A crossbar array of magnetoresistive memory devices for in-memory computing.

Implementations of artificial neural networks that borrow analogue techniques could potentially offer low-power alternatives to fully digital approaches1-3. One notable example is in-memory computing based on crossbar arrays of non-volatile memories4-7 that execute, in an analogue manner, multiply-accumulate operations prevalent in artificial neural networks. Various non-volatile memories-including resistive memory8-13, phase-change memory14,15 and flash memory16-19-have been used for such approaches. However, it remains challenging to develop a crossbar array of spin-transfer-torque magnetoresistive random-access memory (MRAM)20-22,  despite the technology's practical advantages such as endurance and large-scale commercialization5. The difficulty stems from the low resistance of MRAM, which would result in large power consumption in a conventional crossbar array that uses current summation for analogue multiply-accumulate operations. Here we report a 64 × 64 crossbar array based on MRAM cells that overcomes the low-resistance issue with an architecture that uses resistance summation for analogue multiply-accumulate operations. The array is integrated with readout electronics in 28-nanometre complementary metal-oxide-semiconductor technology. Using this array, a two-layer perceptron is implemented to classify 10,000 Modified National Institute of Standards and Technology digits with an accuracy of 93.23 per cent (software baseline: 95.24 per cent). In an emulation of a deeper, eight-layer Visual Geometry Group-8 neural network with measured errors, the classification accuracy improves to 98.86 per cent (software baseline: 99.28 per cent). We also use the array to implement a single layer in a ten-layer neural network to realize face detection with an accuracy of 93.4 per cent.

Zero-shot test time adaptation via knowledge distillation for personalized speech denoising and dereverberation.

A personalization framework to adapt compact models to test time environments and improve their speech enhancement (SE) performance in noisy and reverberant conditions is proposed. The use-cases are when the end-user device encounters only one or a few speakers and noise types that tend to reoccur in the specific acoustic environment. Hence, a small personalized model that is sufficient to handle this focused subset of the original universal SE problem is postulated. The study addresses a major data shortage issue: although the goal is to learn from a specific user's speech signals and the test time environment, the target clean speech is unavailable for model training due to privacy-related concerns and technical difficulty of recording noise and reverberation-free voice signals. The proposed zero-shot personalization method uses no clean speech target. Instead, it employs the knowledge distillation framework, where the more advanced denoising results from an overly large teacher work as pseudo targets to train a small student model. Evaluation on various test time conditions suggests that the proposed personalization approach can significantly enhance the compact student model's test time performance. Personalized models outperform larger non-personalized baseline models, demonstrating that personalization achieves model compression with no loss in dereverberation and denoising performance.

Characterization of the coformycin biosynthetic gene cluster in Streptomyces kaniharaensis.

Coformycin and pentostatin are structurally related N-nucleoside inhibitors of adenosine deaminase characterized by an unusual 1,3-diazepine nucleobase. Herein, the cof gene cluster responsible for coformycin biosynthesis is identified. Reconstitution of the coformycin biosynthetic pathway in vitro demonstrates that it overlaps significantly with the early stages of l-histidine biosynthesis. Committed entry into the coformycin pathway takes place via conversion of a shared branch point intermediate to 8-ketocoformycin-[Formula: see text]-monophosphate catalyzed by CofB, which is a homolog of succinylaminoimidazolecarboxamide ribotide (SAICAR) synthetase. This reaction appears to proceed via a Dieckmann cyclization and a retro-aldol elimination, releasing ammonia and D-erythronate-4-phosphate as coproducts. Completion of coformycin biosynthesis involves reduction and dephosphorylation of the CofB product, with the former reaction being catalyzed by the NADPH-dependent dehydrogenase CofA. CofB also shows activation by adenosine triphosphate (ATP) despite the reaction requiring neither a phosphorylated nor an adenylated intermediate. This may serve to help regulate metabolic partitioning between the l-histidine and coformycin pathways.

Comparative advantages of a type-II superlattice barrier over an AlGaSb barrier for enhanced performance of InAs/GaSb LWIR nBn photodetectors.

The barrier layer in InAs/GaSb LWIR nBn detector is usually composed of AlGaSb alloy, which has a non-negligible valence band offset and is sensitive to chemical solutions. In this work, we investigated a type-II superlattice (T2SL) barrier that is homogeneous with the T2SL absorber layer in order to resolve these drawbacks of the AlGaSb barrier. The lattice mismatch of the T2SL barrier was smaller than that of the AlGaSb barrier. At -70mV and 80 K, the dark current density and the noise equivalent temperature difference of the nBn devices with the T2SL barrier were 4.4×10-6A/cm2 and 33 mK, respectively.

Identification of a Pyrrole Intermediate Which Undergoes C-Glycosidation and Autoxidation to Yield the Final Product in Showdomycin Biosynthesis.

Showdomycin is a C-nucleoside bearing an electrophilic maleimide base. Herein, the biosynthetic pathway of showdomycin is presented. The initial stages of the pathway involve non-ribosomal peptide synthetase (NRPS) mediated assembly of a 2-amino-1H-pyrrole-5-carboxylic acid intermediate. This intermediate is prone to air oxidation whereupon it undergoes oxidative decarboxylation to yield an imine of maleimide, which in turn yields the maleimide upon acidification. It is also shown that this pyrrole intermediate serves as the substrate for the C-glycosidase SdmA in the pathway. After coupling with ribose 5-phosphate, the resulting C-nucleoside undergoes a similar sequence of oxidation, decarboxylation and deamination to afford showdomcyin after exposure to air. These results suggest that showdomycin could be an artifact due to aerobic isolation; however, the autoxidation may also serve to convert an otherwise inert product of the biosynthetic pathway to an electrophilic C-nucleotide thereby endowing showdomycin with its observed bioactivities.

Using technology and remote support services to promote independent living of adults with intellectual disability and related developmental disabilities.

BACKGROUND: The use of remote support technologies is a newer form of service that can contribute to increased independence while giving adults with intellectual and developmental disabilities a sense of home safety. This research reviewed the use of remote support services, which is a waiver service that includes smart home technologies and remote support staff that can be called upon, when needed. METHOD: Using focus groups and telephone interviews, the present authors asked users of remote support services about their experience, including what they liked most and least about their experience with these technologies. RESULTS: Overall, increased independence and a sense of security and home safety were identified as the two principal benefits. Remote support technologies may be a part of the solution to addressing the lack of direct support professionals available to provide in-home care. CONCLUSIONS: The present authors discuss the benefits of remote support technologies and offer recommendations for future research regarding remote support technologies and the potential benefits of this newer form of support service.

Assessment of Dysarthria Using One-Word Speech Recognition with Hidden Markov Models.

BACKGROUND: The gold standard in dysarthria assessment involves subjective analysis by a speech-language pathologist (SLP). We aimed to investigate the feasibility of dysarthria assessment using automatic speech recognition. METHODS: We developed an automatic speech recognition based software to assess dysarthria severity using hidden Markov models (HMMs). Word-specific HMMs were trained using the utterances from one hundred healthy individuals. Twenty-eight patients with dysarthria caused by neurological disorders, including stroke, traumatic brain injury, and Parkinson's disease were participated and their utterances were recorded. The utterances of 37 words from the Assessment of Phonology and Articulation for Children test were recorded in a quiet control booth in both groups. Patients were asked to repeat the recordings for evaluating the test-retest reliability. Patients' utterances were evaluated by two experienced SLPs, and the consonant production accuracy was calculated as a measure of dysarthria severity. The trained HMMs were also employed to evaluate the patients' utterances by calculating the averaged log likelihood (aLL) as the fitness of the spoken word to the word-specific HMM. RESULTS: The consonant production accuracy reported by the SLPs strongly correlated (r = 0.808) with the aLL, and the aLL showed excellent test-retest reliability (intraclass correlation coefficient, 0.964). CONCLUSION: This leads to the conclusion that dysarthria assessment using a one-word speech recognition system based on word-specific HMMs is feasible in neurological disorders.

High-Field Electron Transport and High Saturation Velocity in Multilayer Indium Selenide Transistors.

Creating a high-frequency electron system demands a high saturation velocity (υsat). Herein, we report the high-field transport properties of multilayer van der Waals (vdW) indium selenide (InSe). The InSe is on a hexagonal boron nitride substrate and encapsulated by a thin, noncontinuous In layer, resulting in an impressive electron mobility reaching 2600 cm2/(V s) at room temperature. The high-mobility InSe achieves υsat exceeding 2 × 107 cm/s, which is superior to those of other gapped vdW semiconductors, and exhibits a 50-60% improvement in υsat when cooled to 80 K. The temperature dependence of υsat suggests an optical phonon energy (ℏωop) for InSe in the range of 23-27 meV, previously reported values for InSe. It is also notable that the measured υsat values exceed what is expected according to the optical phonon emission model due to weak electron-phonon scattering. The superior υsat of our InSe, despite its relatively small ℏωop, reveals its potential for high-frequency electronics, including applications to control cryogenic quantum computers in close proximity.

Downregulation of TRIB3 enhances the sensitivity of lung cancer cells to amino acid deprivation by suppressing AKT activation.

Tribbles pseudokinase 3 (TRIB3), a member of the mammalian Tribbles family, is implicated in multiple biological processes. This study aimed to investigate the biological functions of TRIB3 in lung cancer and its effect on amino acid-deprived lung cancer cells. TRIB3 mRNA expression was elevated in lung cancer tissues and cell lines compared to normal lung tissues and cells. TRIB3 knockdown markedly reduced the viability and proliferation of H1299 lung cancer cells. Deprivation of amino acids, particularly arginine, glutamine, lysine, or methionine, strongly increased TRIB3 expression via ATF4 activation in H1299 lung cancer cells. Knockdown of TRIB3 led to transcriptional downregulation of ATF4 and reduced AKT activation induced by amino acid deprivation, ultimately increasing the sensitivity of H1299 lung cancer cells to amino acid deprivation. Additionally, TRIB3 knockdown enhanced the sensitivity of H1299 cells to V-9302, a competitive antagonist of transmembrane glutamine flux. These results suggest that TRIB3 is a pro-survival regulator of cell viability in amino acid-deficient tumor microenvironments and a promising therapeutic target for lung cancer treatment.

Discovery of a Novel Potent EGFR Inhibitor Against EGFR Activating Mutations and On-Target Resistance in NSCLC.

PURPOSE: Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKI) serve as the standard first-line therapy for EGFR-mutated non-small cell lung cancer (NSCLC). Despite the sustained clinical benefits achieved through optimal EGFR-TKI treatments, including the third-generation EGFR-TKI osimertinib, resistance inevitably develops. Currently, there are no targeted therapeutic options available postprogression on osimertinib. Here, we assessed the preclinical efficacy of BI-4732, a novel fourth-generation EGFR-TKI, using patient-derived preclinical models reflecting various clinical scenarios. EXPERIMENTAL DESIGN: The antitumor activity of BI-4732 was evaluated using Ba/F3 cells and patient-derived cell/organoid/xenograft models with diverse EGFR mutations. Intracranial antitumor activity of BI-4732 was evaluated in a brain-metastasis mouse model. RESULTS: We demonstrated the remarkable antitumor efficacy of BI-4732 as a single agent in various patient-derived models with EGFR_C797S-mediated osimertinib resistance. Moreover, BI-4732 exhibited activity comparable to osimertinib in inhibiting EGFR-activating (E19del and L858R) and T790M mutations. In a combination treatment strategy with osimertinib, BI-4732 exhibited a synergistic effect at significantly lower concentrations than those used in monotherapy. Importantly, BI-4732 displayed potent antitumor activity in an intracranial model, with low efflux at the blood-brain barrier. CONCLUSIONS: Our findings highlight the potential of BI-4732, a selective EGFR-TKI with high blood-brain barrier penetration, targeting a broad range of EGFR mutations, including C797S, warranting clinical development.

Examining the Relationship between Adaptive Behavior and Intelligence.

Adaptive behavior and intelligence are both essential components of defining and diagnosing intellectual disability. The exact relationship between these two constructs still warrants some clarification. Previous studies have examined the correlation between adaptive behavior and intelligence and have reported differing results. Overall, there seems to be agreement that a modest to moderate correlation exists between adaptive behavior and intelligence and that the strength of this relationship may increase as ability level decreases further below the population mean. Using the Diagnostic Adaptive Behavior Scale and a sample of 57 youth aged from 4 to 21 years old, we examined the correlation coefficients between the full-scale IQ scores and their scores obtained on conceptual, social, and practical adaptive skill domain scores, as well as the total adaptive behavior score. The results obtained indicated a modest to moderate correlation between adaptive behavior and intelligence. The strongest statistically significant correlation coefficient was between the full-scale IQ score and the conceptual adaptive skills domain score (r = 0.64). The correlation between the full-scale IQ score and the practical adaptive skills domain (r = 0.39) and social adaptive skills domain (r = 0.28; ns) were more modest. The correlation coefficient between the full-scale IQ score and the total adaptive behavior score also showed a moderate relationship with intelligence (r = 0.46). These findings are consistent with previous research, documenting that adaptive behavior and intelligence are two related but independent constructs. We discuss these findings and their implications.

New estimation method of limit pressures for thick curved pipes under internal pressure applicable to various bend angles.

In this study, a new estimation method of limit pressures (loads) is suggested for reliability design of curved pipes under high internal pressure and temperature. The curved pipes are used in boiler pipes in a supercritical thermal power plants. To find any design parameters and their dimensions in reliability design of curved pipes, various boilers in supercritical thermal power plants in operation were investigated. In order to analyse the effect of the design parameters on the limit pressure, the design of experiment (DOE) was applied to design a curved pipes with various combinations of design parameters, and then the FE limit load analyses were performed to obtain limit pressures. The thickness of the curved pipe has the greatest effect on the limit pressure among the design parameters. Although the bend angle is design parameter, the proposed estimation methods for easily calculating the limit load do not include the bend angle and then there have been difficulties in reliability design of curved pipes with any band angle. Therefore, to solve such difficulties, two estimation methods of limit pressure (load) including bend angle were suggested and the validity of the proposed estimation methods of limit load (plastic pressure) under internal pressure was objectively verified through statistical error analysis with the 60 FE analysis results which are different from the data used when the method was derived. The proposed estimation method applicable to various bend angles shows the best results in the evaluation of mean error, maximum error, and standard deviation of error, which are evaluation criteria. The proposed estimation method shows a very good result compared to existing methods, having the mean error of 0.89%, a maximum error of 2.50%, and a standard deviation of 0.70% for all data regardless of the bend angle.

Plasma Nitridation Effect on ß-Ga2O3 Semiconductors.

The electrical and optoelectronic performance of semiconductor devices are mainly affected by the presence of defects or crystal imperfections in the semiconductor. Oxygen vacancies are one of the most common defects and are known to serve as electron trap sites whose energy levels are below the conduction band (CB) edge for metal oxide semiconductors, including ß-Ga2O3. In this study, the effects of plasma nitridation (PN) on polycrystalline ß-Ga2O3 thin films are discussed. In detail, the electrical and optical properties of polycrystalline ß-Ga2O3 thin films are compared at different PN treatment times. The results show that PN treatment on polycrystalline ß-Ga2O3 thin films effectively diminish the electron trap sites. This PN treatment technology could improve the device performance of both electronics and optoelectronics.

Conductivity-Controlled Polyvinylidene Fluoride Nanofiber Stack for Absorption-Dominant Electromagnetic Interference Shielding Materials.

This work presents a novel method for achieving lightweight electromagnetic interference (EMI) shielding materials with high EMI shielding effectiveness (SE) through absorption-dominant mechanisms, utilizing only organic polymer nanofibers (NFs). Instead of incorporating high-density fillers, the approach involves adjusting the concentrations of iron chloride in the NFs and subsequent vapor phase polymerization (VPP) to control the polymerization density of poly(3,4-ethylenedioxythiophene) (PEDOT) on the surface of polyvinylidene fluoride (PVDF) NFs. This process results in NF layers with varying conductivity, creating a conductivity gradient structure. The conductivity gradient structure of the NF layers significantly enhances absorptivity by reducing impedance mismatches between the shielding material and the surrounding air, as well as between different interlayers. This reduction in impedance mismatches allows for efficient dissipation of absorbed electromagnetic (EM) waves within the highly conductive NF layer. This improved absorptivity is also attributed to the attenuation of EM wave energy through multiple reflections and scattering within the NF pores. Moreover, the gradient structure of the NF layers promotes interfacial polarization, further contributing to the effective absorption of electromagnetic waves. As a result, a high absolute EMI SE (SSEt) of 12,390 dB·cm2 g-1 with low reflectivity (0.32) was achieved without compromising the lightweight and flexible properties.

Synergistic Enhancement of Filtering Efficiency and Antibacterial Performance of a Nanofiber Air Filter Decorated with Electropolarized Lithium-Doped ZnO Nanorods.

According to clinical case reports, bacterial co-infection with COVID-19 can significantly increase mortality, with Staphylococcus aureus (S. aureus) being one of the most common pathogens causing complications such as pneumonia. Thus, during the pandemic, research on imparting air filters with antibacterial properties was actively initiated, and several antibacterial agents were investigated. However, air filters with inorganic nanostructures on organic nanofibers (NFs) have not been investigated extensively. This study aimed to demonstrate the efficiency of electropolarized poly(vinylidene fluoride-trifluoroethylene) (PVDF-TrFE) NFs decorated with Li-doped ZnO nanorods (NRs) to improve the filtering ability and antibacterial activity of the ultrathin air filter. The surfactant was loaded onto the ZnO─known for its biocompatibility and low toxicity─nanoparticles (NPs) and transferred to the outer surface of the NFs, where Li-doped ZnO NRs were grown. The Li-doped ZnO NR-decorated NF effectively enhanced the physical filtration efficiency and antibacterial properties. Additionally, by exploiting the ferroelectric properties of Li-doped ZnO NRs and PVDF-TrFE NFs, the filter was electropolarized to increase its Coulombic interaction with PMs and S. aureus. As a result, the filter exhibited a 90% PM1.0 removal efficiency and a 99.5% sterilization rate against S. aureus. The method proposed in this study provides an effective route for simultaneously improving the air filter performance and antibacterial activity.

CD8α+ dendritic cells potentiate antitumor and immune activities against murine ovarian cancers.

Dendritic cell (DC)-based immunotherapies have been shown to be a potential treatment option for various cancers; however, the exact strategies in ovarian cancer remain unknown. Here, we report the effectiveness of mouse CD8α+ DCs derived from bone marrow hematopoietic stem cells (BM-HSCs), equivalent to human CD141+ DCs, which have proven to be a highly superior subset. Mono-DCs from monocytes and stem-DCs from HSCs were characterized by CD11c+ CD80+ CD86+ and CD8α+ Clec9a+ expression, respectively. Despite a lower dose compared with Mono-DCs, mice treated with pulsed Stem-DCs showed a reduced amount of ascitic fluid and lower body weights compared with those of vehicle-treated mice. These mice treated with pulsed stem-DCs appeared to have fewer tumor implants, which were usually confined in the epithelium of tumor-invaded organs. All mice treated with DCs showed longer survival than the vehicle group, especially in the medium/high dose pulsed Stem-DC treatment groups. Moreover, the stem-DC-treated group demonstrated a low proportion of myeloid-derived suppressor cells and regulatory T cells, high interleukin-12 and interferon-γ levels, and accumulation of several tumor-infiltrating lymphocytes. Together, these results indicate that mouse CD8α+ DCs derived from BM-HSCs decrease tumor progression and enhance antitumor immune responses against murine ovarian cancer, suggesting that better DC vaccines can be used as an effective immunotherapy in EOC treatment. Further studies are necessary to develop potent DC vaccines using human CD141+ DCs.

Recent Advances in Triboelectric Nanogenerators: From Technological Progress to Commercial Applications.

Serious climate changes and energy-related environmental problems are currently critical issues in the world. In order to reduce carbon emissions and save our environment, renewable energy harvesting technologies will serve as a key solution in the near future. Among them, triboelectric nanogenerators (TENGs), which is one of the most promising mechanical energy harvesters by means of contact electrification phenomenon, are explosively developing due to abundant wasting mechanical energy sources and a number of superior advantages in a wide availability and selection of materials, relatively simple device configurations, and low-cost processing. Significant experimental and theoretical efforts have been achieved toward understanding fundamental behaviors and a wide range of demonstrations since its report in 2012. As a result, considerable technological advancement has been exhibited and it advances the timeline of achievement in the proposed roadmap. Now, the technology has reached the stage of prototype development with verification of performance beyond the lab scale environment toward its commercialization. In this review, distinguished authors in the world worked together to summarize the state of the art in theory, materials, devices, systems, circuits, and applications in TENG fields. The great research achievements of researchers in this field around the world over the past decade are expected to play a major role in coming to fruition of unexpectedly accelerated technological advances over the next decade.

Surgical management of lateral lesions with intentional replantation in single-rooted mandibular first premolars with radicular groove: 2 case reports.

BACKGROUND: The authors' aim was to describe 2 endodontically treated mandibular first premolars with apical and mesiolingual radiolucencies on radiographs with different approaches that were resolved with intentional replantation. CASE DESCRIPTION: In case 1, a 58-year-old man reported biting sensitivity on endodontically treated mandibular first premolar with good quality restorations. A periapical radiograph (PAX) and cone-beam computed tomography (CBCT) image revealed 2 low-density areas located at the apical and mesiolingual aspects of the root. A radicular groove accessory canal was noted on the mesial root surface during intentional replantation. The patient has been asymptomatic. At a 3-year follow-up, complete healing was observed on PAX and CBCT images. In case 2, a 40-year-old woman reported pinching pain of her mandibular right quadrant that returned a few months after initial root canal treatment. Radiographs revealed periapical radiolucency at the apexes of the mandibular first premolar with a missed lingual canal. Nonsurgical retreatment was performed in 2 visits with calcium hydroxide dressing. Two months later, endodontic microsurgery was performed owing to ongoing symptoms. In addition, CBCT images showed extensive bone loss on the mesiolingual aspect of the root. Intentional replantation was performed 2 weeks later because she had intolerable pain. A radicular groove accessory canal was observed on the mesial root surface during the procedure. The patient reported substantial relief of pain. The radiolucencies healed by the 25-month follow-up as observed on PAX and CBCT images. PRACTICAL IMPLICATIONS: Intentional replantation is recommended in mandibular first premolars with a mesiolingual lesion that cannot be accessed easily with endodontic microsurgery and after conservative retreatment has been performed.

Enhanced Output Performance of a Flexible Piezoelectric Nanogenerator Realized by Lithium-Doped Zinc Oxide Nanowires Decorated on MXene.

A flexible piezoelectric composite is composed of a polymer matrix and piezoelectric ceramic fillers to achieve good mechanical flexibility and processability. The overall piezoelectric performance of a composite is largely determined by the piezoelectric filler inside. Thus, different dispersion methods and additives that can promote the dispersion of piezoelectric ceramics and optimal composite structures have been actively investigated. However, relatively few attempts have been made to develop a filler that can effectively contribute to the performance enhancement of piezoelectric devices. In the present work, we introduce the fabrication and performance of the composite piezoelectric devices composed of Li-doped ZnO nanowires (Li: ZnO NWs) grown on the surface of MXene (Ti3C2) via the hydrothermal process. Through this approach, a semiconductor-metal hybrid structure is formed, increasing the overall permittivity. Moreover, the Ti3C2 layer can serve as a local ground in the composite so that the ferroelectric phase-transformed Li: ZnO NWs grown on its surface can be more effectively polarized during the poling process. In addition, the NW-covered surface of Ti3C2 prevents the aggregation of metallic Ti3C2 particles, promoting a more uniform electric field distribution during the poling process. As a result, the output performance of the piezoelectric nanogenerator (PENG) fabricated with a Li: ZnO NW/Ti3C2 composite was greatly improved compared to that of the devices fabricated with Li: ZnO NWs without the Ti3C2 platform. Specifically, the Li: ZnO NW/Ti3C2 composite piezoelectric nanogenerator (PENG) demonstrated a twofold higher output power density (∼9 µW/cm2) compared with the values obtained from the PENG devices based on Li: ZnO NWs. The approach introduced in this work can be easily adopted for an effective ferroelectric filler design to improve the output performance of the piezoelectric composite.

Invisible populations: Who is missing from research in intellectual disability?

It is estimated that approximately 41% of adults with intellectual and developmental disability (IDD) are served through the developmental disabilities (DD) system in the US. The remaining 59% include individuals who meet diagnostic criteria but are not actively receiving paid services or may not be known to the DD system. Scholars have referred to this group as the "hidden majority." Very little is known about the health and well-being of these adults. It remains to be seen if the hidden majority is comparably susceptible to mental health difficulties, given how little is known about this population by DD systems. The purpose of this manuscript is to highlight where one may identify individuals belonging to this hidden population and how researchers might effectively recruit from this group so as to ensure more representative samples of all people with IDD.