Fgfr2b signaling is essential for the maintenance of the alveolar epithelial type 2 lineage during lung homeostasis in mice.

Fibroblast growth factor receptor 2b (Fgfr2b) signaling is essential throughout lung development to form the alveolar epithelial lineage. However, its role in alveolar epithelial type 2 cells (AT2s) homeostasis was recently considered dispensable. SftpcCreERT2; Fgfr2bflox/flox; tdTomatoflox/flox mice were used to delete Fgfr2b expression in cells belonging to the AT2 lineage, which contains mature AT2s and a novel SftpcLow lineage-traced population called "injury activated alveolar progenitors" or IAAPs. Upon continuous tamoxifen exposure for either 1 or 2 weeks to delete Fgfr2b, a shrinking of the AT2 population is observed. Mature AT2s exit the cell cycle, undergo apoptosis and fail to form alveolospheres in vitro. However, the lung morphometry appears normal, suggesting the involvement of compensatory mechanisms. In mutant lungs, IAAPs which escaped Fgfr2b deletion expand, display enhanced alveolosphere formation in vitro and increase drastically their AT2 signature, suggesting differentiation towards mature AT2s. Interestingly, a significant increase in AT2s and decrease in IAPPs occurs after a 1-week tamoxifen exposure followed by an 8-week chase period. Although mature AT2s partially recover their alveolosphere formation capabilities, the IAAPs no longer display this property. Single-cell RNA seq analysis confirms that AT2s and IAAPs represent stable and distinct cell populations and recapitulate some of their characteristics observed in vivo. Our results underscore the essential role played by Fgfr2b signaling in the maintenance of the AT2 lineage in the adult lung during homeostasis and suggest that the IAAPs could represent a new population of AT2 progenitors.

Deep ultra-violet plasmonics: exploiting momentum-resolved electron energy loss spectroscopy to probe germanium.

Germanium is typically used for solid-state electronics, fiber-optics, and infrared applications, due to its semiconducting behavior at optical and infrared wavelengths. In contrast, here we show that the germanium displays metallic nature and supports propagating surface plasmons in the deep ultraviolet (DUV) wavelengths, that is typically not possible to achieve with conventional plasmonic metals such as gold, silver, and aluminum. We measure the photonic band spectrum and distinguish the plasmonic excitation modes: bulk plasmons, surface plasmons, and Cherenkov radiation using a momentum-resolved electron energy loss spectroscopy. The observed spectrum is validated through the macroscopic electrodynamic electron energy loss theory and first-principles density functional theory calculations. In the DUV regime, intraband transitions of valence electrons dominate over the interband transitions, resulting in the observed highly dispersive surface plasmons. We further employ these surface plasmons in germanium to design a DUV radiation source based on the Smith-Purcell effect. Our work opens a new frontier of DUV plasmonics to enable the development of DUV devices such as metasurfaces, detectors, and light sources based on plasmonic germanium thin films.

Identification of a novel subset of alveolar type 2 cells enriched in PD-L1 and expanded following pneumonectomy.

Alveolar type 2 (AT2) cells are heterogeneous cells, with specialised AT2 subpopulations within this lineage exhibiting stem cell properties. However, the existence of quiescent, immature cells within the AT2 lineage that are activated during lung regeneration is unknown.SftpcCreERT2/+;tdTomatoflox/flox mice were used for the labelling of AT2 cells and labelled subpopulations were analysed by flow cytometry, quantitative PCR, assay for transposase-accessible chromatin using sequencing (ATAC-seq), gene arrays, pneumonectomy and culture of precision-cut lung slices. Single-cell RNA-sequencing (scRNA-seq) data from human lungs were analysed.In mice, we detected two distinct AT2 subpopulations, with low tdTomato level (TomLow) and high tdTomato level (TomHigh). TomLow cells express lower levels of the AT2 differentiation markers Fgfr2b and Etv5, while TomHigh, as bona fide mature AT2 cells, show higher levels of Sftpc, Sftpb, Sftpa1, Fgfr2b and Etv5 expression. ATAC-seq analysis indicates that TomLow and TomHigh cells constitute two distinct cell populations, with specific silencing of Sftpc, Rosa26 and cell cycle gene loci in the TomLow population. Upon pneumonectomy, the number of TomLow but not TomHigh cells increases and TomLow cells show upregulated expression of Fgfr2b, Etv5, Sftpc, Ccnd1 and Ccnd2 compared to Sham. TomLow cells overexpress programmed cell death 1 ligand 1 (PD-L1), an immune inhibitory membrane receptor ligand, which is used by flow cytometry to differentially isolate these two subpopulations. In the human lung, data mining of a recent scRNA-seq AT2 data set demonstrates the existence of a PD-L1 Pos population. Therefore, we have identified a novel population of AT2 quiescent, immature progenitor cells in mouse that expand upon pneumonectomy and we have provided evidence for the existence of such cells in human.

The nicotinamide phosphoribosyltransferase antagonist FK866 inhibits growth of prostate tumour spheroids and increases doxorubicin retention without changes in drug transporter and cancer stem cell protein expression.

Nicotinamide phosphoribosyltransferase (NAMPT) is a rate-limiting enzyme for nicotinamide adenine dinucleotide (NAD) synthesis and is involved in cancer cell proliferation through regulation of energy production pathways. Therefore, NAMPT inhibitors are promising drugs for cancer therapy by limiting energy supply of tumours. Herein, we demonstrated that the NAMPT inhibitor FK866 ((E)-N-(4-(1-Benzoylpiperidin-4-yl)butyl)-3-(pyridin-3-yl)acrylamide) dose-dependently inhibited growth and cell motility of DU-145 prostate tumour spheroids and decreased the intracellular ATP concentration. The apoptosis marker cleaved caspase-3 remained unchanged, but the autophagy marker microtubule-associated protein 1A/1B-light chain 3 (LC3) was upregulated. Growth inhibition was reversed upon co-administration of NAD to the cell culture medium. FK866 decreased calcein as well as pheophorbide A efflux from tumour spheroids and increased doxorubicin toxicity, indicating interference with function of drug efflux transporters. DU-145 multicellular tumour spheroids expressed the stem cell associated markers CD133, CD44, Oct4, Nanog, Sox2, and drug transporters ABCB1, ABCG2, and ABCC1 which are associated with stem cell properties in cancer cells. The ABCB1 inhibitor zosuquidar, the ABCG2 inhibitor Ko143, and the ABCC1 inhibitor MK571 increased calcein retention. Neither protein expression of stem cell markers, nor drug transporters was significantly changed upon FK866 treatment. In conclusion, our data suggest that FK866 inhibits prostate cancer cell proliferation by interference with the energy metabolism, and function of drug efflux transporters.

Potential biomarkers for testicular germ cell tumour: Risk assessment, diagnostic, prognostic and monitoring of recurrence.

Testicular germ cell tumour (TGCT) is considered a relatively rare malignancy usually occurring in young men between 15 and 35 years of age, and both genetic and environmental factors contribute to its development. The majority of patients are diagnosed in an early-stage of TGCTs with an elevated 5-year survival rate after therapy. However, approximately 25% of patients show an incomplete response to chemotherapy or tumours relapse. The current therapies are accompanied by several adverse effects, including infertility. Aside from classical serum biomarker, many studies reported novel biomarkers for TGCTs, but without proper validation. Cancer cells share many similarities with embryonic stem cells (ESCs), and since ESC genes are not transcribed in most adult tissues, they could be considered ideal candidate targets for cancer-specific diagnosis and treatment. Added to this, several microRNAs (miRNA) including miRNA-371-3p can be further investigated as a molecular biomarker for diagnosis and monitoring of TGCTs. In this review, we will illustrate the findings of recent investigations in novel TGCTs biomarkers applicable for risk assessment, screening, diagnosis, prognosis, prediction and monitoring of the relapse.

Spin photonics in 3D whispering gallery mode resonators.

Whispering gallery modes are known for possessing orbital angular momentum, however the interplay of local spin density, orbital angular momentum, and the near-field interaction with quantum emitters is far less explored. Here, we study the spin-orbit interaction of a circularly polarized dipole with the whispering gallery modes (WGMs) of a spherical resonator. Using an exact dyadic Green's function approach, we show that the near-field interaction between the photonic spin of a circularly polarized dipole and the local electromagnetic spin density of whispering gallery modes gives rise to unidirectional behaviour where modes with either positive or negative orbital angular momentum are excited. We show that this is a manifestation of spin-momentum locking with the whispering gallery modes of the spherical resonator. We also discuss requirements for possible experimental demonstrations using Zeeman transitions in cold atoms or quantum dots, and outline potential applications of these previously overlooked properties. Our work firmly establishes local spin density, momentum and decay as a universal right-handed electromagnetic triplet for near-field light-matter interaction.

Desialylation of Spermatozoa and Epithelial Cell Glycocalyx Is a Consequence of Bacterial Infection of the Epididymis.

Urinary tract infections caused by uropathogenic Escherichia coli (UPEC) pathovars belong to the most frequent infections in humans. In men, pathogens can also spread to the genital tract via the continuous ductal system, eliciting bacterial prostatitis and/or epididymo-orchitis. Antibiotic treatment usually clears pathogens in acute epididymitis; however, the fertility of patients can be permanently impaired. Because a premature acrosome reaction was observed in an UPEC epididymitis mouse model, and sialidases on the sperm surface are considered to be activated via proteases of the acrosome, we aimed to investigate whether alterations of the sialome of epididymal spermatozoa and surrounding epithelial cells occur during UPEC infection. In UPEC-elicited acute epididymitis in mice, a substantial loss of N-acetylneuraminic acid residues was detected in epididymal spermatozoa and epithelial cells using combined laser microdissection/HPLC-ESI-MS analysis. In support, a substantial reduction of sialic acid residues bound to the surface of spermatozoa was documented in men with a recent history of E. coli-associated epididymitis. In vitro, such an UPEC induced N-acetylneuraminic acid release from human spermatozoa was effectively counteracted by a sialidase inhibitor. These findings strongly suggest a substantial remodeling of the glycocalyx of spermatozoa and epididymal epithelial cells by endogenous sialidases after a premature acrosome reaction during acute epididymitis.

Label-free capture of breast cancer cells spiked in buffy coats using carbon nanotube antibody micro-arrays.

We demonstrate the rapid and label-free capture of breast cancer cells spiked in buffy coats using nanotube-antibody micro-arrays. Single wall carbon nanotube arrays were manufactured using photo-lithography, metal deposition, and etching techniques. Anti-epithelial cell adhesion molecule (EpCAM) antibodies were functionalized to the surface of the nanotube devices using 1-pyrene-butanoic acid succinimidyl ester functionalization method. Following functionalization, plain buffy coat and MCF7 cell spiked buffy coats were adsorbed on to the nanotube device and electrical signatures were recorded for differences in interaction between samples. A statistical classifier for the 'liquid biopsy' was developed to create a predictive model based on dynamic time warping to classify device electrical signals that corresponded to plain (control) or spiked buffy coats (case). In training test, the device electrical signals originating from buffy versus spiked buffy samples were classified with ∼100% sensitivity, ∼91% specificity and ∼96% accuracy. In the blinded test, the signals were classified with ∼91% sensitivity, ∼82% specificity and ∼86% accuracy. A heatmap was generated to visually capture the relationship between electrical signatures and the sample condition. Confocal microscopic analysis of devices that were classified as spiked buffy coats based on their electrical signatures confirmed the presence of cancer cells, their attachment to the device and overexpression of EpCAM receptors. The cell numbers were counted to be ∼1-17 cells per 5 µl per device suggesting single cell sensitivity in spiked buffy coats that is scalable to higher volumes using the micro-arrays.

Static micro-array isolation, dynamic time series classification, capture and enumeration of spiked breast cancer cells in blood: the nanotube-CTC chip.

We demonstrate the rapid and label-free capture of breast cancer cells spiked in blood using nanotube-antibody micro-arrays. 76-element single wall carbon nanotube arrays were manufactured using photo-lithography, metal deposition, and etching techniques. Anti-epithelial cell adhesion molecule (anti-EpCAM), Anti-human epithelial growth factor receptor 2 (anti-Her2) and non-specific IgG antibodies were functionalized to the surface of the nanotube devices using 1-pyrene-butanoic acid succinimidyl ester. Following device functionalization, blood spiked with SKBR3, MCF7 and MCF10A cells (100/1000 cells per 5 µl per device, 170 elements totaling 0.85 ml of whole blood) were adsorbed on to the nanotube device arrays. Electrical signatures were recorded from each device to screen the samples for differences in interaction (specific or non-specific) between samples and devices. A zone classification scheme enabled the classification of all 170 elements in a single map. A kernel-based statistical classifier for the 'liquid biopsy' was developed to create a predictive model based on dynamic time warping series to classify device electrical signals that corresponded to plain blood (control) or SKBR3 spiked blood (case) on anti-Her2 functionalized devices with ∼90% sensitivity, and 90% specificity in capture of 1000 SKBR3 breast cancer cells in blood using anti-Her2 functionalized devices. Screened devices that gave positive electrical signatures were confirmed using optical/confocal microscopy to hold spiked cancer cells. Confocal microscopic analysis of devices that were classified to hold spiked blood based on their electrical signatures confirmed the presence of cancer cells through staining for DAPI (nuclei), cytokeratin (cancer cells) and CD45 (hematologic cells) with single cell sensitivity. We report 55%-100% cancer cell capture yield depending on the active device area for blood adsorption with mean of 62% (∼12 500 captured off 20 000 spiked cells in 0.1 ml blood) in this first nanotube-CTC chip study.

MoS2 actuators: reversible mechanical responses of MoS2-polymer nanocomposites to photons.

New molybdenum disulfide (MoS2)-based polymer composites and their reversible mechanical responses to light are presented, suggesting MoS2 as an excellent candidate for energy conversion. Homogeneous mixtures of MoS2/polydimethylsiloxane (PDMS) nanocomposites (0.1-5 wt.%) were prepared and their near infrared (NIR) mechanical responses studied with increasing pre-strains. NIR triggering resulted in an extraordinary change in stress levels of the actuators by ~490 times. Actuation responses of MoS2 polymer composites depended on applied pre-strains. At lower levels of pre-strains (3-9%) the actuators showed reversible expansion while at high levels (15-50%), the actuators exhibited reversible contraction. An opto-mechanical conversion (η)∼0.5-3 MPa W(-1) was calculated. The ratio of maximum stress due to photo-actuation (σmax) at 50% strain to the minimum stress due to photo-actuation (σmin) at 3% strain was found to be ∼315-322% for MoS2 actuators (for 0.1 to 5 wt.% additive), greater than single layer graphene (∼188%) and multi-wall nanotube (∼172%) photo-mechanical actuators. Unlike other photomechanical actuators, the MoS2 actuators exhibited strong light-matter interactions and an unambiguous increase in amplitude of photomechanical response with increasing strains. A power law dependence of σmax/σmin on strains with a scaling exponent of ß = 0.87-1.32 was observed, suggesting that the origin of photomechanical response is intertwined dynamically with the molecular mechanisms at play in MoS2 actuators.

Association between plasminogen activator inhibitor 1 gene mutation and different subgroups of recurrent miscarriage and implantation failure.

PURPOSE: To compare plasminogen activator inhibitor type1 (PAI-1) mutation rates in different groups of patients with the record of recurrent miscarriage (RM) or implantation failure (IF) with special emphasis on the number of missed pregnancies and/or implantation failures (RM ≥ 2, IF ≥ 2, RM + IF ≥ 2, RM ≥ 3, IF ≥ 3 and RM + IF ≥ 3). METHOD: Case-control study from PCR products and RFLP data of DNA from blood of patients who referred to the infertility clinic including 595 patients (421 RM ≥ 2, 119 IF ≥ 2 and 55 RM + IF ≥ 2) as the case groups and 100 healthy women as the control group. RESULTS: All six different subgroups of patients showed increased frequencies of the mutant allele (4G) in comparison to the control group (p < 0.001) suggesting a role for PAI-1 mutation in RM and IF. CONCLUSIONS: The different patient subgroups suffer similar rates of risk in developing RM and IF when compared to controls.

Induction of Stem-Cell-Derived Cardiomyogenesis by Fibroblast Growth Factor 10 (FGF10) and Its Interplay with Cardiotrophin-1 (CT-1).

For heart regeneration purposes, embryonic stem cell (ES)-based strategies have been developed to induce the proliferation of cardiac progenitor cells towards cardiomyocytes. Fibroblast growth factor 10 (FGF10) contributes to cardiac development and induces cardiomyocyte differentiation in vitro. Yet, among pro-cardiogenic factors, including cardiotrophin-1 (CT-1), the hyperplastic function of FGF10 in cardiomyocyte turnover remains to be further characterized. We investigated the proliferative effects of FGF10 on ES-derived cardiac progenitor cells in the intermediate developmental stage and examined the putative interplay between FGF10 and CT-1 in cardiomyocyte proliferation. Mouse ES cells were treated with FGF10 and/or CT-1. Differential expression of cardiomyocyte-specific gene markers was analyzed at transcript and protein levels. Substantial upregulation of sarcomeric α-actinin was detected by qPCR, flow cytometry, Western blot and immunocytochemistry. FGF10 enhanced the expression of other structural proteins (MLC-2a, MLC-2v and TNNT2), transcriptional factors (NKX2-5 and GATA4), and proliferation markers (Aurora B and YAP-1). FGF10/CT-1 co-administration led to an upregulation of proliferation markers, suggesting the synergistic potential of FGF10 + CT-1 on cardiomyogenesis. In summary, we provided evidence that FGF10 and CT-1 induce cardiomyocyte structural proteins, associated transcription factors, and cardiac cell proliferation, which could be applicable in therapies to replenish damaged cardiomyocytes.

Cell-Surface Programmed Death Ligand-1 Expression Identifies a Sub-Population of Distal Epithelial Cells Enriched in Idiopathic Pulmonary Fibrosis.

Idiopathic lung fibrosis (IPF) is a fatal lung disease characterized by chronic epithelial injury and exhausted repair capacity of the alveolar compartment, associated with the expansion of cells with intermediate alveolar epithelial cell (AT2) characteristics. Using SftpcCreERT2/+: tdTomatoflox/flox mice, we previously identified a lung population of quiescent injury-activated alveolar epithelial progenitors (IAAPs), marked by low expression of the AT2 lineage trace marker tdTomato (Tomlow) and characterized by high levels of Pd-l1 (Cd274) expression. This led us to hypothesize that a population with similar properties exists in the human lung. To that end, we used flow cytometry to characterize the CD274 cell-surface expression in lung epithelial cells isolated from donor and end-stage IPF lungs. The identity and functional behavior of these cells were further characterized by qPCR analysis, in vitro organoid formation, and ex vivo precision-cut lung slices (PCLSs). Our analysis led to the identification of a population of CD274pos cells expressing intermediate levels of SFTPC, which was expanded in IPF lungs. While donor CD274pos cells initiated clone formation, they did not expand significantly in 3D organoids in AT2-supportive conditions. However, an increased number of CD274pos cells was found in cultured PCLS. In conclusion, we demonstrate that, similar to IAAPs in the mouse lung, a population of CD274-expressing cells exists in the normal human lung, and this population is expanded in the IPF lung and in an ex vivo PCLS assay, suggestive of progenitor cell behavior. CD274 function in these cells as a checkpoint inhibitor may be crucial for their progenitor function, suggesting that CD274 inhibition, unless specifically targeted, might further injure the already precarious lung epithelial compartment in IPF.

The Multifunctional Contribution of FGF Signaling to Cardiac Development, Homeostasis, Disease and Repair.

The current focus on cardiovascular research reflects society's concerns regarding the alarming incidence of cardiac-related diseases and mortality in the industrialized world and, notably, an urgent need to combat them by more efficient therapies. To pursue these therapeutic approaches, a comprehensive understanding of the mechanism of action for multifunctional fibroblast growth factor (FGF) signaling in the biology of the heart is a matter of high importance. The roles of FGFs in heart development range from outflow tract formation to the proliferation of cardiomyocytes and the formation of heart chambers. In the context of cardiac regeneration, FGFs 1, 2, 9, 16, 19, and 21 mediate adaptive responses including restoration of cardiac contracting rate after myocardial infarction and reduction of myocardial infarct size. However, cardiac complications in human diseases are correlated with pathogenic effects of FGF ligands and/or FGF signaling impairment. FGFs 2 and 23 are involved in maladaptive responses such as cardiac hypertrophic, fibrotic responses and heart failure. Among FGFs with known causative (FGFs 2, 21, and 23) or protective (FGFs 2, 15/19, 16, and 21) roles in cardiac diseases, FGFs 15/19, 21, and 23 display diagnostic potential. The effective role of FGFs on the induction of progenitor stem cells to cardiac cells during development has been employed to boost the limited capacity of postnatal cardiac repair. To renew or replenish damaged cardiomyocytes, FGFs 1, 2, 10, and 16 were tested in (induced-) pluripotent stem cell-based approaches and for stimulation of cell cycle re-entry in adult cardiomyocytes. This review will shed light on the wide range of beneficiary and detrimental actions mediated by FGF ligands and their receptors in the heart, which may open new therapeutic avenues for ameliorating cardiac complications.

Ultrafast electron cycloids driven by the transverse spin of a surface acoustic wave.

Spin-momentum locking is a universal wave phenomenon promising for applications in electronics and photonics. In acoustics, Lord Rayleigh showed that surface acoustic waves exhibit a characteristic elliptical particle motion strikingly similar to spin-momentum locking. Although these waves have become one of the few phononic technologies of industrial relevance, the observation of their transverse spin remained an open challenge. Here, we observe the full spin dynamics by detecting ultrafast electron cycloids driven by the gyrating electric field produced by a surface acoustic wave propagating on a slab of lithium niobate. A tubular quantum well wrapped around a nanowire serves as an ultrafast sensor tracking the full cyclic motion of electrons. Our acousto-optoelectrical approach opens previously unknown directions in the merged fields of nanoacoustics, nanophotonics, and nanoelectronics for future exploration.

Publisher Correction: Exfoliated WS2-Nafion Composite based Electromechanical Actuators.

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has been fixed in the paper.

Publisher Correction: Exfoliated WS2-Nafion Composite based Electromechanical Actuators.

A correction to this article has been published and is linked from the HTML version of this paper. The error has been fixed in the paper.

Ultrasensitive Label-Free Sensing of IL-6 Based on PASE Functionalized Carbon Nanotube Micro-Arrays with RNA-Aptamers as Molecular Recognition Elements.

This study demonstrates the rapid and label-free detection of Interleukin-6 (IL-6) using carbon nanotube micro-arrays with aptamer as the molecular recognition element. Single wall carbon nanotubes micro-arrays biosensors were manufactured using photo-lithography, metal deposition, and etching techniques. Nanotube biosensors were functionalized with 1-Pyrenebutanoic Acid Succinimidyl Ester (PASE) conjugated IL-6 aptamers. Real time response of the sensor conductance was monitored with increasing concentration of IL-6 (1 pg/mL to 10 ng/mL), exposure to the sensing surface in buffer solution, and clinically relevant spiked blood samples. Non-specific Bovine Serum Albumin (BSA), PBS samples, and anti-IgG functionalized devices gave similar signatures in the real time conductance versus time experiments with no significant change in sensor signal. Exposure of the aptamer functionalized nanotube surface to IL-6 decreased the conductance with increasing concentration of IL-6. Experiments based on field effect transistor arrays suggested shift in drain current versus gate voltage for 1 pg and 1 ng of IL-6 exposure. Non-specific BSA did not produce any appreciable shift in the Ids versus Vg suggesting specific interactions of IL-6 on PASE conjugated aptamer surface gave rise to the change in electrical signal. Both Z axis and phase image in an Atomic Force Microscope (AFM) suggested unambiguous molecular interaction of the IL-6 on the nanotube-aptamer surface at 1 pg/mL concentration. The concentration of 1 pg falls below the diagnostic gray zone for cancer (2.3 pg-4 ng/mL), which is an indicator of early stage cancer. Thus, nanotube micro-arrays could potentially be developed for creating multiplexed assays involving cancer biomarker proteins and possibly circulating tumor cells all in a single assay using PASE functionalization protocol.

Exfoliated WS2-Nafion Composite based Electromechanical Actuators.

The ability to convert electrical energy into mechanical motion is of significant interest in many energy conversion technologies. Here, we demonstrate the first liquid phase exfoliated WS2-Nafion nanocomposite based electro-mechanical actuators. Highly exfoliated layers of WS2 mixed with Nafion solution, solution cast and doped with Li+ was studied as electromechanical actuators. Resonant Raman spectroscopy, X-ray photo-electron-spectroscopy, differential scanning calorimetry, dynamic mechanical analysis, and AC impedance spectroscopy were used to study the structure, photoluminescence, water uptake, mechanical and electromechanical actuation properties of the exfoliated nanocomposites. A 114% increase in elastic modulus (dry condition), 160% increase in proton conductivity, 300% increase in water uptake, cyclic strain amplitudes of ~0.15% for 0.1 Hz excitation frequency, tip displacements greater than nanotube-Nafion and graphene-Nafion actuators and continuous operation for more than 5 hours is observed for TMD-Nafion actuators. The mechanism behind the increase in water uptake is a result of oxygen atoms occupying the vacancies in the hydrophilic exfoliated flakes and subsequently bonding with water, not possible in Nafion composites based on carbon nanotube and graphene.

Classification of biosensor time series using dynamic time warping: applications in screening cancer cells with characteristic biomarkers.

The development of biosensors that produce time series data will facilitate improvements in biomedical diagnostics and in personalized medicine. The time series produced by these devices often contains characteristic features arising from biochemical interactions between the sample and the sensor. To use such characteristic features for determining sample class, similarity-based classifiers can be utilized. However, the construction of such classifiers is complicated by the variability in the time domains of such series that renders the traditional distance metrics such as Euclidean distance ineffective in distinguishing between biological variance and time domain variance. The dynamic time warping (DTW) algorithm is a sequence alignment algorithm that can be used to align two or more series to facilitate quantifying similarity. In this article, we evaluated the performance of DTW distance-based similarity classifiers for classifying time series that mimics electrical signals produced by nanotube biosensors. Simulation studies demonstrated the positive performance of such classifiers in discriminating between time series containing characteristic features that are obscured by noise in the intensity and time domains. We then applied a DTW distance-based k-nearest neighbors classifier to distinguish the presence/absence of mesenchymal biomarker in cancer cells in buffy coats in a blinded test. Using a train-test approach, we find that the classifier had high sensitivity (90.9%) and specificity (81.8%) in differentiating between EpCAM-positive MCF7 cells spiked in buffy coats and those in plain buffy coats.