Miracle-dz/UniFAR-FTUs huggingface dataset:
Blockade of Human α7 Nicotinic Acetylcholine Receptor by α-Conotoxin ImI Dendrimer: Insight from Computational Simulations

Nicotinic acetylcholine receptors (nAChRs) are ligand-gated ion channels that are involved in fast synaptic transmission and mediated physiological activities in the nervous system. α-Conotoxin ImI exhibits subtype-specific blockade towards homomeric α7 and α9 receptors. In this study, we established a method to build a 2×ImI-dendrimer/h (human) α7 nAChR model, and based on this model, we systematically investigated the molecular interactions between the 2×ImI-dendrimer and hα7 nAChR. Our results suggest that the 2×ImI-dendrimer possessed much stronger potency towards hα7 nAChR than the α-ImI monomer and demonstrated that the linker between α-ImI contributed to the potency of the 2×ImI-dendrimer by forming a stable hydrogen-bond network with hα7 nAChR. Overall, this study provides novel insights into the binding mechanism of α-ImI dendrimer to hα7 nAChR, and the methodology reported here opens an avenue for the design of more selective dendrimers with potential usage as drug/gene carriers, macromolecular drugs, and molecular probes.
“French Phage Network” Annual Conference 2018—Fourth Meeting Report

The present meeting report aims to cover the scientific activities of the 4th French Bacteriophage Network (Phages.fr) symposium which took place during 24th–25th September 2018, at the Agora du Haut-Carré in Talence (France). The hosting institute was University Bordeaux and 72 participants attended the meeting from both public and private sectors, coming from France, Belgium, Ireland, Germany, Portugal and Canada. The scientific program was structured in three themed oral sessions entitled “ecology and evolution”, “bacteriophage-host molecular interaction”, and “therapy and biotechnology applications” consisting of 21 oral presentations, including three keynote lectures, and a presentation of the activities of the Spanish bacteriophage network. A poster session included 22 presentations.
Staying hepatitis C negative: A systematic review and meta‐analysis of cure and reinfection in people who inject drugs

Direct‐acting antivirals (DAAs) are highly effective in treating hepatitis C. However, there is concern that cure rates may be lower, and reinfection rates higher, among people who inject drugs. We conducted a systematic review of treatment outcomes achieved with DAAs in people who inject drugs (PWID).
Survival Outcomes of Patients with Primary Breast Cancer Following Primary Ovarian Cancer

Background Patients with primary breast cancer following primary ovarian cancer do not comprise a large clinical entity, and reports of the survival outcomes of this cohort are rare. The purpose of this retrospective population-based research was to investigate the survival outcomes of patients with primary breast cancer after primary ovarian cancer. Material/Methods A cohort of patients diagnosed with primary breast cancer following primary ovarian cancer between 1973 and 2014 was drawn from the National Cancer Institute’s Surveillance Epidemiology and End Results (SEER) database. Cox proportional hazards survival regression analysis and Kaplan-Meier were applied to calculate overall survival (OS), cancer-specific survival (CSS), and independent predictors of CSS. Results A total of 1455 patients with primary breast cancer following primary ovarian cancer were identified. The 5-year and 10-year OS rates for the entire cohort were 81.7% and 67.4%, respectively. The 5-year and 10-year CSS rates were 84.2% and 74.3% for ovarian cancer, and 76.0% and 67.8% for breast cancer, respectively. Multivariate analysis revealed that independent predictors of ovarian cancer CSS include age, cancer stage, diagnosis time, and histological subtype. Conclusions Patients diagnosed with breast cancer following ovarian cancer have better survival rates. Patients age, ovarian cancer stage, ovarian cancer histological type, and time of diagnose affect the survival rate.
Allograft Rejection Requires STAT5a/b-Regulated Antiapoptotic Activity in T Cells but Not B Cells1

STATs play key roles in immune function. We examined the role of STAT5a/b in allograft rejection. STAT5a/b-deficient mice showed a 4-fold increased survival time of heart allografts (p < 0.01). Unlike wild type, purified STAT5a/b−/− T cells transferred to Rag1−/− recipients failed to mediate heart allograft rejection until supplemented with STAT5a/b−/− B cells. In vitro, STAT5a/b−/− T cells did not proliferate in response to Con A or alloantigens but entered apoptosis within 48 h (95%). Activated STAT5a/b−/− T cells showed increased expression of proapoptotic (caspases, DNA repair genes, TNF/TNFR-associated factor family genes) and decreased antiapoptotic mRNAs in microarrays, while Western blots confirmed reduced antiapoptotic Bcl-2 and elevated proapoptotic Bax protein expression. Interestingly, at 24 h postactivation, STAT5a/b+/+ and STAT5a/b−/− T cells produced similar levels of IL-2, IL-4, IL-10, and IFN-γ mRNA; ELISPOT assay showed an equivalent number of IL-4- and IFN-γ-producing T cells in both STAT5a/b+/+ and STAT5a/b−/− splenic populations. Sera from STAT5a/b+/+ and STAT5a/b−/− rejectors had donor-specific IgM, IgG1, IgG2a, and IgG2b Ab, while STAT5a/b deficiency had no impact on B cell survival or proliferation in response to LPS. Compared with allografts from STAT5a/b+/+ recipients, heart allografts from STAT5a/b−/− recipients had markedly reduced infiltration by CD4 and CD8 T cells but increased infiltration by B cells and dense endothelial deposition of C4d, a marker of humoral rejection. Thus, activated STAT5a/b−/− T cells produce cytokines prior to entering apoptosis, thereby promoting differentiation of B cells yielding donor-specific IgM and IgG Ab that mediate allograft rejection.
Influence of Preparation Procedure on Physicochemical and Antibacterial Properties of Titanate Nanotubes Modified with Silver

Silver nanoparticles (NPs) are effective antibacterial agents; however, aggregation of NPs and uncontrolled release of Ag+ affect their efficiency and may pose a risk to the environment. To overcome these disadvantages, immobilization of Ag onto titanate nanotubes (TNTs) was investigated. This paper describes the physicochemical and antibacterial properties of silver incorporated titanate nanotubes (Ag/TNTs) prepared using five procedures and containing different Ag amounts (0.11–30.85 wt.%). The methods were (i) sol-gel followed by a hydrothermal process; (ii) photodeposition under ambient conditions; (iii) photodeposition under an inert atmosphere; (iv) NaBH4 reduction; and (v) electroless deposition after activation of TNTs with Sn2+. Depending on the synthesis procedure, the presence of metallic Ag NPs, AgO or AgCl was observed. The electroless method led to an additional deposition of SnO2 NPs. The antibacterial properties of Ag/TNTs were analyzed as a function of Ag content and released against Escherichia coli and Staphylococcus epidermidis. The best bactericidal properties exhibited Ag/TNTs prepared through the photodeposition process due to the higher interaction of exposed Ag NPs with bacteria. An increase of Ag loading resulted in improvement of antibacterial activity of Ag/TNTs although no direct correlation between silver content or release and inhibition of bacterial growth was found.
Stochastic single cell migration leads to robust horizontal cell layer formation in the vertebrate retina

ABSTRACT Developmental programs that arrange cells and tissues into patterned organs are remarkably robust. In the developing vertebrate retina, for example, neurons reproducibly assemble into distinct layers giving the mature organ its overall structured appearance. This stereotypic neuronal arrangement, termed lamination, is important for efficient neuronal connectivity. Although retinal lamination is conserved in many vertebrates, including humans, how it emerges from single cell behaviour is not fully understood. To shed light on this issue, we here investigated the formation of the retinal horizontal cell layer. Using in vivo light sheet imaging of the developing zebrafish retina, we generated a comprehensive quantitative analysis of horizontal single cell behaviour from birth to final positioning. Interestingly, we find that all parameters analysed, including cell cycle dynamics, migration paths and kinetics, as well as sister cell dispersal, are very heterogeneous. Thus, horizontal cells show individual non-stereotypic behaviour before final positioning. Yet these initially variable cell dynamics always generate the correct laminar pattern. Consequently, our data show that the extent of single cell stochasticity in the lamination of the vertebrate retina is underexplored. Summary: Long-term in vivo lightsheet imaging of a large cohort of HCs shows that cell cycle and migration parameters vary substantially before final positioning. This provides evidence that retinal lamination contains variable and stochastic elements.
Strongly Enhanced Phosphor Efficiency in GaInN White Light-Emitting Diodes Using Remote Phosphor Configuration and Diffuse Reflector Cup

Enhancement of phosphor efficiency is reported for GaInN-based white light-emitting diodes (LEDs) employing a large separation between the primary LED emitter and the wavelength converter, and a diffuse reflector cup. Ray-tracing simulations show that extraction efficiency of wavelength-converted light is enhanced by 75%. The experimental improvement in phosphor efficiency of blue-pumped yellow phosphor is 15.4% compared with conventional phosphor-based white LEDs. The improvement is attributed to reduced re-absorption of wavelength-converted light by the LED chip.
Kinetics of Crystallization and Thermal Degradation of an Isotactic Polypropylene Matrix Reinforced with Graphene/Glass-Fiber Filler

Polypropylene composites reinforced with a filler mixture of graphene nanoplatelet-glass fiber were prepared by melt mixing, while conventional composites containing graphene nanoplatelet and glass fiber were prepared for comparative reasons. An extensive study of thermally stimulated processes such as crystallization, nucleation, and kinetics was carried out using Differential Scanning Calorimetry and Thermogravimetric Analysis. Moreover, effective activation energy and kinetic parameters of the thermal decomposition process were determined by applying Friedman’s isoconversional differential method and multivariate non-linear regression method. It was found that the graphene nanoplatelets act positively towards the increase in crystallization rate and nucleation phenomena under isothermal conditions due to their large surface area, inherent nucleation activity, and high filler content. Concerning the thermal degradation kinetics of polypropylene graphene nanoplatelets/glass fibers composites, a change in the decomposition mechanism of the matrix was found due to the presence of graphene nanoplatelets. The effect of graphene nanoplatelets dominates that of the glass fibers, leading to an overall improvement in performance.
The Contribution of Surrounding Margins in the Promotion of Natural Enemies in Mediterranean Apple Orchards

(1) Habitat management can enhance beneficial arthropod populations and provide ecosystem services such as biological control. However, the implementation of ecological infrastructures inside orchards has a number of practical limitations. Therefore, planting/growing insectary plants in the margins of orchards should be considered as an alternative approach. (2) Here, we assessed the efficacy of a flower margin composed by four insectary plant species (Achillea millefolium, Lobularia maritima, Moricandia arvensis and Sinapis alba), which was placed on an edge of four Mediterranean apple orchards to attract natural enemies of two apple tree aphids (Dysaphis plantaginea and Eriosoma lanigerum). We also characterized the natural enemies present in the aphid colonies. (3) Our results show that the implementation of a flower margin at the edge of apple orchards attracts predators (Syrphidae, Thysanoptera, Araneae, Heteroptera, Coleoptera) and parasitoids. Parasitoids are the main natural enemies present in aphid colonies in our area. (4) The implementation of the flower margins successfully recruited natural enemy populations, and the presence of parasitoids in the surroundings of the orchards increased the parasitism of D. plantaginea colonies.
Profile of children with cerebral palsy spectrum disorder and a normal MRI study

Objective This study looks at what profile can be expected in children with cerebral palsy spectrum disorder (CP) and a normal MRI. Methods The data were excerpted from the Canadian Cerebral Palsy Registry database. Only patients who had undergone MRI were included in the analysis. Neuroimaging classification was ascertained by university-based pediatric neuroradiologists and split into 2 categories: normal and abnormal MRIs. Six factors were then compared between those 2 groups: prematurity, perinatal adversity, presence of more than 1 comorbidity, CP subtype, bimanual dexterity (Manual Ability Classification System [MACS]), and gross motor function (Gross Motor Function Classification System [GMFCS]). Results Participants with no perinatal adversity were 5.518 times more likely to have a normal MRI (p < 0.0001, 95% confidence interval [CI] 4.153–7.330). Furthermore, participants with dyskinetic, ataxic/hypotonic, and spastic diplegic forms of CP were 2.045 times more likely to have a normal MRI than those with hemiplegia, triplegia, and quadriplegia (p < 0.0001, 95% CI 1.506–2.778). No significant difference was found in prematurity, GMFCS levels, MACS levels, and the number of comorbidities. Conclusions Normal MRIs were associated with lack of perinatal adversity as well as with the dyskinetic, ataxic/hypotonic, and spastic diplegic CP subtypes. As MRI normality is not strongly associated with the severity of CP, continuous follow-up in children with normal imaging appears warranted. Further advanced imaging modalities, as well as strong consideration for metabolic and genetic testing, may provide additional insights into causal pathways in this population.
Defibrillation of the heart: insights into mechanisms from modelling studies

Despite its critical role in restoring cardiac rhythm and thus in saving human life, cardiac defibrillation remains poorly understood. Further mechanistic inquiry is hampered by the inability of presently available experimental techniques to resolve, with sufficient accuracy, electrical behaviour confined to the depth of the ventricles. The objective of this review article is to demonstrate that realistic 3‐D simulations of the ventricular defibrillation process in close conjunction with experimental observations are capable of bringing a new level of understanding of the electrical events that ensue from the interaction between fibrillating myocardium and applied shock. The article does this by reviewing the results of two studies, one on vulnerability to electric shocks and another on defibrillation. An overview of the modelling tools used in these studies is also provided.
Simian virus 40 T antigen can regulate p53-mediated transcription independent of binding p53

A simian virus 40 (SV40) T-antigen mutant containing only the N-terminal 136 amino acids, able to bind to Rb and p300 but not p53, partially inhibited p53-mediated transcription without affecting the ability of p53 to bind DNA. These results suggest that SV40 T antigen can regulate p53-mediated transcription either directly through protein-protein association or indirectly through interaction with factors which may function to confer p53-mediated transcription.
Tropisetron Facilitates Footshock Suppression of Compulsive Cocaine Seeking

Abstract Background The hallmark characteristics of the murine model of drug addiction include the escalation of cocaine consumption and compulsive punishment-resistant drug seeking. In this study, we evaluated the motivation for drug seeking in cocaine self-administering rats exposed to an escalated dosing regimen that endeavored to mimic the characteristic of escalating drug intake in human addicts. Tropisetron is a 5-HT3 receptor antagonist and α7-nicotinic receptor partial agonist. Utilizing rats trained on the escalated-dosing regimen, we examined the effects of tropisetron on control over compulsive drug-seeking behavior that was defined as footshock-resistant lever pressing. Methods Rats were trained to self-administer cocaine with incremental-infusion doses (from 0.6 to 2.4 mg/kg/infusion) across training sessions (3 h/session) or with a long-access paradigm (i.e., 0.6 mg/kg/infusion, 6 h/d training session). The drug-seeking motivations of 2 groups were estimated by the patterns of drug intake and progressive-ratio schedule. The compulsivity for drug seeking of the group with an escalated dose was further evaluated using the footshock-associated seeking-taking chain task. Results The rats trained on the dose-escalated protocol achieved the same levels of motivated drug seeking as those subjected to a long-access paradigm, as indicated by cocaine intake per training session and breakpoints on a progressive ratio schedule. Tropisetron attenuated compulsive behavior of rats when pressing of the seeking lever potentially led to footshock. Intriguingly, tropisetron did not change the motivation to seek cocaine when footshock was absent. Tropisetron had no effect on locomotor activities or saccharin self-administration. Conclusions These results demonstrate that tropisetron restored control over compulsive cocaine seeking, and they indicate that 5-HT3/α7-nicotinic receptors may be potential therapeutic targets for relieving compulsive drug seeking.
A low voltage bulk-driving PMOS cascode current mirror

Based on the bulk driven PMOS transistor, a low voltage CMOS cascade current mirror (BDCCM) is presented, then the input/output impedance and frequency characteristics are discussed. Based on the simulation and test results of the TSMC 0.25 ¿m 2P4M CMOS process, the minimal input voltage of BDCCM is about 0.3 V. Comparing BDCCM with gate driven cascade current mirror (GDCCM), the input/output linear characteristics and frequency width of BDCCM is lower. So the BDCCM is a good block for low voltage low frequency CMOS analog integrated circuits.
Increased 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase-3 activity in response to EGFR signaling contributes to non–small cell lung cancer cell survival

Constitutive activation of the epidermal growth factor receptor (EGFR) because of somatic mutations of the EGFR gene is commonly observed in tumors of non–small cell lung cancer (NSCLC) patients. Consequently, tyrosine kinase inhibitors (TKI) targeting the EGFR are among the most effective therapies for patients with sensitizing EGFR mutations. Clinical responses to the EGFR-targeting TKIs are evaluated through 2-[18F]fluoro-2-deoxy-glucose (18FDG)-PET uptake, which is decreased in patients responding favorably to therapy and is positively correlated with survival. Recent studies have reported that EGFR signaling drives glucose metabolism in NSCLC cells; however, the precise downstream effectors required for this EGFR-driven metabolic effect are largely unknown. 6-Phosphofructo-2-kinase/fructose-2,6-bisphosphatase (PFKFB3) is an essential glycolytic regulator that is consistently overexpressed in lung cancer. Here, we found that PFKFB3 is an essential target of EGFR signaling and that PFKFB3 activation is required for glycolysis stimulation upon EGFR activation. We demonstrate that exposing NSCLC cells harboring either WT or mutated EGFR to EGF rapidly increases PFKFB3 phosphorylation, expression, and activity and that PFKFB3 inhibition markedly reduces the EGF-mediated increase in glycolysis. Furthermore, we found that prolonged NSCLC cell exposure to the TKI erlotinib drives PFKFB3 expression and that chemical PFKFB3 inhibition synergizes with erlotinib in increasing erlotinib's anti-proliferative activity in NSCLC cells. We conclude that PFKFB3 has a key role in mediating glucose metabolism and survival of NSCLC cells in response to EGFR signaling. These results support the potential clinical utility of using PFKFB3 inhibitors in combination with EGFR-TKIs to manage NSCLC.
A Virtual Sensor for Collision Detection and Distinction with Conventional Industrial Robots

Physical contact inevitably occurs during robot interaction with outside environments. A robot should have the ability to detect and distinguish whether a physical interaction between a human and the robot is contact or collision, so as to ensure human safety and improve interaction performance. In this paper, a virtual sensor that can detect and distinguish contact and collision between humans and industrial robots is proposed. Based on the generalized momentum of the robot, two observers with low-pass and band-pass filter characteristics were designed in this virtual sensor to realize the robot collision detection. Using the different frequency distribution ranges of the lighter contact force signal and the heavier collision force signal, the filter parameters in the two observers were appropriately selected to distinguish between collisions and contacts in close interaction between humans and robots. The virtual sensor does not require acceleration information or inverse dynamics calculations. It only needs to sample the motor driving current and position information of the robot joint, and can easily be applied to conventional industrial robots. The experimental results show that the low-pass and band-pass torque observers can detect different force signals in real-time, and the proposed virtual sensor can be used for collision detection and distinction in human–robot interactions.
Effects of Feedforward in In-Air Remote Pointing

Remote pointing devices like the Wii remote have a wide range of applications and are becoming more important for the manipulation of and interactions with information on a distant display such as smart TVs. Because remote pointing devices are used without external support, however, muscular tremors and motional disparity between the display and motor space can result in usability problems of mouse jitters and instability. In this research, a solution is proposed to those problems using feedforward technology, where a user is provided with predictive information in multisensory modalities while approaching a target. Also, gender effect on the user experience of remote pointing devices is examined. By conducting two experiments and a survey, it was found that the feedforward signal plays a role of precue and is more effective than the typical feedback. It was also found that the modality variations in feedforward were impacted by the gender of the user. The findings can be used to improve user interfaces for remote pointing controllers.