Quantum noise and mixedness of a pumped dissipative non-linear oscillator

Evolutions of quantum noise, characterized by quadrature squeezing parameter and Fano factor, and of mixedness, quantified by quantum von Neumann and linear entropies, of a pumped dissipative non-linear oscillator are studied. The model can describe a signal mode interacting with a thermal reservoir in a parametrically pumped cavity with a Kerr non-linearity. It is discussed that the initial pure states, including coherent states, Fock states, and finite superpositions of coherent states evolve into the same steady mixed state as verified by the quantum relative entropy and the Bures metric. It is shown analytically and verified numerically that the steady state can be well approximated by a nonclassical Gaussian state exhibiting quadrature squeezing and sub-Poissonian statistics for the cold thermal reservoir. A rapid increase is found in the mixedness, especially for the initial Fock states and superpositions of coherent states, during a very short time interval, and then for longer evolution times a decrease in the mixedness to the same, for all the initial states, and relatively low value of the nonclassical Gaussian state.Comment: 10 pages, 12 figure

Master equations for effective Hamiltonians

We reelaborate on a general method for obtaining effective Hamiltonians that describe different nonlinear optical processes. The method exploits the existence of a nonlinear deformation of the su(2) algebra that arises as the dynamical symmetry of the original model. When some physical parameter (usually related to the dispersive limit) becomes small, we immediately get a diagonal effective Hamiltonian that represents correctly the dynamics for arbitrary states and long times. We apply the same technique to obtain how the noise terms in the original model transform under this scheme, providing a systematic way of including damping effects in processes described in terms of effective Hamiltonians.Comment: 10 pages, no figure

Exploring the mechanisms of renoprotection against progressive glomerulosclerosis

In this review, I introduce the strategy developed by our laboratory to explore the mechanisms of renoprotection against progressive glomerulosclerosis leading to renal death. First, I describe the experimental rat model in which disturbances of vascular regeneration and glomerular hemodynamics lead to irreversible glomerulosclerosis. Second, I discuss the possible mechanisms determining the progression of glomerulosclerosis and introduce a new imaging system based on intravital confocal laser scanning microscopy. Third, I provide an in-depth review of the regulatory glomerular hemodynamics at the cellular and molecular levels while focusing on the pivotal role of Ca2+-dependent gap junctional intercellular communication in coordinating the behavior of mesangial cells. Last, I show that local delivery of renoprotective agents, in combination with diagnostic imaging of the renal microvasculature, allows the evaluation of the therapeutic effects of angiotensin II receptor and cyclooxygenase activity local blockade on the progression of glomerulosclerosis, which would otherwise lead to renal death

2,4-Diaminopyrimidines as Potent Inhibitors of Trypanosoma brucei and Identification of Molecular Targets by a Chemical Proteomics Approach

The protozoan parasite Trypanosoma brucei is the causative agent of human African trypanosomiasis (HAT) or sleeping sickness, a fatal disease affecting nearly half a million people in sub-Saharan Africa. Current treatments for HAT have very poor safety profiles and are difficult to administer. There is an urgent need for new, safe and effective treatments for sleeping sickness. This work describes the discovery of 2,4-diaminopyrimidines, exemplified by 4-[4-amino-5-(2-methoxy-benzoyl)-pyrimidin-2-ylamino]-piperidine-1-carboxylic acid phenylamide or SCYX-5070, as potent inhibitors of T. brucei growth in vitro and also in animal models for HAT. To determine the parasite proteins responsible for interaction with SCYX-5070 and related compounds, affinity pull-downs were performed followed by sequence analysis and parasite genome database searching. The work revealed that mitogen-activated protein kinases (MAPKs) and cdc2-related kinases (CRKs) are the major proteins specifically bound to the immobilized compound, suggesting their potential participation in the pharmacological effects of 2,4-diaminopyrimidines against trypanosomatid protozoan parasites. These data strongly support the use of 2,4-diminipyrimidines as leads for the development of new drug candidates for the treatment of HAT

Migration as a form of workforce attrition: a nine-country study of pharmacists

Background There is a lack of evidence to inform policy development on the reasons why health professionals migrate. Few studies have sought to empirically determine factors influencing the intention to migrate and none have explored the relationship between factors. This paper reports on the first international attempt to investigate the migration intentions of pharmacy students and identify migration factors and their relationships. Methods Responses were gathered from 791 final-year pharmacy students from nine countries: Australia, Bangladesh, Croatia, Egypt, Portugal, Nepal, Singapore, Slovenia and Zimbabwe. Data were analysed by means of Principal Components Analysis (PCA) and two-step cluster analysis to determine the relationships between factors influencing migration and the characteristics of subpopulations most likely and least likely to migrate. Results Results showed a significant difference in attitudes towards the professional and sociopolitical environment of the home country and perceptions of opportunities abroad between those who have no intention of migrating and those who intend to migrate on a long-term basis. Attitudes of students planning short-term migration were not significantly different from those of students who did not intend to migrate. These attitudes, together with gender, knowledge of other migrant pharmacists and past experiences abroad, are associated with an increased propensity for migration. Conclusion Given the influence of the country context and environment on migration intentions, research and policy should frame the issue of migration in the context of the wider human resource agenda, thus viewing migration as one form of attrition and a symptom of other root causes. Remuneration is not an independent stand-alone factor influencing migration intentions and cannot be decoupled from professional development factors. Comprehensive human resource policy development that takes into account the issues of both remuneration and professional development are necessary to encourage retention

Catalysing sustainable fuel and chemical synthesis

Concerns over the economics of proven fossil fuel reserves, in concert with government and public acceptance of the anthropogenic origin of rising CO2 emissions and associated climate change from such combustible carbon, are driving academic and commercial research into new sustainable routes to fuel and chemicals. The quest for such sustainable resources to meet the demands of a rapidly rising global population represents one of this century’s grand challenges. Here, we discuss catalytic solutions to the clean synthesis of biodiesel, the most readily implemented and low cost, alternative source of transportation fuels, and oxygenated organic molecules for the manufacture of fine and speciality chemicals to meet future societal demands

Why Are Outcomes Different for Registry Patients Enrolled Prospectively and Retrospectively? Insights from the Global Anticoagulant Registry in the FIELD-Atrial Fibrillation (GARFIELD-AF).

Background: Retrospective and prospective observational studies are designed to reflect real-world evidence on clinical practice, but can yield conflicting results. The GARFIELD-AF Registry includes both methods of enrolment and allows analysis of differences in patient characteristics and outcomes that may result. Methods and Results: Patients with atrial fibrillation (AF) and ≥1 risk factor for stroke at diagnosis of AF were recruited either retrospectively (n = 5069) or prospectively (n = 5501) from 19 countries and then followed prospectively. The retrospectively enrolled cohort comprised patients with established AF (for a least 6, and up to 24 months before enrolment), who were identified retrospectively (and baseline and partial follow-up data were collected from the emedical records) and then followed prospectively between 0-18 months (such that the total time of follow-up was 24 months; data collection Dec-2009 and Oct-2010). In the prospectively enrolled cohort, patients with newly diagnosed AF (≤6 weeks after diagnosis) were recruited between Mar-2010 and Oct-2011 and were followed for 24 months after enrolment. Differences between the cohorts were observed in clinical characteristics, including type of AF, stroke prevention strategies, and event rates. More patients in the retrospectively identified cohort received vitamin K antagonists (62.1% vs. 53.2%) and fewer received non-vitamin K oral anticoagulants (1.8% vs . 4.2%). All-cause mortality rates per 100 person-years during the prospective follow-up (starting the first study visit up to 1 year) were significantly lower in the retrospective than prospectively identified cohort (3.04 [95% CI 2.51 to 3.67] vs . 4.05 [95% CI 3.53 to 4.63]; p = 0.016). Conclusions: Interpretations of data from registries that aim to evaluate the characteristics and outcomes of patients with AF must take account of differences in registry design and the impact of recall bias and survivorship bias that is incurred with retrospective enrolment. Clinical Trial Registration: - URL: http://www.clinicaltrials.gov . Unique identifier for GARFIELD-AF (NCT01090362)

SCYX-7158, an Orally-Active Benzoxaborole for the Treatment of Stage 2 Human African Trypanosomiasis

Human African trypanosomiasis (HAT) is caused by infection with the parasite Trypanosoma brucei and is an important public health problem in sub-Saharan Africa. New, safe, and effective drugs are urgently needed to treat HAT, particularly stage 2 disease where the parasite infects the brain. Existing therapies for HAT have poor safety profiles, difficult treatment regimens, limited effectiveness, and a high cost of goods. Through an integrated drug discovery project, we have discovered and optimized a novel class of boron-containing small molecules, benzoxaboroles, to deliver SCYX-7158, an orally active preclinical drug candidate. SCYX-7158 cured mice infected with T. brucei, both in the blood and in the brain. Extensive pharmacokinetic characterization of SCYX-7158 in rodents and non-human primates supports the potential of this drug candidate for progression to IND-enabling studies in advance of clinical trials for stage 2 HAT

Behavioral responses of terrestrial mammals to COVID-19 lockdowns

COVID-19 lockdowns in early 2020 reduced human mobility, providing an opportunity to disentangle its effects on animals from those of landscape modifications. Using GPS data, we compared movements and road avoidance of 2300 terrestrial mammals (43 species) during the lockdowns to the same period in 2019. Individual responses were variable with no change in average movements or road avoidance behavior, likely due to variable lockdown conditions. However, under strict lockdowns 10-day 95th percentile displacements increased by 73%, suggesting increased landscape permeability. Animals' 1-hour 95th percentile displacements declined by 12% and animals were 36% closer to roads in areas of high human footprint, indicating reduced avoidance during lockdowns. Overall, lockdowns rapidly altered some spatial behaviors, highlighting variable but substantial impacts of human mobility on wildlife worldwide.acceptedVersio