Advanced software techniques for space shuttle data management systems Final report

Airborne/spaceborn computer design and techniques for space shuttle data management system

The Strategy Implementation Approach as an Alternative to Improving Programmes Implementation in Zimbabwe’s Non-Governmental Organisations (NGOs): The Case of a Selected Peace Building NGO

Non-Governmental Organisations (NGOs) in a majority of cases depend on donors for funding. However the global economic crisis has left many traditional donors with very limited financial resources to fund NGOs. As a way of ensuring that the little resources that are at their disposal are efficiently utilised, donors are now targeting NGOs that have sound corporate governance structures and are engaged in sustainable programmes that have the greatest impact on the communities that they serve. This has created intense competition among NGOs, including those operating in Zimbabwe, as they jockey for donor support. However the allocation that Zimbabwe’s NGOs are receiving compared to other countries is relatively small. This paper proposes that the reason why Zimbabwe’s NGOs are not receiving a large share of donor funding is that they are poorly implementing programmes. This poor implementation has resulted in programmes lacking sustainability and having little impact on communities. To assess the study’s proposal, the study used the qualitative research approach. Semi structured interviews were conducted with management from a selected peace building NGO. The findings confirm that there are weaknesses in programmes implementation, mainly related to poor systems-poor programme planning processes, weak financial and human resources policies, and a weak organisational culture. The study recommends that the NGO institutes effective project planning and implementation, human and financial resources management systems. These recommended systems will inadvertently strengthen the organisation’s culture. Keywords: Implementation, sustainable, programme, Non-Governmental Organisation, strategy

Methionine Adenosyltransferase 1a (MAT1A) Enhances Cell Survival During Chemotherapy Treatment and is Associated with Drug Resistance in Bladder Cancer PDX Mice.

Bladder cancer is among the top ten most common cancers, with about ~380,000 new cases and ~150,000 deaths per year worldwide. Tumor relapse following chemotherapy treatment has long been a significant challenge towards completely curing cancer. We have utilized a patient-derived bladder cancer xenograft (PDX) platform to characterize molecular mechanisms that contribute to relapse following drug treatment in advanced bladder cancer. Transcriptomic profiling of bladder cancer xenograft tumors by RNA-sequencing analysis, before and after relapse, following a 21-day cisplatin/gemcitabine drug treatment regimen identified methionine adenosyltransferase 1a (MAT1A) as one of the significantly upregulated genes following drug treatment. Survey of patient tumor sections confirmed elevated levels of MAT1A in individuals who received chemotherapy. Overexpression of MAT1A in 5637 bladder cancer cells increased tolerance to gemcitabine and stalled cell proliferation rates, suggesting MAT1A upregulation as a potential mechanism by which bladder cancer cells persist in a quiescent state to evade chemotherapy

α-Tocopherols modify the membrane dipole potential leading to modulation of ligand binding by P-glycoprotein

Journal ArticleThis is the author accepted manuscript. The final version is available from ASBMB via the DOI in this record.α-Tocopherol (vitamin E) has attracted considerable attention as a potential protective or palliative agent. In vitro, its free radical-scavenging antioxidant action has been widely demonstrated. In vivo, however, vitamin E treatment exhibits negligible benefits against oxidative stress. α-Tocopherol influences lipid ordering within biological membranes and its derivatives have been suggested to inhibit the multi-drug efflux pump, P-glycoprotein (P-gp). This study employs the fluorescent membrane probe, 1-(3-sulfonatopropyl)-4-[β[2-(di-n-octylamino)-6-naphthyl]vinyl] pyridinium betaine, to investigate whether these effects are connected via influences on the membrane dipole potential (MDP), an intrinsic property of biological membranes previously demonstrated to modulate P-gp activity. α-Tocopherol and its non-free radical-scavenging succinate analog induced similar decreases in the MDP of phosphatidylcholine vesicles. α-Tocopherol succinate also reduced the MDP of T-lymphocytes, subsequently decreasing the binding affinity of saquinavir for P-gp. Additionally, α-tocopherol succinate demonstrated a preference for cholesterol-treated (membrane microdomain enriched) cells over membrane cholesterol-depleted cells. Microdomain disruption via cholesterol depletion decreased saquinavir's affinity for P-gp, potentially implicating these structures in the influence of α-tocopherol succinate on P-gp. This study provides evidence of a microdomain dipole potential-dependent mechanism by which α-tocopherol analogs influence P-gp activity. These findings have implications for the use of α-tocopherol derivatives for drug delivery across biological barriers

The occupation of a box as a toy model for the seismic cycle of a fault

We illustrate how a simple statistical model can describe the quasiperiodic occurrence of large earthquakes. The model idealizes the loading of elastic energy in a seismic fault by the stochastic filling of a box. The emptying of the box after it is full is analogous to the generation of a large earthquake in which the fault relaxes after having been loaded to its failure threshold. The duration of the filling process is analogous to the seismic cycle, the time interval between two successive large earthquakes in a particular fault. The simplicity of the model enables us to derive the statistical distribution of its seismic cycle. We use this distribution to fit the series of earthquakes with magnitude around 6 that occurred at the Parkfield segment of the San Andreas fault in California. Using this fit, we estimate the probability of the next large earthquake at Parkfield and devise a simple forecasting strategy.Comment: Final version of the published paper, with an erratum and an unpublished appendix with some proof

Crystallization of a supercooled liquid and of a glass - Ising model approach

Using Monte Carlo simulations we study crystallization in the three-dimensional Ising model with four-spin interaction. We monitor the morphology of crystals which grow after placing crystallization seeds in a supercooled liquid. Defects in such crystals constitute an intricate and very stable network which separate various domains by tensionless domain walls. We also show that the crystallization which occurs during the continuous heating of the glassy phase takes place at a heating-rate dependent temperature.Comment: 7 page

Environmental DNA metabarcoding:Transforming how we survey animal and plant communities

The genomic revolution has fundamentally changed how we survey biodiversity on earth. High-throughput sequencing (?HTS?) platforms now enable the rapid sequencing of DNA from diverse kinds of environmental samples (termed ?environmental DNA? or ?eDNA?). Coupling HTS with our ability to associate sequences from eDNA with a taxonomic name is called ?eDNA metabarcoding? and offers a powerful molecular tool capable of noninvasively surveying species richness from many ecosystems. Here, we review the use of eDNA metabarcoding for surveying animal and plant richness, and the challenges in using eDNA approaches to estimate relative abundance. We highlight eDNA applications in freshwater, marine and terrestrial environments, and in this broad context, we distill what is known about the ability of different eDNA sample types to approximate richness in space and across time. We provide guiding questions for study design and discuss the eDNA metabarcoding workflow with a focus on primers and library preparation methods. We additionally discuss important criteria for consideration of bioinformatic filtering of data sets, with recommendations for increasing transparency. Finally, looking to the future, we discuss emerging applications of eDNA metabarcoding in ecology, conservation, invasion biology, biomonitoring, and how eDNA metabarcoding can empower citizen science and biodiversity educationpublishersversionPeer reviewe

On the Occurrence of Finite-Time-Singularities in Epidemic Models of Rupture, Earthquakes and Starquakes

We present a new kind of critical stochastic finite-time-singularity, relying on the interplay between long-memory and extreme fluctuations. We illustrate it on the well-established epidemic-type aftershock (ETAS) model for aftershocks, based solely on the most solidly documented stylized facts of seismicity (clustering in space and in time and power law Gutenberg-Richter distribution of earthquake energies). This theory accounts for the main observations (power law acceleration and discrete scale invariant structure) of critical rupture of heterogeneous materials, of the largest sequence of starquakes ever attributed to a neutron star as well as of earthquake sequences.Comment: Revtex document of 4 pages including 1 eps figur

The role of conduction system pacing in patients with atrial fibrillation

Conduction system pacing (CSP) has emerged as a promising novel delivery method for Cardiac Resynchronisation Therapy (CRT), providing an alternative to conventional biventricular epicardial (BiV) pacing in indicated patients. Despite increasing popularity and widespread uptake, CSP has rarely been specifically examined in patients with atrial fibrillation (AF), a cohort which forms a significant proportion of the heart failure (HF) population. In this review, we first examine the mechanistic evidence for the importance of sinus rhythm (SR) in CSP by allowing adjustment of atrioventricular delays (AVD) to achieve the optimal electrical response, and thus, whether the efficacy of CSP may be significantly attenuated compared to conventional BiV pacing in the presence of AF. We next evaluate the largest clinical body of evidence in this field, related to patients receiving CSP following atrioventricular nodal ablation (AVNA) for AF. Finally, we discuss how future research may be designed to address the vital question of how effective CSP in AF patients is, and the potential hurdles we may face in delivering such studies