Trapping of a random walk by diffusing traps

We present a systematic analytical approach to the trapping of a random walk by a finite density rho of diffusing traps in arbitrary dimension d. We confirm the phenomenologically predicted e^{-c_d rho t^{d/2}} time decay of the survival probability, and compute the dimension dependent constant c_d to leading order within an eps=2-d expansion.Comment: 16 pages, to appear in J. Phys.

Policy ideas through the prism of knowledge regimes and framing

Policymakers are often confronted with problems that involve ambiguity and uncertainty (Zahariadis, 2003). In order to make sense of such problems and to identify possible solutions, they are on the lookout for policy ideas

Boundaries of Disk-like Self-affine Tiles

Let $T:= T(A, {\mathcal D})$ be a disk-like self-affine tile generated by an integral expanding matrix $A$ and a consecutive collinear digit set ${\mathcal D}$, and let $f(x)=x^{2}+px+q$ be the characteristic polynomial of $A$. In the paper, we identify the boundary $\partial T$ with a sofic system by constructing a neighbor graph and derive equivalent conditions for the pair $(A,{\mathcal D})$ to be a number system. Moreover, by using the graph-directed construction and a device of pseudo-norm $\omega$, we find the generalized Hausdorff dimension $\dim_H^{\omega} (\partial T)=2\log \rho(M)/\log |q|$ where $\rho(M)$ is the spectral radius of certain contact matrix $M$. Especially, when $A$ is a similarity, we obtain the standard Hausdorff dimension $\dim_H (\partial T)=2\log \rho/\log |q|$ where $\rho$ is the largest positive zero of the cubic polynomial $x^{3}-(|p|-1)x^{2}-(|q|-|p|)x-|q|$, which is simpler than the known result.Comment: 26 pages, 11 figure

The extraordinary evolutionary history of the reticuloendotheliosis viruses

The reticuloendotheliosis viruses (REVs) comprise several closely related amphotropic retroviruses isolated from birds. These viruses exhibit several highly unusual characteristics that have not so far been adequately explained, including their extremely close relationship to mammalian retroviruses, and their presence as endogenous sequences within the genomes of certain large DNA viruses. We present evidence for an iatrogenic origin of REVs that accounts for these phenomena. Firstly, we identify endogenous retroviral fossils in mammalian genomes that share a unique recombinant structure with REVs—unequivocally demonstrating that REVs derive directly from mammalian retroviruses. Secondly, through sequencing of archived REV isolates, we confirm that contaminated Plasmodium lophurae stocks have been the source of multiple REV outbreaks in experimentally infected birds. Finally, we show that both phylogenetic and historical evidence support a scenario wherein REVs originated as mammalian retroviruses that were accidentally introduced into avian hosts in the late 1930s, during experimental studies of P. lophurae, and subsequently integrated into the fowlpox virus (FWPV) and gallid herpesvirus type 2 (GHV-2) genomes, generating recombinant DNA viruses that now circulate in wild birds and poultry. Our findings provide a novel perspective on the origin and evolution of REV, and indicate that horizontal gene transfer between virus families can expand the impact of iatrogenic transmission events

Consumers’ evaluation of allocation policies for scarce health care services: Vested interest activation trumps spatial and temporal distance

The allocation of scarce health care service resources often requires trade-offs between individual and collective outcomes (e.g., when some individuals benefit more strongly from a given policy th

The distribution of the therapeutic monoclonal antibodies cetuximab and trastuzumab within solid tumors

<p><b>Abstract</b></p> <p>Background</p> <p>Poor distribution of some anticancer drugs in solid tumors may limit their anti-tumor activity.</p> <p>Methods</p> <p>Here we used immunohistochemistry to quantify the distribution of the therapeutic monoclonal antibodies cetuximab and trastuzumab in relation to blood vessels and to regions of hypoxia in human tumor xenografts. The antibodies were injected into mice implanted with human epidermoid carcinoma A431 or human breast carcinoma MDA-MB-231 transfected with <it>ERBB2 </it>(231-H2N) that express high levels of ErbB1 and ErbB2 respectively, or wild-type MDA-MB-231, which expresses intermediate levels of ErbB1 and low levels of ErbB2.</p> <p>Results</p> <p>The distribution of cetuximab in A431 xenografts and trastuzumab in 231-H2N xenografts was time and dose dependent. At early intervals after injection of 1 mg cetuximab into A431 xenografts, the concentration of cetuximab decreased with increasing distance from blood vessels, but became more uniformly distributed at later times; there remained however limited distribution and binding in hypoxic regions of tumors. Injection of lower doses of cetuximab led to heterogeneous distributions. Similar results were observed with trastuzumab in 231-H2N xenografts. In MDA-MB-231 xenografts, which express lower levels of ErbB1, homogeneity of distribution of cetuximab was achieved more rapidly.</p> <p>Conclusions</p> <p>Cetuximab and trastuzumab distribute slowly, but at higher doses achieve a relatively uniform distribution after about 24 hours, most likely due to their long half-lives in the circulation. There remains poor distribution within hypoxic regions of tumors.</p

Acquiring a pet dog significantly reduces stress of primary carers for children with autism spectrum disorder: a prospective case control study

This study describes the impact of pet dogs on stress of primary carers of children with Autism Spectrum Disorder (ASD). Stress levels of 38 primary carers acquiring a dog and 24 controls not acquiring a dog were sampled at: Pre-intervention (17 weeks before acquiring a dog), post-intervention (3–10 weeks after acquisition) and follow-up (25–40 weeks after acquisition), using the Parenting Stress Index. Analysis revealed significant improvements in the intervention compared to the control group for Total Stress, Parental Distress and Difficult Child. A significant number of parents in the intervention group moved from clinically high to normal levels of Parental Distress. The results highlight the potential of pet dogs to reduce stress in primary carers of children with an ASD

A colorimetric strategy based on dynamic chemistry for direct detection of Trypanosomatid species

Leishmaniasis and Chagas disease are endemic in many countries, and re-emerging in the developed countries. A rapid and accurate diagnosis is important for early treatment for reducing the duration of infection as well as for preventing further potential health complications. In this work, we have developed a novel colorimetric molecular assay that integrates nucleic acid analysis by dynamic chemistry (ChemNAT) with reverse dot-blot hybridization in an array format for a rapid and easy discrimination of Leishmania major and Trypanosoma cruzi. The assay consists of a singleplex PCR step that amplifies a highly homologous DNA sequence which encodes for the RNA component of the large ribosome subunit. The amplicons of the two different parasites differ between them by single nucleotide variations, known as “Single Nucleotide Fingerprint” (SNF) markers. The SNF markers can be easily identified by naked eye using a novel micro Spin-Tube device "Spin-Tube", as each of them creates a specific spot pattern. Moreover, the direct use of ribosomal RNA without requiring the PCR pre-amplification step is also feasible, further increasing the simplicity of the assay. The molecular assay delivers sensitivity capable of identifying up to 8.7 copies per μL with single mismatch specificity. The Spin-Tube thus represents an innovative solution providing benefits in terms of time, cost, and simplicity, all of which are crucial for the diagnosis of infectious disease in developing countries.This research work has received funding from Junta de Andalucía, Consejería de Economía e Innovación (project number 2012-BIO1778), the Spanish Ministerio de Economía y Competitividad (Grants CTQ2012-34778, BIO2016-80519-R, FPI Grant BES-2013- 063020). This research was partially supported by the 7th European Community Framework Program (FP7-PEOPLE-2012-CIG-Project Number 322276)

GTP binding and intramolecular regulation by the ROC domain of Death Associated Protein Kinase 1

The ROCO proteins are a family of large, multidomain proteins characterised by the presence of a Ras of complex proteins (ROC) domain followed by a COR, or C-terminal of ROC, domain. It has previously been shown that the ROC domain of the human ROCO protein Leucine Rich Repeat Kinase 2 (LRRK2) controls its kinase activity. Here, the ability of the ROC domain of another human ROCO protein, Death Associated Protein Kinase 1 (DAPK1), to bind GTP and control its kinase activity has been evaluated. In contrast to LRRK2, loss of GTP binding by DAPK1 does not result in loss of kinase activity, instead acting to modulate this activity. These data highlight the ROC domain of DAPK1 as a target for modifiers of this proteins function, and casts light on the role of ROC domains as intramolecular regulators in complex proteins with implications for a broad range of human diseases

Distinguishing Type 2 Diabetes from Type 1 Diabetes in African American and Hispanic American Pediatric Patients

To test the hypothesis that clinical observations made at patient presentation can distinguish type 2 diabetes (T2D) from type 1 diabetes (T1D) in pediatric patients aged 2 to 18.Medical records of 227 African American and 112 Hispanic American pediatric patients diagnosed as T1D or T2D were examined to compare parameters in the two diseases. Age at presentation, BMI z-score, and gender were the variables used in logistic regression analysis to create models for T2D prediction.The regression-based model created from African American data had a sensitivity of 92% and a specificity of 89%; testing of a replication cohort showed 91% sensitivity and 93% specificity. A model based on the Hispanic American data showed 92% sensitivity and 90% specificity. Similarities between African American and Hispanic American patients include: (1) age at onset for both T1D and T2D decreased from the 1980s to the 2000s; (2) risk of T2D increased markedly with obesity. Racial/ethnic-specific observations included: (1) in African American patients, the proportion of females was significantly higher than that of males for T2D compared to T1D (p<0.0001); (2) in Hispanic Americans, the level of glycated hemoglobin (HbA1c) was significantly higher in T1D than in T2D (p<0.002) at presentation; (3) the strongest contributor to T2D risk was female gender in African Americans, while the strongest contributor to T2D risk was BMI z-score in Hispanic Americans.Distinction of T2D from T1D at patient presentation was possible with good sensitivity and specificity using only three easily-assessed variables: age, gender, and BMI z-score. In African American pediatric diabetes patients, gender was the strongest predictor of T2D, while in Hispanic patients, BMI z-score was the strongest predictor. This suggests that race/ethnic specific models may be useful to optimize distinction of T1D from T2D at presentation