A model for the distribution of aftershock waiting times

In this work the distribution of inter-occurrence times between earthquakes in aftershock sequences is analyzed and a model based on a non-homogeneous Poisson (NHP) process is proposed to quantify the observed scaling. In this model the generalized Omori's law for the decay of aftershocks is used as a time-dependent rate in the NHP process. The analytically derived distribution of inter-occurrence times is applied to several major aftershock sequences in California to confirm the validity of the proposed hypothesis.Comment: 4 pages, 3 figure

Reversible Resistance Induced by FLT3 Inhibition: A Novel Resistance Mechanism in Mutant FLT3-Expressing Cells

Clinical responses achieved with FLT3 kinase inhibitors in acute myeloid leukemia (AML) are typically transient and partial. Thus, there is a need for identification of molecular mechanisms of clinical resistance to these drugs. In response, we characterized MOLM13 AML cell lines made resistant to two structurally-independent FLT3 inhibitors.MOLM13 cells were made drug resistant via prolonged exposure to midostaurin and HG-7-85-01, respectively. Cell proliferation was determined by Trypan blue exclusion. Protein expression was assessed by immunoblotting, immunoprecipitation, and flow cytometry. Cycloheximide was used to determine protein half-life. RT-PCR was performed to determine FLT3 mRNA levels, and FISH analysis was performed to determine FLT3 gene expression.We found that MOLM13 cells readily developed cross-resistance when exposed to either midostaurin or HG-7-85-01. Resistance in both lines was associated with dramatically elevated levels of cell surface FLT3 and elevated levels of phosphor-MAPK, but not phospho-STAT5. The increase in FLT3-ITD expression was at least in part due to reduced turnover of the receptor, with prolonged half-life. Importantly, the drug-resistant phenotype could be rapidly reversed upon withdrawal of either inhibitor. Consistent with this phenotype, no significant evidence of FLT3 gene amplification, kinase domain mutations, or elevated levels of mRNA was observed, suggesting that protein turnover may be part of an auto-regulatory pathway initiated by FLT3 kinase activity. Interestingly, FLT3 inhibitor resistance also correlated with resistance to cytosine arabinoside. Over-expression of FLT3 protein in response to kinase inhibitors may be part of a novel mechanism that could contribute to clinical resistance

Entanglement and correlation functions following a local quench: a conformal field theory approach

We show that the dynamics resulting from preparing a one-dimensional quantum system in the ground state of two decoupled parts, then joined together and left to evolve unitarily with a translational invariant Hamiltonian (a local quench), can be described by means of quantum field theory. In the case when the corresponding theory is conformal, we study the evolution of the entanglement entropy for different bi-partitions of the line. We also consider the behavior of one- and two-point correlation functions. All our findings may be explained in terms of a picture, that we believe to be valid more generally, whereby quasiparticles emitted from the joining point at the initial time propagate semiclassically through the system.Comment: 19 pages, 4 figures, v2 typos corrected and refs adde

An alternative approach to transfer functions? Testing the performance of a functional trait-based model for testate amoebae

publisher: Elsevier articletitle: An alternative approach to transfer functions? Testing the performance of a functional trait-based model for testate amoebae journaltitle: Palaeogeography, Palaeoclimatology, Palaeoecology articlelink: http://dx.doi.org/10.1016/j.palaeo.2016.12.005 content_type: article copyright: © 2016 The Authors. Published by Elsevier B.V

(Dis)located Olympic patriots: sporting connections, administrative communications and imperial ether in interwar New Zealand

During the interwar period (1919-1939) protagonists of the early New Zealand Olympic Committee NZOC worked to renegotiate and improve the country's international sporting participation and involvement in the International Olympic Committee IOC. To this end, NZOC effectively used its locally based administrators and well-placed expatriates in Britain to variously assert the organisation's nascent autonomy, independence and political power, progress Antipodean athlete's causes, and, counter any potential doubt about the nation's peripheral position in imperial sporting dialogues. Adding to the corpus of scholarship on New Zealand's ties and tribulations with imperial Britain (in and beyond sport) (e.g. Beilharz and Cox 2007; Belich 2001, 2007; Coombes 2006; MacLean 2010; Phillips 1984, 1987; Ryan 2004, 2005, 2007), in this paper I examine how the political actions and strategic location of three key NZOC agents (specifically, administrator Harry Amos and expatriates Arthur Porritt and Jack Lovelock) worked in their own particular ways to assert the position of the organisation within the global Olympic fraternity. I argue that the efforts of Amos, Porritt and Lovelock also concomitantly served to remind Commonwealth sporting colleagues (namely Britain and Australia) that New Zealand could not be characterised as, or relegated to being, a distal, subdued, or subservient colonial sporting partner. Subsequently I contend that NZOC's development during the interwar period, and particularly the utility of expatriate agents, can be contextualised against historiographical shifts that encourage us to rethink, reimagine, and rework narratives of empire, colonisation, national identity, commonwealth and belonging

Inserting single Cs atoms into an ultracold Rb gas

We report on the controlled insertion of individual Cs atoms into an ultracold Rb gas at about 400 nK. This requires to combine the techniques necessary for cooling, trapping and manipulating single laser cooled atoms around the Doppler temperature with an experiment to produce ultracold degenerate quantum gases. In our approach, both systems are prepared in separated traps and then combined. Our results pave the way for coherent interaction between a quantum gas and a single or few neutral atoms of another species

Break dosage, cell cycle stage and DNA replication influence DNA double strand break response

DNA double strand breaks (DSBs) can be repaired by non-homologous end joining (NHEJ) or homology-directed repair (HR). HR requires nucleolytic degradation of 5′ DNA ends to generate tracts of single-stranded DNA (ssDNA), which are also important for the activation of DNA damage checkpoints. Here we describe a quantitative analysis of DSB processing in the budding yeast Saccharomyces cerevisiae. We show that resection of an HO endonuclease-induced DSB is less extensive than previously estimated and provide evidence for significant instability of the 3′ ssDNA tails. We show that both DSB resection and checkpoint activation are dose-dependent, especially during the G1 phase of the cell cycle. During G1, processing near the break is inhibited by competition with NHEJ, but extensive resection is regulated by an NHEJ-independent mechanism. DSB processing and checkpoint activation are more efficient in G2/M than in G1 phase, but are most efficient at breaks encountered by DNA replication forks during S phase. Our findings identify unexpected complexity of DSB processing and its regulation, and provide a framework for further mechanistic insights

Co-morbidity and polypharmacy in Parkinson's Disease:insights from a large Scottish primary care database

Background: Parkinson’s disease is complicated by comorbidity and polypharmacy, but the extent and patterns of these are unclear. We describe comorbidity and polypharmacy in patients with and without Parkinson’s disease across 31 other physical, and seven mental health conditions. Methods: We analysed primary health-care data on 510,502 adults aged 55 and over. We generated standardised prevalence rates by age-groups, gender, and neighbourhood deprivation, then calculated age, sex and deprivation adjusted odds ratios (OR) and 95% confidence intervals (95% CI) for those with PD compared to those without, for the prevalence, and number of conditions. Results: Two thousand six hundred forty (0.5%) had Parkinson’s disease, of whom only 7.4% had no other conditions compared with 22.9% of controls (adjusted OR [aOR] 0.43, 95% 0.38–0.49). The Parkinson’s group had more conditions, with the biggest difference found for seven or more conditions (PD 12.1% vs. controls 3.9%; aOR 2.08 95% CI 1.84–2.35). 12 of the 31 physical conditions and five of the seven mental health conditions were significantly more prevalent in the PD group. 44.5% with Parkinson’s disease were on five to nine repeat prescriptions compared to 24.5% of controls (aOR 1.40; 95% CI 1.28 to 1.53) and 19.2% on ten or more compared to 6.2% of controls (aOR 1.90; 95% CI 1.68 to 2.15). Conclusions: Parkinson’s disease is associated with substantial physical and mental co-morbidity. Polypharmacy is also a significant issue due to the complex nature of the disease and associated treatments

Effect of Cellular Quiescence on the Success of Targeted CML Therapy

Similar to tissue stem cells, primitive tumor cells in chronic myelogenous leukemia have been observed to undergo quiescence; that is, the cells can temporarily stop dividing. Using mathematical models, we investigate the effect of cellular quiescence on the outcome of therapy with targeted small molecule inhibitors.According to the models, the initiation of treatment can result in different patterns of tumor cell decline: a biphasic decline, a one-phase decline, and a reverse biphasic decline. A biphasic decline involves a fast initial phase (which roughly corresponds to the eradication of cycling cells by the drug), followed by a second and slower phase of exponential decline (corresponding to awakening and death of quiescent cells), which helps explain clinical data. We define the time when the switch to the second phase occurs, and identify parameters that determine whether therapy can drive the tumor extinct in a reasonable period of time or not. We further ask how cellular quiescence affects the evolution of drug resistance. We find that it has no effect on the probability that resistant mutants exist before therapy if treatment occurs with a single drug, but that quiescence increases the probability of having resistant mutants if patients are treated with a combination of two or more drugs with different targets. Interestingly, while quiescence prolongs the time until therapy reduces the number of cells to low levels or extinction, the therapy phase is irrelevant for the evolution of drug resistant mutants. If treatment fails as a result of resistance, the mutants will have evolved during the tumor growth phase, before the start of therapy. Thus, prevention of resistance is not promoted by reducing the quiescent cell population during therapy (e.g., by a combination of cell activation and drug-mediated killing).The mathematical models provide insights into the effect of quiescence on the basic kinetics of the response to targeted treatment of CML. They identify determinants of success in the absence of drug resistant mutants, and elucidate how quiescence influences the emergence of drug resistant mutants

The Relationship between Telomere Length and Mortality in Chronic Obstructive Pulmonary Disease (COPD)

Some have suggested that chronic obstructive pulmonary disease (COPD) is a disease of accelerated aging. Aging is characterized by shortening of telomeres. The relationship of telomere length to important clinical outcomes such as mortality, disease progression and cancer in COPD is unknown. Using quantitative polymerase chain reaction (qPCR), we measured telomere length of peripheral leukocytes in 4,271 subjects with mild to moderate COPD who participated in the Lung Health Study (LHS). The subjects were followed for approximately 7.5 years during which time their vital status, FEV1 and smoking status were ascertained. Using multiple regression methods, we determined the relationship of telomere length to cancer and total mortality in these subjects. We also measured telomere length in healthy “mid-life” volunteers and patients with more severe COPD. The LHS subjects had significantly shorter telomeres than those of healthy “mid-life” volunteers (p<.001). Compared to individuals in the 4th quartile of relative telomere length (i.e. longest telomere group), the remaining participants had significantly higher risk of cancer mortality (Hazard ratio, HR, 1.48; p = 0.0324) and total mortality (HR, 1.29; p = 0.0425). Smoking status did not make a significant difference in peripheral blood cells telomere length. In conclusion, COPD patients have short leukocyte telomeres, which are in turn associated increased risk of total and cancer mortality. Accelerated aging is of particular relevance to cancer mortality in COPD