Intrinsic Signals Research Articles

Fluorine MR Imaging Probes Dynamic Migratory Profiles of Perfluorocarbon-Loaded Dendritic Cells After Streptozotocin-Induced Inflammation.

The pathogenesis of type 1 diabetes (T1D) involves presentation of islet-specific self-antigens by dendritic cells (DCs) to autoreactive T cells, resulting in the destruction of insulin-producing pancreatic beta cells. We aimed to study the dynamic homing of diabetes-prone DCs to the pancreas and nearby organs with and without induction of pancreatic stress in a T1D susceptible model of repeated streptozotocin (STZ) injection. In vitro labeling of activated bone marrow-derived DCs (BMDCs) from NOD (Nonobese diabetes) mice was performed using zonyl perfluoro-15-crown-5-ether nanoparticles (ZPFCE-NPs). Internalization of particles was confirmed by confocal microscopy. Two groups of NOD.SCID (nonobese diabetic/severe combined immunodeficiency) mice with (induced by low dose STZ administration) or without pancreatic stress were compared. Diabetogenic BMDCs loaded with BDC2.5 mimotope were pre-labeled with ZPFCE-NPs and adoptively transferred into mice. Longitudinal in vivo fluorine MRI (19F MRI) was performed 24h, 36h and 48h after transfer of BMDCs. For ex vivo quantification of labeled cells, 19F NMR and flow cytometry were performed on dissected tissues to validate in vivo 19F MRI data. In vitro flow cytometry and confocal microscopy confirmed high uptake of nanoparticles in BMDCs during the process of maturation. Migration/homing of activated and ZPFCE-NP- labeled BMDCs to different organs was monitored and quantified longitudinally, showing highest cell density in pancreas at 48-h time-point. Based on 19F MRI, STZ induced mild inflammation in the pancreatic region, as indicated by high accumulation of ZPFCE-NP-labeled BMDCs in the pancreas when compared to the vehicle group. Pancreatic draining lymph nodes showed elevated homing of labeled BMDCs in the vehicle groups in contrast to the STZ group after 72h. The effect of STZ was confirmed by increased blood glucose levels. We showed the potential of 19F MRI for the non-invasive visualization and quantification of migrating immune cells in models for pancreatic inflammation after STZ administration. Without any intrinsic background signal, 19F MRI serves as a highly specific imaging tool to study the migration of diabetic-prone BMDCs in T1D models in vivo. This approach could particularly be of interest for the longitudinal assessment of established or novel anti-inflammatory therapeutic approaches in preclinical models.

Rapid electrochemical detection of COVID-19 genomic sequence with dual-function graphene nanocolloids based biosensor

Discovered in December 2019, the Severe Acute Respiratory Syndrome Coronavirus 2 (aka SARS-CoV-2 or 2019-nCoV) has attracted worldwide attention and concerns due to its high transmissibility and the severe health consequences experienced upon its infection, particularly by elderly people. Over 329 million people have been infected till date and over 5.5 million people could not survive the respiratory illness known as COVID-19 syndrome. Rapid and low-cost detection methods are of utmost importance to monitor the diffusion of the virus and to aid in the global fight against the pandemic.We propose here the use of graphene oxide nanocolloids (GONC) as an electroactive nanocarbon material that can act simultaneously as a transducing platform as well as the electroactive label for the detection of 2019-nCoV genomic sequences. The ability of GONC to provide an intrinsic electrochemical signal arising from the reduction of the electrochemically reducible oxygen functionalities present on its surface, allows GONC to be used as a simple and sensitive biosensing platform. Different intrinsic electroactivity of the material was obtained at each step of the genosensing process, starting from the immobilization of a short-stranded DNA probe and followed by the incubation with different concentrations of the target 2019-nCoV DNA strand. Monitoring such variations enabled the quantification of the target analyte over a wide dynamic range between 10−10 and 10−5 M.All in all, this proof-of-concept system serves as a stepping stone for the development of a rapid, sensitive and selective analytical tool for the detection of 2019-nCoV as well as other similar viral vectors. The use of cost-effective electrochemical detection methods coupled with the vast availability and suitability of carbon-based nanomaterials make this sensing system a valid candidate for low-cost and point-of-care analysis.

B-cell intrinsic and extrinsic signals that regulate central tolerance of mouse and human B cells.

The random recombination of immunoglobulin V(D)J gene segments produces unique IgM antibodies that serve as the antigen receptor for each developing B cell. Hence, the newly formed B cell repertoire is comprised of a variety of specificities that display a range of reactivity with self-antigens. Newly generated IgM+ immature B cells that are non-autoreactive or that bind self-antigen with low avidity are licensed to leave the bone marrow with their intact antigen receptor and to travel via the blood to the peripheral lymphoid tissue for further selection and maturation. In contrast, clones with medium to high avidity for self-antigen remain within the marrow and undergo central tolerance, a process that revises their antigen receptor or eliminates the autoreactive B cell altogether. Thus, central B cell tolerance is critical for reducing the autoreactive capacity and avidity for self-antigen of our circulating B cell repertoire. Bone marrow cultures and mouse models have been instrumental for understanding the mechanisms that regulate the selection of bone marrow B cells. Here, we review recent studies that have shed new light on the contribution of the ERK, PI3K, and CXCR4 signaling pathways in the selection of mouse and human immature B cells that either bind or do not bind self-antigen.

Stabilizing Enzymes in Plasmonic Silk Film for Synergistic Therapy of In Situ SERS Identified Bacteria.

Increasing antibiotic resistance becomes a serious threat to public health. Photothermal therapy (PTT) and antibacterial enzyme‐based therapy are promising nonresistant strategies for efficiently killing drug‐resistant bacteria. However, the poor thermostability of enzymes in PTT hinders their synergistic therapy. Herein, antibacterial glucose oxidase (GOx) is embedded in a Ag graphitic nanocapsule (Ag@G) arrayed silk film to fabricate a GOx‐synergistic PTT system (named silk‐GOx‐Ag@G, SGA). The SGA system can stabilize GOx by a vitrification process through the restriction of hydrogen bond and rigid β‐sheet, and keep the antibacterial activity in the hyperthermal PTT environment. Moreover, the arrayed Ag@G possesses excellent chemical stability due to the protection of graphitic shell, providing stable plasmonic effect for integrating PTT and surface enhanced Raman scattering (SERS) analysis even in the GOx‐produced H2O2 environment. With in situ SERS identification of bacterial intrinsic signals in the mouse wound model, such SGA realizes superior synergistic antibacterial effect on the infected Escherichia coli, Staphylococcus aureus, and methicillin‐resistant Staphylococcus aureus in vivo, while without causing significant biotoxicity. This system provides a therapeutic method with low resistance and in situ diagnosis capability for efficiently eliminating bacteria.

Intrinsic signal processed non-linearity tolerant novel 2-Tier star constellation

In coherent optical systems, optical fiber non-linearity is a consistent limiting factor towards the effective signal-to-noise ratio though being mitigated by various digital signal processing based approaches. In this paper, an intrinsic method of signal processing based on the shape of the input constellation is employed to yield a novel non-linearity tolerant geometric constellation. 16-QAM back-to-back coherent system is optimized for minimum value of non-linear interference, and a novel 2-Tier star constellation using sequential quadratic programming algorithm is proposed. The values of second and fourth order moments of input obtained for the optimized 2-Tier star constellation are 1.19 and 1.70 respectively, resulting in an overall reduction of non-linear interference. The complexity of the system proposed is found to be minimal in comparison to the other existing systems employing digital compensation.

Cortical Spreading Depolarizations in a Mouse Model of Subarachnoid Hemorrhage.

Cortical spreading depolarizations (CSDs) are associated with worse outcomes in patients with aneurysmal subarachnoid hemorrhage (SAH). Animal models are required to assess whether CSDs can worsen outcomes or are an epiphenomenon; however, little is known about the presence of CSDs in existing animal models. Therefore, we designed a study to determine whether CSDs occur in a mouse model of SAH. A total of 36 mice were included in the study. We used the anterior prechiasmatic injection model of SAH under isoflurane anesthesia. A needle was inserted through the mouse olfactory bulb with the point terminating at the base of the skull, and arterial blood or saline (100µl) was injected over 10s. Changes in cerebral blood volume over the entire dorsal cortical surface were assessed with optical intrinsic signal imaging for 5min following needle insertion. CSDs occurred in 100% of mice in the hemisphere ipsilateral to olfactory bulb needle insertion (CSD1). Saline-injected mice had 100% survival (n = 10). Blood-injected mice had 88% survival (n = 23 of 26). A second, delayed, CSD ipsilateral to CSD1 occurred in 31% of blood-injected mice. An increase in the time interval between CSD1 and blood injection was associated with the occurrence of a second CSD in blood-injected mice (mean intervals 26.4 vs. 72.7s, p < 0.0001, n = 18 and 8). We observed one blood-injected animal with a second CSD in the contralateral hemisphere and observed terminal CSDs in mice that died following SAH injection. The prechiasmatic injection model of SAH includes CSDs that occur at the time of needle insertion. The occurrence of subsequent CSDs depends on the timing between CSD1 and blood injection. The mouse prechiasmatic injection model could be considered an SAH plus CSD model of the disease. Further work is needed to determine the effect of multiple CSDs on outcomes following SAH.

Function-specific projections from V2 to V4 in macaques

Previous studies have revealed modular projections from area V2 to area V4 in macaques. Specifically, V2 neurons in cytochrome oxidase (CO)-rich thin and CO-sparse pale stripes project to distinct regions in V4. However, how these modular projections relate to the functional subcompartments of V4 remains unclear. In this study, we injected retrograde fluorescent tracers into V4 regions with different functional properties (color, orientation, and direction) that were identified with intrinsic signal optical imaging (ISOI). We examined the labeled neurons in area V2 and their locations with respect to the CO patterns. Covariation was observed between the functional properties of the V4 injection sites and the numbers of labeled neurons in particular CO stripes. This covariation indicates that the color domains in V4 mainly received inputs from thin stripes in V2, whereas V4 orientation domains received inputs from pale stripes. Although motion-sensitive domains are present in both V2 and V4, our results did not reveal a functional specific feedforward projection between them. These results confirmed previous findings of modular projections from V2 to V4 and provided functional specificity for these anatomical projections. Together, these findings indicate that color and form remain separate in ventral mid-level visual processing.

Определение температурных режимов отжига ферромагнитных аморфных проводов, полученных методом Улитовского – Тейлора, при нагреве прямым пропусканием тока

The direct current (dc) heating effect of ferromagnetic amorphous wires (AW) on the electromagnetic properties of the serial Co-based alloy, Co – Fe – Cr – Si – B, is investigated. The Ulitovsky – Taylor method was used to produce AW with diameters D = 40, 70, 82, 98, 123, and 145 μm in a glass shell, that was removed mechanically by elastic bending on a laboratory bench. The developed in situ method of stepwise cyclic dc heating of AW of various diameters enables to choose the optimal values of the current (Ia) for carrying out the selected modes that maximize the magnetic properties. AW electromagnetic properties were monitored by registering the amplitude of the intrinsic electromagnetic signal of electromotive force (EMF) of the AW sample under study. Since reliable direct measurements of AW temperature (Ta) when passing the current (Ia) quite an undertakings, we used indirect method of AW heating temperature estimation by establishing the relationship Ta = f (Ia). For the AW specified diameters, the direct current values were experimentally determined, which ensure optimal heat treatment in the range of temperature stability of the amorphous phase, up to the crystallization temperature, Tx. A calibration curve was constructed using reference temperature points, i.e. Tx and the Curie temperature (Tc). The proposed technique for calibration graph construction I = f(D) may be used for different AWs that have different diameters and same composition; it allows one to determine the modes of current annealing required for the best EMF amplitude values of amorphous wires of the given diameter, up to 100 μm.

Enhanced Signal-Associated Noise in a φ-OTDR System

Owing to their high sensitivity with respect to external measurands, Rayleigh-based distributed optical fiber sensors (DOFS) find their way into applications in many industrial and academic sectors. To further transcend the limit of these sensors in terms of sensing range, low spatial resolution, speed and accuracy of the measurement, improving the signal-to-noise ratio (SNR) of the system plays a pivotal role. Out of the several existing techniques for enhancing the SNR, one such method, solely dedicated to the Rayleigh-based sensors, is through intrinsically increasing the backreflected signal of the fibers. The enhanced backreflected signal provided by such fibers, generally known as reflection-enhanced fibers (REF), is rigorously analysed in the present work. It is inferred from the analysis that the enhanced signal is essentially accompanied by enhanced signal-dependent noises, which can adversely affect their performance. For instance, when a performance comparison is carried out between the REF and a standard single-mode fiber (SMF) under identical experimental conditions, due to their different intrinsic backreflected signal levels, the two fibers experience dissimilar noise regimes leading to an erroneous estimation of the performance of the former. This necessitates the optimisation of the interrogation system and the experimental parameters while employing such fibers for specific sensing applications. Additionally, a distributed temperature measurement is presented by taking advantage of the enhanced SNR of a 100 m long REF exhibiting a sub-mK temperature uncertainty of 0.5 mK at metric spatial resolution yielding a sixfold improvement compared to the 3 mK uncertainty of an SMF.

OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY FINDINGS OF CLASSIC CHOROIDAL NEOVASCULARIZATION IN POLYPOIDAL CHOROIDAL VASCULOPATHY.

To evaluate the flow signals in subretinal hyperreflective material (SHRM) that represents classic choroidal neovascularization (CNV) on fluorescein angiography in eyes with polypoidal choroidal vasculopathy. We retrospectively reviewed 20 eyes with polypoidal choroidal vasculopathy that appeared to have classic CNV on fluorescein angiography, accompanied by SHRM on optical coherence tomography (OCT) at the same location. Using OCT angiography (OCTA), we analyzed intrinsic flow signals in the SHRM (cross-sectional B-scans and en face). The possible association between pretreatment OCT angiography findings and fibrotic scar formation after antivascular endothelial growth factor (VEGF) treatment was evaluated. Six of 20 eyes (30%) showed vascular SHRM; the remaining 14 eyes (70%) showed avascular SHRM at the classic CNV site at baseline. The SHRM corresponded with polypoidal lesions seen on indocyanine green angiography in 5 of 6 eyes with vascular SHRM and in all 14 eyes with avascular SHRM. After anti-VEGF treatment, all 6 eyes with vascular SHRM left a fibrotic scar, whereas all 14 eyes with avascular SHRM showed no scar formation (P < 0.001). Using OCT angiography, we evaluated the flow signals in SHRM that represented classic CNV in eyes with polypoidal choroidal vasculopathy and successfully differentiated true Type 2 macular neovascularization from pseudo classic CNV.

Tactile sensation of natural teeth and dental implants in the somatosensory cortex.

This study aimed to investigate the cortical response characteristics evoked by natural teeth and implants. Five cats were subjected to intrinsic signal optical imaging to measure the cortical responses evoked by natural teeth and implants. The difference in tactile sensation between the implant and natural tooth was compared in detail at the cortical response level. Some similarities were observed between the implants and natural teeth. The stimulating-response curves of the implants and natural teeth were generally S-curves, and both implants and natural teeth preferred labial-lingual direction stimulation. The implants and natural teeth differed in terms of their tactile sensitivity: implants were weaker than natural teeth in terms of both static and dynamic sensitivity. However, after saturation, there was no significant difference in tactile strength between implants and natural teeth. Both natural teeth and implants are able to distinguish the tactile strength and stimulation direction. Although implants are less sensitive than the natural tooth, the maximal tactile function and directional preference of implants are similar to those of natural teeth.

ACPSF1 cooperates with terminator U-tract to dictate archaeal transcription termination efficacy.

Recently, aCPSF1 was reported to function as the long-sought global transcription termination factor of archaea; however, the working mechanism remains elusive. This work, through analyzing transcript-3'end-sequencing data of Methanococcus maripaludis, found genome-wide positive correlations of both the terminator uridine(U)-tract and aCPSF1 with hierarchical transcription termination efficacies (TTEs). In vitro assays determined that aCPSF1 specifically binds to the terminator U-tract with U-tract number-related binding affinity, and in vivo assays demonstrated the two elements are indispensable in dictating high TTEs, revealing that aCPSF1 and the terminator U-tract cooperatively determine high TTEs. The N-terminal KH domains equip aCPSF1 with specific-binding capacity to terminator U-tract and the aCPSF1-terminator U-tract cooperation; while the nuclease activity of aCPSF1 was also required for TTEs. aCPSF1 also guarantees the terminations of transcripts with weak intrinsic terminator signals. aCPSF1 orthologs from Lokiarchaeota and Thaumarchaeota exhibited similar U-tract cooperation in dictating TTEs. Therefore, aCPSF1 and the intrinsic U-rich terminator could work in a noteworthy two-in-one termination mode in archaea, which may be widely employed by archaeal phyla; using one trans-action factor to recognize U-rich terminator signal and cleave transcript 3'-end, the archaeal aCPSF1-dependent transcription termination may represent a simplified archetypal mode of the eukaryotic RNA polymerase II termination machinery.

Bioinspired surface-enhanced Raman scattering substrate with intrinsic Raman signal for the interactive SERS detection of pesticides residues

Although biomimetic surface enhanced Raman scattering (SERS) substrate which makes use of naturally existing raw materials have been fully utilized, it remains challenging to achieve credible quantitative detection. Herein, nanoimprint technology was exploited to engineer internal standard (IS) enabled quantitative flexible biomimetic SERS substrates, in which polydimethylsiloxane (PDMS) with intrinsic Raman signal was utilized as a tool to reversely duplicate surface structures from different agriculture products and then deposited with Ag nanoparticles. The resultant four kinds of biomimetic SERS substrates with different surface geometries all permit highly sensitive assay with enhancement factors (EFs) of about 106 in both drop-dry and in situ SERS detection modes. Moreover, the quantitative degree in the SERS detection was effectively corrected based on the IS strategy. Finally, an ingenious interactive in situ SERS detection was conducted. Interestingly, the maximum recovery rate was achieved when the template food was used as target surface compared with other foods, indicating the significance of manufacturing the highly conformed SERS-active structure from the surface to be tested. The proposed quantitative biomimetic SERS substrate is expected to be widely used in the field of biochemical supervision.

Inhibition of Cdk5 in PV Neurons Reactivates Experience-Dependent Plasticity in Adult Visual Cortex.

Cyclin-dependent kinase 5 (Cdk5) has been shown to play a critical role in brain development, learning, memory and neural processing in general. Cdk5 is widely distributed in many neuron types in the central nervous system, while its cell-specific role is largely unknown. Our previous study showed that Cdk5 inhibition restored ocular dominance (OD) plasticity in adulthood. In this study, we specifically knocked down Cdk5 in different types of neurons in the visual cortex and examined OD plasticity by optical imaging of intrinsic signals. Downregulation of Cdk5 in parvalbumin-expressing (PV) inhibitory neurons, but not other neurons, reactivated adult mouse visual cortical plasticity. Cdk5 knockdown in PV neurons reduced the evoked firing rate, which was accompanied by an increment in the threshold current for the generation of a single action potential (AP) and hyperpolarization of the resting membrane potential. Moreover, chemogenetic activation of PV neurons in the visual cortex can attenuate the restoration of OD plasticity by Cdk5 inhibition. Taken together, our results suggest that Cdk5 in PV interneurons may play a role in modulating the excitation and inhibition balance to control the plasticity of the visual cortex.

Single-cell resolution of plasma cell fate programming in health and disease.

Long considered a homogeneous population dedicated to antibody secretion, plasma cell phenotypic and functional heterogeneity is increasingly recognized. Plasma cells were first segregated based on their maturation level, but the complexity of this subset might well be underestimated by this simple dichotomy. Indeed, in the last decade new functions have been attributed to plasma cells including but not limited to cytokine secretion. However, a proper characterization of plasma cell heterogeneity has remained elusive partly due to technical issues and cellular features that are specific to this cell type. Cell intrinsic and cell extrinsic signals could be at the origin of this heterogeneity. Recent advances in technologies such as single cell RNA-seq, ATAC-seq, or ChIP-seq on low cell numbers helped to elucidate the fate decision in other cell lineages and similar approaches could be implemented to evaluate the heterogeneous fate of activated B cells in health and disease. Here, we summarized published work shedding some lights on the stimuli and genetic program shaping B-cell terminal differentiation at the single cell level in mice and men. We also discuss the fate and heterogeneity of plasma cells during immune responses, vaccination, and in the frame of human plasma cell disorders.

Quantification of intrinsic optical signals in the outer human retina using optical coherence tomography.

Intrinsic optical signals constitute a noninvasive biomarker promising the objective assessment of retinal photoreceptor function. We employed a commercial optical coherence tomography (OCT) system and an OCT signal model for evaluation of optical path length (OPL) changes in the temporal outer retina of five healthy subjects during light adaptation. Data were acquired at 30 time points, in ambient light and during long duration stimulation with white light, and analyzed, employing a signal model based on the sum of seven Gaussian curves corresponding to all relevant anatomical structures of the outer retina. During light stimulation, mean OPL between rod outer segment tips (ROST) and the retinal pigment epithelium (RPE) decreased by 21.4 ± 3.5%. Further, OPL between the external‐limiting membrane (ELM) and the RPE decreased by 5.2 ± 0.9% versus baseline, while OPL between ELM and ROST showed an initial decrease by 2.1 ± 1.6% versus baseline and, thereafter, increased by 2.8 ± 2.1% versus baseline. Thus, the presented approach allowed for assess to dynamic changes in the outer retina in response to light. The change in the subretinal space occurring in the context of light adaptation could be measured using a standard OCT platform and a dedicated signal model.

Disposable Passive Electrochemical Microfluidic Device for Diagnosis of Congenital Disorders of Glycosylation

AbstractA disposable pump‐free electrochemical microfluidic device made by using a multilayer lamination technique is proposed for diagnosis of glycosylation disorders. Thanks to the stacking of polyethylene terephthalate (PET) films and double adhesive layers, it is possible to create a geometry that allows the filling of the tailored channels in a fixed time. In the main channel of this passive microfluidic device, the necessary steps to perform the electrochemical determination of transferrin are performed: labeling of the protein with Os (VI) complex (electrochemical tag), washing with water of the osmium residues and electrochemical detection by adsorptive transfer stripping square wave voltammetry. Electrochemical detection released two electrochemical signals: one from Os (VI) complex due to carbohydrates at −0.9 V, and other from the intrinsic electrochemical signal of glycoprotein due to the amino acids at +0.8 V. The ratio between them establishes an indicator of the degree of glycosylation (called electrochemical index of glycosylation). The method was successfully applied to the analysis of clinical samples from patients with congenital disorders of glycosylation.

Electrolyte-gated carbon nanotube field-effect transistor-based biosensors: Principles and applications

Nowadays, there is a high demand for sensitive and selective real-time analytical methods suitable for a wide range of applications, from personalized telemedicine, drug discovery, food safety, and quality control, to defense, security, as well as environmental monitoring. Biosensors are analytical devices able to detect bio-chemical analytes (e.g., neurotransmitters, cancer biomarkers, bio-molecules, and ions), through the combination of a bio-recognition element and a bio-transduction device. The use of customized bio-recognition elements such as enzymes, antibodies, aptamers, and ion-selective membranes facilitates achieving high selectivity. Among the different bio-transduction devices currently available, electrolyte-gated field-effect transistors, in which the dielectric is represented by an ionic liquid buffer solution containing the targeted analyte, are gaining increasing attention. Indeed, these bio-transduction devices are characterized by superior electronic properties and intrinsic signal amplification that allow the detection of a wide range of bio-molecules with high sensitivity (down to pM concentration). A promising semiconducting material for bio-transduction devices is represented by carbon nanotubes, due to their unique electrical properties, nanosize, bio-compatibility, and their simple low-cost processability. This work provides a comprehensive and critical review of electrolyte-gated carbon nanotube field-effect transistor-based biosensors. First, an introduction to these bio-sensing devices is given. Next, the device configurations and operating principles are presented, and the most used materials and processes are reviewed with a particular focus on carbon nanotubes as the active material. Subsequently, different functionalization strategies reported in the literature, based on enzymes, antibodies, aptamers, and ion-selective membranes, are analyzed critically. Finally, present issues and challenges faced in the area are investigated, the conclusions are drawn, and a perspective outlook over the field of bio-sensing technologies, in general, is provided.

A Novel Method for Estimating the Intrinsic Magnetic Field Spectrum of Kinetic-Range Turbulence

Understanding plasma turbulence below the ion characteristic scales is one of the key open problems of solar wind physics. The bulk of our knowledge about the nature of the kinetic-scale fluctuations comes from the high-cadence measurements of the magnetic field. The spacecraft frame frequencies of the sub-ion scale fluctuations are frequently around the Nyquist frequencies of the magnetic field sampling rate. Thus, the resulting ‘measured’ time series may significantly differ from the ‘true’ ones. It follows that second-order moments (e.g., power spectral density, PSD) of the signal may also be highly affected in both their amplitude and their slope. In this paper, we focus on the estimation of the PSD slope for finitely sampled data and we unambiguously define a so-called local slope in the framework of Continuous Wavelet Transform. Employing Monte Carlo simulations, we derive an empirical formula that assesses the statistical error of the local slope estimation. We illustrate the theoretical results by analyzing measurements of the magnetic field instrument (MFI) on board the Wind spacecraft. Our analysis shows that the trace power spectra of magnetic field measurements of MFI can be modeled as the sum of PSD of an uncorrelated noise and an intrinsic signal. We show that the local slope strongly depends on the signal-to-noise (S/N) ratio, stressing that noise can significantly affect the slope even for S/N around 10. Furthermore, we show that the local slopes below the frequency corresponding to proton inertial length, 5≳kλpi&gt;1, depend on the level of the magnetic field fluctuations in the inertial range (Pin), exhibiting a gradual flattening from about −11/3 for high Pin toward about −8/3 for low Pin.

Colorectal Cancer Stem Cells: An Overview of Evolving Methods and Concepts.

Simple SummaryIn recent years, colorectal cancer stem cells (cCSCs) have been the object of intense investigation for their promise to disclose new aspects of colorectal cancer cell biology, as well as to devise new treatment strategies for colorectal cancer (CRC). However, accumulating studies on cCSCs by complementary technologies have progressively disclosed their plastic nature, i.e., their capability to acquire different phenotypes and/or functions under different circumstances in response to both intrinsic and extrinsic signals. In this review, we aim to recapitulate how a progressive methodological development has contributed to deepening and remodeling the concept of cCSCs over time, up to the present.Colorectal cancer (CRC) represents one of the most deadly cancers worldwide. Colorectal cancer stem cells (cCSCs) are the driving units of CRC initiation and development. After the concept of cCSC was first formulated in 2007, a huge bulk of research has contributed to expanding its definition, from a cell subpopulation defined by a fixed phenotype in a plastic entity modulated by complex interactions with the tumor microenvironment, in which cell position and niche-driven signals hold a prominent role. The wide development of cellular and molecular technologies recent years has been a main driver of advancements in cCSCs research. Here, we will give an overview of the parallel role of technological progress and of theoretical evolution in shaping the concept of cCSCs.