Photodynamic killing of cancer cells by a Platinum(II) complex with cyclometallating ligand

Photodynamic therapy that uses photosensitizers which only become toxic upon light-irradiation provides a strong alternative to conventional cancer treatment due to its ability to selectively target tumour material without affecting healthy tissue. Transition metal complexes are highly promising PDT agents due to intense visible light absorption, yet the majority are toxic even without light. This study introduces a small, photostable, charge-neutral platinum-based compound, Pt(II) 2,6-dipyrido-4-methyl-benzenechloride, complex 1, as a photosensitizer, which works under visible light. Activation of the new photosensitizer at low concentrations (0.1–1 μM) by comparatively low dose of 405 nm light (3.6 J cm−2) causes significant cell death of cervical, colorectal and bladder cancer cell lines, and, importantly, a cisplatin resistant cell line EJ-R. The photo-index of the complex is 8. We demonstrate that complex 1 induces irreversible DNA single strand breaks following irradiation, and that oxygen is essential for the photoinduced action. Neither light, nor compound alone led to cell death. The key advantages of the new drug include a remarkably fast accumulation time (diffusion-controlled, minutes), and photostability. This study demonstrates a highly promising new agent for photodynamic therapy, and attracts attention to photostable metal complexes as viable alternatives to conventional chemotherapeutics, such as cisplatin

Realistic simulations of single-spin nondemolition measurement by magnetic resonance force microscopy

A requirement for many quantum computation schemes is the ability to measure single spins. This paper examines one proposed scheme: magnetic resonance force microscopy, including the effects of thermal noise and back-action from monitoring. We derive a simplified equation using the adiabatic approximation, and produce a stochastic pure state unraveling which is useful for numerical simulations.Comment: 33 pages LaTeX, 9 figure files in EPS format. Submitted to Physical Review

Removal of a single photon by adaptive absorption

We present a method to remove, using only linear optics, exactly one photon from a field-mode. This is achieved by putting the system in contact with an absorbing environment which is under continuous monitoring. A feedback mechanism then decouples the system from the environment as soon as the first photon is absorbed. We propose a possible scheme to implement this process and provide the theoretical tools to describe it

Distinctive diets of eutherian predators in Australia

Introduction of the domestic cat and red fox has devastated Australian native fauna. We synthesized Australian diet analyses to identify traits of prey species in cat, fox and dingo diets, which prey were more frequent or distinctive to the diet of each predator, and quantified dietary overlap. Nearly half (45%) of all Australian terrestrial mammal, bird and reptile species occurred in the diets of one or more predators. Cat and dingo diets overlapped least (0.64 ± 0.27, n = 24 location/time points) and cat diet changed little over 55 years of study. Cats were more likely to have eaten birds, reptiles and small mammals than foxes or dingoes. Dingo diet remained constant over 53 years and constituted the largest mammal, bird and reptile prey species, including more macropods/potoroids, wombats, monotremes and bandicoots/bilbies than cats or foxes. Fox diet had greater overlap with both cats (0.79 ± 0.20, n = 37) and dingoes (0.73 ± 0.21, n = 42), fewer distinctive items (plant material, possums/gliders) and significant spatial and temporal heterogeneity over 69 years, suggesting the opportunity for prey switching (especially of mammal prey) to mitigate competition. Our study reinforced concerns about mesopredator impacts upon scarce/threatened species and the need to control foxes and cats for fauna conservation. However, extensive dietary overlap and opportunism, as well as low incidence of mesopredators in dingo diets, precluded resolution of the debate about possible dingo suppression of foxes and cats

Adiabatic elimination in quantum stochastic models

We consider a physical system with a coupling to bosonic reservoirs via a quantum stochastic differential equation. We study the limit of this model as the coupling strength tends to infinity. We show that in this limit the solution to the quantum stochastic differential equation converges strongly to the solution of a limit quantum stochastic differential equation. In the limiting dynamics the excited states are removed and the ground states couple directly to the reservoirs.Comment: 17 pages, no figures, corrected mistake

Artificial intelligence for dementia drug discovery and trials optimization

Drug discovery and clinical trial design for dementia have historically been challenging. In part these challenges have arisen from patient heterogeneity, length of disease course, and the tractability of a target for the brain. Applying big data analytics and machine learning tools for drug discovery and utilizing them to inform successful clinical trial design has the potential to accelerate progress. Opportunities arise at multiple stages in the therapy pipeline and the growing availability of large medical data sets opens possibilities for big data analyses to answer key questions in clinical and therapeutic challenges. However, before this goal is reached, several challenges need to be overcome and only a multi-disciplinary approach can promote data-driven decision-making to its full potential. Herein we review the current state of machine learning applications to clinical trial design and drug discovery, while presenting opportunities and recommendations that can break down the barriers to implementation

Comparison of the cardiometabolic profiles of adolescents conceived through ART with those of a non-ART cohort

STUDY QUESTION Is the cardiometabolic health of adolescents conceived through ART worse than that of their counterparts conceived without ART? SUMMARY ANSWER The majority of cardiometabolic and vascular health parameters of adolescents conceived through ART are similar or more favourable, than those of their counterparts of similar age and conceived without ART. WHAT IS KNOWN ALREADY It has been proposed that the cardiometabolic health of offspring conceived with ART may be unfavourable compared to that of their counterparts conceived without ART. The literature pertaining to cardiometabolic health of offspring conceived after ART is contradictory, but generally suggests unfavourable cardiometabolic health parameters, such as an increase in blood pressure (BP), vascular dysfunction and adiposity, as well as unfavourable glucose and lipid profiles. With over 8 million children and adults born through ART worldwide, it is important to investigate whether these early signs of adverse cardiometabolic differences persist into adolescence and beyond. STUDY DESIGN, SIZE, DURATION The Growing Up Healthy Study (GUHS) is a prospective cohort study that recruited 303 adolescents and young adults conceived after ART (aged 13–21 years) and born between 1991 and 2001 in Western Australia. Their health parameters, including cardiometabolic factors, were assessed and compared with counterparts from the Raine Study Generation 2 (Gen2). The 2868 Gen2 participants were born 1989–1992 and are representative of the Western Australian adolescent population. At ∼17 years of age (2013–2017), 163 GUHS participants replicated assessments previously completed by Gen2 at a similar age. PARTICIPANTS/MATERIALS, SETTING, METHODS Cardiometabolic parameters were compared between a total of 163 GUHS and 1457 Gen2 adolescents. Separate male (GUHS n = 81, Gen2 n = 735) and female (GUHS n = 82, Gen2 n = 722) analyses were conducted. Assessments consisted of a detailed questionnaire including health, lifestyle and demographic parameters, anthropometric assessments (height, weight, BMI, waist circumference and skinfold thickness), fasting serum biochemistry, arterial stiffness and BP (assessed using applanation tonometry). Abdominal ultrasonography was used to assess the presence and severity of hepatic steatosis, and thickness of abdominal fat compartments. Non-alcoholic fatty liver disease (NAFLD) was diagnosed if there was sonographic fatty liver in the absence of significant alcohol consumption. Chi2, Fisher’s exact and Mann–Whitney U tests, performed in SPSS V25, examined cohort differences and generalized estimating equations adjusted for the following covariates: singleton vs non-singleton pregnancy, birthweight (z-score), gestational age, BMI, smoking, alcohol consumption in the past 6 months and parent cardiovascular status. Arterial stiffness measures and waist circumference were additionally adjusted for height, and female analyses were additionally adjusted for use of oral contraceptives in the preceding 6 months. MAIN RESULTS AND THE ROLE OF CHANCE In adjusted analyses, GUHS females had a lower BMI (22.1 vs 23.3 kg/m2, P = 0.014), and thinner skinfolds (triceps, subscapular, mid-abdominal; 16.9 vs 18.7 mm, P = 0.021, 13.4 vs 15.0 mm, P = 0.027, 19.7 vs 23.2 mm, P < 0.001, respectively), whereas males were not significantly different. Waist circumference was lower in GUHS adolescents (males: 78.1 vs 81.3 cm, P = 0.008, females: 76.7 vs 83.3 cm, P = 0.007). There were no significant differences between the two groups in glucose, insulin, homeostatic model assessment for insulin resistance, low-density lipoprotein cholesterol, non-high-density lipoprotein cholesterol (non-HDL-C), total cholesterol (TC), alanine aminotransferase and high-sensitivity C-reactive protein in both sexes. In females, serum triglycerides were lower in GUHS adolescents (1.0 vs 1.2 mmol/l, P = 0.029). GUHS males had higher serum HDL-C (1.1 vs 1.0 mmol/l, P = 0.004) and a lower TC/HDL-C ratio (3.2 vs 3.6, P = 0.036). There were no significant differences in the prevalence of NAFLD or steatosis severity scores between the cohorts in males and females. GUHS females had less subcutaneous adipose tissue (9.4 vs 17.9 mm, P < 0.001), whereas GUHS males had greater visceral adipose thickness (44.7 vs 36.3 mm, P < 0.001). There was no significant difference in pre-peritoneal adipose thickness. Pulse wave velocity was lower in GUHS males (5.8 vs 6.3 m/s, P < 0.001) and heart rate corrected augmentation index was lower in GUHS females (−8.4 vs −2.7%, P = 0.048). There were no significant differences in BP or heart rate in males or females between the two groups. LIMITATIONS, REASONS FOR CAUTION Despite the substantial study size and the unique study design of the ART cohort, we were unable to differentiate between different types of ART, due to the low number of ICSI cycles (e.g. IVF vs ICSI), draw definite conclusions, or relate the outcomes to the cause of infertility. Considering the differences in time points when both cohorts were studied, external factors could have changed, which could not be accounted for. Given the observational nature of this study, causation cannot be proven. WIDER IMPLICATIONS OF THE FINDINGS Contrary to our hypothesis and previous findings focussing mainly on childhood, this study reports mostly similar or favourable cardiometabolic markers in adolescents conceived with ART compared to those conceived without ART. The greater visceral adipose thickness, particularly present in males, requires further investigation. While these findings are generally reassuring, future well-designed and appropriately powered studies are required to definitively address the issue of cardiometabolic health in ART adults. STUDY FUNDING/COMPETING INTEREST(S) This project was supported by NHMRC project grant number 1042269 and R.J.H. received education grant funding support from Ferring Pharmaceuticals. R.J.H. is the Medical Director of Fertility Specialists of Western Australia and a shareholder in Western IVF. He has received educational sponsorship from MSD, Merck-Serono and Ferring Pharmaceuticals. P.B. is the Scientific Director of Concept Fertility Centre, Subiaco, Western Australia. J.L.Y. is the Medical Director of PIVET Medical Centre, Perth, Western Australia

Trapping atoms in the vacuum field of a cavity

The aim of this work is to find ways to trap an atom in a cavity. In contrast to other approaches we propose a method where the cavity is basically in the vacuum state and the atom in the ground state. The idea is to induce a spatial dependent AC Stark shift by irradiating the atom with a weak laser field, so that the atom experiences a trapping force. The main feature of our setup is that dissipation can be strongly suppressed. We estimate the lifetime of the atom as well as the trapping potential parameters and compare our estimations with numerical simulations.Comment: 8 pages, 8 figure

A Densified Liquid Methane Delivery System for the Altair Ascent Stage

The Altair Lunar Lander is currently carrying options for both cryogenic and hypergolic ascent stage propulsion modules. The cryogenic option uses liquid methane and liquid oxygen to propel Altair from the lunar surface back to rendezvous with the Orion command module. Recent studies have determined that the liquid methane should be densified by subcooling it to 93 K in order to prevent over-pressurization of the propellant tanks during the 210 day stay on the lunar surface. A trade study has been conducted to determine the preferred method of producing; loading, and maintaining the subcooled, densified liquid methane onboard Altair from a ground operations perspective. The trade study took into account the limitations in mass for the launch vehicle and the mobile launch platform as well as the historical reliability of various components and their thermal efficiencies. Several unique problems were encountered, namely delivering a small amount of a cryogenic propellant to a flight tank that is positioned over 350 ft above the launch pad as well as generating the desired delivery temperature of the methane at 93 K which is only 2.3 K above the methane triple point of 90.7 K. Over 20 methods of subcooled liquid methane production and delivery along with the associated system architectures were investigated to determine the best solutions to the problem. The top four cryogenic processing solutions were selected for further evaluation and detailed thermal modeling. This paper describes the results of the preliminary trade analysis of the 20 plus methane densification methods considered. The results of the detailed analysis will be briefed to the Altair Project Office and their propulsion team as well as the Ground Operations Project Office before the down-select is made between cryogenic and hypergolic ascent stages in August 2010

Feedback-control of quantum systems using continuous state-estimation

We present a formulation of feedback in quantum systems in which the best estimates of the dynamical variables are obtained continuously from the measurement record, and fed back to control the system. We apply this method to the problem of cooling and confining a single quantum degree of freedom, and compare it to current schemes in which the measurement signal is fed back directly in the manner usually considered in existing treatments of quantum feedback. Direct feedback may be combined with feedback by estimation, and the resulting combination, performed on a linear system, is closely analogous to classical LQG control theory with residual feedback.Comment: 12 pages, multicol revtex, revised and extende