Eliciting qualitative structure from image curve deformations

A family of qualitative methods is described that determines structure of curves in a scene from their image projections in two or more views. For example, plane curves are distinguished from space curves, and space curves from contour generators. The novelty of the approach is that first, it is unaffected by camera intrinsic parameters, so calibration is not required; second, it is also unaffected by camera motion, so viewer motion need not be known; and third, curves need not be matched point by point. Qualitative scene descriptions can be determined using relative measurements, and affine or projective properties alone. The practical power of this family of methods is demonstrated using a real-time vision system based on B-spline snake-tracking

Study protocol: EXERcise and Cognition In Sedentary adults with Early-ONset dementia (EXERCISE-ON)

<p>Abstract</p> <p>Background</p> <p>Although the development of early-onset dementia is a radical and invalidating experience for both patient and family there are hardly any non-pharmacological studies that focus on this group of patients. One type of a non-pharmacological intervention that appears to have a beneficial effect on cognition in older persons without dementia and older persons at risk for dementia is exercise. In view of their younger age early-onset dementia patients may be well able to participate in an exercise program. The main aim of the EXERCISE-ON study is to assess whether exercise slows down the progressive course of the symptoms of dementia.</p> <p>Methods/Design</p> <p>One hundred and fifty patients with early-onset dementia are recruited. After completion of the baseline measurements, participants living within a 50 kilometre radius to one of the rehabilitation centres are randomly assigned to either an <it>aerobic exercise program in a rehabilitation centre</it> or a <it>flexibility and relaxation program in a rehabilitation centre</it>. Both programs are applied three times a week during 3 months. Participants living outside the 50 kilometre radius are included in a feasibility study where participants join in a <it>daily physical activity program set at home making use of pedometers</it>. Measurements take place at baseline (entry of the study), after three months (end of the exercise program) and after six months (follow-up). Primary outcomes are cognitive functioning; psychomotor speed and executive functioning; (instrumental) activities of daily living, and quality of life. Secondary outcomes include physical, neuropsychological, and rest-activity rhythm measures.</p> <p>Discussion</p> <p>The EXERCISE-ON study is the first study to offer exercise programs to patients with early-onset dementia. We expect this study to supply evidence regarding the effects of exercise on the symptoms of early-onset dementia, influencing quality of life.</p> <p>Trial registration</p> <p>The present study is registered within The Netherlands National Trial Register (ref: NTR2124)</p

Mislocalization of XPF-ERCC1 Nuclease Contributes to Reduced DNA Repair in XP-F Patients

Xeroderma pigmentosum (XP) is caused by defects in the nucleotide excision repair (NER) pathway. NER removes helix-distorting DNA lesions, such as UV–induced photodimers, from the genome. Patients suffering from XP exhibit exquisite sun sensitivity, high incidence of skin cancer, and in some cases neurodegeneration. The severity of XP varies tremendously depending upon which NER gene is mutated and how severely the mutation affects DNA repair capacity. XPF-ERCC1 is a structure-specific endonuclease essential for incising the damaged strand of DNA in NER. Missense mutations in XPF can result not only in XP, but also XPF-ERCC1 (XFE) progeroid syndrome, a disease of accelerated aging. In an attempt to determine how mutations in XPF can lead to such diverse symptoms, the effects of a progeria-causing mutation (XPFR153P) were compared to an XP–causing mutation (XPFR799W) in vitro and in vivo. Recombinant XPF harboring either mutation was purified in a complex with ERCC1 and tested for its ability to incise a stem-loop structure in vitro. Both mutant complexes nicked the substrate indicating that neither mutation obviates catalytic activity of the nuclease. Surprisingly, differential immunostaining and fractionation of cells from an XFE progeroid patient revealed that XPF-ERCC1 is abundant in the cytoplasm. This was confirmed by fluorescent detection of XPFR153P-YFP expressed in Xpf mutant cells. In addition, microinjection of XPFR153P-ERCC1 into the nucleus of XPF–deficient human cells restored nucleotide excision repair of UV–induced DNA damage. Intriguingly, in all XPF mutant cell lines examined, XPF-ERCC1 was detected in the cytoplasm of a fraction of cells. This demonstrates that at least part of the DNA repair defect and symptoms associated with mutations in XPF are due to mislocalization of XPF-ERCC1 into the cytoplasm of cells, likely due to protein misfolding. Analysis of these patient cells therefore reveals a novel mechanism to potentially regulate a cell's capacity for DNA repair: by manipulating nuclear localization of XPF-ERCC1

A Concept to Improve Care for People with Dementia

AbstractDementia is one of the severe causes of mortality in elder groups of human population, and the number of dementia patients is expected to increase all over the world. Globally, the cost to take care of patients with the illness is high. Moreover, the lives for dementia patients are commonly impacted by a variety of challenges, for example, in terms of communication, emotional behaviour, confusion and wandering. Therefore, the future aim is to develop a serious games package which can help to slow down the progression of dementia, better life for the patients and their loved one and reduce the use of medications and the cost for the government sectors. In this study, a conceptual model was formed to present the problems the dementia patients and their caregivers are facing, and non-pharmacological approaches are suggested to slow down the progression of dementia-related impairments and behavioural symptoms by using well-structured serious games with personalised data.Abstract Dementia is one of the severe causes of mortality in elder groups of human population, and the number of dementia patients is expected to increase all over the world. Globally, the cost to take care of patients with the illness is high. Moreover, the lives for dementia patients are commonly impacted by a variety of challenges, for example, in terms of communication, emotional behaviour, confusion and wandering. Therefore, the future aim is to develop a serious games package which can help to slow down the progression of dementia, better life for the patients and their loved one and reduce the use of medications and the cost for the government sectors. In this study, a conceptual model was formed to present the problems the dementia patients and their caregivers are facing, and non-pharmacological approaches are suggested to slow down the progression of dementia-related impairments and behavioural symptoms by using well-structured serious games with personalised data

Genome-Wide Analysis of Factors Affecting Transcription Elongation and DNA Repair: A New Role for PAF and Ccr4-Not in Transcription-Coupled Repair

RNA polymerases frequently deal with a number of obstacles during transcription elongation that need to be removed for transcription resumption. One important type of hindrance consists of DNA lesions, which are removed by transcription-coupled repair (TC-NER), a specific sub-pathway of nucleotide excision repair. To improve our knowledge of transcription elongation and its coupling to TC-NER, we used the yeast library of non-essential knock-out mutations to screen for genes conferring resistance to the transcription-elongation inhibitor mycophenolic acid and the DNA-damaging agent 4-nitroquinoline-N-oxide. Our data provide evidence that subunits of the SAGA and Ccr4-Not complexes, Mediator, Bre1, Bur2, and Fun12 affect transcription elongation to different extents. Given the dependency of TC-NER on RNA Polymerase II transcription and the fact that the few proteins known to be involved in TC-NER are related to transcription, we performed an in-depth TC-NER analysis of a selection of mutants. We found that mutants of the PAF and Ccr4-Not complexes are impaired in TC-NER. This study provides evidence that PAF and Ccr4-Not are required for efficient TC-NER in yeast, unraveling a novel function for these transcription complexes and opening new perspectives for the understanding of TC-NER and its functional interconnection with transcription elongation

Is the relationship between common mental disorder and adiposity bidirectional? Prospective analyses of a UK general population-based study

The direction of the association between mental health and adiposity is poorly understood. Our objective was to empirically examine this link in a UK study. This is a prospective cohort study of 3 388 people (men) aged >= 18 years at study induction who participated in both the UK Health and Lifestyle Survey at baseline (HALS-1, 1984/1985) and the re-survey (HALS-2, 1991/1992). At both survey examinations, body mass index, waist circumference and self-reported common mental disorder (the 30-item General Health Questionnaire, GHQ) were measured. Logistic regression models were used to compute odds ratios (OR) and accompanying 95% confidence intervals (CI) for the associations between (1) baseline common mental disorder (QHQ score > 4) and subsequent general and abdominal obesity and (2) baseline general and abdominal obesity and re-survey common mental disorders. After controlling for a range of covariates, participants with common mental disorder at baseline experienced greater odds of subsequently becoming overweight (women, OR: 1.30, 1.03 - 1.64; men, 1.05, 0.81 -1.38) and obese (women, 1.26, 0.82 - 1.94; men, OR: 2.10, 1.23 - 3.55) than those who were free of common mental disorder. Similarly, having baseline common mental health disorder was also related to a greater risk of developing moderate (1.57, 1.21 - 2.04) and severe (1.48, 1.09 - 2.01) abdominal obesity (women only). Baseline general or abdominal obesity was not associated with the risk of future common mental disorder. These findings of the present study suggest that the direction of association between common mental disorders and adiposity is from common mental disorder to increased future risk of adiposity as opposed to the converse

Acute exercise leads to regulation of Telomere-Associated genes and MicroRNA expression in immune Cells

Telomeres are specialized nucleoprotein structures that protect chromosomal ends from degradation. These structures progressively shorten during cellular division and can signal replicative senescence below a critical length. Telomere length is predominantly maintained by the enzyme telomerase. Significant decreases in telomere length and telomerase activity are associated with a host of chronic diseases; conversely their maintenance underpins the optimal function of the adaptive immune system. Habitual physical activity is associated with longer leukocyte telomere length; however, the precise mechanisms are unclear. Potential hypotheses include regulation of telomeric gene transcription and/or microRNAs (miRNAs). We investigated the acute exercise-induced response of telomeric genes and miRNAs in twenty-two healthy males (mean age = 24.1±1.55 years). Participants undertook 30 minutes of treadmill running at 80% of peak oxygen uptake. Blood samples were taken before exercise, immediately post-exercise and 60 minutes post-exercise. Total RNA from white blood cells was submitted to miRNA arrays and telomere extension mRNA array. Results were individually validated in white blood cells and sorted T cell lymphocyte subsets using quantitative real-time PCR (qPCR). Telomerase reverse transcriptase (TERT) mRNA (P = 0.001) and sirtuin-6 (SIRT6) (P<0.05) mRNA expression were upregulated in white blood cells after exercise. Fifty-six miRNAs were also differentially regulated post-exercise (FDR <0.05). In silico analysis identified four miRNAs (miR-186, miR-181, miR-15a and miR-96) that potentially targeted telomeric gene mRNA. The four miRNAs exhibited significant upregulation 60 minutes post-exercise (P<0.001). Telomeric repeat binding factor 2, interacting protein (TERF2IP) was identified as a potential binding target for miR-186 and miR-96 and demonstrated concomitant downregulation (P<0.01) at the corresponding time point. Intense cardiorespiratory exercise was sufficient to differentially regulate key telomeric genes and miRNAs in white blood cells. These results may provide a mechanistic insight into telomere homeostasis and improved immune function and physical health. Funding NHMR

Projective subgroups for grouping [and discussion]

The history of grouping in computer vision stretches a long way back. One strand could be called geometry–based and focuses on shapes with special regularities such as symmetry. From a mathematical point of view, the subparts of such shapes are related by special transformations. The presented work proposes to systematically classify such ‘special’ transformations by studying projective subgroups that come with fixed structures. These are geometric entities such as points or lines that remain fixed under the projectivities in the subgroups. As subgroups have their own invariants, these can then be used to guide the search for the corresponding groupings

Blocking B7 and CD40 co-stimulatory molecules decreases antiviral T cell activity

Inhibition of co-stimulatory signals for T cells by interrupting CD80/CD86–CD28 and CD40–CD154 interactions is a promising approach to prevent transplant rejection and to induce graft tolerance. However, this tolerizing treatment might affect T cell reactivity towards all the antigens to which the immune system is exposed during treatment. We addressed the question whether such inhibition of co-stimulatory ligands on human antigen presenting cells (APC) would affect T cell reactivity against a virus. This was tested in an in vitro system with freshly isolated human monocytes transduced with adenovirus (ad) containing either murine interferon-γ (mIFN-γ) or green fluorescent protein (GFP) as marker transgene. T cells co-cultured with transduced monocytes proliferated and produced cytokines. These ‘primed’ T cells had strong antiviral activity as they subsequently killed ad/GFP-transduced monocytes and reduced mIFN-γ accumulation in coculture with ad/mIFN-transduced monocytes. However, if priming had occurred in the presence of blocking anti-CD40/CD80/CD86 MoAbs, generation of this antiviral activity was completely prevented. Moreover, T cells primed in the absence of co-stimulatory cells failed to proliferate upon restimulation with adenovirus-transduced monocytes. The results confirm that co-stimulatory signals from APC are required for efficient induction of antiviral T cell activity and point to a potential infectious risk of blocking co-stimulatory signals