A general approach for discriminative de-novo motif discovery from highthroughput data

De novo motif discovery has been an important challenge of bioinformatics for the past two decades. Since the emergence of high-throughput techniques like ChIP-seq, ChIP-exo and protein-binding microarrays (PBMs), the focus of de novo motif discovery has shifted to runtime and accuracy on large data sets. For this purpose, specialized algorithms have been designed for discovering motifs in ChIP-seq or PBM data. However, none of the existing approaches work perfectly for all three high-throughput techniques. In this article, we propose Dimont, a general approach for fast and accurate de novo motif discovery from high-throughput data. We demonstrate that Dimont yields a higher number of correct motifs from ChIP-seq data than any of the specialized approaches and achieves a higher accuracy for predicting PBM intensities from probe sequence than any of the approaches specifically designed for that purpose. Dimont also reports the expected motifs for several ChIP-exo data sets. Investigating differences between in vitro and in vivo binding, we find that for most transcription factors, the motifs discovered by Dimont are in good accordance between techniques, but we also find notable exceptions. We also observe that modeling intra-motif dependencies may increase accuracy, which indicates that more complex motif models are a worthwhile field of research

THEORETICAL MODEL VALIDATION OF MUSCLE FORCES DURING EXTREME MOVEMENTS

Introduction: The validation of the involved muscular forces for a computer model of the human body, which allows simulation of internal forces in patients, was achieved by inverse-dynamic analysis. Methods: Beginning with an extreme vertical jump, joint moments were extracted from high-speed film data and eventually subdivided into muscular forces. The muscle groups responsible for movements were determined by electromyography. A squat jump with both legs and maximum strength was filmed in the sagittal plane with a frequency of 200 Hz. Moments in the hip, knee and ankle joints were determined from the film data. Using surface electrodes of a Neuraxon Myosoft 2008 system and an amplifier system from Multichannel Systems, the muscle groups responsible for movements were electromyographically determined. The muscle insertions and muscle paths were extracted from MRI pictures of patients. Results: With this information joint moments can be subdivided into single muscle forces. Depending on the jump demands, the muscle groups responsible for movements can be divided and analyzed in six extensor groups. Conclusion: Inverse-dynamic muscle force analysis is a basis which can be expanded for the validation of complex movements under extreme internal loads in patients

VOMBAT: prediction of transcription factor binding sites using variable order Bayesian trees

Variable order Markov models and variable order Bayesian trees have been proposed for the recognition of transcription factor binding sites, and it could be demonstrated that they outperform traditional models, such as position weight matrices, Markov models and Bayesian trees. We develop a web server for the recognition of DNA binding sites based on variable order Markov models and variable order Bayesian trees offering the following functionality: (i) given datasets with annotated binding sites and genomic background sequences, variable order Markov models and variable order Bayesian trees can be trained; (ii) given a set of trained models, putative DNA binding sites can be predicted in a given set of genomic sequences and (iii) given a dataset with annotated binding sites and a dataset with genomic background sequences, cross-validation experiments for different model combinations with different parameter settings can be performed. Several of the offered services are computationally demanding, such as genome-wide predictions of DNA binding sites in mammalian genomes or sets of 10(4)-fold cross-validation experiments for different model combinations based on problem-specific data sets. In order to execute these jobs, and in order to serve multiple users at the same time, the web server is attached to a Linux cluster with 150 processors. VOMBAT is available at

MUSCLE ACTIVITY OF THREE SUBJECTS DIFFERING IN WEIGHT AND HEIGHT DURING A VERTICAL JUMP

Introduction: The first measurement was done to evaluate changes of potentials of surface electromyography with different locations of electrode sites and different resistors between the electrodes. The objective of the second was to investigate the activity of muscles in their stimulation sequence, the quantitative participation of the single muscle and cinematic study of vertical jumps. This work is part of a project to determine the internal forces of the human motional apparatus with an anatomical model of muscles. Methods: For each measurement we chose a Noraxon EMG, ECG electrodes from Medicotest, and the electrodes were placed following the description of D.A. Winter. At first we chose the M. gastro. med., M. gastro. lat., and M. soleus of male subject and did a measurement while the subject moved ten times from a ‘standing at attention’ posture to standing on the tips of his toes with a resistor between the electrodes higher than 60 Ohm and one with a resistor lower than 5 Ohm. Then we moved the electrodes 2 cm and 4 cm in the vertical and horizontal directions (resistor of lower than 5 Ohm). Secondly, we chose eight muscles (M. glut. max., M. semitend., M. biceps femoris, M. rectus femoris, M. vastus lat., M. vastus med., M. gastro. med., M. soleus) of three male subjects differing in weight and height and did the measurements while the subjects jumped ten times from a squatting position on a force plate, filmed by a high-speed camera. Results: The measurements with a 60 Ohm resistor and a 5 Ohm resistor differed, as well as the measurements with different locations of electrode sites. The second measurements showed that the M. gas. med. seemed to be the muscle with the highest response, followed by the M. sol. The M. vast. med., M. vast. lat., M. bic. fem. and M. rec. fem. had the same type of reaction. In one case the M. glut. max. seemed to be important while jumping. In an second case the M. semit. showed a high response. The muscles of the tallest subject had the longest activity, and the muscles of the shortest one had the shortest activity. The timedependent angles of knee, hip and foot joints of every subject were nearly identical. Like the EMG, the acceleration phases of the tallest subject took the longest time, while the acceleration phase of the shortest subject took the least time. Conclusions: Firstly, it is possible to see how important the placement and resistor of the electrodes is. Secondly, there is a possible relationship between the beginning of the activity of the muscles and the size of the subjects, as well as a correlation of the angles and the size of the subjects. This effect should be considered in using such calculations of the internal forces of the human motional apparatus in the development of protheses and in sports science

Treatment of meningioma and glioma with protons and carbon ions

The rapid rise of particle therapy across the world necessitates evidence to justify its ever-increasing utilization. This narrative review summarizes the current status of these technologies on treatment of both meningiomas and gliomas, the most common benign and malignant primary brain tumors, respectively. Proton beam therapy (PBT) for meningiomas displays high rates of long-term local control, low rates of symptomatic deterioration, along with the potential for safe dose-escalation in select (but not necessarily routine) cases. PBT is also associated with low adverse events and maintenance of functional outcomes, which have implications for quality of life and cost-effectiveness measures going forward. Data on carbon ion radiation therapy (CIRT) are limited; existing series describe virtually no high-grade toxicities and high local control. Regarding the few available data on low-grade gliomas, PBT provides opportunities to dose-escalate while affording no increase of severe toxicities, along with maintaining appropriate quality of life. Although dose-escalation for low-grade disease has been less frequently performed than for glioblastoma, PBT and CIRT continue to be utilized for the latter, and also have potential for safer re-irradiation of high-grade gliomas. For both neoplasms, the impact of superior dosimetric profiles with endpoints such as neurocognitive decline and neurologic funcionality, are also discussed to the extent of requiring more data to support the utility of particle therapy. Caveats to these data are also described, such as the largely retrospective nature of the available studies, patient selection, and heterogeneity in patient population as well as treatment (including mixed photon/particle treatment). Nevertheless, multiple prospective trials (which may partially attenuate those concerns) are also discussed. In light of the low quantity and quality of available data, major questions remain regarding economic concerns as well

Injury-Free Children and Adolescents: Towards Better Practice in Swedish Football (FIT project)

This interdisciplinary research project will produce evidence-based recommendations on how injuries in Swedish youth football (soccer) can be prevented. Fewer injuries will positively impact athlete health, performance and career longevity and have the potential to promote life-long physical activity and wellbeing. Injury pattern research demonstrates that injuries are a significant problem in (Swedish) youth sport. Football has a higher traumatic and overuse injury rate than many contact/collision sports (e.g., field hockey, basketball). In research on youth football, the incidence of overuse training injuries was measured as high as 15.4 injuries per 1000 training hours, and the incidence of traumatic and overuse match injuries was 47.5 injuries per 1000 match hours. The injury frequency is alarming and applies to the 54% of children aged 7-14 and the 39% of youths aged 15-19 years who participate in Swedish organised sports. A large body of research identifies injury risk factors and preventative strategies; however, as the recent IOC consensus statement on youth athletic development points out, the existing, mostly bio-medical knowledge does not provide effective evidence-based injury prevention strategies. To address this deficit, interdisciplinary and context-driven knowledge on injury development in youth sport is needed. The proposed project will produce scientific evidence through four consecutive studies: a) Questionnaire to register the types, frequency and management of injuries; b) Laboratory testing of biomechanical, clinical and training-specific parameters to establish individual physical and sport-specific dispositions; c) Observation of sporting contexts to understand sporting cultures, coaching methods and coach-athlete relationships; and d) Interviews with coaches and players to recognize knowledge that shapes coaching and training. The sample of youth players will be recruited from Sweden’s most popular and injury-prone sport: football. Each of the four studies will conduct its own data production and analyses, and a collective analysis will produce integrated evidence. Concrete recommendations for best sporting practice will be developed, which will serve sporting federations, sport education institutions, coaches, sport support staff and players

VEGF-dependent induction of CD62E on endothelial cells mediates glioma tropism of adult haematopoietic progenitor cells

Haematopoietic progenitor cells (HPC) are attracted by experimental gliomas in vivo. This attraction is further enhanced by irradiation or hypoxic preconditioning of the glioma cells. Adhesive interactions might be critical to the preferential accumulation of HPC within the glioma tissue. Here, we studied the interactions of HPC with endothelial cells. Exposure of human cerebral endothelial cells (SV-HCEC), human microvascular endothelial cells (HMEC) and brain tumour endothelial cells derived from human glioblastomas (BTEC) to supernatants of glioma cells and primary glioma cells (SN-G) induced the expression of E-selectin (CD62E). CD62E expression was further enhanced when the glioma cells had been exposed to irradiation or hypoxia prior to the collection of supernatants, as well as by irradiation or exposure to hypoxia of the endothelial cells. Vascular cell adhesion molecule 1 (VCAM-1) was constitutively expressed on SV-HCEC, HMEC and BTEC, but was not modulated by SN-G, irradiation or hypoxia. Transendothelial HPC migration was enhanced after CD62E induction in vitro. Neutralizing antibodies to CD62E strongly reduced the homing of lin-Sca-1+c-kit+ cells to orthotopic SMA-560 gliomas in vivo. Tissue microarray sampling normal brain tissue and astrocytomas of WHO grades II-IV revealed a selective expression of CD62E on endothelial cells of tumour vessels. SN-G-induced CD62E expression on endothelial cells in vitro required transforming growth factor (TGF)-β signalling in glioma cells and vascular endothelial growth factor (VEGF)/VEGF receptor 2 (VEGF-R2) signalling in endothelial cells. Further, we observed a nuclear factor kappa B-dependent activation of the CD62E promoter peaking at 12 h after VEGF-R2 activation by glioma-derived VEGF. Taken together, we identify glioma cell-induced CD62E expression on endothelial cells as one mediator of the glioma tropism of HP