Miracle-dz/UniFAR-FTUs huggingface dataset:
In situ Tip-Recordings Found No Evidence for an Orco-Based Ionotropic Mechanism of Pheromone-Transduction in Manduca sexta

The mechanisms of insect odor transduction are still controversial. Insect odorant receptors (ORs) are 7TM receptors with inverted membrane topology. They colocalize with a conserved coreceptor (Orco) with chaperone and ion channel function. Some studies suggest that insects employ exclusively ionotropic odor transduction via OR-Orco heteromers. Other studies provide evidence for different metabotropic odor transduction cascades, which employ second messenger-gated ion channel families for odor transduction. The hawkmoth Manduca sexta is an established model organism for studies of insect olfaction, also due to the availability of the hawkmoth-specific pheromone blend with its main component bombykal. Previous patch-clamp studies on primary cell cultures of M. sexta olfactory receptor neurons provided evidence for a pheromone-dependent activation of a phospholipase Cβ. Pheromone application elicited a sequence of one rapid, apparently IP3-dependent, transient and two slower Ca2+-dependent inward currents. It remains unknown whether additionally an ionotropic pheromone-transduction mechanism is employed. If indeed an OR-Orco ion channel complex underlies an ionotropic mechanism, then Orco agonist-dependent opening of the OR-Orco channel pore should add up to pheromone-dependent opening of the pore. Here, in tip-recordings from intact pheromone-sensitive sensilla, perfusion with the Orco agonist VUAA1 did not increase pheromone-responses within the first 1000 ms. However, VUAA1 increased spontaneous activity of olfactory receptor neurons Zeitgebertime- and dose-dependently. We conclude that we find no evidence for an Orco-dependent ionotropic pheromone transduction cascade in M. sexta. Instead, in M. sexta Orco appears to be a slower, second messenger-dependent pacemaker channel which affects kinetics and threshold of pheromone-detection via changes of intracellular Ca2+ baseline concentrations.
The 1.1 Å resolution structure of a periplasmic phosphate-binding protein from Stenotrophomonas maltophilia: a crystallization contaminant identified by molecular replacement using the entire Protein Data Bank.

During efforts to crystallize the enzyme 2,4-dihydroxyacetophenone dioxygenase (DAD) from Alcaligenes sp. 4HAP, a small number of strongly diffracting protein crystals were obtained after two years of crystal growth in one condition. The crystals diffracted synchrotron radiation to almost 1.0 Å resolution and were, until recently, assumed to be formed by the DAD protein. However, when another crystal form of this enzyme was eventually solved at lower resolution, molecular replacement using this new structure as the search model did not give a convincing solution with the original atomic resolution data set. Hence, it was considered that these crystals might have arisen from a protein impurity, although molecular replacement using the structures of common crystallization contaminants as search models again failed. A script to perform molecular replacement using MOLREP in which the first chain of every structure in the PDB was used as a search model was run on a multi-core cluster. This identified a number of prokaryotic phosphate-binding proteins as scoring highly in the MOLREP peak lists. Calculation of an electron-density map at 1.1 Å resolution based on the solution obtained with PDB entry 2q9t allowed most of the amino acids to be identified visually and built into the model. A BLAST search then indicated that the molecule was most probably a phosphate-binding protein from Stenotrophomonas maltophilia (UniProt ID B4SL31; gene ID Smal_2208), and fitting of the corresponding sequence to the atomic resolution map fully corroborated this. Proteins in this family have been linked to the virulence of antibiotic-resistant strains of pathogenic bacteria and with biofilm formation. The structure of the S. maltophilia protein has been refined to an R factor of 10.15% and an Rfree of 12.46% at 1.1 Å resolution. The molecule adopts the type II periplasmic binding protein (PBP) fold with a number of extensively elaborated loop regions. A fully dehydrated phosphate anion is bound tightly between the two domains of the protein and interacts with conserved residues and a number of helix dipoles.
AZT+methotrexate in high-grade HIV-related non-Hodgkin lymphomas: interim report on feasibility and tolerance.

BACKGROUND 3' azido-3' deoxythymidine (AZT) is a thymidine analogue useful in the treatment of AIDS. We have previously demonstrated that AZT can possess significant antineoplastic activity when combined with de novo thymidylate synthesis inhibitors, such as 5-fluorouracil or methotrexate (MTX). We report here on the feasibility and tolerance of the combination AZT+MTX in the treatment of HIV-related non-Hodgkin lymphomas (NHL). PATIENTS AND METHODS IV-positive patients with high-grade NHL were treated, at weekly intervals, with three consecutive courses of MTX 1 g/m2 plus increasing doses of oral AZT (2, 4 and 6 g/m2) and folinic acid rescue. RESULTS From July 1992 to June 1994, 16 patients were enrolled in the trial after giving informed consent. Grade III-IV neutropenia was observed after 22% of the courses, but was prevented by G-CSF administration in 34/59 courses. Grade III-IV anemia was observed after 15% of the courses. No non hematological toxicity was observed. CONCLUSIONS The combination AZT+MTX was extremely well tolerated in this series of HIV-related NHL patients. If these results are confirmed in terms of antineoplastic efficacy, the protocol will deserve wider application.
Foreshocks and short-term hazard assessment of large earthquakes usingcomplex networks: the case of the 2009 L'Aquila earthquake

Abstract. The monitoring of statistical network properties could be useful for the short-term hazard assessment of the occurrence of mainshocks in the presence of foreshocks. Using successive connections between events acquired from the earthquake catalog of the Istituto Nazionale di Geofisica e Vulcanologia (INGV) for the case of the L'Aquila (Italy) mainshock (Mw = 6.3) of 6 April 2009, we provide evidence that network measures, both global (average clustering coefficient, small-world index) and local (betweenness centrality) ones, could potentially be exploited for forecasting purposes both in time and space. Our results reveal statistically significant increases in the topological measures and a nucleation of the betweenness centrality around the location of the epicenter about 2 months before the mainshock. The results of the analysis are robust even when considering either large or off-centered the main event space windows.
Critical Success Factors in Enterprise Resource Planning (ERP) System Implementation Stages: An Exploratory Study in Oman

Many studies in literature have shown the importance of ERP system in companies' effectiveness, and this is because ERP system have become one of the main prerequisites, a price of entry, and a strong and integrated IT infrastructure for many companies enabling them to compete in the local and global marketplace, and ensuring them to gain a competitive advantage in the global economy particularly with the current e-business era. This study will investigate the critical success factors (CSFs) that can play a role during the implementation process in Omani organizations and will identify the critical success factors that affecting ERP system implementation success during the three implementation stages which are pre-implementation stage, implementation stage and post- implementation stage.
Incremental network programming for wireless sensors

We present an incremental network programming mechanism which re programs wireless sensors quickly by transmitting the incremental changes for the new program version. Using the Rsync algorithm we generate the difference of the two program images, which allows us to distribute just the key changes of the program. Unlike previous approaches, our design does not assume any prior knowledge of the program code structure and can be applied to any hardware platform. To meet the resource constraints of wireless sensors we tuned the Rsync algorithm which was originally made for updating binary files among computationally powerful machines. In our design, the sensor node processes the delivery and the decoding of the difference script in separate steps. This makes it easy to extend for multi-hop network programming. We are able to achieve the speedup of 9.1 for changing a constant and 2.1 to 2.5 for changing a few lines in the source code over the non-incremental delivery.
Solitary metastases from renal cell carcinoma: A review

Nineteen patients with solitary metastatic lesions from renal cell carcinoma, 5 synchronous and 14 metachronous, were seen at the Tata Memorial Hospital over a 7 year period between 1981 and 1987. The mean metastatic interval for the metachronous lesions was 31.2 months. The commonest sites of metastases were bone, lung, and liver. The solitary nature of the metastasis was confirmed by appropriate investigations. All patients underwent nephrectomy for the primary kidney lesion. The metastatic lesions were treated with intent of cure. Only 1 patient with synchronous metastasis survived for 2 years and none survived 5 years while in the metachronous metastasis group, the estimated overall survival was 50% at 2 years and 25% at 5 years. The patients with a long metastasis‐free interval were found to have a better survival. The patients with liver metastasis did poorly as compared to those with metastases at other sites. The stage of the disease also had a bearing on the survival.
A randomized trial of the effect of statin and fibrate therapy on arterial function in CKD.

BACKGROUND Although patients with chronic kidney disease (CKD) are at increased risk of cardiovascular disease (CVD), the roles of lipid-modifying therapies in decreasing CVD risk are unclear. Our aim is to compare the effects of statin and fibrate therapy on arterial function as a risk marker of CVD. STUDY DESIGN Double-blind, randomized, placebo-controlled, parallel-group study. SETTING & PARTICIPANTS Ambulatory patients with stages 3 to 5 CKD. INTERVENTION 6 weeks of atorvastatin, 40 mg/d, or gemfibrozil, 600 mg twice daily, with placebo. OUTCOMES & MEASUREMENTS Primary outcome was arterial function assessed by means of endothelial-dependent flow-mediated dilatation (FMD) and small-artery compliance (C2). Secondary outcomes included endothelial-independent glyceryl trinitrate-mediated dilatation (GTNMD), large-artery compliance (C1), and levels of lipids, lipoproteins, and oxidized low-density lipoprotein, as well as markers of insulin resistance and inflammation. RESULTS Compared with placebo, atorvastatin significantly decreased low-density lipoprotein (-52%), triglyceride (-30%), and oxidized low-density lipoprotein levels (-41%; P < 0.0001). Gemfibrozil significantly decreased triglyceride levels (-40%) and increased high-density lipoprotein levels (+20%; P < 0.0001). Neither atorvastatin nor gemfibrozil had a significant effect on markers of insulin resistance or inflammation. There was no significant change in FMD, GTNMD, or C1 with either atorvastatin or gemfibrozil. There was improvement in C2 with atorvastatin (+1.1 mL/mm Hg x 100) compared with placebo (P = 0.024), but not with gemfibrozil compared with placebo. LIMITATIONS Small sample size leading to inadequate power, short duration of therapy, and use of a heterogeneous group of patients with CKD and dialysis patients. CONCLUSION In patients with advanced CKD, atorvastatin is associated with improvement in dyslipidemia and small-artery stiffness, but not endothelial function. Gemfibrozil improves dyslipidemia, but has no effect on arterial function.
Corticotropin-Releasing Factor Receptors CRF1 and CRF2 Exert Both Additive and Opposing Influences on Defensive Startle Behavior

The corticotropin-releasing factor (CRF) receptors (CRF1 and CRF2) are crucial mediators of physiological and behavioral responses to stress. In animals, CRF1 appears to primarily mediate CRF-induced anxiety-like responses, but the role of CRF2 during stress is still unclear. Here we report the effects of CRF1 and CRF2 on the magnitude and plasticity of defensive startle responses in mice. Startle plasticity is measured by inhibition of startle by sensory stimuli, i.e., prepulse inhibition (PPI), and is disrupted in patients with panic or posttraumatic stress disorders in which CRF neurotransmission may be overactive. Pharmacological blockade of CRF1 reversed both CRF-induced increases in startle and CRF-induced deficits in PPI. CRF2 blockade attenuated high-dose but not low-dose CRF-induced increases in startle and reduced PPI. Conversely, activation of CRF2 enhanced PPI. CRF had no effect on startle and increased PPI in CRF1 knock-out mice. These data indicate that CRF receptors act in concert to increase the magnitude of defensive startle yet in opposition to regulate the flexibility of startle. These data support a new model of respective CRF receptor roles in stress-related behavior such that, although both receptors enhance the magnitude of defensive responses, CRF1 receptors contravene, whereas CRF2 receptors enhance, the impact of sensory information on defensive behavior. We hypothesize that excessive CRF1 activation combined with reduced CRF2 signaling may contribute to information processing deficits seen in panic and posttraumatic stress disorder patients and support CRF1-specific pharmacotherapy.
Pearson–based Analysis of Positioning Error Distribution in Wireless Sensor Networks

In two recent contributions, we have provided a comparative analysis of various optimization algorithms, which can be used for atomic location estimation, and suggested an enhanced version of the Steepest Descent (ESD) algorithm, which we have shown to be competitive with other distributed localization algorithms in terms of estimation accuracy and numerical complexity. Moreover, therein we have conducted a preliminary statistical characterization of the positioning error distribution, by showing that it can be well approximated by the family of Pearson distributions, as well as pointed out that its knowledge may be efficiently used to speed-up the analysis of iterative-based positioning algorithms by avoiding the need of simulating the whole location discovery algorithm, and allowing simulation at the atomic level only. In this contribution, based on the preliminary results shown in, we propose a comprehensive statistical analysis of the positioning error distribution for the ESD algorithm, by providing the parameters of the Pearson fitting distribution with respect to two important design factors for wireless sensor networks (WSNs): i) the ranging error standard deviation, which represents the input parameter for every localization algorithm, and ii) the geometric dilution of precision factor, which provides a simple parameter to account for different network topologies. In particular, we report an extensive number of simulation results that may provide important insights to the system designer: i) allow a parametric analysis to figure out the joint effect of ranging errors and network topology on the performance of the localization algorithms, and ii) give a general framework for modeling the statistics of the positioning error, which may be used for network planning, as well as for the analysis and design of the upper layers of the protocol stack.
Interaction of Gαq and Kir3, G Protein-Coupled Inwardly Rectifying Potassium Channels

Activation of substance P receptors, which are coupled to Gαq, inhibits the Kir3.1/3.2 channels, resulting in neuronal excitation. We have shown previously that this channel inactivation is not caused by reduction of the phosphatidylinositol 4,5-bisphosphate level in membrane. Moreover, Gαq immunoprecipitates with Kir3.2 (J Physiol 564:489–500, 2005), suggesting that Gαq interacts with Kir3.2. Positive immunoprecipitation, however, does not necessarily indicate direct interaction between the two proteins. Here, the glutathione transferase pull-down assay was used to investigate interaction between Gαq and the K+ channels. We found that Gαq interacted with N termini of Kir3.1, Kir3.2, and Kir3.4. However, Gαq did not interact with the C terminus of any Kir3 or with the C or N terminus of Kir2.1. TRPC6 is regulated by the signal initiated by Gαq. Immunoprecipitation, however, showed that Gαq did not interact with TRPC6. Thus, the interaction between Gαq and the Kir3 N terminus is quite specific. This interaction occurred in the presence of GDP or GDP-AlF–4. The Gαq binding could take place somewhere between residues 51 to 90 of Kir3.2; perhaps the segment between 81 to 90 residues is crucial. Gβγ, which is known to bind to N terminus of Kir3, did not compete with Gαq for the binding, suggesting that these two binding regions are different. These findings agree with the hypothesis (J Physiol 564:489–500, 2005) that the signal to inactivate the Kir3 channel could be mainly transmitted directly from Gαq to Kir3.
P2P IPTV measurement: a case study of TVants

With the success of P2P file sharing applications, new emerging P2P applications arise on the Internet for broadcasting new content like voice (VoIP) or video (IPTV). Nowadays, there are a lot of works measuring file sharing [2] or telephony P2P applications [1], but there is still no comprehensive study about P2P IPTV applications [3]. However, we think P2P IPTV applications will be massively used in the future and it is very important to study the effect they will have on the network. We measured network traffic generated by P2P IPTV users watching the last FIFA world cup. We used several applications in different network environments to collect a large amount of various data. FIFA world cup is a large-scale event with live interest and we believe this will allow us to have a representative sample of large-scale P2P IPTV applications. With the huge amount of collected data, we can study users/applications behavior for P2P live streaming system and their impact on the traffic network.
Bloodmeal Analysis Reveals Avian Plasmodium Infections and Broad Host Preferences of Culicoides (Diptera: Ceratopogonidae) Vectors

Changing environmental conditions and human encroachment on natural habitats bring human populations closer to novel sources of parasites, which might then develop into new emerging diseases. Diseases transmitted by host generalist vectors are of special interest due to their capacity to move pathogens into novel hosts. We hypothesize that humans using forests for recreation are exposed to a broad range of parasites from wild animals and their vectors. A corollary of this is that new vector-host, parasite-host, and vector-parasite associations could eventually develop. Thus, we expect to observe atypical vector-host associations. Using molecular bloodmeal analysis via amplification of the mtDNA COI gene we identified the vertebrate hosts of Culicoides (Diptera: Ceratopogonidae) species in a sub-urban forest of Southwestern Germany. Bloodmeals were also checked for haemosporidian infections by amplifying a fragment of the mtDNA cyt b gene. We identified a total of 20 Culicoides species, thirteen of which fed on humans. From 105 screened bloodmeals we obtained high quality sequences for 77 samples, 73 (94.8%) originated from humans, two from livestock (Bos taurus and Equus caballus), and two from wild birds (Sylvia atricapilla and Turdus merula). We found that four Culicoides species previously assumed to feed exclusively on either birds (C. kibunensis) or domestic mammals (C. chiopterus, C. deltus, C. scoticus) fed also on humans. A total of six Culicoides abdomens were infected with avian haemosporidian parasites (Plasmodium or Haemoproteus), four of those abdomens contained blood derived from humans. Our results suggest that parasites of wild animals may be transferred to humans through infectious bites of Culicoides vectors. Further, we show that Culicoides vectors believed to be a specialist on specific vertebrate groups can have plastic feeding preferences, and that Culicoides are susceptible to infection by Plasmodium parasites, though vector viability must still be experimentally demonstrated.
Econometric Analysis of Realized Covariation: High Frequency Based Covariance, Regression, and Correlation in Financial Economics

This paper analyses multivariate high frequency financial data using realised covariation. We provide a new asymptotic distribution theory for standard methods such as regression, correlation analysis and covariance. It will be based on a fixed interval of time (e.g. a day or week), allowing the number of high frequency returns during this period to go to infinity. Our analysis allows us to study how high frequency correlations, regressions and covariances change through time. In particular we provide confidence intervals for each of these quantities.
Insectivorous Bat Diversity and Habitat Use in a Subtropical Mosaic Urban Landscape

Bats are an important component of global biodiversity as they are species-rich taxon. Urbanisation is thought to have a negative impact on diversity because of the destruction of large areas of natural habitat, which many species are unable to survive. A small number of studies on the ecology of insectivorous bats in urban areas have revealed that urbanisation has had a negative impact on bat diversity, but these studies were largely confined to compact Old World cities in temperate regions of the northern hemisphere. Contemporary patterns of urbanisation often create a mosaic of novel habitats, which may enable many species to co-exist within the same landscape. Few studies have investigated the factors affecting bat diversity or habitat use at multiple scales within the same city, and patterns of bat diversity in sprawling cities are poorly known. This study investigated the insectivorous bat diversity of Brisbane, Australia, a subtropical city in which rapid recent growth has created a sprawling mosaic of different urban land cover types. Specifically, the major aims of this study were to determine how patterns of α diversity and species composition (β diversity) of Brisbane’s urban bat assemblage varied among four major habitat types within the city: high density residential, low density residential, parkland and native bushland remnants. Each of these habitat types differed in the nature and extent of both tree cover and built structures. This study also investigated how these components contributed to urban landscape (γ) diversity, and how environmental characteristics at both local and landscape scales influenced observed patterns of habitat use by insectivorous bats. To obtain adequate information to address this study’s aims, effective and cost-efficient survey techniques were required. Previous studies comparing the effectiveness of different bat survey techniques have been conducted in forested rather than urban landscapes. As urban landscapes are distinctly different, survey methods that were effective in forested landscapes may not be so in urban landscapes. Therefore this study also compared the effectiveness of two methods, bat detectors and harp traps, for surveying the richness and composition of the urban bat assemblage.