Discovery and Assessment of New Target Sites for Anti-HIV Therapies

Human immunodeficiency virus (HIV) infects cells by endocytosis and takes over parts of the cell’s reaction pathways in order to reproduce itself and spread the infection. One such pathway taken over by HIV becomes the inflammatory pathway which uses Nuclear Factor κB (NF-κB) as the principal transcription factor. Therefore, knocking out the NF-κB pathway would prevent HIV from reproducing itself. In this report, our goal is to produce a simple model for this pathway with which we can identify potential targets for anti-HIV therapies and test out various hypotheses. We present a very simple model with four coupled first-order ODEs and see what happens if we treat IκK concentration as a parameter that can be controlled (by some unspecified means). In Section 3, we augment this model to account for activation and deactivation of IκK, which is controlled (again, by some unspecified means) by TNF

A deterministic evaluation of heat stress mitigation and feed cost under climate change within the smallholder dairy sector

In the global South, dairying is often promoted as a means of poverty alleviation. Yet, under conditions of climate warming, little is known regarding the ability of small-scale dairy producers to maintain production and/or the robustness of possible adaptation options in meeting the challenges presented, particularly heat stress. The authors created a simple, deterministic model to explore the influence of breed and heat stress relief options on smallholder dairy farmers in Odisha, India. Breeds included indigenous Indian (non-descript), low-grade Jersey crossbreed and high-grade Jersey crossbreed. Relief strategies included providing shade, fanning and bathing. The impact of predicted critical global climate parameters, a 2°C and 4°C temperature rise were explored. A feed price scenario was modelled to illustrate the importance of feed in impact estimation. Feed costs were increased by 10% to 30%. Across the simulations, high-grade Jersey crossbreeds maintained higher milk yields, despite being the most sensitive to the negative effects of temperature. Low-capital relief strategies were the most effective at reducing heat stress impacts on household income. However, as feed costs increased the lower-grade Jersey crossbreed became the most profitable breed. The high-grade Jersey crossbreed was only marginally (4.64%) more profitable than the indigenous breed. The results demonstrate the importance of understanding the factors and practical trade-offs that underpin adaptation. The model also highlights the need for hot-climate dairying projects and programmes to consider animal genetic resources alongside environmentally sustainable adaptation measures for greatest poverty impact

From regional pulse vaccination to global disease eradication: insights from a mathematical model of Poliomyelitis

Mass-vaccination campaigns are an important strategy in the global fight against poliomyelitis and measles. The large-scale logistics required for these mass immunisation campaigns magnifies the need for research into the effectiveness and optimal deployment of pulse vaccination. In order to better understand this control strategy, we propose a mathematical model accounting for the disease dynamics in connected regions, incorporating seasonality, environmental reservoirs and independent periodic pulse vaccination schedules in each region. The effective reproduction number, $R_e$, is defined and proved to be a global threshold for persistence of the disease. Analytical and numerical calculations show the importance of synchronising the pulse vaccinations in connected regions and the timing of the pulses with respect to the pathogen circulation seasonality. Our results indicate that it may be crucial for mass-vaccination programs, such as national immunisation days, to be synchronised across different regions. In addition, simulations show that a migration imbalance can increase $R_e$ and alter how pulse vaccination should be optimally distributed among the patches, similar to results found with constant-rate vaccination. Furthermore, contrary to the case of constant-rate vaccination, the fraction of environmental transmission affects the value of $R_e$ when pulse vaccination is present.Comment: Added section 6.1, made other revisions, changed titl

Prospective memory functioning among ecstasy/polydrug users: evidence from the Cambridge Prospective Memory Test (CAMPROMPT)

Rationale: Prospective memory (PM) deficits in recreational drug users have been documented in recent years. However, the assessment of PM has largely been restricted to self-reported measures that fail to capture the distinction between event-based and time-based PM. The aim of the present study is to address this limitation. Objectives: Extending our previous research, we augmented the range laboratory measures of PM by employing the CAMPROMPT test battery to investigate the impact of illicit drug use on prospective remembering in a sample of cannabis only, ecstasy/polydrug and non-users of illicit drugs, separating event and time-based PM performance. We also administered measures of executive function and retrospective memory in order to establish whether ecstasy/polydrug deficits in PM were mediated by group differences in these processes. Results: Ecstasy/polydrug users performed significantly worse on both event and time-based prospective memory tasks in comparison to both cannabis only and non-user groups. Furthermore, it was found that across the whole sample, better retrospective memory and executive functioning was associated with superior PM performance. Nevertheless, this association did not mediate the drug-related effects that were observed. Consistent with our previous study, recreational use of cocaine was linked to PM deficits. Conclusions: PM deficits have again been found among ecstasy/polydrug users, which appear to be unrelated to group differences in executive function and retrospective memory. However, the possibility that these are attributable to cocaine use cannot be excluded

Exploring teachers' perceptions on physical activity engagement for children and young people with intellectual disabilities

Aim: To explore teacher’s perceptions of barriers and facilitators to physical activity, including enabling, reinforcing and predisposing factors amongst children and young people (CYP) with intellectual disabilities (ID). Method and procedures: The Youth Physical Activity Promotion (YPAP) model was used to inform semi-structured focus groups to explore physical activity of CYP with ID. Participants were 23 (9 male) teachers and teaching assistants, from 3 special educational needs (SEN) schools (1 = Primary, 2 = Secondary) within North West England. Three focus groups were held with between 6 and 8 participants, audio and video recorded and data transcribed. Data were inductively and deductively analysed using Nvivo and represented through pen profiles. Results: Three pen profiles were developed and structured around YPAP model to display themes within the data. Enabling factors (facilities (n=23) and activity type (n=39)); reinforcing factors (influences of peers (n=23), family (n=10) and teachers (n=19) to physical activity engagement); predisposing factors (healthy lifestyle (n=15), enjoyment of physical activity (n=14), adaptations for physical activity (n=10), structured play (n=10), effects of disability on physical activity (n=8) and the CYPs attitudes towards physical activity (n=8)). Conclusion: CYP with ID enjoy engaging in physical activity, particularly activities that are of a fun and unstructured nature which allow for progression of skills and promote independence. Participants recognised that they, as teachers, had an influence on the CYP’s physical activity engagement, however suggested that parents have the most influential role. Similar to previous research, participants noted that CYP with ID had a lack of understanding as regards the importance of physical activity engagement and its benefits to health. It is suggested a strong home-school link for CYP within SEN schools could prove to be a key facilitator for active and healthy lifestyles education and choices

Physical Function, Cognitive Function, and Aortic Stiffness in Older Adults

Please view abstract in the attached PDF file

Intermediate Tail Dependence: A Review and Some New Results

The concept of intermediate tail dependence is useful if one wants to quantify the degree of positive dependence in the tails when there is no strong evidence of presence of the usual tail dependence. We first review existing studies on intermediate tail dependence, and then we report new results to supplement the review. Intermediate tail dependence for elliptical, extreme value and Archimedean copulas are reviewed and further studied, respectively. For Archimedean copulas, we not only consider the frailty model but also the recently studied scale mixture model; for the latter, conditions leading to upper intermediate tail dependence are presented, and it provides a useful way to simulate copulas with desirable intermediate tail dependence structures.Comment: 25 pages, 1 figur

Search for the h_c meson in B^+- ->h_c K^+-

We report a search for the $h_c$ meson via the decay chain $B^{\pm}\to h_c K^{\pm}$, \etac \gamma with $\eta_c \to K_S^0 K^{\pm} \pi^{\mp}$ and $p\bar{p}$. No significant signals are observed. We obtain upper limits on the branching fractions for $B^{\pm} \to \eta_c\gamma K^{\pm}$ in bins of the $\eta_c\gamma$ invariant mass. The results are based on an analysis of 253 fb$^{-1}$ of data collected by the Belle detector at the KEKB $e^+e^-$ collider.Comment: 12 pages, 6 figures, submitted to Phys. Rev.

Convergent Surface Water Distributions in U.S. Cities

Earth's surface is rapidly urbanizing, resulting in dramatic changes in the abundance, distribution and character of surface water features in urban landscapes. However, the scope and consequences of surface water redistribution at broad spatial scales are not well understood. We hypothesized that urbanization would lead to convergent surface water abundance and distribution: in other words, cities will gain or lose water such that they become more similar to each other than are their surrounding natural landscapes. Using a database of more than 1 million water bodies and 1 million km of streams, we compared the surface water of 100 US cities with their surrounding undeveloped land. We evaluated differences in areal (A WB) and numeric densities (N WB) of water bodies (lakes, wetlands, and so on), the morphological characteristics of water bodies (size), and the density (D C) of surface flow channels (that is, streams and rivers). The variance of urban A WB, N WB, and D C across the 100 MSAs decreased, by 89, 25, and 71%, respectively, compared to undeveloped land. These data show that many cities are surface water poor relative to undeveloped land; however, in drier landscapes urbanization increases the occurrence of surface water. This convergence pattern strengthened with development intensity, such that high intensity urban development had an areal water body density 98% less than undeveloped lands. Urbanization appears to drive the convergence of hydrological features across the US, such that surface water distributions of cities are more similar to each other than to their surrounding landscapes. © 2014 The Author(s)

Moments of the Hadronic Invariant Mass Spectrum in B --> X_c l nu Decays at Belle

We present a measurement of the hadronic invariant mass squared (M^2_X) spectrum in charmed semileptonic B meson decays B --> X_c l nu based on 140 fb^-1 of Belle data collected near the Y(4S) resonance. We determine the first, the second central and the second non-central moments of this spectrum for lepton energy thresholds ranging between 0.7 and 1.9 GeV. Full correlations between these measurements are evaluated.Comment: published version of the paper (one figure added, minor changes in the text); 16 pages, 3 figures, 10 table