Miracle-dz/UniFAR-FTUs huggingface dataset:
MicroRNA 339 down‐regulates μ‐opioid receptor at the post‐transcriptional level in response to opioid treatment

μ‐Opioid receptor (MOR) level is directly related to the function of opioid drugs, such as morphine and fentanyl. Although agonist treatment generally does not affect transcription of mor, previous studies suggest that morphine can affect the translation efficiency of MOR transcript via microRNAs (miRNAs). On the basis of miRNA microarray analyses of the hippocampal total RNA isolated from mice chronically treated with μ‐opioid agonists, we found a miRNA (miR‐339‐3p) that was consistently and specifically increased by morphine (2‐fold) and by fentanyl (3.8‐fold). miR‐339‐3p bound to the MOR 3′‐UTR and specifically suppressed reporter activity. Suppression was blunted by adding miR‐339‐3p inhibitor or mutating the miR‐339‐3p target site. In cells endogenously expressing MOR, miR‐339‐3p inhibited the production of MOR protein by destabilizing MOR mRNA. Up‐regulation of miR‐339‐3p by fentanyl (EC50=0.75 nM) resulted from an increase in primary miRNA transcript. Mapping of the miR‐339‐3p primary RNA and its promoter revealed that the primary miR‐339‐3p was embedded in a noncoding 3′‐UTR region of an unknown host gene and was coregulated by the host promoter. The identified promoter was activated by opioid agonist treatment (10 nM fentanyl or 10 μM morphine), a specific effect blocked by the opioid antagonist naloxone (10 μM). Taken together, these results suggest that miR‐339‐3p may serve as a negative feedback modulator of MOR signals by regulating intracellular MOR biosynthesis. —Wu, Q. , Hwang, C. K. , Zheng, H. , Wagley, Y. , Lin, H. ‐Y. , Kim, D. K. , Law, P.‐Y. , Loh, H. H. , Wei, L. ‐N. MicroRNA 339 downregulates mu opioid receptor at the post‐transcriptional level in response to opioid treatment. FASEB J. 27, 522–535 (2013). www.fasebj. org
Interleukin 1 system and sex steroid receptor expression in human breast cancer: interleukin 1alpha protein secretion is correlated with malignant phenotype.

PURPOSE The interleukin 1 (IL-1) system plays an important role in human pathology and is involved in the local control of malignant disease. However, little is known about its expression in breast cancer and its correlation with prognostic parameters such as receptor status and grading. EXPERIMENTAL DESIGN The expression of IL-1alpha and other IL-1 family members was analyzed by reverse transcription-PCR, ELISA, and immunohistochemistry in breast cancer cell lines, tumor-derived fibroblasts, and breast cancer tissue biopsies and compared with sex steroid receptor status and grading. RESULTS In breast cancer cell lines, IL-1alpha and -beta gene expression was present in the phenotypically most malignant cell lines, whereas estrogen receptor (ER) alpha and progesterone receptor mRNA expression was confined to lines that exhibit a rather benign phenotype. Only the highly malignant receptor-negative tumor cell line MDA MB 231 expressed IL-1alpha protein, and none of the cell lines secreted IL-1beta. Biopsies from breast cancer tissue expressed various amounts of IL-1alpha, IL-1beta, and IL-1 receptor antagonist mRNA, but consistently high levels of IL-1tIR. IL-1alpha protein expression was detected in tumor cells and/or adjacent stroma in 88%, and epithelial protein expression was correlated with both poor differentiation (P = 0.002; r = 0.469) and decreasing epithelial ERalpha expression (P = 0.004; r = -0.387). Furthermore, stromal IL-1alpha was predominant in areas with low or absent ERalpha protein expression in neighboring tumor epithelium (P = 0.001; r = -0.457). CONCLUSION We have demonstrated the presence of a functional IL-1 system in breast cancer and found that IL-1alpha is inversely correlated with local sex steroid receptor expression. We hypothesize that the unphysiological expression of IL-1alpha in less differentiated and ERalpha-negative tumors might contribute to their local invasiveness and malignant behavior.
Hedgehogs as Negative Regulators of the Cell Cycle

During the development of multicellular animals, cell proliferation must be precisely controlled, as deregulated proliferation can lead to overgrowth and cancer. In addition, proliferation must be tightly integrated with pattern formation and differentiation to generate the required number of cells in the right organs, and at the right time. All major signaling pathways employed during embryogenesis have been implicated in cell cycle regulation, indicating that no single pathway has been dedicated to this task. Also, the precise role of a particular signaling pathway in regulating proliferation is highly dependent on the cellular context, and may have opposite effects on cell-cycle progression in different cells and tissues. The Hedgehog (Hh) family of signaling proteins is known to control both differentiation and proliferation during development. So far, studies addressing the effect of Hh signaling on proliferation have shown it to have a stimulatory effect on cell-cycle progression. Here we review several recent studies indicating that Hh signaling can also have the opposite effect, directing cell-cycle exit in a number of cell types in vertebrate and in invertebrate embryos.
Coefficients of algebraic functions: formulae and asymptotics

This paper studies the coefficients of algebraic functions. First, we recall the too-little-known fact that these coefficients $f_n$ have a closed form. Then, we study their asymptotics, known to be of the type $f_n \sim C A^n n^{\alpha}$. When the function is a power series associated to a context-free grammar, we solve a folklore conjecture: the appearing critical exponents $\alpha$ can not be $^1/_3$ or $^{-5}/_2$, they in fact belong to a subset of dyadic numbers. We extend what Philippe Flajolet called the Drmota-Lalley-Woods theorem (which is assuring $\alpha=^{-3}/_2$ as soon as a "dependency graph" associated to the algebraic system defining the function is strongly connected): We fully characterize the possible critical exponents in the non-strongly connected case. As a corollary, it shows that certain lattice paths and planar maps can not be generated by a context-free grammar (i.e., their generating function is not $\mathbb{N}-algebraic). We end by discussing some extensions of this work (limit laws, systems involving non-polynomial entire functions, algorithmic aspects).
A box of chocolates

The articles in this issue of Neurology® Neuroimmunology & Neuroinflammation cover a broad range of topics, including new insights into the pathogenesis of natalizumab-associated progressive multifocal leukoencephalopathy (PML), important observations on antibody testing in neuromyelitis optica spectrum disorders (NMOSD), and a study related to degenerative dementia. However, all the articles are of interest. Like the famous box of chocolates anecdote from the movie Forrest Gump, you never know what you are going to get, but you know it will be enjoyable.
Hazardous Effects of Curcumin on Mouse Embryonic Development through a Mitochondria-Dependent Apoptotic Signaling Pathway

In this study, we examined the cytotoxic effects of curcumin, the yellow pigment of Curcuma longa, on the blastocyst stage of mouse embryos, subsequent embryonic attachment, and outgrowth in vitro and in vivo implantation by embryo transfer. Mouse blastocysts were incubated in medium with or without curcumin (6, 12 or 24 μM) for 24 h. Cell proliferation and growth were investigated using dual differential staining, apoptosis was analyzed with terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL), and implantation and post-implantation development of embryos were measured by in vitro development analysis and in vivo embryo transfer, respectively. Blastocysts treated with 24 μM curcumin displayed significantly increased apoptosis and decreased total cell number. Interestingly, we observed no marked differences in the implantation success rates between curcumin-pretreated and control blastocysts during in vitro embryonic development through implantation with a fibronectin-coated culture dish. However, in vitro treatment with 24 μM curcumin was associated with decreased implantation rate and increased resorption of postimplantation embryos in mouse uterus, as well as decreased fetal weight in the embryo transfer assay. Our results collectively indicate that in vitro exposure to curcumin triggers apoptosis and retards early postimplantation development after transfer to host mice. In addition, curcumin induces apoptotic injury effects on mouse blastocysts through ROS generation, and further promotes mitochondria-dependent apoptotic signaling processes to impair sequent embryonic development.
Higher order inference for the consensus mean in inter‐laboratory studies

In inter‐laboratory studies, a fundamental problem of interest is inference concerning the consensus mean, when the measurements are made by several laboratories which may exhibit different within‐laboratory variances, apart from the between laboratory variability. A heteroscedastic one‐way random model is very often used to model this scenario. Under such a model, a modified signed log‐likelihood ratio procedure is developed for the interval estimation of the common mean. Furthermore, simulation results are presented to show the accuracy of the proposed confidence interval, especially for small samples. The results are illustrated using an example on the determination of selenium in non‐fat milk powder by combining the results of four methods. Here, the sample size is small, and the confidence limits for the common mean obtained by different methods produce very different results. The confidence interval based on the modified signed log‐likelihood ratio procedure appears to be quite satisfactory.
Exploring the Relationship Between Web Application Development Tools and Security

How should software engineers choose which tools to use to develop secure web applications? Different developers have different opinions regarding which language, framework, or vulnerability-finding tool tends to yield more secure software than another; some believe that there is no difference at all between such tools. This paper adds quantitative data to the discussion and debate. We use manual source code review and an automated black-box penetration testing tool to find security vulnerabilities in 9 implementations of the same web application in 3 different programming languages. We explore the relationship between programming languages and number of vulnerabilities, and between framework support for security concerns and the number of vulnerabilities. We also compare the vulnerabilities found by manual source code review and automated black-box penetration testing. Our findings are: (1) we do not find a relationship between choice of programming language and application security, (2) automatic framework protection mechanisms, such as for CSRF and session management, appear to be effective at precluding vulnerabilities, while manual protection mechanisms provide little value, and (3) manual source code review is more effective than automated black-box testing, but testing is complementary.
The Exact Cost of Exploring Streets with CAB

A fundamental problem in robotics is to compute a path for a robot from its current location to a given target. In this paper we consider the problem of a robot equipped with an on-board vision system searching for a target t in an unknown environment. We assume that the robot is located at a point s in a polygon that belongs to the well investigated class of polygons called streets . A street is a simple polygon where s and t are located on the polygon boundary and the part of the polygon boundary from s to t is weakly visible to the part from t to s and vice versa. We are interested in the ratio of the length of the path traveled by the robot to the length of the shortest path from s to t which is called the competitive ratio of the strategy. In this work we present the first exact analysis of the continuous angular bisector (CAB) strategy, which has been considered several times before, and show that it has a competitive ratio of ~ 1.6837 in the worst case.
Visual recognition by learning from web data: A weakly supervised domain generalization approach

In this work, we formulate a new weakly supervised domain generalization approach for visual recognition by using loosely labeled web images/videos as training data. Specifically, we aim to address two challenging issues when learning robust classifiers: 1) coping with noise in the labels of training web images/videos in the source domain; and 2) enhancing generalization capability of learnt classifiers to any unseen target domain. To address the first issue, we partition the training samples in each class into multiple clusters. By treating each cluster as a “bag” and the samples in each cluster as “instances”, we formulate a multi-instance learning (MIL) problem by selecting a subset of training samples from each training bag and simultaneously learning the optimal classifiers based on the selected samples. To address the second issue, we assume the training web images/videos may come from multiple hidden domains with different data distributions. We then extend our MIL formulation to learn one classifier for each class and each latent domain such that multiple classifiers from each class can be effectively integrated to achieve better generalization capability. Extensive experiments on three benchmark datasets demonstrate the effectiveness of our new approach for visual recognition by learning from web data.
Predicting Targets of Human Reaching Motions Using Different Sensing Technologies

Rapid recognition of voluntary motions is crucial in human-computer interaction, but few studies compare the predictive abilities of different sensing technologies. This paper thus compares performances of different technologies when predicting targets of human reaching motions: electroencephalography (EEG), electrooculography, camera-based eye tracking, electromyography (EMG), hand position, and the user's preferences. Supervised machine learning is used to make predictions at different points in time (before and during limb motion) with each individual sensing modality. Different modalities are then combined using an algorithm that takes into account the different times at which modalities provide useful information. Results show that EEG can make predictions before limb motion onset, but requires subject-specific training and exhibits decreased performance as the number of possible targets increases. EMG and hand position give high accuracy, but only once the motion has begun. Eye tracking is robust and exhibits high accuracy at the very onset of limb motion. Several advantages of combining different modalities are also shown, including advantages of combining measurements with contextual data. Finally, some recommendations are given for sensing modalities with regard to different criteria and applications. The information could aid human-computer interaction designers in selecting and evaluating appropriate equipment for their applications.
Functional neuroimaging studies in mood disorders

Background: Our understanding of the neural circuitry involved in mood disorders is rapidly expanding through the ever-increasing application of functional brain imaging techniques. Objectives: A selective review of functional neuroimaging studies in patients with primary mood disorders was undertaken in order to identify points of commonality and controversy in the existing literature. Methods: Articles published between 1980 and July 2005 were identified using a range of keywords from relevant on-line databases and key journals. Results: Increased activity within limbic regions has been consistently associated with depressive states and may also be present in manic states too. Dorsal and ventral prefrontal regions appear compromised as suggested by emerging evidence of cortical inefficiency within prefrontal regions or reductions in their connectivity with limbic areas. Most of the functional changes observed are at least partly reversible following clinical remission although deficits in prefrontal regions may be state-related. Conclusions: Despite the use of disparate functional imaging modalities, there is a convergence of findings, and the results described do not appear to differ between unipolar and bipolar depression. However, further data are required in order to fully determine the functional changes occurring during manic states. Future work will also need to elucidate the effects of medication, the utility of specific cognitive tasks, and blood oxygenation level-dependent interactions within these affective states.
A Continuity Correction for Discrete Barrier Options

The payoff of a barrier option depends on whether or not a specified asset price, index, or rate reaches a specified level during the life of the option. Most models for pricing barrier options assume continuous monitoring of the barrier; under this assumption, the option can often be priced in closed form. Many (if not most) real contracts with barrier provisions specify discrete monitoring instants; there are essentially no formulas for pricing these options, and even numerical pricing is difficult. We show, however, that discrete barrier options can be priced with remarkable accuracy using continuous barrier formulas by applying a simple continuity correction to the barrier. The correction shifts the barrier away from the underlying by a factor of exp(bet sig sqrt dt), where bet approx 0.5826, sig is the underlying volatility, and dt is the time between monitoring instants. The correction is justified both theoretically and experimentally.
Evaluation of best practices in the design of online evidence-based practice instructional modules.

OBJECTIVES The research determined to what extent best practices are being followed by freely available online modules aimed at teaching critical thinking and evidence-based practices (EBPs) in health sciences fields. METHODS In phase I, an evaluation rubric was created after reviewing the literature. Individual rubric questions were assigned point values and grouped into sections, and the sections weighted. Phase II involved searching Internet platforms to locate online EBP modules, which were screened to determine if they met predetermined criteria for inclusion. Phase III comprised a first evaluation, in which two authors assessed each module, followed by a second evaluation of the top-scoring modules by five representatives from different health sciences units. RESULTS The rubric's 28 questions were categorized into 4 sections: content, design, interactivity, and usability. After retrieving 170 online modules and closely screening 91, 42 were in the first evaluation and 8 modules were in the second evaluation. Modules in the first evaluation earned, on average, 59% of available points; modules in the second earned an average of 68%. Both evaluations had a moderate level of inter-rater reliability. CONCLUSIONS The rubric was effective and reliable in evaluating the modules. Most modules followed best practices for content and usability but not for design and interactivity. IMPLICATIONS By systematically collecting and evaluating instructional modules, the authors found many potentially useful elements for module creation. Also, by reviewing the limitations of the evaluated modules, the authors were able to anticipate and plan ways to overcome potential issues in module design.
Social involvement of children with autism spectrum disorders in elementary school classrooms.

BACKGROUND Children with autism spectrum disorders (ASD) are increasingly included in general education classrooms in an effort to improve their social involvement. METHODS Seventy-nine children with ASD and 79 randomly selected, gender-matched peers (88.6% male) in 75 early (K-1), middle (2nd-3rd), and late (4th-5th) elementary classrooms across 30 schools completed social network surveys examining each child's reciprocal friendships, peer rejection, acceptance, and social involvement. RESULTS Across grade levels, peers less frequently reciprocated friendships with children with ASD than students in the matched sample. While children with ASD were not more likely to be rejected by peers, they were less accepted and had fewer reciprocal friendships than matched peers at each grade level. Although 48.1% of children with ASD were involved in the social networks of their classrooms, children with ASD were more likely to be isolated or peripheral to social relationships within the classroom across all grade levels, and this difference is even more dramatic in later elementary grades. CONCLUSIONS In inclusive classrooms, children with ASD are only involved in peers' social relationships about half of the time, and appear to be even less connected with increasing grade level. Promoting children with ASD's skills in popular activities to share with peers in early childhood may be a key preventive intervention to protect social relationships in late elementary school grades.
Aeromagnetic, gravity, and Differential Interferometric Synthetic Aperture Radar analyses reveal the causative fault of the 3 April 2017 Mw 6.5 Moiyabana, Botswana, earthquake

On 3 April 2017, a Mw 6.5 earthquake struck Moiyabana, Botswana, nucleating at >20 km focal depth within the Paleoproterozoic Limpopo‐Shashe orogenic belt separating the Archean Zimbabwe and Kaapvaal Cratons. We investigate the lithospheric structures associated with this earthquake using high‐resolution aeromagnetic and gravity data integrated with Differential Interferometric Synthetic Aperture Radar (DInSAR) analysis. Here we present the first results that provide insights into the tectonic framework of the earthquake. The ruptured fault trace delineated by DInSAR aligns with a distinct NW striking and NE dipping magnetic lineament within the Precambrian basement. The fault plane solution and numerical modeling indicate that the cause of the earthquake was 1.8 m displacement along a NW striking and NE dipping normal fault, rupturing at 21–24 km depth. We suggest that this seismic event was due to extensional reactivation of a crustal‐scale Precambrian thrust splay within the Limpopo‐Shashe orogenic belt.
Strategic Demand Information Sharing Between Competitors

We study the incentives of two competing firms — the building block of any supply chain with downstream competition — to exchange private demand signals when demand is uncertain. The novelty and fundamental contribution of our paper lies in its consideration of ex–post or strategic information sharing, where the decision to share or to conceal a private demand signal is made after observing the demand signal. Using a modeling framework with binary demand and binary demand signals, we demonstrate, for the first time in the literature, the existence of a pooling information sharing equilibrium: under certain conditions, competing firms want to share both low– and high–demand signals after receiving them. In addition, we also study the ex–ante version of the model mainly to facilitate comparison with its ex–post counterpart and to benchmark against existing results in the literature. Our analysis of the ex–ante case provides a theoretical proof for as well as an extension of related findings in the existing literature. We also show that not all ex–ante agreements to share information can survive ex–post, and that competitors have an incentive to make sure that any information exchanged is verifiable. As such, our results shed new light on a fundamental piece of the study of information flows in supply chains.