Proximal Function Research Articles

Safety and efficacy of tamoxifen in non-ambulant patients with Duchenne muscular dystrophy: a multicentre, randomised, double-blind, placebo-controlled, phase 3 trial (TAMDMD Group B).

Most patients with Duchenne muscular dystrophy (DMD) are non-ambulant. Preserving proximal motor function is crucial, rarely studied. Tamoxifen, a selective oestrogen receptor modulator, reduced signs of muscular pathology in a DMD mouse model. Our objective was to assess the safety and efficacy of tamoxifen over 48 weeks in non-ambulant DMD patients. In this multicentre, randomised, double-blind, placebo-controlled, phase 3 trial at six European centres boys aged 10-16 years with genetically diagnosed DMD, non-ambulant and off corticosteroid treatment for ≥6 months, randomly assigned (1:1) to either 20 mg/day tamoxifen orally or placebo were included. The primary outcome was change in D2 motor function measure from baseline to week 48. Of 15 non-ambulant male patients with DMD screened, 14 were enrolled from January 24th, 2019, to January 6th, 2021. Eight patients were randomised to the treatment and six to the placebo group. The primary efficacy outcome did not differ significantly between tamoxifen and placebo (7.8 percentage points, 95 % CI, -26.82 to 11.22, p=0.359) with a trend not favouring tamoxifen. No deaths or life-threatening serious AEs occurred. Tamoxifen was safe but due to insufficient clinical evidence, it cannot be recommended as a treatment option for DMD. Trial registration: ClinicalTrials.gov (NCT03354039).

649 Rac1 promotes actin cytoskeleton dependent mitochondrial homeostasis to maintain kidney proximal tubular function after injury

649 Rac1 promotes actin cytoskeleton dependent mitochondrial homeostasis to maintain kidney proximal tubular function after injury

P-2201. A Comprehensive Kidney Biomarker Panel to Assess Kidney Health after Hepatitis C Direct Acting Antiviral Therapy in Persons with HCV monoinfection and HCV/HIV coinfection

Abstract Background Chronic Hepatitis C virus (HCV) infection is associated with greater risk of chronic kidney disease and proteinuria. We examined effects of 12 weeks of elbasvir/grazoprevir, an HCV NS5A inhibitor/NS3/4A Protease Inhibitor on glomerular filtration (creatinine, cystatin C), injury (albuminuria), and 9 novel kidney tubule biomarkers in adults with HCV infection over a 24-week period.Figure.Percent Change (95% Confidence Interval) from Baseline of Urine Kidney Tubule Markers 24 weeks after initiating Elbasvir/Grazoprevir in Patients with HCV Methods We included 36 participants with HCV (7 with HIV coinfection) from the San Francisco Bay Area. Urine biomarkers included kidney tubule function (α-1-microglobulin [α1m], β-2-microglobulin [β2m]) and injury (kidney injury marker-1 [KIM-1], neutrophil gelatinase-associated lipocalcin [NGAL], (interleukin-18 [IL-18]), fibrosis/repair (monocyte chemoattractant protein 1 [MCP-1], chitinase-3-like protein-1 [YKL-40]) and synthetic function (epidermal growth factor [EGF], uromodulin [UMOD]). Biomarkers were measured at baseline, wk 12 (end of treatment), and week 24 (time of assessment for sustained virologic response [SVR]). We used linear mixed regression models with time as the main predictor to assess changes in kidney health, adjusting for demographics and urine creatinine. Results Over two thirds identified as Black/African American;89% were men and median age was 62 years. All but 2 achieved an SVR and 17% had advanced liver fibrosis using the FIB-4 serum marker. Median (interquartile range) for eGFRcr, eGFRcys, and urine albumin to creatinine ratio (ACR) were 82(63-100 ml/min),74(58-87 ml/min), and 10.4(4.9-24 mg/g), respectively at baseline. The percent (%) change from baseline for eGFRcr and ACR at weeks 12 and 24 was not statistically significant; eGFRcys was -11.4% lower (95%CI:-18%,-4.6%) at week 24. After 12 weeks of treatment, there were significant reductions in α1m, β2m, KIM-1, and MCP-1, with smaller reductions seen in most other markers (Figure). At week 24, these reductions were sustained for KIM-1. Conclusion Our findings suggest that HCV treatment with elbasvir/grazoprevir improves proximal tubule function and reduces cellular injury and fibrosis. Further research is needed to understand longer-term trends in kidney health following HCV cure. Disclosures Michelle Estrella, MD, Astra Zeneca: Board Member|Bayer: Grant/Research Support|Boehringer Ingelheim: Board Member Michael Shlipak, MD, Astra-Zeneca: Honoraria|Bayer: Grant/Research Support|Bayer: Honoraria|Boehringer Ingelheim: Honoraria Phyllis C. Tien, MD, MSc, Merck: Grant/Research Support

The Multifactorial Relationship Between Bone Tissue Water and Stiffness at the Proximal Femur

Bone mechanical function is determined by multiple factors, some of which are still being elucidated. Here, we present a multivariate analysis of the role of bone tissue composition in the proximal femur stiffness of cadaver bones (n = 12, age 44–93). Stiffness was assessed by testing under loading conditions simulating a sideways fall onto the hip. Compositional properties of cortical and trabecular tissues were quantified in femoral neck cross sections by Fourier transform infrared (FTIR) spectroscopy and near infrared (NIR) spectroscopy. In addition, cross-sectional areas and cortical thickness and tissue mineral density (TMD) were measured at the femoral neck. Pearson correlation analysis showed a significant (p < 0.05) negative relationship between bone stiffness and cortical and trabecular water content, both total (r = -0.63) and tightly bound to matrix and mineral (r = -55). Additionally, significant (p < 0.05) positive correlations were found between stiffness and bone area, both total (r = 0.67) and trabecular (r = 0.58). However, linear regression using each of these properties to predict bone stiffness resulted in weak models (R2 = 0.36–0.48). Interestingly, we found markedly stronger models (cross-validated R2 = 0.80–0.92) by using partial least squares (PLS) regression to predict stiffness based on combinations of bone properties. The models with highest R2 values were found when including bone water parameters as explanatory variables, both total and tightly bound, in cortical and trabecular. This study provides new insights by revealing a multifactorial relationship in which higher bone water content across different tissue compartments contributes to lower bone stiffness, highlighting bone water as a potential biomarker of bone quality and proximal femur mechanical function.

Mathematical Modeling of Fractals via Proximal F-Iterated Function Systems

Mathematical Modeling of Fractals via Proximal F-Iterated Function Systems

Acoustic Emission Events Clustering Parameters in Laboratory Rock Fracture Experiments

This paper verifies the compliance of the earthquake productivity law (Shebalin et al., 2020a) in laboratory experiments on rock destruction. Westerly granite and Benheim sandstone specimens were subjected to uniaxial loading under uniform compression. An acoustic-emission (AE) recording system made it possible to create catalogues of AE sources similar to earthquake catalogues. The data from experiments conducted at the Rock Friction Laboratory (USGS, Menlo Park, United States) and the Geomechanics and Rheology Laboratory (GFZ, Potsdam) were analyzed. It was found that the AE events in the considered samples are characterized by a unimodal distribution of the nearest-neighbor proximity function. The compliance of the productivity law for acoustic-emission events in laboratory experiments on the destruction of rock samples is shown, which gives grounds to speak about the similarity of grouping processes in real seismicity and in laboratory conditions.

Iron Deficiency and Renal Phosphate Handling: The Role of Maximal Tubular Reabsorption of Phosphate Normalized to Glomerular Filtration Rate (TmP/GFR) in Proximal Tubular Dysfunction.

Phosphate dysregulation is often associated with chronic kidney disease (CKD), and recent studies suggest that it may also be present in non-CKD patients with systemic conditions including iron deficiency anemia. This study aimed to evaluate the relationship between irondeficiency parameters (total iron-binding capacity {TIBC}, hemoglobin, and serum ferritin) and markers of proximal tubular dysfunction (the maximal tubular reabsorption of phosphate normalized to glomerular filtration rate {TmP/GFR} and tubular reabsorption of phosphate {TRP}) in non-CKD patients with iron deficiency anemia. This was a hospital-based analytical cross-sectional study conducted in the outpatient department and/or inpatient wards of the Department of Internal Medicine, Swaroop Rani Nehru (SRN) Hospital associated with Moti Lal Nehru (MLN) Medical College, Prayagraj, Uttar Pradesh, India, between July 2023 and August 2024. This study analyzed 40 anemic patients without CKD, with a mean age of 33.9 years. Most participants (n=24, 60%) were aged 18-35 years, and the majority (n=27, 67.5%) were female. Peripheral smear analysis revealed that 72.5% (n=29) had microcytic hypochromic anemia. Hemoglobin levels averaged 7.7 g/dL, serum iron was 91.0 µg/dL, total iron-binding capacity (TIBC) was 316.3 µg/dL, and serum ferritin was 199.7 ng/mL. Phosphate handling was assessed with TmP/GFR and tubular reabsorption of phosphate (TRP)showing mean values of 4.1 mg/dL and 99.2%, respectively. This study found that TmP/GFR had a significant positive correlation with TIBC (r=0.402, p=0.010), but non-significant negative correlations with hemoglobin and serum iron. TRP was negatively correlated with hemoglobin and serum ferritin, but not significantly. Among patients with microcytic hypochromic anemia, 55.2% (n=16) had increased TmP/GFR, and 61.1% (n=20) of patients with iron deficiency anemia exhibited increased TmP/GFR. Regression analysis revealed that TIBC significantly predicted TmP/GFR (p=0.022), indicating that higher TIBC values are associated with increased TmP/GFR, suggesting a potential link between iron metabolism and renal phosphate handling. Higher TIBC levels were associated with increased TmP/GFR, suggesting that iron deficiency anemia may influence proximal tubular function. The findings emphasize the importance of considering renal phosphate handling in patients with iron deficiency anemia.

Accrual of Alzheimer’s Disease pathology as a function of proximity to parental dementia onset

AbstractBackgroundThere is emerging evidence to substantiate temporal proximity to parental onset (PPO) of dementia as a proxy stage marker in studies of late onset Alzheimer’s Disease (AD). PPO predicts accrual of amyloid pathology cross‐sectionally and longitudinally. However interactions with gender, age, and APOE‐𝜀4 carriage have been inconsistent across datasets and amyloid measures.MethodWe investigated cross‐sectionally a subset of the European Prevention of Alzheimer's Dementia (EPAD) study cohort (n=688) (Table 1). PPO was calculated by substracting a subject’s age from the youngest age of diagnosis of an affected parent. Regressions were used to determine whether PPO predicts CSF fluid Aβ1‐42 in the whole sample or p‐tau in an amyloid‐positive subgroup (n=226). Possible interactions with age, gender, education, APOE‐𝜀 status, family history load, gender of affected parent and CDR score were explored.ResultNearer PPO predicted lower CSF Aβ1‐42 level (p&lt;0.001), interacting significantly with APOE‐𝜀4 carriage only (β=12.683; T=3.295; p=0.001) accounting for effects of age, gender and education level. In APOE‐𝜀4+ subjects, APOE‐𝜀2 provided a protective effect (Figure 1). At least half of APOE‐𝜀4+/APOE‐𝜀2‐ subjects (n=255) within ten years of age of parental onset were amyloid positive (Figure 2). PPO did not predict p‐tau levels in amyloid positive subjects (n=226) (p=0.414).ConclusionIn APOE‐𝜀4+/APOE‐𝜀2‐ individuals, PPO predicts accrual of amyloid but not tau pathology, independently of age. Selectively examining this population as they approach age of parental onset may better elucidate the natural history of preclinical late onset AD.

Proximal tubule cell maturation rate and function are controlled by PPARα signaling in kidney organoids

Human pluripotent stem cell-derived kidney organoids are expected to be a useful tool for new drug discoveries, however, the immaturation of kidney organoids causes difficulties in recapitulating renal pharmacokinetics using organoids. Here, we performed time-course single-cell RNA sequencing of kidney organoids and revealed cell heterogeneity in the maturation rate of the proximal tubule. An unbiased analysis to identify upstream targets of genes that are expressed differentially between cells with low and high maturation rates revealed a higher activation of PPARα signaling in rapidly maturing cells. Treatment with a combination of a PPARα agonist and an RXRα agonist induced genes related to proximal tubule maturation and increased the capacity for protein uptake as well as the sensitivity to nephrotoxicity by cisplatin. This method to promote the maturation rate of proximal tubule cells has the potential to be utilized in microphysiological systems to recapitulate proximal tubule functions and to screen nephrotoxic drugs.

(Invited) Advancing Photocatalysis through Model Systems and Single Particle Measurements

Photocatalytic water splitting using photocatalyst particles holds great promise for achieving efficient and cost effective production of renewable hydrogen (H2). However, demonstrations of photocatalytic water splitting have generally been plagued by low solar-to-hydrogen conversion efficiencies. Gaining deeper insights into loss mechanisms and interactions between different particles and components is essential for enabling rational design of ensembles of high performance photocatalysts for which these losses are minimized. Towards this end, our team has taken a two pronged approach that relies on the development and use of (i) model systems and (ii) single particle measurements. The first approach relies on the use and development of a planar analog photocatalyst for which all parts of a multi-component photocatalyst (e.g. light absorber, co-catalysts, selective coatings) can be integrated with excellent control over feature size, positioning, and density. This planar analog platform also allows for easier access of advanced analytical tools like scanning electrochemical microscopy, which can be used to directly probe spatial variation in performance and better understand interactions between components as a function of proximity and operating conditions. In this talk, I will describe how this approach can be especially useful for quantifying losses associated with undesired “back reactions” occurring at neighboring active sites, which can be a primary loss mechanism in photocatalyst systems. After describing efforts relating to planar analog photocatalysts, I will also present results from our studies of individual photocatalyst particles that rely on local optical and electrochemical probes to measure the relative performance of individual particles in the presence and absence of neighboring particles.

Investigation of renal tubular function with newly diagnosed type 1 diabetes mellitus during diabetic ketoacidosis

BackgroundProximal renal tubular dysfunction occurs during diabetic ketoacidosis (DKA) in type 1 diabetes. However, only a few studies have reported on the multiple proximal renal tubular functions simultaneously. Moreover, to the best of our knowledge, distal renal tubular function has not yet been investigated.MethodsPatients with newly diagnosed type 1 diabetes mellitus were classified into those with DKA and those without DKA, and their proximal and distal renal tubular functions were investigated. The diagnostic criteria for DKA were blood glucose > 200 mg/dL, blood pH < 7.3 or HCO3– < 15 mEq/L, and urine ketone body positivity.ResultsSix patients with DKA and five patients without DKA were included. In patients with DKA, urinary β2-microglobulin levels were significantly higher, while blood pH, HCO3–, and tubular reabsorption of phosphorus were significantly lower than in those without DKA. There were no significant differences in blood glucose, HbA1c, serum phosphorus, urinary N-acetyl-beta-glucosaminidase, and urinary amino acid excretion between patients with and without DKA. Elevated NH3 levels and impaired urinary acidification were not observed in patients with and without DKA.ConclusionsIn patients with newly diagnosed type 1 diabetes mellitus complicated with DKA, multiple proximal renal tubular dysfunctions occur simultaneously, suggesting transient Fanconi syndrome. Distal renal tubular acidosis was unlikely. The diagnostic criteria for DKA are appropriate also in the view of proximal renal tubular dysfunction and are considered suggestive of pathophysiological factors that may cause proximal renal tubular dysfunction.

Approximation of the Absorption Spectrum of Indium Phosphide in the Context of Simulation of the Process of Sensitivity Enhancement

Examines the fundamental rights of Phosphide of India, legitimized by Tellur and, in the last resort, compensated for. Data on the composition of four high-quality images of the InP: Cu photoelectronic spectrum are presented in the individual layers. The work is characterized by the semi-empiric approach to photoconduction of InP: Cu oxide films. It is concluded that the photoresistance Iph (α(ћω)) was analytically approximated as the function of the experimental-complete spectral distribution of the coefficiency phosphorus india. It is proposed to use five approximating functions with the aim of analyzing the coefficient of absorption of Indian phosphorus α(ћω). Completed 5 locations with different signs of median isolation. On the basis of analytical amplitudes, the complete analytical amplitude Iph(α(ћω)) is modelled. Analogously, five conclusions were drawn that indicate a sign of median isolation. Five non-stationary measures of IF photometry have been taken (as two functions: co-efficiency of exposure, as photo energy functions, and time-consuming observations) in normal situations. The answer to the question is the most mathematical and physical solution of the proximate function α(ћω). Obviously, it shows that this the degree of variance is optimal for its implementation (inclusion of this degree of variance in the structure Iph = f(α) and α = f(ћω)) of the complete analytical description of the process photoconductivity. It should be noted that subsequent research may be based on the establishment of physical bases of photoconductivity in the short wave of fundamental transfers of phosphorus from India, as well as research into the properties of air on the high InP: Cu layer, with its stability and stability.

Artificial Neural Network and Gaussian Approach to Predict Rotor-Airframe Acoustic Waveforms

An artificial neural network-based surrogate model and Gaussian process model were developed to predict the acoustic interaction for a fixed-pitch rotor in proximity to a downstream cylindrical airframe typical of small unmanned aerial system platforms. The models were trained to predict the acoustic waveform under representative hover conditions as a function of rotational speed, airframe proximity, and observer angle. Training data were acquired in an anechoic chamber on both isolated rotors and rotor–airframe configurations. The acoustic amplitude and phase of the revolution-averaged interaction were predicted, which required up to 25 harmonics to capture the impulse event caused by the blade’s approach and departure from the airframe. Prediction performance showed, on average, that the artificial neural network models could estimate the acoustic amplitude and phase over the relevant harmonics for unseen conditions with 86% and 75% accuracy, respectively. This enables a time-domain reconstruction of the waveform for the range of geometric and flow parameters tested. In contrast, the Gaussian process matched the amplitude but underpredicted the phase for unseen conditions at 86% and 45% accuracy, respectively.

Follow which leader? Spatial mimicry and broad‐based equity‐ and profit‐sharing plans

AbstractOrganizations have both local and nationally prominent peers from which they can model their human resource management practices. How does a focal organization reconcile the influence of smaller, spatially proximate peer organizations with the influence of prominent, distant organizations? We develop the concept of spatial mimetic gravity to estimate the mimetic pressures a focal organization feels from its geographically proximate and distant peers. We examine the population of craft beer brewers in the United States between 2013 and 2019 and find that the propensity to offer a stock ownership or profit‐sharing plan is a function of a focal brewery's spatial proximity to its peers and their prominence. We help explain why some firms offer broad‐based equity‐sharing and profit‐sharing plans and others do not. In doing so, we argue that organizational spatial mimicry is best understood from a gravity approach, adding a field‐level explanation to previously individually focused theory about organizational choices.

Deconvolution of Human Urine across the Transcriptome and Metabolome.

Early detection of the cell type changes underlying several genitourinary tract diseases largely remains an unmet clinical need, where existing assays, if available, lack the cellular resolution afforded by an invasive biopsy. While messenger RNA in urine could reflect the dynamic signal that facilitates early detection, current measurements primarily detect single genes and thus do not reflect the entire transcriptome and the underlying contributions of cell type-specific RNA. We isolated and sequenced the cell-free RNA (cfRNA) and sediment RNA from human urine samples (n = 6 healthy controls and n = 12 kidney stone patients) and measured the urine metabolome. We analyzed the resulting urine transcriptomes by deconvolving the noninvasively measurable cell type contributions and comparing to plasma cfRNA and the measured urine metabolome. Urine transcriptome cell type deconvolution primarily yielded relative fractional contributions from genitourinary tract cell types in addition to cell types from high-turnover solid tissues beyond the genitourinary tract. Comparison to plasma cfRNA yielded enrichment of metabolic pathways and a distinct cell type spectrum. Integration of urine transcriptomic and metabolomic measurements yielded enrichment for metabolic pathways involved in amino acid metabolism and overlapped with metabolic subsystems associated with proximal tubule function. Noninvasive whole transcriptome measurements of human urine cfRNA and sediment RNA reflects signal from hard-to-biopsy tissues exhibiting low representation in blood plasma cfRNA liquid biopsy at cell type resolution and are enriched in signal from metabolic pathways measurable in the urine metabolome.

Complexity analysis of primal-dual interior-point methods for semidefinite optimization based on a new type of kernel functions

Kernel functions are essential for designing and analyzing interior-point methods (IPMs). They are used to determine search directions and reduce the computational complexity of the interior point method. Currently, IPM based on kernel functions is one of the most effective methods for solving LO [1,20], second-order cone optimization (SOCO) [2], and symmetric optimization (SO) and is a very active research area in mathematicalprogramming. This paper presents a large-update primal-dual IPM for SDO based on a new bi-parameterized hyperbolic kernel function. Then we proved that the proposed large-update IPM has the same complexity bound as the best-known IPMs for solving these problems. Taking advantage of the favorable characteristics of the kernel function, we can deduce that the iteration bound for the large update method is $\mathcal{O}\left( \sqrt{n}\log n\log\dfrac{n}{\varepsilon }\right) $ when a takes a special value utilizing the favorable properties of the kernel function. These theoretical results play an essential role in the design and analysis of IPMs for CQSCO [7] and the Cartesian$\ P_{\ast }\left( \kappa \right) $-SCLCP [8]. The proximity function has never been used. In order to validate the efficacy of our algorithm and verify the effectiveness of our algorithm, examples aregiven to illustrate the applicability of our main results, and we compare our numerical results with some alternatives presented in the literature.

Abstract 06: Role of the Atrial Natriuretic Peptide in Mitochondria-mediated Proximal Tubule Epithelial Oxidative Stress in Type 1 Diabetic Kidney Disease

Introduction: Diabetic kidney disease (DKD) is the leading cause of end-stage renal disease. Most studies of DKD are glomerulo-centric. The recent progress in the control of renal glucose handling by SGLT2i makes the proximal tubule (PT) a prime candidate. Mitochondrial (mito) dysfunction and mito-induced oxidative stress in DKD is well-studied and is known to accelerate tubular injury. Some studies have suggested the role of the Atrial Natriuretic Peptide (ANP) in DKD. ANP is a hormone that regulates renal salt/water homeostasis and renal hemodynamics. We hypothesize that in DKD, ANP is a beneficial factor that improves proximal tubule mitochondrial function via protection from oxidative stress-induced ferroptosis. Methods: Using male ANP knock-out (SS NPPA-/- ) and wild-type (SS WT ) rats on the Dahl SS background, T1DKD was induced by streptozotocin (STZ; 75mg/kg) at 9-10 weeks of age. Baseline, midpoint, and endpoint blood glucose, urine, and body weights were collected. Western blotting was done on isolated cortical tissue and tissue fibrosis was measured in PicroSirius Red staining. ANOVA through Origin 2019b was used for comparisons. Results: STZ- SS WT and STZ-SS NPPA-/- groups exhibited similar body weight (231.7 ± 14.8 vs. 230.9 ± 8.4 g, respectively), two-kidney weight to body weight ratio (31.8 ± 0.9 vs. 28.4 ± 1.5 mg/g), and endpoint hyperglycemia (with blood glucose levels &gt;650 mg/dL). Both, STZ- SS WT and STZ-SS NPPA-/- groups had high diuresis (59.9 ± 3.1 vs. 52.7 ± 3.2 mL/24hr/100gTBW). Histological analysis revealed elevated cortical fibrosis in the STZ-SS NPPA-/- compared to STZ- SS WT (4.6 ± 0.2 vs. 3.1 ± 0.2 % area, respectively, p&lt;0.05). Moreover, in the kidney cortex, STZ-SS NPPA-/- rats compared to STZ- SS WT rats exhibit a significant increase in OXPHOS complexes IV and V (p&lt;0.05) and a decrease in glutathione peroxidase 4 (GPX4; a core regulator of ferroptosis) abundance (1.5 ± 0.2 vs. 1.9 ± 0.1 a.u., respectively, p&lt;0.05). Conclusion: Data showed that lack of ANP may promote DKD-related tubulointerstitial fibrosis and suggested a relationship with renal cortical mitochondrial function. Future studies will provide mechanistic insight into the role of ANP in mito-related oxidative stress and further assess the role of ANP in PT ferroptosis.

Robust support function machines for set-valued data classification

Support function machines (SFMs) have been proposed to handle set-valued data, but they are sensitive to outliers and unstable for re-sampling due to the use of the hinge loss function. To address these problems, we propose a robust SFM model with proximity functions. We first define a family of proximity functions that are used to convert set-valued data into continuous functions in a Banach space, and then we use the margin maximization in a Banach space to construct the pinball SFMs (PinSFMs). We study some properties of the proposed model, and it is interesting to observe that the optimal measure of the proposed model has a specific representation under the total variation norm. Using the representation of the optimal measure, we convert an infinite-dimensional optimization problem into a finite-dimensional optimization problem. Unlike SFMs, we employ a sampling strategy to tackle the finite-dimensional optimization problem. We theoretically show that the sparse solution determines the sparsity of the sampling points though the sampling strategy causes uncertainty for the sampling points. In addition, we achieve kernel versions of proximity functions, and the attractive property of this kernelization is that the proposed model is convex even if indefinite kernels are employed. Experiments on a series of data sets are performed to demonstrate that the proposed model is superior to some existing models in the presence of outliers.

Fabrication of Nephrotoxic Model by Kidney-on-a-Chip Implementing Renal Proximal Tubular Function In Vitro

Fabrication of Nephrotoxic Model by Kidney-on-a-Chip Implementing Renal Proximal Tubular Function In Vitro

A planar bisection strategy for multipoint path synthesis of four-bar linkages

In order to improve the global search ability of the optimization algorithm when solving the path synthesis problem, this paper proposes a synthesis method of a four-bar mechanism based on the bisection strategy of the Lévy-PSO evolutionary algorithm. First, a synthesis equation of the target point is established based on the closed-loop vector method. Use the bisection strategy to cut the hinge coordinate variation range to reduce the probability of premature maturity of the algorithm. The error algorithm of the circular proximity function is used to reduce the search dimension of the optimization algorithm and improve search efficiency. Use the improved particle swarm algorithm based on Lévy to improve global search capabilities. Four multi-point path synthesis problem examples are given to verify the effectiveness and accuracy of the method.