From Dolores Haze to Dakota Fanning: How Nabokov\u27s Little Girl Went from Being a Victim of Sexual Assault to a Fashion Icon

This paper seeks to establish a critical understanding of issues of sexualization and re-appropriation and how they relate to contemporary fashion advertising that specifically utilizes the Lolita Effect

New FTY720-docetaxel nanoparticle therapy overcomes FTY720-induced lymphopenia and inhibits metastatic breast tumour growth

Purpose: Combining molecular therapies with chemotherapy may offer an improved clinical outcome for chemoresistant tumours. Sphingosine-1-phosphate (S1P) receptor antagonist and sphingosine kinase 1 (SK1) inhibitor FTY720 (FTY) has promising anticancer properties, however, it causes systemic lymphopenia which impairs its use in cancer patients. In this study, we developed a nanoparticle (NP) combining docetaxel (DTX) and FTY for enhanced anticancer effect, targeted tumour delivery and reduced systemic toxicity. Methods: Docetaxel, FTY and glucosamine were covalently conjugated to poly(lactic-co-glycolic acid) (PLGA). NPs were characterised by dynamic light scattering and electron microscopy. The cellular uptake, cytotoxicity and in vivo antitumor efficacy of CNPs were evaluated. Results: We show for the first time that in triple negative breast cancer cells FTY provides chemosensitisation to DTX, allowing a four-fold reduction in the effective dose. We have encapsulated both drugs in PLGA complex NPs (CNPs), with narrow size distribution of ~ 100 nm and excellent cancer cell uptake providing sequential, sustained release of FTY and DTX. In triple negative breast cancer cells and mouse breast cancer models, CNPs had similar efficacy to systemic free therapies, but allowed an effective drug dose reduction. Application of CNPs has significantly reversed chemotherapy side effects such as weight loss, liver toxicity and, most notably, lymphopenia. Conclusions: We show for the first time the DTX chemosensitising effects of FTY in triple negative breast cancer. We further demonstrate that encapsulation of free drugs in CNPs can improve targeting, provide low off-target toxicity and most importantly reduce FTY-induced lymphopenia, offering potential therapeutic use of FTY in clinical cancer treatment

Field template-based design and biological evaluation of new sphingosine kinase 1 inhibitors

Purpose: Sphingosine kinase 1 (SK1) is a protooncogenic enzyme expressed in many human tumours and is associated with chemoresistance and poor prognosis. It is a potent therapy target and its inhibition chemosensitises solid tumours. Despite recent advances in SK1 inhibitors synthesis and validation, their clinical safety and chemosensitising options are not well described. In this study, we have designed, synthesised and tested a new specific SK1 inhibitor with a low toxicity profile. Methods: Field template molecular modelling was used for compound design. Lead compounds were tested in cell and mouse cancer models. Results: Field template analysis of three known SK1 inhibitors, SKI-178, 12aa and SK1-I, was performed and compound screening identified six potential new SK1 inhibitors. SK1 activity assays in both cell-free and in vitro settings showed that two compounds were effective SK1 inhibitors. Compound SK-F has potently decreased cancer cell viability in vitro and sensitised mouse breast tumours to docetaxel (DTX) in vivo, without significant whole-body toxicity. Conclusion: Through field template screening, we have identified a new SK1 inhibitor, SK-F, which demonstrated antitumour activity in vitro and in vivo without overt toxicity when combined with DTX

Parametric amplification of a superconducting plasma wave

Many applications in photonics require all-optical manipulation of plasma waves1, which can concentrate electromagnetic energy on sub-wavelength length scales. This is difficult in metallic plasmas because of their small optical nonlinearities. Some layered superconductors support Josephson plasma waves2, 3, involving oscillatory tunnelling of the superfluid between capacitively coupled planes. Josephson plasma waves are also highly nonlinear4, and exhibit striking phenomena such as cooperative emission of coherent terahertz radiation5, 6, superconductor–metal oscillations7 and soliton formation8. Here, we show that terahertz Josephson plasma waves can be parametrically amplified through the cubic tunnelling nonlinearity in a cuprate superconductor. Parametric amplification is sensitive to the relative phase between pump and seed waves, and may be optimized to achieve squeezing of the order-parameter phase fluctuations9 or terahertz single-photon devices

A dynamical stability limit for the charge density wave in K0.3MoO3

We study the response of the one-dimensional charge density wave in K0.3MoO3 to different types of excitation with femtosecond optical pulses. We compare the response to direct excitation of the lattice at mid-infrared frequencies with that to the injection of quasi-particles across the low-energy charge density wave gap and to charge transfer excitations in the near infrared. For all three cases, we observe a fluence threshold above which the amplitude-mode oscillation frequency is softened and the mode becomes increasingly damped. We show that all the data can be collapsed onto a universal curve in which the melting of the charge density wave occurs abruptly at a critical lattice excursion. These data highlight the existence of a universal stability limit for a charge density wave, reminiscent of the empirical Lindemann criterion for the stability of a crystal lattice

Influence of transnational economic alliances on the IFRS convergence decision in India - institutional perspectives

This study contributes to the literature on global governance by highlighting the importance of not losing sight of the nation state as an important player in the transnational governance arena. Specifically, literature on global (accounting) regulation devotes a great deal of attention to the roles of organisations and agencies with transnational remit (such as global standard setters, donor agencies) while often downplaying the significant impacts of the more traditional cross-country links forged through economic relationships and resource dependencies between national and transnational institutional fields. This was specially noted in the case of the indirect influences of the US’s decision to delay IFRS convergence. While being interpreted as an indirect source of influence, such a decision played a very significant role on the convergence negotiations in India. The study shows how the US influence was channelled through Japan with which India has significant trade and economic relations and, most importantly, holds a joint forum specifically to discuss convergence issues. The consequences of India’s links with countries such as US and Japan in the decision-making process provide a vivid indication of the important roles of cross-governmental relationships in the global governance arena, and also question the position of transnational organisations as pervasive powers in such governance. The study’s findings clearly demonstrate that the pursuit of full IFRS convergence strongly favoured by the transnational forces was invariably challenged in the Indian context by the influences of powerful nation states advocating a more cautious approach

Ultra High Efficiency ESP for Fine Particulate and Air Toxics Control

Nearly ninety percent of U.S. coal-fired utility boilers are equipped with electrostatic precipitators (ESP). Cost effective retrofittable ESP technologies are the only means to accomplish Department of Energy's (DOE) goal of a major reduction in fine particulate and air toxic emissions from coal-fired power plants. Particles in the size range of 0.1 to 5 {micro}m typically escape ESPs. Metals, such as arsenic, cadmium, lead, molybdenum and antimony, concentrate on these particles. This is the main driver for improved fine particulate control. Vapor phase emissions of mercury, selenium and arsenic are also of major concern. Current dry ESPs, which operate at temperatures greater than 280 F, provide little control for vapor phase toxics. The need for inherent improvement to ESPs has to be considered keeping in perspective the current trend towards the use of low sulfur coals. Switching to low sulfur coals is the dominant approach for SO{sub 2} emission reduction in the utility industry. Low sulfur coals generate high resistivity ash, which can cause an undesirable phenomenon called ''back corona.'' Higher particulate emissions occur if there is back corona in the ESP. Results of the pilot-scale testing identified the ''low temperature ESP'' concept to have the biggest impact for the two low sulfur coals investigated. Lowering the flue gas temperature to 220 F provided the maximum impact in terms of decreased emissions. Intermediate operating temperatures (reduction from 340 to 270 F) also gave significant ESP performance improvement. A significant reduction in particulate emissions was also noted when the flue gas humidity was increased (temperature held constant) from the baseline condition for these moderately high resistivity ash coals. Independent control of flue gas humidity and temperature was an important and a notable element in this project. Mercury emissions were also measured as a function of flue gas temperature. Mercury emissions decreased as the flue gas temperature was lowered, indicating the native ability of ash to capture the mercury. Pulsed operation of the ESP with the SIR module provided a 2 to 3-fold reduction in emissions at the higher operating temperatures. In light of the positive results from Phase I, we propose proof of concept testing in the field in Phase II. The main objective of the Phase II testing would be to determine the ESP performance improvement as a function of flue gas temperature and humidity for a range of low-sulfur coals being fired by utilities. Equally important will be the long-term evaluation of the risk of corrosion and plugging (due to acid condensation) associated with low temperature operation. The impact of higher flue gas velocities (lower SCA-specific collection area), compared to the laboratory pilot program, would also need to be evaluated. A secondary objective would be to examine mercury capture by the ESP at the different temperatures and with sorbent injection

Concordance and Disconcordance of Serum Levels of Leptin with Leucocyte Telomere Length Across Spectrum of Adult Body Mass Index Among Indian Rural Population

Background: Obesity is a prominent avoidable cause of mortality and a growing health concern in both adults and children throughout the world. The study's goal is to measure leucocyte telomere length and its relationship with leptin throughout the BMI spectrum. Material & Method: This cross sectional study was conducted among patients attending tertiary care hospital fulfilling the inclusion criteria. The serum taken from these samples was numbered and sent to the lab in an ice box for Leptin and Telomere length analysis. Telomere length was measured in leukocytes using the qPCR method. Result: Total of 360 patients with mean age of the patients 47.84±15.84yrs, equally distributed in age group of 25-39yrs, 40-54yrs and >=55yrs of age. A significant negative strength of association of BMI with telomere length (r=-0.21, p<0.05) and a significant association of waist to hip ratio with telomere length (r=0.24, p<0.05). No significant relation between telomere length with the serum level of Leptin (r=0.09, p=0.386).  Conclusion: The mean Telomere length correlated negatively with BMI and age. In the current investigation, leptin had no significant connection with telomere length

A SARS-CoV-2 protein interaction map reveals targets for drug repurposing

The novel coronavirus SARS-CoV-2, the causative agent of COVID-19 respiratory disease, has infected over 2.3 million people, killed over 160,000, and caused worldwide social and economic disruption1,2. There are currently no antiviral drugs with proven clinical efficacy, nor are there vaccines for its prevention, and these efforts are hampered by limited knowledge of the molecular details of SARS-CoV-2 infection. To address this, we cloned, tagged and expressed 26 of the 29 SARS-CoV-2 proteins in human cells and identified the human proteins physically associated with each using affinity-purification mass spectrometry (AP-MS), identifying 332 high-confidence SARS-CoV-2-human protein-protein interactions (PPIs). Among these, we identify 66 druggable human proteins or host factors targeted by 69 compounds (29 FDA-approved drugs, 12 drugs in clinical trials, and 28 preclinical compounds). Screening a subset of these in multiple viral assays identified two sets of pharmacological agents that displayed antiviral activity: inhibitors of mRNA translation and predicted regulators of the Sigma1 and Sigma2 receptors. Further studies of these host factor targeting agents, including their combination with drugs that directly target viral enzymes, could lead to a therapeutic regimen to treat COVID-19