Block Copolymer Cross-Linked Nanoassemblies Improve Particle Stability and Biocompatibility of Superparamagnetic Iron Oxide Nanoparticles

PURPOSE: To develop cross-linked nanoassemblies (CNAs) as carriers for superparamagnetic iron oxide nanoparticles (IONPs). METHODS: Ferric and ferrous ions were co-precipitated inside core-shell type nanoparticles prepared by cross-linking poly(ethylene glycol)-poly(aspartate) block copolymers to prepare CNAs entrapping Fe(3)O(4) IONPs (CNA-IONPs). Particle stability and biocompatibility of CNA-IONPs were characterized in comparison to citrate-coated Fe(3)O(4) IONPs (Citrate-IONPs). RESULTS: CNA-IONPs, approximately 30 nm in diameter, showed no precipitation in water, PBS, or a cell culture medium after 3 or 30 h, at 22, 37, and 43°C, and 1, 2.5, and 5 mg/mL, whereas Citrate-IONPs agglomerated rapidly (\u3e 400 nm) in all aqueous media tested. No cytotoxicity was observed in a mouse brain endothelial-derived cell line (bEnd.3) exposed to CNA-IONPs up to 10 mg/mL for 30 h. Citrate-IONPs (\u3e 0.05 mg/mL) reduced cell viability after 3 h. CNA-IONPs retained the superparamagnetic properties of entrapped IONPs, enhancing T2-weighted magnetic resonance images (MRI) at 0.02 mg/mL, and generating heat at a mild hyperthermic level (40 ~ 42°C) with an alternating magnetic field (AMF). CONCLUSION: Compared to citric acid coating, CNAs with a cross-linked anionic core improved particle stability and biocompatibility of IONPs, which would be beneficial for future MRI and AMF-induced remote hyperthermia applications

Block Copolymer Self-Assembled and Cross-linked Nanoassemblies for Combination Delivery of Iron Oxide and Doxorubicin

We describe the development of nanoscale polymer drug carriers for the combinational delivery of an anticancer drug (doxorubicin: DOX) along with super paramagnetic iron oxide nanoparticles (IONPs). The drug molecules were electrostatically loaded into both block copolymer self-assembled nanoassemblies (SNAs) and cross-linked nanoassemblies (CNAs). Both nanoassemblies entrapped DOX and IONPs either individually or in tandem, maintaining sub-100 nm diameter. The IONP-loaded nanoassemblies generated heat in the presence of an alternating magnetic field (AMF). Incorporation of the drug payload, DOX, showed no adverse effects on the heating profile. Drug release from the SNAs and CNAs was accelerated as temperature increased from the normal body temperature (37°C) to a mild hyperthermic condition (40 ~ 42°C). CNAs released DOX faster than SNAs regardless of an incubation temperature. CNAs co-entrapped IONPs and DOX were more stable than SNAs in aqueous solutions for five days. These results suggest that block copolymer cross-linked nanoassemblies provide viable delivery platforms for combination delivery of inorganic molecules, anticancer drugs, and potentially other various biologically active substances

Hospitality entrepreneurs managing quality of life and business growth

The hospitality industry is dominated by small- and medium-sized enterprises (SMEs).They are often led by entrepreneurs who face the challenge of simultaneously managing business decisions and their own wellbeing. The competitiveness of tourism destinations often depends on these entrepreneurs and therefore understanding their motivations and work patterns is critical. Research on individual wellbeing increasingly builds on the concept of quality of life (QoL). Hospitality and tourism literature so far predominantly focused on investigating QoL for tourists and residents, rather than for entrepreneurs’ QoL, even though being key stakeholders in the hospitality industry. Therefore, this study explores the factors influencing hospitality entrepreneurs’ quality of life (“HE-QoL”) and how these relate to business growth. Results of a 380 hospitality entrepreneurs’ survey identify six distinct factors of HE-QoL. Two groups of HE-QoL are identified with significant differences in fitness level activity, entrepreneurial competencies and business growth. Findings lead to recommendations to reduce stress to improve HE-QoL, and to develop entrepreneurial competencies, which help to cope with entrepreneurial challenges. Tourism destinations and politics can support hospitality entrepreneurs in these actions by creating conditions that foster social exchange in regional communities and trust in political and economic stability

Poaching and firm-sponsored training: first clean evidence

A series of seminal theoretical papers argues that poaching of employees may hamper company-sponsored general training. However, the extent of poaching, its determinants and consequences, remains an open empirical question. We provide a novel empirical identification strategy for poaching and investigate its causes and consequences. We find that only a small number of training firms in Germany are poaching victims. Firms are more likely to poach employees during an economic downturn. Training firms respond to poaching by lowering the share of new apprentice intakes in the following years

Gene expression profile comparison between bone metastatic and non-metastatic prostate cancer cell lines

Astronauts suffer from cardiovascular deconditioning during space flight where they are exposed to microgravity. Alterations under real and simulated microgravity have been found e.g. in the cytoskeleton and apoptosis in endothelial cells (ECs) and smooth muscle cells (SMCs)1, 2. P2 receptors play an important role in a variety of vascular functions of ECs and SMCs. However, the functional role of purinergic signalling in ECs and SMCs under microgravity is still unclear. In this study primary ECs and SMCs were isolated from bovine aorta and characterized using specific markers. Additionally, EC growth medium collected during culture under normal gravity was used as conditioned medium for SMCs and vice versa to mimic a co-culture model. Here we show for the first time that the P2-receptor expression pattern is altered in ECs and SMCs under simulated microgravity achieved by a clinostat. Interestingly, conditioned medium compensated the alterations in the expression of specific P2-receptors. P2X7 was down-regulated in ECs after 24h clinorotation but recovered to the gene and protein expression level found under normal gravity when cultured in conditioned medium from SMCs. Our results showed an altered P2-receptor expression pattern under simulated microgravity. The paracrine effect between ECs and SMCs seems to be an important regulator of cell behaviour under altered gravity conditions. Several artificial P2-receptor ligands are already utilized as drugs. Thus it might be reasonable to consider them for drug development for astronaut treatment of cardiovascular deconditioning in the future

Sentinel lymph node mapping and intraoperative assessment in a prospective, international, multicentre, observational trial of patients with cervical cancer: The SENTIX trial

Background: SENTIX (ENGOT-CX2/CEEGOG-CX1) is an international, multi centre, prospective observational trial evaluating sentinel lymph node (SLN) biopsy without pelvic lymph node dissection in patients with early-stage cervical cancer. We report the final preplanned analysis of the secondary end-points: SLN mapping and outcomes of intraoperative SLN pathology. Methods: Forty-seven sites (18 countries) with experience of SLN biopsy participated in SENTIX. We preregistered patients with stage IA1/lymphovascular space invasion-positive to IB2 (4 cm or smaller or 2 cm or smaller for fertility-sparing treatment) cervical cancer without suspicious lymph nodes on imaging before surgery. SLN frozen section assessment and pathological ultrastaging were mandatory. Patients were registered postoperatively if SLN were bilaterally detected in the pelvis, and frozen sections were negative. Trial registration: ClinicalTrials.gov (NCT02494063). Results: We analysed data for 395 preregistered patients. Bilateral detection was achieved in 91% (355/395), and it was unaffected by tumour size, tumour stage or body mass index, but it was lower in older patients, in patients who underwent open surgery, and in sites with fewer cases. No SLN were found outside the seven anatomical pelvic regions. Most SLN and positive SLN were localised below the common iliac artery bifurcation. Single positive SLN above the iliac bifurcation were found in 2% of cases. Frozen sections failed to detect 54% of positive lymph nodes (pN1), including 28% of cases with macrometastases and 90% with micrometastases. Interpretation: SLN biopsy can achieve high bilateral SLN detection in patients with tumours of 4 cm or smaller. At experienced centres, all SLN were found in the pelvis, and most were located below the iliac vessel bifurcation. SLN frozen section assessment is an unreliable tool for intraoperative triage because it only detects about half of N1 cases. (C) 2020 The Author(s). Published by Elsevier Ltd

Improved eV-scale sterile-neutrino constraints from the second KATRIN measurement campaign

We present the results of the light sterile neutrino search from the second Karlsruhe Tritium Neutrino (KATRIN) measurement campaign in 2019. Approaching nominal activity, 3.76×106 tritium β-electrons are analyzed in an energy window extending down to 40 eV below the tritium end point at E0=18.57  keV. We consider the 3ν+1 framework with three active and one sterile neutrino flavors. The analysis is sensitive to a fourth mass eigenstate m24≲1600  eV2 and active-to-sterile mixing |Ue4|2≳6×10−3. As no sterile-neutrino signal was observed, we provide improved exclusion contours on m24 and |Ue4|2 at 95% C.L. Our results supersede the limits from the Mainz and Troitsk experiments. Furthermore, we are able to exclude the large Δm241 solutions of the reactor antineutrino and gallium anomalies to a great extent. The latter has recently been reaffirmed by the BEST Collaboration and could be explained by a sterile neutrino with large mixing. While the remaining solutions at small Δm241 are mostly excluded by short-baseline reactor experiments, KATRIN is the only ongoing laboratory experiment to be sensitive to relevant solutions at large Δm241 through a robust spectral shape analysis

New Constraint on the Local Relic Neutrino Background Overdensity with the First KATRIN Data Runs

We report on the direct cosmic relic neutrino background search from the first two science runs of the KATRIN experiment in 2019. Beta-decay electrons from a high-purity molecular tritium gas source are analyzed by a high-resolution MAC-E filter around the kinematic endpoint at 18.57 keV. The analysis is sensitive to a local relic neutrino overdensity of 9.7e10 (1.1e11) at a 90% (95%) confidence level. A fit of the integrated electron spectrum over a narrow interval around the kinematic endpoint accounting for relic neutrino captures in the Tritium source reveals no significant overdensity. This work improves the results obtained by the previous kinematic neutrino mass experiments at Los Alamos and Troitsk. We furthermore update the projected final sensitivity of the KATRIN experiment to <1e10 at 90% confidence level, by relying on updated operational conditions.Comment: 7 pages, 7 figure