Quantification of functional hand grip using electromyography and inertial sensor-derived accelerations: Clinical implications

Background Assessing hand injury is of great interest given the level of involvement of the hand with the environment. Knowing different assessment systems and their limitations generates new perspectives. The integration of digital systems (accelerometry and electromyography) as a tool to supplement functional assessment allows the clinician to know more about the motor component and its relation to movement. Therefore, the purpose of this study was the kinematic and electromyography analysis during functional hand movements. Method Ten subjects carried out six functional movements (terminal pinch, termino-lateral pinch, tripod pinch, power grip, extension grip and ball grip). Muscle activity (hand and forearm) was measured in real time using electromyograms, acquired with the Mega ME 6000, whilst acceleration was measured using the AcceleGlove. Results Electrical activity and acceleration variables were recorded simultaneously during the carrying out of the functional movements. The acceleration outcome variables were the modular vectors of each finger of the hand and the palm. In the electromyography, the main variables were normalized by the mean and by the maximum muscle activity of the thenar region, hypothenar, first interosseous dorsal, wrist flexors, carpal flexors and wrist extensors. Conclusions Knowing muscle behavior allows the clinician to take a more direct approach in the treatment. Based on the results, the tripod grip shows greater kinetic activity and the middle finger is the most relevant in this regard. Ball grip involves most muscle activity, with the thenar region playing a fundamental role in hand activity. Clinical relevance Relating muscle activation, movements, individual load and displacement offers the possibility to proceed with rehabilitation by individual component.

An evaluation of potential candidate genes involved in salinity tolerance in striped catfish (Pangasianodon hypopthalmus) using an RNA-SEQ approach

The project investigated the molecular response of Tra catfish (Pangasianodon hypophthalmus) to elevated salinity conditions. We employed Next generation sequencing platform to evaluate differential gene expression profiles of key genes under two salinity conditions. Results of the current project can form the basis for further studies to confirm the functional roles of specific genes that influence salinity tolerance in the target species and more broadly in other freshwater teleost fishes. Ultimately, the approach can contribute to developing superior culture stocks of the target species.

Investigating a disciplinary approach to literacy learning in a secondary school

This paper presents findings from a Design-Based Research (DBR) project undertaken in a large regional high school in Queensland. The study focused on an intervention involving explicit teaching using systemic functional grammar in assessed writing across two Year 8 subjects: English and History. The study’s findings demonstrate that, despite efforts at the whole school and classroom level to support a disciplinary literacy approach to subject learning, there are considerable constraints that need to be considered and overcome in order for students to develop appropriate writing capabilities for particular discipline areas.

A multimarker approach to diagnose and stratify heart failure

Background We have previously demonstrated that circulating NT-proBNP is truncated at the N and C termini. Aims of this study are three-fold: firstly to determine whether the NT-proBNP levels correlate with NYHA functional classes when measuring with different antibody pairs; secondly to evaluate the diagnostic potential of ProBNP and; thirdly to investigate whether combining NT-proBNP assays with or without ProBNP would lead to better diagnostic accuracies. Methods Plasma samples were collected from healthy controls (n = 52) and HF patients (n = 46). Customized AlphaLISA® immunoassays were developed and validated to measure the concentrations of proBNP and NT-proBNP (with antibodies targeting 13–45, 13–76, 28–76). The diagnostic performance and predictive value of proBNP and NT-proBNP assays and their combinations were evaluated. Results Plasma proBNP assay showed acceptable diagnostic performance. NT-proBNP13–76 assay is useful in diagnosing and stratifying HF patients. The diagnostic performance of NT-proBNP13–76 demonstrated improvement over commercial NT-proBNP tests. The combination of NT-proBNP13–76 with NT-proBNP28–76 assays gave the best diagnostic assay performance. Conclusion Our results demonstrate that while there is major heterogeneity in circulating NT-proBNP, specific epitopes of the peptides are extraordinarily stable, providing ideal targets for clinically useful diagnostic assays. Future new clinical diagnostic clinical trials should include a multimarker approach rather than using a single marker to diagnose HF.

Increasing functional variability in the preparatory phase of the takeoff improves elite springboard diving performance

PURPOSE: Previous research demonstrating that specific performance outcome goals can be achieved in different ways is functionally significant for springboard divers whose performance environment can vary extensively. This body of work raises questions about the traditional approach of balking (terminating the takeoff) by elite divers aiming to perform only identical, invariant movement patterns during practice. METHOD: A 12-week training program (2 times per day; 6.5 hr per day) was implemented with 4 elite female springboard divers to encourage them to adapt movement patterns under variable takeoff conditions and complete intended dives, rather than balk. RESULTS: Intraindividual analyses revealed small increases in variability in the board-work component of each diver's pretraining and posttraining program reverse-dive takeoffs. No topological differences were observed between movement patterns of dives completed pretraining and posttraining. Differences were noted in the amount of movement variability under different training conditions (evidenced by higher normalized root mean square error indexes posttraining). An increase in the number of completed dives (from 78.91%-86.84% to 95.59%-99.29%) and a decrease in the frequency of balked takeoffs (from 13.16%-19.41% to 0.63%-4.41%) showed that the elite athletes were able to adapt their behaviors during the training program. These findings coincided with greater consistency in the divers' performance during practice as scored by qualified judges. CONCLUSION: Results suggested that on completion of training, athletes were capable of successfully adapting their movement patterns under more varied takeoff conditions to achieve greater consistency and stability of performance outcomes.

Fatigue Laws Via Functional Equations

In routine industrial design, fatigue life estimation is largely based on S-N curves and ad hoc cycle counting algorithms used with Miner's rule for predicting life under complex loading. However, there are well known deficiencies of the conventional approach. Of the many cumulative damage rules that have been proposed, Manson's Double Linear Damage Rule (DLDR) has been the most successful. Here we follow up, through comparisons with experimental data from many sources, on a new approach to empirical fatigue life estimation (A Constructive Empirical Theory for Metal Fatigue Under Block Cyclic Loading', Proceedings of the Royal Society A, in press). The basic modeling approach is first described: it depends on enforcing mathematical consistency between predictions of simple empirical models that include indeterminate functional forms, and published fatigue data from handbooks. This consistency is enforced through setting up and (with luck) solving a functional equation with three independent variables and six unknown functions. The model, after eliminating or identifying various parameters, retains three fitted parameters; for the experimental data available, one of these may be set to zero. On comparison against data from several different sources, with two fitted parameters, we find that our model works about as well as the DLDR and much better than Miner's rule. We finally discuss some ways in which the model might be used, beyond the scope of the DLDR.

Functional correlation of bacterial LuxS with their quaternary associations: interface analysis of the structure networks

Background The genome of a wide variety of prokaryotes contains the luxS gene homologue, which encodes for the protein S-ribosylhomocysteinelyase (LuxS). This protein is responsible for the production of the quorum sensing molecule, AI-2 and has been implicated in a variety of functions such as flagellar motility, metabolic regulation, toxin production and even in pathogenicity. A high structural similarity is present in the LuxS structures determined from a few species. In this study, we have modelled the structures from several other species and have investigated their dimer interfaces. We have attempted to correlate the interface features of LuxS with the phenotypic nature of the organisms. Results The protein structure networks (PSN) are constructed and graph theoretical analysis is performed on the structures obtained from X-ray crystallography and on the modelled ones. The interfaces, which are known to contain the active site, are characterized from the PSNs of these homodimeric proteins. The key features presented by the protein interfaces are investigated for the classification of the proteins in relation to their function. From our analysis, structural interface motifs are identified for each class in our dataset, which showed distinctly different pattern at the interface of LuxS for the probiotics and some extremophiles. Our analysis also reveals potential sites of mutation and geometric patterns at the interface that was not evident from conventional sequence alignment studies. Conclusion The structure network approach employed in this study for the analysis of dimeric interfaces in LuxS has brought out certain structural details at the side-chain interaction level, which were elusive from the conventional structure comparison methods. The results from this study provide a better understanding of the relation between the luxS gene and its functional role in the prokaryotes. This study also makes it possible to explore the potential direction towards the design of inhibitors of LuxS and thus towards a wide range of antimicrobials.

A pseudo-dynamical systems approach to a class of inverse problems in engineering

A pseudo-dynamical approach for a class of inverse problems involving static measurements is proposed and explored. Following linearization of the minimizing functional associated with the underlying optimization problem, the new strategy results in a system of linearized ordinary differential equations (ODEs) whose steady-state solutions yield the desired reconstruction. We consider some explicit and implicit schemes for integrating the ODEs and thus establish a deterministic reconstruction strategy without an explicit use of regularization. A stochastic reconstruction strategy is then developed making use of an ensemble Kalman filter wherein these ODEs serve as the measurement model. Finally, we assess the numerical efficacy of the developed tools against a few linear and nonlinear inverse problems of engineering interest.

Estimation of light interception in research environments: A joint approach using directional light sensors and 3D virtual plants applied to sunflower (Helianthus annuus) and Arabidopsis thaliana in natural and artificial conditions

Light interception is a major factor influencing plant development and biomass production. Several methods have been proposed to determine this variable, but its calculation remains difficult in artificial environments with heterogeneous light. We propose a method that uses 3D virtual plant modelling and directional light characterisation to estimate light interception in highly heterogeneous light environments such as growth chambers and glasshouses. Intercepted light was estimated by coupling an architectural model and a light model for different genotypes of the rosette species Arabidopsis thaliana (L.) Heynh and a sunflower crop. The model was applied to plants of contrasting architectures, cultivated in isolation or in canopy, in natural or artificial environments, and under contrasting light conditions. The model gave satisfactory results when compared with observed data and enabled calculation of light interception in situations where direct measurements or classical methods were inefficient, such as young crops, isolated plants or artificial conditions. Furthermore, the model revealed that A. thaliana increased its light interception efficiency when shaded. To conclude, the method can be used to calculate intercepted light at organ, plant and plot levels, in natural and artificial environments, and should be useful in the investigation of genotype-environment interactions for plant architecture and light interception efficiency. This paper originates from a presentation at the 5th International Workshop on Functional–Structural Plant Models, Napier, New Zealand, November 2007.

Genomic and functional profiling of gastric cancer

Helicobacter pylori infection is a risk factor for gastric cancer, which is a major health issue worldwide. Gastric cancer has a poor prognosis due to the unnoticeable progression of the disease and surgery is the only available treatment in gastric cancer. Therefore, gastric cancer patients would greatly benefit from identifying biomarker genes that would improve diagnostic and prognostic prediction and provide targets for molecular therapies. DNA copy number amplifications are the hallmarks of cancers in various anatomical locations. Mechanisms of amplification predict that DNA double-strand breaks occur at the margins of the amplified region. The first objective of this thesis was to identify the genes that were differentially expressed in H. pylori infection as well as the transcription factors and signal transduction pathways that were associated with the gene expression changes. The second objective was to identify putative biomarker genes in gastric cancer with correlated expression and copy number, and the last objective was to characterize cancers based on DNA copy number amplifications. DNA microarrays, an in vitro model and real-time polymerase chain reaction were used to measure gene expression changes in H. pylori infected AGS cells. In order to identify the transcription factors and signal transduction pathways that were activated after H. pylori infection, gene expression profiling data from the H. pylori experiments and a bioinformatics approach accompanied by experimental validation were used. Genome-wide expression and copy number microarray analysis of clinical gastric cancer samples and immunohistochemistry on tissue microarray were used to identify putative gastric cancer genes. Data mining and machine learning techniques were applied to study amplifications in a cross-section of cancers. FOS and various stress response genes were regulated by H. pylori infection. H. pylori regulated genes were enriched in the chromosomal regions that are frequently changed in gastric cancer, suggesting that molecular pathways of gastric cancer and premalignant H. pylori infection that induces gastritis are interconnected. 16 transcription factors were identified as being associated with H. pylori infection induced changes in gene expression. NF-κB transcription factor and p50 and p65 subunits were verified using elecrophoretic mobility shift assays. ERBB2 and other genes located in 17q12- q21 were found to be up-regulated in association with copy number amplification in gastric cancer. Cancers with similar cell type and origin clustered together based on the genomic localization of the amplifications. Cancer genes and large genes were co-localized with amplified regions and fragile sites, telomeres, centromeres and light chromosome bands were enriched at the amplification boundaries. H. pylori activated transcription factors and signal transduction pathways function in cellular mechanisms that might be capable of promoting carcinogenesis of the stomach. Intestinal and diffuse type gastric cancers showed distinct molecular genetic profiles. Integration of gene expression and copy number microarray data allowed the identification of genes that might be involved in gastric carcinogenesis and have clinical relevance. Gene amplifications were demonstrated to be non-random genomic instabilities. Cell lineage, properties of precursor stem cells, tissue microenvironment and genomic map localization of specific oncogenes define the site specificity of DNA amplifications, whereas labile genomic features define the structures of amplicons. These conclusions suggest that the definition of genomic changes in cancer is based on the interplay between the cancer cell and the tumor microenvironment.

Evaluation of potential candidate genes involved in salinity tolerance in striped catfish (Pangasianodon hypophthalmus) using an RNA-Seq approach

Increasing salinity levels in freshwater and coastal environments caused by sea level rise linked to climate change is now recognized to be a major factor that can impact fish growth negatively, especially for freshwater teleost species. Striped catfish (Pangasianodon hypophthalmus) is an important freshwater teleost that is now widely farmed across the Mekong River Delta in Vietnam. Understanding the basis for tolerance and adaptation to raised environmental salinity conditions can assist the regional culture industry to mitigate predicted impacts of climate change across this region. Attempt of next generation sequencing using the ion proton platform results in more than 174 million raw reads from three tissue libraries (gill, kidney and intestine). Reads were filtered and de novo assembled using a variety of assemblers and then clustered together to generate a combined reference transcriptome. Downstream analysis resulted in a final reference transcriptome that contained 60,585 transcripts with an N50 of 683 bp. This resource was further annotated using a variety of bioinformatics databases, followed by differential gene expression analysis that resulted in 3062 transcripts that were differentially expressed in catfish samples raised under two experimental conditions (0 and 15 ppt). A number of transcripts with a potential role in salinity tolerance were then classified into six different functional gene categories based on their gene ontology assignments. These included; energy metabolism, ion transportation, detoxification, signal transduction, structural organization and detoxification. Finally, we combined the data on functional salinity tolerance genes into a hypothetical schematic model that attempted to describe potential relationships and interactions among target genes to explain the molecular pathways that control adaptive salinity responses in P. hypophthalmus. Our results indicate that P. hypophthalmus exhibit predictable plastic regulatory responses to elevated salinity by means of characteristic gene expression patterns, providing numerous candidate genes for future investigations.

Genomic approach to organ-specific growth control

Growth is a fundamental aspect of life cycle of all organisms. Body size varies highly in most animal groups, such as mammals. Moreover, growth of a multicellular organism is not uniform enlargement of size, but different body parts and organs grow to their characteristic sizes at different times. Currently very little is known about the molecular mechanisms governing this organ-specific growth. The genome sequencing projects have provided complete genomic DNA sequences of several species over the past decade. The amount of genomic sequence information, including sequence variants within species, is constantly increasing. Based on the universal genetic code, we can make sense of this sequence information as far as it codes proteins. However, less is known about the molecular mechanisms that control expression of genes, and about the variations in gene expression that underlie many pathological states in humans. This is caused in part by lack of information about the second genetic code that consists of the binding specificities of transcription factors and the combinatorial code by which transcription factor binding sites are assembled to form tissue-specific and/or ligand-regulated enhancer elements. This thesis presents a high-throughput assay for identification of transcription factor binding specificities, which were then used to measure the DNA binding profiles of transcription factors involved in growth control. We developed ‘enhancer element locator’, a computational tool, which can be used to predict functional enhancer elements. A genome-wide prediction of human and mouse enhancer elements generated a large database of enhancer elements. This database can be used to identify target genes of signaling pathways, and to predict activated transcription factors based on changes in gene expression. Predictions validated in transgenic mouse embryos revealed the presence of multiple tissue-specific enhancers in mouse c- and N-Myc genes, which has implications to organ specific growth control and tumor type specificity of oncogenes. Furthermore, we were able to locate a variation in a single nucleotide, which carries a susceptibility to colorectal cancer, to an enhancer element and propose a mechanism by which this SNP might be involved in generation of colorectal cancer.

High-performance graphene-based supercapacitors made by a scalable blade-coating approach

Graphene oxide (GO) sheets can form liquid crystals (LCs) in their aqueous dispersions that are more viscous with a stronger LC feature. In this work we combine the viscous LC-GO solution with the blade-coating technique to make GO films, for constructing graphene-based supercapacitors in a scalable way. Reduced GO (rGO) films are prepared by wet chemical methods, using either hydrazine (HZ) or hydroiodic acid (HI). Solid-state supercapacitors with rGO films as electrodes and highly conductive carbon nanotube films as current collectors are fabricated and the capacitive properties of different rGO films are compared. It is found that the HZ-rGO film is superior to the HI-rGO film in achieving high capacitance, owing to the 3D structure of graphene sheets in the electrode. Compared to gelled electrolyte, the use of liquid electrolyte (H2SO4) can further increase the capacitance to 265 F per gram (corresponding to 52 mF per cm2) of the HZ-rGO film.

Gene Expression : From Microarrays to Functional Genomics

The time of the large sequencing projects has enabled unprecedented possibilities of investigating more complex aspects of living organisms. Among the high-throughput technologies based on the genomic sequences, the DNA microarrays are widely used for many purposes, including the measurement of the relative quantity of the messenger RNAs. However, the reliability of microarrays has been strongly doubted as robust analysis of the complex microarray output data has been developed only after the technology had already been spread in the community. An objective of this study consisted of increasing the performance of microarrays, and was measured by the successful validation of the results by independent techniques. To this end, emphasis has been given to the possibility of selecting candidate genes with remarkable biological significance within specific experimental design. Along with literature evidence, the re-annotation of the probes and model-based normalization algorithms were found to be beneficial when analyzing Affymetrix GeneChip data. Typically, the analysis of microarrays aims at selecting genes whose expression is significantly different in different conditions followed by grouping them in functional categories, enabling a biological interpretation of the results. Another approach investigates the global differences in the expression of functionally related groups of genes. Here, this technique has been effective in discovering patterns related to temporal changes during infection of human cells. Another aspect explored in this thesis is related to the possibility of combining independent gene expression data for creating a catalog of genes that are selectively expressed in healthy human tissues. Not all the genes present in human cells are active; some involved in basic activities (named housekeeping genes) are expressed ubiquitously. Other genes (named tissue-selective genes) provide more specific functions and they are expressed preferably in certain cell types or tissues. Defining the tissue-selective genes is also important as these genes can cause disease with phenotype in the tissues where they are expressed. The hypothesis that gene expression could be used as a measure of the relatedness of the tissues has been also proved. Microarray experiments provide long lists of candidate genes that are often difficult to interpret and prioritize. Extending the power of microarray results is possible by inferring the relationships of genes under certain conditions. Gene transcription is constantly regulated by the coordinated binding of proteins, named transcription factors, to specific portions of the its promoter sequence. In this study, the analysis of promoters from groups of candidate genes has been utilized for predicting gene networks and highlighting modules of transcription factors playing a central role in the regulation of their transcription. Specific modules have been found regulating the expression of genes selectively expressed in the hippocampus, an area of the brain having a central role in the Major Depression Disorder. Similarly, gene networks derived from microarray results have elucidated aspects of the development of the mesencephalon, another region of the brain involved in Parkinson Disease.

Structure-Based Phylogeny as a Diagnostic for Functional Characterization of Proteins with a Cupin Fold

Background: The members of cupin superfamily exhibit large variations in their sequences, functions, organization of domains, quaternary associations and the nature of bound metal ion, despite having a conserved beta-barrel structural scaffold. Here, an attempt has been made to understand structure-function relationships among the members of this diverse superfamily and identify the principles governing functional diversity. The cupin superfamily also contains proteins for which the structures are available through world-wide structural genomics initiatives but characterized as ``hypothetical''. We have explored the feasibility of obtaining clues to functions of such proteins by means of comparative analysis with cupins of known structure and function. Methodology/Principal Findings: A 3-D structure-based phylogenetic approach was undertaken. Interestingly, a dendrogram generated solely on the basis of structural dissimilarity measure at the level of domain folds was found to cluster functionally similar members. This clustering also reflects an independent evolution of the two domains in bicupins. Close examination of structural superposition of members across various functional clusters reveals structural variations in regions that not only form the active site pocket but are also involved in interaction with another domain in the same polypeptide or in the oligomer. Conclusions/Significance: Structure-based phylogeny of cupins can influence identification of functions of proteins of yet unknown function with cupin fold. This approach can be extended to other proteins with a common fold that show high evolutionary divergence. This approach is expected to have an influence on the function annotation in structural genomics initiatives.