Miracle-dz/UniFAR-FTUs huggingface dataset:
Dissecting the dynamic turnover of GFP-LC3 in the autolysosome

Determination of autophagic flux is essential to assess and differentiate between the induction or suppression of autophagy. Western blot analysis for free GFP fragments resulting from the degradation of GFP-LC3 within the autolysosome has been proposed as one of the autophagic flux assays. However, the exact dynamics of GFP-LC3 during the autophagy process are not clear. Moreover, the characterization of this assay in mammalian cells is limited. Here we found that lysosomal acidity is an important regulating factor for the step-wise degradation of GFP-LC3, in which the free GFP fragments are first generated but accumulate only when the lysosomal acidity is moderate, such as during rapamycin treatment. When the lysosomal acidity is high, such as during starvation in Earle's balanced salt solution (EBSS), the GFP fragments are further degraded and thus do not accumulate. Much to our surprise, we found that the level of free GFP fragments increased in the presence of several late stage autophagy inhibitors, such as chloroquine or E64D plus pepstatin A. Furthermore, the amount of free GFP fragments depends on the concentrations of these inhibitors. Unsaturating concentrations of chloroquine or bafilomycin A1 increased the level of free GFP fragments while saturating concentrations did not. Data from the present study demonstrate that GFP-LC3 is degraded in a step-wise fashion in the autolysosome, in which the LC3 portion of the fusion protein appears to be more rapidly degraded than GFP. However, the amount of free GFP fragments does not necessarily correlate with autophagic flux if the lysosomal enzyme activity and pH are changed. Therefore, caution must be used when conducting the GFP-LC3 cleavage assay as a determinant of autophagic flux. In order to accurately assess autophagy, it is more appropriate to assess GFP-LC3 cleavage in the presence or absence of saturating or unsaturating concentrations of chloroquine or bafilomycin A1 together with other autophagy markers, such as levels of p62 and endogenous LC3-II.
Evaluating the feasibility of utilizing the small molecule phenamil as a novel biofactor for bone regenerative engineering

Osteoblast cell adhesion and differentiation on biomaterials are important achievements necessary for implants to be useful in bone regenerative engineering. Recombinant bone morphogenetic proteins (BMPs) have been shown to be important for these processes; however, there are many challenges associated with the widespread use of these proteins. A recent report demonstrated that the small molecule phenamil, a diuretic derivative, was able to induce osteoblast differentiation and mineralization in vitro via the canonical BMP signalling cascade (Park et al., 2009). In this study, the feasibility of using phenamil as a novel biofactor in conjunction with a biodegradable poly(lactide‐co‐glycolide acid) (PLAGA) polymeric scaffold for engineering bone tissue was evaluated. The in vitro cellular behaviour of osteoblast‐like MC3T3‐E1 cells cultured on PLAGA scaffolds in the presence of phenamil at 10 μM were characterized with regard to initial cell adhesion, proliferation, alkaline phosphatase (ALP) activity and matrix mineralization. The results demonstrate that phenamil supported cell proliferation, promoted ALP activity and facilitated matrix mineralization of osteoblast‐like MC3T3‐E1 cells. Moreover, in this study, we found that phenamil promoted integrin‐mediated cell adhesion on PLAGA scaffolds. It was also shown that phenamil encapsulated within porous, microsphere PLAGA scaffolds retained its osteogenic activity upon release. Based on these findings, the small molecule phenamil has the potential to serve as a novel biofactor for the repair and regeneration of bone tissues. Copyright © 2012 John Wiley & Sons, Ltd.
The expressed emotion of case managers of the seriously mentally ill: the influence of expressed emotion on clinical outcomes

Background. Expressed emotion (EE) measured from relatives and informal carers has been consistently demonstrated to be associated with clinical outcome in schizophrenic patients. There have also been published studies that have investigated EE in professional carers that have suggested that the quality of the relationship between staff and patient may also be associated with patient outcomes. A large controlled trial of the effectiveness of different intensities of case management provided the opportunity to assess the association between the EE of case managers, including the quality of the relationship they had with patients under their care, and later clinical outcomes. Method. This was a prospective naturalistic study of EE present in a case manager–patient dyad and subsequent patient outcomes. EE was assessed from the Five Minute Speech Sample (FMSS) at least 3 months after the case manager became responsible for the patient's care and a range of clinical outcomes were assessed 6 to 9 months later. Assessment of clinical outcomes was made independent and blind of the EE ratings. Results. High EE ratings were significantly associated with individual case managers and not to symptom or illness factors. High EE was not associated with later clinical outcome, however, the positive relationship between case manager and patient was. The absence of a positive relationship was significantly associated with poorer outcomes. Conclusions. In spite of very low face-to-face contact between case managers and patients, compared with the amount of contact patients have with their informal carers and family, aspects of staff attitudes and behaviour did influence clinical outcome. There are potential implications of these results for staff training and clinical practice.
Nash-reinforcement learning (N-RL) for developing coordination strategies in non-transferable utility games

Social (central) planning is normally used in the literature to optimize the system-wide efficiency and utility of multi-operator systems. Central planning tries to maximize system's benefits by coordinating the operators' strategies and reduce the externalities, assuming that all parties are willing to cooperate. This assumption implies that operators are willing to base their decisions based on group rationality rather than individual rationality, even if increased group benefits results in reduced benefits for some agents. This assumption limits the applicability of social planner's solutions, as perfect cooperation among agents is often infeasible in real world. Recognizing the fact that decisions are normally based on individual rationality in human systems, cooperative game theory methods are normally employed to address the major limitation of social planner's methods. Game theory methods revise the social planner's solution such that not only group benefits are increased, but also there exists no agent whose cooperative gain is less than his non-cooperative gain. However, in most cases, utility is assumed to be transferrable and the literature has not sufficiently focused on non-transferrable utility games. In such games parties are willing to cooperate and coordinate their strategies to increase their benefits, but have no ability to compensate each other to promote cooperation. To a good extent, the transferrable utility assumption is due to the complexity of calculations to find the best response strategies of agents in non-cooperative and cooperative modes, especially in multi-period games. By combining Reinforcement Learning and Nash bargaining solution, this paper develops a new method for applying cooperative game theory to complex multi-period non-transferrable utility games. For illustration, the suggested method is applied to two numerical examples in which two hydropower operators seek developing a fair and efficient cooperation mechanism to increase their gains.
Protein Tyrosine Kinase Fyn Regulates TLR4-Elicited Responses on Mast Cells Controlling the Function of a PP2A-PKCα/β Signaling Node Leading to TNF Secretion

Mast cells produce proinflammatory cytokines in response to TLR4 ligands, but the signaling pathways involved are not fully described. In this study, the participation of the Src family kinase Fyn in the production of TNF after stimulation with LPS was evaluated using bone marrow–derived mast cells from wild-type and Fyn-deficient mice. Fyn−/− cells showed higher LPS-induced secretion of preformed and de novo–synthesized TNF. In both cell types, TNF colocalized with vesicle-associated membrane protein (VAMP)3-positive compartments. Addition of LPS provoked coalescence of VAMP3 and its interaction with synaptosomal-associated protein 23; those events were increased in the absence of Fyn. Higher TNF mRNA levels were also observed in Fyn-deficient cells as a result of increased transcription and greater mRNA stability after LPS treatment. Fyn−/− cells also showed higher LPS-induced activation of TAK-1 and ERK1/2, whereas IκB kinase and IκB were phosphorylated, even in basal conditions. Increased responsiveness in Fyn−/− cells was associated with a lower activity of protein phosphatase 2A (PP2A) and augmented activity of protein kinase C (PKC)α/β, which was dissociated from PP2A and increased its association with the adapter protein neuroblast differentiation–associated protein (AHNAK, desmoyokin). LPS-induced PKCα/β activity was associated with VAMP3 coalescence in WT and Fyn-deficient cells. Reconstitution of MC-deficient Wsh mice with Fyn−/− MCs produced greater LPS-dependent production of TNF in the peritoneal cavity. Our data show that Fyn kinase is activated after TLR4 triggering and exerts an important negative control on LPS-dependent TNF production in MCs controlling the inactivation of PP2Ac and activation of PKCα/β necessary for the secretion of TNF by VAMP3+ carriers.
Flexible Operational Planning Framework Considering Multiple Wind Energy Forecasting Service Providers

While the state-of-the-art wind forecasting platforms use similar inputs, the techniques may vary substantially from one forecast service provider to another. No single forecast will apply optimally to all prediction horizons and site locations. Therefore, power system operators rely on several forecast service providers to hedge against the operational risk rising from the error in single-provider case. In order to accommodate the uncertainties in wind power forecast, each forecasting service provider will deliver multiple wind power output scenarios with different initial conditions and model formulations, and one commitment decision will be produced. The key issue of this research work is to identify which generation schedule is likely to perform better under various conditions or for different types of decisions. The selected plan may not be the optimal one for a particular scenario set, but it will lead to an overall lower cost if it needs to be changed to another plan as getting closer to real-time. Detailed case studies are given to demonstrate the performance of the proposed flexible operation planning framework.
Percutaneous saline-enhanced radiofrequency ablation of unresectable hepatic tumors: initial experience in 26 patients.

OBJECTIVE The purpose of our study was to evaluate the safety and efficacy of percutaneous saline-enhanced radiofrequency ablation for unresectable primary or metastatic hepatic tumors. SUBJECTS AND METHODS Twenty-six patients with 15 hepatocellular carcinomas and 33 hepatic metastases (maximum diameter < or = 8.6 cm) were treated; of these, seven tumors in five patients were treated twice. Thus, 44 radiofrequency treatments were performed. Saline-enhanced and impedance-controlled radiofrequency ablation (0.5-1.1 mL/min of saline, 15-mm conductive portion of the electrode tip, 25-60 W, 5-43 min) was performed using MR imaging guidance. Coagulation necrosis, volume indexes, morbidity, and complications were assessed. RESULTS The volume of coagulation necrosis 1-7 days after radiofrequency ablation was 1.6-126.6 cm(3) (median, 18.9 cm(3)), corresponding to coagulation diameters of 1.5-6.2 cm (median, 3.2 cm). The coagulation volume was significantly larger if there were more than four radiofrequency applications (p = 0.006). Tumors of 3 cm or less in diameter were eight times as likely to be successfully completely ablated (p = 0.01) and volume indexes of lesions treated with the patient under general anesthesia were significantly larger than those treated with the patient under conscious sedation (p < 0.001). Major complications occurred in four patients (15%). Incomplete ablation in 19 (35%) of 54 radiofrequency lesions was due to cooling by a large vessel nearby (n = 2) or to low power applied in painful (n = 11) or critical (n = 6) locations. Residual tumor was observed in 14 (58%) of 24 tumors evaluated 6-8 months after radiofrequency ablation. CONCLUSION Percutaneous saline-enhanced and impedance-controlled radiofrequency ablation can be effective in the treatment of unresectable hepatic tumors and minimizes potential carbonization. A greater number of radiofrequency applications, general anesthesia, and increasing experience provide significantly better results.
Transforming growth factor-beta1 gene polymorphism in renal transplant recipients.

BACKGROUND Cytokine transforming growth factor (TGF) is involved in regulation of tissue repair after injury. More recently, TGF-beta1 codon 10 gene polymorphism has been shown to be associated with circulating TGF-beta levels. We tested whether TGF-beta1 genotype polymorphism was predictive of renal allograft function decline. PATIENTS AND METHODS The study population consisted of 129 consecutive cadaveric or living related renal transplant recipients at our center between 1985 and 2001. The recipient TGF-beta1 genotype polymorphism was determined from peripheral blood leucocytes DNA. The primary endpoint was rate of glomerular filtration rate decline between the first year and the third year of transplant. RESULTS Baseline glomerular filtration rate as estimated by MDRD study equation at 1 year measured 50+/-17 mL/min/1.73 m2. At the end of the 3-year follow-up period, 52 patients (40%) experienced biopsy-confirmed acute rejections. Frequency and severity of allograft rejection did not differ with TGF-beta genotypes. However, the decline in glomerular filtration rate was significantly greater in Leu/Leu (TT) than Leu/Pro (CT) recipients, 6.3+/-16.9 mL/min/1.73 m2 versus 0.1+/-10.2 mL/min/1.73 m2, p=0.04. CONCLUSION Our results demonstrate that recipient TGF-beta1 codon 10 Leu/Leu homozygosity is a potential risk factor of kidney allograft function decline.
A Markovian model for association football possession and its outcomes

We propose a bottom-up approach to the study of possession and its outcomes for association football, based on probabilistic finite state automata with transition probabilities described by a Markov process. We show how even a very simple model yields faithful approximations to the distribution of passing sequences and chances of taking shots for English Premier League teams, which we fit using a whole season of granular game data (380 games). We compare the resulting model with classical top-down distributions traditionally used to describe possessions, showing that the Markov models yield a more accurate asymptotic behaviour.
DIVERGENT EVOLUTION OF DISPERSAL IN A HETEROGENEOUS LANDSCAPE

Abstract The evolution of dispersal is investigated in a landscape of many patches with fluctuating carrying capacities and spatial heterogeneity in temporal fluctuations. Although asynchronous temporal fluctuations select for dispersal, spatial heterogeneity in the distribution of fluctuating environmental variables selects against it. We find evolutionary branching in dispersal rate leading to the evolutionarily stable coexistence of a high- and a low-dispersal phenotype. We study how the opposing forces of selection for and against dispersal change with the relative size and the environmental qualities of the source and sink habitats. Our results suggest that the evolution of dispersal dimorphism could be a first step towards speciation and local adaptation.
Thermal stability of human ferritin: concentration dependence and enhanced stability of an N-terminal fusion mutant.

Though human L-chain ferritin has been known to be more resistant to physical denaturation than H-type ferritin, its stability characteristics and kinetic information have not been reported in detail. Overexpressed recombinant ferritin (FTN) in Escherichia coli formed inclusion bodies through noncovalent molecular interaction and easily dissolved with regaining the iron-uptake activity by a simple pH-shift process at high protein concentration (>600 mg l(-1)). FTN was relatively thermostable at low protein concentration (0.2 g l(-1)), but it became extremely thermolabile at high protein concentration (1.3 g l(-1)), i.e., more than 80% of FTN was coprecipitated within 5 min under the same heat-induced denaturation condition. Aggregation rate constant for initial 5 min at high protein concentration was 6.04 x 10(-3) s(-1) for FTN. Surprisingly, glucagon. ferritin mutant (GFTN), consisting of an N-terminus fusion partner, human glucagon (29-residue alpha-helical peptide), showed significantly enhanced thermal stability even at high protein concentration. That is, in spite of 40-min heat treatment, more than 50% of GFTN the still remained soluble with maintaining the same functional properties. The aggregation rate constants were 2.75 x 10(-4) and 2.80 x 10(-4) s(-1) at low and high concentration, respectively, for GFTN. These results suggest a critical participation of the N-terminal domain of ferritin in the temperature-induced aggregation pathway. Presumably, partially denatured amino terminus of FTN is involved in nonspecific molecular interaction resulting in the off-pathway aggregation. It is notable that the purified GFTN showed the same molar capacity of iron (Fe(+3)) storage as standard ferritin. From the analysis of fluorescence emission spectrum, the physical stability of GFTN was also very comparable to that of standard ferritin under the various denaturation conditions induced by GdnHCl.
Molecular epidemiology of a post‐influenza pandemic outbreak of acute respiratory infections in Korea caused by human adenovirus type 3

An outbreak of upper respiratory tract infections associated with human adenovirus (HAdV) occurred on a national scale in Korea from September to December 2010, following a major H1N1 influenza pandemic. Data from the Korea Influenza and Respiratory Surveillance System (KINRESS) showed an unusually high positive rate accounting for up to 20% of all diagnosed cases. To determine the principal cause of the outbreak, direct polymerase chain reaction (PCR) amplification followed by sequence analysis targeting parts of the hexon gene of HAdV was performed. Serotypes of 1,007 PCR‐diagnosed HAdV‐positive samples from patients with an acute upper respiratory tract illness were determined and epidemiological characteristics including major aged group and clinical symptoms were analyzed. The principal symptom of HAdV infections was fever and the vulnerable aged group was 1–5 years old. Based on sequence analysis, HAdV‐3 was the predominant serotype in the outbreak, with an incidence of 74.3%. From the beginning of 2010 until May, the major serotypes were HAdV‐1, 2, and 5 (70–100%) in any given period. However, an outbreak dominated by HAdV‐3 started between July and August and peaked in September. Phylogenetic analysis revealed that there was no genetic variation in HAdV‐3. The results demonstrated that an outbreak of upper respiratory illness followed by H1N1 influenza pandemic in Korea was caused mainly by emerged HAdV‐3. J. Med. Virol. 87: 10–17, 2015. © 2014 Wiley Periodicals, Inc.
"The harder it gets" Exploring the interdependency of input modalities and task complexity in human-robot collaboration

To enhance successful cooperation in human-robot collaboration tasks, many factors have to be considered. We assume, that for specific levels of task complexity, there is always one complementing input modality which increases the corresponding user satisfaction and performance. In order to identify the ideal mix of these elements, we present two experiments in this paper. The first study was in a public space and the second in a controlled laboratory environment. Besides investigating the correlation of task complexity and input modality, we explored, whether the appearance of the robot also has an impact, within the lab environment. We identified strong interdependencies between task complexity and input modalities. Specifically with hard tasks, differences in performance and satisfaction were often highly significant. Additionally we found, that the perceived task complexity was strongly dependent on the cognitive workload, driven by the used input modality, which also emphasized the strong coherency of these factors. Regarding the influence of the appearance of the robot, we found, that the human-like shape increases users' self confidence, to be able to solve a task without help.
A Novel Three Dimensional Field Effect Transistor Based on Single-Walled Carbon Nanotubes

We present the design, fabrication and testing of a novel three dimensional (3D) Field Effect Transistor based on Single-Walled Carbon Nanotubes (SWNTs). Three Dimensional SWNT transistors are realized utilizing low temperature Dielectrophoretic (DEP) assembly. A 1mum thick conformal Parylene-C (poly-para-xylylene) layer is utilized as the gate dielectric with a non-local top gate electrode around the conducting channel. The preliminary results from 3D Carbon NanoTube Field Effect Transistors (CNTFET) display ambipolar behavior with more prominent p-type than n-type behavior. The transistor exhibits an on-to-off current ratio of ~3 x 104, a maximum transconductance of 0.061 mus, and a mobility of 85- 277 cm2/Vs. This 3D-CNTFET technology can be utilized to realize multi layer, compact and high density nanotube transistors for large scale nanoelectronic circuits.
Label‐free quantitative proteomics and SAINT analysis enable interactome mapping for the human Ser/Thr protein phosphatase 5

Affinity purification coupled to mass spectrometry (AP‐MS) represents a powerful and proven approach for the analysis of protein–protein interactions. However, the detection of true interactions for proteins that are commonly considered background contaminants is currently a limitation of AP‐MS. Here using spectral counts and the new statistical tool, Significance Analysis of INTeractome (SAINT), true interaction between the serine/threonine protein phosphatase 5 (PP5) and a chaperonin, heat shock protein 90 (Hsp90), is discerned. Furthermore, we report and validate a new interaction between PP5 and an Hsp90 adaptor protein, stress‐induced phosphoprotein 1 (STIP1; HOP). Mutation of PP5, replacing key basic amino acids (K97A and R101A) in the tetratricopeptide repeat (TPR) region known to be necessary for the interactions with Hsp90, abolished both the known interaction of PP5 with cell division cycle 37 homolog and the novel interaction of PP5 with stress‐induced phosphoprotein 1. Taken together, the results presented demonstrate the usefulness of label‐free quantitative proteomics and statistical tools to discriminate between noise and true interactions, even for proteins normally considered as background contaminants.