Miracle-dz/UniFAR-FTUs huggingface dataset:
Fear Memory Recall Potentiates Opiate Reward Sensitivity through Dissociable Dopamine D1 versus D4 Receptor-Dependent Memory Mechanisms in the Prefrontal Cortex

Disturbances in prefrontal cortical (PFC) dopamine (DA) transmission are well established features of psychiatric disorders involving pathological memory processing, such as post-traumatic stress disorder and opioid addiction. Transmission through PFC DA D4 receptors (D4Rs) has been shown to potentiate the emotional salience of normally nonsalient emotional memories, whereas transmission through PFC DA D1 receptors (D1Rs) has been demonstrated to selectively block recall of reward- or aversion-related associative memories. In the present study, using a combination of fear conditioning and opiate reward conditioning in male rats, we examined the role of PFC D4/D1R signaling during the processing of fear-related memory acquisition and recall and subsequent sensitivity to opiate reward memory formation. We report that PFC D4R activation potentiates the salience of normally subthreshold fear conditioning memory cues and simultaneously potentiates the rewarding effects of systemic or intra-ventral tegmental area (VTA) morphine conditioning cues. In contrast, blocking the recall of salient fear memories with intra-PFC D1R activation, blocks the ability of fear memory recall to potentiate systemic or intra-VTA morphine place preference. These effects were dependent upon dissociable PFC phosphorylation states involving calcium-calmodulin-kinase II or extracellular signal-related kinase 1–2, following intra-PFC D4 or D1R activation, respectively. Together, these findings reveal new insights into how aberrant PFC DAergic transmission and associated downstream molecular signaling pathways may modulate fear-related emotional memory processing and concomitantly increase opioid addiction vulnerability. SIGNIFICANCE STATEMENT Post-traumatic stress disorder is highly comorbid with addiction. In this study, we use a translational model of fear memory conditioning to examine how transmission through dopamine D1 or D4 receptors, in the prefrontal cortex (PFC), may differentially control acquisition or recall of fear memories and how these mechanisms might regulate sensitivity to the rewarding effects of opioids. We demonstrate that PFC D4 activation not only controls the salience of fear memory acquisition, but potentiates the rewarding effects of opioids. In contrast, PFC D1 receptor activation blocks recall of fear memories and prevents potentiation of opioid reward effects. Together, these findings demonstrate novel PFC mechanisms that may account for how emotional memory disturbances might increase the addictive liability of opioid-class drugs.
Pose2Instance: Harnessing Keypoints for Person Instance Segmentation

Human keypoints are a well-studied representation of people.We explore how to use keypoint models to improve instance-level person segmentation. The main idea is to harness the notion of a distance transform of oracle provided keypoints or estimated keypoint heatmaps as a prior for person instance segmentation task within a deep neural network. For training and evaluation, we consider all those images from COCO where both instance segmentation and human keypoints annotations are available. We first show how oracle keypoints can boost the performance of existing human segmentation model during inference without any training. Next, we propose a framework to directly learn a deep instance segmentation model conditioned on human pose. Experimental results show that at various Intersection Over Union (IOU) thresholds, in a constrained environment with oracle keypoints, the instance segmentation accuracy achieves 10% to 12% relative improvements over a strong baseline of oracle bounding boxes. In a more realistic environment, without the oracle keypoints, the proposed deep person instance segmentation model conditioned on human pose achieves 3.8% to 10.5% relative improvements comparing with its strongest baseline of a deep network trained only for segmentation.
Interleukin 2 Promotes Hepatic Regulatory T Cell Responses and Protects From Biliary Fibrosis in Murine Sclerosing Cholangitis

In the multidrug resistance protein 2 (Mdr2)‐/‐ mouse model, low phospholipid bile instigates biliary epithelial injury, sterile inflammation, and fibrosis, thereby recapitulating disease mechanisms implicated in biliary atresia (BA) and primary sclerosing cholangitis. We hypothesize that T lymphocytes contribute to the biliary injury and fibrosis in murine sclerosing cholangitis (SC) and that they are susceptible to suppression by regulatory T cells (Tregs). In juvenile Mdr2‐/‐ mice, intrahepatic CD8+ lymphocytes were expanded, and contraction of intrahepatic Tregs coincided with rising serum alanine transferase and alkaline phosphatase (ALP) levels between days 14‐30 of life. Antibody‐mediated depletion of intrahepatic CD8+ lymphocytes during that time reduced ALP levels and the expression of osteopontin (Opn), a pro‐fibrogenic cytokine. Depletion of intrahepatic Tregs with anti‐CD25 antibody between days 7‐30 increased intrahepatic CD8+ T cells, Opn expression, and fibrosis. Conversely, expansion of intrahepatic Tregs with interleukin 2/anti‐interleukin 2 immune complexes (IL‐2c) downregulated hepatic expression of Opn and Tnf, reduced frequency of intrahepatic CD8+ lymphocytes, and diminished biliary injury and fibrosis. Treatment with IL‐2c upregulated hepatic Treg expression of CD39, an ectonucleotidase capable of hydrolyzing pro‐inflammatory adenosine triphosphate. In vitro, Tregs expressing CD39 suppressed the proliferation of hepatic CD8+ lymphocytes from Mdr2‐/‐ mice more efficiently than those lacking CD39. In infants with BA, infiltration of interlobular bile ducts with CD8+ cells was associated with biliary expression of Opn and its transcription was negatively correlated with mRNA expression of Treg‐associated genes. Conclusion: Hepatic CD8+ T lymphocytes drive biliary injury and fibrosis in murine SC. Their proliferation is controlled by hepatic Tregs through the purinergic pathway, which is responsive to IL‐2c, suggesting that Treg‐directed low‐dose Il‐2 treatment may be considered as therapy for SC.
Evaluation based analysis of packet delivery ratio for AODV and DSR under UDP and TCP environment

The self-configuration and healing of sensor nodes in ad hoc networks are challenging task. To meet the requirements of this type of networks there is needed to design new efficient routing protocols. The existing routing protocols in the mobile ad hoc network are AODV and DSR. It is very difficult to investigate the routing issues, for example, PDR under different parameters in real time environment. The routing protocols efficiency depends on the number of packets successfully receive on destination. This paper presents the result based investigation these two main protocols with respect to packet delivery ratio under TCP and UDP environment. For the evaluation, Network Simulator (NS-2.35) is used. The simulation results show that under TCP, the Packet Delivery Ratio (PDR) of AODV is not good as compared to DSR but it is very interesting to know that PDR of DSR is excellent under TCP and UDP environment.
Evaluation of the diagnostic and predictive power of PCA3 in the prostate cancer. A different best cut-off in each different scenario. Preliminary results.

INTRODUCTION Aim of this study is to evaluate the diagnostic performance of PCA3 in patients with indication to perform a new biopsy, according to the histological doubt such as High Grade Prostatic Intraepithelial Neoplasia (HGPIN) or Atypical Small Gland Proliferation (ASAP) or the clinical suspicion. MATERIALS AND METHODS One hundred men were enrolled. We used the PCA3 - PROGENSA™ procedure. After the PCA3 test a repeated prostate biopsy was proposed. The histological findings were correlated to the PCA3 scores. We calculated the positive predictive value (PPV), the sensibility, the specificity, the Youden's index, the ROC curves, the area under the curve (AUC) for each cut-off value of PCA3 score. RESULTS These results are preliminary, because at present only 50 of the 100 enlisted men were subjected to rebiopsy. We calculated the best cut-off PCA3 score 20 at the first diagnosis; for patients with HGPIN or ASAP at first biopsy the best sensitivity cut-off is 45; the best cutoff is 45 when you already have a diagnosis of HGPIN, and 35 for ASAP. If we normalize the PCA3 score to the prostate volume, the best cut-off would be 20, with 100% sensitivity with a prostate volume of 65 ml. All results are statistically significant. The real problem, also present in literature, is the constant presence of not diagnosed prostate cancers, for any cut-off value. CONCLUSIONS Our preliminary results suggest that, to get the best diagnostic performance, it would be wrong to maintain a single cut-off, but it should be chosen according to the scenario of the patients subgroup. It is to explore the possibility to search for the PCA3 in the serum to bridge the gap of the aggressive PCa missed by the urinary test.
Bias, Operational Bias, and Generalizability in Phase II/III Trials.

Background Adaptive clinical trial designs improve the ef ﬁ ciency of the drug development process by allowing treatment decisions to be made earlier, while protecting the interests of the patients in the trials. In settings in which a randomized phase II ef ﬁ cacy signal is required to justify starting a large phase III trial, a phase II/III (seamless) design can sometimes be used to adaptively combine randomized phase II and phase III trial components. 1-4 After the phase II part of the trial is enrolled and the phase II outcome is suf ﬁ ciently mature, a go/no-go decision is made regarding whether to continue accrual to the phase III part of the trial. The phase II patients are used in the ﬁ nal phase III analysis, and a separate phase III protocol need not be developed. This design offers ef ﬁ ciency gains relative to performing an independent phase III trial after a positive phase II trial. In general, the phase II analysis is performed con ﬁ dentially solely to make a go/no-go decision, and the phase II results are not released to the public. When the phase II outcome events (eg, progression-free survival [PFS]) are occurring slowly, or when the same end point (eg, overall survival [OS]) is used for the phase II and the phase III analyses, an accrual suspension while waiting for the phase II data to mature may be needed to minimize patient exposure to an ineffective therapy and reap the ef ﬁ ciency bene ﬁ ts of the design. 2 Although suspending/restarting accrual in a phase III trial represents a logistical challenge, this approach is being used in the National Cancer Institute National Clinical Trials Network trials NCT02502266: Cediranib Maleate and Olaparib or Standard in With Recurrent Platinum-Resistant or -Refractory
Classification of Breast Cancer and Grading of Diabetic Retinopathy & Macular Edema using Ensemble of Pre-trained Convolutional Neural Networks

In this manuscript, we present a deep learning based approach for detection and classification of medical conditions such as classification of breast cancer and grading of diabetic retinopathy and macular edema. The performance of a convolutional neural network is dependent on the architecture of the network, amount of training data and data pre-processing. Transfer learning is oft utilized in deep learning so as to counter the limited availability of high quality annotated data. Hence, we create an ensemble of pre-trained classifiers by making use of models with different topologies and data normalization schemes. In general, the variance associated with an ensemble of classifiers is lower compared to a single classifier and thus generalizes better on unseen data. An F1 score based model pruning technique was utilized for deciding the optimal number of classifiers in the ensemble. The proposed technique was tested on two separate biomedical image challenges, namely the (1) classification of breast cancer from histology images [BACH-2018] and (2) grading of diabetic retinopathy and macular edema from fundus images [IDRiD-2018]. On the histology data, our technique was adjudged jointly as the top performing algorithm while for the task of diabetic retinopathy grading, the technique was declared as the 4 best performing algorithm.
Is Montipora dilatata an endangered coral species or an ecotype ? Genes and skeletal microstructure lump seven Hawaiian species into four groups

Image by J. E. Maragos. Foreground: M. capitata; above: M. dilatata; above, lower left: invasive algae (Kappaphycus/Eucheuma spp.) 2 Executive summary Montipora dilatata is considered to be one of the rarest corals known. Thought to be endemic to Hawaii, only a few colonies have ever been found despite extensive surveys. Endangered species status would have major conservation implications; however, coral species boundaries are poorly understood. In order to examine genetic and morphological variation in Hawaiian Montipora, a suite of molecular markers (mitochondrial: COI, CR, Cyt-B, 16S, ATP6; nuclear: ATPsβ, ITS), in addition to a suite of measurements on skeletal microstructure, were examined. The ITS region and mitochondrial markers revealed four distinct clades: I) M. patula/M. verilli, II) M. incrassata, III) M. capitata, IV) M. dilatata/M. flabellata/M. turgescens. The nuclear ATPsβ intron tree had several exceptions that are generally interpreted as resulting from recent hybridization between clades or incomplete lineage sorting. Since the multicopy nuclear ITS region was concordant with the mitochondrial data, incomplete lineage sorting of the ATPsβ intron is a more likely explanation. Principal components analysis (PCA) of microstructure measurements agreed with the genetic clades rather than the nominal taxa. These species groups therefore either represent recent or insipient (CA <1MYA) species or morphological variants of the same biological species. These clades are likely to occur outside of Hawaii according to mitochondrial control region haplotypes from previous studies. Common garden experiments were conducted on distinct morphotypes of M. capitata to test the hypothesis that micro-skeletal traits can be phenotypically plastic in this genus. Although the experiment suffered high mortality from parasitic flatworms, verrucae (rice-grain sized bumps) were documented to form on formerly smooth colonies, indicating plasticity. This study contributes towards understanding the relationship between genetic and morphological variation in this taxonomically challenging group, which is essential for effective conservation and the key to understanding the evolution and biodiversity of reef building corals. Management implications This study identified two closely related species complexes (M. dilatata/M. flabellata/M. turgescens and M. patula/M. verilli) that may occur outside of Hawaii. We found no significant genetic or micro-skeletal differences between nominal taxa within these species complexes; however, this study may not be capable of detecting recent or insipient species (CA <1MYA). Now that these species complexes have been identified, population genetic and/or reproductive studies are necessary to determine if the nominal species within each complex are actively interbreeding. The findings of rapid evolution and …
Lyme disease ecology in a changing world: consensus, uncertainty and critical gaps for improving control

Lyme disease is the most common tick-borne disease in temperate regions of North America, Europe and Asia, and the number of reported cases has increased in many regions as landscapes have been altered. Although there has been extensive work on the ecology and epidemiology of this disease in both Europe and North America, substantial uncertainty exists about fundamental aspects that determine spatial and temporal variation in both disease risk and human incidence, which hamper effective and efficient prevention and control. Here we describe areas of consensus that can be built on, identify areas of uncertainty and outline research needed to fill these gaps to facilitate predictive models of disease risk and the development of novel disease control strategies. Key areas of uncertainty include: (i) the precise influence of deer abundance on tick abundance, (ii) how tick populations are regulated, (iii) assembly of host communities and tick-feeding patterns across different habitats, (iv) reservoir competence of host species, and (v) pathogenicity for humans of different genotypes of Borrelia burgdorferi. Filling these knowledge gaps will improve Lyme disease prevention and control and provide general insights into the drivers and dynamics of this emblematic multi-host–vector-borne zoonotic disease. This article is part of the themed issue ‘Conservation, biodiversity and infectious disease: scientific evidence and policy implications'.
Comparative Study of Interlock Nailing Versus Dynamic Compression Plating in Fractures of Tibia – A Study of Sixty Cases

Background: In modern era high speed vehicular traffic accidents fractures of the tibial shaft are common injuries among the long bones and mainly affect young adults, i.e. individuals at their peak of physical and work capacity. The present study was a comparative study between interlock nailing and Dynamic compression plating (DCP) in the treatment of fractures of tibia. The purpose of the study was to determine the outcome and comparing the two different modalities of the treatment. Material methods: The Study includes sixty consecutive patients with fracture tibia [ closed and open Gustio & Anderson grade 1 only] treated with Dynamic compression platting and interlock nailing 30 in each group and were assessed clinically and radiologically and followed up to three years. Results: 90% patients had good to excellent results with 10% having fair results and no poor results. In DCP group there were 10 excellent, 15 good and 5 fair results whereas in interlock nailing group 15 patients had excellent, 14 patients had good results and 1 patient showed fair result. Conclusion: We conclude that DCP is a better mode of fixation for proximal and distal tibial facture and interlock nailing is ideal implant in diaphysial and segmental fractures
An AIS approach to a color image classification problem in a real time industrial application

An artificial immune system is applied to a pattern recognition problem. Artificial immune systems (AIS) possess nonlinear classification properties along with the biological properties such as self/non-self identification, positive and negative selection. In this paper, we propose a computational implementation of negative selection of immune system along with genetic algorithm to perform a color image classification task. The images used for classification are finished wooden components. The wooden components are kitchen cabinets manufactured by American Woodmark Corporation. The images are obtained from Virginia Polytechnic Institute and State University. The classification addresses the average RGB values of the images and the percentage of correct classification is obtained for a set of test and sample images.
A hand in the action : an arts-based inquiry of metaphor and meaning making as tools for inspiring transformation

This arts-based action research documents the living inquiry of one learner/educator as she strives to make sense of her own and her learner/participants' learning journeys. Using art and metaphor as tools for self-reflection, learners engaged with personal challenges in an effort to transform understandings of our personal ideologies so that we might live more consistently with them. The artist/researcher/teacher worked with a grade 6/7 class in an urban Canadian centre over a period of six weeks to develop puppetry as a tool to inquire into personal challenges. The use of puppets around the world and throughout time to captivate the imagination, create spectacle, speak truth to power, inspire therapeutic communication and reflective engagement, and reflect the human condition made it an intriguing medium for individuals to explore and expand their ways of being in the world. The learner/educator's struggles to develop relevant arts-based curriculum and to democratic learning practices reflected students' struggles to both understand their challenges in new ways and to make sense of arts-based inquiry. The challenges faced pointed to a problem-solution conception of learning in which the end result is predetermined. By reconceiving of the challenges as journeys, the new metaphor creates entrances into new understandings.
Online Learning:Does Learning Really Happen?——Comparison of Chinese and British Online Learning in Intercultural Context

With the rapid development of online education in China,enhancement of online education quality has become the focus of researchers and practitioners' attention and online pedagogy has become a core of online education research.How do students learn online? Does learning really happen in online education? This paper discusses this question in three aspects.First,conditions and characteristics of effective online learning in information era are discussed on basis of knowledge theories,learning theories,and insights from children's learning.Second,the paper presents characteristics of Chinese students' online learning and analyses whether learning really happens according to the conditions of effective online learning.Then the paper discusses the differences in students' online learning style,online learning resources,and online tutoring between China and Britain with the case study method of an intercultural online course.Last the paper summarizes tutoring strategies in British online education and offers insightful suggestions to Chinese online tutors in helping Chinese students learn more effectively.
PersuAIDE ! An Adaptive Persuasive Text Generation System for Fashion Domain

Persuasiveness is a creative art which aims at inducing certain set of beliefs in the target audience. In an e-commerce setting, for a newly launched product, persuasive descriptions are often composed to motivate an online buyer towards a successful purchase. Such descriptions can be catchy taglines, product-summaries, style-tipsetc. In this paper, we present PersuAIDE! - a persuasive system based on linguistic creativity to generate various forms of persuasive sentences from the input product specification. To demonstrate the effectiveness of the proposed system, we have applied the technology to fashion domain, where, for a given fashion product like"red collar shirt" we were able to generate descriptive sentences that not only explain the item but also garner positive attention, making it persuasive. PersuAIDE! identifies fashion related keywords from input specifications and intelligently expands the keywords to creative phrases. Once such compatible phrases are obtained, persuasive descriptions are synthesized from the set of phrases and input keywords with the help of a neural language model trained on a large domain-specific fashion corpus. We evaluate the system on a large fashion corpus collected from different sources using (a) automatic text generation metrics used for Machine Translation and Automatic Summarization evaluation and Readability measurement, and (b) human judgment scores evaluating the persuasiveness and fluency of the generated text. Experimental results and qualitative analysis show that an unsupervised system like ours can produce more creative and better constructed persuasive output than supervised generative counterparts based on neural sequence-to-sequence models and statistical machine translation.