Differential Properties Research Articles

A Prodrug Strategy to Reposition Atovaquone as a Long-Acting Injectable for Malaria Chemoprotection.

Recent malaria drug discovery approaches have been extensively focused on the development of oral, smallmolecule inhibitors for disease treatment whereas parenteral routes of administration have been avoided due to limitations in deploying a shelf-stable injectable even though it could be dosed less frequently. However, an updated target candidate profile from Medicines for Malaria Venture (MMV) and stakeholders have advocated for long-acting injectable chemopreventive agents as an important interventive tool to improve malaria prevention. Here, we present strategies for the development of a long-acting, intramuscular, injectable atovaquone prophylactic therapy. We have generated three prodrug approaches that are contrasted by their differential physiochemical properties and pharmacokinetic profiles: mCBK068, a docosahexaenoic acid ester of atovaquone formulated in sesame oil, mCKX352, a heptanoic acid ester of atovaquone formulated as a solution in sesame oil, and mCBE161, an acetic acid ester of atovaquone formulated as an aqueous suspension. As a result, from a single 20 mg/kg intramuscular injection, mCKX352 and mCBE161 maintain blood plasma exposure of atovaquone above the minimal efficacious concentration for >70 days and >30 days, respectively, in cynomolgus monkeys. The differences in plasma exposure are reflective of the prodrug strategy, which imparts altered chemical properties that ultimately influence aqueous solubility and depot release kinetics. On the strength of the pharmacokinetic and safety profiles, mCBE161 is being advanced as a first-in-class clinical candidate for first-in-human trials.

The bidirectional role of GABAA and GABAB receptors during the differentiation process of neural precursor cells of the subventricular zone.

The intricate process of neuronal differentiation integrates multiple signals to induce transcriptional, morphological, and electrophysiological changes that reshape the properties of neural precursor cells during their maturation and migration process. An increasing number of neurotransmitters and biomolecules have been identified as molecular signals that trigger and guide this process. In this sense, taurine, a sulfur-containing, non-essential amino acid widely expressed in the mammal brain, modulates the neuronal differentiation process. In this study, we describe the effect of taurine acting via the ionotropic GABAA receptor and the metabotropic GABAB receptor on the neuronal differentiation and electrophysiological properties of precursor cells derived from the subventricular zone of the mouse brain. Taurine stimulates the number of neurites and favors the dendritic complexity of the neural precursor cells, accompanied by changes in the somatic input resistance and the strength of inward and outward membranal currents. At the pharmacological level, the blockade of GABAA receptors inhibits these effects, whereas the stimulation of GABAB receptors has no positive effects on the taurine-mediated differentiation process. Strikingly, the blockade of the GABAB receptor with CGP533737 stimulates neurite outgrowth, dendritic complexity, and membranal current kinetics of neural precursor cells. The effects of taurine on the differentiation process involve Ca2+ mobilization and the activation of intracellular signaling cascades since chelation of intracellular calcium with BAPTA-AM, and inhibition of the CaMKII, ERK1/2, and Src kinase inhibits the neurite outgrowth of neural precursor cells of the subventricular zone.

Geometric Modeling of Umbrella Surfaces

In this study, we present a novel method for modeling the canopy surface of an umbrella. Our approach involves representing the area between the ribs on the canopy as a trimmed bilinear patch. Furthermore, we conduct an in-depth exploration of various differential geometric properties of the umbrella surface. We introduce a method for unfolding the canopy surface onto a plane, which serves as a valuable technique for fabricating a cardboard template to accurately cut canopy fabrics. To validate the effectiveness of our geometric modeling method, we apply it to several umbrella models, showcasing its practical application and benefits.

Engineered CD147-Deficient THP-1 Impairs Monocytic Myeloid-Derived Suppressor Cell Differentiation but Maintains Antibody-Dependent Cellular Phagocytosis Function for Jurkat T-ALL Cells with Humanized Anti-CD147 Antibody.

CD147 is upregulated in cancers, including aggressive T-ALL. Traditional treatments for T-ALL often entail severe side effects and the risk of relapse, highlighting the need for more efficacious therapies. ADCP contributes to the antitumor response by enhancing the ability of phagocytic cells to engulf cancer cells upon antibody binding. We aimed to engineer CD147KO THP-1 cells and evaluated their differentiation properties compared to the wild type. A humanized anti-CD147 antibody, HuM6-1B9, was also constructed for investing the phagocytic function of CD147KO THP-1 cells mediated by HuM6-1B9 in the phagocytosis of Jurkat T cells. The CD147KO THP-1 was generated by CRISPR/Cas9 and maintained polarization profiles. HuM6-1B9 was produced in CHO-K1 cells and effectively bound to CD147 with high binding affinity (KD: 2.05 ± 0.30 × 10-9 M). Additionally, HuM6-1B9 enhanced the phagocytosis of Jurkat T cells by CD147KO THP-1-derived LPS-activated macrophages (M-LPS), without self-ADCP. The formation of THP-1-derived mMDSC was limited in CD147KO THP-1 cells, highlighting the significant impact of CD147 deletion. Maintaining expression markers and phagocytic function in CD147KO THP-1 macrophages supports future engineering and the application of induced pluripotent stem cell-derived macrophages. The combination of HuM6-1B9 and CD147KO monocyte-derived macrophages holds promise as an alternative strategy for T-ALL.

A Modification to the Novel Toy Model of the Riemann Zeta Function Roots Equation

It is true that my previous series of papers about the Riemann Hypothesis has raised lots of discussions or the concerns among the mathematics society. Indeed, some professionals may think that the Riemann Zeta function at s = 1 or ∑_(n=1)^∞▒1/n is actually divergent and may tend to an infinity, how it can be acted as a denominator in a proof or something like 1/∞ ? This author’s idea is there may be no need to evaluate such kind of summation as one may consider the sum just as an (imaginary) constant (but NOT the complex number). Or we may only consider such summation as a kind of improper integrals with a black-boxed answer. In other words, the true final value of the summation ∑_(n=1)^∞▒1/n is NOT an concerning serious issue. The function ∑_(n=1)^∞▒1/n^s is in practice a smooth function and equals to log N or the logarithmic function for s = 1 or have the infinite differentiable properties except n = 0, that is why the commercial software Maple Soft can compute the Zeta function’s associated Taylor series successfully. In fact, from the above series together with the harmonic properties, one may calculate the artifical Zeta function’s root model equation such as the 0.5 +/- β*cot(ln(x))/(αx+1)n (will be discussed in my next paper of the series). Indeed, this is NOT the best model. Actually, the true Riemann Zeta non-trivial Root model equation is: {z = x + yI | z∈0.5±(y_1⩽y⩽y_2 )I} where y1= (±cot(k))/ln(k) , y2 = (±tan(k))/ln(k) with 0<k<2π. Certainly, this author cannot avoid mistakes. Some of the defects in the previous paper such as one in the linguistic proof of the RH will be stated and amended. Lastly, this author wants to remind that the present series of paper is first to establish a model equation for zeta function’s roots and the Plank’s like constant. This author then applies the telescopic and logarithmic methods for a 3 cases proof of the RH. Also, we have a Matlab code for the evaluation of RH complex contour integral. Finally, the RH problem will be transformed into a linguistic one and hence we may have solved the Riemann Hypothesis issue completely through a 4 cases of truth table collaborations with the logical inference [7] & [15] to the causality (structural) organization of the sentences [16] or just named as “Logical & Organized Context”.

Exploring optoelectronic and thermal characteristics of Janus MoSeTe and WSeTe monolayers under mechanical strain

This paper reveals the effect of external strain on the electronic, thermal and optical properties of Janus MSeTe (M=Mo, W) using first principles. Phonon spectrum calculations confirm the dynamic stability of the system. Biaxial stretching can effectively modulate its thermal properties. Uniaxial, biaxial and shear strains modulate the band structure, structural parameters, averaged differential charge density and optical properties of the MSeTe system to different degrees. The increase of compressive and shear strains leads to a gradual decrease of the band gap and triggers a semiconductor-metal phase transition at the critical point. The intrinsic system exhibits strong light absorption in the visible and ultraviolet regions, while strain induces a redshift of the light-absorbing edge, which enhances the response to the infrared and visible wavelength bands. These findings provide a theoretical basis and application potential for the design of optoelectronic devices and thermoelectric materials.

M. tuberculosis PrrA binds the dosR promoter and regulates mycobacterial adaptation to hypoxia

The PrrAB two-component system (TCS) is essential for Mycobacterium tuberculosis viability. Previously, it was demonstrated that PrrA binds DNA in the absence of PrrB-mediated transphosphorylation and that non-cognate serine/threonine-kinases phosphorylate PrrA threonine-6 (T6). Therefore, we investigated the differential binding affinity and regulatory properties of the M. tuberculosis-derived wild-type PrrA, PrrA phosphomimetic (D58E, T6E), and PrrA phosphoablative (D58A, T6A) proteins with the prrAMtb, dosRMtb, and cydAMtb genes. While we hypothesized greater DNA binding affinity and more pronounced regulation by PrrA phosphomimetic variants, recombinant, wild-type PrrAMtb bound DNA with greatest affinity. Collectively, wild-type PrrAMtb recombinant protein displayed the highest binding affinity to the dosRMtb promoter (KD 3.46 ± 2.09 nM), followed by the prrAMtb promoter (KD 9.00 ± 2.66 nM). To establish PrrAMtb regulatory activity, we constructed M. smegmatis ΔprrABMsmeg::prrAMtb strains with each of the PrrAMtb variants and extrachromosomal prrAMtb, dosRMtb, and cydAMtb promoter-mCherry reporter fusions. Our findings showed that PrrAMtb is autoregulatory and induces dosRMtb expression only during in vitro, hypoxic growth. Combined expression of prrABMtb in M. smegmatis ΔprrAB significantly induced cydAMtb promoter-mCherry expression. Our studies advanced the understanding of PrrA function and PrrAB phosphorylation-mediated regulatory mechanisms and control of mycobacterial dosR and cydA hypoxic and low-oxygen responsive genes.

The assessment of left ventricular diastolic function: guidance and recommendations from the British Society of Echocardiography.

Impairment of left ventricular (LV) diastolic function is common amongst those with left heart disease and is associated with significant morbidity. Given that, in simple terms, the ventricle can only eject the volume with which it fills and that approximately one half of hospitalisations for heart failure (HF) are in those with normal/'preserved' left ventricular ejection fraction (HFpEF) (Bianco et al. in JACC Cardiovasc Imaging. 13:258-271, 2020. 10.1016/j.jcmg.2018.12.035), where abnormalities of ventricular filling are the cause of symptoms, it is clear that the assessment of left ventricular diastolic function (LVDF) is crucial for understanding global cardiac function and for identifying the wider effects of disease processes. Invasive methods of measuring LV relaxation and filling pressures are considered the gold-standard for investigating diastolic function. However, the high temporal resolution of trans-thoracic echocardiography (TTE) with widely validated and reproducible measures available at the patient's bedside and without the need for invasive procedures involving ionising radiation have established echocardiography as the primary imaging modality. The comprehensive assessment of LVDF is therefore a fundamental element of the standard TTE (Robinson et al. in Echo Res Pract7:G59-G93, 2020. 10.1530/ERP-20-0026). However, the echocardiographic assessment of diastolic function is complex. In the broadest and most basic terms, ventricular diastole comprises an early filling phase when blood is drawn, by suction, into the ventricle as it rapidly recoils and lengthens following the preceding systolic contraction and shortening. This is followed in late diastole by distension of the compliant LV when atrial contraction actively contributes to ventricular filling. When LVDF is normal, ventricular filling is achieved at low pressure both at rest and during exertion. However, this basic description merely summarises the complex physiology that enables the diastolic process and defines it according to the mechanical method by which the ventricles fill, overlooking the myocardial function, properties of chamber compliance and pressure differentials that determine the capacity for LV filling. Unlike ventricular systolic function where single parameters are utilised to define myocardial performance (LV ejection fraction (LVEF) and Global Longitudinal Strain (GLS)), the assessment of diastolic function relies on the interpretation of multiple myocardial and blood-flow velocity parameters, along with left atrial (LA) size and function, in order to diagnose the presence and degree of impairment. The echocardiographic assessment of diastolic function is therefore multifaceted and complex, requiring an algorithmic approach that incorporates parameters of myocardial relaxation/recoil, chamber compliance and function under variable loading conditions and the intra-cavity pressures under which these processes occur. This guideline outlines a structured approach to the assessment of diastolic function and includes recommendations for the assessment of LV relaxation and filling pressures. Non-routine echocardiographic measures are described alongside guidance for application in specific circumstances. Provocative methods for revealing increased filling pressure on exertion are described and novel and emerging modalities considered. For rapid access to the core recommendations of the diastolic guideline, a quick-reference guide (additional file 1) accompanies the main guideline document. This describes in very brief detail the diastolic investigation in each patient group and includes all algorithms and core reference tables.

In vitro and in vivo studies of a biodegradable Zn-4Ag-0.1Sc alloy with high strength-elongation product, cytocompatibility, osteogenic differentiation, and anti-infection properties for guided bone-regeneration membrane applications

Zinc-silver (Zn-Ag) alloys are generally promising guided bone-regeneration membrane (GBRM) materials due to their moderate degradability, osteogenic differentiation, and antibacterial properties. However, Zn-Ag alloys often display microstructural inhomogeneity and mechanical instability due to the formation of coarse Ag-rich second phases. In this study, Zn-4Ag and Zn-4Ag-0.1Sc (denoted ZA and ZAS, respectively) were comparatively investigated, and the ZAS exhibited a suitable degradation rate, high strength-elongation product, cytocompatibility, antibacterial capacity, and in vitro and in vivo osteogenic properties, making it highly appropriate for GBRM applications. Among all the as-cast and hot-rolled (HR) samples, the HR ZAS had the highest ultimate tensile strength of ∼260.5 MPa, tensile yield strength of ∼202.0 MPa, and elongation of ∼72.7%. The HR ZAS also exhibited a higher degradation rate of ∼36.5 µm/a in Hanks’ solution than those of the HR ZA, while its diluted extract was more cytocompatible and capable of osteogenic differentiation toward both MG-63 and MC3T3-E1 cells. The HR ZAS showed an exceptionally effective antibacterial ability against S. aureus in both in vitro antibacterial testing and in vivo subcutaneous infection models. Further, the HR ZAS demonstrated better osteogenic and histocompatibility properties than those of pure Zn in a rat skull defect model.

Secure state estimation of networked switched systems under denial-of-service attacks

This paper studies the problem of secure state estimation of networked switched systems in the presence of denial-of-service (DoS) attacks, as well as disturbances and measurement noise. Firstly, a state transformation rule is designed to partition the original system into two subsystems, facilitating the design of discrete and continuous state observers. Secondly, by modifying the traditional super-twisting sliding-mode method and taking into account the frequency and duration characteristics of DoS attacks, we employ dynamic differential properties between different modes to design a switching law identification strategy. We show that this strategy can accurately estimate the switching state without imposing any requirement on the switching times and sequences. Thirdly, based on the identified activated mode, a set of mode-dependent continuous state sliding-mode observers is designed, that achieves continuous state estimation in finite time. The practicality and applicability of the developed results are validated through numerical simulations.

Norisoboldine, a Natural Alkaloid from Lindera aggregata (Sims) Kosterm, Promotes Osteogenic Differentiation via S6K1 Signaling Pathway and Prevents Bone Loss in OVX Mice.

Norisoboldine (NOR) is a major isoquinoline alkaloid component in the traditional Chinese herbal plant Lindera aggregata (Sims) Kosterm, with previously reported anti-osteoclast differentiation and antiarthritis properties. However, the roles of NOR on osteoblasts, bone marrow mesenchymal stem cells (BMSCs), and osteoporosis in vivo have never been well established. This study investigates the ability of NOR to improve bone formation in vitro and in vivo. Osteoblasts and BMSCs are used to study the effect of NOR on osteogenic and adipogenic differentiation. It finds that NOR promotes osteogenic differentiation of osteoblasts and BMSCs, while inhibiting adipogenic differentiation of BMSCs by reducing the relative expression of peroxisome proliferator-activated receptorγ (Ppar-γ) and adiponectin, C1Q and collagen domain containing (Adipoq). Mechanistic studies show that NOR increases osteoblast differentiation through the mechanistic target of rapamycin kinase (mTOR)/ribosomal protein S6 kinase; polypeptide 1 (S6K1) pathway, and treatment with an mTOR inhibitor rapamycin blocked the NOR-induced increase in mineral accumulation. Finally, the study evaluates the therapeutic potential of NOR in a mouse model of ovariectomy (OVX)-induced bone loss. NOR prevents bone loss in both trabecular and cortical bone by increasing osteoblast number and phospho-S6K1 (p-S6K1) expression in osteoblasts. NOR effects in enhancing osteoblast-induced bone formation via S6K1 pathway, suggesting the potential of NOR in osteoporosis treatment by increasing bone formation.

Neuronal Subtypes and Connectivity of the Adult Mouse Paralaminar Amygdala.

The paralaminar nucleus of the amygdala (PL) comprises neurons that exhibit delayed maturation. PL neurons are born during gestation but mature during adolescent ages, differentiating into excitatory neurons. These late-maturing PL neurons contribute to the increase in size and cell number of the amygdala between birth and adulthood. However, the function of the PL upon maturation is unknown, as the region has only recently begun to be characterized in detail. In this study, we investigated key defining features of the adult mouse PL; the intrinsic morpho-electric properties of its neurons, and its input and output circuit connectivity. We identify two subtypes of excitatory neurons in the PL based on unsupervised clustering of electrophysiological properties. These subtypes are defined by differential action potential firing properties and dendritic architecture, suggesting divergent functional roles. We further uncover major axonal inputs to the adult PL from the main olfactory network and basolateral amygdala. We also find that axonal outputs from the PL project reciprocally to these inputs and to diverse targets including the amygdala, frontal cortex, hippocampus, hypothalamus, and brainstem. Thus, the adult mouse PL is centrally placed to play a major role in the integration of olfactory sensory information, to coordinate affective and autonomic behavioral responses to salient odor stimuli.

The atmospheric aerosol spatial distribution and tropical intra-seasonal oscillations over the South Asian region

Intra-seasonal oscillations (ISO) are well known to modulate the weather phenomena which in turn are known to influence the atmospheric aerosol loading. This study investigates how aerosol loading is modulated in ISO spatio-temporal scales over the Indian region using long-term satellite aerosol optical depth data from Moderate Resolution Imaging Spectroradiometer (MODIS) sensor, onboard Terra Satellite. It is shown that Madden-Julian Oscillation (MJO) and Equatorial Rossby waves (ER) have the highest effect (15–20% of the mean) followed by Mixed-Rossby-gravity and Tropical depressions (MT), and Kelvin wave (KE) (5–15%). Further, a dipolar pattern in aerosol loading was observed, with poles over the Arabian Sea and the Bay of Bengal. These variabilities were found to be mainly driven by anomalous winds associated with the ISOs. Similar to aerosol, dipolar signatures in the atmospheric aerosol radiative forcing (ARF) were also observed with clearer patterns. However, the forcing poles are not centered exactly where aerosol poles were observed, indicating the effect of differential properties of aerosols on the aerosol radiative forcing. Quantitatively, at the surface level, modulation in ARF is up to 3 Wm-2 (15%) for MJO and ER, and up to 2 Wm-2 (5%) for KE and MT; in the atmosphere and at the top of the atmosphere, modulation is up to 2 Wm-2 (15%) for MJO and ER, and up to 1 Wm-2 (5%) for KE and MT.

Tannic acid and quaternized chitosan mediated puerarin-loaded octacalcium phosphate /sodium alginate scaffold for bone tissue engineering

Current limitations in mechanical performance and foreign body reactions (FBR) often lead to implant failure, restricting the application of bioceramic scaffolds. This study presents a novel 3D-printed scaffold that combines the release of anti-inflammatory drugs with osteogenic stimulation. Initially, the inorganic and organic phases were integrated to ensure the scaffold's mechanical integrity through catechol chemistry and the electrostatic interactions between tannic acid and quaternary ammonium chitosan. Subsequently, layers of polydopamine-encapsulated puerarin-loaded zeolitic imidazolate framework-8 (ZIF-8) were self-assembled onto the stent's surface, creating the drug-loaded scaffold that improved drug release without altering the scaffold's structure. Compared with unloaded scaffolds, the puerarin-loaded scaffold demonstrated excellent osteogenic differentiation properties along with superior anti-inflammatory and osteogenic effects in a range of in vitro and in vivo studies. RNA sequencing clarified the role of the TNF and NF/κB signaling pathways in these effects, further supporting the scaffold's osteogenic potential. This study introduces a novel approach for creating drug-loaded scaffolds, providing a unique method for treating cancellous bone defects.

Regulation of mesenchymal stem cell differentiation by autophagy.

Autophagy, a process that isolates intracellular components and fuses them with lysosomes for degradation, plays an important cytoprotective role by eliminating harmful intracellular substances and maintaining cellular homeostasis. Mesenchymal stem cells (MSCs) are multipotent progenitor cells with the capacity for self-renewal that can give rise to a subset of tissues and therefore have potential in regenerative medicine. However, a variety of variables influence the biological activity of MSCs following their proliferation and transplantation in vitro. The regulation of autophagy in MSCs represents a possible mechanism that influences MSC differentiation properties under the right microenvironment, affecting their regenerative and therapeutic potential. However, a deeper understanding of exactly how autophagy is mobilized to function as well as clarifying the mechanisms by which autophagy promotes MSCs differentiation is still needed. Here, we review the current literature on the complex link between MSCs differentiation and autophagy induced by various extracellular or intracellular stimuli and the molecular targets that influence MSCs lineage determination, which may highlight the potential regulation of autophagy on MSCs' therapeutic capacity, and provide a broader perspective on the clinical application of MSCs in the treatment of a wide range of diseases.

Osteogenic potential of adipose stem cells on hydroxyapatite-functionalized decellularized amniotic membrane

Amniotic membrane (AM) is an attractive source for bone tissue engineering because of its low immunogenicity, contains biomolecules and proteins, and osteogenic differentiation properties. Hydroxyapatite is widely used as bone scaffolds due to its biocompatibility and bioactivity properties. The aim of this study is to design and fabricate scaffold based on hydroxyapatite-coated decellularized amniotic membrane (DAM-HA) for bone tissue engineering purpose. So human amniotic membranes were collected from healthy donors and decellularized (DAM). Then a hydroxyapatite-coating was created by immersion in 10X SBF, under variable parameters of pH and incubation time. Hydroxyapatite-coating was characterized and the optimal sample was selected. Human adipose-derived mesenchymal stem cell behaviors were assessed on control, amniotic membrane, and coated amniotic membrane. The results of the SEM, MTT assay, and Live-Dead staining showed that DAM and DAM-HA support cell adhesion, viability and proliferation. Osteogenic differentiation was evaluated by assessment of alkaline phosphatase activity and expression of osteogenic markers. Maximum gene expression values compared to control occurred in 14 days for alkalin phosphatase, while the highest values for osteocalcin and osteopontin in 21 days. These gene expression values in DAM and DAM-HA for alkalin phosphatase is 6.41 and 8.47, for osteocalcin is 3.95 and 5.94 and for osteopontin is 5.59 and 9.9 respectively. The results of this study indicated DAM supports the survival and growth of stem cells. Also, addition of hydroxyapatite component to DAM promotes osteogenic differentiation while maintaining viability. Therefore, hydroxyapatite-coated decellularized amniotic membrane can be a promising choice for bone tissue engineering applications.

Impact of vitamin C on the development, differentiation and functional properties ofTcells.

Vitamin C plays a multifaceted role in various biological processes and is well-known to facilitate pleiotropic activities in both innate and adaptive immune responses, where the antioxidant capacity of vitamin C is most likely highly relevant since immune responses mainly occur in reducing environments. Beyond its antioxidant properties, vitamin C can enhance the transcription potential of genes by promoting DNA demethylation through ten-eleven-translocation (Tet) methylcytosine dioxygenases, which have been recently demonstrated to be critical for the development and differentiation of T cells. In this minireview, we will provide a broader overview on the impact of vitamin C on signaling and regulatory activities in both innate and adaptive immune cells. Particularly, we will summarize recent findings on the decisive role of finely tuned vitamin C concentrations for T cell development, T helper cell differentiation, and optimal T cell-mediated immune responses.

Immunological isolation and characterization of neuronal progenitors from human dental pulp: A laboratory-based investigation.

Dental pulp stem cells (DPSCs) contain a population of stem cells with a broad range of differentiation potentials, as well as more lineage-committed progenitors. Such heterogeneity is a significant obstacle to experimental and clinical applications. The aim of this study is to isolate and characterize a homogenous neuronal progenitor cell population from human DPSCs. Polysialylated-neural cell adhesion molecule (PSA-NCAM+) neural progenitors were isolated from the dental pulp of three independent donors using magnetic-activated cell sorting (MACS) technology. Immunofluorescent staining with a panel of neural and non-neural markers was used to characterize the magnetically isolated PSA-NCAM+ fraction. PSA-NCAM+ cells were then cultured in Neurobasal A supplemented with neurotrophic factors: dibutyryl cyclic-AMP, neurotrophin-3, B27 and N2 supplements to induce neuronal differentiation. Both PSA-NCAM+ and differentiated PSA-NCAM+ cells were used in Ca2+ imaging studies to assess the functionality of P2X3 receptors as well as membrane depolarization. PSA-NCAM+ neural progenitors were isolated from a heterogeneous population of hDPSCs using magnetic-activated cell sorting and anti-PSA-NCAM MicroBeads. Flow cytometry analysis demonstrated that immunomagnetic sorting significantly increased the purity of PSA-NCAM+ cells. Immunofluorescent staining revealed expression of pan-neuronal and mature neuronal markers, PGP9.5 and MAP2, respectively, as well as weak expression of the mature sensory markers, peripherin and islet1. ATP-induced response was mediated predominately by P2X3 receptors in both undifferentiated and differentiated cells, with a greater magnitude observed in the latter. In addition, membrane depolarizations were also detected in cells before and after differentiation when loaded with fast-voltage-responding fluorescent molecule, FluoVolt™ in response to potassium chloride. Interestingly, only differentiated PSA-NCAM+ cells were capable of spontaneous membrane oscillations. In summary, DPSCs contain a population of neuronal progenitors with enhanced neural differentiation and functional neural-like properties that can be effectively isolated with magnetic-activated cell sorting (MACS).

Mixture Differential Cryptanalysis on Round-Reduced SIMON32/64 Using Machine Learning

With the development of artificial intelligence (AI), deep learning is widely used in various industries. At CRYPTO 2019, researchers used deep learning to analyze the block cipher for the first time and constructed a differential neural network distinguisher to meet a certain accuracy. In this paper, a mixture differential neural network distinguisher using ResNet is proposed to further improve the accuracy by exploring the mixture differential properties. Experiments are conducted on SIMON32/64, and the accuracy of the 8-round mixture differential neural network distinguisher is improved from 74.7% to 92.3%, compared with that of the previous differential neural network distinguisher. The prediction accuracy of the differential neural network distinguisher is susceptible to the choice of the specified input differentials, whereas the mixture differential neural network distinguisher is less affected by the input difference and has greater robustness. Furthermore, by combining the probabilistic expansion of rounds and the neutral bit, the obtained mixture differential neural network distinguisher is extended to 11 rounds, which can realize the 12-round actual key recovery attack on SIMON32/64. With an appropriate increase in the time complexity and data complexity, the key recovery accuracy of the mixture differential neural network distinguisher can be improved to 55% as compared to 52% of the differential neural network distinguisher. The mixture differential neural network distinguisher proposed in this paper can also be applied to other lightweight block ciphers.

Nonlinear optimal control for robotic exoskeletons with electropneumatic actuators

Nonlinear optimal control for robotic exoskeletons with electropneumatic actuators