Random Copolymer Effect in Self-Assembled Hydrogen-Bonded P(S-co-4VP)(PDP) Side-Chain Polymers

Random copolymers of styrene and 4-vinylpyridine P(S(1-x)-co-4VP(x)) were synthesized to study the effect of the random copolymer "repulsion" on the self-assembly in hydrogen-bonded complexes with pentadecylphenol (one PDP molecule per 4VP group). The major trends observed as a function of the fraction of styrene monomers 1 - x in the random copolymer are a decrease in order-disorder transition temperature, T(ODT), and a decrease in the periodic length scale of the ordered lamellar state. The lower T(ODT) results from a partial shielding in the disordered state of the highly unfavorable styrene/4-vinylpyridine interactions by the PDP alkyl tails. The reduced layer thickness in the ordered state is due to the relaxation into a more coil-like conformation of the alkyl tails of the PDP amphiphiles, made possible by the presence of styrene units. The self-assembly properties of P(S(1-x)-co-4VP(x))(PDP)(1.0) are compared with those of the lamellar self-assembled homopolymer-based P4VP(PDP)(x) system, where x denotes the number of PDP molecules per 4VP repeat unit. As in P(S(1-x)-co-4VP(x))(PDP)(1.0), in P4VP(PDP)(x) also only a fraction x of the total number of monomers of the macromolecule may potentially hydrogen bond with PDP molecules at any given instant. In contrast to P(S(1-x)-co-4VP(x))(PDP)(1.0), for P4VP(PDP),, however, the long period is found to increase for decreasing values of x

Noodzaak voor genetisch beheer van de Nederlandse trekpaardenpopulatie

The Dutch Draught horse is a rare Dutch horse breed. To conserve rare breeds, it is of great importance to monitor population size and increase in inbreeding and kinship in a population. When screening the Dutch Draught horse population, it turned out that inbreeding (and potential consequences) should be controlled by the studbook (KVTH) with participation of breeders. During the most recent generation (2010-2017) fewer foals were born annually compared to the generation before. Also, the percentage of foals that is used in breeding at a later age decreased steadily. At the same time there is a considerable increase in the kinship between horses that are used in breeding. The increase in inbreeding passes the FAO threshold of 0.5% per generation. In light of the increase in kinship, we expect that the increase in inbreeding will even be higher in the future. Screening the population clearly showed that genetic management is needed to be able to better control inbreeding (and potential accompanying consequences). It is possible to drastically reduce the inbreeding increase through genetic management

The combined use of steroids and immune checkpoint inhibitors in brain metastasis patients:a systematic review and meta-analysis

BACKGROUND: Immune checkpoint inhibitors (ICI) have been a breakthrough for selected cancer patients, including those with brain metastases (BMs). Likewise, steroids have been an integral component of symptomatic management of BM patients. However, clinical evidence on the interaction between ICI and steroids in BM patients is conflicting and has not adequately been summarized thus far. Hence, the aim of this study was to perform a systematic literature review and meta-analysis on the association between steroid use and overall survival (OS) in BM patients receiving ICI. METHODS: A systematic literature search was performed. Pooled effect estimates were calculated using random-effects models across included studies. RESULTS: After screening 1145 abstracts, 15 observational studies were included. Fourteen studies reported sufficient data for meta-analysis, comprising 1102 BM patients of which 32.1% received steroids. In the steroid group, median OS ranged from 2.9 to 10.2 months. In the nonsteroid group, median OS ranged from 4.9 to 25.1 months. Pooled results demonstrated significantly worse OS (HR = 1.84, 95% CI 1.22-2.77) and systemic progression-free survival (PFS; HR = 2.00, 95% CI 1.37-2.91) in the steroid group. Stratified analysis showed a consistent effect across the melanoma subgroup; not in the lung cancer subgroup. No significant association was shown between steroid use and intracranial PFS (HR = 1.31, 95% CI 0.42-4.07). CONCLUSIONS: Administration of steroids was associated with significantly worse OS and PFS in BM patients receiving ICI. Further research on dose, timing, and duration of steroids is needed to elucidate the cause of this association and optimize outcomes in BM patients receiving ICI

4-(4-Ethyl­phenyl­diazen­yl)phenol

The crystal structure of the title compound, C14H14N2O, determined at 100 K, shows that the mol­ecules are not planar in the solid state, in contrast to other diazene (azobenzene) derivatives. The dihedral angle between the planes of the two aromatic rings is 42.32 (7)°. The mol­ecules are linked by inter­molecular O—H⋯N hydrogen bonds, forming an infinite one-dimensional chain

Cellular and molecular mechanism of cardiac regeneration: A comparison of newts, zebrafish, and mammals

Cardiovascular disease is the leading cause of death worldwide. Current palliative treatments can slow the progression of heart failure, but ultimately, the only curative treatment for end-stage heart failure is heart transplantation, which is only available for a minority of patients due to lack of donors' hearts. Explorative research has shown the replacement of the damaged and lost myocardium by inducing cardiac regeneration from preexisting myocardial cells. Lower vertebrates, such as the newt and zebrafish, can regenerate lost myocardium through cardiomyocyte proliferation. The preexisting adult cardiomyocytes replace the lost cells through subsequent dedifferentiation, proliferation, migration, and re-differentiation. Similarly, neonatal mice show complete cardiac regeneration post-injury; however, this regenerative capacity is remarkably diminished one week after birth. In contrast, the adult mammalian heart presents a fibrotic rather than a regenerative response and only shows signs of partial pathological cardiomyocyte dedifferentiation after injury. In this review, we explore the cellular and molecular responses to myocardial insults in different adult species to give insights for future interventional directions by which one can promote or activate cardiac regeneration in mammals

Analysis of Released Circulating Tumor Cells During Surgery for Non-Small Cell Lung Cancer:are they what they appear to be?

Purpose: Tumor cells from patients with lung cancer are expelled from the primary tumor into the blood, but difficult to detect in the peripheral circulation. We studied the release of circulating tumor cells (CTCs) during surgery to test the hypothesis that CTC counts are influenced by hemodynamic changes (caused by surgical approach) and manipulation. Experimental Design: Patients undergoing video-assisted thoracic surgery (VATS) or open surgery for (suspected) primary lung cancer were included. Blood samples were taken before surgery (T0) from the radial artery (RA), from both the RA and pulmonary vein (PV) when the PV was located (T1) and when either the pulmonary artery (T2 open) or the PV (T2VATS) was dissected. The CTCs were enumerated using the CellSearch system. Single-cell whole-genome sequencing was performed on isolated CTCs for aneuploidy. Results: CTCs were detected in 58 of 138 samples (42%) of 31 patients. CTCs were more often detected in the PV (70%) compared with the RA (22%, P <0.01) and in higher counts ( P <0.01). After surgery, the RA but not the PV showed less often CTCs (P = 0.02). Type of surgery did not influence CTC release. Only six of 496 isolated CTCs showed aneuploidy, despite matched primary tumor tissue being aneuploid. Euploid so-called CTCs had a different morphology than aneuploid. Conclusions: CTCs defined by CellSearch were identified more often and in higher numbers in the PV compared with the RA, suggesting central clearance. The majority of cells in the PV were normal epithelial cells and outnumbered CTCs. Release of CTCs was not influenced by surgical approach

The bipartite TAD organization of the X-inactivation center ensures opposing developmental regulation of Tsix and Xist

The mouse X-inactivation center (Xic) locus represents a powerful model for understanding the links between genome architecture and gene regulation, with the non-coding genes Xist and Tsix showing opposite developmental expression patterns while being organized as an overlapping sense/antisense unit. The Xic is organized into two topologically associating domains (TADs) but the role of this architecture in orchestrating cis-regulatory information remains elusive. To explore this, we generated genomic inversions that swap the Xist/Tsix transcriptional unit and place their promoters in each other’s TAD. We found that this led to a switch in their expression dynamics: Xist became precociously and ectopically upregulated, both in male and female pluripotent cells, while Tsix expression aberrantly persisted during differentiation. The topological partitioning of the Xic is thus critical to ensure proper developmental timing of X inactivation. Our study illustrates how the genomic architecture of cis-regulatory landscapes can affect the regulation of mammalian developmental processes

TNO at TRECVID 2013 : multimedia event detection and instance search

We describe the TNO system and the evaluation results for TRECVID 2013 Multimedia Event Detection (MED) and instance search (INS) tasks. The MED system consists of a bag-of-word (BOW) approach with spatial tiling that uses low-level static and dynamic visual features, an audio feature and high-level concepts. Automatic speech recognition (ASR) and optical character recognition (OCR) are not used in the system. In the MED case with 100 example training videos, support-vector machines (SVM) are trained and fused to detect an event in the test set. In the case with 0 example videos, positive and negative concepts are extracted as keywords from the textual event description and events are detected with the high-level concepts. The MED results show that the SIFT keypoint descriptor is the one which contributes best to the results, fusion of multiple low-level features helps to improve the performance, and the textual event-description chain currently performs poorly. The TNO INS system presents a baseline open-source approach using standard SIFT keypoint detection and exhaustive matching. In order to speed up search times for queries a basic map-reduce scheme is presented to be used on a multi-node cluster. Our INS results show above-median results with acceptable search times.This research for the MED submission was performed in the GOOSE project, which is jointly funded by the enabling technology program Adaptive Multi Sensor Networks (AMSN) and the MIST research program of the Dutch Ministry of Defense. The INS submission was partly supported by the MIME project of the creative industries knowledge and innovation network CLICKNL.peer-reviewe

Single tube liquid biopsy for advanced non-small cell lung cancer

The need for a liquid biopsy in non-small cell lung cancer (NSCLC) patients is rapidly increasing. We studied the relation between overall survival (OS) and the presence of four cancer biomarkers from a single blood draw in advanced NSCLC patients: EpCAM(high) circulating tumor cells (CTC), EpCAM(low) CTC, tumor-derived extracellular vesicles (tdEV) and cell-free circulating tumor DNA (ctDNA). EpCAM(high) CTC were detected with CellSearch, tdEV in the CellSearch images and EpCAM(low) CTC with filtration after CellSearch. ctDNA was isolated from plasma and mutations present in the primary tumor were tracked with deep sequencing methods. In 97 patients, 21% had >= 2 EpCAM(high) CTC, 15% had >= 2 EpCAM(low) CTC, 27% had >= 18 tdEV and 19% had ctDNA with >= 10% mutant allele frequency. Either one of these four biomarkers could be detected in 45% of the patients and all biomarkers were present in 2%. In 11 out of 16 patients (69%) mutations were detected in the ctDNA. Two or more unfavorable biomarkers were associated with poor OS. The presence of EpCAM(high) CTC and elevated levels of tdEV and ctDNA was associated with a poor OS; however, the presence of EpCAM(low) CTC was not. This single tube approach enables simultaneous analysis of multiple biomarkers to explore their potential as a liquid biopsy