Speech Emotion Recognition Incorporating Relative Difficulty and Labeling Reliability.

Emotions in speech are expressed in various ways, and the speech emotion recognition (SER) model may perform poorly on unseen corpora that contain different emotional factors from those expressed in training databases. To construct an SER model robust to unseen corpora, regularization approaches or metric losses have been studied. In this paper, we propose an SER method that incorporates relative difficulty and labeling reliability of each training sample. Inspired by the Proxy-Anchor loss, we propose a novel loss function which gives higher gradients to the samples for which the emotion labels are more difficult to estimate among those in the given minibatch. Since the annotators may label the emotion based on the emotional expression which resides in the conversational context or other modality but is not apparent in the given speech utterance, some of the emotional labels may not be reliable and these unreliable labels may affect the proposed loss function more severely. In this regard, we propose to apply label smoothing for the samples misclassified by a pre-trained SER model. Experimental results showed that the performance of the SER on unseen corpora was improved by adopting the proposed loss function with label smoothing on the misclassified data.

Structural basis of the fanconi anemia-associated mutations within the FANCA and FANCG complex.

Monoubiquitination of the Fanconi anemia complementation group D2 (FANCD2) protein by the FA core ubiquitin ligase complex is the central event in the FA pathway. FANCA and FANCG play major roles in the nuclear localization of the FA core complex. Mutations of these two genes are the most frequently observed genetic alterations in FA patients, and most point mutations in FANCA are clustered in the C-terminal domain (CTD). To understand the basis of the FA-associated FANCA mutations, we determined the cryo-electron microscopy (EM) structures of Xenopus laevis FANCA alone at 3.35 Å and 3.46 Å resolution and two distinct FANCA-FANCG complexes at 4.59 and 4.84 Å resolution, respectively. The FANCA CTD adopts an arc-shaped solenoid structure that forms a pseudo-symmetric dimer through its outer surface. FA- and cancer-associated point mutations are widely distributed over the CTD. The two different complex structures capture independent interactions of FANCG with either FANCA C-terminal HEAT repeats, or the N-terminal region. We show that mutations that disturb either of these two interactions prevent the nuclear localization of FANCA, thereby leading to an FA pathway defect. The structure provides insights into the function of FANCA CTD, and provides a framework for understanding FA- and cancer-associated mutations.

ClpL is a functionally active tetradecameric AAA+ chaperone, distinct from hexameric/dodecameric ones.

AAA+ (ATPases associated with diverse cellular activities) chaperones are involved in a plethora of cellular activities to ensure protein homeostasis. The function of AAA+ chaperones is mostly modulated by their hexameric/dodecameric quaternary structures. Here we report the structural and biochemical characterizations of a tetradecameric AAA+ chaperone, ClpL from Streptococcus pneumoniae. ClpL exists as a tetradecamer in solution in the presence of ATP. The cryo-EM structure of ClpL at 4.5 Å resolution reveals a striking tetradecameric arrangement. Solution structures of ClpL derived from small-angle X-ray scattering data suggest that the tetradecameric ClpL could assume a spiral conformation found in active hexameric/dodecameric AAA+ chaperone structures. Vertical positioning of the middle domain accounts for the head-to-head arrangement of two heptameric rings. Biochemical activity assays with site-directed mutagenesis confirmed the critical roles of residues both in the integrity of the tetradecameric arrangement and activities of ClpL. Non-conserved Q321 and R670 are crucial in the heptameric ring assembly of ClpL. These results establish that ClpL is a functionally active tetradecamer, clearly distinct from hexameric/dodecameric AAA+ chaperones.

Versatile Strategy for Tuning ORR Activity of a Single Fe-N4 Site by Controlling Electron-Withdrawing/Donating Properties of a Carbon Plane.

Replacement of Pt-based oxygen reduction reaction (ORR) catalysts with non-precious metal catalysts (NPMCs) such as Fe/N/C is one of the most important issues in the commercialization of proton exchange membrane fuel cells (PEMFCs). Despite numerous studies on Fe/N/C catalysts, a fundamental study on the development of a versatile strategy is still required for tuning the kinetic activity of a single Fe-N4 site. Herein, we report a new and intuitive design strategy for tuning and enhancing the kinetic activity of a single Fe-N4 site by controlling electron-withdrawing/donating properties of a carbon plane with the incorporation of sulfur functionalities. The effect of electron-withdrawing/donating functionalities was elucidated by experimentation and theoretical calculations. Finally, the introduction of an oxidized sulfur functionality decreases the d-band center of iron by withdrawing electrons, thereby facilitating ORR at the Fe-N4 site by lowering the intermediate adsorption energy. Furthermore, this strategy can enhance ORR activity without a decrease in the stability of the catalyst. This simple and straightforward approach can be a cornerstone to develop optimum NPMCs for application in the cathodes of PEMFCs.

Spontaneous Generation of H2O2 and Hydroxyl Radical through O2 Reduction on Copper Phosphide under Ambient Aqueous Condition.

Copper phosphide (Cu xP) was synthesized and tested for its reactivity for generating H2O2 through spontaneous reduction of dioxygen under ambient aqueous condition. The in situ generated H2O2 was subsequently decomposed to generate OH radicals, which enabled the degradation of organic compounds in water. The oxygen reduction reaction proceeded along with the concurrent oxidation of phosphide to phosphate, then copper ions and phosphate ions were dissolved out during the reaction. The reactivity of Cu xP was gradually reduced during 10 cycles with consuming 8.7 mg of Cu xP for the successive removal of 17 µmol 4-chlorophenol. CoP which was compared as a control sample under the same experimental condition also produced H2O2 through activating dioxygen but did not degrade organic compounds at all. The electrochemical analysis for the electron transfers on Cu xP and CoP showed that the number of electrons transferred to O2 is 3 and 2, respectively, which explains why OH radical is generated on Cu xP, not on CoP. The Cu+ species generated on the Cu xP surface can participate in Fenton-like reaction with in situ generated H2O2. Cu xP is proposed as a solid reagent that can activate dioxygen to generate reactive oxygen species in ambient aqueous condition, which is more facile to handle and store than liquid/gas reagents (e.g., H2O2, Cl2, O3).

Investigation of the Support Effect in Atomically Dispersed Pt on WO3-x for Utilization of Pt in the Hydrogen Evolution Reaction.

Single-atom catalysts (SACs) have attracted growing attention because they maximize the number of active sites, with unpredictable catalytic activity. Despite numerous studies on SACs, there is little research on the support, which is essential to understanding SAC. Herein, we systematically investigated the influence of the support on the performance of the SAC by comparing with single-atom Pt supported on carbon (Pt SA/C) and Pt nanoparticles supported on WO3-x (Pt NP/WO3-x ). The results revealed that the support effect was maximized for atomically dispersed Pt supported on WO3-x (Pt SA/WO3-x ). The Pt SA/WO3-x exhibited a higher degree of hydrogen spillover from Pt atoms to WO3-x at the interface, compared with Pt NP/WO3-x , which drastically enhanced Pt mass activity for hydrogen evolution (up to 10 times). This strategy provides a new framework for enhancing catalytic activity for HER, by reducing noble metal usage in the field of SACs.

Four-fold Channel-Nicked Human Ferritin Nanocages for Active Drug Loading and pH-Responsive Drug Release.

Human ferritins are emerging platforms for non-toxic protein-based drug delivery, owing to their intrinsic or acquirable targeting abilities to cancer cells and hollow cage structures for drug loading. However, reliable strategies for high-level drug encapsulation within ferritin cavities and prompt cellular drug release are still lacking. Ferritin nanocages were developed with partially opened hydrophobic channels, which provide stable routes for spontaneous and highly accumulated loading of FeII -conjugated drugs as well as pH-responsive rapid drug release at endoplasmic pH. Multiple cancer-related compounds, such as doxorubicin, curcumin, and quercetin, were actively and heavily loaded onto the prepared nicked ferritin. Drugs on these minimally modified ferritins were effectively delivered inside cancer cells with high toxicity.

Designing a Highly Active Metal-Free Oxygen Reduction Catalyst in Membrane Electrode Assemblies for Alkaline Fuel Cells: Effects of Pore Size and Doping-Site Position.

To promote the oxygen reduction reaction of metal-free catalysts, the introduction of porous structure is considered as a desirable approach because the structure can enhance mass transport and host many catalytic active sites. However, most of the previous studies reported only half-cell characterization; therefore, studies on membrane electrode assembly (MEA) are still insufficient. Furthermore, the effect of doping-site position in the structure has not been investigated. Here, we report the synthesis of highly active metal-free catalysts in MEAs by controlling pore size and doping-site position. Both influence the accessibility of reactants to doping sites, which affects utilization of doping sites and mass-transport properties. Finally, an N,P-codoped ordered mesoporous carbon with a large pore size and precisely controlled doping-site position showed a remarkable on-set potential and produced 70% of the maximum power density obtained using Pt/C.

VipD of Legionella pneumophila targets activated Rab5 and Rab22 to interfere with endosomal trafficking in macrophages.

Upon phagocytosis, Legionella pneumophila translocates numerous effector proteins into host cells to perturb cellular metabolism and immunity, ultimately establishing intracellular survival and growth. VipD of L. pneumophila belongs to a family of bacterial effectors that contain the N-terminal lipase domain and the C-terminal domain with an unknown function. We report the crystal structure of VipD and show that its C-terminal domain robustly interferes with endosomal trafficking through tight and selective interactions with Rab5 and Rab22. This domain, which is not significantly similar to any known protein structure, potently interacts with the GTP-bound active form of the two Rabs by recognizing a hydrophobic triad conserved in Rabs. These interactions prevent Rab5 and Rab22 from binding to downstream effectors Rabaptin-5, Rabenosyn-5 and EEA1, consequently blocking endosomal trafficking and subsequent lysosomal degradation of endocytic materials in macrophage cells. Together, this work reveals endosomal trafficking as a target of L. pneumophila and delineates the underlying molecular mechanism.

Boosting Alkaline Hydrogen Oxidation Activity of Ru Single-Atom Through Promoting Hydroxyl Adsorption on Ru/WC1- x Interfaces.

The sluggish kinetics of the hydrogen oxidation reaction (HOR) in alkaline conditions continue to pose a significant challenge for the practical implementation of anion-exchange membrane fuel cells. Developing single-atom catalysts can accelerate the pace of new HOR catalyst discovery for highly cost-effective and active HOR performance. However, single-atom catalysts (SACs) for the alkaline HOR have rarely been reported, and fundamental studies on the rational design of SACs are still required. Herein, the design of Ru SAC supported on the tungsten carbide (Ru SA/WC1- x ) via in situ high-temperature annealing strategy is reported. The resulting Ru SA/WC1- x catalyst exhibits remarkably enhanced HOR performance in alkaline media, a level of activity that can not be achieved with carbon-supported Ru SAC. Electrochemical results and density functional theory demonstrate that promoting the hydroxyl adsorption on Ru SA/WC1- x interfaces, which is derived from the low potential of zero charge of WC1- x support, has a significant effect on enhancing the HOR performance of SACs. This enhancement leads to 5.8 and 60.1 times higher Ru mass activity of Ru SA/WC1- x than Ru nanoparticles on carbon and Ru single-atom on N-doped carbon, respectively. This work provides new insights into the design of highly active SACs for alkaline HOR.

Controlling Long-Term Plasticity in Neuromorphic Computing Through Modulation of Ferroelectric Polarization.

Electrolyte-gated transistors (EGTs) have significant potential for neuromorphic computing because they can control the number of ions by mimicking neurotransmitters. However, fast depolarization of the electric double layer (EDL) makes it difficult to achieve long-term plasticity (LTP). Additionally, most research utilizing organic ferroelectric materials has been focused on basic biological functions, and the impact on nonvolatile memory properties is still lacking. Herein, we present a polyvinylidene fluoride (PVDF)-based ion-gel synaptic device using PVDF and poly(vinylidene fluoride-co-hexafluoropropylene) (P(VDF-HFP)) to implement LTP through the introduction of ferroelectric materials. The PVDF-based polymer slows the escape rate of TFSI anions from the electrolyte/channel layer through residual polarization. The fabricated synaptic devices successfully demonstrate LTP by controlling ion adsorption under the influence of PVDF-based polymers. Furthermore, it implements synaptic functions including paired pulse facilitation (PPF), high-pass filtering, and neurotransmitter control. To validate the potential of neuromorphic computing, we successfully achieved high recognition rates for artificial/convolutional neural network (A/CNN) simulations via sequential adsorption and desorption under ferroelectric polarization with long-term potentiation/depression (LTP/D). This study provides a rational ion adsorption strategy utilizing the ferroelectric polarization caused by the introduction of a PVDF-based polymer in the dielectric layer.

Functionally antagonistic polyelectrolyte for electro-ionic soft actuator.

Electro-active ionic soft actuators have been intensively investigated as an artificial muscle for soft robotics due to their large bending deformations at low voltages, small electric power consumption, superior energy density, high safety and biomimetic self-sensing actuation. However, their slow responses, poor durability and low bandwidth, mainly resulting from improper distribution of ionic conducting phase in polyelectrolyte membranes, hinder practical applications to real fields. We report a procedure to synthesize efficient polyelectrolyte membranes that have continuous conducting network suitable for electro-ionic artificial muscles. This functionally antagonistic solvent procedure makes amphiphilic Nafion molecules to assemble into micelles with ionic surfaces enclosing non-conducting cores. Especially, the ionic surfaces of these micelles combine together during casting process and form a continuous ionic conducting phase needed for high ionic conductivity, which boosts the performance of electro-ionic soft actuators by 10-time faster response and 36-time higher bending displacement. Furthermore, the developed muscle shows exceptional durability over 40 days under continuous actuation and broad bandwidth below 10 Hz, and is successfully applied to demonstrate an inchworm-mimetic soft robot and a kinetic tensegrity system.

Insight into Defect Engineering of Atomically Dispersed Iron Electrocatalysts for High-Performance Proton Exchange Membrane Fuel Cell.

Atomically dispersed and nitrogen coordinated iron catalysts (Fe-NCs) demonstrate potential as alternatives to platinum-group metal (PGM) catalysts in oxygen reduction reaction (ORR). However, in the context of practical proton exchange membrane fuel cell (PEMFC) applications, the membrane electrode assembly (MEA) performances of Fe-NCs remain unsatisfactory. Herein, improved MEA performance is achieved by tuning the local environment of the Fe-NC catalysts through defect engineering. Zeolitic imidazolate framework (ZIF)-derived nitrogen-doped carbon with additional CO2 activation is employed to construct atomically dispersed iron sites with a controlled defect number. The Fe-NC species with the optimal number of defect sites exhibit excellent ORR performance with a high half-wave potential of 0.83 V in 0.5 M H2 SO4 . Variation in the number of defects allows for fine-tuning of the reaction intermediate binding energies by changing the contribution of the Fe d-orbitals, thereby optimizing the ORR activity. The MEA based on a defect-engineered Fe-NC catalyst is found to exhibit a remarkable peak power density of 1.1 W cm-2 in an H2 /O2 fuel cell, and 0.67 W cm-2  in an H2 /air fuel cell, rendering it one of the most active atomically dispersed catalyst materials at the MEA level.

Single-molecule fingerprinting of protein-drug interaction using a funneled biological nanopore.

In drug discovery, efficient screening of protein-drug interactions (PDIs) is hampered by the limitations of current biophysical approaches. Here, we develop a biological nanopore sensor for single-molecule detection of proteins and PDIs using the pore-forming toxin YaxAB. Using this YaxAB nanopore, we demonstrate label-free, single-molecule detection of interactions between the anticancer Bcl-xL protein and small-molecule drugs as well as the Bak-BH3 peptide. The long funnel-shaped structure and nanofluidic characteristics of the YaxAB nanopore enable the electro-osmotic trapping of diverse folded proteins and high-resolution monitoring of PDIs. Distinctive nanopore event distributions observed in the two-dimensional (ΔI/Io-versus-IN) plot illustrate the ability of the YaxAB nanopore to discriminate individual small-molecule drugs bound to Bcl-xL from non-binders. Taken together, our results present the YaxAB nanopore as a robust platform for label-free, ultrasensitive, single-molecule detection of PDIs, opening up a possibility for low-cost, highly efficient drug discovery against diverse drug targets.

Identification, structural, and biochemical characterization of a group of large Csn2 proteins involved in CRISPR-mediated bacterial immunity.

Many prokaryotic organisms acquire immunity against foreign genetic material by incorporating a short segment of foreign DNA called spacer into chromosomal loci, termed clustered regularly interspaced short palindromic repeats (CRISPRs). The encoded RNAs are processed into small fragments that guide the silencing of the invading genetic elements. The CRISPR-associated (Cas) proteins are the main executioners of these processes. Herein, we report the crystal structure of Stu0660 of Streptococcus thermophilus, a Cas protein involved in the acquisition of new spacers. By homotetramerization, Stu0660 forms a central channel which is decorated with basic amino acids and binds linear double-stranded DNA (dsDNA), but not circular dsDNA. Despite undetectably low sequence similarity, two N-terminal domains of Stu0660 are similar to the entire structure of an Enterococcus faecalis Csn2 protein, which also forms a homotetramer and binds dsDNA. Thus, this work identifies a previously unknown group of Stu0660-like Csn2 proteins (∼350 residues), which are larger than the known canonical Csn2 proteins (∼220 residues) by containing an extra C-terminal domain. The commonly present central channel in the two subgroups appears as a design to selectively interact with linear dsDNA.

Recent advances in amorphous electrocatalysts for oxygen evolution reaction.

Oxygen evolution reaction (OER) has attracted great attention as an important half-reaction in the electrochemical splitting of water for green hydrogen production. However, the inadequacy of highly efficient and stable electrocatalysts has impeded the development of this technology. Amorphous materials with long-range disordered structures have exhibited superior electrocatalytic performance compared to their crystalline counterparts due to more active sites and higher structural flexibility. This review summarizes the preparation methods of amorphous materials involving oxides, hydroxide, phosphides, sulfides, and their composites, and introduces the recent progress of amorphous OER electrocatalysts in acidic and alkaline media. Finally, the existing challenges and future perspectives for amorphous electrocatalysts for OER are discussed. Therefore, we believe that this review will guide designing amorphous OER electrocatalysts with high performance for future energy applications.

Structural basis for assembly and disassembly of the IGF/IGFBP/ALS ternary complex.

Insulin-like growth factors (IGFs) have pleiotropic roles in embryonic and postnatal growth and differentiation. Most serum IGFs are bound in a ternary complex with IGF-binding protein 3 (IGFBP3) and acid-labile subunit (ALS), extending the serum half-life of IGFs and regulating their availability. Here, we report cryo-EM structure of the human IGF1/IGFBP3/ALS ternary complex, revealing the detailed architecture of a parachute-like ternary complex and crucial determinants for their sequential and specific assembly. In vitro biochemical studies show that proteolysis at the central linker domain of IGFBP3 induces release of its C-terminal domain rather than IGF1 release from the ternary complex, yielding an intermediate complex that enhances IGF1 bioavailability. Our results provide mechanistic insight into IGF/IGFBP3/ALS ternary complex assembly and its disassembly upon proteolysis for IGF bioavailability, suggesting a structural basis for human diseases associated with IGF1 and IGFALS gene mutations such as complete ALS deficiency (ACLSD) and IGF1 deficiency.

Perovskite-based electrocatalysts for oxygen evolution reaction in alkaline media: A mini review.

Water electrolysis is one of the attractive technologies for producing clean and sustainable hydrogen fuels with high purity. Among the various kinds of water electrolysis systems, anion exchange membrane water electrolysis has received much attention by combining the advantages of alkaline water electrolysis and proton exchange membrane water electrolysis. However, the sluggish kinetics of the oxygen evolution reaction, which is based on multiple and complex reaction mechanisms, is regarded as a major obstacle for the development of high-efficiency water electrolysis. Therefore, the development of high-performance oxygen evolution reaction electrocatalysts is a prerequisite for the commercialization and wide application of water electrolysis systems. This mini review highlights the current progress of representative oxygen evolution reaction electrocatalysts that are based on a perovskite structure in alkaline media. We first summarize the research status of various kinds of perovskite-based oxygen evolution reaction electrocatalysts, reaction mechanisms and activity descriptors. Finally, the challenges facing the development of perovskite-based oxygen evolution reaction electrocatalysts and a perspective on their future are discussed.

A Dynamic Substrate Pool Revealed by cryo-EM of a Lipid-Preserved Respiratory Supercomplex.

Aims: Mitochondrial respiratory supercomplexes mediate redox electron transfer, generating a proton gradient for ATP synthesis. To provide structural information on the function of supercomplexes in physiologically relevant conditions, we conducted cryoelectron microscopy studies with supercomplexes in a lipid-preserving state. Results: Here, we present cryoelectron microscopy structures of bovine respiratory supercomplex I1III2IV1 by using a lipid-preserving sample preparation. The preparation greatly enhances the intercomplex quinone transfer activity. The structures reveal large intercomplex motions that result in different shapes and sizes of the intercomplex space between complexes I and III, forming a dynamic substrate pool. Biochemical and structural analyses indicated that intercomplex phospholipids mediate the intercomplex motions. An analysis of the different classes of focus-refined complex I showed that structural switches due to quinone reduction led to the formation of a novel channel that could transfer reduced quinones to the intercomplex substrate pool. Innovation and Conclusion: Our results indicate potential mechanism for the facilitated electron transfer involving a dynamic substrate pool and intercomplex movement by which supercomplexes play an active role in the regulation of metabolic flux and reactive oxygen species.

In Situ Formation of Ag Nanoparticles for Fiber Strain Sensors: Toward Textile-Based Wearable Applications.

Wearable electronic devices have attracted significant attention as important components in several applications. Among various wearable electronic devices, interest in textile electronic devices is increasing because of their high deformability and portability in daily life. To develop textile electronic devices, fiber-based electronic devices should be fundamentally studied. Here, we report a stretchable and sensitive fiber strain sensor fabricated using only harmless materials during an in situ formation process. Despite using a mild and harmless reducing agent instead of typical strong and hazardous reducing agents, the developed fiber strain sensors feature a low initial electrical resistance of 0.9 Ω/cm, a wide strain sensing range (220%), high sensitivity (∼5.8 × 104), negligible hysteresis, and high stability against repeated stretching-releasing deformation (5000 cycles). By applying the fiber sensors to various textiles, we demonstrate that the smart textile system can monitor various gestures in real-time and help users maintain accurate posture during exercise. These results will provide meaningful insights into the development of next-generation wearable applications.