TTFields alone and in combination with chemotherapeutic agents effectively reduce the viability of MDR cell sub-lines that over-express ABC transporters

<p>Abstract</p> <p>Background</p> <p>Exposure of cancer cells to chemotherapeutic agents may result in reduced sensitivity to structurally unrelated agents, a phenomenon known as multidrug resistance, MDR. The purpose of this study is to investigate cell growth inhibition of wild type and the corresponding MDR cells by Tumor Treating Fields - TTFields, a new cancer treatment modality that is free of systemic toxicity. The TTFields were applied alone and in combination with paclitaxel and doxorubicin.</p> <p>Methods</p> <p>Three pairs of wild type/MDR cell lines, having resistivity resulting from over-expression of ABC transporters, were studied: a clonal derivative (C11) of parental Chinese hamster ovary AA8 cells and their emetine-resistant sub-line Emt^R1; human breast cancer cells MCF-7 and their mitoxantrone-resistant sub lines MCF-7/Mx and human breast cancer cells MDA-MB-231 and their doxorubicin resistant MDA-MB-231/Dox cells. TTFields were applied for 72 hours with and without the chemotherapeutic agents. The numbers of viable cells in the treated cultures and the untreated control groups were determined using the XTT assay. Student t-test was applied to asses the significance of the differences between results obtained for each of the three cell pairs.</p> <p>Results</p> <p>TTFields caused a similar reduction in the number of viable cells of wild type and MDR cells. Treatments by TTFields/drug combinations resulted in a similar increased reduction in cell survival of wild type and MDR cells. TTFields had no effect on intracellular doxorubicin accumulation in both wild type and MDR cells.</p> <p>Conclusions</p> <p>The results indicate that TTFields alone and in combination with paclitaxel and doxorubicin effectively reduce the viability of both wild type and MDR cell sub-lines and thus can potentially be used as an effective treatment of drug resistant tumors.</p

Shell-Controlled Photoluminescence in CdSe/CNT Nanohybrids

A new type of nanohybrids containing carbon nanotubes (CNTs) and CdSe quantum dots (QDs) was prepared using an electrostatic self-assembly method. The CdSe QDs were capped by various mercaptocarboxylic acids, including thioglycolic acid (TGA), dihydrolipoic acid (DHLA) and mercaptoundecanoic acid (MUA), which provide shell thicknesses of ~5.2, 10.6 and 15.2 Å, respectively. The surface-modified CdSe QDs are then self-assembled onto aridine orange-modified CNTs via electrostatic interaction to give CdSe/CNT nanohybrids. The photoluminescence (PL) efficiencies of the obtained nanohybrids increase significantly with the increase of the shell thickness, which is attributed to a distance-dependent photo-induced charge-transfer mechanism. This work demonstrates a simple mean for fine tuning the PL properties of the CdSe/CNT nanohybrids and gains new insights to the photo-induced charge transfer in such nanostructures

Relativistic Dynamics and Extreme Mass Ratio Inspirals

It is now well-established that a dark, compact object (DCO), very likely a massive black hole (MBH) of around four million solar masses is lurking at the centre of the Milky Way. While a consensus is emerging about the origin and growth of supermassive black holes (with masses larger than a billion solar masses), MBHs with smaller masses, such as the one in our galactic centre, remain understudied and enigmatic. The key to understanding these holes - how some of them grow by orders of magnitude in mass - lies in understanding the dynamics of the stars in the galactic neighbourhood. Stars interact with the central MBH primarily through their gradual inspiral due to the emission of gravitational radiation. Also stars produce gases which will subsequently be accreted by the MBH through collisions and disruptions brought about by the strong central tidal field. Such processes can contribute significantly to the mass of the MBH and progress in understanding them requires theoretical work in preparation for future gravitational radiation millihertz missions and X-ray observatories. In particular, a unique probe of these regions is the gravitational radiation that is emitted by some compact stars very close to the black holes and which could be surveyed by a millihertz gravitational wave interferometer scrutinizing the range of masses fundamental to understanding the origin and growth of supermassive black holes. By extracting the information carried by the gravitational radiation, we can determine the mass and spin of the central MBH with unprecedented precision and we can determine how the holes "eat" stars that happen to be near them.Comment: Update from the first version, 151 pages, accepted for publication @ Living Reviews in Relativit

Prognostic model to predict postoperative acute kidney injury in patients undergoing major gastrointestinal surgery based on a national prospective observational cohort study.

Background: Acute illness, existing co-morbidities and surgical stress response can all contribute to postoperative acute kidney injury (AKI) in patients undergoing major gastrointestinal surgery. The aim of this study was prospectively to develop a pragmatic prognostic model to stratify patients according to risk of developing AKI after major gastrointestinal surgery. Methods: This prospective multicentre cohort study included consecutive adults undergoing elective or emergency gastrointestinal resection, liver resection or stoma reversal in 2-week blocks over a continuous 3-month period. The primary outcome was the rate of AKI within 7 days of surgery. Bootstrap stability was used to select clinically plausible risk factors into the model. Internal model validation was carried out by bootstrap validation. Results: A total of 4544 patients were included across 173 centres in the UK and Ireland. The overall rate of AKI was 14·2 per cent (646 of 4544) and the 30-day mortality rate was 1·8 per cent (84 of 4544). Stage 1 AKI was significantly associated with 30-day mortality (unadjusted odds ratio 7·61, 95 per cent c.i. 4·49 to 12·90; P < 0·001), with increasing odds of death with each AKI stage. Six variables were selected for inclusion in the prognostic model: age, sex, ASA grade, preoperative estimated glomerular filtration rate, planned open surgery and preoperative use of either an angiotensin-converting enzyme inhibitor or an angiotensin receptor blocker. Internal validation demonstrated good model discrimination (c-statistic 0·65). Discussion: Following major gastrointestinal surgery, AKI occurred in one in seven patients. This preoperative prognostic model identified patients at high risk of postoperative AKI. Validation in an independent data set is required to ensure generalizability

On the robustness of attenuation measurements on teleseismic P waves: insights from micro-array analysis of the 2017 North Korean nuclear test

SUMMARY Despite their importance as a fundamental constraint on Earth properties, regional-scale measurements of body-wave seismic attenuation are scarce. This is partially a result of the difficulty in producing robust estimates of attenuation. In this paper, we focus on measuring differential attenuation on records of teleseismic P waves. We examine a unique data set of five records of the North Korean nuclear test of 2017 measured at five broad-band seismic stations deployed within a few metres of each other but using different installation procedures. Given their extreme proximity, we expect zero differential intrinsic attenuation between the different records. However, we find that different attenuation measurement methods and implementation parameters in fact produce significant apparent differential attenuation (Δt*). Frequency-domain methods yield a wide range of Δt* estimates between stations, depending on measurement bandwidth and nuances of signal processing. This measurement instability increases for longer time windows. Time domain methods are largely insensitive to the frequency band being considered but are sensitive to the time window that is chosen. We determine that signal-generated noise can affect measurements in both the frequency and time domain. In some cases, the range of results amounts to a significant fraction of the range of differential attenuation across the conterminous United States as determined by a recent study. We suggest some approaches to manage the inherent instability in these measurements and recommend best practices to confidently estimate body wave attenuation