Miracle-dz/UniFAR-FTUs huggingface dataset:
Increased amphetamine-induced hyperactivity and reward in mice overexpressing the dopamine transporter

The dopamine transporter (DAT) plays a key role in the regulation of dopaminergic signaling wherein it controls both the spatial and temporal actions of dopamine. Here we evaluated the behavioral and neurochemical consequences of increased DAT function by generating DAT transgenic mice (DAT-tg) that overexpress the transporter. These mice were generated by pronuclear injection of a bacterial artificial chromosome containing the mouse DAT locus, yielding an anatomical expression pattern of DAT-tg identical to WT. In DAT-tg mice there is a 3-fold increase in the levels of total and membrane-expressed DAT, but synaptic plasma membrane fractions of DAT-tg mice show only a 30% increase in transporter levels. Functional studies reveal that in the DAT-tg animals there is a 50% increase in the rate of dopamine (DA) uptake resulting in extracellular levels of DA that are decreased by ≈40%. Behaviorally, DAT-tg animals display similar locomotor stimulation when treated with DAT blockers such as GBR12909, methylphenidate, and cocaine. However, these mice demonstrate markedly increased locomotor responses to amphetamine compared with WT animals. Furthermore, compared with controls, there is a 3-fold greater increase in the amount of DA released by amphetamine in DAT-tg mice that correlates with the 3-fold increase in protein expression. Finally, DAT-tg animals show reduced operant responding for natural reward while displaying preference for amphetamine at much lower doses (0.2 and 0.5 mg/kg) than WT mice (2 mg/kg). These results suggest that overexpression of DAT leads to a marked increase in sensitivity to psychomotor and rewarding properties of amphetamine.
Deep Crisp Boundaries: From Boundaries to Higher-Level Tasks

Edge detection has made significant progress with the help of deep convolutional networks (ConvNet). These ConvNet-based edge detectors have approached human level performance on standard benchmarks. We provide a systematical study of these detectors’ outputs. We show that the detection results did not accurately localize edge pixels, which can be adversarial for tasks that require crisp edge inputs. As a remedy, we propose a novel refinement architecture to address the challenging problem of learning a crisp edge detector using ConvNet. Our method leverages a top-down backward refinement pathway, and progressively increases the resolution of feature maps to generate crisp edges. Our results achieve superior performance, surpassing human accuracy when using standard criteria on BSDS500, and largely outperforming the state-of-the-art methods when using more strict criteria. More importantly, we demonstrate the benefit of crisp edge maps for several important applications in computer vision, including optical flow estimation, object proposal generation, and semantic segmentation.
Thalidomide alone or with dexamethasone for previously untreated multiple myeloma.

PURPOSE To evaluate the activity of thalidomide in patients with asymptomatic multiple myeloma and of thalidomide-dexamethasone in patients with previously untreated symptomatic myeloma. PATIENTS AND METHODS Twenty-eight patients with previously untreated asymptomatic myeloma were treated with thalidomide 100 to 200 mg orally (PO) at bedtime (qhs) with serial increments of 50 to 100 mg at weekly intervals, as tolerated to a maximum of 600 mg PO qhs. Forty consecutive previously untreated patients with symptomatic myeloma were also treated as above (maximum dose 400 mg) and received dexamethasone 20 mg/m(2) for 4 days beginning on days 1, 9, and 17; the second and third cycles of repeated dexamethasone were begun on day 30. Both groups of patients were treated for at least 3 months. RESULTS The response rate was 36% for patients treated with thalidomide alone and 72% for patients treated with thalidomide-dexamethasone, the latter including complete remission in 16% of patients. The median time to remission was 4.2 months with thalidomide alone and 0.7 months with thalidomide-dexamethasone. Grade 3 toxicity included infections (nine patients) and thrombotic/embolic events (seven patients). Five deaths have occurred as a result of multiple myeloma (two patients), infection (one patient), unknown cause (one patient), and a possible thromboembolic event (one patient). CONCLUSION Thalidomide alone was effective in patients with newly diagnosed myeloma. The combination with dexamethasone induced a high frequency of response, rapid onset of remission, and low incidence of serious irreversible toxicity. These observations support further studies of this promising combination for patients with newly diagnosed multiple myeloma.
Mechanisms of hopperburn: an overview of insect taxonomy, behavior, and physiology.

Hopperburn is a non-contagious disease of plants caused by the direct feeding damage of certain leafhoppers and planthoppers. Although long studied, especially with Empoasca spp. leafhoppers (Cicadellidae: Typhlocybinae), the mechanisms underlying hopperburn have only recently been elucidated. Hopperburn is caused by a dynamic interaction between complex insect feeding stimuli (termed hopperburn initiation) and complex plant responses (termed the hopperburn cascade). Herein we review the nature of the feeding stimuli in hopperburn initiation, especially for Empoasca spp. , which we also compare with the planthopper Nilaparvata lugens. Contrary to previous reports, Empoasca hopperburn is not caused solely by toxic saliva. Instead, it is caused by a plant wound response triggered by a unique type of stylet movement, which is then exacerbated by saliva. Electrical penetration graph monitoring has revealed that all Empoasca spp. are cell rupture feeders, not sheath feeders, and that certain tactics of that feeding strategy are more damaging than others. Measuring the proportions of the most damaging feeding led to development of a resistance index, the Stylet Penetration Index, which can predict hopperburn severity in different plants or under different environmental conditions and can supplement or replace traditional, field-based resistance indices.
Heuristic Based Task Scheduling In Grid

Grid computing is concerned with coordinated resource sharing and problem solving in dynamic, multi-institutional virtual organizations. Efficient scheduling of complex applications in a grid environment reveals several challenges due to its high heterogeneity, dynamic behavior and space shared utilization. Objectives of scheduling algorithms are increase in system throughput, efficiency and reduction in task completion time. The main focus of this paper is to highlight the merits of resource and task selection technique based on certain heuristics. Keyword- Grid Computing, Task Scheduling, Min-Min, Max-Min, Suffrage, Makespan.
Phosphorylation-mediated PTEN conformational closure and deactivation revealed with protein semisynthesis

The tumor suppressor PIP3 phosphatase PTEN is phosphorylated on four clustered Ser/Thr on its C-terminal tail (aa 380–385) and these phosphorylations are proposed to induce a reduction in PTEN’s plasma membrane recruitment. How these phosphorylations affect the structure and enzymatic function of PTEN is poorly understood. To gain insight into the mechanistic basis of PTEN regulation by phosphorylation, we generated semisynthetic site-specifically tetra-phosphorylated PTEN using expressed protein ligation. By employing a combination of biophysical and enzymatic approaches, we have found that purified tail-phosphorylated PTEN relative to its unphosphorylated counterpart shows reduced catalytic activity and membrane affinity and undergoes conformational compaction likely involving an intramolecular interaction between its C-tail and the C2 domain. Our results suggest that there is a competition between membrane phospholipids and PTEN phospho-tail for binding to the C2 domain. These findings reveal a key aspect of PTEN’s regulation and suggest pharmacologic approaches for direct PTEN activation. DOI: http://dx.doi. org/10.7554/eLife.00691. 001
Physiological Correlates of Multiple-Sprint Ability and Performance in International-Standard Squash Players

Wilkinson, M, Cooke, M, Murray, S, Thompson, KG, St. Clair Gibson, A, and Winter, EM. Physiological correlates of multiple-sprint ability and performance in international-standard squash players. J Strength Cond Res 26(2): 540–547, 2012—From measures on a battery of fitness tests in elite-standard squash players on different tiers of a national performance program, we examined the relationships among test scores and player rank, and fitness factors important for squash-specific multiple-sprint ability. Thirty-one (20 men, 11 women) squash players from the England Squash performance program participated: n = 12 senior; n = 7 transition; n = 12 talented athlete scholarship scheme (TASS) players. In 1 test session and in a fixed order, the players completed a battery of tests to assess countermovement jump height, reactive strength, change-of-direction speed, and multiple-sprint ability on squash-specific tests and endurance fitness. Two-way analysis of variance compared senior, transition, and TASS players by sex on all measures except jump height where only senior and transition players were compared. Effect size (ES) was calculated for all comparisons. Pearson's correlation examined relationships among test scores and multiple-sprint ability. Spearman's ρ investigated relationships among test scores and players' rank in men and women separately. Regardless of sex, seniors outperformed TASS players on all except the endurance test (p < 0.05, ES at least 1.1). Seniors had better multiple-sprint ability than did transition players (p < 0.01, ES = 1.2). Transition outperformed TASS players on the reactive-strength test (p < 0.05, ES = 1.0). Men outperformed women in all tests at all performance program tiers (p < 0.05, ES at least 0.5). In men, rank was related to multiple-sprint ability, fastest-multiple-sprint-test repetition, and change-of-direction speed (ρ = 0.78, 0.86, 0.59, respectively). In women, rank was related to fastest multiple-sprint-test repetition (ρ = 0.65). In men and women, multiple-sprint ability was related to change-of-direction speed (r = 0.9 and 0.84) and fastest-multiple-sprint-test repetition (r = 0.96 for both) and to reactive strength in men (r = −0.71). The results confirm that high-intensity variable-direction exercise capabilities are important for success in elite squash.
Histopathologic, immunohistochemical and ultrastructural features of a granular cell tumour in an Australian parakeet (Melopsittacus undulatus)

An adult male Australian parakeet (Melopsittacus undulatus) presented a firm nodular lesion in the lateral metacarpal region of the right wing. Microscopically, there were neoplastic cells, round and polyhedral in shape, with abundant, slightly eosinophilic granular cytoplasm; they were strongly periodic-acid Schiff-positive and resistant to diastase digestion. Some groups of neoplastic cells were immunopositive for smooth muscle actin and desmin. There was no immunopositivity for S-100 protein, CD68 and cytokeratin. Ultrastructurally, the neoplastic cells were round and polygonal in shape, and they were characterized by abundant cytoplasm with numerous homogeneous osmophilic bodies covered by an electron-dense membrane (lysosomes). The histopathologic, immunohistochemical and ultrastructural features of the neoplastic tissue are consistent with a granular cell tumour, which has been described in different animal species and anatomic locations; however, this seems to be an infrequent neoplasm in Australian parakeets. The immunopositivity of the neoplastic cells for smooth muscle actin and desmin, as well as slight positivity for muscle with Masson's trichrome, suggest that this is a tumour of myogenic origin.
Robust cooperative sensing via state estimation in cognitive radio networks

Cooperative sensing, a key enabling technology for dynamic spectrum access, is vulnerable to various sensing-targeted attacks, such as the primary user emulation or spectrum sensing data falsification. These attacks can easily disrupt the primary signal detection process, thus crippling the operation of dynamic spectrum access. While such sensing-targeted attacks can be easily launched by an attacker, it is very challenging to design a robust cooperative spectrum sensing scheme due mainly to the practical constraints inherent in spectrum sensing, particularly the shared/open nature of the wireless medium and the unpredictability of signal propagation. In this paper, we develop an efficient, yet simple attack detection framework, called IRIS (robust cooperatIve sensing via iteRatIve State estimation), that safeguards the incumbent detection process by checking the consistency among sensing reports via the estimation of system states, namely, the primary user's transmit-power and path-loss exponent. The key insight behind the design of IRIS is that the sensing results are governed by the network topology and the law of signal propagation, which cannot be easily compromised by an attacker. Consequently, the sensing reports must demonstrate consistency among themselves in estimating system states. Our analytical and simulation results show that, by performing consistency-checks, IRIS provides high attack-detection capability, and preserves satisfactory performance in estimating the system states even under very challenging attack scenarios. Based on these observations, we propose a new incumbent detection rule that can further improve the spectrum efficiency. IRIS can be readily deployed in infrastructure-based cognitive radio networks, such as IEEE 802.22 WRANs, with manageable processing and communication overheads.
Mortality following a brain tumour diagnosis in patients with multiple sclerosis

Objectives As brain tumours and their treatment may theoretically have a poorer prognosis in inflammatory central nervous system diseases such as multiple sclerosis (MS), all-cause mortality following a brain tumour diagnosis was compared between patients with and without MS. The potential role of age at tumour diagnosis was also examined. Setting Hospital inpatients in Sweden with assessment of mortality in hospital or following discharge. Participants Swedish national registers identified 20 543 patients with an MS diagnosis (1969–2005) and they were matched individually to produce a comparison cohort of 204 163 members of the general population without MS. Everyone with a primary brain tumour diagnosis was selected for this study: 111 with MS and 907 without MS. Primary and secondary outcome measures 5-year mortality risk following brain tumour diagnosis and age at brain tumour diagnosis. Results A non-statistically significant lower mortality risk among patients with MS (lower for those with tumours of high-grade and uncertain-grade malignancy and no notable difference for low-grade tumours) produced an unadjusted HR (and 95% CI) of 0.75 (0.56 to 1.02). After adjustment for age at diagnosis, grade of malignancy, sex, region of residence and socioeconomic index, the HR is 0.91 (0.67–1.24). The change in estimate was largely due to adjustment for age at brain tumour diagnosis, as patients with MS were on average 4.7 years younger at brain tumour diagnosis than those in the comparison cohort (p<0.001). Conclusions Younger age at tumour diagnosis may contribute to mortality reduction in those with high-grade and uncertain-grade brain tumours. Survival following a brain tumour is not worse in patients with MS; even after age at brain tumour diagnosis and grade of malignancy are taken into account.
The ECP/Eo Count Ratio in Children with Asthma

We hypothesized that the serum eosinophil eationic protein (ECP) concentration to peripheral blood eosinophil count ratio (ECP/Eo ratio), reflecting active eosinophils, could better correlate with asthma severity in asthmatic patients, than each of these parameters alone. One hundred twenty children with mild to moderate persistent stable asthma were included into the study. At the first visit, previous asthma medications were withheld and patients were administered β‐2 agonists “as needed. ” At the second visit peripheral blood eosinophil count, serum ECP, sIL‐2R, and sICAM‐1 were measured, and spirometry and histamine challenge tests were performed. During the study, patients filled daily diary cards to assess symptoms score. One hundred seventeen patients completed the study. The univariate logistic regression analysis showed that asthma severity is related to PC20H, ECP, ECP/Eo ratio, sIL‐2R, and sICAM‐1. In general, patients with higher level of ECP, ECP/Eo ratio, sIL‐2R, sICAM‐1 and with lower PC20H exhibited the higher risk of moderate asthma. Multivariate regression analysis showed that only PC20H and ECP/Eo ratio were the best predictors of asthma severity; higher PC20H (1 mg/mL change) slightly decrease (OR = 0.656; 95% CI: 0.44–0.99) and higher ECP/Eo ratio (0.1 pg/cell change) increase (OR = 1.84; 95% CI: 1.02–3.34) a risk of moderate asthma. These data show that the ECP/Eo ratio is a better and more useful marker than ECP or peripheral blood eosinophil count separately in assessing asthma in children.
A Functional Role for 4qA/B in the Structural Rearrangement of the 4q35 Region and in the Regulation of FRG1 and ANT1 in Facioscapulohumeral Dystrophy

The number of D4Z4 repeats in the subtelomeric region of chromosome 4q is strongly reduced in patients with Facio-Scapulo-Humeral Dystrophy (FSHD). We performed chromosome conformation capture (3C) analysis to document the interactions taking place among different 4q35 markers. We found that the reduced number of D4Z4 repeats in FSHD myoblasts was associated with a global alteration of the three-dimensional structure of the 4q35 region. Indeed, differently from normal myoblasts, the 4qA/B marker interacted directly with the promoters of the FRG1 and ANT1 genes in FSHD cells. Along with the presence of a newly identified transcriptional enhancer within the 4qA allele, our demonstration of an interaction occurring between chromosomal segments located megabases away on the same chromosome 4q allows to revisit the possible mechanisms leading to FSHD.
Aberrant Cytoplasm Localization and Protein Stability of SIRT1 is Regulated by PI3K/IGF-1R Signaling in Human Cancer Cells

SIRT1, an NAD-dependent histone/protein deacetylase, has classically been thought of as a nuclear protein. In this study, we demonstrate that SIRT1 is mainly localized in the nucleus of normal cells, but is predominantly localized in the cytoplasm of the cancer / transformed cells we tested. We found this predominant cytoplasmic localization of SIRT1 is regulated by elevated mitotic activity and PI3K/IGF-1R signaling in cancer cells. We show that aberrant cytoplasmic localization of SIRT1 is due to increased protein stability and is regulated by PI3K/IGF-1R signaling. In addition, we determined that SIRT1 is required for PI3K-mediated cancer cell growth. Our study represents the first identification that aberrant cytoplasm localization is one of the specific alternations to SIRT1 that occur in cancer cells, and PI3K/IGF-1R signaling plays an important role in the regulation of cytoplasmic SIRT1 stability. Our findings suggest that the over-expressed cytoplasmic SIRT1 in cancer cells may greatly contribute to its cancer-specific function by working downstream of the PI3K/IGF-1R signaling pathway.
Interleukin-32 Promotes Osteoclast Differentiation but Not Osteoclast Activation

Background Interleukin-32 (IL-32) is a newly described cytokine produced after stimulation by IL-2 or IL-18 and IFN-γ. IL-32 has the typical properties of a pro-inflammatory mediator and although its role in rheumatoid arthritis has been recently reported its effect on the osteoclastogenesis process remains unclear. Methodology/Principal Findings In the present study, we have shown that IL-32 was a potent modulator of osteoclastogenesis in vitro, whereby it promoted the differentiation of osteoclast precursors into TRAcP+ VNR+ multinucleated cells expressing specific osteoclast markers (up-regulation of NFATc1, OSCAR, Cathepsin K), but it was incapable of inducing the maturation of these multinucleated cells into bone-resorbing cells. The lack of bone resorption in IL-32-treated cultures could in part be explain by the lack of F-actin ring formation by the multinucleated cells generated. Moreover, when IL-32 was added to PBMC cultures maintained with soluble RANKL, although the number of newly generated osteoclast was increased, a significant decrease of the percentage of lacunar resorption was evident suggesting a possible inhibitory effect of this cytokine on osteoclast activation. To determine the mechanism by which IL-32 induces such response, we sought to determine the intracellular pathways activated and the release of soluble mediators in response to IL-32. Our results indicated that compared to RANKL, IL-32 induced a massive activation of ERK1/2 and Akt. Moreover, IL-32 was also capable of stimulating the release of IL-4 and IFN-γ, two known inhibitors of osteoclast formation and activation. Conclusions/Significance This is the first in vitro report on the complex role of IL-32 on osteoclast precursors. Further clarification on the exact role of IL-32 in vivo is required prior to the development of any potential therapeutic approach.
PtdIns(3,4,5)P3 is a regulator of myosin-X localization and filopodia formation

Phosphatidylinositol (3,4,5)-trisphosphate [PtdIns(3,4,5)P3] is a key regulator of cell signaling that acts by recruiting proteins to the cell membrane, such as at the leading edge during cell migration. Here, we show that PtdIns (3,4,5)P3 plays a central role in filopodia formation via the binding of myosin-X (Myo10), a potent promoter of filopodia. We found that the second pleckstrin homology domain (Myo10-PH2) of Myo10 specifically binds to PtdIns(3,4,5)P3, and that disruption of this binding led to impairment of filopodia and partial re-localization of Myo10 to microtubule-associated Rab7-positive endosomal vesicles. Given that the localization of Myo10 was dynamically restored to filopodia upon reinstatement of PtdIns(3,4,5)P3-binding, our results indicate that PtdIns(3,4,5)P3 binding to the Myo10-PH2 domain is involved in Myo10 trafficking and regulation of filopodia dynamics.
Inhibition of Quorum Sensing-Controlled Virulence Factor Production in Pseudomonas aeruginosa PAO1 by Ayurveda Spice Clove (Syzygium Aromaticum) Bud Extract

Quorum sensing controls the virulence determinants in most proteobacteria. In this work, the hexane, chloroform and methanol extracts of an Ayurveda spice, namely clove (Syzygium aromaticum), shown anti-quorum sensing activity. Hexane and methanol extracts of clove inhibited the response of C. violaceum CV026 to exogenously supplied N‐hexanoylhomoserine lactone, in turn preventing violacein production. Chloroform and methanol extracts of clove significantly reduced bioluminescence production by E. coli [pSB1075] grown in the presence of N-(3-oxododecanoyl)-l-homoserine lactone. We demonstrated that clove extract inhibited quorum sensing-regulated phenotypes in Pseudomonas aeruginosa PA01, including expression of lecA::lux (by hexane extract), swarming (maximum inhibition by methanol extract), pyocyanin (maximum inhibition by hexane extract). This study shows that the presence of natural compounds that exhibit anti-quorum sensing activity in the clove extracts may be useful as the lead of anti-infective drugs.