From Past till Presence – The Quality of German Physical Activity Kindergarten (PAK)

Physical Activity Education (PAE) has always been playing an important role in the history of Early Childhood Education (ECE) in Germany and its institutionalized form called “Kindergarten”. As a key feature of Kindergarten quality Physical Activity (PA) was originally considered to be either a compensation for children’s health dangers along with the neglect by their hard working mothers or a mere medium for other developmental fields such as cognition or social behavior. The subjectively observed outcome for the pedagogues was far from empirically objective evidence. Till the 1970s neither the technical term “quality” nor any empirical quality standards existed in German ECE to assess the effect of PA in Kindergarten. This fairly hasn’t changed yet although some general findings of high quality effects can be reported as well as PA specific results from a recent review on systematic PAE programmes. Despite this fact, Germany’s organized sports associations (OSA) installed 1759 Physical Activity Kindergarten (PAK) with great expectations in their overall positive developmental effect. For quality assurance some criteria were developed to achieve a minimum standard level. Subsequently a very popular license originated without having evidence for its positive outcome. A randomized, controlled longitudinal study is still to come

Smac mimetic-derived augmentation of chemotherapeutic response in experimental pancreatic cancer

<p>Abstract</p> <p>Background</p> <p>Pancreatic ductal adenocarcinoma (PDAC) is highly resistant to conventional chemotherapy, in part due to the overexpression of inhibitors of apoptosis proteins (IAPs). Smac is an endogenous IAP-antagonist, which renders synthetic Smac mimetics attractive anticancer agents. We evaluated the benefits of combining a Smac mimetic, JP1201 (JP), with conventional chemotherapy agents used for PDAC management.</p> <p>Methods</p> <p>Cell viability assays and protein expression analysis were performed using WST-1 reagent and Western blotting, respectively. Apoptosis was detected by annexin V/propidium iodide staining. <it>In vivo </it>tumor growth and survival studies were performed in murine PDAC xenografts.</p> <p>Results</p> <p>JP and gemcitabine (Gem) inhibited PDAC cell proliferation with additive effects in combination. The percentage of early apoptotic cells in controls, JP, Gem and JP + Gem was 17%, 26%, 26% and 38%, respectively. JP-induced apoptosis was accompanied by PARP-1 cleavage. Similar additive anti-proliferative effects were seen for combinations of JP with doxorubicin (Dox) and docetaxel (DT). The JP + Gem combination caused a 30% decrease in tumor size <it>in vivo </it>compared to controls. Median animal survival was improved significantly in mice treated with JP + Gem (38 d) compared to controls (22 d), JP (28 d) or Gem (32 d) (p = 0.01). Animal survival was also improved with JP + DT treatment (32 d) compared to controls (16 d), JP (21 d) or DT alone (27 d).</p> <p>Conclusions</p> <p>These results warrant further exploration of strategies that promote chemotherapy-induced apoptosis of tumors and highlight the potential of Smac mimetics in clinical PDAC therapy.</p

Efficient generation of neural stem cell-like cells from adult human bone marrow stromal cells

Clonogenic neural stem cells (NSCs) are self-renewing cells that maintain the capacity to differentiate into brain-specific cell types, and may also replace or repair diseased brain tissue. NSCs can be directly isolated from fetal or adult nervous tissue, or derived from embryonic stem cells. Here, we describe the efficient conversion of human adult bone marrow stromal cells (hMSC) into a neural stem cell-like population (hmNSC, for human marrow-derived NSC-like cells). These cells grow in neurosphere-like structures, express high levels of early neuroectodermal markers, such as the proneural genes NeuroD1, Neurog2, MSl1 as well as otx1 and nestin, but lose the characteristics of mesodermal stromal cells. In the presence of selected growth factors, hmNSCs can be differentiated into the three main neural phenotypes: astroglia, oligodendroglia and neurons. Clonal analysis demonstrates that individual hmNSCs are multipotent and retain the capacity to generate both glia and neurons. Our cell culture system provides a powerful tool for investigating the molecular mechanisms of neural differentiation in adult human NSCs. hmNSCs may therefore ultimately help to treat acute and chronic neurodegenerative diseases

Joint analysis of histopathology image features and gene expression in breast cancer

BACKGROUND Genomics and proteomics are nowadays the dominant techniques for novel biomarker discovery. However, histopathology images contain a wealth of information related to the tumor histology, morphology and tumor-host interactions that is not accessible through these techniques. Thus, integrating the histopathology images in the biomarker discovery workflow could potentially lead to the identification of new image-based biomarkers and the refinement or even replacement of the existing genomic and proteomic signatures. However, extracting meaningful and robust image features to be mined jointly with genomic (and clinical, etc.) data represents a real challenge due to the complexity of the images. RESULTS We developed a framework for integrating the histopathology images in the biomarker discovery workflow based on the bag-of-features approach - a method that has the advantage of being assumption-free and data-driven. The images were reduced to a set of salient patterns and additional measurements of their spatial distribution, with the resulting features being directly used in a standard biomarker discovery application. We demonstrated this framework in a search for prognostic biomarkers in breast cancer which resulted in the identification of several prognostic image features and a promising multimodal (imaging and genomic) prognostic signature. The source code for the image analysis procedures is freely available. CONCLUSIONS The framework proposed allows for a joint analysis of images and gene expression data. Its application to a set of breast cancer cases resulted in image-based and combined (image and genomic) prognostic scores for relapse-free survival

Механизм осаждения частиц загрязнений в капиллярных каналах

Несмотря на экономическое значение научные вопросы применения в регенерации отработанных моторных масел процесса фильтрации практически не рассматривались [8]. Существующие модели фильтрации основаны на моделировании фильтрующей среды как массива сферических "коллекторов". Взвешенные в фильтрующей среде частицы перемещаются в пространстве между " коллекторами". В нашем исследовании предполагается, что частицы, взвешенные в фильтрующейся среде, перемещаются через многочисленные капилляры, пронизывающие насквозь фильтрующий материал. Рассмотрены силы, действующих на частицу в капилляре, увлекаемую потоком жидкости. Получены уравнения, описывающие траекторию движения частицы. Определены условия осаждения частицы в капилляре. Получены формулы, определяющие эффективность осаждения частиц в капилляре

Draft Genome Sequences of Three Porcine Streptococcus suis Isolates Which Differ in Their Susceptibility to Penicillin

The draft genome sequences of three Streptococcus suis isolates, IMT40343, IMT40201, and IMT40738, are presented here. These isolates were obtained from bronchoalveolar lavage fluid of healthy and diseased weaners from different German piglet-producing farms and differed in their susceptibility to penicillin

Unification of M- and F- Theory Calabi-Yau Fourfold Vacua

We consider splitting type phase transitions between Calabi-Yau fourfolds. These transitions generalize previously known types of conifold transitions between threefolds. Similar to conifold configurations the singular varieties mediating the transitions between fourfolds connect moduli spaces of different dimensions, describing ground states in M- and F-theory with different numbers of massless modes as well as different numbers of cycles to wrap various p-branes around. The web of Calabi-Yau fourfolds obtained in this way contains the class of all complete intersection manifolds embedded in products of ordinary projective spaces, but extends also to weighted configurations. It follows from this that for some of the fourfold transitions vacua with vanishing superpotential are connected to ground states with nonzero superpotential.Comment: plain TeX, 22p

(0,2) Mirror Symmetry

We generalize the previously established (0,2) triality of exactly solvable models, Landau-Ginzburg theories and Calabi-Yau manifolds to a number of different classes of (0,2) compactifications derived from (2,2) vacua. For the resulting models we show that the known (2,2) mirror constructions induce mirror symmetry in the (0,2) context.Comment: plain TeX, harvmac incl., 38(b)/22(l) pp., 3 PS figs., epsf incl., references adde

The SARS-coronavirus-host interactome

Coronaviruses (CoVs) are important human and animal pathogens that induce fatal respiratory, gastrointestinal and neurological disease. The outbreak of the severe acute respiratory syndrome (SARS) in 2002/2003 has demonstrated human vulnerability to (Coronavirus) CoV epidemics. Neither vaccines nor therapeutics are available against human and animal CoVs. Knowledge of host cell proteins that take part in pivotal virus-host interactions could define broad-spectrum antiviral targets. In this study, we used a systems biology approach employing a genome-wide yeast-two hybrid interaction screen to identify immunopilins (PPIA, PPIB, PPIH, PPIG, FKBP1A, FKBP1B) as interaction partners of the CoV non-structural protein 1 (Nsp1). These molecules modulate the Calcineurin/NFAT pathway that plays an important role in immune cell activation. Overexpression of NSP1 and infection with live SARS-CoV strongly increased signalling through the Calcineurin/NFAT pathway and enhanced the induction of interleukin 2, compatible with late-stage immunopathogenicity and long-term cytokine dysregulation as observed in severe SARS cases. Conversely, inhibition of cyclophilins by cyclosporine A (CspA) blocked the replication of CoVs of all genera, including SARS-CoV, human CoV-229E and -NL-63, feline CoV, as well as avian infectious bronchitis virus. Non-immunosuppressive derivatives of CspA might serve as broad-range CoV inhibitors applicable against emerging CoVs as well as ubiquitous pathogens of humans and livestock

Survival outcomes in a prospective randomized multicenter Phase III trial comparing patients undergoing anatomical segmentectomy versus standard lobectomy for non-small cell lung cancer up to 2 cm

OBJECTIVES The oncological equivalence of anatomical segmentectomy for early stage non-small cell lung cancer (NSCLC) is still controversial. Primary aim of this study was survival outcomes in combination with improved quality of life after segmentectomy compared with lobectomy in patients with pathological stage Ia NSCLC (up to 2 cm, 7th edition) MATERIALS AND METHODS: We conducted a prospective, randomized, multicenter phase III trial to confirm the non-inferiority of segmentectomy to lobectomy in regard to prognosis (trial No. DRKS00004897). Patients were randomized to undergo either segmentectomy or lobectomy and followed up for 5-years survival and tumor recurrence. The 5-year hazard ratio comparing lobectomy with segmentectomy was required to remain above 0.5. RESULTS Between October 2013 and June 2016, 108 patients with verified or suspected NSCLC up to 2 cm diameter were enrolled; 54 were assigned to lobectomy and 54 (1 drop-out) to segmentectomy. In-hospital and 90 days mortality was 0% in both groups. Overall survival at 5 years was 86.52% in the lobectomy compared to 78.21% in the segmentectomy group (HR = 0.61, (95% CI 0.23-1.66), p-value of non-inferiority test, p-ni = 0.687). Disease free survival was 77.29% for the lobectomy and 77.96% for the segmentectomy patients (HR = 1.50, (95% CI 0.60-3.76), p-ni = 0.019). At a median follow-up of 5 years, no differences were noted in either the locoregional or distant recurrent disease in both groups (9.4% vs 7.4%, p-ni = 0.506). CONCLUSION Overall survival, locoregional and distant recurrences was not significantly difference for patients undergoing either segmentectomy or lobectomy for stage Ia NSCLC. The targeted non-inferiority of segmentectomy to lobectomy could not be proven for primary endpoint overall survival, but was significant for the secondary endpoint of disease free survival