Correct Function Research Articles

Mechanical Design and Testing of Mobile Monitoring Units for Security Systems

Mobile monitoring systems are currently used in many applications related to environmental applications or the monitoring of health status. However, security monitoring systems are usually chosen for a specific object, area or perimeter. The main goal of our article is to present the mechanical design of mobile monitoring units. These units create the basis of a developed mobile monitoring security system, which can be applied to monitor any area of interest, even in demanding weather conditions, involving, for example, windiness or wide operational temperature ranges. Therefore, this article is focused on the mechanical design of mobile monitoring units, which are constructed not only so that they can withstand challenging environmental conditions, but also with regard to their simple transportation, manufacturing process and, if necessary, possible repairs. During the design, emphasis was also placed on the vibrations of the mobile monitoring units and their temperature dependence, because vibrations can significantly affect the correct functioning of the mobile monitoring security system and cause false alarm situations. To confirm the correctness of the simulation models, experiments were performed on the mobile monitoring unit prototypes.

Two Different Brain Injury Patterns Associated with Compound Heterozygosis of the PIGO Gene in a Term Newborn: A Case Report

The glycosylphosphatidylinositol (GPI) is a glycol–lipid that anchors several proteins to the cell surface. The GPI-anchor pathway is crucial for the correct function of proteins involved in cell function, and it is fundamental in early neurogenesis and neural development. The PIG gene family is a group of genes involved in this pathway with six genes identified so far, and defects in these genes are associated with a rare inborn metabolic disorder manifesting with a spectrum of clinical phenotypes in newborns and children. Among them, the PIGO gene encodes for phosphatidylinositol glycan anchor biosynthesis class O protein (PIGO), an enzyme participating in this cascade, and the loss of its function often leads to a severe clinical picture characterized by global developmental delay, seizures, Hirschsprung disease, and other congenital malformations. To date, 19 patients with confirmed PIGO deficiency have been described in the literature with a host of clinical and radiological manifestations. We report a case of a male term newborn with two compound heterozygous variants of the PIGO genes, presenting with encephalopathy, drug-resistant epilepsy, and gastrointestinal abnormalities. Brain MRI first showed diffusion restriction in the ponto-medullary tegmentum, ventral mesencephalon, superior cerebellar peduncles, cerebral peduncles, and globi pallidi. This pattern of lesion distribution has been described as part of the neuroradiological spectrum of PIG genes-related disorders. However, after one month of life, he also showed a previously undescribed MRI pattern characterized by extensive cortical and subcortical involvement of the brain hemispheres. The presence of two different mutations in both the PIGO genes may have been responsible for the particularly severe clinical picture and worse outcome, leading to the death of the newborn in the sixth month of life despite therapeutic attempts. This case expands the neuroradiological spectrum and may bring new insights on glycosylation-related disorders brain manifestations.

Digital twin dynamic force-thermal physics sub-cell for CFRP drilling process

The digital transformation of cutting processes is anticipated to advance digital twin (DT) automated machining, particularly for difficult-to-cut materials. This paper develops a dynamic physical sub-cell for the CFRP drilling process, facilitating real-time force-thermal analysis during tool degradation and enhancing DT machining technology. A comprehensive dynamic model was developed to account for force-thermal effects as the tool wears. This model included five correction functions that consider the wear characteristics of the drill bit, allowing the improved cutting force model to track the dynamic force trajectory accurately. The finite difference method was employed to analyze drilling temperature and heat accumulation, with the heat source generated by the cutting force. The heat source intensity was determined by the heat generation efficiency function. Furthermore, the cutting force at the exit was calculated, as the exit temperature alters the material's thermal properties at the entrance. Taking experimental data from 100 holes at each feed rate as a baseline, optimization algorithms determined the values of each correction coefficient within the comprehensive model. The model's validity was verified by comparing experimental results, showing average errors of 5.14N for thrust, 0.0165N·m for torque, and 7.04°C for temperature. This model was packaged as a dynamic physical sub-cell demo, which can be integrated into a DT machining system for rapid response to multifaceted force-thermal attributes.

Targeted delivery of a selenium-sulfa compound via cationic starch microparticles: Modulation of oxidative stress and pain pathways in fibromyalgia-like symptoms in mice

Cationic starch microparticles (CStMPs) loaded with 4-amino-3 -(phenylselenyl)benzenesulfonamide (4-APSB) were prepared and investigated in a model of fibromyalgia (FM) induced by intermittent cold stress (ICS) in male and female Swiss mice. The CStMPs/4-APSB were characterized by Fourier transform infrared (FTIR) spectroscopy, scanning electron microscopy (SEM), energy-dispersive X-ray (EDX) spectroscopy, zeta potential, and particle size measurements, providing information about their chemical composition, surface charge, morphology/microstructure, and size (1.50 ± 0.5 μm). Following ICS exposure, the animals were treated with free 4-APSB (1 mg/kg), CStMPs/4-APSB (containing 0.13 mg of 4-APSB per mg of microparticles), or CStMPs, from days 5 to 10. The results revealed the successful incorporation of 4-APBS in the CStMPs. Free 4-APSB and CStMPs/4-APSB reversed nociceptive- and depressive-related behaviors in male and female mice exposed to ICS, attenuating the hallmark symptoms of FM. Those treatments (free 4-APSB and CStMPs/4-APSB) normalized the monoamine oxidase (MAO)-A activity in the cerebral cortex and the oxidative damage, providing the correct functioning of the enzyme Ca2+ -ATPase in the cerebral cortex and hippocampus of mice exposed to ICS. The CStMPs/4-APSB modulated the oxidative stress markers, specifically in the spinal cord of mice - an anatomical region intricately linked to pain pathways.

Thyroid Disorders in Patients with Polycystic Ovarian Syndrome in a Tertiary Care Center: An Observational study

Introduction: Polycystic ovarian syndrome is the most common endocrine and metabolic disorder in women of childbearing age, affecting 3–15% of women worldwide, leading to reproductive, metabolic, and psychological issues. Patients with polycystic ovarian syndrome require rigorous thyroid function detection, monitoring, and correction over time. In this study, we aimed to evaluate the clinical presentations and thyroid dysfunction in patients with polycystic ovarian syndrome.Methods: An observational study was done in patients with polycystic ovarian disease presenting to a tertiary care centre over six months, from December 2023 to May 2024 Total population sampling was done. All the women during the study period diagnosed with polycystic ovarian disease based on Rotterdam criteria were included in the study after getting ethical approval from the institutional review board. (Reference number: 20102023/03).Results: The mean age of women in the study was 24.74±5.01 years. A total of 28 (31.46%) patients of polycystic ovarian disease had hyperthyriodism, hypothyroidism was found in 13 (14.60%) and subclinical hypothyroidism was found in 6 (6.74%) patients. All the women had menstrual irregularities. Regarding androgenic characteristics, 53 (59.55%) of patients presented with hirsutism, 43 (48.51%) presented with acne, 13 (14.61%) women had alopecia, and 4 (4.49%) women had acanthosis.Conclusions: Hyperthyroidism, hypothyroidism and subclinical hypothyroidism were prevalent in polycystic ovarian disease patients, emphasizing the need for thorough thyroid evaluation in polycystic ovarian disease patients due to its impact on metabolic and reproductive health. High rates of menstrual irregularities, androgenic symptoms like hirsutism and acne, and fertility challenges were also prevalent, aligning with findings from similar studies.

Belief game: Verifying smart contract functionality in player dynamic interactions

Smart contracts, being security-critical code, facilitate consensus among players and ensure secure and accurate value transfer, and formal verification is necessary to guarantee functional correctness of contracts. Game theory serves as one of the tools in formal verification by assessing whether the outcomes of contract executions meet the expected goals. While most studies employing game theory to verify smart contract functionality assume rational players, in practice, players may invoke and deploy smart contracts involving irrational behavior, casting doubt on the correctness of verification results. The aim of this study is to propose an alternative game model to verify smart contract functionality in dynamic player interactions where irrational behavior is involved. Specifically, a belief-based smart contract execution game (BSC-game) model was introduced, utilizing belief – the probability that a player believes in the irrationality of others – to capture how the irrational behavior of others affects a player’s contract execution decisions. Reasonable economic incentives were introduced to encourage honest behavior of players. Moreover, a computationally feasible method was designed to update players’ beliefs in large-scale dynamic smart contract executions. Theoretical analysis discloses the existence of equilibrium in the BSC-game, as well as the conditions for the number of faulty players within the system’s fault tolerance. We conducted the simulation experiments, and verified the business-oriented smart contract written in G language by the BSC-game model. The results further indicate that although players’ beliefs impact their decisions to execute contracts, reasonable economic incentives can motivate players to execute contracts honestly. This ensures that smart contract functionality aligns with expected goals, showing that the BSC-game model can verify and guarantee the correctness of contract functions. This new approach significantly contributes to bolstering smart contract security and credibility, positively influencing blockchain stability.

Epigenetic Drift Is Involved in the Efficacy of HBV Vaccination

Background/Objectives: HBV infections can lead to serious liver complications that can have fatal consequences. In 2022, around 1.1 million individuals died from HBV-related cirrhosis and hepatocellular carcinoma. Vaccines allow us to save more than 2.5 million lives each year; however, up to 10% of vaccinated individuals may not develop sufficient protective antibody levels. The aim of this study was to investigate the epigenetic drift in the response to HBV vaccine in isolated B cells. Methods: Epigenetic drift was measured by counting rare DNA methylation variants. These epivariants were detected in epigenome-wide data collected from isolated B cell samples from 41 responders and 30 non-responders (age range 22–62 years) to vaccination against HBV. Results: We found an accumulation of epivariants in the NR group, with a significant increase in hyper-methylated aberrations. We identified the chromosomes (1, 3, 11, 12, and 14) and genes (e.g., RUSC1_AS1 or TROVE2) particularly enriched in epivariants in NRs. The literature search and pathway analysis indicate that such genes are involved in the correct functioning of the immune system. Moreover, we observed a correlation between epigenetic drift and DNA methylation entropy in the male population of the cohort. Finally, we confirmed the correlation between epivariant loads and age-related epigenetic clocks. Conclusions: Our findings support the idea that an age-related derangement of the epigenetic architecture is involved in unresponsiveness to the HBV vaccine. Furthermore, the overall results highlight the interconnection between various epigenetic dynamics (such as drift, clocks, and entropy), although these interconnections seem not to be involved in the altered immunological activity.

Variable-structure trajectory correction control of small-caliber ammunition based on cascade fuzzy active disturbance rejection

In this study, a low-cost two-dimensional (2D) trajectory correction mechanism is proposed to address the large trajectory deviation of small-caliber extended-range ammunitions. By controlling the projectile’s roll, a single-channel 2D trajectory correction function can be realized. Moreover, based on the ideal trajectory, a five-degree-of-freedom approximate rigid-body trajectory equation is proposed. A high-order system is transformed into two low-order cascading subsystems using fuzzy control and the self-disturbance rejection control theory, which reduces the parameter tuning complexity. The entire control process is divided into three stages which realizes the second-order variable structure control of non-affine nonlinear subsystems. A low-altitude atmospheric disturbance model is established, and as an example, numerical calculations are performed on the control process and projectile impact point dispersion of a 35 mm small-caliber rocket. The results verify the performance of the proposed trajectory correction under atmospheric disturbances. This study provides a control approach for coupled underactuated nonlinear systems and provides guidance for the design of a low-cost 2D trajectory correction controller for small-caliber ammunitions.

A robust dipole moment of carbon monoxide (CO) is a permanent puzzle for both spectroscopic and ab initio studies

The asymptotically correct semi-empirical dipole moment function (DMF) for the ground X 1 Σ + state of the CO molecule was redetermined in an analytical form for the entire range of interatomic distances r ∈ [ 0 , + ∞ ] by a global least-squared fitting both experimental intensities and ab initio data. The region r ∈ [ 0.8 , 1.9 ] Å that is governed exclusively by the empirical data was broadened by adding experimental relative intensity ratios measured in the emission from high vibrational levels v. Absolute absorption intensities recently obtained for very high 7-0 overtone and accompanied sub-percent measurements for 3-0 band were also included in the fitting procedure. The present DMF reproduces a vast majority of the experimental intensities up to v ≤ 38 within accuracy of measurements, except ‘abnormally’ sensitive 5-0 band, and systematically overestimates the most previous ab initio and semi-empirical functions at r ≥ 1.5 Å . Possible reasons of the observed discrepancies are throughout discussed. The resulting DMF can be used, along with mass-invariant interatomic potential, to upgrade rovibrational line lists for any isotopologues of the CO molecule up to the dissociation threshold. The corresponding FORTRAN subroutine is provided.

Exploring Cationic Substitutions in the Solid Electrolyte NaAlCl4 with Density Functional Theory.

NaAlCl4 is an established solid electrolyte in high-temperature Na-based battery systems, but its ionic conductivity is not sufficiently high for room-temperature applications. We employ density functional theory and thermodynamic corrections to evaluate the efficacy of various elements for substitution, utilizing on-the-fly machine-learned potentials to accelerate the required phonon calculations by 1 order of magnitude at a minor error of -0.7 ± 1.0 meV/atom. All investigated isovalent substitutions are favorable within 4 meV/atom, with potassium and silver as substitutes for sodium and gallium as a substitute for aluminum. The most promising aliovalent substitution was identified for Zn on the tieline between NaAlCl4 and Na2ZnCl4. The structure of latter, with aluminum ions replacing zinc, yields a structure with separate layers for the differently charged cations and vacancies for potential Na conduction. Our investigation may pave the way for more reliable discovery of new Na conductors by inclusion of thermodynamic properties.

Our resolutions and their causes: Twardowski on free will in ethical and legal contexts

AbstractThe paper aimed to reconstruct Twardowski's approach to the problem of free will and his analyses of the consequences of various solutions to this problem in ethics and criminal law. According to Twardowski, if we understand ‘free will’ as the possibility of making resolutions other than actually made, then (most probably) nobody has free will. Our resolutions are determined by a set of mental dispositions (character) and incentives that activate these dispositions. However, the existence of freedom of will such understood is not a necessary condition for the correct functioning of ethical systems or criminal law. On the contrary, ethical systems and criminal law seem to assume that at least some of our resolutions are determined by our relatively stable dispositions. Only then can these resolutions and the actions that follow them be ascribed to certain agents. Twardowski's views on free will are presented here in the context of the metaphilosophical positions of the Lvov–Warsaw School, the central European branch of analytic philosophy. His position is also juxtaposed with Brentano's view of free will and Łukasiewicz's approach to the determinism/indeterminism debate. This juxtaposition illustrates the variety of philosophical positions and the diversity of the metaphilosophical toolkit applied in early analytic philosophy.

Spectral correction of photovoltaic module electrical properties

Except for irradiance and temperature, the distribution of solar spectrum also affects the electrical performance of photovoltaic (PV) modules. To explore the effect, this study conducted long-term experimental measurements on the wide range of full solar radiation spectrum with monocrystalline silicon (m-Si) and cadmium telluride (CdTe), and established new spectral correction function (SCF) under horizontal conditions based on the average photon energy (APE). It is verified with a good agreement R2 of 0.95, and the maximum RMSE is only 0.017 %. Moreover, the application of the SCFs to building vertical façade has also been well verified, and the accuracy of electrical performance prediction can be improved by 14.51 % (m-Si) and 3.57 % (CdTe). In addition, this study combines the annual horizontal total solar radiation spectrum in Beijing and gives the annual spectral gain and loss (SGL) ratio of two PV panels. The power generation performance of the two PV modules under the actual spectrum will be underestimated for about 53.5 % and 99.7 % of the time in the whole year. This study broadens the dimension of evaluating the electrical performance parameters of PV panels and provides a basis and guidance for the accurate prediction and calculation of photovoltaic power generation.

PECULIARITIES OF ORTHODONTIC TREATMENT FOR PATIENTS WITH GENERALIZED PERIODONTITIS AND PREDOMINANCE OF PARASYMPATHETIC NERVOUS SYSTEM ACTIVITY

The use of orthodontic treatment for patients with generalized periodontitis enhances the effectiveness of comprehensive care. However, it is important to consider the reduced capacity for alveolar bone regeneration in these patients. Therefore, as part of the complex treatment of generalized periodontitis, the inclusion of medications to support alveolar bone regeneration is essential. The course of various diseases can be influenced by the state of the patient’s autonomic nervous system. In this study, medications were administered to normalize parasympathetic nervous system activity in patients with generalized periodontitis undergoing orthodontic treatment. The objective of the study was to evaluate the effectiveness of orthodontic treatment in patients with generalized periodontitis, particularly those with a predominance of parasympathetic autonomic nervous system activity. This was assessed by the supplementary use of a combination of drugs designed to stimulate alveolar bone formation and regulate parasympathetic nervous system function. Materials and methods. This study involved 35 young patients (aged 18-35) with generalized periodontitis and a predominance of parasympathetic autonomic nervous system activity, all of whom presented with displacement of the maxillary frontal teeth. These patients underwent orthodontic treatment. To correct the state of the autonomic nervous system over the treatment of generalized periodontitis, patients were prescribed to take a complex of medicines including the preparation “Calcinova” for stimulating osteogenesis. A comprehensive periodontal examination, including the assessment of hygienic indices, was conducted to evaluate periodontal status throughout the treatment. Results. The periodontal examination revealed that almost all patients demonstated an improvement in oral health. Noticeable dynamics in the pathological process were observed as a result of the complex treatment. The analysis of these findings underscores the importance of orthodontic treatment for patients with generalized periodontitis, particularly when combined with methods to correct parasympathetic nervous system activity and promote osteogenesis. This approach was shown to positively affect periodontal tissues and enhance the effectiveness of generalized periodontitis treatment. Conclusions. Correction of parasympathetic autonomic nervous system function enhances the effectiveness of therapy. In this study, a complex of medications was used to improve parasympathetic nervous system activity. The addition of “Calcinova” to stimulate osteogenesis further contributed to achieving more stable treatment outcomes in patients with generalized periodontitis.

Software Development Process Considerations in GNSS-Denied Navigation Project for Drones

This article will discuss the software development process utilised in the GNSS-denied navigation project targeted for drones. The process was implemented in an environment where software developers were oriented to developing a source code only and who showed great reluctance to follow any formal process. The mentioned process was a lightweight AGILE-based process that, by assumption, minimised developers’ engagement in activities other than those related to the source code development. The process described in this paper was designed to support and reflect product quality characteristics like functional completeness and correctness, time behaviour, resource utilisation, analysability, modifiability and testability in an “implicit” way. It allowed the developers to achieve those characteristics in an “invisible” manner. This allowed us to achieve acceptable product quality without needing to engage experienced architects. The described process needs improvements and extensions to satisfy certification needs. However, for the prototyping or research phases, it may be a perfect solution for facilitating future product modifications and saving costs. The process improves product quality by underlying the value of transparency, performing specific actions and incorporating specific attributes related to team tasks. This research also focused on finding a metric related to process acceptance in a given environment, resulting in a three-degree scale showing whether the process needed improvements or was accepted by the environment. Such a metric is a new finding and the metric implies that there are some factors that stand behind any process, which determine whether it will be friendly to the environment (people with their habits, work style, personal traits, etc.) or not. However, investigating factors that determine the process acceptance and that are connected to the environment traits were beyond the scope of this research and will be considered in the future.

LINGUISTIC AND DIDACTIC BASIS FOR THE DEVELOPMENT OF FUTURE DOCTORSʼ SPEAKING COMPETENCY

The article defines the content of the concept of “future doctorʼs speech competence” as an integral quality of a medical student, which is manifested in the general ability and readiness to use language means, the laws of their functioning for the construction and understanding of speech utterances in the context of professional activity of doctors; the linguodidactic principles of development of future doctorsʼ speech competence are substantiated. These include the laws of mother tongue acquisition that contribute to the intensive development of communicative and linguistic skills; general didactic and specific principles that determine the direction in the development of means of developing linguistic skills; forms, methods and techniques that correspond to the main forms of work in higher education; teaching aids, the use of which affects the effectiveness of the content of education. It is noted that the development of future doctorsʼ speech competence can be carried out using the following methods of language teaching: oral presentation by the teacher (narration, explanation, lecture), conversation, work with a textbook, observation and analysis of language phenomena, exercise method, programmed learning and interactive methods. The following interactive learning methods have become valuable for the development of medical students’ language competence: work in small groups, imitation, simulation, discussion, microphone, talk shows, rotating groups. All these methods combine into one whole the activities of the teacher and students, which are aimed at improving language knowledge, developing communicative and speech skills, allow to manage studentsʼ cognitive activity productively and realize educational, educational, developmental, motivational, control and correctional functions of learning in a higher education institution

The influence of continuum lowering on the equilibrium composition of plasma: case study of laser-induced plasma on a WC–Cu target

Abstract Composition of plasma obtained by laser ablation of cermet WC-Cu is calculated under the assumption of local thermodynamical equilibrium. Special attention is paid to the effect of lowering the ionization potential, the influence of which in the Saha equations is reflected both through the exponential Boltzmann term and through the partition functions of atomic and ionic species present in the plasma. The effect on these two terms are separated and quantified. It has been shown that the correction of the partition functions due to the reduction of the ionization potential is of greater importance than the correction of Boltzmann term, at higher temperatures for atomic species. It is thus necessary for the precise determination of the plasma composition, especially at higher temperatures. The effect of lowering the ionization potential on different types of atoms as well as on different ionic states is analyzed. Тhe change of the partition function due to the lowering of ionization energy affects also the concentration of single charged ions in an amount comparable to the correction of the Boltzmann term.

Discretely nonlinearly stable weight-adjusted flux reconstruction high-order method for compressible flows on curvilinear grids

To achieve genuine predictive capability, an algorithm must consistently deliver accurate results over prolonged temporal integration periods, avoiding the unwarranted growth of aliasing errors that compromise the discrete solution. Provable nonlinear stability bounds the discrete approximation and ensures that the discretization does not diverge. Nonlinear stability is accomplished by satisfying a secondary conservation law, namely for compressible flows; the second law of thermodynamics. For high-order methods, discrete nonlinear stability and entropy stability, have been successfully implemented for discontinuous Galerkin (DG) and residual distribution schemes, where the stability proofs depend on properties of L2-norms. In this paper, nonlinearly stable flux reconstruction (NSFR) schemes are developed for three-dimensional compressible flow in curvilinear coordinates. NSFR is derived by merging the energy stable flux reconstruction (ESFR) framework with entropy stable DG schemes. NSFR is demonstrated to use larger time-steps than DG due to the ESFR correction functions, at the cost of larger error levels at design order convergence for equivalent degrees of freedom, while preserving discrete nonlinear stability. NSFR differs from ESFR schemes in the literature since it incorporates the FR correction functions on the volume terms through the use of a modified mass matrix. We also prove that discrete kinetic energy stability cannot be preserved to machine precision for quadrature rules where the surface quadrature is not a subset of the volume quadrature. This result stems from the inverse mapping from the kinetic energy variables to the conservative variables not existing for the kinetic energy projected variables. This paper also presents the NSFR modified mass matrix in a weight-adjusted form. This form reduces the computational cost in curvilinear coordinates because the dense matrix inversion is approximated by a pre-computed projection operator and the inverse of a diagonal matrix on-the-fly and exploits the tensor product basis functions to utilize sum-factorization. The nonlinear stability properties of the scheme are verified on a nonsymmetric curvilinear grid for the inviscid Taylor-Green vortex problem and the correct orders of convergence were obtained on a curvilinear mesh for a manufactured solution. Lastly, we perform a computational cost comparison between conservative DG, overintegrated DG, and our proposed entropy conserving NSFR scheme, and find that our proposed entropy conserving NSFR scheme is computationally competitive with the conservative DG scheme.

MitoMAMMAL: a genome scale model of mammalian mitochondria predicts cardiac and BAT metabolism

Abstract Motivation Mitochondria perform several essential functions in order to maintain cellular homeostasis and mitochondrial metabolism is inherently flexible to allow correct function in a wide range of tissues. Dysregulated mitochondrial metabolism can therefore affect different tissues in different ways which presents experimental challenges in understanding the pathology of mitochondrial diseases. System-level metabolic modelling is therefore useful in gaining in-depth insights into tissue-specific mitochondrial metabolism, yet despite the mouse being a common model organism used in research, there is currently no mouse specific mitochondrial metabolic model available. Results In this work, building upon the similarity between human and mouse mitochondrial metabolism, we have created mitoMammal, a genome-scale metabolic model that contains human and mouse specific gene-product reaction rules. MitoMammal is therefore able to model mouse and human mitochondrial metabolism. To demonstrate this feature, using an adapted E-Flux algorithm, we first integrated proteomic data extracted from mitochondria of isolated mouse cardiomyocytes and mouse brown adipocyte tissue. We then integrated transcriptomic data from in vitro differentiated human brown adipose cells and modelled the context specific metabolism using flux balance analysis. In all three simulations, mitoMammal made mostly accurate, and some novel predictions relating to energy metabolism in the context of cardiomyocytes and brown adipocytes. This demonstrates its usefulness in research relating to cardiac disease and diabetes in both mouse and human contexts. Availability and implementation MitoMammal is formatted in SBML3. The code required for constraint-based modelling used in this work is implemented in Python 3 and is available as a Jupyter Notebook. The mitoMammal metabolic model, along with Jupyter notebooks and data used in this work are available at: https://gitlab.com/habermann_lab/mitomammal. Supplementary Information Supplementary data are available at Bioinformatics Advances online.

Development of quantitative PET/MR imaging for measurements of hepatic portal vein input function: a phantom study

BackgroundAccurate pharmacokinetic modelling in PET necessitates measurements of an input function, which ideally is acquired non-invasively from image data. For hepatic pharmacokinetic modelling two input functions need to be considered, to account for the blood supply from the hepatic artery and portal vein. Image-derived measurements at the portal vein are challenging due to its small size and image artifacts caused by respiratory motion. In this work we seek to demonstrate, using phantom experiments, how a dedicated PET/MR protocol can tackle these challenges and potentially provide input function measurements of the portal vein in a clinical setup.MethodsA custom 3D printed PET/MR phantom was constructed to mimic the liver and portal vein. PET/MR acquisitions were made with emulated respiratory motion. The PET/MR imaging protocol consisted of high-resolution anatomical MR imaging of the portal vein, followed by a PET acquisition in parallel to a dedicated motion-tracking MR sequence. Motion tracking and deformation information were extracted from PET data and subsequently used in PET reconstruction to produce dynamic series of motion-free PET images. Anatomical MR images were used post PET reconstruction for partial volume correction of the input function measurements.ResultsReconstruction of dynamic PET data with motion-compensation provided nearly motion-free series of PET frame data, suitable for image derived input function measurements of the portal vein. After partial volume correction, the individual input function measurements were within a 16.1% error range from the true activity in the portal vein compartment at the time of PET acquisition.ConclusionThe proposed protocol demonstrates clinically feasible PET/MR imaging of the liver for pharmacokinetic studies with accurate quantification of the portal vein input function, including correction for respiratory motion and partial volume effects.

Outcomes in hematopoetic cell transplantation in the setting of mold infections in patients with chronic granulomatous disease.

Chronic granulomatous disease (CGD) is a disorder of immunity characterized by phagocyte dysfunction. Mold infections in patients with CGD are often severe and disseminated. We present patient characteristics, microbiological data, and outcomes for 26 patients with CGD who received hematopoietic cell transplantation (HCT) or gene therapy-modified cells (GT) between 2008 and 2019, with proven fungal infection either before or during their transplant. All patients engrafted, and all but one GT recipient had neutrophil recovery and evidence of functional correction. Eighteen patients (69%) are currently alive and 19 patients (73% of total, 90% of patients with repeat imaging performed) had evidence of radiographic improvement. With 3 exceptions, deaths were not principally related to the fungal infection and duration of antecedent infection did not correlate with death. Aspergillus species accounted for the majority of disease (50%), followed by Phellinus species (18%). Osteomyelitis and disseminated disease were common, as only 11 patients (42%) had disease restricted to pneumonia. Triazole therapy was used in all 26 patients, with combination therapy used in 25 (96%). HCT or gene therapy, with appropriate antifungal therapy, are viable therapies for refractory fungal infections in patients with CGD.