Miracle-dz/UniFAR-FTUs huggingface dataset:
Observer-Based Glucose Control Via Subcutaneous Insulin Administration

Abstract A closed-loop therapy for diabetic patients is proposed, by suitably exploiting a discrete Delay Differential Equation (DDE) model of the glucose-insulin system. To this aim, plasma glucose concentration is regulated by means of subcutaneous insulin administration, in order to track a desired glucose profile. The method of exact input/output feedback linearization and stabilization is used, in order to ensure the local convergence of the tracking error to zero. The use of a state observer for delay systems makes it so that the control law requires only glucose measurements, which are easily achievable according to the present technology. Even if exogenous insulin administration is standardly used for Type I diabetic patients (who do not have a pancreatic insulin release), the use of a DDE model allows to extend the proposed treatment also to Type II diabetes. Performed simulations show the effectiveness of the proposed approach.
HIVEP1 Is a Negative Regulator of NF-κB That Inhibits Systemic Inflammation in Sepsis

Our previous work identified human immunodeficiency virus type I enhancer binding protein 1 (HIVEP1) as a putative driver of LPS-induced NF-κB signaling in humans in vivo. While HIVEP1 is known to interact with NF-ĸB binding DNA motifs, its function in mammalian cells is unknown. We report increased HIVEP1 mRNA expression in monocytes from patients with sepsis and monocytes stimulated by Toll-like receptor agonists and bacteria. In complementary overexpression and gene deletion experiments HIVEP1 was shown to inhibit NF-ĸB activity and induction of NF-ĸB responsive genes. RNA sequencing demonstrated profound transcriptomic changes in HIVEP1 deficient monocytic cells and transcription factor binding site analysis showed enrichment for κB site regions. HIVEP1 bound to the promoter regions of NF-ĸB responsive genes. Inhibition of cytokine production by HIVEP1 was confirmed in LPS-stimulated murine Hivep1-/- macrophages and HIVEP1 knockdown zebrafish exposed to the common sepsis pathogen Streptococcus pneumoniae. These results identify HIVEP1 as a negative regulator of NF-κB in monocytes/macrophages that inhibits proinflammatory reactions in response to bacterial agonists in vitro and in vivo.
Prospective Quantitative Neuroimaging Analysis of Putative Temporal Lobe Epilepsy

Purpose: A prospective study of individual and combined quantitative imaging applications for lateralizing epileptogenicity was performed in a cohort of consecutive patients with a putative diagnosis of mesial temporal lobe epilepsy (mTLE). Methods: Quantitative metrics were applied to MRI and nuclear medicine imaging studies as part of a comprehensive presurgical investigation. The neuroimaging analytics were conducted remotely to remove bias. All quantitative lateralizing tools were trained using a separate dataset. Outcomes were determined after 2 years. Of those treated, some underwent resection, and others were implanted with a responsive neurostimulation (RNS) device. Results: Forty-eight consecutive cases underwent evaluation using nine attributes of individual or combinations of neuroimaging modalities: 1) hippocampal volume, 2) FLAIR signal, 3) PET profile, 4) multistructural analysis (MSA), 5) multimodal model analysis (MMM), 6) DTI uncertainty analysis, 7) DTI connectivity, and 9) fMRI connectivity. Of the 24 patients undergoing resection, MSA, MMM, and PET proved most effective in predicting an Engel class 1 outcome (>80% accuracy). Both hippocampal volume and FLAIR signal analysis showed 76% and 69% concordance with an Engel class 1 outcome, respectively. Conclusion: Quantitative multimodal neuroimaging in the context of a putative mTLE aids in declaring laterality. The degree to which there is disagreement among the various quantitative neuroimaging metrics will judge whether epileptogenicity can be confined sufficiently to a particular temporal lobe to warrant further study and choice of therapy. Prediction models will improve with continued exploration of combined optimal neuroimaging metrics.
Aging Affects the Demands and Patterns in Active Control Under Different Sensory-Conflicted Conditions

Most falls might be attributed to an unexpected perturbation such as a slip. It might be aggravated by the deterioration of the sensory system as people aged. This deterioration increases the demand in active control. However, what levels of demand in active control do older adults need? This study aimed to answer this question by using a novel assessment. Both young and old adults walked in three conditions: normal, slip, and slip with low light conditions. The amount of step length variability, step width variability, and the 95% confidence interval of the ellipse area of heel contact locations was measured to quantify and distinguish different levels of demand and patterns in active control. The results found that less sensory information led to a higher level of demand in active control in both anterior-posterior and medial-lateral directions. Importantly, different patterns in active control were found among different age groups and perturbation conditions. This study extended the current knowledge and further proposed the possibility of multiple patterns in active control. This study also suggests a new method to quantify the levels and patterns in active control under sensory perturbations, and this innovation can be used to guide age-related fall prevention training.
Dissection of the Functional Mechanism of Human Gut Bacterial Strain AD16 by Secondary Metabolites’ Identification, Network Pharmacology, and Experimental Validation

Gut microbiota plays important roles in several metabolic processes, such as appetite and food intake and absorption of nutrients from the gut. It is also of great importance in the maintenance of the health of the host. However, much remains unknown about the functional mechanisms of human gut microbiota itself. Here, we report the identification of one anticancer gut bacterial strain AD16, which exhibited potent suppressive effects on a broad range of solid and blood malignancies. The secondary metabolites of the strain were isolated and characterized by a bioactivity-guided isolation strategy. Five new compounds, streptonaphthalenes A and B (1-2), pestaloficins F and G (3-4), and eudesmanetetraiol A (5), together with nine previously known compounds, were isolated from the effective fractions of AD16. Structures of the new compounds were established by 1D and 2D NMR and MS analysis, and the absolute configurations were determined by the CD method. The analysis of network pharmacology suggested that 3, 2, and 13 could be the key components for the anti-NSCLC activity of AD16. In addition to the PI3K–Akt signaling pathway, the proteoglycans in cancer pathway could be involved in the anti-NSCLC action of AD16.
Sustainable Agriculture Development in Northwest China Under the Impacts of Global Climate Change

Northwest China has one of the most vulnerable agricultural systems in the context of global climate change. We argue that sustainable agriculture development in this region requires a systematic approach toward climate change adaptation, and propose a schematic framework for strategic thinking. We first briefly review the impacts of climate change on various agricultural environmental factors, including light, temperature, water, and atmosphere, and explores the effects of climate change on agricultural practices, such as disaster response, pests and weeds control, fertilizer application, and species selection. The study shows that climate change has increased extreme climate disasters such as drought and heat waves, and has expanded the scope and severity of pests and weeds, which in turn requires a series of changes in farming practices. These effects have profound impacts on farmland management, as well as the sustainability of the agricultural system. Based on the findings, the authors argue that the key adaptation strategies should include: (1) optimizing the geographic distribution of agriculture, (2) cultivating new crop varieties that can better adapt to the changing environment, (3) adjusting cropping timing and structure, (4) developing water-saving irrigation systems, (5) improving capacities of disaster prevention and mitigation at both household and government levels, and (6) strengthening the sciences, technology, and human resources to mitigate the adverse effects of climate change.
Natural Products for the Management of Castration-Resistant Prostate Cancer: Special Focus on Nanoparticles Based Studies

Prostate cancer is the most common type of cancer among men and the second most frequent cause of cancer-related mortality around the world. The progression of advanced prostate cancer to castration-resistant prostate cancer (CRPC) plays a major role in disease-associated morbidity and mortality, posing a significant therapeutic challenge. Resistance has been associated with the activation of androgen receptors via several mechanisms, including alternative dehydroepiandrosterone biosynthetic pathways, other androgen receptor activator molecules, oncogenes, and carcinogenic signaling pathways. Tumor microenvironment plays a critical role not only in the cancer progression but also in the drug resistance. Numerous natural products have shown major potential against particular or multiple resistance pathways as shown by in vitro and in vivo studies. However, their efficacy in clinical trials has been undermined by their unfavorable pharmacological properties (hydrophobic molecules, instability, low pharmacokinetic profile, poor water solubility, and high excretion rate). Nanoparticle formulations can provide a way out of the stalemate, employing targeted drug delivery, improved pharmacokinetic drug profile, and transportation of diagnostic and therapeutic agents via otherwise impermeable biological barriers. This review compiles the available evidence regarding the use of natural products for the management of CRPC with a focus on nanoparticle formulations. PubMed and Google Scholar search engines were used for preclinical studies, while ClinicalTrials.gov and PubMed were searched for clinical studies. The results of our study suggest the efficacy of natural compounds such as curcumin, resveratrol, apigenin, quercetin, fisetin, luteolin, kaempferol, genistein, berberine, ursolic acid, eugenol, gingerol, and ellagic acid against several mechanisms leading to castration resistance in preclinical studies, but fail to set the disease under control in clinical studies. Nanoparticle formulations of curcumin and quercetin seem to increase their potential in clinical settings. Using nanoparticles based on betulinic acid, capsaicin, sintokamide A, niphatenones A and B, as well as atraric acid seems promising but needs to be verified with preclinical and clinical studies.
Non-Conventional Clinical Uses of TSH Receptor Antibodies: The Case of Chronic Autoimmune Thyroiditis

Anti TSH receptor antibodies (TSHrAb) are a family of antibodies with different activity, some of them stimulating thyroid function (TSAb), others with blocking properties (TBAb), it is a common finding that antibodies with different function might coexist in the same patient and can modulate the function of the thyroid. However, most of the labs routinely detect all antibodies binding to the TSH receptor (TRAb, i.e. TSH-receptor antibodies detected by binding assay without definition of functional property). Classical use of TSHr-Ab assay is in Graves’ disease where they are tested for diagnostic and prognostic issues; however, they can be used in specific settings of chronic autoimmune thyroiditis (CAT) as well. Aim of the present paper is to highlight these conditions where detection of TSHr-Ab can be of clinical relevance. Prevalence of TSHrAb is different in in the 2 main form of CAT, i.e. classical Hashimoto’s thyroiditis and in atrophic thyroiditis, where TBAb play a major role. Simultaneous presence of both TSAb and TBAb in the serum of the same patient might have clinical implication and cause the shift from hyperthyroidism to hypothyroidism and vice versa. Evaluation of TRAb is recommended in case of patients with Thyroid Associated Orbitopathy not associated with hyperthyroidism. At present, however, the most relevant recommendation for the use of TRAb assay is in patients with CAT secondary to a known agent; in particular, after treatment with alemtuzumab for multiple sclerosis. In conclusion, the routine use of anti-TSH receptor antibodies (either TRAb or TSAb/TBAb) assay cannot be suggested at the present for diagnosis/follow up of patients affected by CAT; there are, however, several conditions where their detection can be clinically relevant.
Stability Evaluation of Different Oblique Lumbar Interbody Fusion Constructs in Normal and Osteoporotic Condition – A Finite Element Based Study

Introduction: In developed countries, the age structure of the population is currently undergoing an upward shift, resulting a decrease in general bone quality and surgical durability. Over the past decade, oblique lumbar interbody fusion (OLIF) has been globally accepted as a minimally invasive surgical technique. There are several stabilization options available for OLIF cage fixation such as self-anchored stand-alone (SSA), lateral plate-screw (LPS), and bilateral pedicle screw (BPS) systems. The constructs’ stability are crucial for the immediate and long-term success of the surgery. The aim of this study is to investigate the biomechanical effect of the aforementioned constructs, using finite element analysis with different bone qualities (osteoporotic and normal). Method: A bi-segmental (L2–L4) finite element (FE) model was created, using a CT scan of a 24-year-old healthy male. After the FE model validation, CAD geometries of the implants were inserted into the L3–L4 motion segment during a virtual surgery. For the simulations, a 150 N follower load was applied on the models, then 10 Nm of torque was used in six general directions (flexion, extension, right/left bending, and right/left rotation), with different bone material properties. Results: The smallest segmental (L3–L4) ROM (range of motion) was observed in the BPS system, except for right bending. Osteoporosis increased ROMs in all constructs, especially in the LPS system (right bending increase: 140.26%). Osteoporosis also increased the caudal displacement of the implanted cage in all models (healthy bone: 0.06 ± 0.03 mm, osteoporosis: 0.106 ± 0.07 mm), particularly with right bending, where the displacement doubled in SSA and LPS constructs. The displacement of the screws inside the L4 vertebra increased by 59% on average (59.33 ± 21.53%) due to osteoporosis (100% in LPS, rotation). BPS-L4 screw displacements were the least affected by osteoporosis. Conclusions: The investigated constructs provide different levels of stability to the spine depending on the quality of the bone, which can affect the outcome of the surgery. In our model, the BPS system was found to be the most stable construct in osteoporosis. The presented model, after further development, has the potential to help the surgeon in planning a particular spinal surgery by adjusting the stabilization type to the patient’s bone quality.
The diversity of morphological characteristics and chemical content of Celosia cristata plantlets due to gamma ray irradiation

Abstract. Muhallilin I, Aisyah SI, Sukma D. 2019. The diversity of morphological characteristics and chemical content of Celosia cristata plantlets due to gamma ray irradiation. Biodiversitas 20: 862-866. Celosia cristata L. or better known as Jengger Ayam is an ornamental plant that has a unique flower shape with attractive colors. Besides, this plant also contains antioxidants and chemical compounds that are used for traditional medicine to treat high blood pressure, and diabetes or as eye ailments. Increased diversity of C. cristata through hybridization techniques is constrained by flowers forming small grains that makes it difficult for castration and isolation of reproductive organs. This study aimed to increase C. cristata diversity of morphology and chemical content using mutation techniques induced by gamma irradiation. Plantlets were irradiated at 0, 25, 50 and 75 Gy doses. Scoring was conducted for 5 weeks until MV6 generation. Planlets were acclimatized for 3 weeks. The surviving plants were moved onto experimental land until seeded and tested for phytochemicals. Gamma irradiation with 25, 50 and 75 Gy doses produced 4 clones that have morphological changes in color and shape of the stem, leaves, and flowers. Changes in chemical content were observed with the appearance of triterpenoid compounds in 1 clone irradiated with 25 Gy.
Simulating Deep Percolation in Flood-Irrigated Mature Pecan Orchards with RZWQM2

The timing and amount of irrigation water are critical to the optimum production of pecans in semi-arid, irrigated agriculture systems. However, few tools are available to managers for measuring or estimating water use compared to deep percolation (DP) below the root zone. The RZWQM2 model was compared to the daily water balance method at two flood-irrigated mature pecan orchards, with different soil textures and depths to water table, in the lower Rio Grande Valley near Las Cruces, New Mexico, to characterize: (1) DP below the upper 100 cm soil profile, and (2) the effects of DP on water table levels. At site 1 (sandy loam) and site 2 (silty clay loam), comparisons between measured and simulated soil water contents at different soil depths during March to December in 2009 and 2010 demonstrated that RZWQM2 generally provided satisfactory predictions of soil water dynamics but consistently undepredicted soil water content after irrigation. Total estimated and simulated DP at site 1 were 489.1 and 445.2 mm in 2009, and 541.5 and 465.8 mm in 2010, respectively. Thus, at site 1, 25% to 29% of the applied water percolated below the root zone, but the model underpredicted these values by 3 to 4 percentage points. In contrast, total estimated DP at site 2 was 37% and 35% of the total water, and again the model underpredicted by 4 to 5 percentage points. Water table levels at site 1 were affected by DP following irrigation events. This was likely related to the relatively shallow water table and the highly permeable sandy loam soil in the upper layers. Nevertheless, the root zone water balance at site 1 did not appear to be influenced by the water table since downward hydraulic fluxes were predominant below 40 cm depth and soil water content remained constant at 160 cm depth. In contrast, the deeper water table at site 2 was not influenced by DP. Calibration and validation of RZWQM2 with field data at pecan orchards with different soil textures and water table depths allow managers to use the model to address water management issues to minimize DP while optimizing pecan production.
Super-Resolution Microscopy Reveals That Stromal Interaction Molecule 1 Trafficking Depends on Microtubule Dynamics

Store-operated Ca2+ entry (SOCE) is an essential pathway for Ca2+ signaling, and regulates various vital cellular functions. It is triggered by the endoplasmic reticulum Ca2+ sensor stromal interaction molecule 1 (STIM1). Illustration of STIM1 spatiotemporal structure at the nanometer scale during SOCE activation provides structural and functional insights into the fundamental Ca2+ homeostasis. In this study, we used direct stochastic optical reconstruction microscopy (dSTORM) to revisit the dynamic process of the interaction between STIM1, end-binding protein (EB), and microtubules to the ER-plasma membrane. Using dSTORM, we found that“powder-like”STIM1 aggregates into “trabecular-like” architectures toward the cell periphery during SOCE, and that an intact microtubule network and EB1 are essential for STIM1 trafficking. After thapsigargin treatment, STIM1 can interact with EB1 regardless of undergoing aggregation. We generated STIM1 variants adapted from a real-world database and introduced them into SiHa cells to clarify the impact of STIM1 mutations on cancer cell behavior. The p.D76G and p.D84Y variants locating on the Ca2+ binding domain of STIM1 result in inhibition of focal adhesion turnover, Ca2+ influx during SOCE and subsequent cell migration. Inversely, the p.R643C variant on the microtubule interacting domain of STIM1 leads to dissimilar consequence and aggravates cell migration. These findings imply that STIM1 mutational patterns have an impact on cancer metastasis, and therefore could be either a prognostic marker or a novel therapeutic target to inhibit the malignant behavior of STIM1-mediated cancer cells. Altogether, we generated novel insight into the role of STIM1 during SOCE activation, and uncovered the impact of real-world STIM1 variants on cancer cells.
Design of a PIFA with parasitic F‐element miniaturized antenna assembly for lower band ultra‐wideband and IEEE 802.11a applications

In this article, a planar inverted‐FF antenna with suspended rectangular feeding mechanism is presented for lower band ultra‐wideband and IEEE 802.11a wireless local area network applications. By manipulating the optimum strong electromagnetic coupling distance between driven and parasitic F‐shaped radiators on a small ground plane, two closely separate resonances can be merged to form a wide impedance bandwidth of 73.7% (3.0–6.5 GHz) at |S11| < −10 dB. The overall occupied antenna volume is 30 × 15 × 3 mm3 to satisfy the size requirement of modern wireless devices. The impact of the different antenna geometry parameters on the antenna performance is studied. The corresponding measured radiation patterns, gains and group delays are given to fully characterize the performance of this antenna. © 2011 Wiley Periodicals, Inc. Microwave Opt Technol Lett, 2011; View this article online at wileyonlinelibrary.com. DOI 10.1002/mop.26189
Lipid Interactions Between Flaviviruses and Mosquito Vectors

Mosquito-borne flaviviruses, such as dengue (DENV), Zika (ZIKV), yellow fever (YFV), West Nile (WNV), and Japanese encephalitis (JEV) viruses, threaten a large part of the human populations. In absence of therapeutics and effective vaccines against each flaviviruses, targeting viral metabolic requirements in mosquitoes may hold the key to new intervention strategies. Development of metabolomics in the last decade opened a new field of research: mosquito metabolomics. It is now clear that flaviviruses rely on mosquito lipids, especially phospholipids, for their cellular cycle and propagation. Here, we review the biosyntheses of, biochemical properties of and flaviviral interactions with mosquito phospholipids. Phospholipids are structural lipids with a polar headgroup and apolar acyl chains, enabling the formation of lipid bilayer that form plasma- and endomembranes. Phospholipids are mostly synthesized through the de novo pathway and remodeling cycle. Variations in headgroup and acyl chains influence phospholipid physicochemical properties and consequently the membrane behavior. Flaviviruses interact with cellular membranes at every step of their cellular cycle. Recent evidence demonstrates that flaviviruses reconfigure the phospholipidome in mosquitoes by regulating phospholipid syntheses to increase virus multiplication. Identifying the phospholipids involved and understanding how flaviviruses regulate these in mosquitoes is required to design new interventions.