Miracle-dz/UniFAR-FTUs huggingface dataset:
Receptor‐specific inhibition of GABAB‐activated K+ currents by muscarinic and metabotropic glutamate receptors in immature rat hippocampus

It has been shown that the activation of Gq‐coupled receptors (GqPCRs) in cardiac myocytes inhibits the G protein‐gated inwardly rectifying K+ current (IGIRK) via receptor‐specific depletion of phosphatidylinositol 4,5‐bisphosphate (PIP2). In this study, we investigated the mechanism of the receptor‐mediated regulation of IGIRK in acutely isolated hippocampal CA1 neurons by the muscarinic receptor agonist, carbachol (CCh), and the group I metabotropic glutamate receptor (mGluR) agonist, 3,5‐dihydroxyphenylglycine (DHPG). IGIRK was activated by the GABAB receptor agonist, baclofen. When baclofen was repetitively applied at intervals of 2–3 min, the amplitude of the second IGIRK was 92.3 ± 1.7% of the first IGIRK in control. Pretreatment of neurons with CCh or DHPG prior to the second application of baclofen caused a reduction in the amplitude of the second IGIRK to 54.8 ± 1.3% and 51.4 ± 0.6%, respectively. In PLCβ1 knockout mice, the effect of CCh on IGIRK was significantly reduced, whereas the effect of DHPG remained unchanged. The CCh‐mediated inhibition of IGIRK was almost completely abolished by PKC inhibitors and pipette solutions containing BAPTA. The DHPG‐mediated inhibition of IGIRK was attenuated by the inhibition of phospholipase A2 (PLA2), or the sequestration of arachidonic acid. We confirmed that DHPG eliminated the inhibition of IGIRK by arachidonic acid. These results indicate that muscarinic inhibition of IGIRK is mediated by the PLC/PKC signalling pathway, while group I mGluR inhibition of IGIRK occurs via the PLA2‐dependent production of arachidonic acid. These results present a novel receptor‐specific mechanism for crosstalk between GqPCRs and GABAB receptors.
Risk assessment of engineered nanomaterials: a review of available data and approaches from a regulatory perspective

Abstract It has been largely recognised that substantial limitations and uncertainties make the conventional risk assessment (RA) of chemicals unfeasible to apply to engineered nanomaterials (ENMs) today, which leaves the regulators with little support in the near term. The aim of this paper is to discuss the state of the art in the area of the RA of nanomaterials, focusing on the available data and approaches. There is a paucity of reliable information in the online safety databases and the literature is dominated by (eco)toxicity studies, while the nano-exposure research lags behind. Most of the reviewed nano-RA approaches are designed to serve as preliminary risk screening and/or research prioritisation tools and are not intended to support regulatory decision making. In this context, we recommend to further study the possibilities to apply complementary/alternative tools for near-term RA of ENMs in order to facilitate their timely regulation, using the data that are currently available in the literature.
Ligand Bound β1 Integrins Inhibit Procaspase-8 for Mediating Cell Adhesion-Mediated Drug and Radiation Resistance in Human Leukemia Cells

Background Chemo- and radiotherapeutic responses of leukemia cells are modified by integrin-mediated adhesion to extracellular matrix. To further characterize the molecular mechanisms by which β1 integrins confer radiation and chemoresistance, HL60 human acute promyelocytic leukemia cells stably transfected with β1 integrin and A3 Jurkat T-lymphoma cells deficient for Fas-associated death domain protein or procaspase-8 were examined. Methodology/Principal Findings Upon exposure to X-rays, Ara-C or FasL, suspension and adhesion (fibronectin (FN), laminin, collagen-1; 5–100 µg/cm2 coating concentration) cultures were processed for measurement of apoptosis, mitochondrial transmembrane potential (MTP), caspase activation, and protein analysis. Overexpression of β1 integrins enhanced the cellular sensitivity to X-rays and Ara-C, which was counteracted by increasing concentrations of matrix proteins in association with reduced caspase-3 and -8 activation and MTP breakdown. Usage of stimulatory or inhibitory anti β1 integrin antibodies, pharmacological caspase or phosphatidylinositol-3 kinase (PI3K) inhibitors, coprecipitation experiments and siRNA-mediated β1 integrin silencing provided further data showing an interaction between FN-ligated β1 integrin and PI3K/Akt for inhibiting procaspase-8 cleavage. Conclusions/Significance The presented data suggest that the ligand status of β1 integrins is critical for their antiapoptotic effect in leukemia cells treated with Ara-C, FasL or ionizing radiation. The antiapoptotic actions involve formation of a β1 integrin/Akt complex, which signals to prevent procaspase-8-mediated induction of apoptosis in a PI3K-dependent manner. Antagonizing agents targeting β1 integrin and PI3K/Akt signaling in conjunction with conventional therapies might effectively reduce radiation- and drug-resistant tumor populations and treatment failure in hematological malignancies.
VAMP-1 has a highly variable C-terminus generated by alternative splicing.

VAMP-1 (synaptobrevin1) is one of the key proteins in the SNARE complex which is involved in regulated exocytosis. Recently, Isenmann et al. (1998, Mol. Biol. Cell 9, 1649-1660) showed the extreme C-terminal region of VAMP-1A and 1B to be involved in subcellular targeting of the isoforms. Four new splice variants (VAMP-1C to F) were identified in addition to the previously published variants VAMP-1A and VAMP-1B. Interestingly, the four new isoforms also have variable sequences only at the extreme C-terminus. This suggests that the C-terminal region has an important function for VAMP-1 and vesicle targeting. All six variants were a result of alternative splicing that linked exons 1-4 which encode the conserved region of VAMP-1 with one of the exons 5A to 5F that encodes the highly variable extreme C-terminus. Exon (5A-E) encode C-termini of two to five amino acid residues, whereas exon 5F encoded a long C-terminal amino acid extension. The splice variants were differentially expressed in human brain, kidney, and inflammatory cells.
Neighbor-Information-Assisted Tree Routing for ZigBee Networks

In ZigBee networks, the classical Tree Routing algorithm only utilizes the father-child relationship between nodes to establish routes, thus the path usually may not be optimal, which leads to some extra overhead. To address this problem, in this paper, we propose an improved Tree Routing algorithm which utilizes the information of neighbors within two hops. Concretely, our proposed algorithm allows nodes to use the distributed address assignment mechanism (DAAM) to calculate their depth, and decide whether to adopt the algorithm based on two hop neighbors or Tree Routing by the comparison of the overhead from the next hop to destination node. Meanwhile, routing nodes broadcast beacon messages with local neighbor information periodically, so a node can obtain the 2-hop neighbor information easily. Simulation results show that our algorithm improves the success ratio of packet delivery, and reduces 30% of the end to end delay, and at least 30% of the average number of hops compared to the Tree Routing algorithm.
Getting The Benefits Of ICTs In Tourism Destinations: Models, Strategies And Tools

Tourism is a relevant opportunity for economic development and social well being. Information and Communication Technologies (ICTs) are important tools for seizing tourism developmental opportunities arising from integrating and strengthening the local tourism value chain. Nevertheless, ‘productivity paradoxes’ showed that technologies (IT first and the Internet now) cannot produce any significant benefit unless accompanied by complementary organizational changes. Who’s in charge of managing tourism destinations is thus facing a double challenge: the redefinition of traditional destination management activities to suit ICTs and the diffusion of such tools in a fragmented, SMEs-driven sector. In this aim, the present paper presents an ICT-enabled model and the related diffusion strategy as it is applied in different experiences in Italy, Morocco and Jordan. Then a detailed description of how in practice this strategy is implemented and its main components is provided. The results of five-years long research and practical experiences as well as field experimentations as related to the application of the strategy will be used to conclude with a number of insights as related to ICTs diffusion in tourism destinations In particular different clues as related to the diffusion of innovative destination management models and the role of technology in doing so will be discussed.
Influence of marijuana and ecstasy (MDMA) on cognitive function and driving performance

The use of marijuana (delta-9-tetrahydrocannabinol; THC) and ecstasy (+/- 3,4-methylenedioxymethamphetamine; MDMA) has been associated with unsafe driving and cognitive impairment in intoxicated users. In addition, previous studies have observed cognitive decline in abstinent users of these drugs, especially in heavy users. This dissertation presents a unique evaluation of the acute and long-term effects of marijuana and MDMA on cognitive function, driving- and psychomotor performance in recreational users of these drugs. Driving performance was assessed by means of real driving, simulated driving and driving-related task performance. The separate studies in this dissertation show that acute effects of a single low dose of marijuana and MDMA have the potential to impair driving performance. Marijuana impairs visual search when combined with a small dose of alcohol, while MDMA impairs object movement estimation. Abstinent recreational users of marijuana alone or in combination with MDMA show signs of cognitive and driving impairment. Additionally, these abstinent users exhibit impaired cognitive functions and decision making and when confronted with a potentially dangerous traffic situation, abstinent users of MDMA/marijuana are more likely to sustain severe injury than drug naive controls. It is concluded that use of MDMA and/or marijuana has the potency to interfere with complex performance, especially driving, in both intoxicated and abstinent recreational users of these drugs. (A)
Time Course and Role of Morphine Dose and Concentration in Intrathecal Granuloma Formation in Dogs: A Combined Magnetic Resonance Imaging and Histopathology Investigation

Background:Intrathecal morphine infusion leads to intrathecal granulomas. In dogs, the authors examined time course of granuloma formation and the role of concentration in granuloma development. Methods:Dogs were prepared with lumbar intrathecal catheters and vest-mounted pumps. To define the time course of granuloma formation, serial magnetic resonance imaging was performed in animals receiving 10 or 31 days of morphine infusion (12.5 mg/ml at 40 &mgr;l/h). At these times, morphine was removed from the infusate, and further magnetic resonance images were acquired over 14–35 additional days. To assess dose versus concentration, dogs received 28-day infusions of vehicle, 12 mg morphine/day as 12.5 mg/ml at 40 &mgr;l/h, or 1.5 mg/ml at 334 &mgr;l/h (12 mg/day) for 28 days. Additional dogs received 3 mg/day as 12.5 mg/ml at 10 &mgr;l/h. Results:Serial magnetic resonance images in dogs receiving morphine (12.5 mg/ml at 40 &mgr;l/h) revealed pericatheter-enhancing tissues as early as 3 days with a prominent signal by 10 days. Removal of morphine reduced the mass volume within 7 days. At a fixed infusion rate, the incidence of granuloma formation with the continuous intrathecal infusion of morphine ranged from 0 in vehicle-treated dogs to 100% in dogs treated with 12.5 mg/ml at 40 &mgr;l/h (12 mg/day). Infusion of 12 mg/day at 1.5 mg/ml (334 &mgr;l/h) resulted in granuloma in one of four animals. The authors found that infusion of morphine in different concentrations at a fixed rate resulted in a dose-dependent increase in concentration, with the granuloma-producing, dose-yielding lumbar cerebrospinal fluid morphine concentrations around 40 &mgr;g/ml. Conclusions:Serial magnetic resonance imaging showed a rapid formation and regression of the masses initiated by intrathecal morphine infusion. These masses are dependent on local concentration.
An adaptive admission control algorithm for bandwidth brokers

This work focuses on the operation of the bandwidth broker, an entity that is responsible for managing the bandwidth within a network domain and for the communication with bandwidth brokers of neighboring domains. A very important aspect of the bandwidth broker is its admission control module that determines whether the bandwidth reservation requests are going to be accepted or not. We summarize the status of the current research in this field and propose architecture for the admission control module that aims at achieving a satisfactory balance between maximizing the resource utilization for the network provider and minimizing the overhead of the module. This is achieved by gathering and examining sets of book-ahead requests and by adapting the size of the set to be examined so that the network utilization and the computation overhead are appropriately balanced.
Non-classical indications for cardiac resynchronization therapy.

A B S T R A C T Based on randomized controlled studies, cardiac resynchronization therapy (CRT) is currently indicated in patients with systolic heart failure of New York Heart Association (NYHA) functional class III and IV, left ventricular ejection fraction 120 ms). Most of the enrolled patients were in sinus rhythm, were not previously paced and had mainly LBBB. Thus, there are uncertainties regarding several other populations, not included or underrepresented in the main studies. These populations include patients with atrial fibrillation (AF), previous pacemakers considered for upgrade to CRT, RBBB, narrow QRS 120 ms) [1]. These indications are based on randomized controlled trials in which patients with these indications have been enrolled. Most of the patients enrolled into these studies were in sinus rhythm, were not previously paced and had left bundle branch block (LBBB) or another left intraventricular conduction delay [2-5]. There are still uncertainties regarding several other populations that were not included or underrepresented in the main studies. These populations include patients with atrial fibrillation, patients with previous pacemakers who are being considered for upgrade to CRT, patients with right bundle branch block (RBBB), patients with narrow QRS <120 ms, patients with NYHA functional class lower than III, patients with low EF who need pacemakers for other indications and do not have wide QRS yet, and patients with predominantly right heart failure. We will review here our experience and the available literature to try to determine the benefits of CRT in these populations.
Design of memorized controller for event-triggered networked control systems

This paper investigates a memorized state feedback controller and an event-triggering control scheme of uncertain networked control systems with time delay. An event-triggering scheme of networked control systems is designed where sensors transmit samples to controllers only when the state error exceeds a specified threshold. Fewer samples would be transmitted so that the burden of networks will be reduced under the event-trigger. A memorized controller containing information of time-varying delay is designed. Finally, the stability of networked control system with the memorized controller and effectiveness of the event-trigger are demonstrated with simulation results.
Morphology estimation of rice fields using X-band PolSAR data

Synthetic Aperture Radar (SAR) remote sensing techniques play a significant role in modern agricultural crop monitoring by relating the plant structure (height, biomass, yield and growth-stage) to the backscattering behavior of the vegetative canopy. The current trend in crop monitoring is towards precision agriculture, which needs detailed morphology information. By predicting the physical structure, one can just determine the under and overgrowth conditions. In this study, we propose a probabilistic inversion algorithm for a Radiative Transfer Theory (RTT) model which relates the backscattering response of a canopy to its physical structure. The outcomes of the inversion provided promising results by estimating the dimensions of the primary structures with a small bias.
The Drosophila pho-like gene encodes a YY1-related DNA binding protein that is redundant with pleiohomeotic in homeotic gene silencing

Polycomb group proteins (PcG) repress homeotic genes in cells where these genes must remain inactive during Drosophila and vertebrate development. This repression depends on cis-acting silencer sequences, called Polycomb group response elements (PREs). Pleiohomeotic (Pho), the only known sequence-specific DNA-binding PcG protein, binds to PREs but pho mutants show only mild phenotypes compared with other PcG mutants. We characterize pho-like, a gene encoding a protein with high similarity to Pho. Pho-like binds to Pho-binding sites in vitro and pho-like, pho double mutants show more severe misexpression of homeotic genes than do the single mutants. These results suggest that Pho and Pho-like act redundantly to repress homeotic genes. We examined the distribution of five PcG proteins on polytene chromosomes from pho-like, pho double mutants. Pc, Psc, Scm, E(z) and Ph remain bound to polytene chromosomes at most sites in the absence of Pho and Pho-like. At a few chromosomal locations, however, some of the PcG proteins are no longer present in the absence of Pho and Pho-like, suggesting that Pho-like and Pho may anchor PcG protein complexes to only a subset of PREs. Alternatively, Pho-like and Pho may not participate in the anchoring of PcG complexes, but may be necessary for transcriptional repression mediated through PREs. In contrast to Pho and Pho-like, removal of Trithorax-like/GAGA factor or Zeste, two other DNA-binding proteins implicated in PRE function, does not cause misexpression of homeotic genes or reporter genes in imaginal disks.
Training-of-trainers: A strategy to build country capacity for SLMTA expansion and sustainability

Background The Strengthening Laboratory Management Toward Accreditation (SLMTA) programme uses a training-of-trainers (TOT) model to build capacity for programme scale-up. The TOT strategy is designed to maximise utilisation of its graduates whilst minimising inconsistencies and ensuring high programme quality during global expansion. Objectives To describe the SLMTA TOT programme approach. Methods The two-week training, led by carefully selected and trained master trainers, enables effective and authentic implementation of the curriculum by its graduates. The teachback methodology used allows participants to practise teaching the curriculum whilst learning its content. A trainer’s toolkit provides all the materials necessary for teaching and must be followed faithfully during training. Two surveys were conducted to assess the effectiveness of the TOT strategy: one sent to 316 TOT graduates in 25 countries and the other sent to the programme leaders in 10 countries. Results By the end of 2013, 433 SLMTA trainers had been trained who, in turn, taught more than 1900 people to implement SLMTA in 617 laboratories in 47 countries. Ninety-seven percent of the 433 TOT graduates and 87% of the 38 master trainers are based in developing countries. Ninety-two per cent of the graduates have been utilised at least once in programme implementation and, as of August 2013, 87% of them were still actively involved in programme activities. Ninety-seven per cent of the graduates stated that the TOT workshop prepared them well for training or other programme tasks. Conclusion The SLMTA TOT strategy is effective in building local capacity for global programme expansion whilst maintaining programme quality.
Changes in Plasma Solutes after Food

In experiments on 8 healthy young male volunteers, the ingestion of a large meal was found to cause plasma osmolality to rise from 288.8 ± 0.8 (mean ± s.e. mean) to 295.6 ± 0.9 mmol/kg at 4 hours (P < 0.001). There was an accompanying rise in plasma sodium (Na) from 141.9 ± 0.8 to 144.6 ± 0.8 mmol/1, also at 4 hours (P < 0.01), but little change in other plasma electrolytes. Serum total amino acids rose slightly, non-esterified fatty acid fell minimally and changes in blood glucose concentrations were unremarkable. Thirst was experienced at plasma osmolality of 294.8 ± 0.7 mmol/kg. Repeating the experiment either without food, or with the salt content of the meal only, was without effect on plasma Na, other solutes or osmolality. Postprandial hypersomolality and hypernatraemia is probably due to movement of water from the vascular compartment to the gut, or into cells. Plasma osmolality is best measured in the fasting state.
Association of LOXL1 gene polymorphisms with exfoliation syndrome/glaucoma and primary open angle glaucoma in a Turkish population

Purpose To investigate the association of lysyl oxidase like 1 (LOXL1) variants with exfoliation syndrome (XFS), exfoliation glaucoma (XFG), and primary open angle glaucoma (POAG) in a Turkish population. Methods Two LOXL1 single nucleotide polymorphisms (SNPs), rs1048661 (R141L) and rs3825942 (G153D), were analyzed in 300 Turkish patients (100 patients with XFS, 100 patients with XFG, 100 patients with POAG) and 100 control subjects. Results The T allele of rs1048661 was underrepresented in patients with XFS (odds ratio [OR]=0.334, 95% confidence interval [CI]: 0.198–0.564, p=2.54×10−5) and XFG (OR=0.366, 95% CI: 0.219–0.611, p=8.56×10−5) compared to the control subjects. None of the patients with XFS or XFG had the A allele of rs3825942, whereas 16% of the control subjects had that variant (OR=0.025, 95% CI: 0.003–0.188, p=3.69×10−9). No association was observed between the SNPs studied and POAG. By using logistic regression analysis, the effect of rs1048661 remained significant (p=8.45×10−8) after controlling for the effect of rs3825942, whereas rs3825942 was not significant with conditioning on rs1048661. Female gender was protective against the disease controlling with the effect of the two SNPs (OR=0.527, 95% CI: 0.358–0.776, p=0.001). Conclusions The findings of the current study indicate that in a logistic regression analysis model the T allele of rs1048661 is the most important risk-modifying factor for the development of XFS and XFG. Our results also confirm in a Turkish population the findings of previous reports describing the association between LOXL1 polymorphisms and XFS/XFG but not with POAG. The allele and genotype distribution in this cohort appear to be similar to those of Caucasians.