Miracle-dz/UniFAR-FTUs huggingface dataset:
Improvement in the suspension‐culture production of recombinant adeno‐associated virus–LacZ in HEK‐293 cells using polyethyleneimine–DNA complexes in combination with hypothermic treatment

rAAV (recombinant adeno‐associated virus) has become a very useful gene‐delivery vector for gene therapy. However, it is very difficult to generate rAAV using triple transfection on a commercial scale, owing to its low transfection efficiency. An optimal procedure for transfection in suspension‐culture mode was developed for rAAV–LacZ production in suspension‐cultured HEK‐293 (human embryonic kidney‐293) cells mediated by PEI (polyethyleneimine)–DNA complexes in combination with transient severe hypothermia at 4 °C for 1 h in the present study (LacZ is the product of the reporter gene lacZ, which codes for β‐d‐galactosidase). It showed that the PEI/DNA ratio, cell density at the beginning of transfection and cell‐cycle arrest in G2/M‐phase were key factors affecting suspension‐culture triple‐transfection efficiency and rAAV–LacZ productivity. After incubation at 4 °C for 1 h and re‐warming at 37 °C for 18 h, HEK‐293 cells at 1×106 cells/ml were transfected with PEI–DNA complexes at a PEI/DNA ratio of 5:1 (w/w) with final concentrations of 30 μg/ml 25 kDa linear PEI and 6 μg/ml plasmid DNA in culture. After 6 h incubation for transfection, an equal volume of medium was added to the culture for additional 48 h growth until harvest. Finally, the high transfection efficiency of some 75% and rAAV–LacZ titre of (7.48±0.59)×1011 physical particles or 1.86±0.96×1010 infectious particles were achieved in 250 ml shake flasks with 60 ml working volume, indicating a promising application for scale‐up.
Investigating Validation of Armey Curve Hypothesis for G7 Countries using ARDL Model

The effect of the government size on economic growth still keeps its unclear status despite the works in this field. According to the Armey Hypothesis (1995), which one of the studies developed for the volume of government size in economy, the increase in the public volume in economy will increase economic growth up to a certain level, and when the maximum level is reached, the increase in public volume will cause decreases in economic growth. In this study, the issues of whether the Armey Hypothesis is valid or not for G7 countries has been investigated, and the optimum public volume has been determined for G7 countries. In testing Armey Curve hypothesis, we use ARDL cointegration procedure. The results of empirical findings argue that the Armey Hypothesis is valid for US, and Canada, and France when it is invalid for other G7 countries.
Severe Acute Respiratory Syndrome Coronavirus nsp9 Dimerization Is Essential for Efficient Viral Growth

ABSTRACT The severe acute respiratory syndrome coronavirus (SARS-CoV) devotes a significant portion of its genome to producing nonstructural proteins required for viral replication. SARS-CoV nonstructural protein 9 (nsp9) was identified as an essential protein with RNA/DNA-binding activity, and yet its biological function within the replication complex remains unknown. Nsp9 forms a dimer through the interaction of parallel α-helices containing the protein-protein interaction motif GXXXG. In order to study the role of the nsp9 dimer in viral reproduction, residues G100 and G104 at the helix interface were targeted for mutation. Multi-angle light scattering measurements indicated that G100E, G104E, and G104V mutants are monomeric in solution, thereby disrupting the dimer. However, electrophoretic mobility assays revealed that the mutants bound RNA with similar affinity. Further experiments using fluorescence anisotropy showed a 10-fold reduction in RNA binding in the G100E and G104E mutants, whereas the G104V mutant had only a 4-fold reduction. The structure of G104E nsp9 was determined to 2.6-Å resolution, revealing significant changes at the dimer interface. The nsp9 mutations were introduced into SARS-CoV using a reverse genetics approach, and the G100E and G104E mutations were found to be lethal to the virus. The G104V mutant produced highly debilitated virus and eventually reverted back to the wild-type protein sequence through a codon transversion. Together, these data indicate that dimerization of SARS-CoV nsp9 at the GXXXG motif is not critical for RNA binding but is necessary for viral replication.
A multi-period optimal power flow model including battery energy storage

Energy storage devices play a very important role in nowadays inter-connected power systems. They could be used for peak shaving as well as mitigating the fluctuations caused by distributed generation sources. The development of battery technologies makes it possible to integrate large-scale battery energy storage (BES) devices into power systems. In this paper, a multi-period optimal power flow (OPF) model including BES is proposed to study the effect of BES on power generation scheduling. The objective of the proposed model is to minimize the total generation cost considering charging and discharging costs of BES. State of charge (SOC) constraints and other power network constraints are taken into consideration in the model. The proposed model determines the optimal output power in each period as well as the battery charging/discharging schedule. Finally, the numerical example based on IEEE-30 system shows effectiveness and validity of the proposed model.
Cooperative Steering Assist Control System

The paper deals with the design of lateral shared vehicle control taking into account the interaction between the driver and the assistance system. The shared control system is designed in such a way to ensure a good transfer of the control authority without generating negative interference. For that a driver model that allows making valid predictions on the driver behaviour is integrated in the design process of the controller. In order to avoid complex conflict situations such as during lane change maneuver, a decision making algorithm for the control authority shifting is also proposed and implemented. Experimental results provided in the paper, using interactive simulator, show the effectiveness of the approach to ensure shared lateral vehicle control.
Determinants of Capital Flows in the Korean Bond Market

This study shows that interest rate differentials have minor impacts on overall capital flows into the Korean bond market. They are significant factors for private bank capital, however only for short-term interest rates, which takes up ignorable amounts in total capital balances. The most impressive factor is the foreign currency reserves owned by major central banks; these are particularly influential to capital flows throughout the sectors. Global and local risk indicators can also explain the variation of capital flows by sector. The underlying reasons behind these findings are as follows: changes in the proportions of sectoral capital balances after the global financial crisis, introduction of regulations on leverage ratios for international banks, risk management by investors, and increasing flows from foreign currency reserves of major central banks.
Strategic down‐regulation of attentional resources as a mechanism of proactive response inhibition

Efficiently avoiding inappropriate actions in a changing environment is central to cognitive control. One mechanism contributing to this ability is the deliberate slowing down of responses in contexts where full response cancellation might occasionally be required, referred to as proactive response inhibition. The present electroencephalographic (EEG) study investigated the role of attentional processes in proactive response inhibition in humans. To this end, we compared data from a standard stop‐signal task, in which stop signals required response cancellation (‘stop‐relevant’), to data where possible stop signals were task‐irrelevant (‘stop‐irrelevant’). Behavioral data clearly indicated the presence of proactive slowing in the standard stop‐signal task. A novel single‐trial analysis was used to directly model the relationship between response time and the EEG data of the go‐trials in both contexts within a multilevel linear models framework. We found a relationship between response time and amplitude of the attention‐related N1 component in stop‐relevant blocks, a characteristic that was fully absent in stop‐irrelevant blocks. Specifically, N1 amplitudes were lower the slower the response time, suggesting that attentional resources were being strategically down‐regulated to control response speed. Drift diffusion modeling of the behavioral data indicated that multiple parameters differed across the two contexts, likely suggesting the contribution from independent brain mechanisms to proactive slowing. Hence, the attentional mechanism of proactive response control we report here might coexist with known mechanisms that are more directly tied to motoric response inhibition. As such, our study opens up new research avenues also concerning clinical conditions that feature deficits in proactive response inhibition.
Purine Metabolism in B-Cell Lymphocytic Leukemia: A Microarray Approach

B-cell chronic lymphocytic leukemia (B-CLL) is an adult-onset highly heterogeneous malignancy characterized by a cells resistance to apoptosis rather than to highly proliferative cells. In previous research, we evidenced an imbalance of purine metabolism in B-CLL cells. Since the extracellular adenosine has been proved to induce apoptosis via A2b receptor, enzymes involved in adenosine metabolism could play an important role in apoptosis resistance of B-CLL cells. We prepared a microarray chip for the analysis of 50 selected genes that could be of interest in B-CLL: enzymes of purine de-novo, salvage and catabolic pathway, oxidative stress enzymes, and apoptotis-related proteins. Preliminary results identify many genes of purine metabolism that exhibit low or high expression, while genes involved in signal transduction and apoptosis exhibit lower alterations even if of remarkable interest. This application of microarray technique seems promising and at least a subset of these genes will be valid candidates for further studies.
Nanotechnology for cancer diagnostics: promises and challenges

Despite recent progress in the treatment of cancer, the majority of cases are still diagnosed only after tumors have metastasized, leaving the patient with a grim prognosis. However, there may be an opportunity to drastically reduce the burden of cancer, if the disease can be detected early enough. Nanotechnology is in a unique position to transform cancer diagnostics and to produce a new generation of biosensors and medical imaging techniques with higher sensitivity and precision of recognition. This review examines the in vitro and in vivo diagnostic applications of nanoparticles, and other nanodevices that are likely to have an impact on the field in the future. Future developments that may lead to the realization of multifunctional detection and treatment nanoparticle platforms are also discussed.
A novel multisystem disease associated with recessive mutations in the tyrosyl‐tRNA synthetase (YARS) gene

Aminoacyl‐tRNA synthetases (ARSs) are a group of ubiquitously expressed enzymes that are best known for their function in the first step of protein translation but have been increasingly associated with secondary functions including transcription and translation control and extracellular signaling. Mutations in numerous ARSs have been linked to a growing number of both autosomal dominant and autosomal recessive human diseases. The tyrosyl‐tRNA synthetase (YARS) links the amino acid tyrosine to its cognate tRNA. We report two siblings who presented with failure to thrive (FTT), hypertriglyceridemia, developmental delay, liver dysfunction, lung cysts, and abnormal subcortical white matter. Using exome sequencing the siblings were found to harbor bi‐allelic pathogenic‐appearing variants within the YARS gene (NM_003680.3):c.638C>T p.(Pro213Leu) and c.1573G>A p.(Gly525Arg). These YARS variants occur in the catalytic domain and the C‐terminal domain, respectively. Mutations in YARS have been previously associated with an autosomal dominant form of Charcot‐Marie‐Tooth (CMT); our findings suggest the disease spectrum associated with YARS dysregulation is broader than peripheral neuropathy. © 2016 Wiley Periodicals, Inc.
Effectiveness of cardiac resynchronization therapy in mild congestive heart failure: systematic review and meta‐analysis of randomized trials

Cardiac resynchronization therapy (CRT) improves echocardiographic parameters, symptoms, hospitalizations, and mortality in patients with New York Heart Association (NYHA) Class III or IV symptoms with left ventricular systolic dysfunction, sinus rhythm, and a prolonged QRS duration. The effectiveness of CRT in patients with mild heart failure symptoms has not been systematically reviewed.
Language dominance and inhibition abilities in bilingual older adults*

This study aimed to examine the so-called bilingual advantage in older adults’ performance in three cognitive domains and to identify whether language use and bilingual type (dominant vs. balanced) predicted performance. The participants were 106 Spanish–English bilinguals ranging in age from 50 years to 84 years. Three cognitive domains were examined (each by a single test): inhibition (the Simon task), alternating attention (the Trail Making test), and working memory (Month Ordering). The data revealed that age was negatively correlated to performance in each domain. Bilingual type – balanced vs. dominant – predicted performance and interacted with age only on the inhibition measure (the Simon task). Balanced bilinguals showed age-related inhibition decline (i.e., greater Simon effect with increasing age); in contrast, dominant bilinguals showed little or no age-related change. The findings suggest that bilingualism may offer cognitive advantage in older age only for a subset of bilinguals.
IL-6 and Maturation Govern TLR2 and TLR4 Induced TLR Agonist Tolerance and Cross-Tolerance in Dendritic Cells1

Stimulation of naive mouse dendritic cells (DC) with LPS or Pam3CSK4 (P3C) induces production of TNF-α via TLR4- or TLR2-signaling. Although tolerance in macrophages has been studied in detail, we investigated the role of TLR agonist concentration and IL-6 for tolerance in DC. P3C- or LPS-primed DC were nonresponsive to P3C or LPS restimulation in terms of TNF-α but not IL-6 production. The mechanisms involved in tolerance were dependent on the concentration of the TLR ligand used for DC priming. DC primed with LPS or P3C at high concentrations developed a maturation dependent, IL-6 independent tolerance associated with inhibition of TLR signaling upstream of IκB as indicated by decreased IκB degradation. In contrast, priming of DC with LPS or P3C at low concentrations resulted in IL-6-dependent tolerance, which was abolished in IL-6 deficient DC, and was not accompanied by maturation of DC or by down-regulation of TLR2 or TLR4. In homotolerogenic DC primed with LPS or P3C at high concentrations, degradation of IκB upon restimulation with LPS or P3C was inhibited suggesting tolerance mechanism(s) upstream of IκB; in contrast, cross-tolerance in DC primed with LPS or P3C at low concentrations was not associated with reduced IκB degradation suggesting tolerance mechanisms downstream of IκB. Our data indicate that in naive DC TLR4- and TLR2-stimulation results in homo- and cross-tolerance; the mechanisms involved in tolerance depend on the concentration of the TLR agonist used for DC priming and are governed by IL-6 and maturation.
Almost-parameter-free Differential Evolution

A fit parameter setting usually improves greatly the performance of Differential Evolution, hence various strategies for parameter setting have been proposed. However, how to set these is nuisance because each of the strategies only outperforms the other one in some specific aspect. In the paper, an almost-parameter-free Differential Evolution is presented. The algorithm thinks of each individual as a charged particle and utilizes the attraction-repulsion mechanism among them to decide on the step length of the motion of the individual in the direction of the difference. Moreover, Taguchi's parameter design method with the two-level orthogonal array is used to execute the crossover operation for the purpose of obtaining the better combination of factor levels. The proposed algorithm has small population size, and avoids the settings of the scale factor and the crossover probability. Numerical experiments show that the proposed algorithm outperforms the other compared algorithms.
Calcium-dependent Spontaneously Reversible Remodeling of Brain Mitochondria*

An exposure of cultured hippocampal neurons expressing mitochondrially targeted enhanced yellow fluorescent protein to excitotoxic glutamate resulted in reversible mitochondrial remodeling that in many instances could be interpreted as swelling. Remodeling was not evident if glutamate receptors were blocked with MK801, if Ca2+ was omitted or substituted for Sr2+ in the bath solution, if neurons were treated with carbonylcyanide p-trifluoromethoxyphenylhydrazone to depolarize mitochondria, or if neurons were pretreated with cyclosporin A or N-methyl-4-isoleucine-cyclosporin (NIM811) to inhibit the mitochondrial permeability transition. In the experiments with isolated brain synaptic or nonsynaptic mitochondria, Ca2+ triggered transient, spontaneously reversible cyclosporin A-sensitive swelling closely resembling remodeling of organelles in cultured neurons. The swelling was accompanied by the release of cytochrome c, Smac/DIABLO, Omi/HtrA2, and AIF but not endonuclease G. Depolarization with carbonylcyanide p-trifluoromethoxyphenylhydrazone or inhibition of the Ca2+ uniporter with Ru360 prevented rapid onset of the swelling. Sr2+ depolarized mitochondria but failed to induce swelling. Neither inhibitors of the large conductance Ca2+-activated K+ channel (charybdotoxin, iberiotoxin, quinine, and Ba2+) nor inhibitors of the mitochondrial ATP-sensitive K+ channel (5-hydroxydecanoate and glibenclamide) suppressed swelling. Quinine, dicyclohexylcarbodiimide, and Mg2+, inhibitors of the mitochondrial K+/H+ exchanger, as well as external alkalization inhibited a recovery phase of the reversible swelling. In contrast to brain mitochondria, liver and heart mitochondria challenged with Ca2+ experienced sustained swelling without spontaneous recovery. The proposed model suggests an involvement of the Ca2+-dependent transient K+ influx into the matrix causing mitochondrial swelling followed by activation of the K+/H+ exchanger leading to spontaneous mitochondrial contraction both in situ and in vitro.
Sex Reversal: A Fountain of Youth for Sex Chromosomes?

Nonrecombining Y chromosomes are expected to degenerate through the progressive accumulation of deleterious mutations. In lower vertebrates, however, most species display homomorphic sex chromosomes. To address this, paradox I propose a role for sex reversal, which occasionally occurs in ectotherms due to the general dependence of physiological processes on temperature. Because sex-specific recombination patterns depend on phenotypic, rather than genotypic sex, homomorphic X and Y chromosomes are expected to recombine in sex-reversed females. These rare events should generate bursts of new Y haplotypes, which will be quickly sorted out by natural or sexual selection. By counteracting Muller's ratchet, this regular purge should prevent the evolutionary decay of Y chromosomes. I review empirical data supporting this suggestion, and propose further investigations for testing it.
Life Cycle Assessment of the Production of a Large Variety of Meat Analogs by Three Diverse Factories

ABSTRACT Meat analogs have been proposed as a viable ‘lower carbon’ alternative to meats. However, data on the greenhouse gas (GHG) emissions from those products are limited. We performed partial (farm to factory gate) life cycle assessment (LCA) with Simapro 8.1 to calculate the GHG emissions from a wide range of meat analog products from three factories. The mean GHG footprint was 2.19 kg CO2e/kg, and the range was from 1.33 kg CO2e/kg to 2.79 kg CO2e/kg. Most of the GHG emissions (45%) resulted from manufacturing processes, followed by agricultural production and transport of food ingredients. Meat analogs generated relatively low GHG emissions, across all categories, factory sizes and countries of production.
Evaluation of Broth Microdilution Testing Parameters and Agar Diffusion Etest Procedure for Testing Susceptibilities of Aspergillus spp. to Caspofungin Acetate (MK-0991)

ABSTRACT The NCCLS M38-A document does not describe guidelines for testing caspofungin acetate (MK-0991) and other echinocandins against molds. This study evaluated the susceptibilities of 200 isolates of Aspergillus fumigatus, A. flavus, A. nidulans, A. niger, and A. terreus to caspofungin (MICs and minimum effective concentrations [MECs]) by using standard RPMI 1640 (RPMI) and antibiotic medium 3 (M3), two inoculum sizes (103 and 104 CFU/ml), and two MIC determination criteria (complete [MICs-0] and prominent growth inhibition [MICs-2]) at 24 and 48 h. Etest MICs were also determined. In general, caspofungin MIC-2 and MEC pairs were comparable with both media and inocula (geometric mean ranges of MECs and MICs, respectively, with larger inoculum: 0.12 to 0.64 μg/ml and 0.12 to 0.44 μg/ml with RPMI versus 0.04 to 0.51 μg/ml and 0.03 to 0.21 μg/ml with M3); however, MEC results were less influenced by testing conditions than MICs, especially with the larger inoculum. Overall, the agreement between caspofungin Etest MICs and broth dilution values was higher with MECs obtained with M3 (>90%) and the large inoculum than under the other testing conditions. Because RPMI is a more stable and chemically defined medium than M3, the determination at 24 h of the easier visual MECs with RPMI and the inoculum recommended in the M38-A document appears to be a suitable procedure at present for in vitro testing of caspofungin against Aspergillus spp. Future in vitro correlations with in vivo outcome of both microdilution and Etest procedures may detect more-relevant testing conditions.
Automatic and Fast PCM Generation for Occluded Object Detection in High-Resolution Remote Sensing Images

Partial configuration model (PCM) is an occluded object detection method in high-resolution remote sensing images (HR-RSIs) based on the deformable part-based model (DPM). However, it needs extra category predefinition, considerable part-level annotation, and repeated multimodel training. In this letter, an automatic and fast PCM generation method is proposed based on a novel part sharing mechanism. We propose to share parts from one trained DPM model (tDPM) among different models of partial configurations (PCs) to address the above problems. PCs are first designed according to part anchors of tDPM. The model is then generated through corresponding parts selection, root coverage cropping, and elements reweighing. This method avoids the need for manual category predefinition and part-level annotation, while largely reducing the computation of PCM training. Experimental results on three HR-RSI data sets show that the proposed method obtains a training speedup of <inline-formula> <tex-math notation="LaTeX">$6.7\times $ </tex-math></inline-formula> and <inline-formula> <tex-math notation="LaTeX">$2\times $ </tex-math></inline-formula> for each PC of airplane and ship categories, while achieving a comparable accuracy compared with PCM.