Surpassing millisecond coherence in on chip superconducting quantum memories by optimizing materials and circuit design.

The performance of superconducting quantum circuits for quantum computing has advanced tremendously in recent decades; however, a comprehensive understanding of relaxation mechanisms does not yet exist. In this work, we utilize a multimode approach to characterizing energy losses in superconducting quantum circuits, with the goals of predicting device performance and improving coherence through materials, process, and circuit design optimization. Using this approach, we measure significant reductions in surface and bulk dielectric losses by employing a tantalum-based materials platform and annealed sapphire substrates. With this knowledge we predict the relaxation times of aluminum- and tantalum-based transmon qubits, and find that they are consistent with experimental results. We additionally optimize device geometry to maximize coherence within a coaxial tunnel architecture, and realize on-chip quantum memories with single-photon Ramsey times of 2.0 - 2.7 ms, limited by their energy relaxation times of 1.0 - 1.4 ms. These results demonstrate an advancement towards a more modular and compact coaxial circuit architecture for bosonic qubits with reproducibly high coherence.

Safety and effectiveness of the sutureless integrated stented graft prosthesis in an animal model.

Background: Prolonged circulatory arrest time is an independent risk factor for postoperative adverse events of type A aortic dissection (TAAD) surgery. Further reduction of the circulatory arrest time is essential to improve surgical outcomes. This study aimed to evaluate the safety and effectiveness of the novel Sutureless Integrated Stented (SIS) graft prosthesis in an animal experiment. Materials and methods: Straight type of the SIS graft prosthesis was implanted into the descending aorta of 10 adult male sheep, and the use of the device was scored on a scale of 1-10. Aortic digital subtraction angiography (DSA) was performed at 4, 14, and 26 weeks to investigate the prostheses. After 26 weeks, the animals were sacrificed for histological analysis. Results: The immediate success rate of the surgery was 100 %, and the overall mean score of the use of the device was 9.65 ± 0.99. Three animals died from non-device-related causes during follow-up. Aortic DSA showed filling defects in 5 animals. Histological analysis revealed that all prostheses were intact. Except for 2 early deaths, the other 8 prostheses were endothelialized with mild inflammation, foreign body reactions, and intimal fibrosis. The mean cross-sectional area of the sutureless region was reduced by 26.4 % (range, 1.3-39.1 %). Conclusions: The safety and effectiveness of the novel SIS graft prosthesis were acceptable, and the delivery system exhibited a promising performance. Using the SIS graft prosthesis in TAAD surgery was expected to simplify the procedures and shorten the circulatory arrest time. Further large-scale clinical trials are required to verify these findings.

Transcriptomic and Lipidomic Analysis Reveals Complex Regulation Mechanisms Underlying Rice Roots' Response to Salt Stress.

Rice (Oryza sativa L.), a crucial food crop that sustains over half the world's population, is often hindered by salt stress during various growth stages, ultimately causing a decrease in yield. However, the specific mechanism of rice roots' response to salt stress remains largely unknown. In this study, transcriptomics and lipidomics were used to analyze the changes in the lipid metabolism and gene expression profiles of rice roots in response to salt stress. The results showed that salt stress significantly inhibited rice roots' growth and increased the roots' MDA content. Furthermore, 1286 differentially expressed genes including 526 upregulated and 760 downregulated, were identified as responding to salt stress in rice roots. The lipidomic analysis revealed that the composition and unsaturation of membrane lipids were significantly altered. In total, 249 lipid molecules were differentially accumulated in rice roots as a response to salt stress. And most of the major phospholipids, such as phosphatidic acid (PA), phosphatidylcholine (PC), and phosphatidylserine (PS), as well as major sphingolipids including ceramide (Cer), phytoceramide (CerP), monohexose ceramide (Hex1Cer), and sphingosine (SPH), were significantly increased, while the triglyceride (TG) molecules decreased. These results suggested that rice roots mitigate salt stress by altering the fluidity and integrity of cell membranes. This study enhances our comprehension of salt stress, offering valuable insights into changes in the lipids and adaptive lipid remodeling in rice's response to salt stress.

Construction of a dual-signal readout platform for effective glutathione S-transferase sensing based on polyethyleneimine-capped silver nanoclusters and cobalt-manganese oxide nanosheets with oxidase-mimicking activity.

A novel dual-mode fluorometric and colorimetric sensing platform is reported for determining glutathione S-transferase (GST) by utilizing polyethyleneimine-capped silver nanoclusters (PEI-AgNCs) and cobalt-manganese oxide nanosheets (CoMn-ONSs) with oxidase-like activity. Abundant active oxygen species (O2•-) can be produced through the CoMn-ONSs interacting with dissolved oxygen. Afterward, the pink oxDPD was generated through the oxidation of colorless N,N-diethyl-p-phenylenediamine (DPD) by O2•-, and two absorption peaks at 510 and 551 nm could be observed. Simultaneously, oxDPD could quench the fluorescence of PEI-AgNCs at 504 nm via the inner filter effect (IFE). However, in the presence of glutathione (GSH), GSH prevents the oxidation of DPD due to the reducibility of GSH, leading to the absorbance decrease at 510 and 551 nm. Furthermore, the fluorescence at 504 nm was restored due to the quenching effect of oxDPD on decreased PEI-AgNCs. Under the catalysis of GST, GSH and1-chloro-2,4-dinitrobenzo (CDNB) conjugate to generate an adduct, initiating the occurrence of the oxidation of the chromogenic substrate DPD, thereby inducing a distinct colorimetric response again and the significant quenching of PEI-AgNCs. The detection limits for GST determination were 0.04 and 0.21 U/L for fluorometric and colorimetric modes, respectively. The sensing platform illustrated reliable applicability in detecting GST in real samples.

Population genetic analysis based on the polymorphisms mediated by transposons in the genomes of pig.

Transposable elements (TEs) mobility is capable of generating a large number of structural variants (SVs), which can have considerable potential as molecular markers for genetic analysis and molecular breeding in livestock. Our results showed that the pig genome contains mainly TE-SVs generated by short interspersed nuclear elements (51,873/76.49%), followed by long interspersed nuclear elements (11,131/16.41%), and more than 84% of the common TE-SVs (Minor allele frequency, MAF > 0.10) were validated to be polymorphic. Subsequently, we utilized the identified TE-SVs to gain insights into the population structure, resulting in clear differentiation among the three pig groups and facilitating the identification of relationships within Chinese local pig breeds. In addition, we investigated the frequencies of TEs in the gene coding regions of different pig groups and annotated the respective TE types, related genes, and functional pathways. Through genome-wide comparisons of Large White pigs and Chinese local pigs utilizing the Beijing Black pigs, we identified TE-mediated SVs associated with quantitative trait loci and observed that they were mainly involved in carcass traits and meat quality traits. Lastly, we present the first documented evidence of TE transduction in the pig genome.

Large exchange-driven intrinsic circular dichroism of a chiral 2D hybrid perovskite.

In two-dimensional chiral metal-halide perovskites, chiral organic spacers endow structural and optical chirality to the metal-halide sublattice, enabling exquisite control of light, charge, and electron spin. The chiroptical properties of metal-halide perovskites have been measured by transmissive circular dichroism spectroscopy, which necessitates thin-film samples. Here, by developing a reflection-based approach, we characterize the intrinsic, circular polarization-dependent complex refractive index for a prototypical two-dimensional chiral lead-bromide perovskite and report large circular dichroism for single crystals. Comparison with ab initio theory reveals the large circular dichroism arises from the inorganic sublattice rather than the chiral ligand and is an excitonic phenomenon driven by electron-hole exchange interactions, which breaks the degeneracy of transitions between Rashba-Dresselhaus-split bands, resulting in a Cotton effect. Our study suggests that previous data for spin-coated films largely underestimate the optical chirality and provides quantitative insights into the intrinsic optical properties of chiral perovskites for chiroptical and spintronic applications.

Efficacy of Forsythia suspensa (Thunb.) Vahl on mouse and rat models of inflammation-related diseases: a meta-analysis.

Objective: To evaluate the efficacy of the fruits of the medicinal plant Forsythia suspensa (Thunb.) Vahl (FS), in treating inflammation-associated diseases through a meta-analysis of animal models, and also probe deeply into the signaling pathways underlying the progression of inflammation. Materials and methods: All data analyses were performed using Review Manager 5.3 and the results are presented as flow diagrams, risk-of-bias summaries, forest plots, and funnel plots. Summary estimates were calculated using a random- or fixed-effect model, depending on the value of I2. Results: Of the 710 records identified in the initial search, 11 were selected for the final meta-analysis. Each study extracted data from the model and treatment groups for analysis, and the results showed that FS alleviated the inflammatory cytokine levels in serum; oxidant indicator: reactive oxygen species; enzymes of liver function; endotoxin and regulatory cells in blood; and improved the antioxidant enzyme superoxide dismutase. Conclusion: FS effectively reversed the change in acute or chronic inflammation indicators in animal models, and the regulation of multiple channel proteins in inflammatory signaling pathways suggests that FS is a good potential drug for inflammatory disease drug therapy.

Phillyrin: an adipose triglyceride lipase inhibitor supported by molecular docking, dynamics simulation, and pharmacological validation.

CONTEXT: Adipose triglyceride lipase (ATGL), a key enzyme responsible for lipolysis, catalyzes the first step of lipolysis and converts triglycerides to diacylglycerols and free fatty acids (FFA). Our previous work suggested that phillyrin treatment improves insulin resistance in HFD-fed mice, which was associated with ATGL inhibition. In this study, using docking simulation, we explored the binding pose of phillyrin and atglistatin (a mouse ATGL inhibitor) to ATGL in mouse. From the docking results, the interactions with Ser47 and Asp166 were speculated to have caused phillyrin to inhibit ATGL in mice. Further, molecular dynamics simulation of 100 ns and MM-GBSA were conducted for the protein-ligand complex, which indicated that the system was stable and that phillyrin displayed a better affinity to ATGL than did atglistatin throughout the simulation period. Moreover, the results of pharmacological validation were consistent with those of the in silico simulations. In summary, our study illustrates the potential of molecular docking to accurately predict the binding protein produced by AlphaFold and suggests that phillyrin is a potential small molecule that targets and inhibits ATGL enzymatic activity. METHODS: The ATGL-predicted protein structure, verified by PROCHECK, was determined using AlphaFold. Molecular docking, molecular dynamics simulation, and prime molecular mechanic-generalized born surface area were performed using LigPrep, Desmond, and prime MM-GBSA modules of Schrödinger software release 2021-2, respectively. For pharmacological validation, immunoblotting was performed to assess ATGL protein expression. The fluorescence intensity and glycerol concentration were quantified to evaluate the efficiency of phillyrin in inhibiting ATGL.

HSPB6 Deficiency Promotes the Development of Aortic Dissection and Rupture.

To better understand the pathogenesis of acute type A aortic dissection, high-sensitivity liquid chromatography-tandem mass spectrometry/mass spectrometry (LC-MS/MS)-based proteomics and phosphoproteomics approaches were used to identify differential proteins. Heat shock protein family B (small) member 6 (HSPB6) in aortic dissection was significantly reduced in human and mouse aortic dissection samples by real-time PCR, western blotting, and immunohistochemical staining techniques. Using an HSPB6-knockout mouse, we investigated the potential role of HSPB6 in ß-aminopropionitrile monofumarate-induced aortic dissection. We found increased mortality and increased probability of ascending aortic dissection after HSPB6 knockout compared with wild-type mice. Mechanistically, our data suggest that HSPB6 deletion promoted vascular smooth muscle cell apoptosis. More importantly, HSPB6 deletion attenuated cofilin activity, leading to excessive smooth muscle cell stiffness and eventually resulting in the development of aortic dissection and rupture. Our data suggest that excessive stiffness of vascular smooth muscle cells caused by HSPB6 deficiency is a new pathogenetic mechanism leading to aortic dissection.

Ultrathin Magnesium-Based Coating as an Efficient Oxygen Barrier for Superconducting Circuit Materials.

Scaling up superconducting quantum circuits based on transmon qubits necessitates substantial enhancements in qubit coherence time. Over recent years, tantalum (Ta) has emerged as a promising candidate for transmon qubits, surpassing conventional counterparts in terms of coherence time. However, amorphous surface Ta oxide layer may introduce dielectric loss, ultimately placing a limit on the coherence time. In this study, a novel approach for suppressing the formation of tantalum oxide using an ultrathin magnesium (Mg) capping layer is presented. Synchrotron-based X-ray photoelectron spectroscopy studies demonstrate that oxide is confined to an extremely thin region directly beneath the Mg/Ta interface. Additionally, it is demonstrated that the superconducting properties of thin Ta films are improved following the Mg capping, exhibiting sharper and higher-temperature transitions to superconductive and magnetically ordered states. Moreover, an atomic-scale mechanistic understanding of the role of the capping layer in protecting Ta from oxidation is established based on computational modeling. This work provides valuable insights into the formation mechanism and functionality of surface tantalum oxide, as well as a new materials design principle with the potential to reduce dielectric loss in superconducting quantum materials. Ultimately, the findings pave the way for the realization of large-scale, high-performance quantum computing systems.

Hydrogel-involved portable colorimetric sensor based on oxidase mimic Fe/Co-NC for acetylcholinesterase detection and pesticides inhibition assessment.

Herein, we synthesized a novel N-doped carbon layer encapsulated Fe/Co bimetallic nanoparticles (Fe/Co-NC), which exhibited superior oxidase-like activity due to the facilitation of electron penetration and the formation of metal-nitrogen active sites. Fe/Co-NC could catalyze the oxidation of 3,3,5,5-tetramethylbenzidine (TMB) to blue oxTMB. Acetylcholinesterase (AChE) could catalyze the hydrolysis of thioacetylcholine to produce reducing thiocholine, which prevented TMB from oxidation. Thus, a portable hydrogel colorimetric sensor was developed for on-site and visual monitoring of AChE with the detection limit of 0.36 U L-1, and successfully applied to detect AChE in human erythrocyte samples. Furthermore, this platform was used to investigate the inhibition of triazophos on AChE activity.

Flame retardant, high mechanical strength, transparent and water-resistant epoxy composites modified with chitosan derivatives.

Adding bio-based flame retardants to improve the flame retardancy of polymer materials without sacrificing other properties is a great challenge. Herein, a novel flame-retardant CS-DOPA was prepared from chitosan and 10-hydroxy-9,10-dihydro-9-oza-10-phosphaphenanthrene-10-oxide by acid-base neutralization reaction and fully characterized. The 4 wt% CS-DOPA modified EP showed good flame retardancy in both gaseous and condensed phase. The peak heat release rate, total smoke production, CO production, and smoke production rate of EP composites containing 4 wt% CS-DOPA were reduced by 55 %, 34 %, 45 %, and 46 %, respectively, to pass the UL-94 V-1 rating with a limiting oxygen index of 34.1 %. The CS-DOPA contributes to the formation of the condensed phase of the thermo-oxidation-resistant high-quality char layer with non-flammable other and phosphorus-containing free radicals released in the gas phase. In addition, EP/4CS-DOPA has good water resistance, mechanical properties, and transparency, with tensile and flexural strength improved by 12.7 % and 13.9 %, respectively, and still has high strength even after water treatment. The present work provides a green and facile strategy to use chitosan as a main raw material to manufacture EP materials with high performance.

Probing Oxidation-Driven Amorphized Surfaces in a Ta(110) Film for Superconducting Qubit.

Recent advances in superconducting qubit technology have led to significant progress in quantum computing, but the challenge of achieving a long coherence time remains. Despite the excellent lifetime performance that tantalum (Ta) based qubits have demonstrated to date, the majority of superconducting qubit systems, including Ta-based qubits, are generally believed to have uncontrolled surface oxidation as the primary source of the two-level system loss in two-dimensional transmon qubits. Therefore, atomic-scale insight into the surface oxidation process is needed to make progress toward a practical quantum processor. In this study, the surface oxidation mechanism of native Ta films and its potential impact on the lifetime of superconducting qubits were investigated using advanced scanning transmission electron microscopy (STEM) techniques combined with density functional theory calculations. The results suggest an atomistic model of the oxidized Ta(110) surface, showing that oxygen atoms tend to penetrate the Ta surface and accumulate between the two outermost Ta atomic planes; oxygen accumulation at the level exceeding a 1:1 O/Ta ratio drives disordering and, eventually, the formation of an amorphous Ta2O5 phase. In addition, we discuss how the formation of a noninsulating ordered TaO1-δ (δ < 0.1) suboxide layer could further contribute to the losses of superconducting qubits. Subsurface oxidation leads to charge redistribution and electric polarization, potentially causing quasiparticle loss and decreased current-carrying capacity, thus affecting superconducting qubit coherence. The findings enhance the comprehension of the realistic factors that might influence the performance of superconducting qubits, thus providing valuable guidance for the development of future quantum computing hardware.

Impact of Varying the Photoanode/Catalyst Interfacial Composition on Solar Water Oxidation: The Case of BiVO4(010)/FeOOH Photoanodes.

Photoanodes used in a water-splitting photoelectrochemical cell are almost always paired with an oxygen evolution catalyst (OEC) to efficiently utilize photon-generated holes for water oxidation because the surfaces of photoanodes are typically not catalytic for the water oxidation reaction. Suppressing electron-hole recombination at the photoanode/OEC interface is critical for the OEC to maximally utilize the holes reaching the interface for water oxidation. In order to explicitly demonstrate and investigate how the detailed features of the photoanode/OEC interface affect interfacial charge transfer and photocurrent generation for water oxidation, we prepared two BiVO4(010)/FeOOH photoanodes with different Bi:V ratios at the outermost layer of the BiVO4 interface (close to stoichiometric vs Bi-rich) while keeping all other factors in the bulk BiVO4 and FeOOH layers identical. The resulting two photoanodes show striking differences in the photocurrent onset potential and photocurrent density for water oxidation. The ambient pressure X-ray photoelectron spectroscopy results show that these two BiVO4(010)/FeOOH photoanodes show drastically different Fe2+:Fe3+ ratios in FeOOH both in the dark and under illumination with water, demonstrating the immense impact of the interfacial composition and structure on interfacial charge transfer. Using computational studies, we reveal the effect of the surface Bi:V ratio on the hydration of the BiVO4 surface and bonding with the FeOOH layer, which in turn affect the band alignments between BiVO4 and FeOOH. These results explain the atomic origin of the experimentally observed differences in electron and hole transfer and solar water oxidation performance of the two photoanodes having different interfacial compositions.

Multi-signal aptasensor for thrombin detection based on catalytically active gold nanoparticles and fluorescent silicon quantum dots.

A multi-signal aptasensor for thrombin determination is proposed based on catalytically active gold nanoparticles (AuNPs) and fluorescent silicon quantum dots (SiQDs). Yellow 4-Nitrophenol (4-NP) could be converted to colorless 4-Aminophenol (4-AP) by catalytically active aptamer-modified AuNPs (S1-AuNPs). The SiQDs emitted strong blue fluorescence at 455 nm at the excitation wavelength of 367 nm. When thrombin was absent, S1-AuNPs could catalytically reduce yellow 4-NP to colorless 4-AP. When thrombin was added, the aptamer could be transformed into a G-quadruplex structure, which masked the surface-active catalytic sites of AuNPs and restrained the reduction of 4-NP. Thus, the fluorescence of SiQDs was greatly quenched by 4-NP through the inner filter effect (IFE), and the solution color remained yellow. As the concentration of thrombin increased, the catalytic activity of S1-AuNPs decreased. The concentration of 4-NP that was converted to 4-AP declined and the unconverted 4-NP increased. In this process, the absorption peak of 4-NP at 400 nm increased while the fluorescence emission of SiQDs at 455 nm decreased. The linear ranges of the fluorometric and colorimetric aptasensor were 0.5-30 nM and 0.3-30 nM, respectively. The limits of detection (LOD) for the two modes were 0.15 nM and 0.13 nM. Furthermore, a portable sensing platform was constructed by combining the smartphone-based device with the software ImageJ for the determination of thrombin. With the advantages of cost-effectiveness, simplicity of operation and broad applicability, this aptasensor provided a new perspective for on-site determination of thrombin in the clinical field.

Cobalt Oxide-Coated Single Crystalline Bismuth Vanadate Photoanodes for Efficient Photoelectrochemical Chlorine Generation.

Bismuth vanadate (BiVO4) is an outstanding photoanode material for photoelectrochemical water splitting. In this work, a series of single crystalline BiVO4 photoanodes are synthesized by pulsed laser deposition (PLD). Once coated with a thin layer of cobalt oxide (CoOx) cocatalyst, also by PLD, the photoanodes support efficient photoelectrochemical generation of chlorine (Cl2) from brine under simulated solar light. The activity of the chlorine generation reaction (ClER) is optimized when the thickness of CoOx is about 3 nm, with the faradic efficiency of ClER exceeding 60%. Detailed studies show that the CoOx cocatalyst layer is amorphous, uniform in thickness, and chemically robust. As such, the cocatalyst also effectively protects the underlying BiVO4 photoanodes against chlorine corrosion. This work provides insights into using artificial photosynthesis for byproducts that carry significant economic value while avoiding the energetically expensive oxygen evolution reactions.

The relationship of intent to be COVID-19 vaccinated with depression, anxiety, insomnia, pain and smoking among Chinese patients with a pacemaker.

Background: This study examined the intent to be COVID-19 vaccinated and its correlates among patients with a pacemaker. Methods: This observational study was carried out between July 1, 2021, and May 17, 2022 in Beijing, China. Patients with a pacemaker were consecutively invited by a research physician to participate in the study. Intent to be COVID-19 vaccinated, depression, anxiety, insomnia, pain and smoking were measured with standard scales or questions. Results: Of the 206 participating patients, 72.82% (N = 150; 95% confidence interval [CI]: 66.74%-78.89%) expressed an intention to be COVID-19 vaccinated. Intent to be COVID-19 vaccinated was not significantly associated with severity of depression, anxiety, and insomnia. Multiple logistic regression analysis revealed that patients believing that COVID-19 vaccines provided protection and smokers were more likely to express an intention to receive COVID-19 vaccines. In contrast, older patients and those with higher level of physical pain were less likely to express an intention to be vaccinated against COVID-19. Conclusions: Specific vaccination promotion strategies should be implemented targeting this vulnerable segment of the population.

Analysis of the potential relationship between COVID-19 and Behcet's disease using transcriptome data.

To investigate the potential role of COVID-19 in relation to Behcet's disease (BD) and to search for relevant biomarkers. We used a bioinformatics approach to download transcriptomic data from peripheral blood mononuclear cells (PBMCs) of COVID-19 patients and PBMCs of BD patients, screened the common differential genes between COVID-19 and BD, performed gene ontology (GO) and pathway analysis, and constructed the protein-protein interaction (PPI) network, screened the hub genes and performed co-expression analysis. In addition, we constructed the genes-transcription factors (TFs)-miRNAs network, the genes-diseases network and the genes-drugs network to gain insight into the interactions between the 2 diseases. We used the RNA-seq dataset from the GEO database (GSE152418, GSE198533). We used cross-analysis to obtain 461 up-regulated common differential genes and 509 down-regulated common differential genes, mapped the PPI network, and used Cytohubba to identify the 15 most strongly associated genes as hub genes (ACTB, BRCA1, RHOA, CCNB1, ASPM, CCNA2, TOP2A, PCNA, AURKA, KIF20A, MAD2L1, MCM4, BUB1, RFC4, and CENPE). We screened for statistically significant hub genes and found that ACTB was in low expression of both BD and COVID-19, and ASPM, CCNA2, CCNB1, and CENPE were in low expression of BD and high expression of COVID-19. GO analysis and pathway analysis was then performed to obtain common pathways and biological response processes, which suggested a common association between BD and COVID-19. The genes-TFs-miRNAs network, genes-diseases network and genes-drugs network also play important roles in the interaction between the 2 diseases. Interaction between COVID-19 and BD exists. ACTB, ASPM, CCNA2, CCNB1, and CENPE as potential biomarkers for 2 diseases.

Chemical Profiles of the Oxides on Tantalum in State of the Art Superconducting Circuits.

Over the past decades, superconducting qubits have emerged as one of the leading hardware platforms for realizing a quantum processor. Consequently, researchers have made significant effort to understand the loss channels that limit the coherence times of superconducting qubits. A major source of loss has been attributed to two level systems that are present at the material interfaces. It is recently shown that replacing the metal in the capacitor of a transmon with tantalum yields record relaxation and coherence times for superconducting qubits, motivating a detailed study of the tantalum surface. In this work, the chemical profile of the surface of tantalum films grown on c-plane sapphire using variable energy X-ray photoelectron spectroscopy (VEXPS) is studied. The different oxidation states of tantalum that are present in the native oxide resulting from exposure to air are identified, and their distribution through the depth of the film is measured. Furthermore, it is shown how the volume and depth distribution of these tantalum oxidation states can be altered by various chemical treatments. Correlating these measurements with detailed measurements of quantum devices may elucidate the underlying microscopic sources of loss.