Miracle-dz/UniFAR-FTUs huggingface dataset:
Repeat Length and RNA Expression Level Are Not Primary Determinants in CUG Expansion Toxicity in Drosophila Models

Evidence for an RNA gain-of-function toxicity has now been provided for an increasing number of human pathologies. Myotonic dystrophies (DM) belong to a class of RNA-dominant diseases that result from RNA repeat expansion toxicity. Specifically, DM of type 1 (DM1), is caused by an expansion of CUG repeats in the 3′UTR of the DMPK protein kinase mRNA, while DM of type 2 (DM2) is linked to an expansion of CCUG repeats in an intron of the ZNF9 transcript (ZNF9 encodes a zinc finger protein). In both pathologies the mutant RNA forms nuclear foci. The mechanisms that underlie the RNA pathogenicity seem to be rather complex and not yet completely understood. Here, we describe Drosophila models that might help unravelling the molecular mechanisms of DM1-associated CUG expansion toxicity. We generated transgenic flies that express inducible repeats of different type (CUG or CAG) and length (16, 240, 480 repeats) and then analyzed transgene localization, RNA expression and toxicity as assessed by induced lethality and eye neurodegeneration. The only line that expressed a toxic RNA has a (CTG)240 insertion. Moreover our analysis shows that its level of expression cannot account for its toxicity. In this line, (CTG)240.4, the expansion inserted in the first intron of CG9650, a zinc finger protein encoding gene. Interestingly, CG9650 and (CUG)240.4 expansion RNAs were found in the same nuclear foci. In conclusion, we suggest that the insertion context is the primary determinant for expansion toxicity in Drosophila models. This finding should contribute to the still open debate on the role of the expansions per se in Drosophila and in human pathogenesis of RNA-dominant diseases.
Intraretinal hyperreflective foci on spectral-domain optical coherence tomographic images of patients with retinitis pigmentosa

Background The purpose of this study was to observe the characteristic findings of spectral-domain optical coherence tomography (SD-OCT) images in the retinas of patients with retinitis pigmentosa and to evaluate their distribution patterns in the early and advanced stages of the disease. Methods A total of 184 patients (368 eyes) with retinitis pigmentosa were observed using SD-OCT. We studied the presence or absence of continuous inner/outer segment (IS/OS) lines, presence of thinning of the retinal pigment epithelium-Bruch’s membrane complex, and distribution patterns of hyperreflective foci in the inner and outer nuclear layers (INL and ONL). Results The IS/OS junction had partially disappeared in 275 eyes, which were at the early stage of retinitis pigmentosa (group X), whereas the junction had totally disappeared in 93, which were at the advanced stage of retinitis pigmentosa (group Y). Hyperreflective foci in the INL were observed in a significantly larger proportion of the eyes in group X than in group Y (90% versus 61%, P<0.001), but hyperreflective foci in the ONL were observed in a significantly larger proportion of eyes in group Y than in group X (100% versus 69%, P<0.001). Conclusion Hyperreflective foci in the INL were more frequently observed in retinas with the early stage of retinitis pigmentosa and hyperreflective foci in the ONL were more frequently observed in the advanced stage. Hyperreflective foci may be indicative of changes in the retinal structure at each stage of retinitis pigmentosa.
Intergenerational Public Goods : Transnational Considerations by Todd Sandler * School of Economic , Political and Policy Sciences

This paper analyzes public goods whose benefits cross countries' borders and generations. Once provided, transnational intergenerational public goods (TIPGs) are assets that generate benefits for subsequent generations. For treaties involving TIPGs, a coalition of rich developed countries are apt to shoulder more of the provision burden then a coalition of poor developing countries. This burden inequality worsens if the developed countries unilaterally display altruism to future generations; nevertheless, altruistic benefits may offset reduced spillovers. When current generations strategize with respect to future generations, provision and efficiency suffer; however, the hypothesized unequal burden sharing improves somewhat. For alternative aggregator technologies of public supply, these one-sided burdens may be partly ameliorated. The author is grateful to two anonymous reviewers for their helpful comments on an earlier version of the paper.
Applying Argumentation to Enhance Dialogues in Social Networks

Nowadays, many websites allow social networking between their users in an explicit or implicit way. In this work, we show how argumentation schemes theory can provide a valuable help to formalize and structure on-line discussions and user opinions in decision support and business oriented websites that held social networks among their users. Two real case studies are presented and analysed. Then, guidelines to enhance social decision support and recommendations with argumentation are provided.
Targeting nicotine addiction: the possibility of a therapeutic vaccine

Cigarette smoking is the primary cause of lung cancer, cardiovascular diseases, reproductive disorders, and delayed wound healing all over the world. The goals of smoking cessation are both to reduce health risks and to improve quality of life. The development of novel and more effective medications for smoking cessation is crucial in the treatment of nicotine dependence. Currently, first-line smoking cessation therapies include nicotine replacement products and bupropion. The partial nicotinic receptor agonist, varenicline, has recently been approved by the US Food and Drug Administration (FDA) for smoking cessation. Clonidine and nortriptyline have demonstrated some efficacy, but side effects may limit their use to second-line treatment products. Other therapeutic drugs that are under development include rimonabant, mecamylamine, monoamine oxidase inhibitors, and dopamine D3 receptor antagonists. Nicotine vaccines are among newer products seeking approval from the FDA. Antidrug vaccines are irreversible, provide protection over years and need booster injections far beyond the critical phase of acute withdrawal symptoms. Interacting with the drug in the blood rather than with a receptor in the brain, the vaccines are free of side effects due to central interaction. For drugs like nicotine, which interacts with different types of receptors in many organs, this is a further advantage. Three anti-nicotine vaccines are today in an advanced stage of clinical evaluation. Results show that the efficiency of the vaccines is directly related to the antibody levels, a fact which will help to optimize the vaccine effect. The vaccines are expected to appear on the market between 2011 and 2012.
When Mayors Matter : Estimating the Impact of Mayoral Partisanship on City Policy

U.S. cities are limited in their ability to set policy. Can these constraints mute the impact of mayors’ partisanship on policy outcomes? We hypothesize that mayoral partisanship will more strongly affect outcomes in policy areas where there is less shared authority between local, state, and federal governments. To test this hypothesis, we create a novel dataset combining U.S. mayoral election returns from 1990 to 2006 with city fiscal data. Using regression discontinuity design, we find that cities that elect a Democratic mayor spend a smaller share of their budget on public safety, a policy area where local discretion is high, than otherwise similar cities that elect a Republican or an Independent. We find no differences on tax policy, social policy, and other areas that are characterized by significant overlapping authority. These results suggest that models of national policymaking are only partially applicable to U.S. cities. They also have implications for political accountability: mayors may not be able to influence the full range of policies that are nominally local responsibilities.
A robust cluster based routing protocol for MANET

The main goal of routing protocol is efficient delivery of data from source to destination. All routing protocols are same in this goal, but the way they adopt to achieve it is different. So routing strategy has an egregious role on the performance of an ad hoc network and is one of the challenging issues in mobile ad hoc network (MANET). In this paper we designed a novel self repair cluster based routing protocol based on ad hoc on demand distance vector (AODV). Nodes are organized into a hierarchical structure of multi hop clusters using a stable distributed clustering algorithm. Further Third Party Route Reply is used to improve the performance of routing protocol. We focus on control of the NRL and end-to-end delay while improving the PDR by implementing the third party route reply in route discovery process and the self repair technique inside the cluster for route maintenance.
Active Vision during Action Execution, Observation and Imagery: Evidence for Shared Motor Representations

The concept of shared motor representations between action execution and various covert conditions has been demonstrated through a number of psychophysiological modalities over the past two decades. Rarely, however, have researchers considered the congruence of physical, imaginary and observed movement markers in a single paradigm and never in a design where eye movement metrics are the markers. In this study, participants were required to perform a forward reach and point Fitts’ Task on a digitizing tablet whilst wearing an eye movement system. Gaze metrics were used to compare behaviour congruence between action execution, action observation, and guided and unguided movement imagery conditions. The data showed that participants attended the same task-related visual cues between conditions but the strategy was different. Specifically, the number of fixations was significantly different between action execution and all covert conditions. In addition, fixation duration was congruent between action execution and action observation only, and both conditions displayed an indirect Fitts’ Law effect. We therefore extend the understanding of the common motor representation by demonstrating, for the first time, common spatial eye movement metrics across simulation conditions and some specific temporal congruence for action execution and action observation. Our findings suggest that action observation may be an effective technique in supporting motor processes. The use of video as an adjunct to physical techniques may be beneficial in supporting motor planning in both performance and clinical rehabilitation environments.
Comparison of Several SNR Estimators for QPSK Modulations

The performances of several signal-to-noise ratio (SNR) estimation techniques reported in the literature are compared to identify the "best" estimator. The SNR estimators are investigated by the computer simulation of quartenary phase-shift keying (QPSK) signals in complex additive white Gaussian noise (AWGN). The mean square error is used as a measure of performance. In addition to comparing the relative performances, the absolute levels of performance are also established, the simulated performances are compared for complex AWGN that is derived here. Computer simulations verify the performance of the 'Phase-lock' method is the best estimator for the high SNR range (around higher than 15dB). The 'improved' method is the best estimator for SNR lower than 15dB and higher than 10 dB. for the low SNR range, the 'M2M4' method performs better than the other method.
Modified backpropagation algorithm with adaptive learning rate based on differential errors and differential functional constraints

In this paper, a new adaptive learning rate algorithm to train a single hidden layer neural network is proposed. The adaptive learning rate is derived by differentiating linear and nonlinear errors and functional constraints weight decay term at hidden layer and penalty term at output layer. Since the adaptive learning rate calculation involves first order derivative of linear and nonlinear errors and second order derivatives of functional constraints, the proposed algorithm converges quickly. Simulation results show the advantages of proposed algorithm.
Large-N Limit of N=2 Supersymmetric QN Model in Two Dimensions

We investigate non-perturbative structures of the two-dimensional N = 2 supersymmet- ric nonlinear sigma model on the quadric surface Q N −2 ( )= SO(N )/SO(N − 2) × U (1), which is a Hermitian symmetric space, and therefore Kahler, by using the auxiliary field and large-N methods. This model contains two kinds of non-perturbatively stable vacua; one of them is the same vacuum as that of the supersymmetric P N −1 model, and the other is a new kind of vacuum, which has not yet been known to exist in two-dimensional nonlinear sigma models, the Higgs phase. We show that both of these vacua are asymp- totically free. Although symmetries are broken in these vacua, there appear no massless Nambu-Goldstone bosons, in agreement with Coleman's theorem, due to the existence of two different mechanisms in these vacua, the Schwinger and the Higgs mechanisms.
Distribution and Expression of Picalm in Alzheimer Disease

PICALM, the gene encoding phosphatidylinositol-binding clathrin assembly (picalm) protein, was recently shown to be associated with risk of Alzheimer disease (AD). Picalm is a key component of clathrin-mediated endocytosis. It recruits clathrin and adaptor protein 2 (AP-2) to the plasma membrane and, along with, AP-2 recognizes target proteins. The attached clathrin triskelions cause membrane deformation around the target proteins enclosing them within clathrin-coated vesicles to be processed in lysosomes or endosomes. We examined the distribution of picalm in control and AD brain tissue and measured levels of picalm messenger RNA (mRNA) by real-time polymerase chain reaction. Immunolabeling of brain tissue showed that picalm is predominately present in endothelial cells. This was further supported by the demonstration of picalm in human cerebral microvascular cells grown in culture. Picalm mRNA was elevated in relation to glyceraldehyde-3-phosphate dehydrogenase but not factor VIII-related antigen or CD31 mRNA in the frontal cortex in AD. No change was seen in the temporal cortex or thalamus. The transport of A&bgr; across vessel walls and into the bloodstream is a major pathway of A&bgr; removal from the brain and picalm is ideally situated within endothelial cells to participate in this process. Further research is needed to determine whether PICALM expression is influenced by A&bgr; levels and whether it affects A&bgr; uptake and transport by endothelial cells.
2.5 Gbit/s compact transimpedance amplifier using active inductor in 130nm CMOS technology

This paper presents the analysis and design of a 2.5 Gbit/s transimpedance amplifier (TIA) realized in 130 nm CMOS technology. The proposed TIA uses a common source (CS) amplifier with active inductive peaking (AP-TIA). The TIA is followed by a post amplifier and an output driver to provide an interface to the measurement setup. The post layout simulation demonstrates that the TIA achieves 46.16 dBΩ transimpedance gain with 2 GHz bandwidth for 2 pF input capacitance including the photodiode, ESD, and pad capacitance. The integrated input referred noise current is 1.062 μArms. The complete optical receiver has 76.78 dBΩ transimpedance gain, and optical sensitivity of -21 dBm for BER= 10-12 at data rate of 2.5 Gbit/s. The TIA alone consumes 5.4 mW whereas the total power consumption of the complete optical receiver is 47.3 mW for 1.8 V single supply voltage.
Overexpression of Monocyte Chemoattractant Protein-1 in Adipose Tissues Causes Macrophage Recruitment and Insulin Resistance*

Adipose tissue expression and circulating concentrations of monocyte chemoattractant protein-1 (MCP-1) correlate positively with adiposity. To ascertain the roles of MCP-1 overexpression in adipose, we generated transgenic mice by utilizing the adipocyte P2 (aP2) promoter (aP2-MCP-1 mice). These mice had higher plasma MCP-1 concentrations and increased macrophage accumulation in adipose tissues, as confirmed by immunochemical, flow cytometric, and gene expression analyses. Tumor necrosis factor-α and interleukin-6 mRNA levels in white adipose tissue and plasma non-esterified fatty acid levels were increased in transgenic mice. aP2-MCP-1 mice showed insulin resistance, suggesting that inflammatory changes in adipose tissues may be involved in the development of insulin resistance. Insulin resistance in aP2-MCP-1 mice was confirmed by hyperinsulinemic euglycemic clamp studies showing that transgenic mice had lower rates of glucose disappearance and higher endogenous glucose production than wild-type mice. Consistent with this, insulin-induced phosphorylations of Akt were significantly decreased in both skeletal muscles and livers of aP2-MCP-1 mice. MCP-1 pretreatment of isolated skeletal muscle blunted insulin-stimulated glucose uptake, which was partially restored by treatment with the MEK inhibitor U0126, suggesting that circulating MCP-1 may contribute to insulin resistance in aP2-MCP-1 mice. We concluded that both paracrine and endocrine effects of MCP-1 may contribute to the development of insulin resistance in aP2-MCP-1 mice.
Opioid Activation of Toll-Like Receptor 4 Contributes to Drug Reinforcement

Opioid action was thought to exert reinforcing effects solely via the initial agonism of opioid receptors. Here, we present evidence for an additional novel contributor to opioid reward: the innate immune pattern-recognition receptor, toll-like receptor 4 (TLR4), and its MyD88-dependent signaling. Blockade of TLR4/MD2 by administration of the nonopioid, unnatural isomer of naloxone, (+)-naloxone (rats), or two independent genetic knock-outs of MyD88-TLR4-dependent signaling (mice), suppressed opioid-induced conditioned place preference. (+)-Naloxone also reduced opioid (remifentanil) self-administration (rats), another commonly used behavioral measure of drug reward. Moreover, pharmacological blockade of morphine-TLR4/MD2 activity potently reduced morphine-induced elevations of extracellular dopamine in rat nucleus accumbens, a region critical for opioid reinforcement. Importantly, opioid-TLR4 actions are not a unidirectional influence on opioid pharmacodynamics, since TLR4−/− mice had reduced oxycodone-induced p38 and JNK phosphorylation, while displaying potentiated analgesia. Similar to our recent reports of morphine-TLR4/MD2 binding, here we provide a combination of in silico and biophysical data to support (+)-naloxone and remifentanil binding to TLR4/MD2. Collectively, these data indicate that the actions of opioids at classical opioid receptors, together with their newly identified TLR4/MD2 actions, affect the mesolimbic dopamine system that amplifies opioid-induced elevations in extracellular dopamine levels, therefore possibly explaining altered opioid reward behaviors. Thus, the discovery of TLR4/MD2 recognition of opioids as foreign xenobiotic substances adds to the existing hypothesized neuronal reinforcement mechanisms, identifies a new drug target in TLR4/MD2 for the treatment of addictions, and provides further evidence supporting a role for central proinflammatory immune signaling in drug reward.
Stability of vector bundles from F-theory

We use a recently proposed construction of stable holomorphic vector bundles V on elliptically fibered Calabi-Yau n-fold Zn in terms of F-theory compactifications on local singularities to describe stability conditions on V. Specifically, the requirement that the F-theory compactification manifold is Calabi-Yau implies a a stability criterion on V which is formulated in terms of the existence of holomorphic sections of certain line bundles.
Bioinspired Polydopamine Synthesis and Its Electrochemical Characterization

The bioinspired polymer polydopamine is synthesized and deposited on semiconductive glass substrates under different synthesis conditions (pH and oxidant type). Electrochemical methods are used to verify polymer deposition on the substrate and to examine the charge transfer properties of the obtained coatings. The presence of aromatic rings from the polymer is assessed by Raman spectroscopy. The experiment was designed to fit within a physical chemistry course and can also be suitable for courses on polymers, materials science, and electrochemistry.
Initial alignment technology of strapdown inertial navigation system based-on stationary base

Initial alignment is one of the key technologies of strapdown inertial navigation system, the accuracy of strapdown inertial navigation system is directly affected by the accuracy of initial alignment, and the rapid reaction capability of strapdown inertial navigation system is decided by the alignment time. In this paper, the output error and the random drift of the inertial accelerometers and gyroscopes, and the frequency domain analysis of the classical control theory were used to study initial alignment error model. On the basis of Kalman filter principle, the state equation and observation equation were established, and the simulation and analysis of initial alignment were done at the same time. Simulation results show that the algorithm is simple and is easy to achieve, and effectively shortens the time of initial alignment, it is a more ideal alignment program.
Roles of Zinc Signaling in the Immune System

Zinc (Zn) is an essential micronutrient for basic cell activities such as cell growth, differentiation, and survival. Zn deficiency depresses both innate and adaptive immune responses. However, the precise physiological mechanisms of the Zn-mediated regulation of the immune system have been largely unclear. Zn homeostasis is tightly controlled by the coordinated activity of Zn transporters and metallothioneins, which regulate the transport, distribution, and storage of Zn. There is growing evidence that Zn behaves like a signaling molecule, facilitating the transduction of a variety of signaling cascades in response to extracellular stimuli. In this review, we highlight the emerging functional roles of Zn and Zn transporters in immunity, focusing on how crosstalk between Zn and immune-related signaling guides the normal development and function of immune cells.
Digital Propaganda: The Tyranny of Ignorance

The existence of propaganda is inexorably bound to the nature of communication and communications technology. Mass communication by citizens in the digital age has been heralded as a means to counter elite propaganda; however, it also provides a forum for misinformation, aggression and hostility. The extremist group Britain First has used Facebook as a way to propagate hostility towards Muslims, immigrants and social security claimants in the form of memes, leading to a backlash from sites antithetical to their message. This article provides a memetic analysis, which addresses persuasion, organisation, political echo chambers and self-correcting online narratives; arguing that propaganda can be best understood as an evolving set of techniques and mechanisms which facilitate the propagation of ideas and actions. This allows the concept to be adapted to fit a changing political and technological landscape and to encompass both propaganda and counter-propaganda in the context of horizontal communications networks.
Integrated facilities design using a contour distance metric

The unequal area facility design problem has been studied in the literature generally by considering block layout separate from detailed design. This paper shows a tractable method for concurrently optimizing department shape and location within the facility, and selection of the appropriate number of Input/Output (I/O) stations per department and then optimally locating them. The distance metric used is the contour distance that measures transport between I/O stations along the perimeters of departmental boundaries. This distance metric better reflects allowable material flow for many industrial applications and it directly implies the optimal aisle structure for the facility.