A mechanistic perspective on plastically flexible coordination polymers

Mechanical flexibility in single crystals of covalently bound materials is a fascinating and poorly understood phenomenon. We present here the first example of a plastically flexible one‐dimensional (1D) coordination polymer. The compound [Zn(μ‐Cl)2(3,5‐dichloropyridine)2]n is flexible over two crystallographic faces. Remarkably, the single crystal remains intact when bent to 180°. A combination of microscopy, diffraction, and spectroscopic studies have been used to probe the structural response of the crystal lattice to mechanical bending. Deformation of the covalent polymer chains does not appear to be responsible for the observed macroscopic bending. Instead, our results suggest that mechanical bending occurs by displacement of the coordination polymer chains. Based on experimental and theoretical evidence, we propose a new model for mechanical flexibility in 1D coordination polymers. Moreover, our calculations propose a cause of the different mechanical properties of this compound and a structurally similar elastic material

Genetic dissection of apoptosis and cell cycle control in response of colorectal cancer treated with preoperative radiochemotherapy

BACKGROUND: In previous analyses we identified therapy-induced upregulation of the CDK inhibitor p21(CIP/WAF-1 )and consequently decreased tumor cell proliferation or loss of Bax as adverse factors for survival in rectal cancer treated with radiochemotherapy. Here, we address the individual role of p53 and its transcriptional targets, p21(CIP/WAF-1 )and Bax, on apoptosis induced by individual components of multimodal anticancer therapy, i.e. 5-fluorouracil (5-FU), ionising γ-radiation (IR) and heat shock/hyperthermia. METHODS: We analysed tumor samples 66 patients with rectal carcinoma treated by a neoadjuvant approach with radiochemotherapy ± heat shock/hyperthermia for the expression and mutation of p53 and the expression of p21(CIP/WAF-1 )and Bax. These data were correlated with the tumor response. The functional relevance of p53, p21(CIP/WAF-1 )and Bax was investigated in isogeneic HCT116 cell mutants treated with 5-FU, IR and heat shock. RESULTS: Rectal carcinoma patients who received an optimal heat shock treatment showed a response that correlated well with Bax expression (p = 0.018). Local tumor response in the whole cohort was linked to expression of p21(CIP/WAF-1 )(p < 0.05), but not p53 expression or mutation. This dichotomy of p53 pathway components regulating response to therapy was confirmed in vitro. In isogeneic HCT116 cell mutants, loss of Bax but not p53 or p21(CIP/WAF-1 )resulted in resistance against heat shock. In contrast, loss of p21(CIP/WAF-1 )or, to a lesser extent, p53 sensitized predominantly for 5-FU and IR. CONCLUSION: These data establish a different impact of p53 pathway components on treatment responses. While chemotherapy and IR depend primarily on cell cycle control and p21, heat shock depends primarily on Bax. In contrast, p53 status poorly correlates with response. These analyses therefore provide a rational approach for dissecting the mode of action of single treatment modalities that may be employed to circumvent clinically relevant resistance mechanisms in rectal cancer

Kilogram scale throughput performance of the KATRIN tritium handling system

The Karlsruhe Tritium Neutrino (KATRIN) experiment aims to determine the effective mass of the electron antineutrino by investigating the tritium β-spectrum close to the energetic endpoint. To achieve this, there are stringent and challenging requirements on the stability of the gaseous tritium source. The tritium loop system has the task to provide the 95 %. KATRIN started full tritium operation in early 2019. This paper focusses on the observed radiochemical effects and confirms that non-negligible quantities during initial tritium operation have to be expected

Influencing physician prescribing in an international context : the role of systems, policies, and patients

Niet-evidence based geneesmiddelengebruik leidt tot hogere kosten en sub-optimale gezondheidszorg. Daarom worden er maatregelen en strategieën ontwikkeld om het geneesmiddelengebruik beter en meer gebaseerd op bestaande kennis te maken. UMCG-onderzoeker Heidrun Sturm onderzocht welke factoren huisartsen beïnvloeden bij het voorschrijven van medicijnen aan patiënten met chronisch hartfalen in veertien Europese landen. De belangrijkste verklaring voor verschillen in voorschrijven binnen Europa blijken de klinische kenmerken van de patiënt te zijn. Verder is het land waar de behandeling plaatsvindt een factor. Daarbij bleek de kracht van de eerstelijns zorg belangrijk. In landen waarbij de eerste lijn sterker georganiseerd is (waar patiënten bijvoorbeeld alleen na verwijzing terecht kunnen bij een specialist) wordt minder volgens de richtlijnen voorgeschreven dan in landen waarin de eerste lijn minder sterk is.