3°) (p < 0.001). However, there was no significant difference in PPTA among the patients with MPP syndrome, chondromalacia patella, and IPFP syndrome. Furthermore, the ROC analysis revealed that the area under curve, sensitivity, and specificity for predicting the risk of patellofemoral joint disorders were 0.696, 70.3% and 57.6%, respectively, at a PPTA cutoff of 138.3°. Therefore, the smaller PPTA may be associated with MPP syndrome, chondromalacia patella, and IPFP syndrome. Furthermore, PPTA could be a predictive factor for the risk of patellofemoral joint disease in patients with anterior knee pain.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Being a component of the Ras/Raf/MEK/ERK signaling pathway crucial for cellular responses, the VRAF murine sarcoma viral oncogene homologue B1 (BRAF) kinase has emerged as a promising target for ...anticancer drug discovery due to oncogenic mutations that lead to pathway hyperactivation. Despite the discovery of several small-molecule BRAF kinase inhibitors targeting oncogenic mutants, their clinical utility has been limited by challenges such as off-target effects and suboptimal pharmacological properties. This study focuses on identifying miniprotein inhibitors for the oncogenic V600E mutant BRAF, leveraging their potential as versatile drug candidates. Using a structure-based de novo design approach based on binding affinity to V600E mutant BRAF and hydration energy, 39 candidate miniprotein inhibitors comprising three helices and 69 amino acids were generated from the substructure of the endogenous ligand protein (14-3-3). Through in vitro binding and kinase inhibition assays, two miniproteins (63 and 76) were discovered as novel inhibitors of V600E mutant BRAF with low-micromolar activity, with miniprotein 76 demonstrating a specific impediment to MEK1 phosphorylation in mammalian cells. These findings highlight miniprotein 76 as a potential lead compound for developing new cancer therapeutics, and the structural features contributing to its biochemical potency against V600E mutant BRAF are discussed in detail.
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