Molecular and Clinical Implications of Variant Repeats in Myotonic Dystrophy Type 1

Myotonic dystrophy type 1 (DM1) is one of the most variable monogenic diseases at phenotypic, genetic, and epigenetic level. The disease is multi-systemic with the age at onset ranging from birth to late age. The underlying mutation is an unstable expansion of CTG repeats in the DMPK gene, varying in size from 50 to >1000 repeats. Generally, large expansions are associated with an earlier age at onset. Additionally, the most severe, congenital DM1 form is typically associated with local DNA methylation. Genetic variability of DM1 mutation is further increased by its structural variations due to presence of other repeats (e.g., CCG, CTC, CAG). These variant repeats or repeat interruptions seem to confer an additional level of epigenetic variability since local DNA methylation is frequently associated with variant CCG repeats independently of the expansion size. The effect of repeat interruptions on DM1 molecular pathogenesis is not investigated enough. Studies on patients indicate their stabilizing effect on DMPK expansions because no congenital cases were described in patients with repeat interruptions, and the age at onset is frequently later than expected. Here, we review the clinical relevance of repeat interruptions in DM1 and genetic and epigenetic characteristics of interrupted DMPK expansions based on patient studies.     

The international publication productivity of Latin American countries in the economics and business administration fields

The present study compares the international publication productivityof Latin American countries in the fields of business administration and economicsfrom 1995 to 1999. Only four countries – Argentina, Brazil, Chile, andMexico – have a substantial research production in these areas. Amongthese countries, Chile showed the most favorable results according to variousindicators of publication productivity. This revised version was published online in June 2006 with corrections to the Cover Date.     

Ionic liquids as an attractive alternative solvent for thermal lens measurements

The use of ionic liquids (ILs) as a solvent for thermal lens measurements has been investigated. It was found that ILs provide a better medium for thermal lens measurements than water. Specifically, not only the ILs offer at least 20 times higher sensitivity than water but that the enhancement can be appropriately adjusted by changing either the cation or the anion of the ILs. For example, the sensitivity in [BMIm]+[Tf2N]- is approximately 26 times higher than in water. It can be increased up to 31 times by changing the anion to [PF6]- (i.e., [BMIm]+[PF6]-) or to 35 times by changing the cation to [OMIm]+ (i.e., [OMIm]+[Tf2N]-). In fact, the sensitivity of thermal lens measurements in ILs is comparable to those in volatile organic solvents such as benzene, carbon tetrachloride, and hexane. However, the ILs are more desirable as they have virtually no vapor pressure. Furthermore, additional sensitivity enhancement (up to 42 times higher than that in water) can be achieved by simply adding surfactants into the ILs. Based on the thermal conductivity (k) and dn/dT values, calculated from the measured thermal time constant tc and thermal lens strength theta, it is evident that the observed sensitivity enhancement by the ILs is due to their relatively better thermooptical properties. More specifically, the enhancement is due not to the relatively modest lowering of the thermal conductivity but rather to the substantial increase in their dn/dT values. Because of the relationship between dn/dT and drho/dT, it is expected that ILs can serve as an attractive and superior solvent not only for thermal lens measurements but also for other photothermal and photoacoustic techniques as well. Also equally important is the fact that the thermal lens technique in particular and photothermal techniques, in general, can offer a unique means to determine themooptical and thermal physical properties of the ILs (e.g., thermal conductivity, thermal diffusivity, and phase transition temperatures). This type of data is currently lacking but is of extreme importance for implementing ILs as a solvent in various industrial applications.     

Composite nanowire-based probes for magnetic resonance force microscopy

We present a nanowire-based methodology for the fabrication of ultrahigh sensitivity and resolution probes for atomic resolution magnetic resonance force microscopy (MRFM). The fabrication technique combines electrochemical deposition of multifunctional metals into nanoporous polycarbonate membranes and chemically selective electroless deposition of optical nanoreflector onto the nanowire. The completed composite nanowire structure contains all the required elements for an ultrahigh sensitivity and resolution MRFM sensor with (a) a magnetic nanowire segment providing atomic resolution magnetic field imaging gradients as well as large force gradients for high sensitivity, (b) a noble metal enhanced nanowire segment providing efficient scattering cross-section from a sub-wavelength source for optical readout of nanowire vibration, and (c) a nonmagnetic/nonplasmonic nanowire segment providing the cantilever structure for mechanical detection of magnetic resonance.     

Dynamic Measurements of the Thermal Conductivity of Insulators

Measurements of the thermal conductivity of insulators that are commonly used in civil engineering are as a rule performed using Pönsgen??s guarded hot-plate method under steady-state conditions. Achieving these steady-state conditions is a time consuming and relatively expensive procedure. Therefore, the application of a method that is less time consuming and less costly to common building insulating materials is of interest. The method should also have the accuracy and repeatability comparable to that of presently used methods. One such method is the transient hot-wire method (predominantly used for liquids, non-Newtonian fluids, plastics, semi-plastics, and similar materials), a dynamic method that uses a very thin pure platinum wire that functions as a thermal source in combination with a temperature sensor that detects temperature transients. This article describes the application of the transient hot-wire method to most commonly used building thermal insulating materials. The transient hot-wire measurements of the thermal conductivity were performed on many building material samples. For the sake of comparison, the thermal conductivity of samples made from the same materials was also tested using the stationary Pönsgen??s guarded hot-plate method. This article describes the comparison and evaluation of the measurement results obtained from both methods as well as the estimation of pertinent measurement uncertainties. The results are presented in graphical and numerical form in tables and diagrams for each type of thermal insulator.     

Dissecting learning tactics in MOOC using ordered network analysis

Background

Select and enact appropriate learning tactics that advance learning has been considered a critical set of skills to successfully complete highly flexible online courses, such as Massive open online courses (MOOCs). However, limited by analytic methods that have been used in the past, such as frequency distribution, sequence mining and process mining, we lack a deep, complete and detailed understanding of the learning tactics used by MOOC learners.

Objectives

In the present study, we proposed four major dimensions to better interpret and understand learning tactics, which are frequency, continuity, sequentiality and role of learning actions within tactics. The aim of this study was to examine to what extent can a new analytic technique, the ordered network analysis (ONA), deepen the understanding of MOOC learning tactics compared to using other methods.

Methods

In particular, we performed a fine-grained analysis of learning tactics detected from more than 4 million learning events in the behavioural trace data of 8788 learners who participated in a large-scale MOOC ‘Flipped Classroom’.

Results and Conclusions

We detected eight learning tactics, and then chose one typical tactic as an example to demonstrate how the ONA technique revealed all four dimensions and provided deeper insights into this MOOC learning tactic. Most importantly, based on the comparison with different methods such as process mining, we found that the ONA method provided a unique opportunity and novel insight into the roles of different learning actions in tactics which was neglected in the past.

Takeaway

In summary, we conclude that ONA is a promising technique that can benefit the research on learning tactics, and ultimately benefit MOOC learners by strengthening the strategic support.     

Automatic identification of knowledge-transforming content in argument essays developed from multiple sources

Developing knowledge-transforming skills in writing may help students increase learning by actively building knowledge, regardless of the domain. However, many undergraduate students struggle to transform knowledge when drafting essays based on multiple sources. Writing analytics can be used to scaffold knowledge transforming as writers bring evidence to bear in supporting claims. We investigated how to automatically identify sentences representing knowledge transformation in argumentative essays. A synthesis of cognitive theories of writing and Bloom's typology identified 22 linguistic features to model processes of knowledge transforming in a corpus of 38 undergraduates' essays. Findings indicate undergraduates mostly paraphrase or copy information from multiple sources rather than engage deeply with sources' content. Eight linguistic features were important for discriminating evidential sentences as telling versus transforming source knowledge. We trained a machine learning algorithm that accurately classified nearly three of four evidential sentences as knowledge-telling or knowledge-transforming, offering potential for use in future research.