Miracle-dz/UniFAR-FTUs huggingface dataset:
Mechanistic, Functional, and Clinical Aspects of Pro‐inflammatory Cytokine Mediated Regulation of ADME Gene Expression in 3D Human Liver Spheroids

During systemic inflammation, pro‐inflammatory cytokines alter metabolism and transport of drugs affecting the clinical outcome. We used an in vivo like human 3D liver spheroid model to study the effects and mechanisms of pro‐inflammatory cytokines on the expression of 9 different genes encoding enzymes responsible for the metabolism of > 90% of clinically used drugs. Treatment of spheroids with pathophysiologically relevant concentrations of IL‐1β, IL‐6, or TNFα resulted in a pronounced decrease in mRNA expression of CYP3A4 and UGT2B10 within 5 hours. The reduction of CYP1A2, CYP2C9, CYP2C19, and CYP2D6 mRNA expression was less pronounced, whereas the pro‐inflammatory cytokines caused increased CYP2E1, and UGT1A3 mRNA expression. The cytokines did not influence expression of key nuclear proteins, nor the activities of specific kinases involved in the regulation of genes encoding drug metabolizing enzymes. However, ruxolitinib, a JAK1/2 inhibitor, inhibited the IL‐6 dependent increase in CYP2E1 and the decrease in CYP3A4 and UGT2B10 mRNA expression. We evaluated the effect of TNFα in hepatocytes in 2D plates and found a rapid decrease in drug‐metabolizing enzyme mRNA both in the absence or presence of the cytokines. Taken together, these data suggest that pro‐inflammatory cytokines regulate multiple gene‐ and cytokine‐specific events seen in in vivo and in 3D but not in 2D liver models. We propose that the 3D spheroid system is suitable for the prediction of drug metabolism under conditions of inflammation and constitutes a versatile system for short‐ and long‐term preclinical and mechanistic studies of cytokine‐induced changes in drug metabolism.
Quantum entropy and central limit theorem

Significance Convolution has a significant impact on many scientific disciplines, ranging from probability theory and harmonic analysis to information theory. Here, we introduce a framework to study quantum convolution in discrete-variable (DV) quantum systems. We establish a maximal entropy principle and a quantum central limit theorem for DV quantum systems. We also provide a bound on the rate of convergence in the central limit theorem that we call the magic gap. The magic gap has some similarities to the Cheeger constant in graph theory. Our convolutional framework provides an approach to study stabilizer and magic states.
Global Prevalence and Incidence of Amyotrophic Lateral Sclerosis

Background and Objectives Amyotrophic lateral sclerosis (ALS) is a rare neurodegenerative disorder affecting upper and lower motor neurons. Due to its rarity and rapidly progressive nature, studying the epidemiology of ALS is challenging, and a comprehensive picture of the global burden of this disease is lacking. The objective of this systematic review was to describe the global incidence and prevalence of ALS. Methods We searched MEDLINE, Embase, Global Health, PsycInfo, Cochrane Library, and CINAHL to identify articles published between January 1, 2010, and May 6, 2021. Studies that were population based and reported estimates of prevalence, incidence, and/or mortality of ALS were eligible for inclusion. This study focuses on the incidence and prevalence. Quality assessment was performed using a tool developed to evaluate methodology relevant to prevalence and incidence studies. This review was registered with PROSPERO, CRD42021250559. Results This search generated 6,238 articles, of which 140 were selected for data extraction and quality assessment. Of these, 85 articles reported on the incidence and 61 on the prevalence of ALS. Incidence ranged from 0.26 per 100,000 person-years in Ecuador to 23.46 per 100,000 person-years in Japan. Point prevalence ranged from 1.57 per 100,000 in Iran to 11.80 per 100,000 in the United States. Many articles identified cases with ALS from multiple data sources. Discussion There is variation in reported incidence and prevalence estimates of ALS across the world. While registries are an important and powerful tool to quantify disease burden, such resources are not available everywhere. This results in gaps in reporting of the global epidemiology of ALS, as highlighted by the degree of variation (and quality) in estimates of incidence and prevalence reported in this review.
Inverse Abel transform algorithms to determine the radial profile of the photoelastic coefficient of glass optical fibers

We compare two algorithms to determine the radial profile of the photoelastic coefficient C in glass optical fibers. We first measure the retardance profile of a transversally illuminated fiber as a function of tensile load. The radial profile C(r) is obtained from the inverse Abel transform of this retardance profile. Our first algorithm expands the measured retardance in its Fourier coefficients before computing the inverse Abel transform. With the second algorithm the expected result of the inverse Abel transform is expanded and the forward Abel transform of that expansion is compared to the measured retardance. We apply both approaches on the retardance measurement of commercially available single mode and multi-mode fibers.
The effect of experimentally induced gluteal muscle weakness on joint kinematics, reaction forces, and dynamic balance performance during deep bilateral squats

Squatting is a common daily activity and fundamental exercise in resistance training and closed kinetic chain programs. The aim of this study was to investigate the effects of an experimentally induced weakness of the gluteal muscles on joint kinematics, reactions forces (JRFs), and dynamic balance performance during deep bilateral squats in healthy young adults. Ten healthy adults received sequential blocks of (1) branch of the superior gluteal nerve to the tensor fasciae latae (SGNtfl) muscle, (2) superior gluteal nerve (SGN), and (3) inferior gluteal nerve (IGN) on the dominant right leg. At the control condition and following each block, the participants were instructed to perform deep bilateral squats standing on two force plates. Hip, knee, ankle, and pelvis kinematics did not differ significantly following iatrogenic weakness of gluteal muscles. The most important finding was the significant differences in JRFs following SGN and IGN block, with the affected hip, patellofemoral, and ankle joint demonstrating lower JRFs, whereas the contralateral joints demonstrated significantly higher JRFs, especially the patellofemoral joint which demonstrated an average maximum difference of 1.43 x body weight compared with the control condition. When performing a deep bilateral leg squat under SGN and IGN block, the subjects demonstrated an increased center of pressure (CoP) range and standard deviation (SD) in mediolateral compared with the control condition. These results imply that squat performance changes significantly following weakness of gluteal muscles and should be considered when assessing and training athletes or patients with these injuries.
Adjoint based data assimilation in compressible flows with application to pressure determination from PIV data

The analysis of complex fluid mechanical phenomena is based on experimental and numerical analysis. Both approaches provide suitable data, but no complete and exactly matching picture of a flow, which is to be examined. Experimental data are usually incomplete, because not every state variable is accessible by measurements and numerical solutions are often affected by initial and boundary conditions which do not match to the real flow conditions. To obtain a complete set of information of a real flow state, both approaches can be combined by means of data assimilation. The focus of the present thesis is the derivation and the implementation of an adjoint based data assimilation framework for compressible flows. Numerical simulations are adapted to experimental data, in order to obtain not measured quantities and other information out of the numerical solution. The derivation of the adjoint equations, their implementation and application as well as several introductory examples are presented. The data assimilation framework is validated and applied to a current problem in the field of fluid mechanics, the pressure determination from velocity data. The thesis concludes with the experimental investigation of a free jet using particle image velocimetry and the application of the data assimilation framework to determine the instantaneous pressure based on the obtained velocity fields.
HOXD‐AS2‐STAT3 feedback loop attenuates sensitivity to temozolomide in glioblastoma

Glioblastoma multiforme (GBM) is the deadliest glioma and its resistance to temozolomide (TMZ) remains intractable. Long non‐coding RNAs (lncRNAs) play crucial roles in that and this study aimed to investigate underlying mechanism of HOXD‐AS2‐affected temozolomide sensitivity in glioblastoma.
Spectre des réseaux topologiques finis

Soit {−λ n } n∈N le spectre du laplacien sur un reseau topologique fini; grâce au principe de minimax et a une formule de Poisson generalisee, on etudie le comportement asymptotique de λ n et on montre que la formule asymptotique de H. Weyl reste vraie
ATM phosphorylates the FATC domain of DNA-PKcs at threonine 4102 to promote non-homologous end joining

Abstract Ataxia-telangiectasia mutated (ATM) drives the DNA damage response via modulation of multiple signal transduction and DNA repair pathways. Previously, ATM activity was implicated in promoting the non-homologous end joining (NHEJ) pathway to repair a subset of DNA double-stranded breaks (DSBs), but how ATM performs this function is still unclear. In this study, we identified that ATM phosphorylates the DNA-dependent protein kinase catalytic subunit (DNA-PKcs), a core NHEJ factor, at its extreme C-terminus at threonine 4102 (T4102) in response to DSBs. Ablating phosphorylation at T4102 attenuates DNA-PKcs kinase activity and this destabilizes the interaction between DNA-PKcs and the Ku-DNA complex, resulting in decreased assembly and stabilization of the NHEJ machinery at DSBs. Phosphorylation at T4102 promotes NHEJ, radioresistance, and increases genomic stability following DSB induction. Collectively, these findings establish a key role for ATM in NHEJ-dependent repair of DSBs through positive regulation of DNA-PKcs.
LARGEST SPACE FOR THE STABILIZABILITY OF THE LINEARIZED COMPRESSIBLE NAVIER-STOKES SYSTEM IN ONE DIMENSION

In this paper we determine the largest space in which the linearized compressible Navier-Stokes system in one dimension, with periodic boundary conditions, is stabilizable with any prescribed exponential decay rate, by an interior control acting only in the velocity equation. As a consequence, it also follows that this largest space for the stabilizability with any prescribed exponential decay rate is also the largest one for the null controllability of the same system.
Historical and social science perspectives on food allergy

This article provides an overview of the insights social scientists, historians and other health humanities scholars have made to our understanding of food allergies. It shows how humanities and social science scholars have tended to address three pivotal issues related to food allergies: first, they have addressed the epidemiology of food allergies, including the apparent rise in the rate of food allergies and the emergence of theories that purport to explain why food allergies may be increasing. These include theories related to changes in food consumption and the hygiene hypothesis. Second, humanities and social science scholars have researched how risks related to food allergies have been constructed, understood, experienced and mitigated. Third, humanities and social science scholars have investigated the experiences of food allergy sufferers and those who care for them, providing valuable qualitative insights that can inform how we respond to food allergy and our understanding of the aetiology of food allergy. The article concludes with three recommendations. First, there should be a more interdisciplinary approach to food allergy research that involves social scientists and health humanities scholars. Second, humanities and social sciences scholars should be more willing to unpack and scrutinise the theories put forward to explain the aetiology of food allergies, rather than accepting them at face value. And finally, humanities and social sciences scholars can play a major role in ensuring that the experiences of patients and their carers are articulated and fed into debates about food allergy, including its causes and how to respond to it.
Acyl‐CoA dehydrogenase substrate promiscuity: Challenges and opportunities for development of substrate reduction therapy in disorders of valine and isoleucine metabolism

Toxicity of accumulating substrates is a significant problem in several disorders of valine and isoleucine degradation notably short‐chain enoyl‐CoA hydratase (ECHS1 or crotonase) deficiency, 3‐hydroxyisobutyryl‐CoA hydrolase (HIBCH) deficiency, propionic acidemia (PA), and methylmalonic aciduria (MMA). Isobutyryl‐CoA dehydrogenase (ACAD8) and short/branched‐chain acyl‐CoA dehydrogenase (SBCAD, ACADSB) function in the valine and isoleucine degradation pathways, respectively. Deficiencies of these acyl‐CoA dehydrogenase (ACAD) enzymes are considered biochemical abnormalities with limited or no clinical consequences. We investigated whether substrate reduction therapy through inhibition of ACAD8 and SBCAD can limit the accumulation of toxic metabolic intermediates in disorders of valine and isoleucine metabolism. Using analysis of acylcarnitine isomers, we show that 2‐methylenecyclopropaneacetic acid (MCPA) inhibited SBCAD, isovaleryl‐CoA dehydrogenase, short‐chain acyl‐CoA dehydrogenase and medium‐chain acyl‐CoA dehydrogenase, but not ACAD8. MCPA treatment of wild‐type and PA HEK‐293 cells caused a pronounced decrease in C3‐carnitine. Furthermore, deletion of ACADSB in HEK‐293 cells led to an equally strong decrease in C3‐carnitine when compared to wild‐type cells. Deletion of ECHS1 in HEK‐293 cells caused a defect in lipoylation of the E2 component of the pyruvate dehydrogenase complex, which was not rescued by ACAD8 deletion. MCPA was able to rescue lipoylation in ECHS1 KO cells, but only in cells with prior ACAD8 deletion. SBCAD was not the sole ACAD responsible for this compensation, which indicates substantial promiscuity of ACADs in HEK‐293 cells for the isobutyryl‐CoA substrate. Substrate promiscuity appeared less prominent for 2‐methylbutyryl‐CoA at least in HEK‐293 cells. We suggest that pharmacological inhibition of SBCAD to treat PA should be investigated further.
Serotonin syndrome—A focused review

Serotonin syndrome is a potentially life‐threatening syndrome with manifestations spanning from mild adverse effects to life‐threatening toxicity. The syndrome is caused by overstimulation of serotonin receptors by serotonergic drugs. Since the use of serotonergic drugs is increasing, primarily due to the widespread use of selective serotonin reuptake inhibitors, cases of serotonin syndrome have likely seen a parallel increase. The true incidence of serotonin syndrome remains unknown due to its diffuse clinical presentation.
MIMO based 3D imaging system at 360 GHz

A MIMO radar imaging system at 360 GHz is presented as a part of the comprehensive approach of the European FP7 project TeraSCREEN, using multiple frequency bands for active and passive imaging. The MIMO system consists of 16 transmitter and 16 receiver antennas within one single array. Using a bandwidth of 30 GHz, a range resolution up to 5 mm is obtained. With the 16×16 MIMO system 256 different azimuth bins can be distinguished. Mechanical beam steering is used to measure 130 different elevation angles where the angular resolution is obtained by a focusing elliptical mirror. With this system a high resolution 3D image can be generated with 4 frames per second, each containing 16 million points. The principle of the system is presented starting from the functional structure, covering the hardware design and including the digital image generation. This is supported by simulated data and discussed using experimental results from a preliminary 90 GHz system underlining the feasibility of the approach.
Coordinate invariance and energy expressions in general relativity

The invariance of various definitions proposed for the energy and momentum of the gravitational field is examined. We use the boundary conditions that ${g}_{\ensuremath{\mu}\ensuremath{\nu}}$ approaches the Lorentz metric as $\frac{1}{r}$, but allow ${g}_{\ensuremath{\mu}\ensuremath{\nu},\ensuremath{\alpha}}$ to vanish as slowly as $\frac{1}{r}$. This permits "coordinate waves. " It is found that none of the expressions giving the energy as a two-dimensional surface integral are invariant within this class of frames. In a frame containing coordinate waves they are ambiguous, since their value depends on the location of the surface at infinity (unlike the case where ${g}_{\ensuremath{\mu}\ensuremath{\nu},\ensuremath{\alpha}}$ vanishes faster than $\frac{1}{r}$). If one introduces the prescription of space-time averaging of the integrals, one finds that the definitions of Landau-Lifshitz and Papapetrou-Gupta yield (equal) coordinate-invariant results. However, the definitions of Einstein, M\o{}ller, and Dirac become unambiguous, but not invariant.
The interaction between intestinal microenvironment and stroke

Stroke is not only a major cause of disability but also the third leading cause of death, following heart disease and cancer. It has been established that stroke causes permanent disability in 80% of survivors. However, current treatment options for this patient population are limited. Inflammation and immune response are major features that are well‐recognized to occur after a stroke. The gastrointestinal tract hosts complex microbial communities, the largest pool of immune cells, and forms a bidirectional regulation brain‐gut axis with the brain. Recent experimental and clinical studies have highlighted the importance of the relationship between the intestinal microenvironment and stroke. Over the years, the influence of the intestine on stroke has emerged as an important and dynamic research direction in biology and medicine.
Screening and Targeting Risk Factors for Prodromal Synucleinopathy: Taking Steps toward a Prescriptive Multi-modal Framework

As the prevalence of Parkinson’s disease (PD) grows, so too does the population at-risk of developing PD, those in the so-called prodromal period. This period can span from those experiencing subtle motor deficits yet not meeting full diagnostic criteria or those with physiologic markers of disease alone. Several disease-modifying therapies have failed to show a neuroprotective effect. A common criticism is that neurodegeneration, even in the early motor stages, has advanced too far for neuro-restoration-based interventions to be effective. Therefore, identifying this early population is essential. Once identified, these patients could then potentially benefit from sweeping lifestyle modifications to alter their disease trajectory. Herein, we review the literature on risk factors for, and prodromal symptoms of, PD with an emphasis on ones which may be modifiable in the earliest possible stages. We propose a process for identifying this population and speculate on some strategies which may modulate disease trajectory. Ultimately, this proposal warrants prospective studies.
Virulence-associated type III secretion systems in Gram-negative bacteria

Virulence-associated bacterial type III secretion systems are multiprotein molecular machines that promote the pathogenicity of bacteria towards eukaryotic host cells. These machines form needle-like structures, named injectisomes, that span both bacterial and host membranes, forming a direct conduit for the delivery of bacterial proteins into host cells. Once within the host, these bacterial effector proteins are capable of manipulating a multitude of host cell functions. In recent years, the knowledge of assembly, structure and function of these machines has grown substantially and is presented and discussed in this review.
Overview of micro/nanofabrication technologies and applications

It has been revealed that materials and structures on the micro and nanometer scale demonstrate many characteristics different from their macro dimensions.Nanotechnology has become a hot topic in current research and industrial applications.Miniaturisation relies on functional structures and devices of micro and nanometer dimensions.An overview is presented of micro/nanofabrication technologies which are the basis for the realisation of micro and nanoscale structures.A brief description of the difference between such fabrication and conventional machining is given,and a few principles on how to choose an appropriate micro/nanofabrication technology for a specific application are suggested.Current challenges are presented,together with a prediction of future developments.
Secondary electrocardiographic stratification of NSTEMI to identify an acutely occluded culprit artery

In the United States, approximately 720 000 adults will experience a myocardial infarction (MI) every year. The 12-lead electrocardiogram (ECG) is quintessential for the classification of a MI. About 30% of all MIs exhibit ST-segment elevation on the 12-lead ECG and is therefore classified as an ST-Elevation Myocardial Infarction (STEMI), which is treated emergently with percutaneous coronary intervention to restore blood flow. However, in the remaining 70% of MIs, the 12-lead ECG lacks ST-segment elevation and instead exhibits a motley of changes, including ST-segment depression, T-wave inversion, or, in up to 20% of patients, have no changes whatsoever; as such, these MIs are classified as a Non-ST Elevation Myocardial Infarction (NSTEMI). Of this larger classification of MIs, 33% of NSTEMI actually have an occlusion of the culprit artery consistent with a Type I MI . This is a serious clinical problem because NSTEMI with an occluded culprit artery have similar myocardial damage like STEMI and are more likely to suffer from adverse outcomes compared to NSTEMI without an occluded culprit artery. In this review article, we review the extant literature on NSTEMI with an occluded culprit artery. Afterward, we generate and discuss hypotheses for the absence of ST-segment elevation on the 12-lead ECG: (1) transient occlusion (2) collateral blood flow and chronically occluded artery and (3) ECG-silent myocardial regions. Lastly, we describe and define novel ECG features that are associated with an occluded culprit artery in NSTEMI which include T-wave morphology abnormalities and novel markers of ventricular repolarization heterogeneity.
Genetic algorithm and adaptive genetic algorithm based on splitting operators

To solve the primary problems in genetic algorithms,such as prematurity and the slowing convergence speed,the splitting operators are proposed and introduced into the simple genetic algorithms and the adaptive genetic algorithms.These improved algorithms are compared with simple genetic algorithm and the adaptive genetic algorithm respectively by the testing on several functions.The results show that the improved algorithms with splitting operators not only can converge to the global optimal solutions,but also make a progress in the convergence speed.