Stiffer alginate gels deposit more efficiently in microchannel flows

The behavior of crosslinking polymer solutions as they transition from liquid-like to solid-like material in flow determines success or failure in several applications, from 3D printing to oil recovery in the earth's subsurface to a wide variety of biological flows. Dilute polymer solutions flow easily, while concentrated polymers or crosslinked polymer gels can clog pores, nozzles, or channels. We have recently uncovered and described a third regime of flow dynamics in polymers that occurs when crosslinking happens during flow: intermittent flows. In a model system of alginate and calcium meeting at a Y-shaped junction in a microfluidic channel, a persistent and regular pattern of intermittent flow occurs when driven at a constant volume flow rate. At the junction, calcium crosslinks alginate to form an alginate gel, which subsequently deposits on the channel wall. As gel continues to deposit, it obstructs the channel, causing the driving pressure to increase to maintain a constant flow rate. At a critical pressure, corresponding to a critical shear stress, the fluid pulls the gel from the wall, removing the gel from the device and resulting in a clear channel. The gel deposit begins again, and the process then repeats as long as flow continues. Chemical concentrations and flow rate control both the frequency of ablation and the critical shear stress. In this work, we provide an analytical framework to quantitatively describe the intermittent behavior as a result of diffusively driven deposition in a high Peclet number flow where convection dominates. Fitting the experimental data to the model allows estimation of the deposition efficiency, or the fraction of flowing material that sticks to the channel walls. By correlating the results of the model with bulk rheology measurements, we find that deposition efficiency increases with the stiffness of the gel formed in flow.Comment: 11 pages, 5 figure

Lost Generation: System Resilience and Flexibility

Whole energy system modelling is a valuable tool to support the development of policy to decarbonise energy systems, and has been used extensively in the UK for this purpose. However, quantitative insights produced by such models methods necessarily omit potentially important features of physical and engineering reality. The authors argue that important socio-technical insights can be gained by studying critical events such as the loss of 2.1 GW generation from the electricity system of Great Britain in August, 2019. The present paper uses this event as a starting point for a discussion of the need for additional tools, drawn from the System Architecture literature, to support the design and realisation of future fully decarbonised systems with high penetrations of renewable energy, capable of providing high levels of resilience and flexibility

Differential expression analysis with global network adjustment

<p>Background: Large-scale chromosomal deletions or other non-specific perturbations of the transcriptome can alter the expression of hundreds or thousands of genes, and it is of biological interest to understand which genes are most profoundly affected. We present a method for predicting a gene’s expression as a function of other genes thereby accounting for the effect of transcriptional regulation that confounds the identification of genes differentially expressed relative to a regulatory network. The challenge in constructing such models is that the number of possible regulator transcripts within a global network is on the order of thousands, and the number of biological samples is typically on the order of 10. Nevertheless, there are large gene expression databases that can be used to construct networks that could be helpful in modeling transcriptional regulation in smaller experiments.</p> <p>Results: We demonstrate a type of penalized regression model that can be estimated from large gene expression databases, and then applied to smaller experiments. The ridge parameter is selected by minimizing the cross-validation error of the predictions in the independent out-sample. This tends to increase the model stability and leads to a much greater degree of parameter shrinkage, but the resulting biased estimation is mitigated by a second round of regression. Nevertheless, the proposed computationally efficient “over-shrinkage” method outperforms previously used LASSO-based techniques. In two independent datasets, we find that the median proportion of explained variability in expression is approximately 25%, and this results in a substantial increase in the signal-to-noise ratio allowing more powerful inferences on differential gene expression leading to biologically intuitive findings. We also show that a large proportion of gene dependencies are conditional on the biological state, which would be impossible with standard differential expression methods.</p> <p>Conclusions: By adjusting for the effects of the global network on individual genes, both the sensitivity and reliability of differential expression measures are greatly improved.</p&gt

Measuring the decoherence rate in a semiconductor charge qubit

We describe a method by which the decoherence time of a solid state qubit may be measured. The qubit is coded in the orbital degree of freedom of a single electron bound to a pair of donor impurities in a semiconductor host. The qubit is manipulated by adiabatically varying an external electric field. We show that, by measuring the total probability of a successful qubit rotation as a function of the control field parameters, the decoherence rate may be determined. We estimate various system parameters, including the decoherence rates due to electromagnetic fluctuations and acoustic phonons. We find that, for reasonable physical parameters, the experiment is possible with existing technology. In particular, the use of adiabatic control fields implies that the experiment can be performed with control electronics with a time resolution of tens of nanoseconds.Comment: 9 pages, 6 figures, revtex

Good images, effective messages? Working with students and educators on academic practice understanding

Work at Northumbria University has focussed on activity that extends opportunities for students to engage directly with the skills development necessary for sound academic practice. This has included highly visual campaigns on the "Plagiarism trap", providing access to Turnitin plagiarism detection software, guides and sessions to highlight use of associated referencing tools. Sessions on a variety of topics, such as supporting study skills and reading originality reports, have been provided for students on taught, undergraduate and postgraduate programmes. This provision has included students working on collaborative partners' sites and also those on research programmes. Alongside the activities with students, "designing out" approaches have been embedded in staff development within the educator community at Northumbria. Formative use of Turnitin is integrated throughout programmes and academic practice development is formally recognised within the University Learning and Teaching Strategy's focus on information literacy. This article outlines and reviews these activities in a critical institutional context and evaluates responses from a variety of students and educators to determine how effective these measures have been

Reducing outcome measures in mental health: a systematic review of the methods

Economic and Social Research Council (ESRC) Grant number ES/J500057/1 and South London and Maudsley NHS Trust

Gene expression of INPP5F as an independent prognostic marker in fludarabine-based therapy of chronic lymphocytic leukemia

Chronic lymphocytic leukemia (CLL) is a heterogeneous disease. Various disease-related and patient-related factors have been shown to influence the course of the disease. The aim of this study was to identify novel biomarkers of significant clinical relevance. Pretreatment CD19-separated lymphocytes (n = 237;discovery set) and peripheral blood mononuclear cells (n = 92;validation set) from the REACH trial, a randomized phase III trial in relapsed CLL comparing rituximab plus fludarabine plus cyclophosphamide with fludarabine plus cyclophosphamide alone, underwent gene expression profiling. By using Cox regression survival analysis on the discovery set, we identified inositol polyphosphate-5-phosphatase F (INPP5F) as a prognostic factor for progression-free survival (P<0.001;hazard ratio (HR),1.63;95% confidence interval (CI),1.35-1.98) and overall survival (Po0.001;HR, 1.47;95% CI, 1.18-1.84),regardless of adjusting for known prognostic factors. These findings were confirmed on the validation set, suggesting that INPP5F may serve as a novel, easy-to-assess future prognostic biomarker for fludarabine-based therapy in CLL

Deterministic delivery of externally cold and precisely positioned single molecular ions

We present the preparation and deterministic delivery of a selectable number of externally cold molecular ions. A laser cooled ensemble of Mg^+ ions subsequently confined in several linear Paul traps inter-connected via a quadrupole guide serves as a cold bath for a single or up to a few hundred molecular ions. Sympathetic cooling embeds the molecular ions in the crystalline structure. MgH^+ ions, that serve as a model system for a large variety of other possible molecular ions, are cooled down close to the Doppler limit and are positioned with an accuracy of one micrometer. After the production process, severely compromising the vacuum conditions, the molecular ion is efficiently transfered into nearly background-free environment. The transfer of a molecular ion between different traps as well as the control of the molecular ions in the traps is demonstrated. Schemes, optimized for the transfer of a specific number of ions, are realized and their efficiencies are evaluated. This versatile source applicable for broad charge-to-mass ratios of externally cold and precisely positioned molecular ions can serve as a container-free target preparation device well suited for diffraction or spectroscopic measurements on individual molecular ions at high repetition rates (kHz).Comment: 11 pages, 8 figure

Kynurenine pathway inhibition reduces central nervous system inflammation in a model of human African trypanosomiasis

Human African trypanosomiasis, or sleeping sickness, is caused by the protozoan parasites &lt;i&gt;Trypanosoma brucei rhodesiense&lt;/i&gt; or &lt;i&gt;Trypanosoma brucei gambiense&lt;/i&gt;, and is a major cause of systemic and neurological disability throughout sub-Saharan Africa. Following early-stage disease, the trypanosomes cross the blood-brain barrier to invade the central nervous system leading to the encephalitic, or late stage, infection. Treatment of human African trypanosomiasis currently relies on a limited number of highly toxic drugs, but untreated, is invariably fatal. Melarsoprol, a trivalent arsenical, is the only drug that can be used to cure both forms of the infection once the central nervous system has become involved, but unfortunately, this drug induces an extremely severe post-treatment reactive encephalopathy (PTRE) in up to 10% of treated patients, half of whom die from this complication. Since it is unlikely that any new and less toxic drug will be developed for treatment of human African trypanosomiasis in the near future, increasing attention is now being focussed on the potential use of existing compounds, either alone or in combination chemotherapy, for improved efficacy and safety. The kynurenine pathway is the major pathway in the metabolism of tryptophan. A number of the catabolites produced along this pathway show neurotoxic or neuroprotective activities, and their role in the generation of central nervous system inflammation is well documented. In the current study, Ro-61-8048, a high affinity kynurenine-3-monooxygenase inhibitor, was used to determine the effect of manipulating the kynurenine pathway in a highly reproducible mouse model of human African trypanosomiasis. It was found that Ro-61-8048 treatment had no significant effect (P = 0.4445) on the severity of the neuroinflammatory pathology in mice during the early central nervous system stage of the disease when only a low level of inflammation was present. However, a significant (P = 0.0284) reduction in the severity of the neuroinflammatory response was detected when the inhibitor was administered in animals exhibiting the more severe, late central nervous system stage, of the infection. &lt;i&gt;In vitro&lt;/i&gt; assays showed that Ro-61-8048 had no direct effect on trypanosome proliferation suggesting that the anti-inflammatory action is due to a direct effect of the inhibitor on the host cells and not a secondary response to parasite destruction. These findings demonstrate that kynurenine pathway catabolites are involved in the generation of the more severe inflammatory reaction associated with the late central nervous system stages of the disease and suggest that Ro-61-8048 or a similar drug may prove to be beneficial in preventing or ameliorating the PTRE when administered as an adjunct to conventional trypanocidal chemotherap