Miracle-dz/UniFAR-FTUs huggingface dataset:
Elevated Levels of the Vesicular Monoamine Transporter and a Novel Repetitive Behavior in the Drosophila Model of Fragile X Syndrome

Fragile X Syndrome (FXS) is characterized by mental impairment and autism in humans, and it often features hyperactivity and repetitive behaviors. The mechanisms for the disease, however, remain poorly understood. Here we report that the dfmr1 mutant in the Drosophila model of FXS grooms excessively, which may be regulated differentially by two signaling pathways. Blocking metabotropic glutamate receptor signaling enhances grooming in dfmr1 mutant flies, whereas blocking the vesicular monoamine transporter (VMAT) suppresses excessive grooming. dfmr1 mutant flies also exhibit elevated levels of VMAT mRNA and protein. These results suggest that enhanced monoamine signaling correlates with repetitive behaviors and hyperactivity associated with FXS.
Pathological Choice: The Neuroscience of Gambling and Gambling Addiction

Gambling is pertinent to neuroscience research for at least two reasons. First, gambling is a naturalistic and pervasive example of risky decision making, and thus gambling games can provide a paradigm for the investigation of human choice behavior and “irrationality. ” Second, excessive gambling involvement (i.e., pathological gambling) is currently conceptualized as a behavioral addiction, and research on this condition may provide insights into addictive mechanisms in the absence of exogenous drug effects. This article is a summary of topics covered in a Society for Neuroscience minisymposium, focusing on recent advances in understanding the neural basis of gambling behavior, including translational findings in rodents and nonhuman primates, which have begun to delineate neural circuitry and neurochemistry involved.
Birth to three matters: a review of the literature

The views expressed in this report are the authors' and do not necessarily reflect those of the Department for Education and Skills. Introduction: Birth to Three Matters 10 Why Birth to Three? 1 0 About the Birth to Three Matters pack 1 1 The relationship between the cards and the literature review 1 3 Chapter 1: The complex nature of the growth, development and learning of babies and young children 14 Principles Which Underpin the Framework 1 4 Research, disciplines, assumptions and values 16 Is children's development and learning compartmentalised or holistic? 1 7 Continuity and discontinuity in children's lives, development and learning 1 9 Risk and resilience 2 0 Can theories provide universal explanations for children's development and learning? 2 3 Defining children's needs 2 5 What this review does and does not cover 2 6 Summary of key 'messages' 2 9 Chapter 2: Influential research and theories concerned with early childhood 3 1 How theories of child development can help us 3 1 The issue of theories as cultural constructions 3 2 3 Biology and maturation 3 3 Biological explanations of childhood 34 Freud and the Psychoanalytic tradition 3 4 Learning theories 3 6 Conditioning and Behaviourist theory 36 Social learning theory 36 Cognitive developmental theories 3 7 Jean Piaget's Cognitive Development Theory 37 Vygotsky's theory of child development 4 0 Ecological systems theory 4 0 Information Processing Theories 4 1 Perception and understanding – the role of the senses 41 Theories about Language Development 4 2 Theories about Early Childhood Education and Care 4 3 Recognising and reflecting on our own theories 4 4 Summary of key 'messages' 4 4 Chapter 3: A Strong Child 45 Me, Myself and I: a growing awareness of self and the role of Attachment 4 6 Special children and attachments 50 The importance of familiarity and knowledge of cultural practices 52 What can we learn from attachment research? 5 3 Being Acknowledged and Affirmed: developing a sense of self 55 Developing self assurance 6 0 4 A Sense of Belonging 6 1 Belonging in one's family 62 Belonging in an Early Childhood Education and Care setting 65 Summary of key messages 6 8 Chapter 4: A Skilful Communicator 70 Being together 7 0 Finding a voice 7 4 Bilingualism 7 8 Signing as first language 7 9 Listening and Responding 8 0 Making Meaning 8 2 Making meaning and print literacy …
Multiconductor transmission line modeling of SWCNT bundles in common-mode excitation

The multiconductor transmission line formalism is applied to the modeling of bundles of metallic and semiconducting single-walled carbon nanotubes. The developed approach accounts for the effects of electron transport at nanoscale and for the propagation of the voltages and currents along the bundle at the macroscopic level. The expressions of the matrices of the per-unit-length equivalent impedances and admittances of the bundle are derived considering the effect of wrapping and twisting of the nanotubes along the length of the bundle. Numerical calculations are performed in order to predict the current distribution among the metallic nanotubes of the bundle and the attenuation/transmission characteristics of the resulting multiconductor nano-transmission line.
Research and Inspection: Hmi and OFSTED, 1981-1996 - a commentary

This paper traces the changing relationship between research and inspection under both HMI and OFSTED, from the early 1980s to 1996. Drawing on a mix of internal and external sources it describes the changes within HMI to make traditional inspection methods more transparent and consistent and to make more use of quantitative data and performance indicators in the 1980s. However, changes within HMI were overtaken by events as education moved rapidly up the political agenda from the mid-1980s. With the demise of HMI in 1992, research within OFSTED took on a more prominent role and a modest but innovative research programme was established. However, the shift by OFSTED in the mid-1990s to take on a more explicit campaigning role to raise educational standards, rather than simply be a regulatory organisation, put the research under pressure to fit in with this new style. The paper draws on examples of the way these pressures worked out in both externally commissioned and internal research exercises. The result was that some studies were sidelined, while others were given excessive prominence that could not be justified by the scale and nature of the research.
A Review of Current Evidence-Based Clinical Applications for Breast Magnetic Resonance Imaging

Magnetic resonance imaging (MRI) is an important new tool for imaging of the breast. MRI has now been demonstrated to be the most sensitive imaging method for detecting breast carcinoma, allowing depiction of cancers that are occult on mammography, ultrasound, and clinical breast examination. This is tempered by imperfect specificity due to overlap in the features of benign and malignant lesions, and by higher examination cost and more limited availability compared to other breast imaging tests. This article describes the current evidence-based clinical indications for use of breast MRI. Specifically, MRI has been shown to be advantageous for cancer assessment for screening patients at high risk, evaluating patients with a new breast cancer diagnosis, monitoring patients undergoing neoadjuvant chemotherapy, and evaluating patients with metastatic axillary adenocarcinoma and unknown primary site. This tool has also been shown to be useful for the evaluation of silicone breast implant integrity. Employment of breast MRI as a problem solving technique for equivocal mammographic or clinical findings is controversial. For each of these clinical applications, the evidence regarding the diagnostic accuracy of breast MRI will be reviewed. An understanding of the current evidence will facilitate the most appropriate utilization of this important medical resource.
Rimonabant-Induced Δ9-Tetrahydrocannabinol Withdrawal in Rhesus Monkeys: Discriminative Stimulus Effects and Other Withdrawal Signs

Marijuana-dependent individuals report using marijuana to alleviate withdrawal, suggesting that pharmacotherapy of marijuana withdrawal could promote abstinence. To identify potential pharmacotherapies for marijuana withdrawal, this study first characterized rimonabant-induced Δ9-tetrahydrocannabinol (Δ9-THC) withdrawal in rhesus monkeys by using drug discrimination and directly observable signs. Second, drugs were examined for their capacity to modify cannabinoid withdrawal. Monkeys receiving chronic Δ9-THC (1 mg/kg/12 h s.c.) discriminated the cannabinoid antagonist rimonabant (1 mg/kg i.v.) under a fixed ratio schedule of stimulus-shock termination. The discriminative stimulus effects of rimonabant were dose-dependent (ED50 = 0.25 mg/kg) and accompanied by head shaking. In the absence of chronic Δ9-THC treatment (i.e., in nondependent monkeys), a larger dose (3.2 mg/kg) of rimonabant produced head shaking and tachycardia. Temporary discontinuation of Δ9-THC treatment resulted in increased responding on the rimonabant lever, head shaking, and activity during the dark cycle. The rimonabant discriminative stimulus was attenuated fully by Δ9-THC (at doses larger than mg/kg/12 h) and the cannabinoid agonist CP 55940 [5-(1,1-dimethylheptyl)-2-[5-hydroxy-2-(3-hydroxypropyl)cyclohexyl]phenol], and partially by the cannabinoid agonist WIN 55212-2 [(R)-(+)-[2, 3-dihydro-5-methyl-3-(4-morpholinylmethyl)pyrrolo[1,2,3-de]-1,4-benzoxazin-6-yl]-1-naphthalenylmethanone mesylate] and the α2-adrenergic agonist clonidine. In contrast, a benzodiazepine (diazepam) and monoamine agonist (cocaine) did not attenuate the rimonabant discriminative stimulus. Head shaking was attenuated by all test compounds. These results show that the discriminative stimulus effects of rimonabant in Δ9-THC-treated monkeys are a more pharmacologically selective measure of cannabinoid withdrawal than rimonabant-induced head shaking. These results suggest that cannabinoid and noncannabinoid (α2-adrenergic) agonists are potentially useful therapeutics for marijuana dependence inasmuch as they attenuate the subjective experience of Δ9-THC withdrawal.
FepA- and TonB-Dependent Bacteriophage H8: Receptor Binding and Genomic Sequence

ABSTRACT H8 is derived from a collection of Salmonella enterica serotype Enteritidis bacteriophage. Its morphology and genomic structure closely resemble those of bacteriophage T5 in the family Siphoviridae. H8 infected S. enterica serotypes Enteritidis and Typhimurium and Escherichia coli by initial adsorption to the outer membrane protein FepA. Ferric enterobactin inhibited H8 binding to E. coli FepA (50% inhibition concentration, 98 nM), and other ferric catecholate receptors (Fiu, Cir, and IroN) did not participate in phage adsorption. H8 infection was TonB dependent, but exbB mutations in Salmonella or E. coli did not prevent infection; only exbB tolQ or exbB tolR double mutants were resistant to H8. Experiments with deletion and substitution mutants showed that the receptor-phage interaction first involves residues distributed over the protein's outer surface and then narrows to the same charged (R316) or aromatic (Y260) residues that participate in the binding and transport of ferric enterobactin and colicins B and D. These data rationalize the multifunctionality of FepA: toxic ligands like bacteriocins and phage penetrate the outer membrane by parasitizing residues in FepA that are adapted to the transport of the natural ligand, ferric enterobactin. DNA sequence determinations revealed the complete H8 genome of 104.4 kb. A total of 120 of its 143 predicted open reading frames (ORFS) were homologous to ORFS in T5, at a level of 84% identity and 89% similarity. As in T5, the H8 structural genes clustered on the chromosome according to their function in the phage life cycle. The T5 genome contains a large section of DNA that can be deleted and that is absent in H8: compared to T5, H8 contains a 9,000-bp deletion in the early region of its chromosome, and nine potentially unique gene products. Sequence analyses of the tail proteins of phages in the same family showed that relative to pb5 (Oad) of T5 and Hrs of BF23, the FepA-binding protein (Rbp) of H8 contains unique acidic and aromatic residues. These side chains may promote binding to basic and aromatic residues in FepA that normally function in the adsorption of ferric enterobactin. Furthermore, a predicted H8 tail protein showed extensive identity and similarity to pb2 of T5, suggesting that it also functions in pore formation through the cell envelope. The variable region of this protein contains a potential TonB box, intimating that it participates in the TonB-dependent stage of the phage infection process.
Kinesin Adapter JLP Links PIKfyve to Microtubule-based Endosome-to-Trans-Golgi Network Traffic of Furin*

JIPs (c-Jun N-terminal kinase interacting proteins), which scaffold JNK/p38 MAP kinase signaling modules, also bind conventional kinesins and are implicated in microtubule-based membrane trafficking in neuronal cells. Here we have identified a novel splice variant of the Jip4 gene product JLPL (JNK-interacting leucine zipper protein) in yeast-two hybrid screens with the phosphoinositide kinase PIKfyve. The interaction was confirmed by pulldown and coimmunoprecipitation assays in native cells. It engages the PIKfyve cpn60_TCP1 consensus sequence and the last 75 residues of the JLP C terminus. Subpopulations of both proteins cofractionated and populated similar structures at the cell perinuclear region. Because PIKfyve is essential in endosome-to-trans-Golgi network (TGN) cargo transport, we tested whether JLP is a PIKfyve functional partner in this trafficking pathway. Short interfering RNA (siRNA)-mediated depletion of endogenous JLP or PIKfyve profoundly delayed the microtubule-based transport of chimeric furin (Tac-furin) from endosomes to the TGN in a CHO cell line, which was rescued upon ectopic expression of siRNA-resistant JLP or PIKfyve constructs. Peptides from the contact sites in PIKfyve and JLP, or a dominant-negative PIKfyve mutant introduced into cells by ectopic expression or microinjection, induced a similar defect. Because Tac-TGN38 delivery from endosomes to the TGN, unlike that of Tac-furin, does not require intact microtubules, we monitored the effect of JLP and PIKfyve depletion or the interacting peptides administration on Tac-TGN38 trafficking. Remarkably, neither maneuver altered the Tac-TGN38 delivery to the TGN. Our data indicate that JLP interacts with PIKfyve and that both proteins and their association are required in microtubule-based, but not in microtubule-independent, endosome-to-TGN cargo transport.
Transfers and exchanges of esterified cholesterol between plasma lipoproteins.

Knowledge concerning the formation and transport of esterified cholesterol in plasma is fundamental to an understanding of the mechanisms by which cholesterol is delivered to peripheral tissues from the liver and removed from these tissues for recycling or excretion through the liver. Hepatic cholesterol enters the plasma in man predominantly in the unesterified, or free, form as a component of lipoproteins secreted by the liver. In the plasma most of this cholesterol is converted to cholesteryl esters which have their origin within the plasma high density lipoproteins (HDL) in a transesterification reaction catalysed by the enzyme lecithin:cholesterol acyltransferase (LCAT) (Glomset, 1968). The newly formed cholesteryl esters are subsequently incorporated into the hydrophobic core of lipoprotein particles in all plasma lipoprotein fractions. In the postabsorptive state, esterified cholesterol accounts for about 70% of the cholesterol in human plasma and is transported primarily in low density lipoproteins (LDL) (Goodman, 1965). In most other mammalian species, however, HDL are the major transport vehicle for plasma esterified cholesterol (Goodman, 1965). This process of esterification and incorporation of cholesteryl esters into the hydrophobic core of lipoproteins enables the delivery of cholesterol to peripheral tissues to be controlled by the regulated uptake of plasma lipoproteins by tissues. An esterification of plasma cholesterol is required also for the removal of cholesterol from peripheral tissues. Free cholesterol equilibrates rapidly between cell membranes and the surface monolayer of plasma lipoproteins (Hagerman & Gould, 1951). A continuing esterification of the free cholesterol on the surface (, plasma lipoproteins maintains a concentration gradient which can drive a net movement
A Phase I Trial of Combined Ridaforolimus and MK-2206 in Patients with Advanced Malignancies

Purpose: The PI3K/Akt/mTOR signaling pathway is aberrantly activated in many cancers. Combining ridaforolimus, an mTOR inhibitor, with MK-2206, an Akt inhibitor, may more completely block the PI3K pathway and inhibit tumor growth. Experimental Design: This phase I study assessed dose-limiting toxicities (DLT) and maximum tolerated dose (MTD) for the combination of oral ridaforolimus plus oral MK-2206 in patients with advanced solid tumors. Efficacy was evaluated in patients with biomarker-identified estrogen receptor–positive breast cancer (low RAS gene signature and high Ki67 index) or castration-resistant prostate cancer (PTEN deficiency) with PI3K pathway addiction. Results: Thirty-five patients were enrolled: 11 patients in part A (three breast cancer) and 24 biomarker-eligible patients in part B (16 breast cancer, eight prostate cancer). One patient with breast cancer from part A was also found to be biomarker-eligible when tested after she had clinical response. The MTD was 10 mg/d ridaforolimus 5 d/wk + 90 mg/wk MK-2206; 1 of 17 patients experienced DLT (grade 3 rash) at this dose. The most common adverse events at MTD were rash (44.4%), stomatitis (38.9%), diarrhea (27.8%), and decreased appetite (27.8%). By investigator assessment, 2 of 16 (12.5%) evaluable patients with breast cancer had partial response; by central assessment, 2 of 14 (14.3%) evaluable patients had complete response. Two patients had durable stable disease (SD) for 416 and 285 days, respectively. No patients with prostate cancer responded; one patient had SD for ≥6 months. Conclusions: Combination ridaforolimus and MK-2206 showed promising activity and good tolerability in heavily pretreated patients with hormone-positive and -negative breast cancer exhibiting PI3K pathway dependence. Clin Cancer Res; 21(23); 5235–44. ©2015 AACR.
The Study of Realistic Image Rendition Algorithms Based on Human Visual System

Realistic image rendition is to reproduce the human perception of natural scenes, where the "realistic" means providing machine vision with the ideal images according to human visual system. The main characteristics of realistic image rendition involve color constancy, lightness constancy, image enhancement and high dynamic range compression. In this paper, the developments on realistic image rendition are investigated, human visual system structure and characteristics are described in detail and some excellent algorithms are studied and discussed, especially the classical Retinex series algorithms and tone mapping algorithms. In the end, the performances of these algorithms are simulated and shown.
Response-time guarantees in ATM networks

We present a method for providing response time guarantees in Asynchronous Transfer Mode (ATM) networks. The method is based on traditional real time CPU Response Time Analysis (RTA), and is intended to be used for admission control of hard real time traffic. The method determines if a new connection can be admitted without violating the strict timing requirements specified for the new as well as old connections. We illustrate the merits of our method by comparing it with Weighted Fair Queuing (WFQ) and the Calculus for Network Delays (CND). Two types of comparisons are made. In the first, we evaluate how well the associated analysis can accommodate different traffic scenarios and loads, and in the second comparison we use simulation to compare observed worst case behaviors with estimates obtained by the analysis. The comparisons clearly indicate that RTA outperforms both WFQ and CND for a set of realistic traffic scenarios.
How to Avoid Going Bump in the Night

The cognitive map theory has been a dominant influence over research into hippocampal function since the publication of O'Keefe and Nadel's The Hippocampus as a Cognitive Map in 1978 (now freely available at http://www.cognitivemap.net). The main premise of the theory is articulated in the book's first paragraph: “We shall argue that the hippocampus is the core of a neural memory system, providing an objective spatial framework within which the items and events of an organism's experience are located and interrelated” (O'Keefe and Nadel, 1978). The existence of “place cells” in the hippocampus—principal cells that fire selectively when the animal occupies restricted locations in an environment—is one of the primary pieces of evidence in support of the theory (O'Keefe and Nadel, 1978; Ekstrom et al., 2003). Early investigations of place cells characterized some of these cells as “misplace cells” (O'Keefe and Nadel, 1978), which fired in a specific location only when an unexpected object or reward was located in that place, or when an expected object or reward was missing. Thus, object-related influences on place cells were known from the very first investigations. Many subsequent experiments concentrated on the influences of distal landmarks on place cells, however (O'Keefe and Conway, 1978; but see Wible et al., 1986; Wiener et al., 1989). These experiments showed that place fields were controlled primarily by landmarks in the periphery of the environment, in that rotation of these landmarks caused place fields to rotate correspondingly. In contrast, rotation of the recording apparatus generally had no effect on the place fields. Thus, it became widely viewed that place cells were selective for spatial locations defined by the distances and angles to distal visual cues. Over the past decade, however, it has become clear that proximal, apparatus-based cues can control place cell firing if these cues are matched in salience to the distal landmarks (Young et al., 1994; Shapiro et al., 1997; Zinyuk et al., 2000; Knierim, 2002a). In addition, the importance of self-motion cues in updating the spatial representation in the hippocampus also has been demonstrated (McNaughton et al., 1996; Knierim, 2002b). It is clear that the location-specific firing of place cells arises from an interaction between proximal, distal, and self-motion cues, the details of which are still being debated.
The Iterative Distributed Re-authentication Scheme Based on EAP-AKA in 3G/UMTS-WLAN Heterogeneous Mobile Networks

3G/UMTS-WLAN heterogeneous mobile network is a complementary platform for the trend of Beyond-3G (B3G) wireless data communications. However, the design of a securing authentication protocol in 3G/UMTS-WLAN heterogeneous mobile networks is a challenging task. Even though EAP authentication and key agreement protocol (EAP-AKA) is adopted by 3rd generation partnership protocol (3GPP) to achieve authentication and security services in 3G/UMTS-WLAN interworking networks, it suffers a main drawback that is high re-authentication delay due to centralized re-authentication sessions within the RADIUS server and unnecessary multiple rounds of challenge-response messages traveling between the RADIUS server and UEs. In this paper, the iterative distributed re-authentication scheme is proposed to substitute for the fast re-authentication in EAP-AKA, and iterative process and distributed process within access points (APs) are introduced for reducing re-authentication latency. Also, the simulation model based on Network Simulator 2 (NS-2) is used to provide a proof-of-concept implementation in authentication session time, and the simulation results show that the reduction of authentication session time in the proposed scheme reaches up to 84.4% and 71.2% comparing to the full authentication scheme and the fast re-authentication scheme, respectively.