Miracle-dz/UniFAR-FTUs huggingface dataset:
Biopharmaceutical Characterization of Nebulized Antimicrobial Agents in Rats: 1. Ciprofloxacin, Moxifloxacin, and Grepafloxacin

ABSTRACT The aim of this study was to evaluate the biopharmaceutical characteristics of three fluoroquinolones (FQs), ciprofloxacin (CIP), moxifloxacin (MXF), and grepafloxacin (GRX), after delivery via a nebulized aerosol to rats. Bronchoalveolar lavages (BAL) were conducted 0.5, 2, 4, and 6 h after FQ intravenous administration and nebulized aerosol delivery to estimate epithelial lining fluid (ELF) drug concentrations. Plasma drug concentrations were also measured, and profiles of drug concentrations versus time after intravenous administration and nebulized aerosol delivery were virtually superimposable, attesting for rapid and complete systemic absorption of FQs. ELF drug concentrations were systematically higher than corresponding plasma drug concentrations, whatever the route of administration, and average ELF-to-unbound plasma drug concentration ratios post-distribution equilibrium did not change significantly between the ways of administration and were equal: 4.0 ± 5.3 for CIP, 12.6 ± 7.3 for MXF, and 19.1 ± 10.5 for GRX (means ± standard deviations). The impact of macrophage lysis on estimated ELF drug concentrations was significant for GRX but reduced for MXF and CIP; therefore, simultaneous pharmacokinetic modeling of plasma and ELF drug concentrations was only performed for the latter two drugs. The model was characterized by a fixed volume of ELF (VELF), passive diffusion clearance (QELF), and active efflux clearance (CLout) between plasma and ELF, indicating active efflux transport systems. In conclusion, this study demonstrates that ELF drug concentrations of these three FQs are several times higher than plasma drug concentrations, probably due to the presence of efflux transporters at the pulmonary barrier level, but no biopharmaceutical advantage of FQ nebulization was observed compared with intravenous administration.
Modeling and experimental validation of series connected battery pack modules

For applications such as electrified automotive powertrains, which require high power density and operating voltages, the lithium-ion battery is an ideal candidate. When individual batteries are combined into packs, a battery management system is needed to safely operate packs consisting of hundreds of cells in series and parallel configurations. While much attention has been given to modeling and analysis of single cells, there has been less attention given to modeling and analysis of pack configurations regarding voltages and currents in the strings that make up the pack. Such analyses have an impact on investigations regarding pack balancing. Moreover, relatively little research has appeared in the open literature regarding experimental validation of models with regard to voltage and current characteristics in pack configurations. In this article we present a dynamic model for a lithium-ion series battery pack based on the voltage-current relationship of individual cells in various operating scenarios such as charge balancing. Resulting models are validated in the lab using a special purpose battery pack by comparing the simulated pack model with the bench top battery pack.
Dependence of light attenuation and backscattering on collagen concentration and chondrocyte density in agarose scaffolds

Optical coherence tomography (OCT) has been applied for high resolution imaging of articular cartilage. However, the contribution of individual structural elements of cartilage on OCT signal has not been thoroughly studied. We hypothesize that both collagen and chondrocytes, essential structural components of cartilage, act as important light scatterers and that variation in their concentrations can be detected by OCT through changes in backscattering and attenuation. To evaluate this hypothesis, we established a controlled model system using agarose scaffolds embedded with variable collagen concentrations and chondrocyte densities. Using OCT, we measured the backscattering coefficient (µb) and total attenuation coefficient (µt) in these scaffolds. Along our hypothesis, light backscattering and attenuation in agarose were dependent on collagen concentration and chondrocyte density. Significant correlations were found between µt and chondrocyte density (ρ = 0.853, p < 0.001) and between µt and collagen concentration (ρ = 0.694, p < 0.001). µb correlated significantly with chondrocyte density (ρ = 0.504, p < 0.001) but not with collagen concentration (ρ = 0.103, p = 0.422) of the scaffold. Thus, quantitation of light backscattering and, especially, attenuation could be valuable when evaluating the integrity of soft tissues, such as articular cartilage with OCT.
Stimulatory effects of the multi‐kinase inhibitor sorafenib on human bladder cancer cells

BACKGROUND AND PURPOSE Sorafenib is an inhibitor of several intracellular signalling kinases with anti‐proliferative, anti‐angiogenic and pro‐apoptotic effects in tumour cells. Sorafenib is used in the therapy of advanced renal cell carcinoma, and several phase II clinical trials are being carried out in patients with urothelial carcinomas.
Transcriptomic Changes in Coral Holobionts Provide Insights into Physiological Challenges of Future Climate and Ocean Change

Tropical reef-building coral stress levels will intensify with the predicted rising atmospheric CO2 resulting in ocean temperature and acidification increase. Most studies to date have focused on the destabilization of coral-dinoflagellate symbioses due to warming oceans, or declining calcification due to ocean acidification. In our study, pH and temperature conditions consistent with the end-of-century scenarios of the Intergovernmental Panel on Climate Change (IPCC) caused major changes in photosynthesis and respiration, in addition to decreased calcification rates in the coral Acropora millepora. Population density of symbiotic dinoflagellates (Symbiodinium) under high levels of ocean acidification and temperature (Representative Concentration Pathway, RCP8.5) decreased to half of that found under present day conditions, with photosynthetic and respiratory rates also being reduced by 40%. These physiological changes were accompanied by evidence for gene regulation of calcium and bicarbonate transporters along with components of the organic matrix. Metatranscriptomic RNA-Seq data analyses showed an overall down regulation of metabolic transcripts, and an increased abundance of transcripts involved in circadian clock control, controlling the damage of oxidative stress, calcium signaling/homeostasis, cytoskeletal interactions, transcription regulation, DNA repair, Wnt signaling and apoptosis/immunity/ toxins. We suggest that increased maintenance costs under ocean acidification and warming, and diversion of cellular ATP to pH homeostasis, oxidative stress response, UPR and DNA repair, along with metabolic suppression, may underpin why Acroporid species tend not to thrive under future environmental stress. Our study highlights the potential increased energy demand when the coral holobiont is exposed to high levels of ocean warming and acidification.
Jet Impingement Heat Transfer Using Air-Laden Nanoparticles With Encapsulated Phase Change Materials

Nanoparticles made of polymer encapsulated phase change materials (PCM) are added in air to enhance the heat transfer performance of air jet impingement flows applied to cooling processes. Encapsulation prevents agglomeration of the PCM (paraffin) nanoparticles when they are in the liquid phase. The sizes of the particles are chosen to be small enough so that they maintain near velocity equilibrium with the air stream. Small solid paraffin particles can absorb a significant amount of energy rapidly from a heat source by changing phase from solid to liquid. Nanoparticle volume fraction is found to play an important role in determining the overall pressure drop and heat transfer of the jet impingement process. Specifically, air jets laden with 2.5% particulate volume fraction were shown to improve the average heat transfer coefficient by 58 times in the air flow speed range of 4.6 to 15.2m/s when compared to that of pure air alone. In addition, the structural integrity of the encapsulating shells was demonstrated to be excellent by the repeated use of the nanoparticles in closed loop testing. [DOI: 10.1115/1.4023563]
PI(4,5)P2 forms dynamic cortical structures and directs actin distribution as well as polarity in Caenorhabditis elegans embryos

ABSTRACT Asymmetric division is crucial for embryonic development and stem cell lineages. In the one-cell Caenorhabditis elegans embryo, a contractile cortical actomyosin network contributes to asymmetric division by segregating partitioning-defective (PAR) proteins to discrete cortical domains. In the current study, we found that the plasma membrane lipid phosphatidylinositol 4,5-bisphosphate (PIP2) localizes to polarized dynamic structures in C. elegans zygotes, distributing in a PAR-dependent manner along the anterior–posterior (A–P) embryonic axis. PIP2 cortical structures overlap with F-actin, and coincide with the actin regulators RHO-1 and CDC-42, as well as ECT-2. Particle image velocimetry analysis revealed that PIP2 and F-actin cortical movements are coupled, with PIP2 structures moving slightly ahead of F-actin. Importantly, we established that PIP2 cortical structure formation and movement is actin dependent. Moreover, we found that decreasing or increasing the level of PIP2 resulted in severe F-actin disorganization, revealing interdependence between these components. Furthermore, we determined that PIP2 and F-actin regulate the sizing of PAR cortical domains, including during the maintenance phase of polarization. Overall, our work establishes that a lipid membrane component, PIP2, modulates actin organization and cell polarity in C. elegans embryos. Highlighted Article: PI(4,5)P2 is distributed in dynamic cortical structures and regulates asymmetric division by controlling actin organization as well as cell polarity in the one-cell C. elegans embryo.
Recombinational DSBs‐intersected genes converge on specific disease‐ and adaptability‐related pathways

Motivation: The budding yeast Saccharomyces cerevisiae is a model species powerful for studying the recombination of eukaryotes. Although many recombination studies have been performed for this species by experimental methods, the population genomic study based on bioinformatics analyses is urgently needed to greatly increase the range and accuracy of recombination detection. Here, we carry out the population genomic analysis of recombination in S.cerevisiae to reveal the potential rules between recombination and evolution in eukaryotes. Results: By population genomic analysis, we discover significantly more and longer recombination events in clinical strains, which indicates that adverse environmental conditions create an obviously wider range of genetic combination in response to the selective pressure. Based on the analysis of recombinational double strand breaks (DSBs)‐intersected genes (RDIGs), we find that RDIGs significantly converge on specific disease‐ and adaptability‐related pathways, indicating that recombination plays a biologically key role in the repair of DSBs related to diseases and environmental adaptability, especially the human neurological disorders. By evolutionary analysis of RDIGs, we find that the RDIGs highly prevailing in populations of yeast tend to be more evolutionarily conserved, indicating the accurate repair of DSBs in these RDIGs is critical to ensure the eukaryotic survival or fitness. Supplementary information: Supplementary data are available at Bioinformatics online.
The optimization of extraction process of white mulberry leaves and the characteristic bioactive properties its powder extract

Summary Introduction: Powder extracts from white mulberry leaves (Morus alba L.) are desirable due to their simplicity of use. Powders intended for use in food and dietary supplements can be obtained by various methods, including water extraction and spray drying. Objective: The aim of the work was to optimize the aqueous process of extraction of white mulberry leaves and characterization of bioactive properties of the obtained extract powder. Methods: The DNJ and flavonoids (quercetin, kaempferol) contents and were analysed by high performance liquid chromatography (HPLC). Total phenolic contents were determined using the Folin-Ciocalteu phenol reagent and antioxidant activity by ABTS and DPPH assays. Results: The mulberry leaf extraction process has been optimized. The obtained powdered mulberry leaf extract proved to be a good source of bioactive compounds. Characteristic phenolic compounds detected in mulberry leaves and their powder extract were quercetin and kaempferol. The sum of polyphenols was 10.9 mg GAE/g dry matter in the raw material, whereas in the powder extract 42.6 mg GAE/g dry matter. In addition, it was found that the obtained powdered extract is characterized by a five-fold higher, in comparison to the raw material, the content of antioxidant activity measured by ABTS and DPPH tests. The content of 1-deoxynojirimycin (DNJ) in the powder extract was nearly four times higher than in dry mulberry leaves. Conclusion: The optimized process of water extraction of white mulberry leaves allows to keep valuable bioactive components and to obtain their high concentration.
Complementation of hypersensitivity to DNA interstrand crosslinking agents demonstrates that XRCC2 is a Fanconi anaemia gene

Background Fanconi anaemia (FA) is a heterogeneous inherited disorder clinically characterised by progressive bone marrow failure, congenital anomalies and a predisposition to malignancies. Objective Determine, based on correction of cellular phenotypes, whether XRCC2 is a FA gene. Methods Cells (900677A) from a previously identified patient with biallelic mutation of XRCC2, among other mutations, were genetically complemented with wild-type XRCC2. Results Wild-type XRCC2 corrects each of three phenotypes characteristic of FA cells, all related to the repair of DNA interstrand crosslinks, including increased sensitivity to mitomycin C (MMC), chromosome breakage and G2–M accumulation in the cell cycle. Further, the p.R215X mutant of XRCC2, which is harboured by the patient, is unstable. This provides an explanation for the pathogenesis of this mutant, as does the fact that 900677A cells have reduced levels of other proteins in the XRCC2–RAD51B-C-D complex. Also, FANCD2 monoubiquitination and foci formation, but not assembly of RAD51 foci, are normal in 900677A cells. Thus, XRCC2 acts late in the FA–BRCA pathway as also suggested by hypersensitivity of 900677A cells to ionising radiation. These cells also share milder sensitivities towards olaparib and formaldehyde with certain other FA cells. Conclusions XRCC2/FANCU is a FA gene, as is another RAD51 paralog gene, RAD51C/FANCO. Notably, similar to a subset of FA genes that act downstream of FANCD2, biallelic mutation of XRCC2/FANCU has not been associated with bone marrow failure. Taken together, our results yield important insights into phenotypes related to FA and its genetic origins.
Econometric Estimation of Capital-Labor Substitution Elasticities for Ukrainian CGE Model

The paper presents econometric estimation of the capital-labor substitution elasticities for 10 economic activities based on the 2003-2009 data. Elasticities are estimated in the context of computable general equilibrium methodology, particularly, based on the constant elasticity of substitution production functions and cost minimization assumptions. Choice of methods and approaches to elasticities estimation is based on the literature review. Thus paper considers issues of minimum statistical data amount requirements needed to obtain reliable estimates, choice of functional forms to be used for approximation and specification of economic indicators to represent variables of production functions. According to the received estimates, values of Ukrainian capital-labor substitution elasticities are rather low (0.13-0.82). At the same time, service industries are characterized by lower elasticity values, compared to the real sector of Ukrainian economy, which can be explained by the fact that services have higher intensity of labor employment. Despite the availability of relatively small amount of historical data and some methodological aspects, obtained estimates call into question the appropriateness of the utilization of certain production functions for modelling the investigated processes. In particular, this includes the case of Cobb-Douglas production functions that have unitary elasticity of substitution. In general, given the characteristics of CGE modelling approach, the obtained elasticity's point estimates should be used as initial values of exogenous parameters, which should be reconsidered and changed during the sensitivity analysis and verification of results reliability.
Hotspot Based Yield Prediction with Consideration of Correlations

Design for manufacturability and yield has becomes a major issue for advanced VLSI technology nodes. The demand for a yield prediction capability has been growing significantly. Unfortunately, systematic yield prediction and analysis is still behind in both research and availability of commercial tools. A major reason for that is the high dependency of such research on hard to come by data from fabs. Thus a new approach that limits this dependency is needed. In this paper, we propose a novel and practical approach that enables systematic yield prediction with limited fab information and data. This approach is based on the information of hotspot definitions and their yield scores. The required inputs are more practical and realistic and less confidential. The dependency on the fab data is minimal. In this approach, we propose an algorithm that properly incorporates spatial correlations between yield variables when computing full chip total yield. The predicted total yield score is accurate and robust. We further demonstrate the high level of accuracy by both theory and simulation.
Exploring post-sterilization regret in an underdeveloped region of rural West Bengal

The present study tries to explore post-sterilization regret in an underdeveloped region in the state of West Bengal, India. Although the state of West Bengal has witnessed fertility transition during the recent past and the adoption of female sterilization has increased substantially, the level of infant and child mortality remained at a high level, particularly among the marginalized. Data of 766 sterilization users belonging to 45 villages of Birbhum district of West Bengal were collected in a smallscale research study. Multivariate binary logit regressions were used to identify the socio-demographic characteristics associated with poststerilization regret.Women who have living children of both sexes and have participated in decision making regarding sterilization were significantly less likely to report regret, while those who had an incidence of child loss, reported post-sterilization health problems,did not have informed choice before sterilization and belonging to marginalized communities were more likely to report post-sterilization regret.
Robust fuzzy control for stochastic Markovian jumping systems via sliding mode method

This paper considers the problem of sliding mode control for stochastic Markovian jumping systems by means of fuzzy method. The Takagi–Sugeno (T–S) fuzzy stochastic model subject to state-dependent noise is presented. A key feature in this work is to remove the restricted condition that each local system model had to share the same input channel, which is usually assumed in some existing results. The integral sliding surface is constructed for every mode and the connections among various sliding surfaces are established via a set of coupled matrices. Moreover, the present sliding mode controller including the transition rates of modes can cope with the effect of Markovian switching. It is shown that both the reachability of sliding surfaces and the stability of sliding mode dynamics can be ensured. Finally, numerical simulation results are given.
Socioeconomic development index ranking calculations of cities with fuzzy clustering method: case of Turkey

In economy policies, socioeconomic indicators have an important place in determining the development levels. The determination and classification of the current social and economic structure of cities is considerably important in analyzing the development of cities and their probable development tendencies and in developing the regional development policies in parallel with this. In this study, cities are classified by fuzzy clustering c-means method according to their development levels with the help of socio-economic indicators. The aim is to determine the homogeneous city groups having the same characteristics based on these indicators. The data gathered from the study have been compared with some other classification studies in the literature. In this paper, development levels of cities were classified with socioeconomic indicators using FCM. Development Index values used for cities classification upon socioeconomic indicators. Results were also compared with DPT and Is-Bank development index values and interpreted.
Cell Signaling Switches HOX-PBX Complexes from Repressors to Activators of Transcription Mediated by Histone Deacetylases and Histone Acetyltransferases

ABSTRACT The Hoxb1 autoregulatory element comprises three HOX-PBX binding sites. Despite the presence of HOXB1 and PBX1, this enhancer fails to activate reporter gene expression in retinoic acid-treated P19 cell monolayers. Activation requires cell aggregation in addition to RA. This suggests that HOX-PBX complexes may repress transcription under some conditions. Consistent with this, multimerized HOX-PBX binding sites repress reporter gene expression in HEK293 cells. We provide a mechanistic basis for repressor function by demonstrating that a corepressor complex, including histone deacetylases (HDACs) 1 and 3, mSIN3B, and N-CoR/SMRT, interacts with PBX1A. We map a site of interaction with HDAC1 to the PBX1 N terminus and show that the PBX partner is required for repression by the HOX-PBX complex. Treatment with the deacetylase inhibitor trichostatin A not only relieves repression but also converts the HOX-PBX complex to a net activator of transcription. We show that this activation function is mediated by the recruitment of the coactivator CREB-binding protein by the HOX partner. Interestingly, HOX-PBX complexes are switched from transcriptional repressors to activators in response to protein kinase A signaling or cell aggregation. Together, our results suggest a model whereby the HOX-PBX complex can act as a repressor or activator of transcription via association with corepressors and coactivators. The model implies that cell signaling is a direct determinant of HOX-PBX function in the patterning of the animal embryo.
Improvement of input side currents of a three phase rectifier using Cúk converter in discontinuous-capacitor-voltage mode operation

The characteristics of Cuk converters in discontinuous-capacitor-voltage mode are studied. A Cuk converter in this mode of operation is an inherent power factor corrector and features soft turn of switching. This paper proposes a Cuk converter in discontinuous-capacitor-voltage mode (DCVM) operation in order to reduce the total harmonic distortion (THD) of a three-phase rectifier. In the proposed circuit pulse width modulation (PWM) is used to regulate the output voltage. A small series LC filter is used at the input side to suppress the low frequency harmonics components that may pass to the input. Some simulation results are presented. The variation of output voltage, THD of input current and power factor with duty cycle of the proposed converter circuit are also presented in this paper.