Miracle-dz/UniFAR-FTUs huggingface dataset:
Endocannabinoids and striatal function: implications for addiction-related behaviours

Since the identification and cloning of the major cannabinoid receptor expressed in the brain almost 25 years ago research has highlighted the potential of drugs that target the endocannabinoid system for treating addiction. The endocannabinoids, anandamide and 2-arachidonoyl glycerol, are lipid-derived metabolites found in abundance in the basal ganglia and other brain areas innervated by the mesocorticolimbic dopamine systems. Cannabinoid CB1 receptor antagonists/inverse agonists reduce reinstatement of responding for cocaine, alcohol and opiates in rodents. However, compounds acting on the endocannabinoid system may have broader application in treating drug addiction by ameliorating associated traits and symptoms such as impulsivity and anxiety that perpetuate drug use and interfere with rehabilitation. As a trait, impulsivity is known to predispose to addiction and facilitate the emergence of addiction to stimulant drugs. In contrast, anxiety and elevated stress responses accompany extended drug use and may underlie the persistence of drug intake in dependent individuals. In this article we integrate and discuss recent findings in rodents showing selective pharmacological modulation of impulsivity and anxiety by cannabinoid agents. We highlight the potential of selective inhibitors of endocannabinoid metabolism, directed at fatty acid amide hydrolase and monoacylglycerol lipase, to reduce anxiety and stress responses, and discuss novel mechanisms underlying the modulation of the endocannabinoid system, including the attenuation of impulsivity, anxiety, and drug reward by selective CB2 receptor agonists.
A Quantitative Proteomic Approach of the Different Stages of Colorectal Cancer Establishes OLFM4 as a New Nonmetastatic Tumor Marker*

Expression profiles represent new molecular tools that are useful to characterize the successive steps of tumor progression and the prediction of recurrence or chemotherapy response. In this study, we have used quantitative proteomic analysis to compare different stages of colorectal cancer. A combination of laser microdissection, OFFGEL separation, iTRAQ labeling, and MALDI-TOF/TOF MS was used to explore the proteome of 28 colorectal cancer tissues. Two software packages were used for identification and quantification of differentially expressed proteins: Protein Pilot and iQuantitator. Based on ∼1,190,702 MS/MS spectra, a total of 3138 proteins were identified, which represents the largest database of colorectal cancer realized to date and demonstrates the value of our quantitative proteomic approach. In this way, individual protein expression and variation have been identified for each patient and for each colorectal dysplasia and cancer stage (stages I–IV). A total of 555 proteins presenting a significant fold change were quantified in the different stages, and this differential expression correlated with immunohistochemistry results reported in the Human Protein Atlas database. To identify a candidate biomarker of the early stages of colorectal cancer, we focused our study on secreted proteins. In this way, we identified olfactomedin-4, which was overexpressed in adenomas and in early stages of colorectal tumors. This early stage overexpression was confirmed by immunohistochemistry in 126 paraffin-embedded tissues. Our results also indicate that OLFM4 is regulated by the Ras-NF-κB2 pathway, one of the main oncogenic pathways deregulated in colorectal tumors.
Reorganization of the Adult Auditory System: Perceptual and Physiological Evidence From Monaural Fitting of Hearing Aids

Changes in the sensory environment modify our sensory experience and may result in experience-related or learning-induced reorganization within the central nervous system. Hearing aids change the sensory environment by stimulating a deprived auditory system; therefore, they may be capable of inducing changes within the central auditory system. Examples of studies that have shown hearing aid induced perceptual and/or physiological changes in the adult human auditory system are discussed. Evidence in the perceptual domain is provided by studies that have investigated (a) speech perception, (b) intensity discrimination, and (c) loudness perception. Evidence in the physiological domain is provided by studies that have investigated acoustic reflex thresholds and event-related potentials. Despite the controversy in the literature concerning the rate, extent, and clinical significance of the acclimatization effect, there is irrefutable evidence that the deprived auditory system of some listeners can be modified with hearing aid experience.
Vaginal Yolk Sac Tumor in an Infant: A Case Report and Literature Review of the Last 30 Years

Vaginal yolk sac tumor is a rare malignant germ-cell tumor occurring most commonly in young girls. The treatment has evolved over the last 3 decades from radical surgery to conservative surgery with chemotherapy to chemotherapy alone. Here we present a case of a 6-month-old girl successfully treated with upfront surgery followed by chemotherapy. We include a literature review of studies on vaginal yolk sac tumor published in the last 30 years. We discuss the role of upfront surgery where possible followed by chemotherapy as a safe alternative to chemotherapy alone for the treatment of this rare malignancy.
Authorship Identification Using a Reduced Set of Linguistic Features

The proposed solution for authorship attribution combines a couple of the most important features identified in previous research in this domain with classification algorithms in order to detect the correct author. We consider that the most relevant aspect of our work is the small number of linguistic features and the use of the same framework to solve both the open and the closed class authorship problem, by only changing the classification algorithm. This approach obtained an overall 77% accuracy with regard to the total number of correctly classified documents.
Supplementary materials for : “ Adaptation to inversion of the visual field : a new twist on an old problem . ”

The control problem studied here is schematized in Supplementary Figure 1 and works as follows: the agent is presented with a visual target presented on a fixed 2D plane. Given the perceived location of the target the agent must then try to touch it. To keep the simulations simple, the attempt to strike the target is open loop (i.e. the agent is not able to modify their choice in mid-flight) and happens in a single time step or trial. Let, x(t) ∈ R and x(t) ∈ R, be the real and perceived location of the target on trial t. Here we will denote the elements of a vector using subscripts, e.g. x1(t) is the first element of x at trial t, and for convenience we will often drop the trial index, e.g. we may just write x or x. The target is viewed through one of three transformations, which are induced by prisms in the experimental setup,
Impact of small cell deployments on mobility performance in LTE-Advanced systems

The use of small cell deployments in heterogeneous networks (HetNet) environments is considered a promising strategy to cope with the explosion in mobile traffic. In the deployments, there is a concern that the large number of small cells causes the signalling load on the network nodes to increase due to frequent handovers (HOs) and mobility robustness to be degraded due to increased handover failures (HOFs) and radio link failures (RLFs). To examine these impacts caused by the introduction of small cells, in this paper, we evaluate mobility performance on small cell deployments in LTE-Advanced systems. The simulation results show that the number of HOs occurs at most 3.5 times compared to a macro cell-only deployment even in the case where there are 20 small cells per macro cell and assuming a worst case scenario in which the small cells are located separately and their coverage does not overlap with each other. The results also show that the number of HOFs increases slightly compared to the macro-only case, but these HOFs can be eliminated by applying a handover optimization technique. Contrary to the fact that it is said that we have to deal with frequent HOs and HOFs in small cell deployments, it is concluded that mobility issues have little impact on small cell deployments in HetNet environments.
Bridging Layperson's Queries with Medical Concepts- GRIUM@CLEF2015 eHealth Task 2

Concepts are often used in Medical Information Retrieval. In any conceptbased method one has to extract concepts from texts (query or document). MetaMap is often used for this task. However, if the query is issued by a layperson, the query may not contain the appropriate concept expressions and MetaMap will fail to extract correct concepts. In this situation we need to explore other resources to help extract concepts from such query. In our participation in CLEF2015 eHealth task 2, we investigated the utilization of two resources - UMLS Concept Definition and Wikipedia Articles - to bridge user queries and the intended medical concepts. Our results suggest that such resources could be useful to some extent. In this report, we describe the methods tested as well as their results.
Early Markers of HIV-1 Disease Progression in a Prospective Cohort of Seroconverters in Bangkok, Thailand: Implications for Vaccine Trials

Background: Some candidate HIV-1 vaccines may not prevent HIV-1 infection but may alter the course of disease. Surrogate endpoints based on early laboratory makers in HIV-1–infected persons who are antiretroviral therapy (ART)–naive will be useful for evaluating vaccine efficacy in slowing disease progression (VEp). We examined pretreatment HIV-1 viral loads and CD4 cell counts in recent HIV-1 seroconverters to inform selection of these endpoints. Methods: We studied 130 newly HIV-1–infected injection drug users identified from a prospective cohort of initially uninfected persons in Bangkok during 1995 through 1998. We analyzed trends in HIV-1 viral loads and CD4 cell counts as well as progression to the surrogate endpoint, defined as 2 consecutive CD4 cell counts of fewer than 350 cells/mm3, during 24 months after the first HIV-1 seropositive (FP) visit. Results: Median HIV-1 RNA copies/mL with interquartile ranges were 43,693 (14,320–94,767) at the FP visit, 46,924 (16,273–104,314) at 6 months, 28,446 (11,292–54,325) at 12 months, and 18,080 (8713–54,059) at 18 months. HIV-1 viral loads at the FP visit and at 18 months were positively correlated (r = 0.53, P < 0.0001). Of 130 participants, 12% reached the surrogate endpoint by 6 months, 16% by 12 months, and 27% by 18 months. In Cox regression analyses, HIV-1 viral loads of more than 50,000 copies/mL at the FP visit (hazard ratio [HR] = 2.3, 95% confidence interval [CI]: 1.1–4.8) and first CD4 cell count of 500 or fewer cells/mm3 (HR = 7.6, 95% CI: 3.2–17.6) were independently associated with faster progression to the surrogate endpoint. Conclusions: Participants with high HIV-1 RNA levels and low CD4 cell counts close to the time of seroconversion were more likely to experience early immunologic progression. Approximately one quarter of seroconverters reached the surrogate immunologic endpoint within 18 months of their FP visit and before starting ART, suggesting the utility of this endpoint for analyses of VEp in some ongoing and planned HIV-1 vaccine efficacy trials.
Rates of convergence of nearest neighbor estimation under arbitrary sampling

Rates of convergence for nearest neighbor estimation are established in a general framework in terms of metric covering numbers of the underlying space. The first result is to find explicit finite sample upper bounds for the classical independent and identically distributed (i.i.d.) random sampling problem in a separable metric space setting. The convergence rate is a function of the covering numbers of the support of the distribution. For example, for bounded subsets of R/sup r/, the convergence rate is O(1/n/sup 2/r/). The main result is to extend the problem to allow samples drawn from a completely arbitrary random process in a separable metric space and to examine the performance in terms of the individual sample sequences. The authors show that for every sequence of samples the asymptotic time-average of nearest neighbor risks equals twice the time-average of the conditional Bayes risks of the sequence. Finite sample upper bounds under arbitrary sampling are again obtained in terms of the covering numbers of the underlying space. In particular, for bounded subsets of R/sup r/ the convergence rate of the time-averaged risk is O(1/n/sup 2/r/). The authors then establish a consistency result for k/sub n/-nearest neighbor estimation under arbitrary sampling and prove a convergence rate matching established rates for i.i. d. sampling. Finally, they show how their arbitrary sampling results lead to some classical i.i. d. sampling results and in fact extend them to stationary sampling. The framework and results are quite general while the proof techniques are surprisingly elementary. >
The Experience of Sexual Emotions

Abstract In this article we propose an emotion perspective on the study of sexual experience. First we discuss the contents of experience, which are based on three sources of information: the environment or situation being appraised, autonomic response, and both readiness for and feedback from behavioral response. Then we describe a working memory model to help explain how the experience of sexual emotions is constructed. Finally, we illustrate the application of an emotion perspective through discussion of gender differences in the processing of sexual information and through psychophysiological studies on sexual response.
The sclerostin-neutralizing antibody AbD09097 recognizes an epitope adjacent to sclerostin's binding site for the Wnt co-receptor LRP6

The glycoprotein sclerostin has been identified as a negative regulator of bone growth. It exerts its function by interacting with the Wnt co-receptor LRP5/6, blocks the binding of Wnt factors and thereby inhibits Wnt signalling. Neutralizing anti-sclerostin antibodies are able to restore Wnt activity and enhance bone growth thereby presenting a new osteoanabolic therapy approach for diseases such as osteoporosis. We have generated various Fab antibodies against human and murine sclerostin using a phage display set-up. Biochemical analyses have identified one Fab developed against murine sclerostin, AbD09097 that efficiently neutralizes sclerostin's Wnt inhibitory activity. In vitro interaction analysis using sclerostin variants revealed that this neutralizing Fab binds to sclerostin's flexible second loop, which has been shown to harbour the LRP5/6 binding motif. Affinity maturation was then applied to AbD09097, providing a set of improved neutralizing Fab antibodies which particularly bind human sclerostin with enhanced affinity. Determining the crystal structure of AbD09097 provides first insights into how this antibody might recognize and neutralize sclerostin. Together with the structure–function relationship derived from affinity maturation these new data will foster the rational design of new and highly efficient anti-sclerostin antibodies for the therapy of bone loss diseases such as osteoporosis.
Role of the cerebellar deep nuclei in respiratory modulation

The cerebellum contains three deep nuclei, i.e., the fastigial, interposed and lateral nucleus. Recent studies demonstrate that these nuclei play different roles in respiratory modulation. Activation of fastigial nuclear neurons predominantly increases ventilation via elevation of respiratory frequency and/or tidal volume. Ablation of the fastigial nucleus did not significantly alter eupneic breathing, but did markedly attenuate the respiratory response to medium and severe hypercapnia as well as hypoxia. The fastigial nucleus contains respiratory-modulated neurons and about 25% of these neurons do not show their respiratory-related phasic activity until exposed to hypercapnia. The fastigial nucleus also contains CO2/H+ chemosensitive sites that contributed to the respiratory response to hypercapnia. Therefore, it is concluded that fastigial nuclear facilitatory influence on chemoreflexes emerges during hypercapnia via recruiting intrinsic chemoreception and respiratory-modulated neurons. Full expression of the fastigial nucleus-mediated respiratory responses depends on the integrity of the medullary gigantocellular nucleus at least partially via monosynaptic projections. Additionally, the fastigial nucleus receives inhibitory inputs primarily from Purkinje cells located in the medial vermis and recent observations indicate that simulation of these Purkinje cells inhibits respiration. As compared to chemoreflexes, fastigial nuclear role in the respiratory mechanoreflexes is not significant. The studies related to the role of the interposed and lateral nucleus in eupneic breathing are limited and the results appear controversial. However, there is evidence to show that the interposed nucleus contains respiratory-modulated neurons and is involved in coughing motor control
BCL2-CISD2

CISD2, an ER BCL2-associated autophagy regulator also known as NAF-1, is responsible for the human degenerative disorder Wolfram Syndrome 2. In order to interrogate the physiological role of CISD2 we generated and characterized the Cisd2 gene deletion in mice. Cisd2 null mice manifest significant degeneration in skeletal muscle tissues, which is accompanied with augmented autophagy, dysregulated Ca2+ homeostasis and elongated mitochondria. Our findings describe a novel role for BCL2-CISD2 in the homeostatic maintenance of skeletal muscle. It remains to be elucidated how and if the antagonism of the BECN1 autophagy-initiating complex and modulation of ER Ca2+ homeostasis by BCL2-CISD2 are interconnected.
Multisubject fMRI data analysis via two dimensional multi-set canonical correlation analysis

Multisubject analysis helps to jointly analyze themedical data from multiple subjects, to make insightful inferences. Multi set canonical correlation analysis (MCCA), which extends the application of canonical correlation analysis to more than two datasets, is one such statistical technique to perform multisubject analysis. MCCA aims to compute optimal data transformations such that overall correlation of transformed datasets is maximized. But, the conventional approach is directly applicable to vector data, which requires the image data to be reshaped into vectors. Vectorization of images disturbs their spatial structure and increases computational complexity. We propose a new two dimensional MCCA approach that operates directly on the image data. Experiments are performed against fMRI data sets acquired through block-paradigm right finger tapping task.
Tracing on heterogeneous grids to improve the concavity performance of snake algorithms

Existing contour tracing algorithms operate on binary images at pixel level to traverse the boundary of an object. However, if the original grayscale image has obscure edge transitions, it can be very challenging to extract binary objects properly for pixelwise tracing. A more reliable approach can be to consider a rough approximation of the objects and perform tracing on that, followed by a final adjustment. We can use e.g. the quadtree representation which belongs to the family of heterogeneous grid representations. In this paper, we show how a contour tracing algorithm operating at pixel level can be extended to a heterogeneous grid representation. The robustness of our method is demonstrated in snake algorithms to improve their concavity performance.
CD14 and TLR4 are expressed early in tammar (Macropus eugenii) neonate development

SUMMARY Marsupials are born in a relatively underdeveloped state and develop during a period of intensive maturation in the postnatal period. During this period, the young marsupial lacks a competent immune system, but manages to survive despite the potential of exposure to environmental pathogens. Passive immune transfer via the milk is one well-recognised strategy to compensate the neonate, but there also may be innate immune mechanisms in place. In this study, CD14 and Toll-like receptor 4 (TLR4), integral molecular components of pathogen recognition, were identified and characterised for the first time in a marsupial, the tammar wallaby (Macropus eugenii). Functional motifs of tammar CD14 and the toll/interleukin receptor (TIR) domain of TLR4 were highly conserved. The lipopolysaccharide (LPS) binding residues and the TLR4 interaction site of CD14 were conserved in all marsupials. The TIR signalling domain had 84% identity within marsupials and 77% with eutherians. Stimulation of adult tammar leukocytes resulted in the induction of a biphasic pattern of CD14 and TLR4 expression, and coincided with increased production of the pro-inflammatory cytokine TNF-α. Differential patterns of expression of CD14 and TLR4 were observed in tammar pouch young early in development, suggesting that early maturation of the innate immune system in these animals may have developed as an immune survival strategy to protect the marsupial neonate from exposure to microbial pathogens.
Design of substrate integrated waveguide based power divider for S-band applications

In this paper, a SI W based power divider for S-band applications is proposed. The proposed power divider is designed using Y-junction configuration on Rogers R04360 substrate with dielectric constant of 6.15 and substrate thickness of 1.52 mm. The high dielectric constant substrate is selected for the sake of minimizing the dimension of power divider. The proposed power divider is numerically analyzed in terms of return loss and output power equality. Besides that, various characteristic of power divider is also investigated as an effect of different vias diameter of SIW and different types of transition structure. Based on the numerical analysis, the proposed SIW based power divider demonstrates a good performance over the frequency range of 2-3.6 GHz with return loss less than -15 dB in the 2-2.4 and 2.7-3.6 GHz band. The output power equality achieves 3.4 ± 0.2 dB approximately.
A skill-based system for object perception and manipulation for automating kitting tasks

The automation of kitting tasks-collecting a set of parts for one particular car into a kit-has a huge impact in the automotive industry. It considerably increases the automation levels of tasks typically conducted by human workers. Collecting the parts involves picking up objects from pallets and bins as well as placing them in the respective compartments of the kitting box. In this paper, we present a complete system for automated kitting with a mobile manipulator thereby focusing on depalletizing tasks and placing. In order to allow for low cycle times, we present particularly efficient solutions to object perception as well as motion planning and execution. For easy portability to different platforms, all components are integrated into a skill-based framework that is tightly coupled with a task planning component. We present results of experiments at both a research laboratory environment and at the industrial site of PSA Peugeot Citroën serving as a proof of concept for the overall system design and implementation.