Controlling Chaos: Periodic Defect Braiding in Active Nematics Confined to a Cardioid.

This work examines self-mixing in active nematics, a class of fluids in which mobile topological defects drive chaotic flows in a system comprised of biological filaments and molecular motors. We present experiments that demonstrate how geometrical confinement can influence the braiding dynamics of the defects. Notably, we show that confinement in cardioid-shaped wells leads to realization of the golden braid, a maximally efficient mixing state of exactly three defects with no defect creation or annihilation. We characterize the golden braid state using different measures of topological entropy and the Lyapunov exponent. In particular, topological entropy measured from the stretching rate of material lines agrees well with an analytical computation from braid theory. Increasing the size of the confining cardioid produces a transition from the golden braid, to the fully chaotic active turbulent state.

Sex-Dependent Transcriptional Changes in Response to Stress in Patients with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: A Pilot Project.

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a complex, multi-symptom illness characterized by debilitating fatigue and post-exertional malaise (PEM). Numerous studies have reported sex differences at the epidemiological, cellular, and molecular levels between male and female ME/CFS patients. To gain further insight into these sex-dependent changes, we evaluated differential gene expression by RNA-sequencing (RNA-Seq) in 33 ME/CFS patients (20 female, 13 male) and 34 matched healthy controls (20 female and 14 male) before, during, and after an exercise challenge intended to provoke PEM. Our findings revealed that pathways related to immune-cell signaling (including IL-12) and natural killer cell cytotoxicity were activated as a result of exertion in the male ME/CFS cohort, while female ME/CFS patients did not show significant enough changes in gene expression to meet the criteria for the differential expression. Functional analysis during recovery from an exercise challenge showed that male ME/CFS patients had distinct changes in the regulation of specific cytokine signals (including IL-1ß). Meanwhile, female ME/CFS patients had significant alterations in gene networks related to cell stress, response to herpes viruses, and NF-κß signaling. The functional pathways and differentially expressed genes highlighted in this pilot project provide insight into the sex-specific pathophysiology of ME/CFS.

Engineering functional protein interfaces for immunologically modified field effect transistor (ImmunoFET) by molecular genetic means.

The attachment and interactions of analyte receptor biomolecules at solid-liquid interfaces are critical to development of hybrid biological-synthetic sensor devices across all size regimes. We use protein engineering approaches to engineer the sensing interface of biochemically modified field effect transistor sensors (BioFET). To date, we have deposited analyte receptor proteins on FET sensing channels by direct adsorption, used self-assembled monolayers to tether receptor proteins to planar FET SiO2 sensing gates and demonstrated interface biochemical function and electrical function of the corresponding sensors. We have also used phage display to identify short peptides that recognize thermally grown SiO2. Our interest in these peptides is as affinity domains that can be inserted as translational fusions into receptor proteins (antibody fragments or other molecules) to drive oriented interaction with FET sensing surfaces. We have also identified single-chain fragment variables (scFvs, antibody fragments) that recognize an analyte of interest as potential sensor receptors. In addition, we have developed a protein engineering technology (scanning circular permutagenesis) that allows us to alter protein topography to manipulate the position of functional domains of the protein relative to the BioFET sensing surface.

Multicentre analysis of incidental findings on low-resolution CT attenuation correction images: an extended study.

OBJECTIVE: To review new incidental findings detected on low-resolution CT attenuation correction (CTAC) images acquired during single-photon emission CT-CT myocardial perfusion imaging as an extension to our initial study. METHODS: CTAC images acquired as part of myocardial perfusion imaging performed using single-photon emission CT at four UK nuclear medicine centres were evaluated as part of a multicentre study. New incidental findings that were considered to be clinically significant were evaluated further. Positive-predictive value (PPV) was determined at the time of definitive diagnosis. RESULTS: Out of 3485 patients, 962 (28%) patients had a positive finding on the CTAC image, of which 824 (24%) were new findings. 84 (2.4%) patients had findings that were considered clinically significant at the time of the CTAC report and which had not been previously diagnosed. However, only 10 (0.29%) of these had findings that were confirmed as clinically significant, with the potential to be detrimental to patient outcome, after follow-up and definitive diagnosis. CONCLUSION: The overall PPV from all centres over the 2-year period was 12%. Each centre achieved what we considered to be low PPVs with no significant difference between the present and initial studies. The additional data from the combined studies show that, statistically, there is no significant difference between the PPVs from any of the centres. We conclude that routine reporting of CTAC images is not beneficial. ADVANCES IN KNOWLEDGE: This study combined with the previous study offers a unique evaluation of new clinically significant incidental findings on low-resolution CT images in an attempt to determine the benefit of reporting the CTAC images.

Clinical evaluation of the computed tomography attenuation correction map for myocardial perfusion imaging: the potential for incidental pathology detection.

The benefits of hybrid imaging in nuclear medicine have been proven to increase the diagnostic accuracy and sensitivity of many procedures by localizing or characterizing lesions or by correcting emission data to more accurately represent radiopharmaceutical distribution. Single-photon emission computed tomography/computed tomography (SPECT/CT) has a significant role in the diagnosis and follow-up of ischaemic heart disease with attenuation correction data being obtained on an integrated CT scanner. Initially, the CT component of hybrid SPECT/CT systems was what could be described as low specification utilizing fixed output parameters. As technology has progressed, the CT component of newer systems has specifications that are identical to that of stand-alone diagnostic systems. Irrespective of the type of scanner used, the computed tomography attenuation correction (CTAC) for myocardial perfusion imaging produces low-quality, limited-range CT images of the chest that include the mediastinum, lung fields and surrounding soft tissues. The diagnostic potential of this data set is unclear; yet, examples exist whereby significant pathology can be identified and investigated further. Despite guidance from a number of professional bodies suggesting that evaluation of the resulting images for every medical exposure be carried out, there is no indication as to whether this should include the evaluation of CTAC images. This review aims to initiate discussion by examining the ethical, legal, financial and practical issues (e.g. CT specification and image quality) surrounding the clinical evaluation of the CTAC for myocardial perfusion imaging images. Reference to discussions that have taken place, and continue to take place, in other modalities, current European and UK legislations, and guidelines and research in the field will be made.

Detection of clinically relevant levels of protein analyte under physiologic buffer using planar field effect transistors.

Electrochemical detection of protein binding at physiological salt concentration by planar field effect transistor platforms has yet to be documented convincingly. Here we report detection of streptavidin and clinically relevant levels of biotinylated monokine induced by interferon gamma (MIG) at physiological salt concentrations with AlGaN heterojunction field effect transistors (HFETs). The AlGaN HFETs are functionalized with a silane linker and analyte-specific affinity elements. Polarity of sensor responses is as expected from n-type HFETs to negatively and positively charged analytes. Sensitivity of the HFET sensors increases when salt concentration decreases, and the devices also exhibit dose-dependent responses to analyte. Detection of clinically relevant MIG concentrations at physiological salt levels demonstrates the potential for AlGaN devices to be used in development of in vivo biosensors.