Midwest Institute for Minimally Invasive Therapies

Microkinetic models are key for evaluating industrial processes' efficiency and chemicals' environmental impact. Manual construction of these models is difficult and time-consuming, prompting a shift to automated methods. This study introduces SiMBA (Simplest Mechanism Builder Algorithm), a novel approach for generating microkinetic models from kinetic data. SiMBA operates through four phases: mechanism generation, mechanism translation, parameter estimation, and model comparison. Our approach systematically proposes reaction mechanisms, using matrix representations and a parallelized backtracking algorithm to manage complexity. These mechanisms are then translated into microkinetic models represented by ordinary differential equations, and optimized to fit available data. Models are compared using information criteria to balance accuracy and complexity, iterating until convergence to an optimal model is reached. Case studies on an aldol condensation reaction, and the dehydration of fructose demonstrate SiMBA's effectiveness in distilling complex kinetic behaviors into simple yet accurate models. While SiMBA predicts intermediates correctly for all case studies, it does not chemically identify intermediates, requiring expert input for complex systems. Despite this, SiMBA significantly enhances mechanistic exploration, offering a robust initial mechanism that accelerates the development and modeling of chemical processes.

The industrialization of catalytic processes requires reliable kinetic models for their design, optimization and control. Mechanistic models require significant domain knowledge, while data-driven and hybrid models lack interpretability. Automated knowledge discovery methods, such as ALAMO (Automated Learning of Algebraic Models for Optimization), SINDy (Sparse Identification of Nonlinear Dynamics), and genetic programming, have gained popularity but suffer from limitations such as needing model structure assumptions, exhibiting poor scalability, and displaying sensitivity to noise. To overcome these challenges, we propose two methodological frameworks, ADoK-S and ADoK-W (Automated Discovery of Kinetic rate models using a Strong/Weak formulation of symbolic regression), for the automated generation of catalytic kinetic models using a robust criterion for model selection. We leverage genetic programming for model generation and a sequential optimization routine for model refinement. The frameworks are tested against three case studies of increasing complexity, demonstrating their ability to retrieve the underlying kinetic rate model with limited noisy data from the catalytic systems, showcasing their potential for chemical reaction engineering applications.

Abstract Heart failure (HF) with preserved ejection fraction (HFpEF) represents a major unmet medical need owing to its diverse pathophysiology and lack of effective therapies. Potent synthetic, agonists (MR-356 and MR409) of growth hormone-releasing hormone (GHRH) improve the phenotype of models of HF with reduced ejection fraction (HFrEF) and in cardiorenal models of HFpEF. Endogenous GHRH exhibits a broad range of regulatory influences in the cardiovascular (CV) system, aging and plays a role in several cardiometabolic conditions including obesity and diabetes. Whether agonists of GHRH can improve the phenotype of cardiometabolic HFpEF remains untested and unknown. Here we tested the hypothesis that MR-356 can mitigate/reverse the cardiometabolic HFpEF phenotype. C57BL6N mice received a high fat diet (HFD) plus the nitric oxide synthase inhibitor (L-NAME) for 9 weeks. After 5 weeks of HFD+L-NAME regimen, animals were randomized to receive daily injections of MR-356 or placebo during a 4-week period. Control animals received no HFD+L-NAME or agonist treatment. Our results showed the unique potential of MR-356 to treat several HFpEF-like features including cardiac hypertrophy, fibrosis, capillary rarefaction, and pulmonary congestion. MR-356 improved cardiac performance by improving diastolic function, global longitudinal strain (GLS), and exercise capacity. Importantly, the increased expression of cardiac pro-brain natriuretic peptide (pro-BNP), inducible nitric oxide synthase (iNOS) and vascular endothelial growth factor-A (VEGF-A) was restored to normal levels suggesting that MR-356 reduced myocardial stress associated with metabolic inflammation in HFpEF. Thus, agonists of GHRH may be an effective therapeutic strategy for the treatment of cardiometabolic HFpEF phenotype.

An analysis of an oscillatory magnetohydrodynamic (MHD) convective flow of a second order (viscoelastic), incompressible, and electrically conducting fluid through a porous medium bounded by two infinite vertical parallel porous plates is presented. The two porous plates with slip-flow condition and the no-slip condition are subjected respectively to a constant injection and suction velocity. The pressure gradient in the channel varies periodically with time. A magnetic field of uniform strength is applied in the direction perpendicular to the planes of the plates. The induced magnetic field is neglected due to the assumption of a small magnetic Reynolds number. The temperature of the plate with no-slip condition is non-uniform and oscillates periodically with time and the temperature difference of the two plates is assumed high enough to induce heat radiation. The entire system rotates in unison about the axis perpendicular to the planes of the plates. Adopting complex variable notations, a closed form solution of the problem is obtained. The analytical results are evaluated numerically and then presented graphically to discuss in detail the effects of different parameters of the problem. The velocity, temperature and the skin-friction in terms of its amplitude and phase angle have been shown graphically to observe the effects of the viscoelastic parameter γ, rotation parameter Ω, suction parameter λ , Grashof number Gr, Hartmann number M, the pressure A, Prandtl number Pr, radiation parameter N and the frequency of oscillation ω .

The aim of this study is to establish optimum machining conditions for EDSG of AISI D2 die steel through an experimental investigation using Taguchi Methodology. To achieve combined grinding and electrical discharge machining, metal matrix composite electrodes (Cu-SiCp) were processed through powder metallurgy route. A rotary spindle attachment was developed to perform the EDSG experimental runs on EDM machine. Relationships were developed between various input parameters such as peak current, speed, pulse-on time, pulse-off time, abrasive particle size, and abrasive particle concentration, and output characteristics such as material removal rate and surface roughness. The optimized parameters were further validated by conducting confirmation experiments.

Oribasius was an eminent Byzantine physician who lived in the fourth century. His greatest contribution to medical history was his anthology of all important medical works of his time, entitled Synagogue Medicae. This complete medical encyclopedia of his era consisted of more than 70 volumes. A significant part of this work has been lost. What remains, however, allows us to glimpse the surprising richness and knowledge of ancient medicine. Chapters 25 and 26 of the original 42nd book of Oribasius are of specific interest to the plastic surgeon, because they deal with reconstruction of facial defects. Reconstructive procedures for defects in the eyebrows, forehead, cheeks, nose, and ears are described. Advancement flaps are suggested for the reconstruction, and recommendations are made about debridement, flap design, and thickness of flaps. It becomes obvious from these texts that Greek, Roman, and Byzantine surgeons had the knowledge and experience to perform several reconstructive procedures of the face and nose. This knowledge was passed to the Arabs and then to Western Europe in the 15th century and became part of the foundation for modern plastic surgery.

The goals of any treatment for ischemic vascular disease are to relieve pain, allow wound healing, and regain/maintain ambulatory abilities. To determine if endovascular therapy could accomplish these goals in patients with limbs at risk, we undertook a retrospective analysis of the results of percutaneous transluminal angioplasty (PTA) and thrombolysis in leg salvage. Over an 8-year period ending in 1993, 327 patients (209 males, 118 females) with limb-threatening ischemia (defined as one or more of the following: ischemic rest pain, ischemic ulceration, or gangrene) in 361 limbs were seen. These patients had an ankle-brachial index < or = 0.40 in nondiabetic patients and/or toe-brachial index < or = 0.30 in diabetic patients. The patients were treated with thrombolysis and/or PTA according to standard techniques; intravascular stenting was used occasionally as required to treat PTA deficiencies or inadequate recanalization. Among the 327 patients, 805 arteries and 25 thrombosed arterial grafts were treated. The arteries treated were: 6 aorta (0.75%), 75 iliac (9.3%), 34 common femoral (4.2%), 3 deep femoral (0.4%), 235 superficial femoral (29.2%), 219 popliteal (27.2%), 193 infrapopliteal (24.0%), and 40 pedal (5.0%). The patients were treated primarily with PTA (n = 307); urokinase thrombolysis (n = 99) and stents (n = 12) were used less frequently. Procedural success was 92.5%. Patients were followed from 6 months to 8 years (mean 3 years). Eighty-three patients were retreated during this time. Of the 249 patients available for this follow-up, total salvage was achieved in 181 (72.7%). Nineteen patients (7.6%) underwent minor amputations (e.g., toes); 4 patients (1.6%) had transmetatarsal amputation. Fifteen patients (3.6%) had above-knee amputation despite successful recanalization. In all, 32 patients (8.8%) had the amputation level extended from above to below knee, bringing the total leg salvage rate to 82% (defined as patients able to ambulate without any prosthesis). Using life-table analysis, the 5 year survival rate was 71%. This study shows that endovascular therapy for leg salvage is as effective as reconstructive vascular surgery in achieving wound healing and maintaining ambulation and has a more favorable 5-year survival rate.