Miracle-dz/UniFAR-FTUs huggingface dataset:
Generation of a host cell line containing a MAR‐rich landing pad for site‐specific integration and expression of transgenes

In recent years, targeted gene integration (TI) has been introduced as a strategy for the generation of recombinant mammalian cell lines for the production of biotherapeutics. Besides reducing the immense heterogeneity within a pool of recombinant transfectants, TI also aims at shortening the duration of the current cell line development process. Here we describe the generation of a host cell line carrying Matrix‐Attachment Region (MAR)‐rich landing pads (LPs), which allow for the simultaneous and site‐specific integration of multiple genes of interest (GOIs). We show that several copies of each chicken lysozyme 5'MAR‐based LP containing either BxB1 wild type or mutated recombination sites, integrated at one random chromosomal locus of the host cell genome. We further demonstrate that these LP‐containing host cell lines can be used for the site‐specific integration of several GOIs and thus, generation of transgene‐expressing stable recombinant clones. Transgene expression was shown by site‐specific integration of heavy and light chain genes coding for a monospecific antibody (msAb) as well as for a bi‐specific antibody (bsAb). The genetic stability of the herein described LP‐based recombinant clones expressing msAb or bsAb was demonstrated by cultivating the recombinant clones and measuring antibody titers over 85 generations. We conclude that the host cell containing multiple copies of MAR‐rich landing pads can be successfully used for stable expression of one or several GOIs.
Circadian regulation of protein cargo in extracellular vesicles

The circadian clock controls many aspects of physiology, but it remains undescribed whether extracellular vesicles (EVs), including exosomes, involved in cell-cell communications between tissues are regulated in a circadian pattern. We demonstrate a 24-hour rhythmic abundance of individual proteins in small EVs using liquid chromatography–mass spectrometry in circadian-synchronized tendon fibroblasts. Furthermore, the release of small EVs enriched in RNA binding proteins was temporally separated from those enriched in cytoskeletal and matrix proteins, which peaked during the end of the light phase. Last, we targeted the protein sorting mechanism in the exosome biogenesis pathway and established (by knockdown of circadian-regulated flotillin-1) that matrix metalloproteinase 14 abundance in tendon fibroblast small EVs is under flotillin-1 regulation. In conclusion, we have identified proteomic time signatures for small EVs released by tendon fibroblasts, which supports the view that the circadian clock regulates protein cargo in EVs involved in cell-cell cross-talk.
Compact 1 × 4 patch antenna array by means of EBG structures with enhanced bandwidth

In this paper, a novel design of compact 1 × 4 patch antenna array using electromagnetic band gap (EBG) for wideband operation is introduced. Three unequal arms fed by CPW‐to‐slotline through a coupling system of 100 Ω T‐shaped slotline transitions are utilized for broadening the impedance bandwidth with multiple resonances. By adding two conventional mushroom‐type EBG (CMT‐EBG) structures on both sides of 100 Ω slotline transitions, dual wideband patch array is obtained. The proposed 1 × 4 patch array with CMT‐EBG includes two bands with the measured ranges (S11≤−10 dB) of 6.71–6.97 GHz and 8.60–11.51 GHz. Moreover, more size reduction is achieved by using an edge‐shorted mushroom‐type EBG (ESM‐EBG) for the proposed array. This design with the ESM‐EBG indicates almost 37% size reduction compared with the proposed array without EBG. In this paper, an equivalent circuit model of the proposed 1 × 4 array with EBG is also introduced to describe the process of its bandwidth enhancement. © 2016 Wiley Periodicals, Inc. Microwave Opt Technol Lett 58:2983–2989, 2016
Beneficial effect of ursodeoxycholic acid in patients with acyl‐CoA oxidase 2 (ACOX2) deficiency–associated hypertransaminasemia

A variant (p.Arg225Trp) of peroxisomal acyl‐CoA oxidase 2 (ACOX2), involved in bile acid (BA) side‐chain shortening, has been associated with unexplained persistent hypertransaminasemia and accumulation of C27‐BAs, mainly 3α,7α,12α‐trihydroxy‐5β‐cholestanoic acid (THCA). We aimed to investigate the prevalence of ACOX2 deficiency‐associated hypertransaminasemia (ADAH), its response to ursodeoxycholic acid (UDCA), elucidate its pathophysiological mechanism and identify other inborn errors that could cause this alteration.
Shifting Priorities and Neoliberal Ideologies in Refugee Health Intervention Design in the US

ABSTRACT We discuss the design of a technology-based vaccine education intervention for Somali refugees in the US. Originally conceived of as a culturally and linguistically appropriate project to be co-designed by refugees, funder demands for a “social enterprise” led to future iterations being developed for a “generic” audience. We explore epistemological negotiations and shifting priorities that shaped intervention design, highlighting how nonprofits engage neoliberal ideologies such as “social enterprise” and “design thinking” while attempting to meet community needs. We argue that social enterprises and design thinking can suffuse neoliberal ideologies into nonprofits to the detriment of community-engaged solutions.
Green syntheses of graphene and its applications in internet of things (IoT)—a status review

Internet of Things (IoT) is a trending technological field that converts any physical object into a communicable smarter one by converging the physical world with the digital world. This innovative technology connects the device to the internet and provides a platform to collect real-time data, cloud storage, and analyze the collected data to trigger smart actions from a remote location via remote notifications, etc. Because of its wide-ranging applications, this technology can be integrated into almost all the industries. Another trending field with tremendous opportunities is Nanotechnology, which provides many benefits in several areas of life, and helps to improve many technological and industrial sectors. So, integration of IoT and Nanotechnology can bring about the very important field of Internet of Nanothings (IoNT), which can re-shape the communication industry. For that, data (collected from trillions of nanosensors, connected to billions of devices) would be the ‘ultimate truth’, which could be generated from highly efficient nanosensors, fabricated from various novel nanomaterials, one of which is graphene, the so-called ‘wonder material’ of the 21st century. Therefore, graphene-assisted IoT/IoNT platforms may revolutionize the communication technologies around the globe. In this article, a status review of the smart applications of graphene in the IoT sector is presented. Firstly, various green synthesis of graphene for sustainable development is elucidated, followed by its applications in various nanosensors, detectors, actuators, memory, and nano-communication devices. Also, the future market prospects are discussed to converge various emerging concepts like machine learning, fog/edge computing, artificial intelligence, big data, and blockchain, with the graphene-assisted IoT field to bring about the concept of ‘all-round connectivity in every sphere possible’.
High-Resolution 3D Fabrication of Glass Fiber-Reinforced Polymer Nanocomposite (FRPN) Objects by Two-Photon Direct Laser Writing

This paper reports on the nanofabrication of a fiber-reinforced polymer nanocomposite (FRPN) by two-photon direct laser writing (TP-DLW) using silica nanowires (SiO2 NWs) as nanofillers, since they feature a refractive index very close to that of the photoresist used as a polymeric matrix. This allows for the best resolution offered by the TP-DLW technique, even with high loads of SiO2 NWs, up to 70 wt %. The FRPN presented an increase of approximately 4 times in Young’s modulus (8.23 GPa) and nanohardness (120 MPa) when compared to those of the bare photoresist, indicating how the proposed technique is well-suited for applications with higher structural requirements. Moreover, three different printing configurations can be implemented thanks to the use of silicon chips, on which the SiO2 NWs are grown, as fabrication substrates. First, they can be effectively used as an adhesive layer when the laser beam is focused at the interface with the silicon substrate. Second, they can be used as a sacrificial layer, when the laser beam is focused in a plane inside the SiO2 NW layer. Third, only the outer shell of the object is printed so that the SiO2 NW tangle acts as the internal skeleton for the structure being fabricated in the so-called shell and scaffold printing strategy.
Examining the Relationship between Discrimination and Prescription Drug Misuse: Findings from a National Survey of Black Americans

Abstract Background: Research shows that substance use may be a way individuals cope with psychosocial stressors. Less is known about whether discrimination contributes to prescription drug misuse. Methods: Using a national sample of Black Americans, we examined whether two psychosocial stressors (i.e., everyday and lifetime major discrimination) were associated with lifetime prescription drug misuse (i.e., opioids, tranquilizers, sedatives, or stimulants). Results: Our logistic regression models separately examining the influence of everyday and major discrimination controlling for relevant demographic, health, and other drug use variables showed that only everyday discrimination was associated with higher odds of prescription drug misuse. In the model simultaneously considering both types of discrimination, only unit increases in everyday discrimination were associated with higher odds of prescription drug misuse. Conclusions: Encounters with everyday discrimination may be an important psychosocial stressor linked to prescription drug misuse in Black adults and possibly other racial-ethnic minorities. Intervention strategies aiming to reduce prescription drug misuse should consider developing ways to curb the negative health-related consequences of discriminatory experiences. Strategies to combat discrimination-related prescription drug misuse and limitations of this study are discussed.
The genetic basis of selfing rate evolution

Evolution of selfing is common in plant populations, but the genetic basis of selfing rate evolution remains unclear. Although the effects of genetic properties on fixation for mating‐unrelated alleles have been investigated, loci that modify the selfing rate (selfing modifiers) differ from mating‐unrelated loci in several aspects. Using population genetic models, I investigate the genetic basis of selfing rate evolution. For mating‐unrelated alleles, selfing promotes fixation only for recessive mutations, but for selfing modifiers, because the selection coefficient depends on the background selfing rate, selfing can promote fixation even for dominant modifiers. For mating‐unrelated alleles, the fixation probability from standing variation is independent of dominance and decreases with an increased background selfing rate. However, for selfing modifiers, the fixation probability peaks at an intermediate selfing rate and when alleles are recessive, because a change of its selection coefficient necessarily involves a change of the inbreeding coefficient, because both depend on the level of inbreeding depression. Furthermore, evolution of selfing involving multiple modifier loci is more likely when selfing is controlled by few large‐effect rather than many slight‐effect modifiers. I discuss how these characteristics of selfing modifiers have implications for the unidirectional transition from outcrossing to selfing and other empirical patterns.
Hippocampal interneurons are direct targets for circulating glucocorticoids

The hippocampus has become a significant target of stress research in recent years because of its role in cognitive functioning, neuropathology, and regulation of the hypothalamic–pituitary–adrenal (HPA) axis. Despite the pervasive impact of stress on psychiatric and neurological disease, many of the circuit‐ and cell‐dependent mechanisms giving rise to the limbic regulation of the stress response remain unknown. Hippocampal excitatory neurons generally express high levels of glucocorticoid receptors (GRs) and are therefore positioned to respond directly to serum glucocorticoids. These neurons are, in turn, regulated by neighboring interneurons, subtypes of which have been shown to respond to stress exposure. However, GR expression among hippocampal interneurons is not well characterized. To determine whether key interneuron populations are direct targets for glucocorticoid action, we used two transgenic mouse lines to label parvalbumin‐positive (PV+) and somatostatin‐positive (SST+) interneurons. GR immunostaining of labeled interneurons was characterized within the dorsal and ventral dentate hilus, dentate cell body layer, and CA1 and CA3 stratum oriens and stratum pyramidale. While nearly all hippocampal SST+ interneurons expressed GR across all regions, GR labeling of PV+ interneurons showed considerable subregion variability. The percentage of PV+, GR+ cells was highest in the CA3 stratum pyramidale and lowest in the CA1 stratum oriens, with other regions showing intermediate levels of expression. Together, these findings indicate that, under baseline conditions, hippocampal SST+ interneurons are a ubiquitous glucocorticoid target, while only distinct populations of PV+ interneurons are direct targets. This anatomical diversity suggests functional differences in the regulation of stress‐dependent hippocampal responses.
Model Predictive Control and Direct Power Control for PWM Rectifiers With Active Power Ripple Minimization

Direct power control (DPC) and model predictive control (MPC) are two well-known methods to achieve direct control of active power and reactive power in pulse-width modulation rectifiers. They both select a voltage vector, according to a switching table or by minimizing a cost function, and then apply it in the next control period. The use of only one voltage vector during one control period leads to high power ripples and variable switching frequency, especially in DPC. Recently duty-cycle control was proposed in DPC to achieve steady-state performance improvement. This paper proposes an improved MPC with duty-cycle control and compares it with prior DPC with duty-cycle control in terms of power ripple reduction, dynamic response, and robustness against external load disturbance. The duration of the selected vector is determined by minimizing the active power ripple during one control period. Simulation and experimental results are presented to confirm the theoretical study.
Diverse Molecular Mechanisms Underlying Pathogenic Protein Mutations: Beyond the Loss-of-Function Paradigm.

Most known disease-causing mutations occur in protein-coding regions of DNA. While some of these involve a loss of protein function (e.g., through premature stop codons or missense changes that destabilize protein folding), many act via alternative molecular mechanisms and have dominant-negative or gain-of-function effects. In nearly all cases, these non-loss-of-function mutations can be understood by considering interactions of the wild-type and mutant protein with other molecules, such as proteins, nucleic acids, or small ligands and substrates. Here, we review the diverse molecular mechanisms by which pathogenic mutations can have non-loss-of-function effects, including by disrupting interactions, increasing binding affinity, changing binding specificity, causing assembly-mediated dominant-negative and dominant-positive effects, creating novel interactions, and promoting aggregation and phase separation. We believe that increased awareness of these diverse molecular disease mechanisms will lead to improved diagnosis (and ultimately treatment) of human genetic disorders. Expected final online publication date for the Annual Review of Genomics and Human Genetics, Volume 23 is October 2022. Please see http://www.annualreviews. org/page/journal/pubdates for revised estimates.
Top‐down self‐regulation processes as determinants of oral hygiene self‐care behaviour: A systematic scoping review

Understanding the psychological mechanisms that moderate oral hygiene self‐care behavior is anticipated to benefit efforts to change such behavior. Top‐down self‐regulatory (TSR) processes represent one group of relatively unexplored, yet potentially influential, moderating factors. This systematic scoping review aims to explore whether there is evidence that TSR processes moderate oral hygiene self‐care engagement within the current literature.
The hexosamine pathway and coat complex II promote malignant adaptation to nutrient scarcity

We present adaptive mechanisms of resistance of lung adenocarcinoma to their harsh microenvironment, which typically contains a lower glucose concentration compared with normal tissue. The glucose-requiring hexosamine biosynthetic pathway (HBP), which produces UDP-N-acetylglucosamine for glycosylation reactions, promotes lung adenocarcinoma (LUAD) progression. However, lung tumor cells often reside in low-nutrient microenvironments, and whether the HBP is involved in the adaptation of LUAD to nutrient stress is unknown. Here, we show that the HBP and the coat complex II (COPII) play a key role in cell survival during glucose shortage. HBP up-regulation withstood low glucose-induced production of proteins bearing truncated N-glycans, in the endoplasmic reticulum. This function for the HBP, alongside COPII up-regulation, rescued cell surface expression of a subset of glycoproteins. Those included the epidermal growth factor receptor (EGFR), allowing an EGFR-dependent cell survival under low glucose in anchorage-independent growth. Accordingly, high expression of the HBP rate-limiting enzyme GFAT1 was associated with wild-type EGFR activation in LUAD patient samples. Notably, HBP and COPII up-regulation distinguished LUAD from the lung squamous-cell carcinoma subtype, thus uncovering adaptive mechanisms of LUAD to their harsh microenvironment.
Urban Freight and Rail - The State of the Art

whole, or in part, from a dominant position as road transport services have grown and developed in capability and levels of sophistication that have not, regrettably, been matched by rail service providers. Rail’s generic weaknesses, particularly in door-to-door capability, cost – compared to road transport alternatives, which largely exclude consideration of external costs – and service availability have been the principal causes of the decline in rail’s share of the urban freight market. The development of city planning, zoning and rebuilding practice has also created problems by effectively sterilising operational and commercial options that were formerly open to rail.
Metabolic profile of the Warburg effect as a tool for molecular prognosis and diagnosis of cancer

ABSTRACT Introduction Adaptations of eukaryotic cells to environmental changes are important for their survival. However, under some circumstances, microenvironmental changes promote that eukaryotic cells utilize a metabolic signature resembling a unicellular organism named the Warburg effect. Most cancer cells share the Warburg effect displaying lactic fermentation and high glucose uptake. The Warburg effect also induces a metabolic rewiring stimulating glutamine consumption and lipid synthesis, also considered cancer hallmarks. Amino acid metabolism alteration due to the Warburg effect increases plasma levels of proline and branched-chain amino acids in several cancer types. Proline and lipids are probably used as electron transfer molecules in carcinogenic cells. In addition, branched-chain amino acids fuel the Krebs cycle, protein synthesis, and signaling in cancer cells. Areas covered This review covers how metabolomics studies describe changes in some metabolites and proteins associated with the Warburg effect and related metabolic pathways. Expert opinion In this review, we analyze the metabolic signature of the Warburg effect and related phenotypes and propose some Warburg effect-related metabolites and proteins (lactate, glucose uptake, glucose transporters, glutamine, branched-chain amino acids, proline, and some lipogenic enzymes) as promising cancer biomarkers.
Mobile Robot Navigation in Static and Dynamic Environments using Various Soft Computing Techniques

The applications of the autonomous mobile robot in many fields such as industry, space, defence and transportation, and other social sectors are growing day by day. The mobile robot performs many tasks such as rescue operation, patrolling, disaster relief, planetary exploration, and material handling, etc. Therefore, an intelligent mobile robot is required that could travel autonomously in various static and dynamic environments. The present research focuses on the design and implementation of the intelligent navigation algorithms, which is capable of navigating a mobile robot autonomously in static as well as dynamic environments. Navigation and obstacle avoidance are one of the most important tasks for any mobile robots. The primary objective of this research work is to improve the navigation accuracy and efficiency of the mobile robot using various soft computing techniques. In this research work, Hybrid Fuzzy (H-Fuzzy) architecture, Cascade Neuro-Fuzzy (CN-Fuzzy) architecture, Fuzzy-Simulated Annealing (Fuzzy-SA) algorithm, Wind Driven Optimization (WDO) algorithm, and Fuzzy-Wind Driven Optimization (Fuzzy-WDO) algorithm have been designed and implemented to solve the navigation problems of a mobile robot in different static and dynamic environments. The performances of these proposed techniques are demonstrated through computer simulations using MATLAB software and implemented in real time by using experimental mobile robots. Furthermore, the performances of Wind Driven Optimization algorithm and Fuzzy-Wind Driven Optimization algorithm are found to be most efficient (in terms of path length and navigation time) as compared to rest of the techniques, which verifies the effectiveness and efficiency of these newly built techniques for mobile robot navigation. The results obtained from the proposed techniques are compared with other developed techniques such as Fuzzy Logics, Genetic algorithm (GA), Neural Network, and Particle Swarm Optimization (PSO) algorithm, etc. to prove the authenticity of the proposed developed techniques.
Relational Instability in Couples Seeking Therapy: The Contribution of Attachment, Caregiving and Sex

Abstract Attachment theory postulates that three behavioral systems—attachment, caregiving, and sex—are essential for optimal relationship functioning in couples. We examined the contribution of attachment insecurities, perceived partner support, and sexual satisfaction to relational instability in 274 couples seeking relationship therapy. The results underscore the importance of all three systems for relationship stability, showing that for both men and women, avoidance of intimacy, low perceived partner support, and low sexual satisfaction were significant and concurrent predictors of relational instability. As such, intervening on factors associated with all three behavioral systems might help reduce relationship instability in couples experiencing relationship distress.