Experimental Evidence Research Articles

Experimental and numerical analyses of grid couplings in quasi-static and dynamic conditions

Grid couplings typically comprise flexible, spring-like elements connecting two toothed hubs. They are used in heavy machinery to transmit power from prime movers to driven parts, even in the presence of positioning errors and deviations. The main objective of this paper is to introduce a comprehensive three-dimensional model, which can be used to predict coupling stiffness characteristics and load distributions at the spring/hub tooth contacts. The modelling principles are presented with emphasis being placed on the spring/hub contact simulation based on a combination of finite elements and Winkler elastic foundations. A series of comparisons with experimental evidence from a specific test rig are shown, which prove the validity of the model and its applicability to industrial couplings.

BDNF and Cerebellar Ataxia.

Brain-derived neurotrophic factor (BDNF) has been proposed as a treatment for neurodegeneration, including diseases of the cerebellum, where BDNF levels or those of its main receptor, TrkB, are often diminished relative to controls, thereby serving as replacement therapy. Experimental evidence indicates that BDNF signaling countered cerebellar degeneration, sensorimotor deficits, or both, in transgenic ATXN1 mice mutated for ataxin-1, Cacna1a knock-in mice mutated for ataxin-6, mice injected with lentivectors encoding RNA sequences against human FXN into the cerebellar cortex, Kcnj6Wv (Weaver) mutant mice with granule cell degeneration, and rats with olivocerebellar transaction, similar to a BDNF-overexpressing transgenic line interbred with Cacng2stg mutant mice. In this regard, this study discusses whether BDNF is effective in cerebellar pathologies where BDNF levels are normal and whether it is effective in cases with combined cerebellar and basal ganglia damage.

The role of iron(II) excess and phosphate to synthesize hydroxychloride green rust

Green rust (GR) is a chemically reactive mineral of interest for environmental remediation. However, the lack of stability of this compound is a major drawback for practical applications. In this study, the precipitation of hydroxychloride green rust type 1 (GR1Cl) from soluble FeII and FeIII species was studied by analyzing pH titration curves and employing XRD, Raman and Mössbauer spectroscopies to find optimal conditions for synthesizing GR1Cl. Using the stoichiometric condition for FeII-FeIII corresponding to the [FeII3FeIII(OH)8]Cl compound, FeIIIO(OH)2.9Cl0.1 was formed in a first step during the addition of NaOH and then transformed into a mixture of GR1Cl and Fe3O4. The addition of phosphate anions (PO4) at a molar ratio PO4: Fe = 1: 10 in the initial solution was shown to avoid the formation of undesired magnetite. Interestingly, GR1Cl was also the only product without adding PO4 using an excess of FeII species in solution, i.e. for an initial ferric molar fraction x = FeIII: Fetot of 0.2. First experimental evidences of a hydroxyphosphate green rust type 2 GR2PO4 were also provided by XRD and Raman spectroscopy. Therefore, this work may attract interest for a better understanding of the geochemical cycle of iron and phosphate in natural environments such as hydromorphic soils or hydrothermal chimneys where fougerite, the mineral homologue of synthetic GR, is supposed to play a significant role.

Variations in the level of available phosphorus with changes in the status of water-soluble organic matter derived from different organic materials in soil

The combined application of organic material and phosphorus fertilizer is an effective method to enhance phosphorus use efficiency for plant growth. This is partly because the presence of water-soluble organic matter (WSOM) derived from different organic materials can enhance the level of available phosphorus in the soil; however, it is poorly understood how this level varies with changes in the WSOM status (i.e., decomposed, dissolved, and retained) in the soil depending on WSOM types. This study aimed to (i) understand how changes in the WSOM status enhances the available phosphorus level in the soil, and (ii) determine the WSOM type that contributes to such enhancement. The incubation test showed that fractions of 73%–92% and 8%–27% of WSOM-derived organic carbon were retained and dissolved, respectively, at the beginning of incubation, while 31%–45% was decomposed during the incubation period. The WSOM derived from cattle manure compost (CM) and sewage sludge compost (SSC) that was initially retained was maintained until the late stage of the incubation test, whereas that derived from hydrothermal decomposed liquid fertilizer (HDLF) was rapidly desorbed during the first 14 days of the incubation period. The available phosphorus level was higher under the combined application of CM- and SSC-derived WSOM than under the single phosphorus application throughout the incubation period, while it was high only during the first 3 days of incubation under the application of HDLF-derived WSOM. The amounts of retained organic carbon at each sampling point during the incubation period compared to those at the beginning were positively and linearly correlated to the available phosphorus levels that were enhanced by the WSOM present in the soil. This study for the first time provides quantitative experimental evidence that 1) the longer the WSOM continues to be retained, the higher the amount of available phosphorus remaining in the soil, and 2) the available phosphorus level decreases with WSOM sorption or decomposition. Furthermore, it was shown that highly humified WSOM has a great potential for the maintenance of higher available phosphorus levels. This study provides the insight that a combined application of highly humified organic materials with a chemical fertilizer is necessary for not only cost effective but also sustainable fertilization design.

P110CUX1 promotes acute myeloid leukemia progression via regulating pyridoxal phosphatase expression and activating PI3K/AKT/mTOR signaling pathway.

As an evolutionarily conserved transcription factor, Cut-like homeobox 1 (CUX1) plays crucial roles in embryonic and nervous system development, cell differentiation, and DNA damage repair. One of its major isoforms, p110CUX1, exhibits stable DNA binding capabilities and contributes to the regulation of cell cycle progression, proliferation, migration, and invasion. While p110CUX1 has been implicated in the progression of various malignant tumors, its involvement in acute myeloid leukemia (AML) remains uncertain. This study aims to elucidate the role of p110CUX1 in AML. Our findings reveal heightened expression levels of both p110CUX1 and pyridoxal phosphatase (PDXP) in AML cell lines. Overexpression of p110CUX1 promotes AML cell proliferation while inhibiting apoptosis and differentiation, whereas knockdown of PDXP yields contrasting effects. Mechanistically, p110CUX1 appears to facilitate AML development by upregulating PDXP expression and activating the PI3K/AKT/mTOR signaling pathway. Animal experimental corroborate the pro-AML effect of p110CUX1. These results provide experimental evidence supporting the involvement of the p110CUX1-PDXP-PI3K/AKT/mTOR axis in AML progression. Hence, targeting p110CUX1 may hold promise as a therapeutic strategy for AML.

Cholesterol Accelerates Aggregation of α-Synuclein Simultaneously Increasing the Toxicity of Amyloid Fibrils.

A hallmark of Parkinson disease (PD) is a progressive degeneration of neurons in the substantia nigra pars compacta, hypothalamus, and thalamus. Although the exact etiology of irreversible neuronal degeneration is unclear, a growing body of experimental evidence indicates that PD could be triggered by the abrupt aggregation of α-synuclein (α-Syn), a small membrane protein that is responsible for cell vesicle trafficking. Phospholipids uniquely alter the rate of α-Syn aggregation and, consequently, change the cytotoxicity of α-Syn oligomers and fibrils. However, the role of cholesterol in the aggregation of α-Syn remains unclear. In this study, we used Caenorhabditis elegans that overexpressed α-Syn to investigate the effect of low (15%), normal (30%), and high (60%) concentrations of cholesterol on α-Syn aggregation. We found that an increase in the concentration of cholesterol in diets substantially shortened the lifespan of C. elegans. Using biophysical methods, we also investigated the extent to which large unilamellar vesicles (LUVs) with low, normal, and high concentrations of cholesterol altered the rate of α-Syn aggregation. We found that only lipid membranes with a 60% concentration of cholesterol substantially accelerated the rate of protein aggregation. Cell assays revealed that α-Syn fibrils formed in the presence of LUVs with different concentrations of cholesterol exerted very similar levels of cytotoxicity to rat dopaminergic neurons. These results suggest that changes in the concentration of cholesterol in the plasma membrane, which in turn could be caused by nutritional preferences, could accelerate the onset and progression of PD.

Spectroscopic Evidence of Ultrafast Topological Phase Transition by Light-Driven Strain.

Enabling reversible control over the topological invariants, transitioning them from nontrivial to trivial states, has fundamental implications for quantum information processing and spintronics. It offers a promising avenue for establishing an efficient on/off switch mechanism for robust and dissipationless spin-currents. While mechanical strain has traditionally been advantageous for such manipulation of topological invariants, it often comes with the drawback of in-plane fractures, rendering it unsuitable for high-speed, time-dependent operations. This study employs ultrafast optical and THz spectroscopy to explore topological phase transitions induced by light-driven strain in Bi2Se3. Bi2Se3 requires substantial strain for Z2 switching. Our observations provide experimental evidence of ultrafast switching behavior, demonstrating a transition from a topological insulator with spin-momentum-locked surfaces to hybridized states and normal insulating phases under ambient conditions. Notably, applying light-induced strong out-of-plane strain effectively suppresses surface-bulk coupling, facilitating the differentiation of surface and bulk conductance even at room temperature─significantly surpassing the Debye temperature. We expect various time-dependent sequences of transient hybridization and manipulation of topological invariant through photoexcitation intensity adjustments. The sudden surface and bulk transport alterations near the transition point enable coherent conductance modulation at hypersound frequencies. Our findings on the potential of light-triggered ultrafast switching of topological invariants hold promise for high-speed topological switching and its related applications.

4hJCHOCH Spin Coupling in a Lewisx Trisaccharide as Evidence of Inter-Residue C-H···O Hydrogen Bonding in Aqueous Solution.

Prior studies of the solution conformation of the Lewisx (Lex) trisaccharide, αFuc-(1→3)[βGal-(1→4)]-βGlcNAc, suggest that nonclassical inter-residue C-H···O hydrogen bonding in aqueous solution contributes to the stabilization of its 3D structure and affects its biological properties. Experimental evidence for this hydrogen bond in aqueous solution has been reported in the form of a 4hJCHOCH NMR spin-coupling constant between C5'Fuc and H1″Gal measured by 2D NMR methods in unlabeled samples. A methyl glycoside of Lex (MeβLex) was prepared containing selective 13C-labeling at C5'Fuc, and the H1″Gal signal was examined in high-field 1H NMR spectra for evidence of splitting or line-broadening caused by the 13C at C5'Fuc. High-resolution 1H NMR spectra obtained at high field and at different temperatures using different FID processing parameters showed no resolved splitting of the H1″Gal signal or evidence of line-broadening. Spectral simulation showed that this splitting and/or line-broadening would be observable if the reported J-value (∼1.1 Hz) is correct. DFT calculations on MeβLex and a carbon analog (O5″Gal replaced by a CH2 group) gave very small and nearly identical calculated 4hJC5',H1″ values, suggesting that the coupling is essentially zero. DFT calculations also showed that an alternate inter-residue 3hJH5',H1″ is small. Based on NMR analyses and DFT calculations, we found that 4hJC5',H1″ in MeβLex has an upper limit of ∼0.4 Hz and that the value could be lower, possibly zero, calling into question its value as experimental proof of persistent nonclassical hydrogen bonding in aqueous solutions of MeβLex and related structures.

Natural Products with Potential for the Treatment of Pain: Global Evidence from the NAPRALERT Database.

Natural products (NPs) continue to inform the discovery and development of a diversity of drugs, both marketed and investigational. Pain, one of the most common of human experiences and profound challenges in medicine and biology, has emerged at the core of an urgent societal problem, in the United States and globally. The present study employs a retrospective analysis of an extensive set of published literature curated in the NAPRALERT database to identify NPs with experimental evidence of bioactivity supporting the selection and prioritization of NP leads with promise in pain management. The NAPRALERT pain data set currently documents >38,000 pain-relevant experiments reported in >1,750 distinct journals. The evidence presented here was annotated from >10,000 distinct scientific publications identifying NP extracts and isolates with experimental biological data indicating positive mitigation of pain, inflammation, and/or modulation of nociceptive signaling targets. Correlation of ethnomedical uses with experimental data represents a value-added approach to the selection and prioritization of leads. Dissemination of this unique NP/pain data set, with experimental data and information applicable to basic, translational, and clinical science stakeholders alike, furnishes practical evidence in support of a rational selection of NPs for directed pain research. A large portion of the NAPRALERT pain-relevant data set, along with a set of query tools designed to assist user-directed selection and prioritization of leads, are presented as Supporting Information in order to mitigate the limitations inherent in presenting such a large data set in (print) format. To support user efforts, this report involves explication of NAPRALERT data organization and the articulation of rational approaches to user-guided selection of evidence-based NP leads.

Experimental evidence on colchicine's mode of action in human carotid artery plaques

Abstract Background and aims Atherosclerosis driven by inflammation is a major cause of cardiovascular events. Recent clinical trials have demonstrated the therapeutic potential of anti-inflammatory treatments. Consequently, colchicine is recommended in current guidelines as a second-line therapy for secondary prevention, although the drug's mechanism of action is not fully understood. Methods To this end, we performed a multiomic study of the effect of colchicine on human carotid plaques. Sections from endarterectomy specimens were exposed ex vivo to colchicine at concentrations of 2 ng/ml and 10 ng/ml for 24 hours and compared with untreated segments of the same plaque. Changes in gene expression were analyzed by RNA sequencing, and plaque secretomes were subjected to proteomic analysis by mass spectrometry. In situ cell proliferation was examined histologically. Results Our data suggest that colchicine primarily suppresses neutrophil and platelet degranulation, collagen degradation, and macrophage proliferation in atheromatous plaques in a dose-dependent manner, while stimulating myofibroblast activation. Conclusion Our study demonstrates multifactorial pathways by which colchicine, the first anti-inflammatory drug recommended by cardiovascular guidelines, acts on human atherosclerotic lesions. Targeting neutrophil and platelet degranulation, collagen degradation and macrophage proliferation could provide significant therapeutic benefit in atherosclerotic cardiovascular disease without the adverse side effects of colchicine.

Difference in structural changes of surfactant aggregates near solid surface under shear flow versus those in the bulk.

In water, the nonionic surfactant pentaethylene glycol monododecyl ether (C12E5) forms multi-lamellar vesicles upon application of shear, attributed to buckling instability of the surfactant layers. In the standard setup for applying shear, a pair of solid substrates is moved in opposite directions, and a non-slip condition at the solid surface is assumed. Based on theoretical predictions, the effective viscosity of the fluid surrounding the membrane is modified in this process, and this confinement may affect membrane fluctuation. However, only a few studies have analyzed the structural changes near the substrate. From this viewpoint, the structural changes in surfactant aggregates near a solid substrate under the application of shear were investigated herein using neutron reflectometry (NR). By increasing the shear rate, shear thickening at a lower shear rate and shear thinning at a higher shear rate were observed, similar to that in the bulk. However, a discontinuous change in the lamellar structure accompanying the condensation of the surfactant was observed in the NR experiments. This study presents the first experimental evidence indicating that the ramping speed of shear rates governs the shear-induced structuring of surfactant aggregates near the surface.

How effective are eHealth literacy interventions? A meta-analysis of experimental studies

Abstract The rapid evolution of digital health emphasises the need for effective eHealth literacy (eHL) to ensure equitable access to health information and improve patient outcomes. This systematic review and meta-analysis aim to assess the effectiveness of eHL interventions, addressing the significant gap in knowledge about which strategies are most beneficial. Adhering to PRISMA guidelines, we systematically retrieved, quantitatively pooled and critically appraised available experimental evidence on the effectiveness of eHL interventions across different populations. PubMed, Scopus, Web of Science, Embase, Cochrane Library, and ClinicalTrials.gov were searched for studies reporting original quantitative outcomes of eHL, assessed by the eHealth Literacy Scale or other validated scales. Data were pooled using a random-effects model, with critical appraisal of the included studies. From the 504 records screened, 15 studies met the inclusion criteria. They encompass interventions targeting adults with chronic diseases (6 studies), older adults (5), and young people (4) and examine either individualistic or collaborative approaches (respectively, 9 and 5 studies, and 1 assessing both). The meta-analysis revealed significant improvements in eHL, both pre- vs post-intervention (UMD 5.81, 95%CI 3.38-8.26, N = 1,025) and experimental vs control groups (OR 3.65, 95%CI 2.06-6.46, N = 1,258). Meta-regression showed a significant correlation between pre/post-intervention outcomes and baseline eHL levels (slope=-0.91, p-value=0.009). Our findings support the effectiveness of tailored interventions in significantly enhancing eHL, providing key insights (role of baseline eHL levels and intervention approach) for intervention design and implementation that are adaptable to various demographic contexts. This research was supported by the National Plan for Complementary Investments to the NRRP Hub Life Science-Digital Health (PNC-E3-2022-23683267, DHEAL-COM).

Unraveling the Molecular Mechanisms of SIRT7 in Angiogenesis: Insights from Substrate Clues

Angiogenesis, a vital physiological or pathological process regulated by complex molecular networks, is widely implicated in organismal development and the pathogenesis of various diseases. SIRT7, a member of the Sirtuin family of nicotinamide adenine dinucleotide + (NAD+) dependent deacetylases, plays crucial roles in cellular processes such as transcriptional regulation, cell metabolism, cell proliferation, and genome stability maintenance. Characterized by its enzymatic activities, SIRT7 targets an array of substrates, several of which exert regulatory effects on angiogenesis. Experimental evidence from in vitro and in vivo studies consistently demonstrates the effects of SIRT7 in modulating angiogenesis, mediated through various molecular mechanisms. Consequently, understanding the regulatory role of SIRT7 in angiogenesis holds significant promise, offering novel avenues for therapeutic interventions targeting either SIRT7 or angiogenesis. This review delineates the putative molecular mechanisms by which SIRT7 regulates angiogenesis, taking its substrates as a clue, endeavoring to elucidate experimental observations by integrating knowledge of SIRT7 substrates and established angiogenenic mechanisms.

Effects of Abelmoschus manihot (L.) and its combination with irbesartan in the treatment of diabetic nephropathy via the gut–kidney axis

BackgroundClinical observations have recently shown that Abelmoschus manihot (L.) in the form of Huangkui capsule (HKC) and in combination with irbesartan (EB) is an effective therapy for diabetic nephropathy (DN) in patients with type 2 diabetes (T2D). The present study aims to explore the mechanisms underlying the therapeutic efficacies of HKC and its combination with EB in DN via the gut-kidney axis.MethodsHKC, EB, and their combination or vehicle were administered in db/db mice, which is an animal model for the study of T2D and DN. Comparative analyses of the gut microbiota, serum metabolites, and kidney transcriptomics before and after drug administration were performed.ResultsAfter treatment with HKC, EB, and their combination for 4 weeks, the urinary albumin-to-creatinine ratios decreased significantly in the db/db mice with DN. In terms of the gut microbiota, the abundances of Faecalitalea, Blautia, and Streptococcus increased but those of Bacteroidetes, Firmicutes, Enterobacteriaceae, and Desulfovibrio decreased. Parallelly, serum metabolites, mainly including quercetin 3′-glucuronide and L-dopa, were elevated while cortisol and cytochalasin B were reduced. Furthermore, the S100a8, S100a9, Trem1, and Mmp7 genes in the kidneys were downregulated. These altered elements were associated with proteinuria/albuminuria reduction. However, EB had no effects on the changes in blood pressure and specific differentially expressed genes in the kidneys.ConclusionThe present study provides experimental evidence that HKC regulates the gut microbiota, circulating metabolites, and renal gene activities, which are useful for better understanding of the action mechanisms of A. manihot in the treatment of DN through the gut-kidney axis.

LncRNA MEG3 promotes aortic valve calcification by inducing osteoblast differentiation via Wnt catenin signaling pathway

Abstract Background Calcific aortic valve stenosis (CAVS) is the most common valvular heart disease in elderly population. This study aimed to investigate the role of long non-coding RNAs (lncRNAs) in the development of CAVS. Methods ldlr-/-mice were feeding with western diet for 6 months to induce CAVS. RNA-seq analysis was performed to identify differentially expressed molecular signaling between aortic valves of CAVS mice and control mice. The degree of aortic stenosis was detected by ultrasound. Calcium salt deposits were detected by Haematoxylin and eosin (H&E) staining, Von Kossa staining and alizarin red S staining. PCR and western blotting were employed to detect osteogenic differentiation markers after various interventions. Results A mouse CAVS model was successfully established, as evidenced by increased thickness and calcium deposition in the aortic valve leaflets and increased transvalvular peak jet velocity. RNA-seq analysis showed that lncRNA MEG3 was significantly enriched in aortic valves of CAVS mice as compared to that of control mice. MEG3 expression in aortic valve, assessed by RNA in situ hybridization and PCR, was also significantly upregulated during the osteoblast differentiation of AVICs in vitro. Gain- and loss-of-function experiments indicate that MEG3 could indeed promote osteoblast differentiation of primary AVICs as evidenced by increased calcified nodule formation and expressions of osteoblast differentiation markers (Runx2 and osterix). Consistent with these in vitro data, MEG3 knockdown in vivo through tail injection of antisense oligonucleotide chain MEG3 (ASO-MEG3) at 6 weeks interval for 12 weeks significantly attenuated aortic valve calcification in CAVS mice. Subsequent KEGG analysis demonstrated that the Wnt/β-catenin signaling pathway was significantly enriched during the CAVS progression. Overexpression of MEG3 activated the Wnt/β-catenin signaling pathway and upregulated osteogenic protein expressions, while this upregulation could be significantly ameliorated by Dickkopf 1, a Wnt/β-catenin pathway inhibitor. Conclusion Present study demonstrates that LncRNA MEG3 could promote aortic valve calcification by inducing osteoblast differentiation via activating Wnt/β-catenin signaling pathway. Our results provide experimental evidence of targeting MEG3 and Wnt/β-catenin signaling pathway as potential promising therapeutic option for prevention and treatment of aortic valve calcification.

Central Bank Digital Currencies: Experimental Evidence of Deposit Conversion

Abstract In this paper, we provide unique experimental evidence of depositors’ behaviour in presence of a possibility to convert commercial bank deposits into central bank digital currency (CBDC). Theoretically and experimentally we analyse whether such an option incentivises bank runs. We find that the availability of the deposit conversion option does not lead to a significant outflow of deposits. However, when conversion is restricted, depositors are eager to actively use it as a coordination tool. These findings highlight the importance of considering coordination and decision time in determining the choice to convert deposits into CBDC. Our study evidences that policy-makers should balance accessibility and control measures to maintain financial stability, ensuring that CBDC implementation supports the resilience of the banking system.

Experimental evidence of negative agricultural impacts and effectiveness of mitigation strategies of invasive green iguanas (Iguana iguana) in Puerto Rico

Losses in crop yield due to invasive insects, weeds, pathogens, and herbivores cost trillions of dollars per year globally. To prevent further spread of invasive agricultural pest species, continuous monitoring and prevention are crucial. Once introduced, however, assessing the impact of an invasive pest on agricultural production and testing management strategies are essential. The green iguana (Iguana iguana), a globally widespread invasive herbivore, is considered a possible agricultural pest although no quantitative data on its impact are available. In this study, we evaluated the impact of the invasive green iguana on cucumber (Cucumis sativus, var. Dasher II) and lettuce (Lactuca sativa, var. Black-seeded Simpson) yield by testing the efficacy of two management strategies – Neem-based pesticide and mesh fencing – compared to open field cultivation in Puerto Rico. Mesh fencing led to 20% more growth and doubled cucumber yield compared to open field cultivation, while spraying Neem led to an 18% increase in plant growth but no effect on cucumber yield. We found no difference in lettuce growth or yield among treatment and control plots. This study supports categorizing the green iguana as an invasive agricultural pest species and demonstrates the reptile’s potential to reduce crop yield. It also shows that Neem application at the manufacturer’s suggested concentration is not an effective mitigation technique for reducing crop loss due to green iguana herbivory. Government agencies in regions where the green iguana has the potential to be introduced should consider the species a threat to food production when developing monitoring programs and drafting regulations.

Student reasoning about quantum mechanics while working with physical experiments

Instruction in quantum mechanics is becoming increasingly important as the field is not only a key part of modern physics research but is also important for emerging technologies. However, many students regard quantum mechanics as a particularly challenging subject, in part because it is considered very mathematical and abstract. One potential way to help students understand and contextualize unintuitive quantum ideas is to provide them opportunities to work with physical apparatus demonstrating these phenomena. In order to understand how working with quantum experiments affects students’ reasoning, we performed think-aloud lab sessions with two pairs of students as they worked through a sequence of quantum optics experiments that demonstrated particle-wave duality of photons. Analyzing the in-the-moment student thinking allowed us to identify the resources students activated while reasoning through the experimental evidence of single-photon interference, as well as student ideas about what parts of the experiments were quantum versus classical. This work will aid instructors in helping their students construct an understanding of these topics from their own ideas and motivate future investigations into the use of hands-on opportunities to facilitate student learning about quantum mechanics. Published by the American Physical Society 2024

Computationally Driven Discovery of T Center-like Quantum Defects in Silicon.

Quantum technologies would benefit from the development of high-performance quantum defects acting as single-photon emitters or spin-photon interfaces. Finding such a quantum defect in silicon is especially appealing in view of its favorable spin bath and high processability. While some color centers in silicon have been emerging in quantum applications, there remains a need to search for and develop new high-performance quantum emitters. By searching a high-throughput computational database of more than 22,000 charged complex defects in silicon, we identify a series of defects formed by a group III element combined with carbon ((A-C)Si with A = B, Al, Ga, In, Tl) and substituting on a silicon site. These defects are analogous structurally, electronically, and chemically to the well-known T center in silicon ((C-C-H)Si), and their optical properties are mainly driven by an unpaired electron on the carbon p orbital. They all emit in the telecom, and some of these color centers show improved properties compared to the T center in terms of computed radiative lifetime, emission efficiency, or smaller optical linewidth. The kinetic barrier computations and previous experimental evidence show that these T center-like defects can be formed through the capture of a diffusing carbon by a substitutional group III atom. We also show that the synthesis of hydrogenated T center-like defects followed by a dehydrogenation annealing step could facilitate the formation of these defects. Our work motivates further studies on the synthesis and control of this new family of quantum defects and demonstrates the use of high-throughput computational screening to discover new color center candidates.

Clinical and experimental evidence for differences between cardiac troponin I and T in acute and chronic cardiovascular conditions

Abstract Background Clinical and scientific practice operate under the assumption that systemic levels of cardiac troponin I (cTnI) and troponin T (cTnT) are indicative of the same underlying pathophysiological mechanisms and can be utilized interchangeably. Purpose To assess cTnI and cTnT levels and their ratio for differences in various cardiovascular conditions. Methods Individuals from three prospective clinical studies with a centrally adjudicated diagnosis were categorized into three groups: no known cardiac disease, chronic cardiac disease, and acute cardiac disease. Circulating cTnI and cTnT concentrations were measured using high-sensitivity assays (hs-cTnI-Architect, hs-cTnT-Elecsys) and the cTnI/cTnT ratio was calculated. Findings were validated using a second hs-cTnI assay (hs-cTnI-Clarity) and externally validated in independent cohorts. The cTnI/cTnT ratio was also assessed in five different non-lethal and lethal experimental models of cardiomyocyte injury. Results Of the 9704 included individuals, 9% had no known cardiac disease, 69% chronic cardiac disease, and 22% acute cardiac disease. No known cardiac disease and chronic cardiac disease were associated with a disproportional increase in cTnT compared to cTnI (cTnI/cTnT ratio, median 0.50, IQR 0.38-0.69 and 0.53, IQR 0.37-0.80). In contrast, cTnI concentrations were increased compared to cTnT in patients with acute cardiac disease, resulting in a cTnI/cTnT ratio of 1.62 (IQR 0.77-4.31). Findings were consistent using an alternative cTnI assay and in external validation cohorts (n=2776) where the cTnI/cTnT ratio was lower in those without cardiac disease (0.33 (IQR 0.25-0.50), 0.64 (IQR 0.40-1.05)) and with chronic cardiac disease (0.50 (IQR 0.32-0.75), 0.60 (IQR 0.38-1.00)), compared to those with acute cardiac disease (2.22 (IQR 1.08-5.27), 2.28 (IQR 1.01-5.67)). Non-lethal cardiomyocyte injury models showed a predominant release of cTnT with cTnI/cTnT ratios <0.5, and lethal injury models a predominant release of cTnI with cTnI/cTnT ratios >1. Conclusion Differences in cTnI and cTnT levels were observed in individuals with chronic and acute cardiac conditions, leading to distinct cTnI/cTnT ratios in both clinical and experimental settings. As a result, the interchangeability of cTnI and cTnT in present-day clinical and scientific settings needs to be reevaluated.Central illustration