Initial Selection Research Articles

Fedgac: optimizing generalization in personalized federated learning via adaptive initialization and strategic client selection

Fedgac: optimizing generalization in personalized federated learning via adaptive initialization and strategic client selection

Superior initiator reactivity and electrochemical properties of In(OTf)3 over Sn(OTf)2 for 1,3-dioxolane based solid polymer electrolyte

The in-situ polymerization of 1,3-dioxolane (PDOL) in battery cells has attracted extensive attention, however, the differences of Lewis acid initiators on the DOL monomer conversion (C%) and electrochemical properties has been ignored. Here, it is demonstrated that compare with Sn(OTf)2 Lewis acid initiator, the gelation of DOL is achieved at the lower addition of In(OTf)3. By optimizing their content in the gelation process, their C% are comparable which are 95.7 % and 93.5 % for In(OTf)3 and Sn(OTf)2, respectively. However, the higher ionic conductivity (7.1 × 10−4 S cm−1 at room temperature), electrochemical window (~4.5 V) and Li+ transference number (0.42) are obtained for DOL initiated with In(OTf)3, due to its lower molecular weight which is helpful to the intermolecular Li+ transport along PDOL main chain; In addition, the Li/Li symmetrical cell of In(OTf)3 can be stably cycled for >500 h at 3 mA cm−2, with an over-potential of 178mv. The storage and cycling impedances of half cells further proves the stable interface of In(OTf)3 initiated DOL toward to lithium metal in comparison with those of Sn(OTf)2. Scanning electron microscopy results show a denser and thinner interface in the DOL catalyzed by In(OTf)3. Finally, the assembled Li/LiFePO4 battery delivers specific discharge capacity and capacity retention rates of 115.5mAh g−1 and 85 %, respectively after 300 cycles at 1C. Through the initiator selection, the DOL synthesis and electrochemical properties can be tuned, which further broadens the design idea of PDOL based solid polymer electrolyte.

Polymer dispersity modulation by statistical copolymerization of (α-alkyl)acrylate monomers with disparate reactivity: Enhanced monomer conversion and tailored dispersity for dielectric elastomer application

Polymer dispersity (Ð) is an important parameter in determining polymer properties. We report a new strategy for Ð modulation by statistically copolymerizing steric-hindered itaconates with methacrylate and acrylate monomers via organocatalyzed controlled radical polymerization. Due to the disparate monomer reactivity, Ð values can be tunable in a broad range (1.1–1.6) in a batch system. This strategy has demonstrated the sequential and topological generality for Ɖ modulations, serving as a model tool for Ð modulation in any segment of A-B diblock, B-A-B and A-B-A triblock, and 3-arm star A-B diblock copolymers. The unique aspects of this method are that the segment after Ð modulation can initiate polymerization of various types of monomers (e.g., methacrylate, acrylate) by the labile tertiary carbon-iodide chain-end without any external assistance or special initiator and monomer selection, the metal-free nature and the renewable substitution of petroleum-based methacrylate and acrylate monomers with bio-based itaconates without sacrificing inherent properties. This work broadens the application scope of Ð modulation to many other emerging technologies, such as antifreezing thermoplastic dielectric elastomers used as film capacitors in the field of energy storage.

Nonlinear optimal control for robotic exoskeletons with electropneumatic actuators

Nonlinear optimal control for robotic exoskeletons with electropneumatic actuators

Distributed Multi-Area Intraday Economic Dispatch Using Modified Critical Region Projection Algorithm

Convergence acceleration is always a critical issue in distributed multi-area scheduling. The critical region projection (CRP) algorithm based on multi-parametric quadratic programming (MPQP) shows better convergence performance for multi-area static economic dispatch. However, its imperfect decomposition framework cannot be directly applied to dynamic economic dispatch. Therefore, this paper modifies the CRP algorithm to achieve fast distributed multi-area intra-day economic dispatch (MAIDED). First, we introduce slack variables to each area and add the corresponding penalty term into their objective functions to present a primal decomposition framework with penalty relaxation. It is more realistic than the decomposition framework of traditional CRP (TCRP). Then, an iterative algorithm of double spatial scale search (DSSS) is developed to improve the convergence rate of distributed solving based on the similar optimal value function in adjacent critical regions (CRs). Moreover, we design an initial value selection method based on data fitting to further reduce the number of iterations. Finally, three interconnected power systems of different sizes are used for numerical testing to demonstrate that the proposed modified CRP (MCRP) algorithm can meet the practical application and has higher convergence efficiency. <italic xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">Note to Practitioners</i> —This paper is motivated by the problem of distributed MAIDED for power systems but it also applies to other multi-agent networks with a coordinator. The convergence speed of the existing distributed optimization algorithm is slow, which increases the risk of communication failure and attack. Meanwhile, more iterations will result in increased communication and computing costs. This paper modified the TCRP algorithm for high-efficient distributed MAIDED. The penalty relaxation is used to ensure that the decomposition framework is consistent with the actual system operation. The DSSS algorithm and the initial value selection method based on data fitting are designed to effectively reduce the number of iterations. In this paper, the DSSS is that the coordinator enlarges the CRs uploaded from each area to perform a rough optimization for approaching the global optimal solution fast, and then in the next iteration, conducts a precise optimization like the TCRP algorithm to determine the precise optimal solution. The numerical testing of the interconnected power systems of different sizes indicates that the MCRP algorithm has fewer iterations and calculation times than the TCRP algorithm. Future work will extend the MCRP algorithm to solve the distributed multi-area unit commitment problem.

Calculation and Analysis of Equilibrium Position of Aerostatic Bearings Based on Bivariate Interpolation Method

The solution of equilibrium positions is a critical component in the calculation of the dynamic characteristic coefficients of aerostatic bearings. The movement of the rotor in one direction leads to bidirectional variations in the air film force, resulting in low efficiency when using conventional calculation methods. It can even lead to iterative divergence if the initial value is improperly selected. This study concentrates on the orifice throttling aerostatic bearings and proposes a novel method called the bivariate interpolation method (BIM) to calculate the equilibrium position. The equilibrium equation for the rotor under the combined influence of air film forces, gravity, and external loads is established. A calculation program based on the finite difference method is developed to determine the equilibrium position. The process of solving the equilibrium position and the convergence is compared with the secant method and the search method. Furthermore, the variation trend of the equilibrium position and stiffness when the external loads changes are studied based on the BIM. Finally, the correctness of the BIM to solve the equilibrium position is proved by comparing it with the experiment results. The calculation results indicate that the BIM successfully resolves the problem of initial value selection and exhibits superior computational efficiency and accuracy. The equilibrium position initially moves away from the direction of the external load as the load increases, and then this gradually approaches the load direction. The main stiffness increases with increases in the external load, while the variation in cross stiffness depends on the direction of the external load.

Clinical impact of preemptive pharmacogenomic testing on antiplatelet therapy in a real-world setting.

CYP2C19 genotyping to guide antiplatelet therapy after patients develop acute coronary syndromes (ACS) or require percutaneous coronary interventions (PCIs) reduces the likelihood of major adverse cardiovascular events (MACE). Evidence about the impact of preemptive testing, where genotyping occurs while patients are healthy, is lacking. In patients initiating antiplatelet therapy for ACS or PCI, we compared medical records data from 67 patients who received CYP2C19 genotyping preemptively (results >7 days before need), against medical records data from 67 propensity score-matched patients who received early genotyping (results within 7 days of need). We also examined data from 140 patients who received late genotyping (results >7 days after need). We compared the impact of genotyping approaches on medication selections, specialty visits, MACE and bleeding events over 1 year. Patients with CYP2C19 loss-of-function alleles were less likely to be initiated on clopidogrel if they received preemptive rather than early or late genotyping (18.2%, 66.7%, and 73.2% respectively, p = 0.001). No differences were observed by genotyping approach in the number of specialty visits or likelihood of MACE or bleeding events (all p > 0.21). Preemptive genotyping had a strong impact on initial antiplatelet selection and a comparable impact on patient outcomes and healthcare utilization, compared to genotyping ordered after a need for antiplatelet therapy had been identified.

Patient-Reported Outcomes and Mortality in Cutaneous Chronic Graft-vs-Host Disease

Chronic graft-vs-host disease (GVHD) is associated with impaired quality of life and symptom burden. The independent association of skin involvement with patient-reported outcomes (PROs) and their utility as a clinical prognostic marker remain unknown. Identification of patients with cutaneous chronic GVHD and impaired PROs could assist in initial risk stratification and treatment selection. To compare the association of sclerotic and epidermal-type chronic GVHD with longitudinal PROs and to evaluate whether PROs can identify patients with cutaneous chronic GVHD at high risk for death. This multicenter prospective cohort study involved patients from the Chronic GVHD Consortium of 9 US medical centers, enrolled between August 2007 and April 2012, and followed up until December 2020. Participants included adults 18 years and older with a diagnosis of chronic GVHD requiring systemic immunosuppression and with skin involvement during the study period. Patient-reported symptom burden was assessed using the Lee Symptom Scale (LSS) skin subscale with higher scores indicating worse outcomes. Quality of life was measured using the Functional Assessment of Cancer Therapy-Bone Marrow Transplantation (FACT-BMT) instrument with lower scores indicating worse outcomes. Nonrelapse mortality, overall survival, and their association with PROs at diagnosis were also assessed. Among 436 patients with cutaneous chronic GVHD (median [IQR] age at transplant, 51 [41.5-56.6] years; 261 [59.9%] male), 229 patients had epidermal-type chronic GVHD (52.5%), followed by 131 with sclerotic chronic GVHD (30.0%), and 76 with combination disease (17.4%). After adjusting for confounders, patients with sclerotic chronic GVHD had mean FACT-BMT scores 6.1 points worse than those with epidermal disease (95% CI, 11.7-0.4; P = .04). Patients with combination disease had mean LSS skin subscale scores 9.0 points worse than those with epidermal disease (95% CI, 4.2-13.8; P < .001). Clinically meaningful differences were defined as at least 7 points lower for FACT-BMT and 11 points higher for LSS skin subscale. At diagnosis, clinically meaningful worsening in FACT-BMT score was associated with an adjusted odds of nonrelapse mortality increased by 9.1% (95% CI, 2.0%-16.7%; P = .01). Similarly, for clinically meaningful worsening in LSS skin subscale score, adjusted odds of nonrelapse mortality increased by 16.4% (95% CI, 5.4%-28.5%; P = .003). These associations held true after adjusting for clinical severity by the National Institutes of Health Skin Score. The results of this cohort study demonstrated that skin chronic GVHD was independently associated with long-term PRO impairment, with sclerotic and combination disease carrying the highest morbidity. The degree of impairment at skin chronic GVHD diagnosis was a prognostic marker for mortality. Therefore, PROs could be useful for risk stratification and treatment selection in clinical practice and clinical trials.

Genetic Transformation of Potato without Antibiotic-Assisted Selection

The genetic engineering of plants often relies on the use of antibiotic or herbicide resistance genes for the initial selection of primary transgenic events. Nevertheless, the commercial release of genetically modified crops containing any marker gene encounters several challenges stemming from the lack of consumer acceptance. The development of strategies enabling the generation of marker-free transgenic plants presents an alternative to address public concerns regarding the safety of biotech crops. This study examined the capabilities of highly regenerative potato cultivars to develop transgenic plants without the presence of selective substances in their media. Internodal segments of in vitro potato plants were inoculated with the Agrobacterium strain AGL0 carrying plasmids, which contained the GFP or RFP gene driven by the CaMV 35S promoter to monitor the transformation process by observing in vivo green or red fluorescence. Despite the absence of selective pressure, inoculated explants demonstrated comparable or even higher transient expression compared to experiments based on antibiotic assistant selection. Consequently, under non-selective conditions, non-transgenic, chimeric, and fully fluorescent potato plantlets were concurrently developed. Among the five tested cultivars, the regeneration efficiency of non-chimeric transgenic plants varied from 0.9 (‘Chicago’) to 2.7 (#12-36-42) plants per 100 detached plantlets. Depending on the regenerative characteristics of potato varieties (early, intermediate, or late), a specific time interval can be determined when a blind collection of transgenic plantlets is more successful, streamlining the transformation procedure. The results indicate that the outlined procedure is simple and reproducible, consistently achieving the transformation efficiency of 7.3–12.0% (per 100 inoculated explants) in potato cultivars without selective pressure. The described transformation procedure holds the potential for obtaining cisgenic or intragenic potato plants with new valuable traits that do not carry marker genes.

Influence of Different Forms on BIPV Gymnasium Carbon-Saving Potential Based on Energy Consumption and Solar Energy in Multi-Climate Zones

In this study, the influence of the gymnasium building form on energy consumption and photovoltaic (PV) potential was investigated to address its high energy consumption and carbon emissions issues. Five cities in different climate zones in China (Harbin, Beijing, Shanghai, Guangzhou, and Kunming) were selected as case study environments to simulate and calculate the energy use intensity (EUI), photovoltaic power generation potential (PVPG), and CO2 emission (CE) indicators for 10 typical gymnasium building forms, while also assessing the impact of building orientation. This study found that changes in gymnasium building orientation can cause a 0.5–2.5% difference in EUI under the five climatic conditions, whereas changes in building form can cause a 1.9–6.4% difference in EUI. After integrating a building-integrated photovoltaic (BIPV) system on the roof, changes in building orientation and form can lead to a 0–14.4% and 7.6–11.1% difference in PVPG and a 7.8–68.1% and 8.7–72.0% difference in CE. The results demonstrate that both the choice of form and orientation contribute to a reduction in carbon emissions from BIPV gymnasiums, with the rational choice of form having a higher potential for carbon savings than orientation. These research findings can guide the initial selection of gymnasium designs to pursue low-carbon goals.

Crystal facet-controlled brookite TiO2 nanostructures coupled with Ru nanoparticles for enhancing selective hydrogenation of benzene to cyclohexene

Coupling active metal nanoparticles (NPs) with oxide nanocrystals enclosed by specific facets is a promising strategy to enhance their catalytic performances. Here, brookite TiO2 nanoplates exposed with {11 1¯} facets, nanorods enclosed by {121} facets, and nanosheets exposed with {211} facets were synthesized and coupled with Ru NPs, aiming at improving their catalytic efficiency in selective hydrogenation of benzene to cyclohexene (SHBC) and discriminating the critical roles of brookite facets. The comprehensive characterizations recognized that the successive exposure of brookite TiO2 {11 1¯}, {121}, and {211} facets resulted in a more suitable adsorption strength of C6H6 and an increment of chemisorption capacity of C6H6 on medium-strength acid sites, contributing to a promotion of the turnover frequency (TOF) of C6H6. The kinetics investigations, density functional theory (DFT) simulations, and Mulliken population analysis unveiled that the increased Ti3+ species as a result of the successive exposure of brookite TiO2 {11 1¯}, {121}, and {211} facets brought in an increment of the net production rate of C6H10 in SHBC, and the electronic interaction between C6H10 and these facets is gradually weakened, which contributed to an improvement of C6H10 selectivity. As a consequence, an initial C6H10 selectivity (S0) of 91 % and a C6H10 yield of 47 % achieved on the brookite TiO2-supported Ru catalyst enclosed by TiO2 {211} facets.

The predictive validity of cognitive ability and personality tests toward police on-the-job training

This study investigates the predictive validity of psychometric tests included in the Norwegian Police University College selection process for 106 accepted trainees. Predictor variables were from the Scales (lst, verbal admin, lt-no) cognitive ability tests and the Shapes (basic) personality test, distributed by the contractor Aon Assessment Norway AS (formerly cut-e). The criterion variable was from the on-the-job training phase of the police bachelor program, in which instructors rated trainees’ work behaviors two years after initial selection. The results revealed a lack of predictive validity, as witnessed in both correlational analysis and a regression approach controlling for police academy performance. Contrary to expectations, cognitive ability test scores negatively predicted trainee work behaviors in the regression model. These results are compared with those of other relevant studies and are evaluated in light of this study's main strengths and weaknesses. The results of this study deserve an exploratory interpretation, given the limited sample size and a lack of hitherto peer-reviewed psychometric documentation for the tests. This study substantiates the need for further research with respect to the use of psychometric tests in law enforcement selection, particularly contractor-distributed tests, which are rarely studied.

Selection-Dependent Differences in Youth Elite Basketball Players’ Relative Age, Maturation-Related Characteristics, and Motor Performance

ABSTRACT Purpose: The aim of the present study was to investigate the influence of players’ relative age, maturation-related characteristics, and motor performance tests on two different stages of talent selection (regional and national level) in youth elite basketball. Methods: Relative age, maturation-related variables (height, weight, maturity offset, maturity timing) and motor performance (Countermovement jump, Standing long jump, Modified agility T-test, Linear sprint 20 m) of N = 68 male youth basketball players (M age = 14.39 ± 0.28 years) were assessed during the initial selection tournament for the German U15 national team. Pre-selection biases regarding relative age and maturity timing on the regional level were investigated utilizing one-sample t-tests. Differences in relative age, maturation-related characteristics and motor performance between players selected (n = 27) and non-selected (n = 41) for the youth national team were examined via independent samples’ t-tests and logistic regression analyses. Results: Strong pre-selection biases toward early-born and early-maturing players were confirmed on the regional level. Significant advantages in height and weight and higher values in maturity offset and maturity timing were found for selected players. Among the motor variables, only Countermovement jump performance was significantly better in selected players. When controlling for relative age and biological maturation regression models including motor performance variables did not significantly discriminate players’ selection status. Conclusion: Coaches working in national, but also preceding selection stages (regional and club level) should raise their awareness to relative age and biological maturation when evaluating players’ potential and current (motor) performance.

Safety and clinical validity of tumor genomic testing for guiding active surveillance selection in men with NCCN intermediate-risk prostate cancer.

336 Background: Clinicopathologic features are considered the gold standard for predicting prostate cancer (PCa) disease severity and guiding decisions on the use of active surveillance (AS) or definitive treatment (DT). However, tumor genomic testing has been shown to provide valuable information as an addition to clinical risk stratification measures, allowing for more accurate identification of AS candidates. This study evaluated the safety of genomic testing for guiding AS selection in patients with National Comprehensive Cancer Network (NCCN) intermediate-risk PCa. Methods: In this retrospective observational cohort study, patients with NCCN intermediate-risk PCa underwent Prolaris testing at diagnosis from 9/2015–12/2018. The Prolaris test combines a molecular cell cycle progression score with clinicopathologic features (USCF Cancer of the Prostate Risk Assessment [CAPRA] score, inclusive of Gleason score), generating a Combined Clinical Risk (CCR) score to identify patients as candidates for AS or DT. Patients with a CCR-based 10-year disease-specific mortality (DSM) risk ≤3.2% were recommended to AS. Clinical follow up data, including initial treatment selection and time to metastasis, were retrospectively collected from the treating clinics. Kaplan-Meier estimates were used to evaluate the safety of AS in patients who initially selected AS. Cox proportional hazards models were used to evaluate CCR as a predictor of metastasis in all patients. Results: In total, 3204 patients were included in this analysis, with 1468 (46%) recommended to AS and 1736 (54%) recommended to DT. Among the 973 (30%) patients who initially selected AS, 613 (63%) were recommended to AS and 360 (37%) were recommended to DT. In patients who were recommended to AS and initially selected AS, the observed risk of metastasis within 5 years of diagnosis was 0.37% (95% confidence interval [CI], 0.09%–1.47%). Patients who were recommended to AS had a significantly lower rate of metastasis than patients who were recommended to DT after accounting for initial treatment decision (AS vs DT) and CAPRA score (hazard ratio 4.20 [95% CI, 1.41–18.04], P-value = 0.03). Conclusions: For patients with NCCN intermediate-risk PCa who were identified by genomic testing as candidates for AS, AS is safe based on the very low observed metastasis risk. The CCR score is a strong predictor of metastasis beyond clinicopathologic factors.

Association of tameness and sociability but no sign of domestication syndrome in mice selectively bred for active tameness.

Domesticated animals have been developed by selecting desirable traits following the initial unconscious selection stage, and now exhibit phenotypes desired by humans. Tameness is a common behavioural trait found in all domesticated animals. At the same time, these domesticated animals exhibit a variety of morphological, behavioural, and physiological traits that differ from their wild counterparts of their ancestral species. These traits are collectively referred to as domestication syndrome. However, whether this phenomenon exists is debatable. Previously, selective breeding has been used to enhance active tameness, a motivation to interact with humans, in wild heterogeneous stock mice derived from eight wild inbred strains. In the current study, we used tame mice to study how selective breeding for active tameness affects behavioural and morphological traits. A series of behavioural and morphological analyses on mice showed an increased preference for social stimuli and a longer duration of engagement in non-aggressive behaviour. However, no differences were observed in exploratory or anxiety-related behaviours. Similarly, selection for tameness did not affect ultrasonic vocalisations in mice, and no changes were observed in known morphological traits associated with domestication syndrome. These results suggest that there may be a link between active tameness and sociability and provide insights into the relationship between tameness and other behaviours in the context of domestication.

Watch and Wait for Rectal Cancer

About one third of all colorectal carcinomas (CRC) are localised in the rectum. As part of a multimodal therapy concept, neoadjuvant therapy achieves downstaging of the tumour in 50-60% of cases and a so-called complete clinical response (cCR), defined as clinically (and radiologically) undetectable residual tumour after completion of neoadjuvant therapy, in 10-30% of cases.In view of the perioperative morbidity and mortality associated with radical rectal resection, including the occurrence of a symptom complex known as low anterior resection syndrome (LARS) and the need for deviation, at least temporarily, the question of the risk-benefit balance of organ resection in the presence of cCR has been raised. In this context, the therapeutic concept of a "watch-and-wait" approach with omission of immediate organ resection and inclusion in a structured surveillance regime, has emerged.For a safe, oncological implementation of this option, it is necessary to develop standards in the definition of a suitable patient clientele and the implementation of the concept. In addition to the initial correct selection of the patient group that is suitable for a primarily non-surgical procedure, the inherent goal is the early and sufficient detection of tumour recurrence (so-called local regrowth) during the "watch-and-wait" phase (surveillance).In this context, in this paper we address the questions of: 1. the optimal timing of initial re-staging, 2. the criteria for assessing the clinical response and selecting the appropriate patient clientele, 3. the rhythm and design of the surveillance protocol.

Refractive Errors Among Members of the Armed Forces of the Czech Republic.

Objective: To evaluate the prevalence of refractive errors among members of the Armed Forces of the Czech Republic, to recommend a safe way of correcting refractive errors with regard to the specific needs of military personnel (especially members of combat units and flying personnel), and to propose a system for solving these errors in order to increase combat effectivity. Methodology: Questionnaire to determine previous refractive surgery and spectacle correction wear. Measurement of refraction with a hand-held autorefractometer and evaluation of current visual acuity on ETDRS optotypes (Landolt rings). Results: 259 servicemen (518 eyes) were investigated. The return rate of the questionnaires was 100%. The incidence of myopia greater than -0.75D was 22% (113 eyes), myopia greater than -0.5D 32% (166 eyes). The mean value of myopia was -0.78 D (SD ±0.6). Hypermetropia values ranged from +0.25 to +5.0 D. The mean value of hypermetropia was 0.63 D (SD ±0.7). Astigmatism values ranged from -0.25 to -3.75. The mean value of astigmatism was -0.55 Dcyl (SD ±0.49). The average visual acuity was 84.1 letters ETDRS SD (±6.1), visual acuity worse than 80 letters was manifested by 23% of the members of the monitored group. 25 people (10%) had undergone laser refractive surgery. Visual acuity after laser refractive surgery was measured in 19 people (38 eyes). Mean uncorrected post-laser visual acuity was 83.87 (SD ±6.1) ETDRS letters. The mean follow-up period after laser refractive surgery was 6.78 (SD ±4.8) years. Conclusion: Despite the initial selection of military personnel and entry limitations, the prevalence of refractive errors is comparable to the general population. However, in contrast with the general population, refractive errors larger than -3.0 D were not represented in the group. Due to the finding of insufficient correction of refractive errors, increased emphasis should be placed on identifying and regularly observing military personnel with refractive errors

Nine lensed quasars and quasar pairs discovered through spatially extended variability in Pan-STARRS

We present the proof of concept of a method for finding strongly lensed quasars using their spatially extended photometric variability through difference imaging in cadenced imaging survey data. We applied the method to Pan-STARRS, starting with an initial selection of 14 107 Gaia multiplets with quasar-like infrared colours from WISE. We identified 229 candidates showing notable spatially extended variability during the Pan-STARRS survey period. These include 20 known lenses and an additional 12 promising candidates for which we obtained long-slit spectroscopy follow-up. This process resulted in the confirmation of four doubly lensed quasars, four unclassified quasar pairs, and one projected quasar pair. Only three are pairs of stars or quasar+star projections. The false-positive rate accordingly is 25%. The lens separations are between 0.81″ and 1.24″, and the source redshifts lie between z = 1.47 and z = 2.46. Three of the unclassified quasar pairs are promising dual-quasar candidates with separations ranging from 6.6 to 9.3 kpc. We expect that this technique is a particularly efficient way to select lensed variables in the upcoming Rubin-LSST, which will be crucial given the expected limitations for spectroscopic follow-up.

Poised for growth: Exploring the relationship between accelerator program design and startup performance

AbstractResearch SummaryAccelerator programs provide valuable market feedback and education to participants that may improve startup performance. However, it is unclear whether the average effect of accelerator participation on startup performance post acceleration is positive, and if so, how this effect varies with accelerator program design. We analyze data from 8580 startups that made it past the initial selection stage at 408 accelerators in 176 countries between 2013 and 2019. We compare accelerated and non‐accelerated startups and find a positive average effect of accelerator participation on startup performance post acceleration. Moreover, we find that this effect varies substantially with program design, and depends on venture stage, industry, and founder expertise. Our findings highlight the impact of program design on the benefits that startups derive from accelerator participation.Managerial SummaryThe purpose of this study is to determine whether participation in startup accelerator programs generally leads to improved startup performance post acceleration and how the benefits of participation might vary with the design of these programs. We analyze data from 8580 startups that applied to and passed the initial selection phase at 408 accelerators in 176 countries over multiple cohorts between 2013 and 2019. Our results indicate that on average, startups that participate in accelerators perform better than those that are also selected but not accelerated. Furthermore, we find that the benefits that startups gain from being accelerated vary with the design of the program. Our findings highlight the importance of accelerator program design in influencing the extent of improvement in startup performance post acceleration.

Targeting PDE4A for therapeutic potential: exploiting drug repurposing approach through virtual screening and molecular dynamics

cAMP-specific 3′,5′-cyclic phosphodiesterase 4 A (PDE4A) holds a pivotal role in modulating intracellular levels of cyclic adenosine monophosphate (cAMP). Targeting PDE4A with novel therapeutic agents shows promise in addressing neurological disorders (e.g. Alzheimer’s and Parkinson’s diseases), mood disorders (depression, anxiety), inflammatory conditions (asthma, chronic obstructive pulmonary disease), and even cancer. In this study, we present a comprehensive approach that integrates virtual screening and molecular dynamics (MD) simulations to identify potential inhibitors of PDE4A from the existing pool of FDA-approved drugs. The initial compound selection was conducted focusing on binding affinity scores, which led to the identification of several high-affinity compounds with potential PDE4A binding properties. From the refined selection process, two promising compounds, Fluspirilene and Dihydroergocristine, emerged as strong candidates, displaying substantial affinity and specificity for the PDE4A binding site. Interaction analysis provided robust evidence of their binding capabilities. To gain deeper insights into the dynamic behavior of Fluspirilene and Dihydroergocristine in complex with PDE4A, we conducted 300 ns MD simulations, principal components analysis (PCA), and free energy landscape (FEL) analysis. These analyses revealed that Fluspirilene and Dihydroergocristine binding stabilized the PDE4A structure and induced minimal conformational changes, highlighting their potential as potent binders. In conclusion, our study systematically explores repurposing existing FDA-approved drugs as PDE4A inhibitors through a comprehensive virtual screening pipeline. The identified compounds, Fluspirilene and Dihydroergocristine, exhibit a strong affinity for PDE4A, displaying characteristics that support their suitability for further development as potential therapeutic agents for conditions associated with PDE4A dysfunction. Communicated by Ramaswamy H. Sarma