Distal motor latency and residuallatency as sensitive markersof anti-MAG polyneuropathy

Abstract.: There is debate whether the terminal latency index (TLI) is a sensitive marker for polyneuropathy with anti-myelinassociated-glycoprotein antibodies (anti-MAGP). We examined 6 patients with an anti-MAGP and 6 patients with a chronic inflammatory demyelinating polyneuropathy (CIDP). The electroneurographic features studied were: distal compound motor action potential (CMAP), distal motor latency (DML), motor conduction velocity (MCV) elbow to wrist (distal MCV), MCV axilla to elbow (proximal MCV), MCV distal/proximal, terminal latency index (TLI), residual latency (RL), F-wave, and modified F ratio.We found significant differences between anti-MAGP and CIDP for DML and for RL.No significant differences were found for TLI and the other measures. The TLI values were not significant probably because our patients had a longer duration of disease,which supports the hypothesis of a distal to proximal progression of conduction slowing over time. We propose that a residual latency >4.0 and a distal motor latency >7.0 are strongly suggestive for an anti- MAG

AIML and sequence-to-sequence models to build artificial intelligence chatbots: insights from a comparative analysis

A chatbot is a software that is able to autonomously communicate with a human being through text and due to its usefulness, an increasing number of businesses are implementing such tools in order to provide timely communication to their clients. In the past, whilst literature has focused on implementing innovative chatbots and the evaluation of such tools, limited studies have been done to critically comparing such conversational systems. In order to address this gap, this study critically compares the Artificial Intelligence Mark-up Language (AIML), and Sequence-to-Sequence models for building chatbots. In this endeavor, two chatbots were developed to implement each model and were evaluated using a mixture of glass box and black box evaluation, based on 3 metrics, namely, user’s satisfaction, the information retrieval rate, and the task completion rate of each chatbot. Results showed that the AIML chatbot ensured better user satisfaction, and task completion rate, while the Sequence-to-Sequence model had better information retrieval rate

Designing Chatbots for Crises: A Case Study Contrasting Potential and Reality

Chatbots are becoming ubiquitous technologies, and their popularity and adoption are rapidly spreading. The potential of chatbots in engaging people with digital services is fully recognised. However, the reputation of this technology with regards to usefulness and real impact remains rather questionable. Studies that evaluate how people perceive and utilise chatbots are generally lacking. During the last Kenyan elections, we deployed a chatbot on Facebook Messenger to help people submit reports of violence and misconduct experienced in the polling stations. Even though the chatbot was visited by more than 3,000 times, there was a clear mismatch between the users’ perception of the technology and its design. In this paper, we analyse the user interactions and content generated through this application and discuss the challenges and directions for designing more effective chatbots

Human microRNA hsa-miR-125a-5p interferes with expression of hepatitis B virus surface antigen

MicroRNAs are small non-coding RNAs that modulate gene expression at post-transcriptional level, playing a crucial role in cell differentiation and development. Recently, some reports have shown that a limited number of mammalian microRNAs are also involved in anti-viral defense. In this study, the analysis of the hepatitis B virus (HBV) genome by the computer program MiRanda led to the identification of seven sites that are potential targets for human liver microRNAs. These sites were found to be clustered in a 995-bp segment within the viral polymerase ORF and the overlapping surface antigen ORF, and conserved among the most common HBV subtypes. The HBV genomic targets were then subjected to a validation test based on cultured hepatic cells (HepG2, HuH-7 and PLC/PRF/5) and luciferase reporter genes. In this test, one of the selected microRNAs, hsa-miR-125a-5p, was found to interact with the viral sequence and to suppress the reporter activity markedly. The microRNA was then shown to interfere with the viral translation, down-regulating the expression of the surface antigen. Overall, these results support the emerging concept that some mammalian microRNAs play a role in virus-host interaction. Furthermore, they provide the basis for the development of new strategies for anti-HBV intervention

The Hepatitis B Virus Ribonuclease H Is Sensitive to Inhibitors of the Human Immunodeficiency Virus Ribonuclease H and Integrase Enzymes

Nucleos(t)ide analog therapy blocks DNA synthesis by the hepatitis B virus (HBV) reverse transcriptase and can control the infection, but treatment is life-long and has high costs and unpredictable long-term side effects. The profound suppression of HBV by the nucleos(t)ide analogs and their ability to cure some patients indicates that they can push HBV to the brink of extinction. Consequently, more patients could be cured by suppressing HBV replication further using a new drug in combination with the nucleos(t)ide analogs. The HBV ribonuclease H (RNAseH) is a logical drug target because it is the second of only two viral enzymes that are essential for viral replication, but it has not been exploited, primarily because it is very difficult to produce active enzyme. To address this difficulty, we expressed HBV genotype D and H RNAseHs in E. coli and enriched the enzymes by nickel-affinity chromatography. HBV RNAseH activity in the enriched lysates was characterized in preparation for drug screening. Twenty-one candidate HBV RNAseH inhibitors were identified using chemical structure-activity analyses based on inhibitors of the HIV RNAseH and integrase. Twelve anti-RNAseH and anti-integrase compounds inhibited the HBV RNAseH at 10 μM, the best compounds had low micromolar IC50 values against the RNAseH, and one compound inhibited HBV replication in tissue culture at 10 μM. Recombinant HBV genotype D RNAseH was more sensitive to inhibition than genotype H. This study demonstrates that recombinant HBV RNAseH suitable for low-throughput antiviral drug screening has been produced. The high percentage of compounds developed against the HIV RNAseH and integrase that were active against the HBV RNAseH indicates that the extensive drug design efforts against these HIV enzymes can guide anti-HBV RNAseH drug discovery. Finally, differential inhibition of HBV genotype D and H RNAseHs indicates that viral genetic variability will be a factor during drug development. © 2013 Tavis et al

The PDZ Protein Canoe/AF-6 Links Ras-MAPK, Notch and Wingless/Wnt Signaling Pathways by Directly Interacting with Ras, Notch and Dishevelled

Over the past few years, it has become increasingly apparent that signal transduction pathways are not merely linear cascades; they are organized into complex signaling networks that require high levels of regulation to generate precise and unique cell responses. However, the underlying regulatory mechanisms by which signaling pathways cross-communicate remain poorly understood. Here we show that the Ras-binding protein Canoe (Cno)/AF-6, a PDZ protein normally associated with cellular junctions, is a key modulator of Wingless (Wg)/Wnt, Ras-Mitogen Activated Protein Kinase (MAPK) and Notch (N) signaling pathways cross-communication. Our data show a repressive effect of Cno/AF-6 on these three signaling pathways through physical interactions with Ras, N and the cytoplasmic protein Dishevelled (Dsh), a key Wg effector. We propose a model in which Cno, through those interactions, actively coordinates, at the membrane level, Ras-MAPK, N and Wg signaling pathways during progenitor specification

EU Cooperation with Non-Member Neighboring Countries: The Principle of Variable Geometry

The European Union (EU) represents a large and highly integrated bloc which contributed 19.4% of global GDP and over 30% of global exports in 2012. As of July 1, 2013 it consists of 28 member states. All of them belong to the customs union and the Single European Market (SEM) in which most formal and informal barriers to the free movement of goods, services, people and capital have been removed. In addition, most members share a common currency (Euro) and form a free-travel Schengen zone. The important policy areas such as external trade, customs, competition, other regulations related to SEM, monetary policy (in the case of the Eurozone), certain iscal and other macroeconomic policies, part of indirect taxation, research, energy policy, etc. have been transferred to the competence of supranational EU bodies. Several other questions such as immigration and asylum, visas, common border management, justice and home affairs, and foreign and security policy remain subject to coordination and common decisions. [...