Miracle-dz/UniFAR-FTUs huggingface dataset:
Simultaneous inhibition of multiple oncogenic miRNAs by a multi-potent microRNA sponge

The roles of oncogenic miRNAs are widely recognized in many cancers. Inhibition of single miRNA using antagomiR can efficiently knock-down a specific miRNA. However, the effect is transient and often results in subtle phenotype, as there are other miRNAs contribute to tumorigenesis. Here we report a multi-potent miRNA sponge inhibiting multiple miRNAs simultaneously. As a model system, we targeted miR-21, miR-155 and miR-221/222, known as oncogenic miRNAs in multiple tumors including breast and pancreatic cancers. To achieve efficient knockdown, we generated perfect and bulged-matched miRNA binding sites (MBS) and introduced multiple copies of MBS, ranging from one to five, in the multi-potent miRNA sponge. Luciferase reporter assay showed the multi-potent miRNA sponge efficiently inhibited 4 miRNAs in breast and pancreatic cancer cells. Furthermore, a stable and inducible version of the multi-potent miRNA sponge cell line showed the miRNA sponge efficiently reduces the level of 4 target miRNAs and increase target protein level of these oncogenic miRNAs. Finally, we showed the miRNA sponge sensitize cells to cancer drug and attenuate cell migratory activity. Altogether, our study demonstrates the multi-potent miRNA sponge is a useful tool to examine the functional impact of simultaneous inhibition of multiple miRNAs and proposes a therapeutic potential.
Electromechanical emulation of hydrokinetic generators for renewable energy research

The pace of research and development efforts to integrate renewable power sources into modern electric utilities continues to increase. These efforts are motivated by a desire for cleaner, cheaper and more diverse sources of energy. As new analyses and controls approaches are developed to manage renewable sources and tie them into the grid, the need for these controls to be tested in hardware becomes paramount. In particular, hydrokinetic power is appealing due to its high energy density and superior forecastability; however, its development has lagged behind that of wind and solar due in part to the difficulty of acquiring hardware results on an integrated system. Thus, as an alternative to constructing an elaborate wave-tank or locating a power lab riverside, this paper presents a method based on electromechanical emulation of the energy source using a commercially available induction motor drive. Using an electromechanical emulator provides an option for universities and other laboratories to expand their research on hydrokinetics in a typical laboratory setting.
Dihydrofolate reductase 19-bp deletion polymorphism modifies the association of folate status with memory in a cross-sectional multi-ethnic study of adults.

BACKGROUND Folate status has been positively associated with cognitive function in many studies; however, some studies have observed associations of poor cognitive outcomes with high folate. In search of an explanation, we hypothesized that the association of folate with cognition would be modified by the interaction of high-folate status with a common 19-bp deletion polymorphism in the dihydrofolate reductase (DHFR) gene. To our knowledge, the cognitive effects of this gene have not been studied previously. OBJECTIVE We examined the association between cognitive outcomes with the 19-bp deletion DHFR polymorphism, folate status, and their interaction with high or normal plasma folate. DESIGN This was a pooled cross-sectional study of the following 2 Boston-based cohorts of community living adults: the Boston Puerto Rican Health Study and the Nutrition, Aging, and Memory in Elders study. Individuals were genotyped for the DHFR 19-bp deletion genotype, and plasma folate status was determined. Cognitive outcomes included the Mini-Mental State Examination, Center for Epidemiologic Studies Depression Scale, and factor scores for the domains of memory, executive function, and attention from a set of cognitive tests. RESULTS The prevalence of the homozygous deletion (del/del) genotype was 23%. In a multivariable analysis, high folate status (>17.8 ng/mL) was associated with better memory scores than was normal-folate status (fourth-fifth quintiles compared with first-third quintiles: β ± SE = -0.22 ± 0.06, P < 0.01). Carriers of the DHFR del/del genotype had worse memory scores (β ± SE = -0.24 ± 0.10, P < 0.05) and worse executive scores (β = -0.19, P < 0.05) than did those with the del/ins and ins/ins genotypes. Finally, we observed an interaction such that carriers of the del/del genotype with high folate had significantly worse memory scores than those of both noncarriers with high-folate and del/del carriers with normal-folate (β-interaction = 0.26 ± 0.13, P < 0.05). CONCLUSIONS This study identifies a putative gene-nutrient interaction that, if confirmed, would predict that a sizable minority carrying the del/del genotype might not benefit from high-folate status and could see a worsening of memory. An understanding of how genetic variation affects responses to high-folate exposure will help weigh risks and benefits of folate supplementation for individuals and public health.
Enzyme-responsive doxorubicin release from dendrimer nanoparticles for anticancer drug delivery

Background Since cancer cells are normally over-expressed cathepsin B, we synthesized dendrimer-methoxy poly(ethylene glycol) (MPEG)-doxorubicin (DOX) conjugates using a cathepsin B-cleavable peptide for anticancer drug targeting. Methods Gly-Phe-Leu-Gly peptide was conjugated with the carboxylic acid end groups of a dendrimer, which was then conjugated with MPEG amine and doxorubicin by aid of carbodiimide chemistry (abbreviated as DendGDP). Dendrimer-MPEG-DOX conjugates without Gly-Phe-Leu-Gly peptide linkage was also synthesized for comparison (DendDP). Nanoparticles were then prepared using a dialysis procedure. Results The synthesized DendGDP was confirmed with 1H nuclear magnetic resonance spectroscopy. The DendDP and DendGDP nanoparticles had a small particle size of less than 200 nm and had a spherical morphology. DendGDP had cathepsin B-sensitive drug release properties while DendDP did not show cathepsin B sensitivity. Further, DendGDP had improved anticancer activity when compared with doxorubicin or DendDP in an in vivo CT26 tumor xenograft model, ie, the volume of the CT26 tumor xenograft was significantly inhibited when compared with xenografts treated with doxorubicin or DendDP nanoparticles. The DendGDP nanoparticles were found to be relatively concentrated in the tumor tissue and revealed stronger fluorescence intensity than at other body sites while doxorubicin and DendDP nanoparticles showed strong fluorescence intensity in the various organs, indicating that DendGDP has cathepsin B sensitivity. Conclusion DendGDP is sensitive to cathepsin B in tumor cells and can be used as a cathepsin B-responsive drug targeting strategy. We suggest that DendGDP is a promising vehicle for cancer cell targeting.
Utilization of Health Services in the Burkina Faso Health System: Empirical Evidence of Health System Fragmentation and Integration

In this paper, the utilization of health services in the context of health system fragmentation in Burkina Faso is analyzed using household living condition survey data. The methodology explores the relationships between population health risk factors and health services utilization. The results of the analysis highlighted eight reference care providers in the Burkina Faso health system; thus, the probability of service use in the first level of the system, assumed to be its point of entry, is significantly and negatively associated with age and sex, with a lower probability for female gender. As a whole, the health risk factors positively influence the probability of service use at the higher levels of the health system and in the private sector. The results suggest that utilization of the traditional health sector remains predominated by the elderly. These results thus suggest the need for coordination of care across the levels of the public healthcare sector, on the one hand, and the presence of interaction and integration between the traditional or private sector and the public sector, on the other hand.
Application of Manifold Separation to Parametric Localization for Incoherently Distributed Sources

By using the manifold separation technique (MST), we develop a computationally efficient yet accurate estimator for localization of multiple incoherently distributed (ID) sources. In this paper, we have made the following main contributions: first, we use the MST to derive a closed-form expression for the ID signal covariance matrix that is applicable to the case with arbitrary array geometries or large angular spreads; second, we find that the two-dimensional spatial spectrum can be computed efficiently by using the discrete Fourier transform algorithms coupled with the unweighted (or Gaussian-weighted) moving average for the uniformly (or Gaussian) distributed ID sources; finally, we employ the first-order Taylor expansion to formulate a weighted least-squares approach that can improve the estimation performance significantly. Numerical results demonstrate that with less complexity, the proposed estimator offers better estimation performance compared with several classical estimators.
A flexible approach for compiling scilab to reconfigurable multi-core embedded systems

The mapping process of high performance embedded applications to today's reconfigurable multiprocessor System-on-Chip devices suffers from a complex toolchain and programming process. Thus, the efficient programming of such architectures in terms of achievable performance and power consumption is limited to experts only. Enabling them to nonexperts requires a simplified programming process that hides the complexity of the underlying hardware - introduced by software parallelism of multiple cores and the flexibility of reconfigurable architectures - to the end user. The Architecture oriented paraLlelization for high performance embedded Multi-core systems using scilAb (ALMA) European project aims to bridge these hurdles through the introduction and exploitation of a Scilab- and architecture-description-language-based toolchain which enables the efficient mapping of applications on multiprocessor platforms from high level of abstraction. This holistic solution of the toolchain allows the complexity of both the application and the architecture to be hidden, which leads to a better acceptance, reduced development costs, and shorter time-to-market.
Low Preoperative Platelet Count Predicts Risk of Subclinical Posthepatectomy Liver Failure in Right Lobe Donors for Liver Transplantation

Living donor right hepatectomy (LDRH) is a common procedure in adult‐to‐adult living donor liver transplantation, but it is associated with a higher risk of posthepatectomy liver failure (PHLF) compared with left hepatectomy because of a smaller remnant. We identified risk factors for PHLF and other complications in LDRH, verified the appropriateness of the criteria, and explored the possibility of adjusting the minimum remnant liver volume (RLV) based on individual risk. Between October 2005 and November 2017, 254 donors undergoing LDRH at Kyoto University Hospital were enrolled. Clinical data were collected retrospectively. All complications were graded according to the Clavien‐Dindo classification. No donors had grade 4 or 5 complications or clinically significant grade B or C PHLF. Grade A PHLF occurred in 30 donors (11.8%). Male sex (P = 0.01), lower preoperative platelet count (PLT; P = 0.01), higher prothrombin time–international normalized ratio (P = 0.03), higher total bilirubin (P = 0.01), smaller RLV (P = 0.03), and greater blood loss (P = 0.04) were associated with increased risk of PHLF in the univariate analysis, whereas PLT, RLV, and blood loss remained significant in the multivariate analysis. Grade 2 or 3 complications were observed in 32 (12.6%) donors. Higher body mass index (BMI; P = 0.002) and larger blood loss (P = 0.02) were identified as risk factors for complications (Clavien‐Dindo grade ≥ 2) in univariate analysis. Only BMI remained significant in the multivariate analysis. In conclusion, LDRH is performed safely with acceptable morbidity under the current criteria. Minimum RLV may be marginally adjusted by PLT and reducing intraoperative blood loss minimizes PHLF risk. Liver Transplantation 00 000–000 2018 AASLD.
Cue-Induced Ethanol Seeking in Drosophila melanogaster Is Dose-Dependent

Alcohol use disorder generates devastating social, medical and economic burdens, making it a major global health issue. The persistent nature of memories associated with intoxication experiences often induces cravings and triggers relapse in recovering individuals. Despite recent advances, the neural and molecular mechanisms underlying these memories are complex and not well understood. This makes finding effective pharmacological targets challenging. The investigation of persistent alcohol-associated memories in the fruit fly, Drosophila melanogaster, presents a unique opportunity to gain a comprehensive understanding of the memories for ethanol reward at the level of genes, molecules, neurons and circuits. Here we characterize the dose-dependent nature of ethanol on the expression of memory for an intoxication experience. We report that the concentration of ethanol, number of ethanol exposures, length of ethanol exposures, and timing between ethanol exposures are critical in determining whether ethanol is perceived as aversive or appetitive, and in how long the memory for the intoxicating properties of ethanol last. Our study highlights that fruit flies display both acute and persistent memories for ethanol-conditioned odor cues, and that a combination of parameters that determine the intoxication state of the fly influence the seemingly complex retention and expression of memories associated with intoxication. Our thorough behavioral characterization provides the opportunity to interrogate the biological underpinnings of these observed preference differences in future studies.
Autumn tree colours as a handicap signal

Many species of deciduous trees display striking colour changes in autumn. Here, we present a functional hypothesis: bright autumn coloration serves as an honest signal of defensive commitment against autumn colonizing insect pests. According to this hypothesis, individuals within a signalling species show variation in the expression of autumn coloration, with defensively committed trees producing a more intense display. Insects are expected to be averse to the brightest tree individuals and, hence, preferentially colonize the least defensive hosts. We predicted that tree species suffering greater insect damage would, on average, invest more in autumn–colour signalling than less troubled species. Here, we show that autumn coloration is stronger in species facing a high diversity of damaging specialist aphids. Aphids are likely to be an important group of signal receivers because they are choosy, damaging and use colour cues in host selection. In the light of further aspects of insect and tree biology, these results support the notion that bright autumn colours are expensive handicap signals revealing the defensive commitment of individual trees to autumn colonizing insect pests.
Predicting suicide attempts in young adults with histories of childhood abuse

Background Although childhood abuse is an important correlate of suicidality, not all individuals who were abused as children attempt suicide. Aims To identify correlates and moderators of suicide attempts in adults reporting childhood physical abuse, contact sexual abuse, or both. Method A French-Canadian, school-based cohort (n=1684) was prospectively followed. Results The identity of the abuser moderated the relationship of abuse frequency and suicide attempts, with individuals abused by their immediate family being at highest risk. Although paternal education exhibited negative associations (OR=0.71, 95% CI 0.58–0.88), several externalising phenotypes had positive associations with suicide attempts: disruptive disorders (OR=3.10, 95% CI 1.05–9.15), conduct problems (OR=1.09, 95% CI 1.01–1.19) and childhood aggression (OR=1.41, 95% CI 1.08–1.83). Conclusions Characteristics of the abuser and abusive acts may be important additional indicators of risk for suicide attempts. Future research needs to employ developmental approaches to examine the extent and mechanisms by which childhood abuse contributes to the shared variance of suicidality, maladaptive traits and psychopathology.
Acrylamide Binding to Its Cellular Targets: Insights from Computational Studies

Acrylamide (AC, CH2=CH–CONH2, Chart 1), present in heated foodstuffs [Rice, 2005], has been classified by the International Agency for Research on Cancer as ‘‘probably carcinogenic to humans” (group 2A) (IARC, 1994). The Scientific Committee on Toxicity, Ecotoxicity and the Environment (CSTEE) in the European Union (EU) demonstrated that AC exposure to humans should be controlled as low as possible because of its inherently toxic properties [Zhang et. al., 2009; Dearfield et. al., 1995]. AC is a low molecular-weight, odorless, and colorless compound. It is readily soluble in water and can rapidly polymerize from a monomer state to a polymer form [Klaunig, 2008]. AC is biotransformed in vivo to its epoxide glycidamide (GDE) by cytochrome P450 2E1 (CYP2E1) [Ghanayem et. al., 2005]. GDE has genotoxic properties in both in vitro and in vivo test systems [Kurebayashi & Ohno, 2008]. In spite of the possible carcinogenic nature of AC, no consistent effect of AC exposure on cancer incidence in humans could be identified [Rice, 2005]. This strikingly contrasts with AC subministration in both mice and rats, which may cause tumors at multiple sites [Besaratinia & Pfeifer, 2005; 2007]. A plausible hypothesis is this might be caused, at least partially, by the fact that AC interacts differently with the mouse and human proteins. AC may interact with cysteine residues not engaged in S-S bridges. Indeed, the double bond of conjugated vinyl compounds has strong affinity with SH groups [Friedman, 2003; Carere, 2006].
Systematic Reviews and Meta- and Pooled Analyses Association Between Television Viewing Time and All-Cause Mortality: A Meta-Analysis of Cohort Studies

Findings on the association between television (TV) viewing and all-cause mortality in epidemiologic studies have been inconsistent. Therefore, we conducted a meta-analysis of data from prospective cohort studies to quantify this association. Relevant articles were identified by searching MEDLINE (PubMed; National Library of Medicine, Bethesda, Maryland) and EMBASE (Elsevier B.V., Amsterdam, the Netherlands) from inception to March 1, 2015, and reviewing the reference lists of retrieved articles. Study-specific results were pooled using a random-effects model. Of 2,578 citations identified by the search strategy, 10 cohort studies (61,494 deaths among 647,475 individuals) met the inclusion criteria. The summary relative risk of all-cause mortality for the highest category of TV viewing time versus the lowest was 1.33 (95% confidence interval: 1.20, 1.47), with heterogeneity among studies ( I 2 = 66.7%, P heterogeneity = 0.001). In dose-response meta-analysis, TV viewing time was statistically significantly associated with all-cause mortality risk in a J-shaped fashion ( P nonlinearity = 0.001). These results indicate that prolonged TV viewing time might increase the risk of all-cause mortality. Given the high prevalence of excessive TV viewing, public health recommendations or interventions aimed at decreasing the amount of TV viewing time in modern societies are warranted.
PI3K-Akt-mTOR axis sustains rotavirus infection via the 4E-BP1 mediated autophagy pathway and represents an antiviral target

ABSTRACT Rotavirus infection is a major cause of severe dehydrating diarrhea in infants younger than 5 y old and in particular cases of immunocompromised patients irrespective to the age of the patients. Although vaccines have been developed, antiviral therapy is an important complement that cannot be substituted. Because of the lack of specific approved treatment, it is urgent to facilitate the cascade of further understanding of the infection biology, identification of druggable targets and the final development of effective antiviral therapies. PI3K-Akt-mTOR signaling pathway plays a vital role in regulating the infection course of many viruses. In this study, we have dissected the effects of PI3K-Akt-mTOR signaling pathway on rotavirus infection using both conventional cell culture models and a 3D model of human primary intestinal organoids. We found that PI3K-Akt-mTOR signaling is essential in sustaining rotavirus infection. Thus, blocking the key elements of this pathway, including PI3K, mTOR and 4E-BP1, has resulted in potent anti-rotavirus activity. Importantly, a clinically used mTOR inhibitor, rapamycin, potently inhibited both experimental and patient-derived rotavirus strains. This effect involves 4E-BP1 mediated induction of autophagy, which in turn exerts anti-rotavirus effects. These results revealed new insights on rotavirus-host interactions and provided new avenues for antiviral drug development.
A Heuristic for Reachability Problem in Asynchronous Binary Automata Networks

On demand of efficient reachability analysis due to the inevitable complexity of large-scale biological models, this paper is dedicated to a novel approach: PermReach, for reachability problem of our new framework, Asynchronous Binary Automata Networks (ABAN). ABAN is an expressive modeling framework which contains all the dynamics behaviors performed by Asynchronous Boolean Networks. Compared to Boolean Networks (BN), ABAN has a finer description of state transitions (from a local state to another, instead of symmetric Boolean functions). To analyze the reachability properties on large-scale models (like the ones from systems biology), previous works exhibited an efficient abstraction technique called Local Causality Graph (LCG). However, this technique may be not conclusive. Our contribution here is to extend these results by tackling those complex intractable cases via a heuristic technique. To validate our method, tests were conducted in large biological networks, showing that our method is more conclusive than existing ones.
Inhibition of water channels by HgCl2 in intact wheat root cells

To assess the extent of water flow through channels in the membranes of intact higher plant cells, the effects of HgCl2 on hydraulic conductivity (LP) of wheat (Triticum aestivum L.) root cells were investigated using a pressure probe. The LP of root cells was reduced by 75% in the presence of 100 &mgr;M HgCl2. The K+-channel blocker tetraethylammonium had no effect on the LP at concentrations that normally block K+ channels. HgCl2 rapidly depolarized the membrane potential (Vm) of the root cells. The dose-response relationship of inhibition of LP and depolarization of Vm were not significantly different, with half-maximal inhibition occurring at 4. 6 and 7.8 &mgr;M, respectively. The inhibition of LP and the depolarization of Vm caused by HgCl2 were partially reversed by beta-mercaptoethanol. The inhibition of LP by HgCl2 was similar in magnitude to that caused by hypoxia, and the addition of HgCl2 to hypoxia-treated cells did not result in further inhibition. We compared the LP of intact cells with that predicted from a model of cortical cells incorporating water flow across both the plasma membrane and the tonoplast using measured values of water permeability from isolated membranes, and found that HgCl2 has other effects in addition to the direct inhibition of water channels.