Miracle-dz/UniFAR-FTUs huggingface dataset:
Drosophila melanogaster as a model for lead neurotoxicology and toxicogenomics research

Drosophila melanogaster is an excellent model animal for studying the neurotoxicology of lead. It has been known since ancient Roman times that long-term exposure to low levels of lead results in behavioral abnormalities, such as what is now known as attention deficit hyperactivity disorder (ADHD). Because lead alters mechanisms that underlie developmental neuronal plasticity, chronic exposure of children, even at blood lead levels below the current CDC community action level (10 μg/dl), can result in reduced cognitive ability, increased likelihood of delinquency, behaviors associated with ADHD, changes in activity level, altered sensory function, delayed onset of sexual maturity in girls, and changes in immune function. In order to better understand how lead affects neuronal plasticity, we will describe recent findings from a Drosophila behavioral genetics laboratory, a Drosophila neurophysiology laboratory, and a Drosophila quantitative genetics laboratory who have joined forces to study the effects of lead on the Drosophila nervous system. Studying the effects of lead on Drosophila nervous system development will give us a better understanding of the mechanisms of Pb neurotoxicity in the developing human nervous system.
Emerging clinical applications of selected biomarkers in melanoma

Melanoma is a lethal skin disease with a mostly predictable clinical course according to a known constellation of clinical and pathologic features. The distinction of melanoma from benign melanocytic nevus is typically unequivocol; however, there is a subset of tumors known for its diagnostic challenges, development of late metastases, and difficulties in treatment. Several melanocytic tissue biomarkers are available that can facilitate the histopathologic interpretation of melanoma as well as provide insight into the biologic potential and mutational status of this disease. This review describes the clinical application of some of these established and emerging tissue biomarkers available to assess melanocytic differentiation, vascular invasion, mitotic capacity, and mutation status. The selected tissue biomarkers in this review include MiTF, Sox10, D2-40, PHH3, H3KT (anti-H3K79me3T80ph), anti-BRAFV600E, and anti-BAP-1.
Panic and panic disorder in the United States.

OBJECTIVE The goal of this study was to determine the prevalence of DSM-III-R panic disorder and to describe its correlates. METHOD The study was part of the National Comorbidity Survey, the first psychiatric epidemiologic survey of the entire U.S. population and the first to use DSM-III-R criteria for diagnosis. The 8,098 survey respondents, aged 15-54 years, were given the Composite International Diagnostic Interview. For this report, the data on panic were analyzed, and from them the prevalence of panic disorder and related experiences in the U.S. population was estimated. RESULTS About 15% of the survey respondents reported the occurrence of a panic attack over their lifetimes, and 3% reported a panic attack in the preceding month. About 1% met the DSM-III-R criteria for panic disorder in the month preceding the interview. Panic attacks and panic disorder had a bimodal age distribution and were associated with female sex and lower educational achievement. Fifty percent of the survey respondents with panic disorder reported no symptoms of agoraphobia. The pattern of prevalence of correlated sociodemographic factors was similar for persons with panic attacks, panic disorder, and panic disorder with agoraphobia. CONCLUSIONS There appears to be no obvious threshold for the diagnosis of panic disorder. Panic disorder and agoraphobia, although highly comorbid, also occur separately.
Toward a pluri-component, multimodal, and dynamic organization of the ventral semantic stream in humans: lessons from stimulation mapping in awake patients

For many decades, neural basis underlying cognitive functions was conceived in a localizationist framework. Owing to the development of connectomics, an alternative hodotopical account was proposed, in which brain functions are sub-served by the interactions of large-scale distributed and parallel subnetworks (Catani, 2007; de Benedictis and Duffau, 2011). In this setting, the processing of visual information is divided in a dorsal stream dedicated to the analysis of the spatial position (“where”) and in a ventral stream specialized in object identification (“what”; Underleider and Haxby, 1994). By analogy, a dual-stream model for auditory language processing was suggested, with a dorsal stream involved in mapping sound to articulation and a ventral stream involved in mapping sound to meaning (Hickok and Poeppel, 2004). Nonetheless, the neural structures supporting the ventral route is still controversial. We have recently proposed a new model of language, in which the subcortical anatomical constraints have been incorporated (Duffau et al., 2013): beyond a well-recognized dorsal phonological/articulatory stream underlain by the superior longitudinal fascicle, the neuroanatomy subserving a parallel ventral stream involved in multimodal semantics was described. Here, our purpose is to detail the dynamic functional anatomy of this multi-component ventral route, constituted by direct and indirect pathways (explaining a possible compensation following brain injury) and implied in pluri-modal semantic processes—i.e., in verbal and non-verbal comprehension, control and noetic consciousness.
Micrometastatic Dormancy in Uveal Melanoma: A Comprehensive Review of the Evidence, Mechanisms, and Implications for Future Adjuvant Therapies.

Uveal melanoma is the most common intraocular malignancy in adults, arising from melanocytes within the iris, ciliary body, and choroid. In recent decades, the annual incidence of uveal melanoma has remained stable, estimated at 6 to 7 cases per million. Although major, morbidity-limiting advances have been made in eye-preserving local tumor control, the 5-year survival rate has remained unchanged, hovering between 72% and 84%. Despite effective local tumor control with radioactive plaque brachytherapy, external or charged particle radiation, or enucleation, as many as 50% of patients ultimately develop metastases. Metastatic spread is hematogenous and involves the liver in >90% of patients. Strikingly, the development of overt metastases can occur >15 years following the initial diagnosis of uveal melanoma. In fact, long-term follow-up data revealed that the number one cause of death in these patients remained metastatic uveal melanoma. This was true for >20 years following the initial ocular diagnosis, despite the fact that uveal melanoma predominantly arises in the elderly who often have numerous other comorbidities. Patients with clinically apparent uveal melanoma metastases live on average <6 months following diagnosis. This implies that these patients who died of metastatic uveal melanoma 20 years after initial ocular diagnosis usually did not have overt metastatic disease for the preceding 19 years.
Hematopoietic Stem/Progenitor Cell Proliferation and Differentiation Is Differentially Regulated by High-Density and Low-Density Lipoproteins in Mice

Rationale Hematopoietic stem/progenitor cells (HSPC) are responsible for maintaining the blood system as a result of their self-renewal and multilineage differentiation capacity. Recently, studies have suggested that HDL cholesterol may inhibit and impaired cholesterol efflux may increase HSPC proliferation and differentiation. Objectives We hypothesized that LDL may enhance HSPC proliferation and differentiation while HDL might have the opposing effect which might influence the size of the pool of inflammatory cells. Methods and Results HSPC number and function were studied in hypercholesterolemic LDL receptor knockout (LDLr−/−) mice on high fat diet. Hypercholesterolemia was associated with increased frequency of HSPC, monocytes and granulocytes in the peripheral blood (PB). In addition, an increased proportion of BM HSPC was in G2M of the cell cycle, and the percentage of HSPC and granulocyte-macrophage progenitors (GMP) increased in BM of LDLr−/− mice. When BM Lin-Sca-1+cKit+ (i.e. “LSK”) cells were cultured in the presence of LDL in vitro we also found enhanced differentiation towards monocytes and granulocytes. Furthermore, LDL promoted lineage negative (Lin−) cells motility. The modulation by LDL on HSPC differentiation into granulocytes and motility was inhibited by inhibiting ERK phosphorylation. By contrast, when mice were infused with human apoA-I (the major apolipoprotein of HDL) or reconstituted HDL (rHDL), the frequency and proliferation of HSPC was reduced in BM in vivo. HDL also reversed the LDL-induced monocyte and granulocyte differentiation in vitro. Conclusion Our data suggest that LDL and HDL have opposing effects on HSPC proliferation and differentiation. It will be of interest to determine if breakdown of HSPC homeostasis by hypercholesterolemia contributes to inflammation and atherosclerosis progression.
Linear Output-Feedback Control of Stochastic Linear Systems with State- and Control-dependent Disturbances

The stochastic regulation problem for linear systems with state- and control-dependent noise and a noisy linear output equation is considered. The optimal, quadratic cost, output-feedback control law in a class of linear controllers is found. The result represent an extension to the incomplete information case of the class of optimal control problems just considered in the 70's by McLane. As a result, the optimal control law result to be similar to the Linear-Quadratic- Gaussian (LQG) regulator, but a new non-negative matrix (associated to the quadratic-variation of the control-dependent noise) must to be added to the output noise covariance.
Pattern Recognition using Chaotic Transients

This paper proposes a novel nonlinear transient computation device described as the LTCM that uses the chaotic attractor provided by the Lorenz system of equations to perform pattern recognition. Previous work on nonlinear transient computation has demonstrated that such de- vices can process time varying input signals. This paper investigates the ability of the LTCM to correctly classify static, linearly inseperable data sets commonly used as benchmarks in the pattern recognition research community. The results from the LTCM are compared with those from support vector machines and multi-layer perceptrons on the same data sets.
Nitrogen deposition and lake nitrogen concentrations: a regional analysis of terrestrial controls and aquatic linkages

Loading of nutrients from terrestrial ecosystems strongly influences the productivity and biogeochemistry of aquatic ecosystems. Human activities can supplement and even dominate nutrient loading to many lakes, particularly in agricultural and urbanized settings. For lakes in more remote regions such as the Adirondack Mountains of New York, N deposition represents the primary potential anthropogenic nutrient source. We combined a spatial model of N deposition with data on lake-N concentrations and spatial data on watershed configuration to identify the sources of watershed N loading for over 250 lakes in the Adirondacks. The analysis indicates that while wetlands are stronger sources of N loading per unit area than forests in the absence of inorganic N deposition, wetlands retain essentially all N deposition, while forests retained ∼87% of N deposition. Since forests cover close to 90% of the watersheds, upland forests are, on average, the single largest source of N loading to Adirondack lakes. Direct dep.
Topic-based sentiment analysis for the social web: The role of mood and issue-related words

General sentiment analysis for the social web has become increasingly useful for shedding light on the role of emotion in online communication and offline events in both academic research and data journalism. Nevertheless, existing general‐purpose social web sentiment analysis algorithms may not be optimal for texts focussed around specific topics. This article introduces 2 new methods, mood setting and lexicon extension, to improve the accuracy of topic‐specific lexical sentiment strength detection for the social web. Mood setting allows the topic mood to determine the default polarity for ostensibly neutral expressive text. Topic‐specific lexicon extension involves adding topic‐specific words to the default general sentiment lexicon. Experiments with 8 data sets show that both methods can improve sentiment analysis performance in corpora and are recommended when the topic focus is tightest.
Anomalous splenic notches: a cadaveric study with clinical importance.

OBJECTIVE To study the anomalous splenic notches and discuss their clinical importance. BACKGROUND The lobulated form of the spleen in early developmental phase is represented by notches at a later period which occur at the superior border. The superior border which separates the gastric impression from the diaphragmatic surface has notches near its lateral end. METHODS Considering the fact that there is paucity of literature on the presence of splenic notches, we performed the study on 100 formalin fixed cadaveric spleens to observe the presence of notches. RESULTS The notches were observed on the superior and inferior border in ninety eight and two cases, respectively. The anomalous presence of fissures on the diaphragmatic surface was observed in two cases. DISCUSSION In view of the observations, we as anatomists feel that standard anatomy textbooks should incorporate the fact that presence of notches is confined not only to superior border but they can also be found in the inferior border. Presence of notches in the inferior border may be important for surgeons attempting splenic surgeries and radiologists interpreting CT scans. In the present study, we discuss the morphological and clinical aspect of anomalous notches and fissures in the spleen (Tab. 1, Fig. 5, Ref. 10).
Randomized, Placebo-Controlled Trial of Titrated Intravenous Lamifiban for Acute Coronary Syndromes

Background—Platelet glycoprotein IIb/IIIa inhibitors reduce the rate of death or myocardial infarction among patients with acute coronary syndromes without persistent ST-segment elevation, but their effects may depend on plasma concentrations. We tested whether the addition of lamifiban, titrated to achieve target plasma concentrations, to standard care would improve clinical outcomes. Methods and Results—We randomized 5225 patients at 389 centers in 29 countries to receive a bolus and ≤72-hour infusion of lamifiban or placebo, adjusted for renal function, with aspirin and heparin. The primary end point was the composite of death, myocardial infarction, or severe, recurrent ischemia at 30 days. Baseline characteristics did not differ significantly by treatment. The primary end point occurred in 11.8% of lamifiban-treated patients and in 12.8% of placebo-treated patients (OR, 0.914; 95% CI, 0.769 to 1.087;P =0.329). Bleeding was more common in lamifiban-treated patients, but intracranial hemorrhage was not increased. Among the subgroup who had plasma lamifiban concentrations measured, 91% had a concentration >18 ng/mL at steady state, but their outcomes did not differ from those with lower concentrations. Conclusions—Lamifiban showed no significant effects on clinical outcomes in patients with non–ST-elevation acute coronary syndromes, despite achievement of adequate plasma concentrations.
The influence of Aegopodium podagraria L. extract and tincture on behavioural reactions of random-bred mice

Aegopodium podagraria is used as a sedative in trad itional medicine. The effect of its aerial part ext ract and tincture on levels of depression and anxiety, as we ll as on locomotor activity, exploratory behaviour and memory of male and female mice was investigated. The extract showed dose-dependent and sex specific antidepressi ve effect (at a dose of 100 mg/kg but not at a dose of 1 g/kg in female mice) with the worsening of the results of the passive avoidance test. The extract at a dose of 100 mg/kg tended to reduce anxiety signs in the animals of b oth sexes , in male mice such reduction was also seen under the in fluence of the extract at a dose of 1 g/kg and the tincture at doses of 1 and 5 ml/kg (the latter did not consider ably changed the other parameters measured). The re sults indicate favourable central activity of A. podagraria extrac t in mice.
The Mode of Action of the Bacillus thuringiensis Vegetative Insecticidal Protein Vip3A Differs from That of Cry1Ab δ-Endotoxin

ABSTRACT The Vip3A protein, secreted by Bacillus spp. during the vegetative stage of growth, represents a new family of insecticidal proteins. In our investigation of the mode of action of Vip3A, the 88-kDa Vip3A full-length toxin (Vip3A-F) was proteolytically activated to an approximately 62-kDa core toxin either by trypsin (Vip3A-T) or lepidopteran gut juice extracts (Vip3A-G). Biotinylated Vip3A-G demonstrated competitive binding to lepidopteran midgut brush border membrane vesicles (BBMV). Furthermore, in ligand blotting experiments with BBMV from the tobacco hornworm, Manduca sexta (Linnaeus), activated Cry1Ab bound to 120-kDa aminopeptidase N (APN)-like and 250-kDa cadherin-like molecules, whereas Vip3A-G bound to 80-kDa and 100-kDa molecules which are distinct from the known Cry1Ab receptors. In addition, separate blotting experiments with Vip3A-G did not show binding to isolated Cry1A receptors, such as M. sexta APN protein, or a cadherin Cry1Ab ecto-binding domain. In voltage clamping assays with dissected midgut from the susceptible insect, M. sexta, Vip3A-G clearly formed pores, whereas Vip3A-F was incapable of pore formation. In the same assay, Vip3A-G was incapable of forming pores with larvae of the nonsusceptible insect, monarch butterfly, Danaus plexippus (Linnaeus). In planar lipid bilayers, both Vip3A-G and Vip3A-T formed stable ion channels in the absence of any receptors, supporting pore formation as an inherent property of Vip3A. Both Cry1Ab and Vip3A channels were voltage independent and highly cation selective; however, they differed considerably in their principal conductance state and cation specificity. The mode of action of Vip3A supports its use as a novel insecticidal agent.
Functional disconnection between the prefrontal and parietal cortices during working memory processing in schizophrenia: a[15(O)]H2O PET study.

OBJECTIVE The prefrontal-parietal circuits have been reported to play an important role in working memory. The purpose of this study was to use direct neuroimaging to address whether interregional correlation in the prefrontal-parietal circuits is impaired in schizophrenia. METHOD [(15)O]H(2)O positron emission tomography was used to compare regional blood flow changes in 12 schizophrenic and 12 healthy comparison subjects during the n-back sequential-picture working memory task. Interregional correlation was assessed by correlating the regional activation of the lateral prefrontal area with that of other activated areas in each subject group. RESULTS Dorsolateral prefrontal activation was observed around the right superior frontal sulcus in the healthy subjects, and ventrolateral prefrontal activation below the right inferior frontal sulcus was observed in the schizophrenic patients. Activation in the right lateral prefrontal cortex was significantly correlated with activation in the bilateral inferior parietal region in the healthy subjects but was not correlated with any regional activation in the patients. CONCLUSIONS The findings suggest prefrontal-parietal functional disconnection, particularly prefrontal dissociation and abnormal prefrontal-parietal interaction, during working memory processing in schizophrenia.
Oxytocin enhances attention to the eye region in rhesus monkeys

Human and non-human primates rely on the ability to perceive and interpret facial expressions to guide effective social interactions. The neuropeptide oxytocin (OT) has been shown to have a critical role in the perception of social cues, and in humans to increase the number of saccades to the eye region. To develop a useful primate model for the effects of OT on information processing, we investigated the influence of OT on gaze behavior during face processing in rhesus macaques. Forty-five minutes after a single intranasal dose of either 24IU OT or saline, monkeys completed a free-viewing task during which they viewed pictures of conspecifics displaying one of three facial expressions (neutral, open-mouth threat or bared-teeth) for 5 s. The monkey was free to explore the face on the screen while the pattern of eye movements was recorded. OT did not increase overall fixations to the face compared to saline. Rather, when monkeys freely viewed conspecific faces, OT increased fixations to the eye region relative to the mouth region. This effect of OT was particularly pronounced when face position on the screen was manipulated so that the eye region was not the first facial feature seen by the monkeys. Together these findings are consistent with prior evidence in humans that intranasal administration of OT specifically enhances visual attention to the eye region compared to other informative facial features, thus validating the use of non-human primates to mechanistically explore how OT modulates social information processing and behavior.
A Novel Intron Element Operates Posttranscriptionally To Regulate Human N-mycExpression

ABSTRACT Precisely regulated expression of oncogenes and tumor suppressor genes is essential for normal development, and deregulated expression can lead to cancer. The human N-myc gene normally is expressed in only a subset of fetal epithelial tissues, and its expression is extinguished in all adult tissues except transiently in pre-B lymphocytes. The N-myc gene is overexpressed due to genomic amplification in the childhood tumor neuroblastoma. In previous work to investigate mechanisms of regulation of human N-mycgene expression, we observed that N-mycpromoter–chloramphemicol acelyltransferase reporter constructs containing sequences 5′ to exon 1 were active in all cell types examined, regardless of whether endogenous N-myc RNA was detected. In contrast, inclusion of the first exon and a portion of the first intron allowed expression only in those cell types with detectable endogenous N-myc transcripts. We investigated further the mechanisms by which this tissue-specific control of N-myc expression is achieved. Using nuclear run-on analyses, we determined that the N-myc gene is actively transcribed in all cell types examined, indicating a posttranscriptional mode of regulation. Using a series of N-myc intron 1 deletion constructs, we localized a 116-bp element (tissue-specific element [TSE]) within the first intron that directs tissue-specific N-myc expression. The TSE can function independently to regulate expression of a heterologous promoter-reporter minigene in a cell-specific pattern that mirrors the expression pattern of the endogenous N-myc gene. Surprisingly, the TSE can function in both sense and antisense orientations to regulate gene expression. Our data indicate that the human N-myc TSE functions through a posttranscriptional mechanism to regulate N-myc expression.
Collision and packet loss analysis in a LoRaWAN network

Internet of things (IoT) is considered as the next technological revolution. Therefore, many solutions are developed either in free, i.e. ISM bands or in non free bands with the ultimate aim of affording connectivity over several kilometers. Based on this feature, in urban environment the density of IoT devices will be extremely high. In this paper we propose to analyze the collision and packet loss when LoRaWAN is considered. Based on the LoRaWAN features, we develop closed-form expressions of collision and packet loss probabilities. Simulation results confirm our theoretical developments. We also show that our theoretical expressions are more accurate than the Poisson distributed process to describe the collisions.