Finding the optimal design of a passive microfluidic mixer.

The ability to thoroughly mix two fluids is a fundamental need in microfluidics. While a variety of different microfluidic mixers have been designed by researchers, it remains unknown which (if any) of these mixers are optimal (that is, which designs provide the most thorough mixing with the smallest possible fluidic resistance across the mixer). In this work, we automatically designed and rationally optimized a microfluidic mixer. We accomplished this by first generating a library of thousands of different randomly designed mixers, then using the non-dominated sorting genetic algorithm II (NSGA-II) to optimize the random chips in order to achieve Pareto efficiency. Pareto efficiency is a state of allocation of resources (e.g. driving force) from which it is impossible to reallocate so as to make any one individual criterion better off (e.g. pressure drop) without making at least one individual criterion (e.g. mixing performance) worse off. After 200 generations of evolution, Pareto efficiency was achieved and the Pareto-optimal front was found. We examined designs at the Pareto-optimal front and found several design criteria that enhance the mixing performance of a mixer while minimizing its fluidic resistance; these observations provide new criteria on how to design optimal microfluidic mixers. Additionally, we compared the designs from NSGA-II with some popular microfluidic mixer designs from the literature and found that designs from NSGA-II have lower fluidic resistance with similar mixing performance. As a proof of concept, we fabricated three mixer designs from 200 generations of evolution and one conventional popular mixer design and tested the performance of these four mixers. Using this approach, an optimal design of a passive microfluidic mixer is found and the criteria of designing a passive microfluidic mixer are established

Multimode quantum interference of photons in multiport integrated devices

We report the first demonstration of quantum interference in multimode interference (MMI) devices and a new complete characterization technique that can be applied to any photonic device that removes the need for phase stable measurements. MMI devices provide a compact and robust realization of NxM optical circuits, which will dramatically reduce the complexity and increase the functionality of future generations of quantum photonic circuits

Early warnings of the potential for malaria transmission in rural Africa using the hydrology, entomology and malaria transmission simulator (HYDREMATS)

<p>Abstract</p> <p>Background</p> <p>Early warnings of malaria transmission allow health officials to better prepare for future epidemics. Monitoring rainfall is recognized as an important part of malaria early warning systems. The Hydrology, Entomology and Malaria Simulator (HYDREMATS) is a mechanistic model that relates rainfall to malaria transmission, and could be used to provide early warnings of malaria epidemics.</p> <p>Methods</p> <p>HYDREMATS is used to make predictions of mosquito populations and vectorial capacity for 2005, 2006, and 2007 in Banizoumbou village in western Niger. HYDREMATS is forced by observed rainfall, followed by a rainfall prediction based on the seasonal mean rainfall for a period two or four weeks into the future.</p> <p>Results</p> <p>Predictions made using this method provided reasonable estimates of mosquito populations and vectorial capacity, two to four weeks in advance. The predictions were significantly improved compared to those made when HYDREMATS was forced with seasonal mean rainfall alone.</p> <p>Conclusions</p> <p>HYDREMATS can be used to make reasonable predictions of mosquito populations and vectorial capacity, and provide early warnings of the potential for malaria epidemics in Africa.</p

Conversion of Central Subfield Thickness Measurements of Diabetic Macular Edema Across Cirrus and Spectralis Optical Coherence Tomography Instruments

Purpose: Develop equations to convert Cirrus central subfield thickness (CST) to Spectralis CST equivalents and vice versa in eyes with diabetic macular edema (DME). Methods: The DRCR Retina Network Protocol O data were split randomly to train (70% sample) and validate (30% sample) conversion equations. Data from an independent study (CADME) also validated the equations. Bland-Altman 95% limits of agreement between predicted and observed values evaluated the equations. Results: Protocol O included 374 CST scan pairs from 187 eyes (107 participants). The CADME study included 150 scan pairs of 37 eyes (37 participants). Proposed conversion equations are Spectralis = 40.78 + 0.95 × Cirrus and Cirrus = 1.82 + 0.94 × Spectralis regardless of age, sex, or CST. Predicted values were within 10% of observed values in 101 (90%) of Spectralis and 99 (88%) of Cirrus scans in the validation data; and in 136 (91%) of the Spectralis and 148 (99%) of the Cirrus scans in the CADME data. Adjusting for within-eye correlations, 95% of conversions are estimated to be within 17% (95% confidence interval, 14%-21%) of CST on Spectralis and within 22% (95% confidence interval, 18%-28%) of CST on Cirrus. Conclusions: Conversion equations developed in this study allow the harmonization of CST measurements for eyes with DME using a mix of current Cirrus and Spectralis device images. Translational Relevance: The CSTs measured on Cirrus and Spectralis devices are not directly comparable owing to outer boundary segmentation differences. Converting CST values across spectral domain optical coherence tomography instruments should benefit both clinical research and standard care efforts

Quality of Reasoning in International Criminal Tribunals

It is not unreasonable to say that international criminal law is, for the most part, a judge made law. For better or worse, given the diffused nature of its sources of law as well as the institutions built to enforce it, the rising case law gave the international criminal courts a chance and a burden to develop international criminal law into an expansive, and familiar, branch of international law. In this Chapter, I attempt to analyse and elaborate the main vehicle through which this transformation has taken place – the judgements of the courts – in terms of the quality of their reasoning. I will piece together some general rules of thumb that have been created in the branch of international criminal law to assess the quality of reasoning of the different International Criminal Courts. My focus will be the work of the International Criminal Court, although the work of the ICC rests to a large degree on the work of the previous ad hoc tribunals. As such, I will analyse the criticisms that have been levelled at the international criminal tribunals in terms of their interpretation and reasoning, highlight some of the continuing concerns and assess the ICC’s current practice

Enrichment analysis of Alu elements with different spatial chromatin proximity in the human genome

Transposable elements (TEs) have no longer been totally considered as “junk DNA” for quite a time since the continual discoveries of their multifunctional roles in eukaryote genomes. As one of the most important and abundant TEs that still active in human genome, Alu, a SINE family, has demonstrated its indispensable regulatory functions at sequence level, but its spatial roles are still unclear. Technologies based on 3C(chromosomeconformation capture) have revealed the mysterious three-dimensional structure of chromatin, and make it possible to study the distal chromatin interaction in the genome. To find the role TE playing in distal regulation in human genome, we compiled the new released Hi-C data, TE annotation, histone marker annotations, and the genome-wide methylation data to operate correlation analysis, and found that the density of Alu elements showed a strong positive correlation with the level of chromatin interactions (hESC: r=0.9, P<2.2×1016; IMR90 fibroblasts: r = 0.94, P < 2.2 × 1016) and also have a significant positive correlation withsomeremote functional DNA elements like enhancers and promoters (Enhancer: hESC: r=0.997, P=2.3×10−4; IMR90: r=0.934, P=2×10−2; Promoter: hESC: r = 0.995, P = 3.8 × 10−4; IMR90: r = 0.996, P = 3.2 × 10−4). Further investigation involving GC content and methylation status showed the GC content of Alu covered sequences shared a similar pattern with that of the overall sequence, suggesting that Alu elements also function as the GC nucleotide and CpG site provider. In all, our results suggest that the Alu elements may act as an alternative parameter to evaluate the Hi-C data, which is confirmed by the correlation analysis of Alu elements and histone markers. Moreover, the GC-rich Alu sequence can bring high GC content and methylation flexibility to the regions with more distal chromatin contact, regulating the transcription of tissue-specific genes

Ashwagandha Derived Withanone Targets TPX2-Aurora A Complex: Computational and Experimental Evidence to its Anticancer Activity

Cancer is largely marked by genetic instability. Specific inhibition of individual proteins or signalling pathways that regulate genetic stability during cell division thus hold a great potential for cancer therapy. The Aurora A kinase is a Ser/Thr kinase that plays a critical role during mitosis and cytokinesis and is found upregulated in several cancer types. It is functionally regulated by its interactions with TPX2, a candidate oncogene. Aurora A inhibitors have been proposed as anticancer drugs that work by blocking its ATP binding site. This site is common to other kinases and hence these inhibitors lack specificity for Aurora A inhibition in particular, thus advocating the need of some alternative inhibition route. Previously, we identified TPX2 as a cellular target for withanone that selectively kill cancer cells. By computational approach, we found here that withanone binds to TPX2-Aurora A complex. In experiment, withanone treatment to cancer cells indeed resulted in dissociation of TPX2-Aurora A complex and disruption of mitotic spindle apparatus proposing this as a mechanism of the anticancer activity of withanone. From docking analysis, non-formation/disruption of the active TPX2-Aurora A association complex could be discerned. Our MD simulation results suggesting the thermodynamic and structural stability of TPX2-Aurora A in complex with withanone further substantiates the binding. We report a computational rationale of the ability of naturally occurring withanone to alter the kinase signalling pathway in an ATP-independent manner and experimental evidence in which withanone cause inactivation of the TPX2-Aurora A complex. The study demonstrated that TPX2-Aurora A complex is a target of withanone, a potential natural anticancer drug

Thyroid-Disrupting Chemicals: Interpreting Upstream Biomarkers of Adverse Outcomes

Background There is increasing evidence in humans and in experimental animals for a relationship between exposure to specific environmental chemicals and perturbations in levels of critically important thyroid hormones (THs). Identification and proper interpretation of these relationships are required for accurate assessment of risk to public health. Objectives We review the role of TH in nervous system development and specific outcomes in adults, the impact of xenobiotics on thyroid signaling, the relationship between adverse outcomes of thyroid disruption and upstream causal biomarkers, and the societal implications of perturbations in thyroid signaling by xenobiotic chemicals. Data sources We drew on an extensive body of epidemiologic, toxicologic, and mechanistic studies. Data synthesis THs are critical for normal nervous system development, and decreased maternal TH levels are associated with adverse neuropsychological development in children. In adult humans, increased thyroid-stimulating hormone is associated with increased blood pressure and poorer blood lipid profiles, both risk factors for cardiovascular disease and death. These effects of thyroid suppression are observed even within the “normal” range for the population. Environmental chemicals may affect thyroid homeostasis by a number of mechanisms, and multiple chemicals have been identified that interfere with thyroid function by each of the identified mechanisms. Conclusions Individuals are potentially vulnerable to adverse effects as a consequence of exposure to thyroid-disrupting chemicals. Any degree of thyroid disruption that affects TH levels on a population basis should be considered a biomarker of adverse outcomes, which may have important societal outcomes

The PAV trial: Does lactobacillus prevent post-antibiotic vulvovaginal candidiasis? Protocol of a randomised controlled trial [ISRCTN24141277]

BACKGROUND: Complementary and alternative medicines are used by many consumers, and increasingly are being incorporated into the general practitioner's armamentarium. Despite widespread usage, the evidence base for most complementary therapies is weak or non-existent. Post-antibiotic vulvovaginitis is a common problem in general practice, for which complementary therapies are often used. A recent study in Melbourne, Australia, found that 40% of women with a past history of vulvovaginitis had used probiotic Lactobacillus species to prevent or treat post-antibiotic vulvovaginitis. There is no evidence that this therapy is effective. This study aims to test whether oral or vaginal lactobacillus is effective in the prevention of post-antibiotic vulvovaginitis. METHODS/DESIGN: A randomised placebo-controlled blinded 2 × 2 factorial design is being used. General practitioners or pharmacists approach non-pregnant women, aged 18–50 years, who present with a non-genital infection requiring a short course of oral antibiotics, to participate in the study. Participants are randomised in a four group factorial design either to oral lactobacillus powder or placebo and either vaginal lactobacillus pessaries or placebo. These interventions are taken while on antibiotics and for four days afterwards or until symptoms of vaginitis develop. Women self collect a vaginal swab for culture of Candida species and complete a survey at baseline and again four days after completing their study medications. The sample size (a total of 496 – 124 in each factorial group) is calculated to identify a reduction of half in post-antibiotic vulvovaginitis from 23%, while allowing for a 25% drop-out. An independent Data Monitoring Committee is supervising the trial. Analysis will be intention-to-treat, with two pre-specified main comparisons: (i) oral lactobacillus versus placebo and (ii) vaginal lactobacillus versus placebo

GLUT 5 Is Not Over-Expressed in Breast Cancer Cells and Patient Breast Cancer Tissues

F18 2-Fluoro 2-deoxyglucose (FDG) has been the gold standard in positron emission tomography (PET) oncologic imaging since its introduction into the clinics several years ago. Seeking to complement FDG in the diagnosis of breast cancer using radio labeled fructose based analogs, we investigated the expression of the chief fructose transporter-GLUT 5 in breast cancer cells and human tissues. Our results indicate that GLUT 5 is not over-expressed in breast cancer tissues as assessed by an extensive immunohistochemistry study. RT-PCR studies showed that the GLUT 5 mRNA was present at minimal amounts in breast cancer cell lines. Further knocking down the expression of GLUT 5 in breast cancer cells using RNA interference did not affect the fructose uptake in these cell lines. Taken together these results are consistent with GLUT 5 not being essential for fructose uptake in breast cancer cells and tissues