Mixed Conjugates Research Articles

A Dai-Liao-type projection method for monotone nonlinear equations and signal processing

Abstract In this article, inspired by the projection technique of Solodov and Svaiter, we exploit the simple structure, low memory requirement, and good convergence properties of the mixed conjugate gradient method of Stanimirović et al. [New hybrid conjugate gradient and broyden-fletcher-goldfarbshanno conjugate gradient methods, J. Optim. Theory Appl. 178 (2018), no. 3, 860–884] for unconstrained optimization problems to solve convex constrained monotone nonlinear equations. The proposed method does not require Jacobian information. Under monotonicity and Lipschitz continuity assumptions, the global convergence properties of the proposed method are established. Computational experiments indicate that the proposed method is computationally efficient. Furthermore, the proposed method is applied to solve the ℓ 1 {\ell }_{1} -norm regularized problems to decode sparse signals and images in compressive sensing.

Constructing self-supporting surfaces with planar quadrilateral elements

We present a simple yet effective method for constructing 3D self-supporting surfaces with planar quadrilateral (PQ) elements. Starting with a triangular discretization of a self-supporting surface, we first compute the principal curvatures and directions of each triangular face using a new discrete differential geometry approach, yielding more accurate results than existing methods. Then, we smooth the principal direction field to reduce the number of singularities. Next, we partition all faces into two groups in terms of principal curvature difference. For each face with small curvature difference, we compute a stretch matrix that turns the principal directions into a pair of conjugate directions. For the remaining triangular faces, we simply keep their smoothed principal directions. Finally, applying a mixed-integer programming solver to the mixed principal and conjugate direction field, we obtain a planar quadrilateral mesh. Experimental results show that our method is computationally efficient and can yield high-quality PQ meshes that well approximate the geometry of the input surfaces and maintain their self-supporting properties.

Synthesis and controlled drug delivery studies of a novel Ubiquinol-Polyethylene glycol-Vitamin E adduct

CoQ10 and Vitamin E are used in medicinal applications, but they are both lipophilic molecules and the poor solubility in aqueous media results in an inefficient administration, poor bioavailability and potential toxicity. A mixed conjugate Ubiquinol-Polyethylene glycol-Vitamin E was synthesized and characterized to improve the bioavailability of CoQ10 and Vitamin E. The synthesized mixed PEG conjugate was characterized by 1H NMR spectroscopy and MALDI spectrometry. The in vitro release of the conjugate was measured at various pH conditions and in human plasma and the evaluation of free CoQ10 and Vitamin E were also conducted. The obtained results demonstrated that more CoQ10 and Vitamin E were released from PEG conjugate at pH 7.4 and in plasma within the 24 h. The antioxidant activity evaluation was carried out by DPPH assay. Our results indicated that the chemical modification after esterification with PEG of the two drugs Ubiquinol and Vitamin E doesn't significantly affected their antioxidant potential.

The theme vowels of Latin verbs

Latin verbs are traditionally divided into four conjugations, three of which can be readily identified by the terminal vowels of their stems – the so-called ‘theme vowels’. The identification of the theme vowel of the third conjugation is a more controversial matter. This article presents an analysis of the conjugation of regular Latin verbs, in terms of the framework of Distributed Morphology. The analysis departs from earlier analyses in two notable respects: first, following Sommer (1948), the so-called ‘mixed conjugation’ verbs are taken to form a subset of the fourth conjugation, rather than the third, which means that underlyingly their stems end on the theme vowel /iː/; and second, the stems of third-conjugation verbs are analysed as ending on the theme vowel /i/. The earlier part of the article presents the analysis, while the later part argues for those aspects of the analysis that differ from earlier analyses like those of Allen and Greenough (1903), Lieber (1981), Embick (2015) and Halle (2019). As some of the phonological rules postulated apply only to a single conjugation, the idea is briefly explored that the behaviour of Latin theme vowels can be analysed in terms of cophonologies.

Multi pH-sensitive polymer-drug conjugate mixed micelles for efficient co-delivery of doxorubicin and curcumin to synergistically suppress tumor metastasis.

Combination therapy has been proved to be an effective strategy to inhibit metastasis, however, its efficacy is always compromised by the poor delivery efficiency of drugs. In this study, multi pH-sensitive polymer-drug conjugate mixed micelles were fabricated by the self-assembly of PEOz-PLA-ace-Cur, a conjugate of curcumin (Cur) with poly(2-ethyl-2-oxazoline)-poly(d,l-lactide) (PEOz-PLA) through the linkage of the pH-cleavable acetal bond, and PEOz-PLA-imi-DOX, a conjugate of doxorubicin (DOX) with PEOz-PLA through the linkage of the pH-cleavable benzoic imine bond. The mixed conjugate micelles (PP-Cur/PP-DOX-Mix-PMs) with accurately and conveniently controlled mass ratio of the two drugs were demonstrated to have a small particle size (40-128 nm), high drug loading capacity and pH-dependent drug release behavior. Notably, PP-Cur5/PP-DOX1-Mix-PMs exhibited slower DOX release under physiological conditions compared with PEOz-PLA-imi-DOX micelles, resulting in deeply reduced side effects in vivo. Furthermore, the mixed conjugate micelles showed synergistically enhanced inhibition of MDA-MB-231 cell growth and metastasis evidenced by the results of in vitro anti-invasion, wound healing and anti-migration assessment, and in vivo bioluminescence imaging in nude mice, and significant reduction of the side effects of DOX compared with dual drug physically loaded polymeric micelles. Mechanistic studies demonstrated that the possible inhibitory mechanism of PP-Cur5/PP-DOX1-Mix-PMs on tumor metastasis could be assigned to their inhibition of the invasion, migration, intravasation and extravasation of tumor cells. In conclusion, the multi pH-sensitive polymer-drug conjugate mixed micelles with synergistically enhanced anti-tumor and anti-metastasis activity are potential candidates for safe and effective cancer combination therapy.

A Novel Method of Dynamic Force Identification and Its Application

In this paper, an efficient mixed spectral conjugate gradient (EMSCG, for short) method is presented for solving unconstrained optimization problems. In this work, we construct a novel formula performed by using a conjugate gradient parameter which takes into account the advantages of Fletcher–Reeves (FR), Polak–Ribiere–Polyak (PRP), and a variant Polak-Ribiere-Polyak (VPRP), prove its stability and convergence, and apply it to the dynamic force identification of practical engineering structure. The analysis results show that the present method has higher efficiency, stronger robust convergence quality, and fewer iterations. In addition, the proposed method can provide more efficient and numerically stable approximation of the actual force, compared with the FR method, PRP method, and VPRP method. Therefore, we can make a clear conclusion that the proposed method in this paper can provide an effective optimization solution. Meanwhile, there is reason to believe that the proposed method can offer a reference for future research.

Variation of PEAR1 DNA methylation influences platelet and leukocyte function

BackgroundPlatelet-endothelial aggregation receptor 1 (PEAR-1) is a transmembrane receptor involved in platelet activation and megakaryopoiesis whose expression is driven by DNA methylation. PEAR1 variants were associated with differential platelet response to activation and cardiovascular outcomes. We aimed at investigating the link between PEAR1 methylation and platelet and leukocyte function markers in a family-based population.ResultsWe measured PEAR1 methylation in 605 Moli-family participants with available blood counts, plasma P-selectin and C-reactive protein, whole blood platelet P-selectin, and platelet-leukocyte mixed conjugate measurements. We performed principal component analysis (PCA) to identify groups of highly correlated CpG sites. We used linear mixed regression models (using age, gender, BMI, smoking, alcohol drinking, being a proband for family recruitment, being a member of myocardial infarction (MI) family as fixed effects, and family as a random effect) to evaluate associations between PEAR1 methylation and phenotypes. PEAR1 methylation Factor2, characterized by the previously identified megakaryocyte-specific CpG sites, was inversely associated with platelet-monocyte conjugates, P-selectin, and WBC counts, while positively associated with the platelet distribution width (PDW) and with leukocyte CD11b and L-selectin. Moreover, PEAR1 Factor2 methylation was negatively associated with INFLAscore, a low-grade inflammation score. The latter was partially mediated by the PEAR1 methylation effect on platelet variables. PEAR1 methylation association with WBC measurements and INFLAscore was confirmed in the independent cohort FLEMENGHO.ConclusionsWe report a significant link between epigenetic signatures in a platelet functional gene and inflammation-dependent platelet function variability measured in two independent cohorts.

A New Smoothed L0 Regularization Approach for Sparse Signal Recovery

Sparse signal reconstruction, as the main link of compressive sensing (CS) theory, has attracted extensive attention in recent years. The essence of sparse signal reconstruction is how to recover the original signal accurately and effectively from an underdetermined linear system equation (ULSE). For this problem, we propose a new algorithm called regularization reweighted smoothed L0 norm minimization algorithm, which is simply called RRSL0 algorithm. Three innovations are made under the framework of this method: (1) a new smoothed function called compound inverse proportional function (CIPF) is proposed; (2) a new reweighted function is proposed; and (3) a mixed conjugate gradient (MCG) method is proposed. In this algorithm, the reweighted function and the new smoothed function are combined as the sparsity promoting objective, and the constraint condition y-Φx22 is taken as a deviation term. Both of them constitute an unconstrained optimization problem under the Tikhonov regularization criterion and the MCG method constructed is used to optimize the problem and realize high-precision reconstruction of sparse signals under noise conditions. Sparse signal recovery experiments on both the simulated and real data show the proposed RRSL0 algorithm performs better than other popular approaches and achieves state-of-the-art performances in signal and image processing.

Aspects of the Morphophonology of the Verb in Latin and in German and English

Aspects of the Morphophonology of the Verb in Latin and in German and English

Drug targeting to decrease cardiotoxicity - determination of the cytotoxic effect of GnRH-based conjugates containing doxorubicin, daunorubicin and methotrexate on human cardiomyocytes and endothelial cells.

Background: Cardiomyopathy induced by the chemotherapeutic agents doxorubicin and daunorubicin is a major limiting factor for their application in cancer therapy. Chemotactic drug targeting potentially increases the tumor selectivity of drugs and decreases their cardiotoxicity. Increased expression of gonadotropin-releasing hormone (GnRH) receptors on the surface of tumor cells has been reported. Thus, the attachment of the aforementioned chemotherapeutic drugs to GnRH-based peptides may result in compounds with increased therapeutic efficacy. The objective of the present study was to examine the cytotoxic effect of anticancer drug–GnRH-conjugates against two essential cardiovascular cell types, such as cardiomyocytes and endothelial cells. Sixteen different previously developed GnRH-conjugates containing doxorubicin, daunorubicin and methotrexate were investigated in this study. Their cytotoxicity was determined on primary human cardiac myocytes (HCM) and human umbilical vein endothelial cells (HUVEC) using the xCELLigence SP system, which measures impedance changes caused by adhering cells on golden electrode arrays placed at the bottom of the wells. Slopes of impedance–time curves were calculated and for the quantitative determination of cytotoxicity, the difference to the control was analysed.Results: Doxorubicin and daunorubicin exhibited a cytotoxic effect on both cell types, at the highest concentrations tested. Doxorubicin-based conjugates (AN-152, GnRH-III(Dox-O-glut), GnRH-III(Dox-glut-GFLG) and GnRH-III(Dox=Aoa-GFLG) showed the same cytotoxic effect on cardiomyocytes. Among the daunorubicin-based conjugates, [4Lys(Ac)]-GnRH-III(Dau=Aoa), GnRH-III(Dau=Aoa-YRRL), {GnRH-III(Dau=Aoa-YRRL-C)}2 and {[4N-MeSer]-GnRH-III(Dau-C)}2 had a significant but decreased cytotoxic effect, while the other conjugates – GnRH-III(Dau=Aoa), GnRH-III(Dau=Aoa-K(Dau=Aoa)), [4Lys(Dau=Aoa)]-GnRH-III(Dau=Aoa), GnRH-III(Dau=Aoa-GFLG), {GnRH-III(Dau-C)}2 and [4N-MeSer]-GnRH-III(Dau=Aoa) – exerted no cytotoxic effect on cardiomyocytes. Mixed conjugates containing methotrexate and daunorubicin – GnRH-III(Mtx-K(Dau=Aoa)) and [4Lys(Mtx)]-GnRH-III(Dau=Aoa) – showed no cytotoxic effect on cardiomyocytes, as well.Conclusion: Based on these results, anticancer drug–GnRH-based conjugates with no cytotoxic effect on cardiomyocytes were identified. In the future, these compounds could provide a more targeted antitumor therapy with no cardiotoxic adverse effects. Moreover, impedimetric cytotoxicity analysis could be a valuable technique to determine the effect of drugs on cardiomyocytes.

Complex analysis of concentrated antibody-gold nanoparticle conjugates’ mixtures using asymmetric flow field-flow fractionation

Conjugates of gold nanoparticles (GNPs) with antibodies are powerful analytical tools. It is crucial to know the conjugates’ state in both the concentrated and mixed solutions used in analytical systems. Herein, we have applied asymmetrical flow field-flow fractionation (AF4) to identify the conjugates’ state. The influence of a conjugate’s composition and concentration on aggregation was studied in a true analytical solution (a concentrated mixture with stabilizing components). GNPs with an average diameter of 15.3±1.2nm were conjugated by adsorption with eight antibodies of different specificities. We found that, while the GNPs have a zeta potential of −31.6mV, the conjugates have zeta potentials ranging from −5.8 to −11.2mV. Increased concentrations (up to 184nM, OD520=80) of the mixed conjugate (mixture of eight conjugates) did not change the form of fractograms, and the peak areas’ dependence on concentration was strongly linear (R2 values of 0.99919 and 0.99845 for absorption signal and light scattering, respectively). Based on the gyration (Rg) and hydrodynamic (Rh) radii measured during fractionation, we found that the nanoparticles were divided into two populations: (1) those with constant radii (Rg=9.9±0.9nm; Rh=14.3±0.5nm); and (2) those with increased radii from 9.9 to 24.4nm for Rg and from 14.3 to 28.1nm for Rh. These results confirm that the aggregate state of the concentrated and mixed conjugates’ preparations is the same as that of diluted preparations and that AF4 efficiently characterizes the conjugates’ state in a true analytical solution.

Synthesis, characterization and evaluation of antiproliferative activity of diisopropylphenyl esters of fatty acids from selected oils

The present investigation describes the synthesis, characterization and evaluation of antiproliferative activity of novel diisopropylphenol (propofol) conjugates of fatty acids. The fatty acids were obtained from oils of Jatropha curcas (jatropha) and Pongamia glabra (karanja) containing unsaturated-rich fatty acids, Sterculia foetida (containing cyclopropene-rich fatty acids), Samia cynthia (eri pupae, containing polyunsaturated-rich fatty acid, 18:3) and Cocos nucifera (coconut, containing medium-chain saturated-rich fatty acids). The synthesized conjugates viz. propofol-jatropha mixed fatty acid conjugates (2,4P-JTA and 2,6P-JTA), propofol-karanja mixed fatty acid conjugates (2,4P-KTA and 2,6P-KTA), propofol-sterculia foetida mixed fatty acid conjugates (2,4P-STA and 2,6P-STA), propofol-eri pupal mixed fatty acid conjugates (2,4P-EFA and 2,6-EFA) and propofol-coconut mixed fatty acid conjugates (2,4P-CCFA and 2,6P-CCFA) were obtained by esterification of the fatty acid mixture to propofol isomers (2,4-diisopropylphenol and 2,6-diisopropylphenol). The prepared derivatives were characterized by FT-IR, NMR (1H, 13C) and GC–MS and were tested for in vitro antiproliferative studies on A549, MDA-MB-231, HeLa, Mia-Pa–Ca and HePG2 cancer cell lines. All the synthesized propofol-mixed fatty acid conjugates showed good to moderate specific growth inhibition of cancer cells on studied cell lines. The results suggest that all the novel propofol-mixed fatty acid conjugates possess antiproliferative properties that reduce the proliferation of cancer cells in vitro.

Pencils of quadrics and Gromov–Witten–Welschinger invariants of $$\mathbb {C}P^3$$ C P 3

We establish a formula for the Gromov–Witten–Welschinger invariants of \(\mathbb {C}P^3\) with mixed real and conjugate point constraints. The method is based on a suggestion by J. Kollar that, considering pencils of quadrics, some real and complex enumerative invariants of \(\mathbb {C}P^3\) could be computed in terms of enumerative invariants of \(\mathbb {C}P^1\times \mathbb {C}P^1\) and of elliptic curves.

Deprotonation of Methyl-Substituted, Five-Membered Aromatic Molecules: A Surprising Case of Mixed Conjugation, Rehybridization, and Induction Contributions

Methyl-substituted, six-membered aromatic molecules are deprotonated to benzylic carbanions, which are stabilized by π conjugation. In contrast, deprotonation of 3(5)-methylpyrazole (NH protected) occurs at an endocylic CH group. Computational analyses showed that the reduction of π conjugation in substituted five-membered rings plays a major role, while the reduced bond angles, in addition to the strengthened induction of Csp(2) versus Csp(3), further favor the deprotonation of endocyclic carbon sites rather than that of the methyl group.

On boundary value problems for Maxwell set of equations in cylindrical domain

In this article solution of the Maxwell set of equations in cylindrical domain with homogeneous boundary conditions is constructed. New approach of expansion of unknown functions into series by two sets of functions orthogonal over the cross-section of domain is used. It is shown that the mixed type conjugation problem, to which the diffraction problem of electromagnetic wave on thin conducting lateral screen placed inside of the waveguide is reduced, is equivalent to two infinite sets of linear algebraic equations.

Over-determined boundary value problems for PDE and their application in the wave propagation theory

The solvability conditions of the over-determined boundary value problems for PDE with constant coefficients in the form of connection between Fourier transforms of boundary functions are obtained. The jump problem on the hyperplane for PDE is formulated and investigated. Two-dimensional Helmholtz equation is considered as an example. It is proved that the mixed type conjugation problem for Helmholtz equation, to which the diffraction problem of the electromagnetic wave on thin conducting ribbons is reduced, is equivalent to one-sided mixed type boundary value problem. The uniqueness theorem is proved for this problem.

Combined effect of a peptide–morpholino oligonucleotide conjugate and a cell-penetrating peptide as an antibiotic

A cell-penetrating peptide (CPP)-morpholino oligonucleotide (MO) conjugate (PMO) that has an antibiotic effect in culture had some contaminating CPPs in earlier preparations. The mixed conjugate had gene-specific and gene-nonspecific effects. An improved purification procedure separates the PMO from the free CPP and MO. The gene-specific effects are a result of the PMO, and the nonspecific effects are a result of the unlinked, unreacted CPP. The PMO and the CPP can be mixed together, as has been shown previously in earlier experiments, and have a combined effect as an antibiotic. Kinetic analysis of these effects confirm this observation. The effect of the CPP is bacteriostatic. The effect of the PMO appears to be bacteriocidal. An assay for mutations that would alter the ability of these agents to affect bacterial viability is negative.

Postprandial cell inflammatory response to a standardised fatty meal in subjects at different degree of cardiovascular risk

A fatty meal may represent a challenge of in vivo acute inflammatory reaction. We evaluated the acute effects of a standardised fatty meal administration on leukocytes and platelets and on their interactions on 61 subjects at different degree of cardiovascular risk, without any clinical event. Before and 2 hours after a fatty meal, blood cells were counted and markers of leukocyte (intracellular myeloperoxidase [MPO] and Mac-1) and platelet (P-selectin and microparticles) activation and mixed platelet-leukocyte conjugates measured by flow-cytometry. After the fatty meal, both white blood cell and platelet count significantly increased, more markedly in subjects with lower cardiovascular risk score. Mac-1 expression too increased (from 32.2 ± 27.2% to 45.6 ± 29.0%, p=0.0016), while MPO decreased (from 83.1 ± 16.3% to 64.5 ± 23.1%, p<0.0001). A trend for increased platelet activation and interaction with leukocytes was also observed. Women were more markedly susceptible to fatty meal challenge, as compared to men, while age did not seem to affect any cell response to fatty meal. Waist-to-hip ratio and body mass index influenced polymorphonuclear cells (PMN) degranulation and platelet count increase, respectively. Cellular responses to the fatty meal, in particular PMN degranulation, were attenuated in subjects at higher degree of cardiovascular risk, who showed a basal mild inflammatory activation status. In conclusion, a fatty meal consumption may represent a model of acute inflammatory response and appears to be modulated by different demographic and cardiovascular risk degree. This model could be applied to study the effect of food-derived antioxidants or nutritional supplements, but its relevance remains to be demonstrated.

An Improved Mixed Conjugate Gradient Method

Conjugate gradient method is an important and efficient method to solve the unconstrained optimization problems, especially for large scale problems. Based on the mixed conjugate gradient method proposed by Jing and Deng [1], we improve the mixed conjugate gradient method and prove the global convergence under a sufficient condition. At last, some numerical experiments from engineering are shown.

A novel tunable optical oscillator for broadband signals

A tunable optical oscillator that generates signals at the micro- to millimeter-wave band for wireless communication applications is suggested. It uses directly modulated semiconductor lasers, in which sideband modes and four-wave mixing (FWM) conjugate modes are injection locked by the simple control of the applied modulation power. The signals at 15 GHz with phase noise of below −95 dBc/Hz at an offset frequency of 100 kHz were experimentally obtained. The frequency of the generated signal is tunable, and the maximum achievable signal frequency is limited mainly by the bandwidth of the receiver.