Miracle-dz/UniFAR-FTUs huggingface dataset:
Reversible inhibition of GABAA receptors by α7‐containing nicotinic receptors on the vertebrate postsynaptic neurons

Nicotinic acetylcholine receptors (nAChRs) are expressed throughout the central nervous system and influence a variety of higher order functions including learning and memory. While the effects of presynaptic nAChRs on transmitter release have been well documented, little is known about possible postsynaptic actions. A major species of neuronal nAChRs contains the α7 gene product and has a high relative permeability to calcium. Both on rodent hippocampal interneurons and on chick ciliary ganglion neurons these α7‐nAChRs are often closely juxtaposed to GABAA receptors. We show here that in both cases activation of α7‐nAChRs on the postsynaptic neuron acutely down‐regulates GABA‐induced currents. Nicotine application to dissociated ciliary ganglion neurons diminished subsequent GABAA receptor responses to GABA. The effect was blocked by α7‐nAChR antagonists, by chelation of intracellular Ca2+ with BAPTA, and by inhibition of both Ca2+–calmodulin‐dependent protein kinase II and mitogen‐activated protein kinase. A similar outcome was obtained in the hippocampus where electrical stimulation to activate cholinergic fibres reduced the amplitude of subsequent GABAA receptor‐mediated inhibitory postsynaptic currents. The reduction showed the same calcium and kinase dependence seen in ciliary ganglion neurons and was absent in hippocampal slices from α7‐nAChR knockout mice. Moreover, α7‐nAChR blockade in hippocampal slices reduced rundown of GABAA receptor‐mediated whole‐cell responses, indicating ongoing endogenous modulation. The results demonstrate regulation of GABAA receptors by α7‐nAChRs on the postsynaptic neuron and identify a new mechanism by which nicotinic cholinergic signalling influences nervous system function.
Permissive Secondary Mutations Enable the Evolution of Influenza Oseltamivir Resistance

Influenza Escape Tricks Tamiflu, or oseltamivir, has been extensively stockpiled by several governments in anticipation of a dangerous influenza pandemic. So far, its large-scale use has not been required, but, despite this, resistance has emerged in seasonal strains mediated by a single point mutation of histidine to tyrosine in the 274 residue (H274Y) of neuraminidase. When the resistant virus was first discovered in 1998, it grew poorly, but by 2008 the virus was reinvigorated and the mutation had spread worldwide in seasonal influenza. So what happened that improved viral fitness so radically? Bloom et al. (p. 1272; see the Perspective by Holmes) show that the H274Y mutation hinders the folding of the neuraminidase enzyme. In the more vigorous recent oseltamivir-resistant isolates, other mutations compensate for the deleterious effect of H274Y and restore fitness to the virus. Compensatory mutations offset the structural costs of acquiring a drug-resistance mutation in a virus. The His274→Tyr274 (H274Y) mutation confers oseltamivir resistance on N1 influenza neuraminidase but had long been thought to compromise viral fitness. However, beginning in 2007–2008, viruses containing H274Y rapidly became predominant among human seasonal H1N1 isolates. We show that H274Y decreases the amount of neuraminidase that reaches the cell surface and that this defect can be counteracted by secondary mutations that also restore viral fitness. Two such mutations occurred in seasonal H1N1 shortly before the widespread appearance of H274Y. The evolution of oseltamivir resistance was therefore enabled by “permissive” mutations that allowed the virus to tolerate subsequent occurrences of H274Y. An understanding of this process may provide a basis for predicting the evolution of oseltamivir resistance in other influenza strains.
Detecting greedy behavior by linear regression and watchdog in vehicular ad hoc networks

Vehicular Ad hoc Networks (VANETs) aim to provide a high safety level to road users and enhance driving conditions for drivers. Thus, they are exposed to several kinds of attacks such as Denial Of Service attacks (DOS), especially the greedy behavior which affects services availability of authentic users. Greedy behavior attack has been well studied for Wireless local area networks (WLAN) and for Mobile Ad hoc Networks (MANETs). However, this attack is less studied for the case of VANETs. Indeed, the detection of a greedy behavior in quasi-static network is much easier than that in a network with low or high mobility. The aim of this paper is to detect greedy behavior in VANETs. More specifically, we propose a new detection algorithm based on a statistical method, linear regression and watchdog software. This algorithm distinguishes the existence or not of a greedy behavior and suspects the compromised nodes using a new appropriate defined metrics. The proposed algorithm is passive, it can be executed by any node in the network and does not require any modification of the IEEE 802.11p protocol.
Online workbenches for neural network connections

The nervous system is the most complex object we know of. It is a spatially distributed, functionally differentiated network formed by axonal connections between defined neuron populations and effector cells. Computer science provides exciting new tools for archiving, analyzing, synthesizing, and modeling on the Web vast amounts of frequently conflicting and incomplete qualitative and quantitative data about the organization and molecular mechanisms of neural networks. To optimize conceptual advances in systems neuroscience, it is important for the research and publishing communities to embrace three exercises: using defined nomenclatures; populating databases; and providing feedback to developers about improved design, performance, and functionality of knowledge management systems and associated visualization tools. J. Comp. Neurol. 500:807–814, 2007. © 2006 Wiley‐Liss, Inc.
Advances in the Molecular Analysis of Breast Cancer: Pathway Toward Personalized Medicine.

BACKGROUND Breast cancer is a heterogeneous disease that encompasses a wide range of clinical behaviors and histological and molecular variants. It is the most common type of cancer affecting women worldwide and is the second leading cause of cancer death. METHODS A comprehensive literature search was performed to explore the advances in molecular medicine related to the diagnosis and treatment of breast cancer. RESULTS During the last few decades, advances in molecular medicine have changed the landscape of cancer treatment as new molecular tests complement and, in many instances, exceed traditional methods for determining patient prognosis and response to treatment options. Personalized medicine is becoming the standard of care around the world. Developments in molecular profiling, genomic analysis, and the discovery of targeted drug therapies have significantly improved patient survival rates and quality of life. CONCLUSIONS This review highlights what pathologists need to know about current molecular tests for classification and prognostic/ predictive assessment of breast carcinoma as well as their role as part of the medical team.
SPEEDING UP KINESIN‐DRIVEN MICROTUBULE GLIDING IN VITRO BY VARIATION OF COFACTOR COMPOSITION AND PHYSICOCHEMICAL PARAMETERS *

So far, there has been a discrepancy between the velocities of kinesin‐dependent microtubule motility measured in vitro and within cells. By changing ATP, Mg2+, and kinesin concentrations, pH and ionic strength, we tried to find conditions that favour microtubule gliding across kinesin‐covered glass surfaces. For porcine brain kinesin, we found that raising the molar Mg2+/ATP ratio can substantially elevate gliding velocity. Gliding became also faster after temperature elevation or lowering the number of kinesin molecules bound to the glass surface. The highest mean gliding velocity (1.8μm/s±0.09μm/s), approaching velocities measured for anterograde transport in vivo, was achieved by combination of favourable factors (2.5m m ATP, 12.5m m Mg2+, 37°C, 450 kinesin molecules/μm2).
Follicular lymphomas in pediatric patients.

The clinicopathologic features of twenty cases of follicular lymphoma (FL) in pediatric patients are described. Fifteen boys and five girls were 2 to 20 yr (mean 10 yr) of age at diagnosis. In ten cases (50%) the lymphoma was localized in lymph nodes and in ten cases (50%) in extranodal sites. Fifteen patients had stage I, two stage II and three stage III disease at the time of presentation. The faucial tonsils were the primary site in seven cases, other head and neck sites in five, inguinal lymph nodes in four and possibly another, and the abdomen in two. Six cases (30%) were classified as follicular small cleaved cell type (FSCC), five (25%) as follicular mixed small cleaved and large cell (FMC), and nine (45%) as follicular large cell (FLC). The architectural pattern was purely follicular (F) in five cases (20%), predominantly follicular (F greater than D) in six (30%), follicular and diffuse (F = D) in six (30%) and predominantly diffuse (F less than D) in three (15%). In one case a progression from F greater than D LC to F less than D LC was documented. All patients attained complete remission (CR). One died of acute lymphoblastic leukemia 7 yr after the original diagnosis of FSCC non-Hodgkin's lymphoma (NHL), but the others are all alive and free of disease with a follow-up ranging from 6 mo to 16 yr (median 4 yr). In three patients therapy was initially deferred with no known adverse influence on outcome. (ABSTRACT TRUNCATED AT 250 WORDS)
Generalization of the Ideal Crack Model for an Arrayed Eddy Current Sensor

The ideal crack model is generalized to an arrayed eddy current sensor with the assumption that its coils are connected in series and fed by a current source. We associate the superposition theorem to the reciprocity theorem to reduce the 3-D electromagnetic problem to a 2-D axisymmetrical one, combined with the evaluation of an integral equation. We derive the formula that permits the evaluation of the impedance variation of each coil, taking account of the interaction between the coils.
Envirodevonomics: A Research Agenda for a Young Field

Environmental quality in many developing countries is poor and generates substantial health and productivity costs. However, existing measures of willingness to pay for environmental quality improvements indicate low valuations by affected households. This paper argues that this seeming paradox is the central puzzle at the intersection of environmental and development economics: Given poor environmental quality and high health burdens in developing countries, why is WTP so low? We develop a conceptual framework for understanding this puzzle and propose four potential explanations: (1) due to low income levels, individuals value increases in income more than marginal improvements in environmental quality, (2) the marginal costs of environmental quality improvements are high, (3) political economy factors undermine efficient policy-making, and (4) market failures such as weak property rights and missing capital markets drive a wedge between true and revealed willingness to pay for environmental quality. We review the available literature on each explanation and discuss how the framework also applies to climate change, which is perhaps the most important issue at the intersection of environment and development economics. The paper concludes with a list of promising and unanswered research questions for the emerging sub-field of "envirodevonomics. "
Analysis of the Kinematical Demands Imposed on Top-Class Assistant Referees During Competitive Soccer Matches

The aim of this study was to describe the kinematical demands placed on soccer assistant referees during the 2003 U-17 World Championship, and to examine the relationship between the results in the fitness tests adopted by FIFA and match activities. Twenty-two international-level assistant referees were observed during 12 matches and computerized analysis of match activities was performed using a two-dimensional photogrammetric video analysis system based on DLT (direct lineal transformation) algorithms. Before the start of the tournament, the assistant referees completed a 2 × 50-m sprint test and a 12-minute run test. Assistant referees covered on average 6137 ± 539 m during the matches, with 20% of the total distance covered at high velocities (speeds faster than 13 km·h−1). During the second half, time spent standing still increased (P < 0.01) and distance covered jogging (P < 0.05), cruising (P < 0.01) and moving sideways (P < 0.001) decreased. The score in the 12-minute run test showed a low correlation with the entire match distance (r = 0.24; P > 0.05) and with the time spent exercising at a high intensity (r = 0.35; P > 0.05). The 50-m sprint time was not significantly correlated (r = −0.38; P > 0.05) with time spent within the high-intensity activities category. The results of this study demonstrate that assistant referees experience unique kinematical demands during soccer officiating and that the score in the battery of fitness tests adopted by FIFA was not correlated to match activities.
DNS-based Load Balancing for Web Services

A key issue for good performance of geographically replicated web services is the efficiency of the load balancing mechanism used to distribute client requests among the replicas. This work revisits the research on DNS-based load balancing mechanisms considering a SOA (Service-Oriented Architecture) scenario. In this kind of load balancing solution the Authoritative DNS (ADNS) of the distributed web service performs the role of the client request scheduler, redirecting the clients to one of the server replicas, according to some load distribution policy. This paper proposes a new policy that combines client load information and server load information in order to reduce the negative effects of the DNS caching on the load balancing. We also present the results obtained through an experimental tesbed built on basis of the TPC-W benchmark.
Comparison of Artificial Neural Network with Logistic Regression as Classification Models for Variable Selection for Prediction of Breast Cancer Patient Outcomes

The aim of this study was to compare multilayer perceptron neural networks (NNs) with standard logistic regression (LR) to identify key covariates impacting on mortality from cancer causes, disease-free survival (DFS), and disease recurrence using Area Under Receiver-Operating Characteristics (AUROC) in breast cancer patients. From 1996 to 2004, 2,535 patients diagnosed with primary breast cancer entered into the study at a single French centre, where they received standard treatment. For specific mortality as well as DFS analysis, the ROC curves were greater with the NN models compared to LR model with better sensitivity and specificity. Four predictive factors were retained by both approaches for mortality: clinical size stage, Scarff Bloom Richardson grade, number of invaded nodes, and progesterone receptor. The results enhanced the relevance of the use of NN models in predictive analysis in oncology, which appeared to be more accurate in prediction in this French breast cancer cohort.
18 A game theoretic framework for rate allocation and charging of Available Bit Rate { ABR ) connections in ATM networks

In this paper we present an abstract, rigorous game-theoretic framework for rate-based control of Available Bit Rate (ABR) services in ATM networks. The framework is based on the idea of the Nash arbitration scheme in cooperative game theory which not only provides the rate settings of users which are Pareto optimal from the network point of view of but are also consistent with the fairness axioms of game theory. We first consider the centralized problem and then show that this procedure can be de-centralized such that users can perform the optimization locally such that the overall rates are network optimal. We then consider the problem of charging of ABR connections considering users' valuations for the best-effort service. We propose a flat-rate charging policy such that the total network revenue is maximum. we show that the above arbitration set-up can be used to characterize a rate allocaBroadband Communications P. Kiihn & R. Ulrich (Eds.) © 1998 IFIP. Published by Chapman & Hall . E "iii c ::;) Usage-based charging schemes for broadband network
A MAGNETIC-BEAD-BASED IMMUNOASSAY FOR RAPID PURIFICA- TION AND DETECTION OF INFLUENZA VIRUSES UTILIZING SUCTION- TYPE MICROFLUIDIC SYSTEMS

The study presents a magnetic-bead-based, suction-type microfluidic system for rapid purification and detection of influenza viral particles from clinical serum samples. Target influenza viral particles in the clinical sample can be first captured by the antibody-conjugated magnetic beads, followed by isolating the viral particles from the bio-samples with the incorporation of a permanent magnet and a suction-type microfluidic control module. Then, another specific secondary developing antibodies labeled with fluorescent dyes were employed to recognize the surface antigen of the virusbound magnetic complexes. Finally, the fluorescent-labeled magnetic complexes can be then detected and analyzed by utilizing an optical detection module. The entire process can be performed automatically within in 30 minutes. The development of the integrated microfluidic chip may provide a promising platform for fast diagnosis of influenza infection.
Kinesin: a molecular motor with a spring in its step

A key step in the processive motion of two–headed kinesin along a microtubule is the ‘docking’ of the neck linker that joins each kinesin head to the motor's dimerized coiled–coil neck. This process is similar to the folding of a protein β–hairpin, which starts in a highly mobile unfolded state that has significant entropic elasticity and finishes in a more rigid folded state. We therefore suggest that neck–linker docking is mechanically equivalent to the thermally activated shortening of a spring that has been stretched by an applied load. This critical tension–dependent step utilizes Brownian motion and it immediately follows the binding of ATP, the hydrolysis of which provides the free energy that drives the kinesin cycle. A simple three–state model incorporating neck–linker docking can account quantitatively for both the kinesin force–velocity relation and the unusual tension–dependence of its Michaelis constant. However, we find that the observed randomness of the kinesin motor requires a more detailed four–state model. Monte Carlo simulations of single–molecule stepping with this model illustrate the possibility of sub–8 nm steps, the size of which is predicted to vary linearly with the applied load.
Co-delivery of siRNA and an anticancer drug for treatment of multidrug-resistant cancer.

AIMS To develop a novel nanomedicine approach for the treatment of multidrug-resistant (MDR) cancer by combining an anticancer drug and suppressors of cellular resistance within one multifunctional nanocarrier-based delivery system (NDS). MATERIALS & METHODS The NDS consisted of cationic liposomes (carrier, 100-140 nm), doxorubicin (DOX, anticancer drug), siRNA targeted to MRP1 and BCL2 mRNA (suppressors of pump and nonpump cellular-resistance, respectively). The resulting approximately 500 nm complex has a zeta potential of +4 mV. RESULTS & DISCUSSION The NDS provides an effective co-delivery of DOX and siRNA as well as cell-death induction and suppression of cellular resistance in MDR lung cancer cells. CONCLUSION We demonstrate NDS-enhanced efficiency of chemotherapy to a level that cannot be achieved by applying its components separately.
Reducing Contrast Makes Speeds in a Video-Based Driving Simulator Harder to Discriminate as Well as Making Them Appear Slower

We investigated the effect of reducing image contrast on speed perception using a video-based driving simulator in which participants viewed pairs of scenes and were asked to judge whether the second scene was faster or slower than the first scene. We predicted two outcomes: (i) that vehicle speeds would become harder to discriminate, and (ii) that vehicle speeds would appear slower. There is previous evidence confirming the latter prediction in a less realistic computer-based driving simulation, but none demonstrating the former. Our results supported both predictions, each of which may have traffic-safety implications when reduced-contrast conditions are experienced in real life, such as with fog or when the driver has cataracts.
Prevalence of Increased Esophageal Muscle Thickness in Patients With Esophageal Symptoms

BACKGROUND:Patients with achalasia, diffuse esophageal spasm (DES), and nutcracker esophagus have a thicker muscularis propria than normal subjects. The goal of our study was to determine the prevalence of increased muscle thickness in a group of unselected patients referred to the esophageal function laboratory for evaluation of the symptoms.METHODS:We studied 40 normal subjects and 94 consecutive patients. Manometry and ultrasound images were recorded concurrently, using a special custom-built catheter. Esophageal muscle thickness and muscle cross-sectional area were measured at 2 and 10 cm above the lower esophageal sphincter (LES). Patients were assigned manometric diagnosis and determination was made if they had increased muscle thickness and muscle cross-sectional area.RESULTS:Nearly all patients with well-defined spastic motor disorders, i.e., achalasia, DES, and nutcracker esophagus, revealed (a) an increase in the muscle thickness/cross-sectional area, (b) increase in esophageal muscle thickness/cross-sectional area was also seen, albeit at a lower prevalence rate, in patients with less well-characterized manometric abnormalities, i.e., hypertensive LES, impaired LES relaxation, and ineffective esophageal motility, and (c) 24% of patients with esophageal symptoms but normal manometry were also found to have an increase in muscle thickness/cross-sectional area. Dysphagia was more likely, and heartburn less likely in patients with increased muscle thickness, but there were no differences in chest pain and regurgitation symptoms between the groups.CONCLUSION:We describe, for the first time, increased muscle thickness in patients with esophageal symptoms and normal manometry. We suggest that increased esophageal muscle thickness is likely to be an important marker of esophageal motor dysfunction.